A new model of diffuse brain injury in rats. Part I: Pathophysiology and biomechanics.

PubMed

Marmarou, A; Foda, M A; van den Brink, W; Campbell, J; Kita, H; Demetriadou, K

1994-02-01

This report describes the development of an experimental head injury model capable of producing diffuse brain injury in the rodent. A total of 161 anesthetized adult rats were injured utilizing a simple weight-drop device consisting of a segmented brass weight free-falling through a Plexiglas guide tube. Skull fracture was prevented by cementing a small stainless-steel disc on the calvaria. Two groups of rats were tested: Group 1, consisting of 54 rats, to establish fracture threshold; and Group 2, consisting of 107 animals, to determine the primary cause of death at severe injury levels. Data from Group 1 animals showed that a 450-gm weight falling from a 2-m height (0.9 kg-m) resulted in a mortality rate of 44% with a low incidence (12.5%) of skull fracture. Impact was followed by apnea, convulsions, and moderate hypertension. The surviving rats developed decortication flexion deformity of the forelimbs, with behavioral depression and loss of muscle tone. Data from Group 2 animals suggested that the cause of death was due to central respiratory depression; the mortality rate decreased markedly in animals mechanically ventilated during the impact. Analysis of mathematical models showed that this mass-height combination resulted in a brain acceleration of 900 G and a brain compression gradient of 0.28 mm. It is concluded that this simple model is capable of producing a graded brain injury in the rodent without a massive hypertensive surge or excessive brain-stem damage.

Do bisphosphonates inhibit direct fracture healing?: A laboratory investigation using an animal model.

PubMed

Savaridas, T; Wallace, R J; Salter, D M; Simpson, A H R W

2013-09-01

Fracture repair occurs by two broad mechanisms: direct healing, and indirect healing with callus formation. The effects of bisphosphonates on fracture repair have been assessed only in models of indirect fracture healing. A rodent model of rigid compression plate fixation of a standardised tibial osteotomy was used. Ten skeletally mature Sprague-Dawley rats received daily subcutaneous injections of 1 µg/kg ibandronate (IBAN) and ten control rats received saline (control). Three weeks later a tibial osteotomy was rigidly fixed with compression plating. Six weeks later the animals were killed. Fracture repair was assessed with mechanical testing, radiographs and histology. The mean stress at failure in a four-point bending test was significantly lower in the IBAN group compared with controls (8.69 Nmm(-2) (sd 7.63) vs 24.65 Nmm(-2) (sd 6.15); p = 0.017). On contact radiographs of the extricated tibiae the mean bone density assessment at the osteotomy site was lower in the IBAN group than in controls (3.7 mmAl (sd 0.75) vs 4.6 mmAl (sd 0.57); p = 0.01). In addition, histological analysis revealed progression to fracture union in the controls but impaired fracture healing in the IBAN group, with predominantly cartilage-like and undifferentiated mesenchymal tissue (p = 0.007). Bisphosphonate treatment in a therapeutic dose, as used for risk reduction in fragility fractures, had an inhibitory effect on direct fracture healing. We propose that bisphosphonate therapy not be commenced until after the fracture has united if the fracture has been rigidly fixed and is undergoing direct osteonal healing.

Acute versus chronic phase mechanisms in a rat model of CRPS.

PubMed

Wei, Tzuping; Guo, Tian-Zhi; Li, Wen-Wu; Kingery, Wade S; Clark, John David

2016-01-19

Tibia fracture followed by cast immobilization in rats evokes nociceptive, vascular, epidermal, and bone changes resembling complex regional pain syndrome (CRPS). In most cases, CRPS has three stages. Over time, this acute picture, allodynia, warmth, and edema observed at 4 weeks, gives way to a cold, dystrophic but still painful limb. In the acute phase (at 4 weeks post fracture), cutaneous immunological and NK1-receptor signaling mechanisms underlying CRPS have been discovered; however, the mechanisms responsible for the chronic phase are still unknown. The purpose of this study is to understand the mechanisms responsible for the chronic phases of CRPS (at 16 weeks post fracture) at both the peripheral and central levels. We used rat tibial fracture/cast immobilization model of CRPS to study molecular, vascular, and nociceptive changes at 4 and 16 weeks post fracture. Immunoassays and Western blotting were carried out to monitor changes in inflammatory response and NK1-receptor signaling in the skin and spinal cord. Skin temperature and thickness were measured to elucidate vascular changes, whereas von Frey testing and unweighting were carried out to study nociceptive changes. All data were analyzed by one-way analysis of variance (ANOVA) followed by Neuman-Keuls multiple comparison test to compare among all cohorts. In the acute phase (at 4 weeks post fracture), hindpaw allodynia, unweighting, warmth, edema, and/or epidermal thickening were observed among 90 % fracture rats, though by 16 weeks (chronic phase), only the nociceptive changes persisted. The expression of the neuropeptide signaling molecule substance P (SP), NK1 receptor, inflammatory mediators TNFα, IL-1β, and IL-6 and nerve growth factor (NGF) were elevated at 4 weeks in sciatic nerve and/or skin, returning to normal levels by 16 weeks post fracture. The systemic administration of a peripherally restricted IL-1 receptor antagonist (anakinra) or of anti-NGF inhibited nociceptive behaviors at 4 weeks but not 16 weeks. However, spinal levels of NK1 receptor, TNFα, IL-1β, and NGF were elevated at 4 and 16 weeks, and intrathecal injection of an NK1-receptor antagonist (LY303870), anakinra, or anti-NGF each reduced nociceptive behaviors at both 4 and 16 weeks. These results demonstrate that tibia fracture and immobilization cause peripheral changes in neuropeptide signaling and inflammatory mediator production acutely, but central spinal changes may be more important for the persistent nociceptive changes in this CRPS model.

Use of the TRPV1 Agonist Capsaicin to Provide Long-Term Analgesia in a Rat Limb Fracture/Open Repair, Internal Fixation Model

DTIC Science & Technology

2011-10-01

AD_________________ Award Number: W81XWH-10-2-0093 TITLE: Use of the TRPV1 Agonist Capsaicin to...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Use of the TRPV1 Agonist Capsaicin to Provide Long-Term Analgesia in a Rat Limb Fracture/Open Repair...Trauma, TRPV1 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a

Effects of enviromental temperature and femoral fracture on wound healing in rats.

PubMed

Crowley, L V; Seifter, E; Kriss, P; Rettura, G; Nakao, K; Levenson, S M

1977-06-01

Femoral fracture, unilateral and bilateral, impaired the healing of dorsal skin incisions and formation of reparative granulation tissue in subcutaneously implanted polyvinyl alcohol sponges judged histologically and by breaking strengths and hydroxyproline contents, respectively, 1 week after injury in pair-fed rats kept at 22 degrees C. When rats were transferred to a room at 30 degrees C immediately after skin incision and sponge implants, with or without unilateral fracture, no differences in healing were observed between the two groups. Rats with skin incision, sponge implants, and either femoral fracture or sham-fracture excreted more urinary nitrogen than preoperatively when kept at 22 degrees. Counterpart groups transferred to a 30 degrees room right after operation excreted less urinary nitrogen than preoperatively, but because of lower food intakes postoperatively, the ratio of urinary nitrogen to food intake nitrogen was increased. With equivalent food intakes, pair-fed rats with fracture kept at 22 degrees postoperatively lost more weight and excreted more nitrogen than corresponding rats transfered to a 30 degrees room.

Whole-body vibration improves fracture healing and bone quality in rats with ovariectomy-induced osteoporosis.

PubMed

Butezloff, Mariana Maloste; Zamarioli, Ariane; Leoni, Graziela Bianchi; Sousa-Neto, Manoel Damião; Volpon, Jose Batista

2015-11-01

To investigate the effect of vibration therapy on the bone callus of fractured femurs and the bone quality of intact femurs in ovariectomized rats. Fifty-six rats aged seven weeks were divided into four groups: control with femoral fracture (CON, n=14), ovariectomized with femoral fracture (OVX, n=14), control with femoral fracture plus vibration therapy (CON+VT, n=14), and ovariectomized with femoral fracture plus vibration therapy (OVX+VT, n=14). Three months after ovariectomy or sham surgery, a complete fracture was produced at the femoral mid-diaphysis and stabilized with a 1-mm-diameter intramedullary Kirschner wire. X-rays confirmed the fracture alignment and fixation. Three days later, the VT groups underwent vibration therapy (1 mm, 60 Hz for 20 minutes, three times per week for 14 or 28 days). The bone and callus quality were assessed by densitometry, three-dimensional microstructure, and mechanical test. Ovariectomized rats exhibited a substantial loss of bone mass and severe impairment in bone microarchitecture, both in the non-fractured femur and the bone callus. Whole-body vibration therapy exerted an important role in ameliorating the bone and fracture callus parameters in the osteoporotic bone. Vibration therapy improved bone quality and the quality of the fracture bone callus in ovariectomized rats.

Short-term muscle atrophy caused by botulinum toxin-A local injection impairs fracture healing in the rat femur.

PubMed

Hao, Yongqiang; Ma, Yongcheng; Wang, Xuepeng; Jin, Fangchun; Ge, Shengfang

2012-04-01

Damaged bone is sensitive to mechanical stimulation throughout the remodeling phase of bone healing. Muscle damage and muscular atrophy associated with open fractures and subsequent fixation are not beneficial to maintaining optimum conditions for mechanical stability. The aim of this study was to investigate whether local muscle atrophy and dysfunction affect fracture healing in a rat femur fracture model. We combined the rat model of a short period atrophy of the quadriceps with femur fracture. Forty-four-month-old male Wistar rats were adopted for this study. Two units of botulinum toxin-A (BXTA) were administered locally into the right side of the quadriceps of each rat, while the same dose of saline was injected into the contralateral quadriceps. After BXTA had been fully absorbed by the quadriceps, osteotomy was performed in both femurs with intramedullary fixation. Gross observation and weighing of muscle tissue, X-ray analysis, callus histology, and bone biomechanical testing were performed at different time points up to 8 weeks post-surgery. Local injection of BXTA led to a significant decrease in the volume and weight of the quadriceps compared to the control side. At the eighth week, the left side femurs of the saline-injected quadriceps almost reached bony union, and fibrous calluses were completely calcified into woven bone. However, a gap was still visible in the BXTA-treated side on X-ray images. As showed by bone histology, there were no mature osseous calluses or woven bone on the BXTA-treated side, but a resorption pattern was evident. Biomechanical testing indicated that the femurs of the BXTA-treated side exhibited inferior mechanical properties compared with the control side. The inferior outcome following BXTA injection, compared with saline injection, in terms of callus resistance may be the consequence of unexpected load and mechanical unsteadiness caused by muscle atrophy and dysfunction. Copyright © 2011 Orthopaedic Research Society.

Enhancement of fracture healing in the rat, modulated by compounds that stimulate inducible nitric oxide synthase: Acceleration of fracture healing via inducible nitric oxide synthase.

PubMed

Rajfer, R A; Kilic, A; Neviaser, A S; Schulte, L M; Hlaing, S M; Landeros, J; Ferrini, M G; Ebramzadeh, E; Park, S-H

2017-02-01

We investigated the effects on fracture healing of two up-regulators of inducible nitric oxide synthase (iNOS) in a rat model of an open femoral osteotomy: tadalafil, a phosphodiesterase inhibitor, and the recently reported nutraceutical, COMB-4 (consisting of L-citrulline, Paullinia cupana, ginger and muira puama), given orally for either 14 or 42 days. Unilateral femoral osteotomies were created in 58 male rats and fixed with an intramedullary compression nail. Rats were treated daily either with vehicle, tadalafil or COMB-4. Biomechanical testing of the healed fracture was performed on day 42. The volume, mineral content and bone density of the callus were measured by quantitative CT on days 14 and 42. Expression of iNOS was measured by immunohistochemistry. When compared with the control group, the COMB-4 group exhibited 46% higher maximum strength ( t -test, p = 0.029) and 92% higher stiffness ( t -test, p = 0.023), but no significant changes were observed in the tadalafil group. At days 14 and 42, there was no significant difference between the three groups with respect to callus volume, mineral content and bone density. Expression of iNOS at day 14 was significantly higher in the COMB-4 group which, as expected, had returned to baseline levels at day 42. This study demonstrates an enhancement in fracture healing by an oral natural product known to augment iNOS expression. Cite this article: R. A. Rajfer, A. Kilic, A. S. Neviaser, L. M. Schulte, S. M. Hlaing, J. Landeros, M. G. Ferrini, E. Ebramzadeh, S-H. Park. Enhancement of fracture healing in the rat, modulated by compounds that stimulate inducible nitric oxide synthase: Acceleration of fracture healing via inducible nitric oxide synthase. Bone Joint Res 2017:6:-97. DOI: 10.1302/2046-3758.62.BJR-2016-0164.R2. © 2017 Park et al.

Local application of an ibandronate/collagen sponge improves femoral fracture healing in ovariectomized rats

PubMed Central

Liu, Yansong; Hou, Zhiyong; Chen, Wei; Jin, Lin; Tian, Ye; Ju, Linlin; Liu, Bo; Dong, Tianhua; Zhang, Fei

2017-01-01

Non-union is a major clinical problem in the healing of fractures, especially in patients with osteoporosis. The systemic administration of drugs is time consuming and large doses are demanding and act slowly, whereas local release acts rapidly, increases the quality and quantity of the bone tissue. We hypothesize that local delivery demonstrates better therapeutic effects on an osteoporotic fracture. The aim of this paper is to investigate the effect of the local application of ibandronate loaded with a collagen sponge on regulating bone formation and remodeling in an osteoporotic rat model of fracture healing. We found that the local delivery of ibandronate exhibited excellent effects on improving the bone microarchitecture and suppressed effects on bone remodeling. At 4 weeks, more callus formation and improvement of mechanical character and microstructure were observed in a local delivery via μCT, mechanical test, histological research and serum analysis. The suppression of bone remodeling was compared with a systemic treatment at 12 weeks, and the structural mechanical properties and microarchitecture were also improved with local delivery. This research identifies an earlier, safer and integrated approach for local delivery of ibandronate with collagen and provides a better strategy for the treatment of osteoporotic fracture in rats. PMID:29108027

Keratinocyte expression of inflammatory mediators plays a crucial role in substance P-induced acute and chronic pain

PubMed Central

2012-01-01

Tibia fracture in rats followed by cast immobilization leads to nociceptive, trophic, vascular and bone-related changes similar to those seen in Complex Regional Pain Syndrome (CRPS). Substance P (SP) mediated neurogenic inflammation may be responsible for some of the signs of CRPS in humans. We therefore hypothesized that SP acting through the SP receptor (NK1) leads to the CRPS-like changes found in the rat model. In the present study, we intradermally injected rats with SP and monitored hindpaw mechanical allodynia, temperature, and thickness as well as tissue levels of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), interleukin 6 (IL-6), and nerve growth factor-β (NGF) for 72 h. Anti-NGF antibody was utilized to block the effects of SP-induced NGF up-regulation. Fracture rats treated with the selective NK1 receptor antagonist LY303870 prior to cast removal were assessed for BrdU, a DNA synthesis marker, incorporation in skin cells to examine cellular proliferation. Bone microarchitecture was measured using micro computed tomography (μCT). We observed that: (1) SP intraplantar injection induced mechanical allodynia, warmth and edema as well as the expression of nociceptive mediators in the hindpaw skin of normal rats, (2) LY303870 administered intraperitoneally after fracture attenuated allodynia, hindpaw unweighting, warmth, and edema, as well as cytokine and NGF expression, (3) LY303870 blocked fracture-induced epidermal thickening and BrdU incorporation after fracture, (4) anti-NGF antibody blocked SP-induced allodynia but not warmth or edema, and (5) LY303870 had no effect on bone microarchitecture. Collectively our data indicate that SP acting through NK1 receptors supports the nociceptive and vascular components of CRPS, but not the bone-related changes. PMID:22824437

Systemic Delivery of Free Chitosan Accelerates Femur Fracture Healing in Rats.

PubMed

Shao, Peng; Wei, Yongzhong; Dass, Crispin R; Zhang, Guoying; Wu, Zhisheng

2018-01-01

Chitosan-containing compounds have been shown to be suitable for bone replacement, but few studies demonstrate the impact of the chitosan as a free drug on the fracture.In this study, we aimed to evaluate possible effects of free chitosan on fracture healing. Thirty adult male Sprague-Dawley rats with a mean body weight of 205 g (range from 200g to 210g) were randomly and equally divided into two groups. Standardized femur fractures were created in all rats. Treatments were administered intraperitoneally twice weekly at 1 mg chitosan per injection and the controls were administered physiological saline. The site of the fracture was compared with the control group at 1, 2 and 4 weeks after surgery (n=5 in each group). The weight, activity and reaction of the rats were observed at all the timepoints. Anterior-posterior radiographs and micro-CT scans of all fractures were taken after surgery, and the parameters included: the volume of callus that was calculated using the Perkins volume formula, BV/TV, BV, BMD of cortical bone, cortical thickness, and cortical number at the fracture sites. After sacrifice, fractured femurs from rats were dissected and carefully cleaned of muscle around the fracture callus to preserve callus integrity. Sections were stained with haematoxylin and eosin for histological evaluation of healing. Radiological (X-ray and micro-CT) evaluation showed that fracture healing of the experimental group was better than control group at the second week and fourth week. Histological evaluation revealed fracture healing of the experimental group was better than control group at the same time. There was no statistically significant difference in fracture healing between the two groups at the first week. Systemic delivery of free chitosan can accelerate the bone healing process in rat femur fracture at the early-middle stage. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Dipyrone has no effects on bone healing of tibial fractures in rats

PubMed Central

Gali, Julio Cesar; Sansanovicz, Dennis; Ventin, Fernando Carvalho; Paes, Rodrigo Henrique; Quevedo, Francisco Carlos; Caetano, Edie Benedito

2014-01-01

OBJECTIVE: To evaluate the effect of dipyrone on healing of tibial fractures in rats. METHODS: Fourty-two Wistar rats were used, with mean body weight of 280g. After being anesthetized, they were submitted to closed fracture of the tibia and fibula of the right posterior paw through manual force. The rats were randomly divided into three groups: the control group that received a daily intraperitoneal injection of saline solution; group D-40, that received saline injection containing 40mg/Kg dipyrone; and group D-80, that received saline injection containing 80mg/Kg dipyrone. After 28 days the rats were sacrificed and received a new label code that was known by only one researcher. The fractured limbs were then amputated and X-rayed. The tibias were disarticulated and subjected to mechanical, radiological and histological evaluation. For statistical analysis the Kruskal-Wallis test was used at a significance level of 5%. RESULTS: There wasn't any type of dipyrone effect on healing of rats tibial fractures in relation to the control group. CONCLUSION: Dipyrone may be used safely for pain control in the treatment of fractures, without any interference on bone healing. Level of Evidence II, Controlled Laboratory Study. PMID:25246852

Enhancement of fracture healing in the rat, modulated by compounds that stimulate inducible nitric oxide synthase

PubMed Central

Rajfer, R. A.; Kilic, A.; Neviaser, A. S.; Schulte, L. M.; Hlaing, S. M.; Landeros, J.; Ferrini, M. G.; Ebramzadeh, E.

2017-01-01

Objectives We investigated the effects on fracture healing of two up-regulators of inducible nitric oxide synthase (iNOS) in a rat model of an open femoral osteotomy: tadalafil, a phosphodiesterase inhibitor, and the recently reported nutraceutical, COMB-4 (consisting of L-citrulline, Paullinia cupana, ginger and muira puama), given orally for either 14 or 42 days. Materials and Methods Unilateral femoral osteotomies were created in 58 male rats and fixed with an intramedullary compression nail. Rats were treated daily either with vehicle, tadalafil or COMB-4. Biomechanical testing of the healed fracture was performed on day 42. The volume, mineral content and bone density of the callus were measured by quantitative CT on days 14 and 42. Expression of iNOS was measured by immunohistochemistry. Results When compared with the control group, the COMB-4 group exhibited 46% higher maximum strength (t-test, p = 0.029) and 92% higher stiffness (t-test, p = 0.023), but no significant changes were observed in the tadalafil group. At days 14 and 42, there was no significant difference between the three groups with respect to callus volume, mineral content and bone density. Expression of iNOS at day 14 was significantly higher in the COMB-4 group which, as expected, had returned to baseline levels at day 42. Conclusion This study demonstrates an enhancement in fracture healing by an oral natural product known to augment iNOS expression. Cite this article: R. A. Rajfer, A. Kilic, A. S. Neviaser, L. M. Schulte, S. M. Hlaing, J. Landeros, M. G. Ferrini, E. Ebramzadeh, S-H. Park. Enhancement of fracture healing in the rat, modulated by compounds that stimulate inducible nitric oxide synthase: Acceleration of fracture healing via inducible nitric oxide synthase. Bone Joint Res 2017:6:–97. DOI: 10.1302/2046-3758.62.BJR-2016-0164.R2. PMID:28188129

CSA-90 Promotes Bone Formation and Mitigates Methicillin-resistant Staphylococcus aureus Infection in a Rat Open Fracture Model.

PubMed

Mills, Rebecca; Cheng, Tegan L; Mikulec, Kathy; Peacock, Lauren; Isaacs, David; Genberg, Carl; Savage, Paul B; Little, David G; Schindeler, Aaron

2018-06-01

Infection of open fractures remains a significant cause of morbidity and mortality to patients worldwide. Early administration of prophylactic antibiotics is known to improve outcomes; however, increasing concern regarding antimicrobial resistance makes finding new compounds for use in such cases a pressing area for further research. CSA-90, a synthetic peptidomimetic compound, has previously demonstrated promising antimicrobial action against Staphylococcus aureus in rat open fractures. However, its efficacy against antibiotic-resistant microorganisms, its potential as a therapeutic agent in addition to its prophylactic effects, and its proosteogenic properties all require further investigation. (1) Does prophylactic treatment with CSA-90 reduce infection rates in a rat open fracture model inoculated with S aureus, methicillin-resistant S aureus (MRSA), and methicillin-resistant Staphylococcus epidermidis (MRSE) as measured by survival, radiographic union, and deep tissue swab cultures? (2) Does CSA-90 reduce infection rates when administered later in the management of an open fracture as measured by survival, radiographic union, and deep tissue swab cultures? (3) Does CSA-90 demonstrate a synergistic proosteogenic effect with bone morphogenetic protein 2 (BMP-2) in a noninfected rat ectopic bone formation assay as assessed by micro-CT bone volume measurement? (4) Can CSA-90 elute and retain its antimicrobial efficacy in vitro when delivered using clinically relevant agents measured using a Kirby-Bauer disc diffusion assay? All in vivo studies were approved by the local animal ethics committee. In the open fracture studies, 12-week-old male Wistar rats underwent open midshaft femoral fractures stabilized with a 1.1-mm Kirschner wire and 10 µg BMP-2 ± 500 µg CSA-90 was applied to the fracture site using a collagen sponge along with 1 x 10 colony-forming units of bacteria (S aureus/MRSA/MRSE; n = 10 per group). In the delayed treatment study, débridement and treatment with 500 µg CSA-90 were performed at Day 1 and Day 5 after injury and bacterial insult (S aureus). All animals were reviewed daily for signs of local infection and/or sepsis. An independent, blinded veterinarian reviewed twice-weekly radiographs, and rats showing osteolysis and/or declining overall health were culled at his instruction. The primary outcome of both fracture studies was fracture infection, incorporating survival, radiographic union, and deep tissue swab cultures. For the ectopic bone formation assay, 0 to 10 µg BMP-2 and 0 to 500 µg CSA-90 were delivered on a collagen sponge into bilateral quadriceps muscle pouches of 8-week-old rats (n = 10 per group). Micro-CT quantification of bone volume and descriptive histologic analysis were performed for all in vivo studies. Modified Kirby-Bauer disc diffusion assays were used to quantify antimicrobial activity in vitro using four different delivery methods, including bone cement. Infection was observed in none of the MRSA inoculated open fractures treated with CSA-90 with 10 of 10 deep tissue swab cultures negative at the time of cull. Median survival was 43 days (range, 11-43 days) in the treated group versus 11 days (range, 8-11 days) in the untreated MRSA inoculated group (p < 0.001). However, delayed débridement and treatment of open fractures with CSA-90 at either Day 1 or Day 5 did not prevent infection, resulting in early culls by Day 21 with positive swab cultures (10 of 10 for each time point). Maximal ectopic bone formation was achieved with 500 μg CSA-90 and 10 μg BMP-2 (mean volume, 9.58 mm; SD, 7.83), creating larger bone nodules than formed with 250 μg CSA-90 and 10 μg BMP-2 (mean volume, 1.7 mm; SD, 1.07; p < 0.001). Disc diffusion assays showed that CSA-90 could successfully elute from four potential delivery agents including calcium sulphate (mean zone of inhibition, 11.35 mm; SD, 0.957) and bone cement (mean, 4.67 mm; SD, 0.516). CSA-90 shows antimicrobial action against antibiotic-resistant Staphylococcal strains in vitro and in an in vivo model of open fracture infection. The antimicrobial properties of CSA-90 combined with further evidence of its proosteogenic potential make it a promising compound to develop further for orthopaedic applications.

Targeted delivery of lovastatin and tocotrienol to fracture site promotes fracture healing in osteoporosis model: micro-computed tomography and biomechanical evaluation.

PubMed

Ibrahim, Nurul 'Izzah; Khamis, Mohd Fadhli; Mod Yunoh, Mohd Faridz; Abdullah, Shahrum; Mohamed, Norazlina; Shuid, Ahmad Nazrun

2014-01-01

Osteoporosis is becoming a major health problem that is associated with increased fracture risk. Previous studies have shown that osteoporosis could delay fracture healing. Although there are potential agents available to promote fracture healing of osteoporotic bone such as statins and tocotrienol, studies on direct delivery of these agents to the fracture site are limited. This study was designed to investigate the effects of two potential agents, lovastatin and tocotrienol using targeted drug delivery system on fracture healing of postmenopausal osteoporosis rats. The fracture healing was evaluated using micro CT and biomechanical parameters. Forty-eight Sprague-Dawley female rats were divided into 6 groups. The first group was sham-operated (SO), while the others were ovariectomized (OVx). After two months, the right tibiae of all rats were fractured at metaphysis region using pulsed ultrasound and were fixed with plates and screws. The SO and OVxC groups were given two single injections of lovastatin and tocotrienol carriers. The estrogen group (OVx+EST) was given daily oral gavages of Premarin (64.5 µg/kg). The Lovastatin treatment group (OVx+Lov) was given a single injection of 750 µg/kg lovastatin particles. The tocotrienol group (OVx+TT) was given a single injection of 60 mg/kg tocotrienol particles. The combination treatment group (OVx+Lov+TT) was given two single injections of 750 µg/kg lovastatin particles and 60 mg/kg tocotrienol particles. After 4 weeks of treatment, the fractured tibiae were dissected out for micro-CT and biomechanical assessments. The combined treatment group (OVx+Lov+TT) showed significantly higher callus volume and callus strength than the OVxC group (p<0.05). Both the OVx+Lov and OVx+TT groups showed significantly higher callus strength than the OVxC group (p<0.05), but not for callus volume. In conclusion, combined lovastatin and tocotrienol may promote better fracture healing of osteoporotic bone.

Characterizing the composition of bone formed during fracture healing using scanning electron microscopy techniques.

PubMed

Perdikouri, Christina; Tägil, Magnus; Isaksson, Hanna

2015-01-01

About 5-10% of all bone fractures suffer from delayed healing, which may lead to non-union. Bone morphogenetic proteins (BMPs) can be used to induce differentiation of osteoblasts and enhance the formation of the bony callus, and bisphosphonates help to retain the newly formed callus. The aim of this study was to investigate if scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) can identify differences in the mineral composition of the newly formed bone compared to cortical bone from a non-fractured control. Moreover, we investigate whether the use of BMPs and bisphosphonates-alone or combined-may have an effect on bone mineralization and composition. Twelve male Sprague-Dawley rats at 9 weeks of age were randomly divided into four groups and treated with (A) saline, (B) BMP-7, (C) bisphosphonates (Zoledronate), and (D) BMP-7 + Zoledronate. The rats were sacrificed after 6 weeks. All samples were imaged using SEM and chemically analyzed with EDS to quantify the amount of C, N, Ca, P, O, Na, and Mg. The Ca/P ratio was the primary outcome. In the fractured samples, two areas of interest were chosen for chemical analysis with EDS: the callus and the cortical bone. In the non-fractured samples, only the cortex was analyzed. Our results showed that the element composition varied to a small extent between the callus and the cortical bone in the fractured bones. However, the Ca/P ratio did not differ significantly, suggesting that the mineralization at all sites is similar 6 weeks post-fracture in this rat model.

Ovariectomized Rats with Established Osteopenia have Diminished Mesenchymal Stem Cells in the Bone Marrow and Impaired Homing, Osteoinduction and Bone Regeneration at the Fracture Site.

PubMed

Tewari, Deepshikha; Khan, Mohd Parvez; Sagar, Nitin; China, Shyamsundar P; Singh, Atul K; Kheruka, Subhash C; Barai, Sukanta; Tewari, Mahesh C; Nagar, Geet K; Vishwakarma, Achchhe L; Ogechukwu, Omeje E; Bellare, Jayesh R; Gambhir, Sanjay; Chattopadhyay, Naibedya

2015-04-01

We investigated deleterious changes that take place in mesenchymal stem cells (MSC) and its fracture healing competence in ovariectomy (Ovx)-induced osteopenia. MSC from bone marrow (BM) of ovary intact (control) and Ovx rats was isolated. (99m)Tc-HMPAO (Technitium hexamethylpropylene amine oxime) labeled MSC was systemically transplanted to rats and fracture tropism assessed by SPECT/CT. PKH26 labeled MSC (PKH26-MSC) was bound in scaffold and applied to fracture site (drill-hole in femur metaphysis). Osteoinduction was quantified by calcein binding and microcomputed tomography. Estrogen receptor (ER) antagonist, fulvestrant was used to determine ER dependence of osteo-induction by MSC. BM-MSC number was strikingly reduced and doubling time increased in Ovx rats compared to control. SPECT/CT showed reduced localization of (99m)Tc-HMPAO labeled MSC to the fracture site, 3 h post-transplantation in Ovx rats as compared with controls. Post-transplantation, Ovx MSC labeled with PKH26 (Ovx PKH26-MSC) localized less to fracture site than control PKH26-MSC. Transplantation of either control or Ovx MSC enhanced calcein binding and bone volume at the callus of control rats over placebo group however Ovx MSC had lower efficacy than control MSC. Fulvestrant blocked osteoinduction by control MSC. When scaffold bound MSC was applied to fracture, osteoinduction by Ovx PKH26-MSC was less than control PKH26-MSC. In Ovx rats, control MSC/E2 treatment but not Ovx MSC showed osteoinduction. Regenerated bone was irregularly deposited in Ovx MSC group. In conclusion, Ovx is associated with diminished BM-MSC number and its growth, and Ovx MSC displays impaired engraftment to fracture and osteoinduction besides disordered bone regeneration.

Influence of ethanol on stiffness, toughness, and ductility of femurs of rats.

PubMed

Kusy, R P; Hirsch, P F; Peng, T C

1989-04-01

Recently, we reported that the ingestion of alcohol in rats reduced the mechanical strength of femurs. Our results showed that, as the dose exceeded 0.012 g of ethanol per gram of body weight, a significant (p less than 0.001) loss of "strength" occurred that was independent of sex according to the relationship, Strength (N) = 140.4 - 6003 dose (g/g). In the present effort, the same flexure tests were reevaluated to include the parameters of stiffness, toughness, and ductility. These latest results confirm that the femurs of rats fed an ethanol liquid diet for 4 weeks are not only weaker but also more compliant and less energy absorbing. Although the femurs of rats fed ethanol are more ductile, the bones are more prone to fracture in fatigue and impact circumstances as well as under simple loading situations. The rat may be an appropriate model to study the mechanisms that lead to the higher incidence of fractures in the alcoholic human.

Post-junctional facilitation of substance P signaling in a tibia fracture rat model of complex regional pain syndrome type I

PubMed Central

Wei, Tzuping; Li, Wen-wu; Guo, Tian-Zhi; Zhao, Rong; Wang, Liping; Clark, David J; Oaklander, Ann Louise; Schmelz, Martin; Kingery, Wade S.

2009-01-01

Tibia fracture in rats evokes nociceptive, vascular, and bone changes resembling complex regional pain syndrome (CRPS). Substance P (SP) signaling contributes to the hindpaw warmth, increased vascular permeability, and edema observed in this model, suggesting that neurogenic inflammatory responses could be enhanced after fracture. Four weeks after tibia fracture we measured SP and calcitonin gene-related peptide (CGRP) protein levels in the sciatic nerve and serum. Hindpaw skin extravasation responses and SP receptor (NK1), CGRP receptor (calcitonin receptor-like receptor, CRLR) and neutral endopeptidase (NEP) protein levels were also determined. Gene expression levels of these peptides, receptors, and peptidase were examined in the DRG and skin. Spontaneous and intravenous SP-evoked extravasation responses were increased ipsilateral, but not contralateral to the fracture. Fracture increased SP and CGRP gene expression in the ipsilateral L4,L5 DRG and neuropeptide protein levels in the sciatic nerve and in serum, but had no effect on electrically-evoked SP and CGRP release. NK1 receptor expression was increased in the ipsilateral hindpaw skin keratinocytes and endothelial cells after injury, but CRLR and NEP expression were unchanged. Fracture also increased epidermal thickness, but had no effect on epidermal skin neurite counts. These results demonstrate that spontaneous and intravenous SP-evoked extravasation responses are enhanced in the ipsilateral hindlimb after fracture and that fracture chronically increases the expression of endothelial and keratinocyte NK1 receptors in the injured limb. We postulate that SP activation of these up-regulated NK1 receptors results in skin warmth, protein leakage, edema, and keratinocyte proliferation in the injured limb. PMID:19464118

Post-junctional facilitation of Substance P signaling in a tibia fracture rat model of complex regional pain syndrome type I.

PubMed

Wei, Tzuping; Li, Wen-Wu; Guo, Tian-Zhi; Zhao, Rong; Wang, Liping; Clark, David J; Oaklander, Anne Louise; Schmelz, Martin; Kingery, Wade S

2009-08-01

Tibia fracture in rats evokes nociceptive, vascular, and bone changes resembling complex regional pain syndrome (CRPS). Substance P (SP) signaling contributes to the hindpaw warmth, increased vascular permeability, and edema observed in this model, suggesting that neurogenic inflammatory responses could be enhanced after fracture. Four weeks after tibia fracture we measured SP and calcitonin gene-related peptide (CGRP) protein levels in the sciatic nerve and serum. Hindpaw skin extravasation responses and SP receptor (NK1), CGRP receptor (calcitonin receptor-like receptor, CRLR) and neutral endopeptidase (NEP) protein levels were also determined. Gene expression levels of these peptides, receptors, and peptidase were examined in the DRG and skin. Spontaneous and intravenous SP-evoked extravasation responses were increased ipsilateral, but not contralateral to the fracture. Fracture increased SP and CGRP gene expression in the ipsilateral L4,L5 DRG and neuropeptide protein levels in the sciatic nerve and in serum, but had no effect on electrically evoked SP and CGRP release. NK1 receptor expression was increased in the ipsilateral hindpaw skin keratinocytes and endothelial cells after injury, but CRLR and NEP expression were unchanged. Fracture also increased epidermal thickness, but had no effect on epidermal skin neurite counts. These results demonstrate that spontaneous and intravenous SP-evoked extravasation responses are enhanced in the ipsilateral hindlimb after fracture and that fracture chronically increases the expression of endothelial and keratinocyte NK1 receptors in the injured limb. We postulate that SP activation of these up-regulated NK1 receptors results in skin warmth, protein leakage, edema, and keratinocyte proliferation in the injured limb.

Local delivery of HMGB1 in gelatin sponge scaffolds combined with mesenchymal stem cell sheets to accelerate fracture healing.

PubMed

Xue, Deting; Zhang, Wei; Chen, Erman; Gao, Xiang; Liu, Ling; Ye, Chenyi; Tan, Yanbin; Pan, Zhijun; Li, Hang

2017-06-27

Fracture nonunion and delayed union continue to pose challenges for orthopedic surgeons. In the present study, we combined HMGB1 gelatin sponges with MSC sheets to promote bone healing after surgical treatment of rat tibial fractures. The HMGB1 gelatin sponge scaffolds supported the expansion of mesenchymal stem cells (MSCs) and promoted the osteogenic differentiation of MSCs and MSC sheets. Lentiviral vectors were then used to overexpress HMGB1 in MSCs. The results indicated that HMGB1 promotes the osteogenic differentiation of MSCs through the STAT3 pathway. Both siRNA and a STAT3 inhibitor downregulated STAT3, further confirming that HMGB1 induces the osteogenic differentiation of MSCs partly via the STAT3 signal pathway. In a rat tibial osteotomy model, we demonstrated the ability of HMGB1 gelatin sponge scaffolds to increase bone formation. The addition of MSC sheets further enhanced fracture healing. These findings support the use of HMGB1-loaded gelatin sponge scaffolds combined with MSC sheets to enhance fracture healing after surgical intervention.

Local delivery of HMGB1 in gelatin sponge scaffolds combined with mesenchymal stem cell sheets to accelerate fracture healing

PubMed Central

Xue, Deting; Zhang, Wei; Chen, Erman; Gao, Xiang; Liu, Ling; Ye, Chenyi; Tan, Yanbin; Pan, Zhijun; Li, Hang

2017-01-01

Fracture nonunion and delayed union continue to pose challenges for orthopedic surgeons. In the present study, we combined HMGB1 gelatin sponges with MSC sheets to promote bone healing after surgical treatment of rat tibial fractures. The HMGB1 gelatin sponge scaffolds supported the expansion of mesenchymal stem cells (MSCs) and promoted the osteogenic differentiation of MSCs and MSC sheets. Lentiviral vectors were then used to overexpress HMGB1 in MSCs. The results indicated that HMGB1 promotes the osteogenic differentiation of MSCs through the STAT3 pathway. Both siRNA and a STAT3 inhibitor downregulated STAT3, further confirming that HMGB1 induces the osteogenic differentiation of MSCs partly via the STAT3 signal pathway. In a rat tibial osteotomy model, we demonstrated the ability of HMGB1 gelatin sponge scaffolds to increase bone formation. The addition of MSC sheets further enhanced fracture healing. These findings support the use of HMGB1-loaded gelatin sponge scaffolds combined with MSC sheets to enhance fracture healing after surgical intervention. PMID:28431400

The effect of methotrexate on the bone healing of mandibular condylar process fracture: an experimental study in rats.

PubMed

Cavalcanti, Samantha Cristine Santos X B; Corrêa, Luciana; Mello, Suzana Beatriz Veríssimo; Luz, João Gualberto C

2014-10-01

Methotrexate (MTX) is an anti-metabolite used in rheumatology and oncology. High doses are indicated for oncological treatment, whereas low doses are indicated for chronic inflammatory diseases. This study evaluated the effect of two MTX treatment schedules on the bone healing of the temporomandibular joint fracture in rats. Seventy-five adult male Wistar rats were used to generate an experimental unilateral medially rotated condylar fracture model that allows an evaluation of bone healing and the articular structures. The animals were subdivided into three groups that each received one of the following treatments intraperitoneally: saline (1 mL/week), low-dose MTX (3 mg/kg/week) and high-dose MTX (30 mg/kg). The histological study comprised fracture site and temporomandibular joint evaluations and bone neoformation was evaluated by histomorphometric analysis. A biochemical parameter of bone formation was also assessed. When compared with saline, high-dose MTX delayed bone fracture repairs. In this latter group, after 90 days, the histological analysis revealed atrophy of the fibrocartilage and the presence of fibrous tissue in the joint space. The histomorphometric analysis revealed diminished bone neoformation. The alkaline phosphatase levels also decreased after MTX treatment. It was concluded that high-dose MTX impaired mandibular condyle repair and induced degenerative articular changes. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

A Novel Low-Molecular-Weight Compound Enhances Ectopic Bone Formation and Fracture Repair

PubMed Central

Wong, Eugene; Sangadala, Sreedhara; Boden, Scott D.; Yoshioka, Katsuhito; Hutton, William C.; Oliver, Colleen; Titus, Louisa

2013-01-01

Background: Use of recombinant human bone morphogenetic protein-2 (rhBMP-2) is expensive and may cause local side effects. A small synthetic molecule, SVAK-12, has recently been shown in vitro to potentiate rhBMP-2-induced transdifferentiation of myoblasts into the osteoblastic phenotype. The aims of this study were to test the ability of SVAK-12 to enhance bone formation in a rodent ectopic model and to test whether a single percutaneous injection of SVAK-12 can accelerate callus formation in a rodent femoral fracture model. Methods: Collagen disks with rhBMP-2 alone or with rhBMP-2 and SVAK-12 were implanted in a standard athymic rat chest ectopic model, and radiographic analysis was performed at four weeks. In a second set of rats (Sprague-Dawley), SVAK-12 was percutaneously injected into the site of a closed femoral fracture. The fractures were analyzed radiographically and biomechanically (with torsional testing) five weeks after surgery. Results: In the ectopic model, there was dose-dependent enhancement of rhBMP-2 activity with use of SVAK-12 at doses of 100 to 500 μg. In the fracture model, the SVAK-12-treated group had significantly higher radiographic healing scores than the untreated group (p = 0.028). Biomechanical testing revealed that the fractured femora in the 200 to 250-μg SVAK-12 group were 43% stronger (p = 0.008) and 93% stiffer (p = 0.014) than those in the control group. In summary, at five weeks the femoral fracture group injected with SVAK-12 showed significantly improved radiographic and biomechanical evidence of healing compared with the controls. Conclusions: A single local dose of a low-molecular-weight compound, SVAK-12, enhanced bone-healing in the presence of low-dose exogenous rhBMP-2 (in the ectopic model) and endogenous rhBMPs (in the femoral fracture model). Clinical Relevance: This study demonstrates that rhBMP-2 responsiveness can be enhanced by a novel small molecule, SVAK-12. Local application of anabolic small molecules has the potential for potentiating and accelerating fracture-healing. Use of this small molecule to lower required doses of rhBMPs might both decrease their cost and improve their safety profile. PMID:23467869

Effects of Boric Acid on Fracture Healing: An Experimental Study.

PubMed

Gölge, Umut Hatay; Kaymaz, Burak; Arpaci, Rabia; Kömürcü, Erkam; Göksel, Ferdi; Güven, Mustafa; Güzel, Yunus; Cevizci, Sibel

2015-10-01

Boric acid (BA) has positive effects on bone tissue. In this study, the effects of BA on fracture healing were evaluated in an animal model. Standard closed femoral shaft fractures were created in 40 male Sprague-Dawley rats under general anesthesia. The rats were allocated into five groups (n = 8 each): group 1, control with no BA; groups 2 and 3, oral BA at doses of 4 and 8 mg/kg/day, respectively; group 4, local BA (8 mg/kg); and group 5, both oral and local BA (8 mg/kg/day orally and 8 mg/kg locally). After closed fracture creation, the fracture line was opened with a mini-incision, and BA was locally administered to the fracture area in groups 4 and 5. In groups 2, 3, and 5, BA was administered by gastric gavage daily until sacrifice. The rats were evaluated by clinical, radiological, and histological examinations. The control group (group 1) significantly differed from the local BA-exposed groups (groups 4 and 5) in the clinical evaluation. Front-rear and lateral radiographs revealed significant differences between the local BA-exposed groups and the control and other groups (p < 0.05). Clinical and radiological evaluations demonstrated adequate agreement between observers. The average histological scores significantly differed across groups (p = 0.007) and were significantly higher in groups 4 and 5 which were the local BA (8 mg/kg) and both oral and local BA (8 mg/kg/day orally and 8 mg/kg locally), respectively, compared to the controls. This study suggests that BA may be useful in fracture healing. Further research is required to demonstrate the most effective local dosage and possible use of BA-coated implants.

Bone matrix, cellularity, and structural changes in a rat model with high-turnover osteoporosis induced by combined ovariectomy and a multiple-deficient diet.

PubMed

Govindarajan, Parameswari; Böcker, Wolfgang; El Khassawna, Thaqif; Kampschulte, Marian; Schlewitz, Gudrun; Huerter, Britta; Sommer, Ursula; Dürselen, Lutz; Ignatius, Anita; Bauer, Natali; Szalay, Gabor; Wenisch, Sabine; Lips, Katrin S; Schnettler, Reinhard; Langheinrich, Alexander; Heiss, Christian

2014-03-01

In estrogen-deficient, postmenopausal women, vitamin D and calcium deficiency increase osteoporotic fracture risk. Therefore, a new rat model of combined ovariectomy and multiple-deficient diet was established to mimic human postmenopausal osteoporotic conditions under nutrient deficiency. Sprague-Dawley rats were untreated (control), laparatomized (sham), or ovariectomized and received a deficient diet (OVX-Diet). Multiple analyses involving structure (micro-computed tomography and biomechanics), cellularity (osteoblasts and osteoclasts), bone matrix (mRNA expression and IHC), and mineralization were investigated for a detailed characterization of osteoporosis. The study involved long-term observation up to 14 months (M14) after laparotomy or after OVX-Diet, with intermediate time points at M3 and M12. OVX-Diet rats showed enhanced osteoblastogenesis and osteoclastogenesis. Bone matrix markers (biglycan, COL1A1, tenascin C, and fibronectin) and low-density lipoprotein-5 (bone mass marker) were down-regulated at M12 in OVX-Diet rats. However, up-regulation of matrix markers and existence of unmineralized osteoid were seen at M3 and M14. Osteoclast markers (matrix metallopeptidase 9 and cathepsin K) were up-regulated at M14. Micro-computed tomography and biomechanics confirmed bone fragility of OVX-Diet rats, and quantitative RT-PCR revealed a higher turnover rate in the humerus than in lumbar vertebrae, suggesting enhanced bone formation and resorption in OVX-Diet rats. Such bone remodeling caused disturbed bone mineralization and severe bone loss, as reported in patients with high-turnover, postmenopausal osteoporosis. Therefore, this rat model may serve as a suitable tool to evaluate osteoporotic drugs and new biomaterials or fracture implants. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Implant-derived magnesium induces local neuronal production of CGRP to improve bone-fracture healing in rats

PubMed Central

Zhang, Yifeng; Xu, Jiankun; Ruan, Ye Chun; Yu, Mei Kuen; O’Laughlin, Micheal; Wise, Helen; Chen, Di; Tian, Li; Shi, Dufang; Wang, Jiali; Chen, Sihui; Feng, Jian Q; Chow, Dick Ho Kiu; Xie, Xinhui; Zheng, Lizhen; Huang, Le; Huang, Shuo; Leung, Kwoksui; Lu, Na; Zhao, Lan; Li, Huafang; Zhao, Dewei; Guo, Xia; Chan, Kaiming; Witte, Frank; Chan, Hsiao Chang; Zheng, Yufeng; Qin, Ling

2017-01-01

Orthopedic implants containing biodegradable magnesium have been used for fracture repair with considerable efficacy; however, the underlying mechanisms by which these implants improve fracture healing remain elusive. Here we show the formation of abundant new bone at peripheral cortical sites after intramedullary implantation of a pin containing ultrapure magnesium into the intact distal femur in rats. This response was accompanied by substantial increases of neuronal calcitonin gene-related polypeptide-α (CGRP) in both the peripheral cortex of the femur and the ipsilateral dorsal root ganglia (DRG). Surgical removal of the periosteum, capsaicin denervation of sensory nerves or knockdown in vivo of the CGRP-receptor-encoding genes Calcrl or Ramp1 substantially reversed the magnesium-induced osteogenesis that we observed in this model. Overexpression of these genes, however, enhanced magnesium-induced osteogenesis. We further found that an elevation of extracellular magnesium induces magnesium transporter 1 (MAGT1)-dependent and transient receptor potential cation channel, subfamily M, member 7 (TRPM7)-dependent magnesium entry, as well as an increase in intracellular adenosine triphosphate (ATP) and the accumulation of terminal synaptic vesicles in isolated rat DRG neurons. In isolated rat periosteum-derived stem cells, CGRP induces CALCRL-and RAMP1-dependent activation of cAMP-responsive element binding protein 1 (CREB1) and SP7 (also known as osterix), and thus enhances osteogenic differentiation of these stem cells. Furthermore, we have developed an innovative, magnesium-containing intramedullary nail that facilitates femur fracture repair in rats with ovariectomy-induced osteoporosis. Taken together, these findings reveal a previously undefined role of magnesium in promoting CGRP-mediated osteogenic differentiation, which suggests the therapeutic potential of this ion in orthopedics. PMID:27571347

Quantification of Skeletal Blood Flow and Fluoride Metabolism in Rats using PET in a Pre-Clinical Stress Fracture Model

PubMed Central

Tomlinson, Ryan E.; Silva, Matthew J.; Shoghi, Kooresh I.

2013-01-01

Purpose Blood flow is an important factor in bone production and repair, but its role in osteogenesis induced by mechanical loading is unknown. Here, we present techniques for evaluating blood flow and fluoride metabolism in a pre-clinical stress fracture model of osteogenesis in rats. Procedures Bone formation was induced by forelimb compression in adult rats. 15O water and 18F fluoride PET imaging were used to evaluate blood flow and fluoride kinetics 7 days after loading. 15O water was modeled using a one-compartment, two-parameter model, while a two-compartment, three-parameter model was used to model 18F fluoride. Input functions were created from the heart, and a stochastic search algorithm was implemented to provide initial parameter values in conjunction with a Levenberg–Marquardt optimization algorithm. Results Loaded limbs are shown to have a 26% increase in blood flow rate, 113% increase in fluoride flow rate, 133% increase in fluoride flux, and 13% increase in fluoride incorporation into bone as compared to non-loaded limbs (p < 0.05 for all results). Conclusions The results shown here are consistent with previous studies, confirming this technique is suitable for evaluating the vascular response and mineral kinetics of osteogenic mechanical loading. PMID:21785919

Aqueous extract of Peperomia pellucida (L.) HBK accelerates fracture healing in Wistar rats.

PubMed

Florence, Ngueguim Tsofack; Huguette, Sakouong Talle Suewellyne; Hubert, Donfack Jean; Raceline, Gounoue Kamkumo; Desire, Dzeufiet Djomeni Paul; Pierre, Kamtchouing; Theophile, Dimo

2017-04-04

Peperomia pellucida (L.) HBK is consumed as vegetable and used in Cameroonian traditional medicine for the management of diseases and for fracture healing. Therefore the aim of this study was to evaluate the effects of the aqueous whole plant extract of Peperomia pellucida on fracture healing in female Wistar rats. A drill hole injury was created by inserting a drill bit inthe diaphysis of the femur. The aqueous extract of the whole plant of Peperomia pellucida was administered orally at the doses of 100, 200 and 400 mg/kg to adult female Wistar rats. The vehicle (distilled water) was given to the control. Besides these rats, one group of rats without fracture received the extract (400 mg/kg). After 14 days of treatment, the rats were sacrificed under anesthesia and the effects of the extract were evaluated on body weight, the relative weights of organs (femurs, uteri and ovaries) and on hematology. Bone (calcium, phosphorus, alkaline phosphatase) and serum biochemical parameters (calcium, phosphorus, alkaline phosphatase) were also evaluated. Radiological and histological tests were carried out on the femurs. The mineral content of the plant extract was also investigated. The extract induced an increase in body weight at high dose and in WBCs count at low doses. Aqueous extract from Peperomia pellucida increased bone calcium at lowest dose but maintained this parameter at normal range at high dose in fractured rat. Alkaline phophatase and phosphorus concentrations reduced significantly (p < 0.01) at the dose of 400 mg/kg as compared to fractured rats. Moreover, radiological tests revealed a dose dependent formation of callus at the level of the fracture gap, confirmed by the formation of a highly dense and compact fibrocartilagenous callus. The mineral content of the plant extract revealed the presence of calcium, phosphorus, magnesium, sodium and potassium. The aqueous extract of P. pellucida accelerates bone healing due partly to the mineral content of the extract. These results confirm its traditional use in the treatment of bone fractures.

Influence of electric field exposure on bone growth and fracture repair in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

McClanahan, B.J.; Phillips, R.D.

1983-01-01

Rats were exposed to a 60-Hz electric field at an unperturbed field strength of 100 kV/m to determine its affect on bone growth and fracture repair. Exposure of immature male and female rats for 20 h/day for 30 days did not alter growth rate, cortical bone area, or medullary cavity area of the tibia. In another experiment, midfibular osteotomies were performed and the juvenile rats were exposed at 100 kV/m for 14 days. Evaluation by resistance to deformation and breaking strength indicated that fracture repair was not as advanced in the exposed animals as in the sham-exposed animals. In anothermore » experiment measurements of resistance to deformation were made in adult rats at 16, 20 and 26 days after osteotmy. Fracture repair was slower in exposed compared to control animals at day 20 and, to a lesser extent, at day 16, but not at day 26. 28 references, 6 tables.« less

Beneficial influence of topical extra virgin olive oil application on an experimental model of penile fracture in rats.

PubMed

Gunes, Mustafa; Ozkol, Halil; Pirincci, Necip; Gecit, Ilhan; Bilici, Salim; Yildirim, Serkan

2015-08-01

Penile fracture (PF) is known as a traumatic rupture of the tunica albuginea of corpus cavernosum. In this study, we aimed to investigate the healing influence of topical extra virgin olive oil (EVOO) on PF through evaluating levels of some oxidative stress biomarkers for the first time. Histopathological evaluation was also realized. A total of 18 male Sprague-Dawley albino rats were divided into three groups of six rats each as control group, in PF (alone) group, and PF + EVOO group. Experimental PF was formed via incising from the proximal dorsal side of the penis in the rats of all groups except control. While in PF (alone) group, fracture was formed and the incision was primarily closed, in PF + EVOO group in addition to foregoing processes, EVOO was also administrated topically twice a day for 3 weeks. At the end of the experiment, all rats were killed and penectomy was carried out. While malondialdehyde, myeloperoxidase, lipid hyroperoxide, and total oxidant status significantly (p < 0.05) increased, reduced glutathione and total free sulfhydryl groups markedly (p < 0.05) decreased in PF (alone) group when compared with PF + EVOO group. Levels of these parameters were reversed to nearly normal values by topical EVOO application. Protection by EVOO is further substantiated via the improved histological findings in PF + EVOO group as against degenerative changes in the rats of PF (alone) group. Our data revealed that EVOO has protective effect in penile cavernosal tissue through probably its antioxidant, free radical defusing, anti-inflammatory, and antimicrobial effects. © The Author(s) 2013.

Nandrolone decanoate appears to increase bone callus formation in young adult rats after a complete femoral fracture.

PubMed

Guimarães, Ana Paula Franttini Garcia Moreno; Butezloff, Mariana Maloste; Zamarioli, Ariane; Issa, João Paulo Mardegan; Volpon, José Batista

2017-11-01

To evaluate the influence of nandrolone decanoate on fracture healing and bone quality in normal rats. Male rats were assigned to four groups (n=28/group): Control group consisting of animals without any intervention, Nandrolone decanoate (DN) group consisting of animals that received intramuscular injection of nandrolone decanoate, Fracture group consisting of animals with a fracture at the mid-diaphysis of the femur, and Fracture and nandrolone decanoate group consisting of animals with a femur fracture and treatment with nandrolone decanoate. Fractures were created at the mid-diaphysis of the right femur by a blunt trauma and internally fixed using an intramedullary steel wire. The DN was injected intramuscularly twice per week (10 mg/kg of body mass). The femurs were measured and evaluated by densitometry and mechanical resistance after animal euthanasia. The newly formed bone and collagen type I levels were quantified in the callus. The treated animals had longer femurs after 28 days. The quality of the intact bone was not significantly different between groups. The bone callus did show a larger mass in the treated rats. The administration of nandrolone decanoate did not affect the quality of the intact bone, but might have enhanced the bone callus formation.

Histopathological evaluation of the effect of locally administered strontium on healing time in mandibular fractures: An experimental study.

PubMed

Durmuş, Kasım; Turgut, Nergiz Hacer; Doğan, Mehtap; Tuncer, Ersin; Özer, Hatice; Altuntaş, Emine Elif; Akyol, Melih

2017-10-01

Mandibular fractures are the most common facial fractures. They can be treated by conservative techniques or by surgery. The authors hypothesized that the application of a single local dose of strontium chloride would accelerate the healing of subcondylar mandibular fractures, shorten the recovery time and prevent complications. The aim of the present pilot study was to evaluate the effects of a single local dose of strontium chloride on the healing of subcondylar mandibular fractures in rats. This randomized experimental study was carried out on 24 male Wistar albino rats. The rats were randomly divided into 3 groups: experimental group 1, receiving 3% strontium chloride; experimental group 2, receiving 5% strontium chloride; and the control group. A full thickness surgical osteotomy was created in the subcondylar area. A single dose of strontium solution (0.3 cc/site) was administered locally by injection on the bone surfaces of the fracture line created. Nothing was administered to the control group. The mandibles were dissected on postoperative day 21. The fractured hemimandibles were submitted to histopathological examination. The median bone fracture healing score was 9 (range: 7-9) in experimental group 1; 8 (range: 7-10) in experimental group 2; and 7.50 (range: 7-8) in the control group. When the groups were compared in terms of bone healing scores, there was a statistically significant difference between experimental group 1 and the control group (p < 0.05). This study is the first to show that local strontium may have positive effects on the healing of subcondylar mandibular fractures. In the authors' opinion, 3% strontium was beneficial for accelerating facial skeleton consolidation and bone regeneration in rat subcondylar mandibular fractures. This treatment procedure may be combined with closed fracture treatment or a conservative approach.

Ca 45 Uptake in Fracture Callus of Normal and Aminoacetonitrile-Treated Rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bolognani, L.; Ponseti, T. V.

1962-04-01

Calcium content and Ca 45 uptake were measured in the fracture callus of normal and AAN-treated rats. It appears that total calcium deposition and Ca 45 uptake are both higher in the young callus, 5 and 10 days after fracture, of the AAN-treated animals. By the 20th day, mineralization of the callus in both groups is similar.

Morphologic and molecular alteration during tibia fracture healing in rat.

PubMed

Yu, M-D; Su, B-H; Zhang, X-X

2018-03-01

To monitor morphological feature and related osteogenic and bone metabolic change during healing of tibia fracture in a rat model. Tibia density and trabecular thickness were evaluated. Histopathology was examined by HE staining. Serous inflammatory factors IL-4, IL-6, TNF-α and metabolic biomarkers ALP, β-CTX, P1NP, were determined by ELISA. The expression of RUNX2, TGF-β1, VEGF-α, BMP-2, BMP-4, and BMP-7 in callus tissue were qualified by RT-PCR. Bone density decreased until week 4 and then increased post-operation. Trabeculae in callus were thickened over time with active osteogenesis. ELISA indicated the most severe inflammation at week 2, with the highest level of TNF-α, IL-6, and the lowest level of IL-4. After 4 weeks, the inflammation was alleviated accompanying with the decline of TNF-α and IL-6, while there was the elevation of IL-4. Bone metabolism showed active osteogenesis and resorption at week 6 with high P1NP and β-CTX. The expression of RUNX2, TGF-β1, VEGF-α, BMP-2, BMP-4, and BMP-7 increased progressively from week 1 to 6. The major lesions at week 2 in sham were tissue necrosis, periosteal reactive hyperplasia, inflammatory cell infiltration, capillary hyperplasia and slight fibro-blast cytopoiesis. At week 4, proliferation was greatly activated, fibrous callus shaped and chondrogenesis and some osteogenesis occurred at week 8. In rat model, bone density started to increase at week 6 after fracture, accompanied with trabeculae thickening, serous inflammatory factors decline, and peaked bone morphogenetic protein/growth factors, which indicated active osteogenesis was conforming to the classical phase of secondary fracture healing.

Characterization of interfragmentary motion associated with common osteosynthesis devices for rat fracture healing studies.

PubMed

Meyers, Nicholaus; Sukopp, Matthias; Jäger, Rudolf; Steiner, Malte; Matthys, Romano; Lapatki, Bernd; Ignatius, Anita; Claes, Lutz

2017-01-01

Rat models are widely used in preclinical studies investigating fracture healing. The interfragmentary movement at a fracture site is critical to the course of healing and therefore demands definition in order to aptly interpret the experimental results. Estimation of this movement requires knowledge of the fixation stiffness and loading. The characteristic loading for the rat femur has been estimated, but the stiffness of fixation used in rat studies has yet to be fully described. This study aimed to determine the 6 degree of freedom stiffness of four commonly used implants, two external fixators (RatExFix and UlmExFix), a locking plate, and a locking intramedullary nail, in all degrees of freedom and estimate the interfragmentary movement under specific physiological loads. The external fixator systems allow the greatest movement. Mounted 45° anterolateral on the femur, the RatExFix allows an average of 0.88 mm of motion in each anatomic direction while the stiffer UlmExFix allows about 0.6 mm of motion. The nail is far stiffer than the other implants investigated while the plate allows movement of an intermediate magnitude. Both the nail and plate demonstrate higher axial than shear stiffness. The relatively large standard deviations in external fixator shear motion imply strong dependence on bone axis alignment across the gap and the precise orientation of the specimen relative to the loading. The smaller standard deviation associated with the nail and plate results from improved alignment and minimization of the influence of rotational positioning of the specimen due to the reduced implant eccentricity relative to the specimen axis. These results show that the interfragmentary movement is complex and varies significantly between fixation devices but establishes a baseline for the evaluation of the results of different studies.

Characterization of interfragmentary motion associated with common osteosynthesis devices for rat fracture healing studies

PubMed Central

Steiner, Malte; Matthys, Romano; Lapatki, Bernd; Ignatius, Anita; Claes, Lutz

2017-01-01

Rat models are widely used in preclinical studies investigating fracture healing. The interfragmentary movement at a fracture site is critical to the course of healing and therefore demands definition in order to aptly interpret the experimental results. Estimation of this movement requires knowledge of the fixation stiffness and loading. The characteristic loading for the rat femur has been estimated, but the stiffness of fixation used in rat studies has yet to be fully described. This study aimed to determine the 6 degree of freedom stiffness of four commonly used implants, two external fixators (RatExFix and UlmExFix), a locking plate, and a locking intramedullary nail, in all degrees of freedom and estimate the interfragmentary movement under specific physiological loads. The external fixator systems allow the greatest movement. Mounted 45° anterolateral on the femur, the RatExFix allows an average of 0.88 mm of motion in each anatomic direction while the stiffer UlmExFix allows about 0.6 mm of motion. The nail is far stiffer than the other implants investigated while the plate allows movement of an intermediate magnitude. Both the nail and plate demonstrate higher axial than shear stiffness. The relatively large standard deviations in external fixator shear motion imply strong dependence on bone axis alignment across the gap and the precise orientation of the specimen relative to the loading. The smaller standard deviation associated with the nail and plate results from improved alignment and minimization of the influence of rotational positioning of the specimen due to the reduced implant eccentricity relative to the specimen axis. These results show that the interfragmentary movement is complex and varies significantly between fixation devices but establishes a baseline for the evaluation of the results of different studies. PMID:28453556

Epistatic Effects Contribute to Variation in BMD in Fischer 344 × Lewis F2 Rats

PubMed Central

Koller, Daniel L; Liu, Lixiang; Alam, Imranul; Sun, Qiwei; Econs, Michael J; Foroud, Tatiana; Turner, Charles H

2008-01-01

To further delineate the factors underlying the complex genetic architecture of BMD in the rat model, a genome screen for epistatic interactions was conducted. Several significant interactions were identified, involving both previously identified and novel QTLs. Introduction The variation in several of the risk factors for osteoporotic fracture, including BMD, has been shown to be caused largely by genetic differences. However, the genetic architecture of BMD is complex in both humans and in model organisms. We have previously reported quantitative trait locus (QTL) results for BMD from a genome screen of 595 female F2 progeny of Fischer 344 and Lewis rats. These progeny also provide an excellent opportunity to search for epistatic effects, or interaction between genetic loci, that contribute to fracture risk. Materials and Methods Microsatellite marker data from a 20-cM genome screen was analyzed along with weight-adjusted BMD (DXA and pQCT) phenotypic data using the R/qtl software package. Genotype and phenotype data were permuted to determine a genome-wide significance threshold for the epistasis or interaction LOD score corresponding to an α level of 0.01. Results and Conclusions Novel loci on chromosomes 12 and 15 showed a strong epistatic effect on total BMD at the femoral midshaft by pQCT (LOD = 5.4). A previously reported QTL on chromosome 7 was found to interact with a novel locus on chromosome 20 to affect whole lumbar BMD by pQCT (LOD = 6.2). These results provide new information regarding the mode of action of previously identified rat QTLs, as well as identifying novel loci that act in combination with known QTLs or with other novel loci to contribute to the risk factors for osteoporotic fracture. PMID:17907919

Epistatic effects contribute to variation in BMD in Fischer 344 x Lewis F2 rats.

PubMed

Koller, Daniel L; Liu, Lixiang; Alam, Imranul; Sun, Qiwei; Econs, Michael J; Foroud, Tatiana; Turner, Charles H

2008-01-01

To further delineate the factors underlying the complex genetic architecture of BMD in the rat model, a genome screen for epistatic interactions was conducted. Several significant interactions were identified, involving both previously identified and novel QTLs. The variation in several of the risk factors for osteoporotic fracture, including BMD, has been shown to be caused largely by genetic differences. However, the genetic architecture of BMD is complex in both humans and in model organisms. We have previously reported quantitative trait locus (QTL) results for BMD from a genome screen of 595 female F(2) progeny of Fischer 344 and Lewis rats. These progeny also provide an excellent opportunity to search for epistatic effects, or interaction between genetic loci, that contribute to fracture risk. Microsatellite marker data from a 20-cM genome screen was analyzed along with weight-adjusted BMD (DXA and pQCT) phenotypic data using the R/qtl software package. Genotype and phenotype data were permuted to determine a genome-wide significance threshold for the epistasis or interaction LOD score corresponding to an alpha level of 0.01. Novel loci on chromosomes 12 and 15 showed a strong epistatic effect on total BMD at the femoral midshaft by pQCT (LOD = 5.4). A previously reported QTL on chromosome 7 was found to interact with a novel locus on chromosome 20 to affect whole lumbar BMD by pQCT (LOD = 6.2). These results provide new information regarding the mode of action of previously identified rat QTLs, as well as identifying novel loci that act in combination with known QTLs or with other novel loci to contribute to the risk factors for osteoporotic fracture.

Short-term effect of zoledronic acid upon fracture resistance of the mandibular condyle and femoral head in an animal model.

PubMed

Camacho-Alonso, Fabio; López-Jornet, Pía; Vicente-Hernández, Ascensión

2013-05-01

The aim of this study was to compare the effects in terms of resistance to fracture of the mandibular condyle and femoral head following different doses of zoledronic acid in an animal model. A total of 80 adult male Sprague-Dawley rats were included in a prospective randomized study. The animals were randomly divided into four groups of 20 rats each. Group 1 (control) received sterile saline solution, while groups 2, 3 and 4 received a accumulated dose of 0.2 mg, 0.4 mg and 0.6 mg of zoledronic acid, respectively. The animals were sacrificed 28 days after the last dose, and the right hemimandible and the right femur were removed. The fracture strength was measured (in Newtons) with a universal test machine using a 1 kN load connected to a metal rod with one end angled at 30 degrees. The cross-head speed was 1 mm/min. Later, the specimens were observed under a scanning electron microscope with backscattered electron imaging (SEM-BSE). At last, chemical analysis and elemental mapping of the mineral bone composition were generated using a microanalytical system based on energy-dispersive and X-ray spectrometry (EDX). A total of 160 fracture tests were performed. The fracture resistance increased in mandible and femur with a higher accumulated dose of zoledronic acid. Statistically significant differences were recorded versus the controls with all the studies groups. The chemical analysis in mandible showed a significantly increased of calcium and phosphorous to compare the control with all of the study groups; however, in femur no statistically significant differences between the four study groups were observed. The administration of bisphosphonates increases the fracture resistance in mandible and femur.

Design of experiments confirms optimization of lithium administration parameters for enhanced fracture healing.

PubMed

Vachhani, Kathak; Pagotto, Andrea; Wang, Yufa; Whyne, Cari; Nam, Diane

2018-01-03

Fracture healing is a lengthy process which fails in 5-10% of cases. Lithium, a low-cost therapeutic used in psychiatric medicine, up-regulates the canonical Wingless pathway crucial for osteoblastic mineralization in fracture healing. A design-of-experiments (DOE) methodology was used to optimize lithium administration parameters (dose, onset time and treatment duration) to enhance healing in a rat femoral fracture model. In the previously completed first stage (screening), onset time was found to significantly impact healing, with later (day 7 vs. day 3 post-fracture) treatment yielding improved maximum yield torque. The greatest strength was found in healing femurs treated at day 7 post fracture, with a low lithium dose (20 mg/kg) for 2 weeks duration. This paper describes the findings of the second (optimization) and third (verification) stages of the DOE investigation. Closed traumatic diaphyseal femur fractures were induced in 3-month old rats. Healing was evaluated on day 28 post fracture by CT-based morphometry and torsional loading. In optimization, later onset times of day 10 and 14 did not perform as well as day 7 onset. As such, efficacy of the best regimen (20 mg/kg dose given at day 7 onset for 2 weeks duration) was reassessed in a distinct cohort of animals to complete the DOE verification. A significant 44% higher maximum yield torque (primary outcome) was seen with optimized lithium treatment vs. controls, which paralleled the 46% improvement seen in the screening stage. Successful completion of this robustly designed preclinical DOE study delineates the optimal lithium regimen for enhancing preclinical long-bone fracture healing. Copyright © 2017 Elsevier Ltd. All rights reserved.

Deferoxamine restores callus size, mineralization, and mechanical strength in fracture healing after radiotherapy.

PubMed

Donneys, Alexis; Ahsan, Salman; Perosky, Joseph E; Deshpande, Sagar S; Tchanque-Fossuo, Catherine N; Levi, Benjamin; Kozloff, Ken M; Buchman, Steven R

2013-05-01

Therapeutic augmentation of fracture-site angiogenesis with deferoxamine has proven to increase vascularity, callus size, and mineralization in long-bone fracture models. The authors posit that the addition of deferoxamine would enhance pathologic fracture healing in the setting of radiotherapy in a model where nonunions are the most common outcome. Thirty-five Sprague-Dawley rats were divided into three groups. Fracture, irradiated fracture, and irradiated fracture plus deferoxamine. The irradiated fracture and irradiated fracture plus deferoxamine groups received a human equivalent dose of radiotherapy [7 Gy/day for 5 days, (35 Gy)] 2 weeks before mandibular osteotomy and external fixation. The irradiated fracture plus deferoxamine group received injections of deferoxamine into the fracture callus after surgery. After a 40-day healing period, mandibles were dissected, clinically assessed for bony union, imaged with micro-computed tomography, and tension tested to failure. Compared with irradiated fractures, metrics of callus size, mineralization, and strength in deferoxamine-treated mandibles were significantly increased. These metrics were restored to a level demonstrating no statistical difference from control fractures. In addition, the authors observed an increased rate of achieving bony unions in the irradiated fracture plus deferoxamine-treated group when compared with irradiated fracture (67 percent and 20 percent, respectively). The authors' data demonstrate nearly total restoration of callus size, mineralization, and biomechanical strength, and a threefold increase in the rate of union with the use of deferoxamine. The authors' results suggest that the administration of deferoxamine may have the potential for clinical translation as a new treatment paradigm for radiation-induced pathologic fractures.

AKT Pathway Affects Bone Regeneration in Nonunion Treated with Umbilical Cord-Derived Mesenchymal Stem Cells.

PubMed

Qu, Zhiguo; Guo, Shengnan; Fang, Guojun; Cui, Zhenghong; Liu, Ying

2015-04-01

We have previously grafted human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) with blood plasma to treat rat tibia nonunion. To further examine the biological characteristics of this process, we applied an established hUC-MSCs-treated rat nonunion model with the addition of an inhibitor of AKT. SD rats (80) were randomly divided into four groups: a fracture group (positive control); a nonunion group (negative control); a hUC-MSCs grafting with blood plasma group; and a hUC-MSCs grafting with blood plasma & AKT blocker group. The animals were sacrificed under deep anesthesia at 4 and 8 weeks post fracture for analysis. The fracture line became less defined at 4 weeks and disappeared at 8 weeks postoperatively in both the hUC-MSCs grafting with blood plasma and grafting with blood plasma & the AKT blocker, which is similar to the fracture group. Histological immunofluorescence studies showed that the numbers of hUC-MSCs in the calluses were significantly higher in the hUC-MSCs grafting with blood plasma than those in group with the AKT blocker. More bone morphogenetic protein 2 and bone sialoprotein expression and less osteoprotegerin and bone gla protein expression were observed in the AKT blocker group compared to the hUC-MSCs grafting with blood plasma. AKT gene expression in the AKT blocker group was decreased 50% compared to the hUC-MSCs with plasma group and decreased 70% compared to the fracture group, while the elastic modulus was decreased. In summary, our work demonstrates that AKT may play a role in modulating osteogenesis induced by hUC-MSCs.

Development of Magnetic Resonance Imaging Biomarkers for Traumatic Brain Injury

DTIC Science & Technology

2014-09-01

beta4 improves functional neurological outcome in a rat model of embolic stroke. Neuroscience 169:674–682. Morris DC, Zhang ZG, Zhang J, Xiong Y, Zhang...score of 15 with abrasion and a small laceration on his left eyebrow without closure and left clavicle fracture . His major clinical symptoms were left...Issue 11 | e80296 patient was a victim of an assault and suffered brief loss of consciousness and femur fracture . He presented in the ED with a GCS

Raloxifene improves skeletal properties in an animal model of cystic chronic kidney disease

PubMed Central

Newman, Christopher L.; Creecy, Amy; Granke, Mathilde; Nyman, Jeffry S.; Tian, Nannan; Hammond, Max A.; Wallace, Joseph M.; Brown, Drew M.; Chen, Neal; Moe, Sharon M.; Allen, Matthew R.

2015-01-01

Patients with chronic kidney disease (CKD) have an increased risk of fracture. Raloxifene is a mild anti-resorptive agent that reduces fracture risk in the general population. Here we assessed the impact of raloxifene on the skeletal properties of animals with progressive CKD. Male Cy/+ rats that develop autosomal dominant cystic kidney disease were treated with either vehicle or raloxifene for five weeks. They were assessed for changes in mineral metabolism and skeletal parameters (microCT, histology, whole bone mechanics, and material properties). Their normal littermates served as controls. Animals with CKD had significantly higher parathyroid hormone levels compared to normal controls as well as inferior structural and mechanical skeletal properties. Raloxifene treatment resulted in lower bone remodeling rates and higher cancellous bone volume in the rats with CKD. While it had little effect on cortical bone geometry it resulted in higher energy to fracture and modulus of toughness values than vehicle-treated rats with CKD, achieving levels equivalent to normal controls. Animals treated with raloxifene had superior tissue-level mechanical properties as assessed by nanoindentation and higher collagen D-periodic spacing as assessed by atomic force microscopy. Thus, raloxifene can positively impact whole bone mechanical properties in CKD through its impact on skeletal material properties. PMID:26489025

Surgery results in exaggerated and persistent cognitive decline in a rat model of the Metabolic Syndrome.

PubMed

Feng, Xiaomei; Degos, Vincent; Koch, Lauren G; Britton, Steven L; Zhu, Yinggang; Vacas, Susana; Terrando, Niccolò; Nelson, Jeffrey; Su, Xiao; Maze, Mervyn

2013-05-01

Postoperative cognitive decline can be reproduced in animal models. In a well-validated rat model of the Metabolic Syndrome, we sought to investigate whether surgery induced a more severe and persistent form of cognitive decline similar to that noted in preliminary clinical studies. In rats that had been selectively bred for low and high exercise endurance, the low capacity runners (LCR) exhibited features of Metabolic Syndrome (obesity, dyslipidemia, insulin resistance, and hypertension). Tibial fracture surgery was performed under isoflurane anesthesia in LCR and high capacity runner (HCR) rats and cognitive function was assessed postoperatively in a trace-fear conditioning paradigm and Morris Water Maze; non-operated rats were exposed to anesthesia and analgesia (sham). Group sizes were n = 6. On postoperative D7, LCR rats had shorter freezing times than postoperative HCR rats. Five months postoperatively, LCR rats had a flatter learning trajectory and took longer to locate the submerged platform than postoperative HCR rats; dwell-time in the target quadrant in a probe trial was shorter in the postoperative LCR compared to HCR rats. LCR and HCR sham rats did not differ in any test. Postoperatively, LCR rats diverged from HCR rats exhibiting a greater decline in memory, acutely, with persistent learning and memory decline, remotely; this could not be attributed to changes in locomotor or swimming performance. This Metabolic Syndrome animal model of surgery-induced cognitive decline corroborates, with high fidelity, preliminary findings of postoperative cognitive dysfunction in Metabolic Syndrome patients.

Modeling Staphylococcus epidermidis-Induced Non-Unions: Subclinical and Clinical Evidence in Rats

PubMed Central

Lovati, Arianna Barbara; Romanò, Carlo Luca; Bottagisio, Marta; Monti, Lorenzo; De Vecchi, Elena; Previdi, Sara; Accetta, Riccardo; Drago, Lorenzo

2016-01-01

S. epidermidis is one of the leading causes of orthopaedic infections associated with biofilm formation on implant devices. Open fractures are at risk of S. epidermidis transcutaneous contamination leading to higher non-union development compared to closed fractures. Although the role of infection in delaying fracture healing is well recognized, no in vivo models investigated the impact of subclinical low-grade infections on bone repair and non-union. We hypothesized that the non-union rate is directly related to the load of this commonly retrieved pathogen and that a low-grade contamination delays the fracture healing without clinically detectable infection. Rat femurs were osteotomized and stabilized with plates. Fractures were infected with a characterized clinical-derived methicillin-resistant S. epidermidis (103, 105, 108 colony forming units) and compared to uninfected controls. After 56 days, bone healing and osteomyelitis were clinically assessed and further evaluated by micro-CT, microbiological and histological analyses. The biofilm formation was visualized by scanning electron microscopy. The control group showed no signs of infection and a complete bone healing. The 103 group displayed variable response to infection with a 67% of altered bone healing and positive bacterial cultures, despite no clinical signs of infection present. The 105 and 108 groups showed severe signs of osteomyelitis and a non-union rate of 83–100%, respectively. The cortical bone reaction related to the periosteal elevation in the control group and the metal scattering detected by micro-CT represented limitations of this study. Our model showed that an intra-operative low-grade S. epidermidis contamination might prevent the bone healing, even in the absence of infectious signs. Our findings also pointed out a dose-dependent effect between the S. epidermidis inoculum and non-union rate. This pilot study identifies a relevant preclinical model to assess the role of subclinical infections in orthopaedic and trauma surgery and to test specifically designed diagnostic, prevention and therapeutic strategies. PMID:26796958

Short-term effect of zoledronic acid upon fracture resistance of the mandibular condyle and femoral head in an animal model

PubMed Central

López-Jornet, Pía; Vicente-Hernández, Ascensión

2013-01-01

Objective: The aim of this study was to compare the effects in terms of resistance to fracture of the mandibular condyle and femoral head following different doses of zoledronic acid in an animal model. Study design: A total of 80 adult male Sprague-Dawley rats were included in a prospective randomized study. The animals were randomly divided into four groups of 20 rats each. Group 1 (control) received sterile saline solution, while groups 2, 3 and 4 received a accumulated dose of 0.2 mg, 0.4 mg and 0.6 mg of zoledronic acid, respectively. The animals were sacrificed 28 days after the last dose, and the right hemimandible and the right femur were removed. The fracture strength was measured (in Newtons) with a universal test machine using a 1 kN load connected to a metal rod with one end angled at 30 degrees. The cross-head speed was 1 mm/min. Later, the specimens were observed under a scanning electron microscope with backscattered electron imaging (SEM-BSE). At last, chemical analysis and elemental mapping of the mineral bone composition were generated using a microanalytical system based on energy-dispersive and X-ray spectrometry (EDX). Results: A total of 160 fracture tests were performed. The fracture resistance increased in mandible and femur with a higher accumulated dose of zoledronic acid. Statistically significant differences were recorded versus the controls with all the studies groups. The chemical analysis in mandible showed a significantly increased of calcium and phosphorous to compare the control with all of the study groups; however, in femur no statistically significant differences between the four study groups were observed. Conclusions: The administration of bisphosphonates increases the fracture resistance in mandible and femur. Key words:Zoledronic acid, bisphosphonates, animal experimentation, fracture test. PMID:23524420

Effects of Roughly Focused Extracorporeal Shock Waves Therapy on the Expressions of Bone Morphogenetic Protein-2 and Osteoprotegerin in Osteoporotic Fracture in Rats

PubMed Central

Huang, Hai-Ming; Li, Xiao-Lin; Tu, Shu-Qiang; Chen, Xiao-Feng; Lu, Chang-Chun; Jiang, Liang-Hua

2016-01-01

Background: Roughly focused extracorporeal shock waves therapy (ESWT) is characterized by a wide focal area, a large therapy zone, easy positioning, and less pain during treatment. The purpose of this study was to investigate the effects of roughly focused ESWT on the expression of osteoprotegerin (OPG) and bone morphogenetic protein-2 (BMP-2) in osteoporotic fractures in rats. Methods: Seventy-two female Sprague-Dawley (SD) rats, 3 months old, were divided into sham-operated group (n = 6) and an ovariectomized (OVX) group (n = 66). Sixty OVX SD rats were used as a model of double proximal tibial osteotomy and inner fixation. The osteotomy site in the left tibia was treated with roughly focused ESWT once at an energy density of 0.26 mJ/mm2, 60 doses/min, and 2000 pact quantities. The contralateral right tibia was left untreated and served as a control. Expression of OPG and BMP-2 in the callus of the osteoporotic fracture area was assessed using immunohistochemistry, real-time polymerase chain reaction (PCR), and Western blotting analysis. Results: Bone mineral density (BMD) at the proximal tibia, femur, and L5 spine was significantly reduced after ovariectomy. BMD of proximal tibia was 12.9% less in the OVX group than that in the sham-operated group. Meanwhile, bilateral oophorectomy resulted in a lower trabecular bone volume fraction (BV/TV) in the proximal tibia of the sham-OVX animals. Three months after bilateral oophorectomy, BV/TV was 14.29% of baseline BV/TV in OVX legs versus 45.91% in the sham-OVX legs (P < 0.001). These data showed that the SD rats became a suitable model of osteoporosis, 3 months after they were OVX. Immunohistochemical analysis showed higher levels of BMP-2 and OPG expression in the treatment group than those in the control group. Compared with the contralateral controls, decreased expression of OPG and BMP-2 at 3 days after roughly focused ESWT, followed by a later increase at 7 days, was indicated by real-time PCR and Western blotting analysis. The OPG messenger RNA (mRNA) expression levels peaked at 6 weeks after the shock wave treatment, paired with a much earlier (at 4 weeks) increase of BMP-2, and declined close to normal at 8 weeks. Conclusions: Roughly focused ESWT may promote the expression of OPG and BMP-2 in the osteoporotic fracture area in rats. BMP-2 and OPG may act synergistically and may lead to a significant enhancement of bone formation and remodeling. PMID:27779163

Experimental models for cancellous bone healing in the rat

PubMed Central

Bernhardsson, Magnus; Sandberg, Olof; Aspenberg, Per

2015-01-01

Background and purpose — Cancellous bone appears to heal by mechanisms different from shaft fracture healing. There is a paucity of animal models for fractures in cancellous bone, especially with mechanical evaluation. One proposed model consists of a screw in the proximal tibia of rodents, evaluated by pull-out testing. We evaluated this model in rats by comparing it to the healing of empty drill holes, in order to explain its relevance for fracture healing in cancellous bone. To determine the sensitivity to external influences, we also compared the response to drugs that influence bone healing. Methods — Mechanical fixation of the screws was measured by pull-out test and related to the density of the new bone formed around similar, but radiolucent, PMMA screws. The pull-out force was also related to the bone density in drill holes at various time points, as measured by microCT. Results — The initial bone formation was similar in drill holes and around the screw, and appeared to be reflected by the pull-out force. Both models responded similarly to alendronate or teriparatide (PTH). Later, the models became different as the bone that initially filled the drill hole was resorbed to restore the bone marrow cavity, whereas on the implant surface a thin layer of bone remained, making it change gradually from a trauma-related model to an implant fixation model. Interpretation — The similar initial bone formation in the different models suggests that pull-out testing in the screw model is relevant for assessment of metaphyseal bone healing. The subsequent remodeling would not be of clinical relevance in either model. PMID:26200395

Histopathological effects of fibrin glue on penile fracture in a rat model.

PubMed

Tasdemir, Cemal; Samdanci, Emine T; Turtay, Muhammet G; Firat, Cemal; Oguzturk, Hakan; Ozdemir, Hulya

2011-12-01

To evaluate both histopathological effects and potential clinical application of fibrin glue on the penile cavernosal tissue. Experimental penile fracture was formed by incising from the proximal dorsal side of the penis in 32 Wistar Albino rats. The rats were randomly assigned to four main groups of eight animals each. In the control group, the incision was not repaired and it was left to secondary healing. In the primary repair group, the incision was primarily repaired. In the fibrin glue group, glue was applied only to the incision. In the final group, fibrin glue was applied to the incision following primary repair. Three weeks later, penectomy tissue was examined histopathologically. When the control group was compared with primary repair+fibrin glue group, the differences in cavernous tissue healing with fibrosis and inflammation were statistically significant (p = 0.04 and 0.01, respectively). The primary repair+fibrin glue group, showed the best cavernous healing with fibrosis observed in only one rat. . There was no significant difference between the control group and the other groups according to cavernous tissue healing with fibrosis and inflammation (p = 0.11 and 0.12). Hyperemia was observed in the all groups of rats. Fibrin glue can be used in cavernoseal surgeries due to its adhesive and potentially anti-inflammatory features.

Selection of animal models for pre-clinical strategies in evaluating the fracture healing, bone graft substitutes and bone tissue regeneration and engineering.

PubMed

Bigham-Sadegh, Amin; Oryan, Ahmad

2015-06-01

In vitro assays can be useful in determining biological mechanism and optimizing scaffold parameters, however translation of the in vitro results to clinics is generally hard. Animal experimentation is a better approximation than in vitro tests, and usage of animal models is often essential in extrapolating the experimental results and translating the information in a human clinical setting. In addition, usage of animal models to study fracture healing is useful to answer questions related to the most effective method to treat humans. There are several factors that should be considered when selecting an animal model. These include availability of the animal, cost, ease of handling and care, size of the animal, acceptability to society, resistance to surgery, infection and disease, biological properties analogous to humans, bone structure and composition, as well as bone modeling and remodeling characteristics. Animal experiments on bone healing have been conducted on small and large animals, including mice, rats, rabbits, dogs, pigs, goats and sheep. This review also describes the molecular events during various steps of fracture healing and explains different means of fracture healing evaluation including biomechanical, histopathological and radiological assessments.

NELL-1 Injection Maintains Long-Bone Quantity and Quality in an Ovariectomy-Induced Osteoporotic Senile Rat Model

PubMed Central

Kwak, Jinny; Zara, Janette N.; Chiang, Michael; Ngo, Richard; Shen, Jia; James, Aaron W.; Le, Khoi M.; Moon, Crystal; Zhang, Xinli; Gou, Zhongru; Ting, Kang

2013-01-01

Over 10 million Americans have osteoporosis, and is the predominant cause of fractures in the elderly. Treatment of fractures in the setting of osteoporosis is complicated by a suboptimal bone regenerative response due to a decline in the number of osteoblasts, their function, and survival. Consequently, an osteogenic therapeutic to prevent and treat fractures in patients with osteoporosis is needed. Nel-like molecule-1 (NELL-1), a novel osteoinductive growth factor, has been shown to promote bone regeneration. In this study, we aim to demonstrate the capacity of recombinant NELL-1 to prevent ovariectomy (OVX)-induced osteoporosis in a senile rat model. Ten-month-old female Sprague-Dawley rats underwent either sham surgery or OVX. Subsequently, 50 μL of 600 μg/mL NELL-1 lyophilized onto a 0–50-μm tricalcium phosphate (TCP) carrier was injected into the femoral bone marrow cavity while phosphate-buffered saline (PBS) control was injected into the contralateral femur. Our microcomputed tomography results showed that OVX+PBS/TCP control femurs showed a continuous decrease in the bone volume (BV) and bone mineral density (BMD) from 2 to 8 weeks post-OVX. In contrast, OVX+NELL-1/TCP femurs showed resistance to OVX-induced bone resorption showing BV and BMD levels similar to that of SHAM femurs at 8 weeks post-OVX. Histology showed increased endosteal-woven bone, as well as decreased adipocytes in the bone marrow of NELL-1-treated femurs compared to control. NELL-1-treated femurs also showed increased immunostaining for bone differentiation markers osteopontin and osteocalcin. These findings were validated in vitro, in which addition of NELL-1 in OVX bone marrow stem cells resulted in increased osteogenic differentiation. Thus, NELL-1 effectively enhances in situ osteogenesis in the bone marrow, making it potentially useful in the prevention and treatment of osteoporotic fractures. PMID:23083222

Spatially offset raman spectroscopy for non-invasive assessment of fracture healing

NASA Astrophysics Data System (ADS)

Ding, Hao; Lu, Guijin; West, Christopher; Gogola, Gloria; Kellam, James; Ambrose, Catherine; Bi, Xiaohong

2016-02-01

Fracture non-unions and bone re-fracture are common challenges for post-fracture management. To achieve better prognosis and treatment evaluation, it is important to be able to assess the quality of callus over the time course of healing. This study evaluated the potential of spatially offset Raman spectroscopy for assessing the fracture healing process in situ. We investigated a rat model of fracture healing at two weeks and 4 weeks post fracture with a fractured femur and a contralateral control in each animal. Raman spectra were collected from the depilated thighs on both sides transcutaneously in situ with various source/detection offsets. Bone signals were recovered from SORS spectra, and then compared with those collected from bare bones. The relative intensity of mineral from fractured bone was markedly decreased compared to the control. The fractured bones demonstrated lower mineral and carbonate level and higher collagen content in the callus at the early time point. Compared to week 2, collagen mineralization and mineral carbonation increased at 4 weeks post fracture. Similarly, the material properties of callus determined by reference point indentation also increased in the 4-week group, indicating improved callus quality with time. The results from Raman analysis are in agreement with radiographic and material testing, indicating the potential of this technique in assessing fracture healing in vivo.

Genomic expression analysis of rat chromosome 4 for skeletal traits at femoral neck.

PubMed

Alam, Imranul; Sun, Qiwei; Liu, Lixiang; Koller, Daniel L; Liu, Yunlong; Edenberg, Howard J; Econs, Michael J; Foroud, Tatiana; Turner, Charles H

2008-10-08

Hip fracture is the most devastating osteoporotic fracture type with significant morbidity and mortality. Several studies in humans and animal models identified chromosomal regions linked to hip size and bone mass. Previously, we identified that the region of 4q21-q41 on rat chromosome (Chr) 4 harbors multiple femoral neck quantitative trait loci (QTLs) in inbred Fischer 344 (F344) and Lewis (LEW) rats. The purpose of this study is to identify the candidate genes for femoral neck structure and density by correlating gene expression in the proximal femur with the femoral neck phenotypes linked to the QTLs on Chr 4. RNA was extracted from proximal femora of 4-wk-old rats from F344 and LEW strains, and two other strains, Copenhagen 2331 and Dark Agouti, were used as a negative control. Microarray analysis was performed using Affymetrix Rat Genome 230 2.0 arrays. A total of 99 genes in the 4q21-q41 region were differentially expressed (P < 0.05) among all strains of rats with a false discovery rate <10%. These 99 genes were then ranked based on the strength of correlation between femoral neck phenotypes measured in F2 animals, homozygous for a particular strain's allele at the Chr 4 QTL and the expression level of the gene in that strain. A total of 18 candidate genes were strongly correlated (r(2) > 0.50) with femoral neck width and prioritized for further analysis. Quantitative PCR analysis confirmed 14 of 18 of the candidate genes. Ingenuity pathway analysis revealed several direct or indirect relationships among the candidate genes related to angiogenesis (VEGF), bone growth (FGF2), bone formation (IGF2 and IGF2BP3), and resorption (TNF). This study provides a shortened list of genetic determinants of skeletal traits at the hip and may lead to novel approaches for prevention and treatment of hip fracture.

Genomic expression analysis of rat chromosome 4 for skeletal traits at femoral neck

PubMed Central

Alam, Imranul; Sun, Qiwei; Liu, Lixiang; Koller, Daniel L.; Liu, Yunlong; Edenberg, Howard J.; Econs, Michael J.; Foroud, Tatiana; Turner, Charles H.

2008-01-01

Hip fracture is the most devastating osteoporotic fracture type with significant morbidity and mortality. Several studies in humans and animal models identified chromosomal regions linked to hip size and bone mass. Previously, we identified that the region of 4q21-q41 on rat chromosome (Chr) 4 harbors multiple femoral neck quantitative trait loci (QTLs) in inbred Fischer 344 (F344) and Lewis (LEW) rats. The purpose of this study is to identify the candidate genes for femoral neck structure and density by correlating gene expression in the proximal femur with the femoral neck phenotypes linked to the QTLs on Chr 4. RNA was extracted from proximal femora of 4-wk-old rats from F344 and LEW strains, and two other strains, Copenhagen 2331 and Dark Agouti, were used as a negative control. Microarray analysis was performed using Affymetrix Rat Genome 230 2.0 arrays. A total of 99 genes in the 4q21-q41 region were differentially expressed (P < 0.05) among all strains of rats with a false discovery rate <10%. These 99 genes were then ranked based on the strength of correlation between femoral neck phenotypes measured in F2 animals, homozygous for a particular strain's allele at the Chr 4 QTL and the expression level of the gene in that strain. A total of 18 candidate genes were strongly correlated (r2 > 0.50) with femoral neck width and prioritized for further analysis. Quantitative PCR analysis confirmed 14 of 18 of the candidate genes. Ingenuity pathway analysis revealed several direct or indirect relationships among the candidate genes related to angiogenesis (VEGF), bone growth (FGF2), bone formation (IGF2 and IGF2BP3), and resorption (TNF). This study provides a shortened list of genetic determinants of skeletal traits at the hip and may lead to novel approaches for prevention and treatment of hip fracture. PMID:18728226

Evaluation of the Parietal Bones in the Rat as a Specific Site for the Testing of Osteogenic Materials. A Simple Animal Model to Study Bone Implant Material.

DTIC Science & Technology

1981-10-01

Intraosseous Appliance in the Treatment of Mandibular Fractures . J Oral Surg 30:344-348, 1977. 6. MELCHER, A.H. and IRVING, J.T.: The Healing...on the observed results. Investigators have prepared osseous defects in monkeys, sheep, and dogs in an attempt to study the effects of bone inducing...occur in the control animals. Sufficient bone must also be available so that the risk of fracture is mitigated. 3. The animal should allow for

The Effect of Rosiglitazone on Bone Quality in a Rat Model of Insulin Resistance and Osteoporosis

NASA Astrophysics Data System (ADS)

Sardone, Laura Donata

Rosiglitazone (RSG) is an insulin-sensitizing drug used to treat Type 2 Diabetes Mellitus (T2DM). Clinical trials show that women taking RSG experience more limb fractures than patients taking other T2DM drugs. The purpose of this study is to understand how RSG (3mg/kg/day and 10mg/kg/day) and the bisphosphonate alendronate (0.7mg/kg/week) alter bone quality in the male, female and female ovariectomized (OVX) Zucker fatty rat model over a 12 week period. Bone quality was evaluated by mechanical testing of cortical and trabecular bone. Microarchitecture, bone mineral density (BMD), cortical bone porosity, bone formation/resorption and mineralization were also measured. Female OVX RSG10mg/kg rats had significantly lower vertebral BMD and compromised trabecular architecture versus OVX controls. Increased cortical porosity and decreased mechanical properties occurred in these rats. ALN treatment prevented these negative effects in the OVX RSG model. Evidence of reduced bone formation and excess bone resorption was detected in female RSG-treated rats.

Diabetes mellitus affects the biomechanical function of the callus and the expression of TGF-beta1 and BMP2 in an early stage of fracture healing.

PubMed

Xu, M T; Sun, S; Zhang, L; Xu, F; Du, S L; Zhang, X D; Wang, D W

2016-01-01

Transforming growth factor beta 1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2) are important regulators of bone repair and regeneration. In this study, we examined whether TGF-β1 and BMP-2 expressions were delayed during bone healing in type 1 diabetes mellitus. Tibial fractures were created in 95 diabetic and 95 control adult male Wistar rats of 10 weeks of age. At 1, 2, 3, 4, and 5 weeks after fracture induction, five rats were sacrificed from each group. The expressions of TGF-β1 and BMP2 in the fractured tibias were measured by immunohistochemistry and quantitative reverse-transcription polymerase chain reaction, weekly for the first 5 weeks post-fracture. Mechanical parameters (bending rigidity, torsional rigidity, destruction torque) of the healing bones were also assessed at 3, 4, and 5 weeks post-fracture, after the rats were sacrificed. The bending rigidity, torsional rigidity and destruction torque of the two groups increased continuously during the healing process. The diabetes group had lower mean values for bending rigidity, torsional rigidity and destruction torque compared with the control group (P<0.05). TGF-β1 and BMP-2 expression were significantly lower (P<0.05) in the control group than in the diabetes group at postoperative weeks 1, 2, and 3. Peak levels of TGF-β1 and BMP-2 expression were delayed by 1 week in the diabetes group compared with the control group. Our results demonstrate that there was a delayed recovery in the biomechanical function of the fractured bones in diabetic rats. This delay may be associated with a delayed expression of the growth factors TGF-β1 and BMP-2.

Influence of 1800 MHz GSM-like electromagnetic radiation exposure on fracture healing.

PubMed

Aslan, Ahmet; Kırdemır, Vecihi; Kocak, Ahmet; Atay, Tolga; Baydar, Metin Lütfi; Özerdemoglu, Remzi Arif; Aydogan, Nevres Hürriyet

2014-02-01

In this study, we aimed to investigate whether 1800 MHz frequency electromagnetic radiation (EMR) has an effect on bone healing. A total of 30 Wistar albino rats were divided into two equal groups. Fractures were created in the right tibias of all rats; next, intramedullary fixations with K-wire were performed. A control group (Group I) was kept under the same experimental conditions except without EMR exposure. Rats in Group II were exposed to an 1800 MHz frequency EMR for 30 min a day for 5 days a week. Next, radiological, mechanical, and histological examinations were performed to evaluate tibial fracture healing. Radiological, histological and mechanical scores were not significantly different between groups (respectively, p = 0.114, p = 0.184 and p = 0.083), and all of these scores were lower than those of the controls. EMR at 1800 MHz frequency emitted from cellular phones has no effect on bone fracture healing. Copyright © 2014 IMSS. Published by Elsevier Inc. All rights reserved.

Overexpression of HSPA1A enhances the osteogenic differentiation of bone marrow mesenchymal stem cells via activation of the Wnt/β-catenin signaling pathway

PubMed Central

Zhang, Wei; Xue, Deting; Yin, Houfa; Wang, Shengdong; Li, Chao; Chen, Erman; Hu, Dongcai; Tao, Yiqing; Yu, Jiawei; Zheng, Qiang; Gao, Xiang; Pan, Zhijun

2016-01-01

HSPA1A, which encodes cognate heat shock protein 70, plays important roles in various cellular metabolic pathways. To investigate its effects on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), its expression level was compared between undifferentiated and differentiated BMSCs. Rat HSPA1A overexpression in BMSCs increased osteoblast-specific gene expression, alkaline phosphatase activity, and mineral deposition in vitro. Moreover, it upregulated β-catenin and downregulated DKK1 and SOST. The enhanced osteogenesis due to HSPA1A overexpression was partly rescued by a Wnt/β-catenin inhibitor. Additionally, using a rat tibial fracture model, a sheet of HSPA1A-overexpressing BMSCs improved bone fracture healing, as determined by imaging and histological analysis. Taken together, these findings suggest that HSPA1A overexpression enhances osteogenic differentiation of BMSCs, partly through Wnt/β-catenin. PMID:27279016

Analysis of fracture healing in osteopenic bone caused by disuse: experimental study.

PubMed

Paiva, A G; Yanagihara, G R; Macedo, A P; Ramos, J; Issa, J P M; Shimano, A C

2016-03-01

Osteoporosis has become a serious global public health issue. Hence, osteoporotic fracture healing has been investigated in several previous studies because there is still controversy over the effect osteoporosis has on the healing process. The current study aimed to analyze two different periods of bone healing in normal and osteopenic rats. Sixty, 7-week-old female Wistar rats were randomly divided into four groups: unrestricted and immobilized for 2 weeks after osteotomy (OU2), suspended and immobilized for 2 weeks after osteotomy (OS2), unrestricted and immobilized for 6 weeks after osteotomy (OU6), and suspended and immobilized for 6 weeks after osteotomy (OS6). Osteotomy was performed in the middle third of the right tibia 21 days after tail suspension, when the osteopenic condition was already set. The fractured limb was then immobilized by orthosis. Tibias were collected 2 and 6 weeks after osteotomy, and were analyzed by bone densitometry, mechanical testing, and histomorphometry. Bone mineral density values from bony calluses were significantly lower in the 2-week post-osteotomy groups compared with the 6-week post-osteotomy groups (multivariate general linear model analysis, P<0.000). Similarly, the mechanical properties showed that animals had stronger bones 6 weeks after osteotomy compared with 2 weeks after osteotomy (multivariate general linear model analysis, P<0.000). Histomorphometry indicated gradual bone healing. Results showed that osteopenia did not influence the bone healing process, and that time was an independent determinant factor regardless of whether the fracture was osteopenic. This suggests that the body is able to compensate for the negative effects of suspension.

A controlled trial of glutamine effects on bone healing.

PubMed

Polat, Onur; Kilicoglu, Sibel Serin; Erdemli, Esra

2007-01-01

Glutamine is considered a nonessential amino acid, but it may be conditionally essential in patients with catabolic conditions. For centuries, researchers have looked for ways to promote and accelerate fracture healing. This controlled animal study examines the effects of glutamine on fracture healing. The left tibias of 10 standardized albino rats were broken at the distal third to produce a closed fracture. L-glutamine/L-alanyl solution (2.0 mL/kg) was administered through the tail veins of half the rats for the first 7 d, and physiologic serum alone was given to the control group. On the 21st day, all rats were euthanized and their left legs removed; after histologic observation, the tibias were examined under light microscopy. In the glutamine-injected group, development of primary callus was quicker and more regular than in the control group. The control group produced insufficient fibrous callus, and the glutamine group attained formed cartilaginous callus. Glutamine was noted to have positive effects on healing of traumatically fractured bone through attainment of positive nitrogen balance. This effect was minimal in enhancing the quality of fracture healing under conditions of stress, but some effect was noted on the speed of healing. Further research is needed in this area.

Effects of local vibration and pulsed electromagnetic field on bone fracture: A comparative study.

PubMed

Bilgin, Hakkı Murat; Çelik, Ferhat; Gem, Mehmet; Akpolat, Veysi; Yıldız, İsmail; Ekinci, Aysun; Özerdem, Mehmet Siraç; Tunik, Selçuk

2017-07-01

The effectiveness of various therapeutic methods on bone fracture has been demonstrated in several studies. In the present study, we tried to evaluate the effect of local low-magnitude, high-frequency vibration (LMHFV) on rat tibia fracture in comparison with pulsed electromagnetic fields (PEMF) during the healing process. Mid-diaphysis tibiae fractures were induced in 30 Sprague-Dawley rats. The rats were assigned into groups such as control (CONT), LMHFV (15 min/day, 7 days/week), and PEMF (3.5 h/day, 7 days/week) for a three-week treatment. Nothing was applied to control group. Radiographs, serum osteocalcin levels, and stereological bone analyses of the three groups were compared. The X-rays of tibiae were taken 21 days after the end of the healing process. PEMF and LMHFV groups had more callus formation when compared to CONT group; however, the difference was not statistically significant (P = 0.375). Serum osteocalcin levels were elevated in the experimental groups compared to CONT (P ≤ 0.001). Stereological tests also showed higher osteogenic results in experimental groups, especially in LMHFV group. The results of the present study suggest that application of direct local LMHFV on fracture has promoted bone formation, showing great potential in improving fracture outcome. Bioelectromagnetics. 38:339-348, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Effects of multi-deficiencies-diet on bone parameters of peripheral bone in ovariectomized mature rat.

PubMed

El Khassawna, Thaqif; Böcker, Wolfgang; Govindarajan, Parameswari; Schliefke, Nathalie; Hürter, Britta; Kampschulte, Marian; Schlewitz, Gudrun; Alt, Volker; Lips, Katrin Susanne; Faulenbach, Miriam; Möllmann, Henriette; Zahner, Daniel; Dürselen, Lutz; Ignatius, Anita; Bauer, Natali; Wenisch, Sabine; Langheinrich, Alexander Claus; Schnettler, Reinhard; Heiss, Christian

2013-01-01

Many postmenopausal women have vitamin D and calcium deficiency. Therefore, vitamin D and calcium supplementation is recommended for all patients with osteopenia and osteoporosis. We used an experimental rat model to test the hypothesis that induction of osteoporosis is more efficiently achieved in peripheral bone through combining ovariectomy with a unique multi-deficiencies diet (vitamin D depletion and deficient calcium, vitamin K and phosphorus). 14-week-old Sprague-Dawley rats served as controls to examine the initial bone status. 11 rats were bilaterally ovariectomized (OVX) and fed with multi-deficiencies diet. Three months later the treated group and the Sham group (n = 8) were euthanized. Bone biomechanical competence of the diaphyseal bone was examined on both, tibia and femur. Image analysis was performed on tibia via µCT, and on femur via histological analysis. Lower torsional stiffness indicated inferior mechanical competence of the tibia in 3 month OVX+Diet. Proximal metaphyseal region of the tibia showed a diminished bone tissue portion to total tissue in the µCT despite the increased total area as evaluated in both µCT and histology. Cortical bone showed higher porosity and smaller cross sectional thickness of the tibial diaphysis in the OVX+Diet rats. A lower ALP positive area and elevated serum level of RANKL exhibited the unbalanced cellular interaction in bone remodeling in the OVX+Diet rat after 3 month of treatment. Interestingly, more adipose tissue area in bone marrow indicated an effect of bone loss similar to that observed in osteoporotic patients. Nonetheless, the presence of osteoid and elevated serum level of PTH, BGP and Opn suggest the development of osteomalacia rather than an osteoporosis. As the treatment and fracture management of both osteoporotic and osteomalacia patients are clinically overlapping, this study provides a preclinical animal model to be utilized in local supplementation of minerals, drugs and growth factors in future fracture healing studies.

Effects of Multi-Deficiencies-Diet on Bone Parameters of Peripheral Bone in Ovariectomized Mature Rat

PubMed Central

El Khassawna, Thaqif; Böcker, Wolfgang; Govindarajan, Parameswari; Schliefke, Nathalie; Hürter, Britta; Kampschulte, Marian; Schlewitz, Gudrun; Alt, Volker; Lips, Katrin Susanne; Faulenbach, Miriam; Möllmann, Henriette; Zahner, Daniel; Dürselen, Lutz; Ignatius, Anita; Bauer, Natali; Wenisch, Sabine; Langheinrich, Alexander Claus; Schnettler, Reinhard; Heiss, Christian

2013-01-01

Many postmenopausal women have vitamin D and calcium deficiency. Therefore, vitamin D and calcium supplementation is recommended for all patients with osteopenia and osteoporosis. We used an experimental rat model to test the hypothesis that induction of osteoporosis is more efficiently achieved in peripheral bone through combining ovariectomy with a unique multi-deficiencies diet (vitamin D depletion and deficient calcium, vitamin K and phosphorus). 14-week-old Sprague-Dawley rats served as controls to examine the initial bone status. 11 rats were bilaterally ovariectomized (OVX) and fed with multi-deficiencies diet. Three months later the treated group and the Sham group (n = 8) were euthanized. Bone biomechanical competence of the diaphyseal bone was examined on both, tibia and femur. Image analysis was performed on tibia via µCT, and on femur via histological analysis. Lower torsional stiffness indicated inferior mechanical competence of the tibia in 3 month OVX+Diet. Proximal metaphyseal region of the tibia showed a diminished bone tissue portion to total tissue in the µCT despite the increased total area as evaluated in both µCT and histology. Cortical bone showed higher porosity and smaller cross sectional thickness of the tibial diaphysis in the OVX+Diet rats. A lower ALP positive area and elevated serum level of RANKL exhibited the unbalanced cellular interaction in bone remodeling in the OVX+Diet rat after 3 month of treatment. Interestingly, more adipose tissue area in bone marrow indicated an effect of bone loss similar to that observed in osteoporotic patients. Nonetheless, the presence of osteoid and elevated serum level of PTH, BGP and Opn suggest the development of osteomalacia rather than an osteoporosis. As the treatment and fracture management of both osteoporotic and osteomalacia patients are clinically overlapping, this study provides a preclinical animal model to be utilized in local supplementation of minerals, drugs and growth factors in future fracture healing studies. PMID:23977109

Human Bone-Forming Chondrocytes Cultured in the Hydrodynamic Focusing Bioreactor Retain Matrix Proteins: Similarities to Spaceflight Results

NASA Technical Reports Server (NTRS)

Duke, P. J.; Hecht, J.; Montufar-Solis, D.

2006-01-01

Fracture healing, crucial to a successful Mars mission, involves formation of a cartilaginous fracture callus which differentiates, mineralizes, ossifies and remodels via the endochondral process. Studies of spaceflown and tailsuspended rats found that, without loading, fracture callus formation and cartilage differentiation within the callus were minimal. We found delayed differentiation of chondrocytes within the rat growth plate on Cosmos 1887, 2044, and Spacelab 3. In the current study, differentiation of human bone-forming chondrocytes cultured in the hydrodynamic focusing bioreactor (HFB) was assessed. Human costochondral chondrocytes in suspension were aggregated overnight, then cultured in the HFB for 25 days. Collagen Type II, aggrecan and unsulfated chondroitin were found extracellularly and chondroitin sulfates 4 and 6 within the cell. Lack of secretion was also found in pancreatic cells of spaceflown rats, and in our SL3 studies. The HFB can be used to study cartilage differentiation in simulated microgravity.

Osteoporosis affects both post-yield microdamage accumulation and plasticity degradation in vertebra of ovariectomized rats

NASA Astrophysics Data System (ADS)

Li, Siwei; Niu, Guodong; Dong, Neil X.; Wang, Xiaodu; Liu, Zhongjun; Song, Chunli; Leng, Huijie

2017-04-01

Estrogen withdrawal in postmenopausal women increases bone loss and bone fragility in the vertebra. Bone loss with osteoporosis not only reduces bone mineral density (BMD), but actually alters bone quality, which can be comprehensively represented by bone post-yield behaviors. This study aimed to provide some information as to how osteoporosis induced by estrogen depletion could influence the evolution of post-yield microdamage accumulation and plastic deformation in vertebral bodies. This study also tried to reveal the part of the mechanisms of how estrogen deficiency-induced osteoporosis would increase the bone fracture risk. A rat bilateral ovariectomy (OVX) model was used to induce osteoporosis. Progressive cyclic compression loading was developed for vertebra testing to elucidate the post-yield behaviors. BMD, bone volume fraction, stiffness degradation, and plastic deformation evolution were compared among rats raised for 5 weeks (ovx5w and sham5w groups) and 35 weeks (ovx35w and sham35w groups) after sham surgery and OVX. The results showed that a higher bone loss in vertebral bodies corresponded to lower stiffness and higher plastic deformation. Thus, osteoporosis could increase the vertebral fracture risk probably through microdamage accumulation and plastic deforming degradation.

A New Experimental Polytrauma Model in Rats: Molecular Characterization of the Early Inflammatory Response

PubMed Central

Weckbach, Sebastian; Perl, Mario; Heiland, Tim; Braumüller, Sonja; Stahel, Philip F.; Flierl, Michael A.; Ignatius, Anita; Gebhard, Florian; Huber-Lang, Markus

2012-01-01

Background. The molecular mechanisms of the immune response after polytrauma are highly complex and far from fully understood. In this paper, we characterize a new standardized polytrauma model in rats based on the early molecular inflammatory and apoptotic response. Methods. Male Wistar rats (250 g, 6–10/group) were anesthetized and exposed to chest trauma (ChT), closed head injury (CHI), or Tib/Fib fracture including a soft tissue trauma (Fx + STT) or to the following combination of injuries: (1) ChT; (2) ChT + Fx + STT; (3) ChT + CHI; (4) CHI; (5) polytrauma (PT = ChT + CHI + Fx + STT). Sham-operated rats served as negative controls. The inflammatory response was quantified at 2 hours and 4 hours after trauma by analysis of “key” inflammatory mediators, including selected cytokines and complement components, in serum and bronchoalveolar (BAL) fluid samples. Results. Polytraumatized (PT) rats showed a significant systemic and intrapulmonary release of cytokines, chemokines, and complement anaphylatoxins, compared to rats with isolated injuries or selected combinations of injuries. Conclusion. This new rat model appears to closely mimic the early immunological response of polytrauma observed in humans and may provide a valid basis for evaluation of the complex pathophysiology and future therapeutic immune modulatory approaches in experimental polytrauma. PMID:22481866

Gap junctions on hippocampal mossy fiber axons demonstrated by thin-section electron microscopy and freeze–fracture replica immunogold labeling

PubMed Central

Hamzei-Sichani, Farid; Kamasawa, Naomi; Janssen, William G. M.; Yasumura, Thomas; Davidson, Kimberly G. V.; Hof, Patrick R.; Wearne, Susan L.; Stewart, Mark G.; Young, Steven R.; Whittington, Miles A.; Rash, John E.; Traub, Roger D.

2007-01-01

Gap junctions have been postulated to exist between the axons of excitatory cortical neurons based on electrophysiological, modeling, and dye-coupling data. Here, we provide ultrastructural evidence for axoaxonic gap junctions in dentate granule cells. Using combined confocal laser scanning microscopy, thin-section transmission electron microscopy, and grid-mapped freeze–fracture replica immunogold labeling, 10 close appositions revealing axoaxonic gap junctions (≈30–70 nm in diameter) were found between pairs of mossy fiber axons (≈100–200 nm in diameter) in the stratum lucidum of the CA3b field of the rat ventral hippocampus, and one axonal gap junction (≈100 connexons) was found on a mossy fiber axon in the CA3c field of the rat dorsal hippocampus. Immunogold labeling with two sizes of gold beads revealed that connexin36 was present in that axonal gap junction. These ultrastructural data support computer modeling and in vitro electrophysiological data suggesting that axoaxonic gap junctions play an important role in the generation of very fast (>70 Hz) network oscillations and in the hypersynchronous electrical activity of epilepsy. PMID:17640909

Skeletal Structural Consequences of Reduced Gravity Environments

NASA Technical Reports Server (NTRS)

Ruff, Christropher B.

1999-01-01

The overall goal of this project is to provide structurally meaningful data on bone loss after exposure to reduced gravity environments so that more precise estimates of fracture risk and the effectiveness of countermeasures in reducing fracture risk can be developed. The project has three major components: (1) measure structural changes in the limb bones of rats subjected to complete and partial nonweightbearing, with and without treatment with ibandronate and periodic full weightbearing; (2) measure structural changes in the limb bones of human bedrest subjects, with and without treatment with alendronate and resistive exercise, and Russian cosmonauts flying on the Mir Space Station; and (3) validate and extend the 2-dimensional structural analyses currently possible in the second project component (bedrest and Mir subjects) using 3-dimensional finite element modeling techniques, and determine actual fracture-producing loads on earth and in space.

Epistasis between QTLs for bone density variation in Copenhagen × dark agouti F2 rats

PubMed Central

Liu, Lixiang; Alam, Imranul; Sun, Qiwei; Econs, Michael J.; Foroud, Tatiana; Turner, Charles H.

2010-01-01

The variation in several of the risk factors for osteoporotic fracture, including bone mineral density (BMD), has been shown to be strongly influenced by genetic differences. However, the genetic architecture of BMD is complex in both humans and in model organisms. We previously reported quantitative trait locus (QTL) results for BMD from a genome screen of 828 F2 progeny of Copenhagen and dark agouti rats. These progeny also provide an excellent opportunity to search for epistatic effects, or interaction between genetic loci, that contribute to fracture risk. Microsatellite marker data from a 20-cM genome screen was analyzed along with weight-adjusted bone density (DXA and pQCT) phenotypic data using the R/qtl software package. Genotype and phenotype data were permuted to determine genome-wide significance thresholds for the full model and epistasis (interaction) LOD scores corresponding to an alpha level of 0.01. A novel locus on chromosome 15 and a previously reported chromosome 14 QTL demonstrated a strong epistatic effect on BMD at the femur by DXA (LOD = 5.4). Two novel QTLs on chromosomes 2 and 12 were found to interact to affect total BMD at the femur midshaft by pQCT (LOD = 5.0). These results provide new information regarding the mode of action of previously identified QTL in the rat, as well as identifying novel loci that act in combination with known QTL or with other novel loci to contribute to BMD variation. PMID:19153792

Epistasis between QTLs for bone density variation in Copenhagen x dark agouti F2 rats.

PubMed

Koller, Daniel L; Liu, Lixiang; Alam, Imranul; Sun, Qiwei; Econs, Michael J; Foroud, Tatiana; Turner, Charles H

2009-03-01

The variation in several of the risk factors for osteoporotic fracture, including bone mineral density (BMD), has been shown to be strongly influenced by genetic differences. However, the genetic architecture of BMD is complex in both humans and in model organisms. We previously reported quantitative trait locus (QTL) results for BMD from a genome screen of 828 F2 progeny of Copenhagen and dark agouti rats. These progeny also provide an excellent opportunity to search for epistatic effects, or interaction between genetic loci, that contribute to fracture risk. Microsatellite marker data from a 20-cM genome screen was analyzed along with weight-adjusted bone density (DXA and pQCT) phenotypic data using the R/qtl software package. Genotype and phenotype data were permuted to determine genome-wide significance thresholds for the full model and epistasis (interaction) LOD scores corresponding to an alpha level of 0.01. A novel locus on chromosome 15 and a previously reported chromosome 14 QTL demonstrated a strong epistatic effect on BMD at the femur by DXA (LOD = 5.4). Two novel QTLs on chromosomes 2 and 12 were found to interact to affect total BMD at the femur midshaft by pQCT (LOD = 5.0). These results provide new information regarding the mode of action of previously identified QTL in the rat, as well as identifying novel loci that act in combination with known QTL or with other novel loci to contribute to BMD variation.

Pulsed ultrasounds accelerate healing of rib fractures in an experimental animal model: an effective new thoracic therapy?

PubMed

Santana-Rodríguez, Norberto; Clavo, Bernardino; Fernández-Pérez, Leandro; Rivero, José C; Travieso, María M; Fiuza, María D; Villar, Jesús; García-Castellano, José M; Hernández-Pérez, Octavio; Déniz, Antonio

2011-05-01

Rib fractures are a frequent traumatic injury associated with a relatively high morbidity. Currently, the treatment of rib fractures is symptomatic. Since it has been reported that pulsed ultrasounds accelerates repair of limb fractures, we hypothesized that the application of pulsed ultrasounds will modify the course of healing in an animal model of rib fracture. We studied 136 male Sprague-Dawley rats. Animals were randomly assigned to different groups of doses (none, 50, 100, and 250 mW/cm(2) of intensity for 3 minutes per day) and durations (2, 10, 20, and 28 days) of treatment with pulsed ultrasounds. In every subgroup, we analyzed radiologic and histologic changes in the bone callus. In addition, we examined changes in gene expression of relevant genes involved in wound repair in both control and treated animals. Histologic and radiologic consolidation was significantly increased by pulsed ultrasound treatment when applied for more than 10 days. The application of 50 mW/cm(2) was the most effective dose. Only the 100 and 250 mW/cm(2) doses were able to significantly increase messenger RNA expression of insulin-like growth factor 1, suppressor of cytokine signaling-2 and -3, and vascular endothelial growth factor and decrease monocyte chemoattractant protein-1 and collagen type II-alpha 1. Our findings indicate that pulsed ultrasound accelerates the consolidation of rib fractures. This study is the first to show that pulsed ultrasound promotes the healing of rib fractures. From a translational point of view, this easy, cheap technique could serve as an effective new therapeutic modality in patients with rib fractures. Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Podoplanin immunopositive lymphatic vessels at the implant interface in a rat model of osteoporotic fractures.

PubMed

Lips, Katrin Susanne; Kauschke, Vivien; Hartmann, Sonja; Thormann, Ulrich; Ray, Seemun; Kampschulte, Marian; Langheinrich, Alexander; Schumacher, Matthias; Gelinsky, Michael; Heinemann, Sascha; Hanke, Thomas; Kautz, Armin R; Schnabelrauch, Matthias; Schnettler, Reinhard; Heiss, Christian; Alt, Volker; Kilian, Olaf

2013-01-01

Insertion of bone substitution materials accelerates healing of osteoporotic fractures. Biodegradable materials are preferred for application in osteoporotic patients to avoid a second surgery for implant replacement. Degraded implant fragments are often absorbed by macrophages that are removed from the fracture side via passage through veins or lymphatic vessels. We investigated if lymphatic vessels occur in osteoporotic bone defects and whether they are regulated by the use of different materials. To address this issue osteoporosis was induced in rats using the classical method of bilateral ovariectomy and additional calcium and vitamin deficient diet. In addition, wedge-shaped defects of 3, 4, or 5 mm were generated in the distal metaphyseal area of femur via osteotomy. The 4 mm defects were subsequently used for implantation studies where bone substitution materials of calcium phosphate cement, composites of collagen and silica, and iron foams with interconnecting pores were inserted. Different materials were partly additionally functionalized by strontium or bisphosphonate whose positive effects in osteoporosis treatment are well known. The lymphatic vessels were identified by immunohistochemistry using an antibody against podoplanin. Podoplanin immunopositive lymphatic vessels were detected in the granulation tissue filling the fracture gap, surrounding the implant and growing into the iron foam through its interconnected pores. Significant more lymphatic capillaries were counted at the implant interface of composite, strontium and bisphosphonate functionalized iron foam. A significant increase was also observed in the number of lymphatics situated in the pores of strontium coated iron foam. In conclusion, our results indicate the occurrence of lymphatic vessels in osteoporotic bone. Our results show that lymphatic vessels are localized at the implant interface and in the fracture gap where they might be involved in the removal of lymphocytes, macrophages, debris and the implants degradation products. Therefore the lymphatic vessels are involved in implant integration and fracture healing.

Podoplanin Immunopositive Lymphatic Vessels at the Implant Interface in a Rat Model of Osteoporotic Fractures

PubMed Central

Lips, Katrin Susanne; Kauschke, Vivien; Hartmann, Sonja; Thormann, Ulrich; Ray, Seemun; Kampschulte, Marian; Langheinrich, Alexander; Schumacher, Matthias; Gelinsky, Michael; Heinemann, Sascha; Hanke, Thomas; Kautz, Armin R.; Schnabelrauch, Matthias; Schnettler, Reinhard; Heiss, Christian; Alt, Volker; Kilian, Olaf

2013-01-01

Insertion of bone substitution materials accelerates healing of osteoporotic fractures. Biodegradable materials are preferred for application in osteoporotic patients to avoid a second surgery for implant replacement. Degraded implant fragments are often absorbed by macrophages that are removed from the fracture side via passage through veins or lymphatic vessels. We investigated if lymphatic vessels occur in osteoporotic bone defects and whether they are regulated by the use of different materials. To address this issue osteoporosis was induced in rats using the classical method of bilateral ovariectomy and additional calcium and vitamin deficient diet. In addition, wedge-shaped defects of 3, 4, or 5 mm were generated in the distal metaphyseal area of femur via osteotomy. The 4 mm defects were subsequently used for implantation studies where bone substitution materials of calcium phosphate cement, composites of collagen and silica, and iron foams with interconnecting pores were inserted. Different materials were partly additionally functionalized by strontium or bisphosphonate whose positive effects in osteoporosis treatment are well known. The lymphatic vessels were identified by immunohistochemistry using an antibody against podoplanin. Podoplanin immunopositive lymphatic vessels were detected in the granulation tissue filling the fracture gap, surrounding the implant and growing into the iron foam through its interconnected pores. Significant more lymphatic capillaries were counted at the implant interface of composite, strontium and bisphosphonate functionalized iron foam. A significant increase was also observed in the number of lymphatics situated in the pores of strontium coated iron foam. In conclusion, our results indicate the occurrence of lymphatic vessels in osteoporotic bone. Our results show that lymphatic vessels are localized at the implant interface and in the fracture gap where they might be involved in the removal of lymphocytes, macrophages, debris and the implants degradation products. Therefore the lymphatic vessels are involved in implant integration and fracture healing. PMID:24130867

Time-Dependent Changes in T1 during Fracture Healing in Juvenile Rats: A Quantitative MR Approach

PubMed Central

Baron, Katharina; Neumayer, Bernhard; Amerstorfer, Eva; Scheurer, Eva; Diwoky, Clemens; Stollberger, Rudolf; Sprenger, Hanna; Weinberg, Annelie M.

2016-01-01

Quantitative magnetic resonance imaging (qMRI) offers several advantages in imaging and determination of soft tissue alterations when compared to qualitative imaging techniques. Although applications in brain and muscle tissues are well studied, its suitability to quantify relaxation times of intact and injured bone tissue, especially in children, is widely unknown. The objective observation of a fracture including its age determination can become of legal interest in cases of child abuse or maltreatment. Therefore, the aim of this study is the determination of time dependent changes in intact and corresponding injured bones in immature rats via qMRI, to provide the basis for an objective and radiation-free approach for fracture dating. Thirty-five MR scans of 7 Sprague-Dawley rats (male, 4 weeks old, 100 ± 5 g) were acquired on a 3T MRI scanner (TimTrio, Siemens AG, Erlangen, Germany) after the surgical infliction of an epiphyseal fracture in the tibia. The images were taken at days 1, 3, 7, 14, 28, 42 and 82 post-surgery. A proton density-weighted and a T1-weighted 3D FLASH sequence were acquired to calculate the longitudinal relaxation time T1 of the fractured region and the surrounding tissues. The calculation of T1 in intact and injured bone resulted in a quantitative observation of bone development in intact juvenile tibiae as well as the bone healing process in the injured tibiae. In both areas, T1 decreased over time. To evaluate the differences in T1 behaviour between the intact and injured bone, the relative T1 values (bone-fracture) were calculated, showing clear detectable alterations of T1 after fracture occurrence. These results indicate that qMRI has a high potential not only for clinically relevant applications to detect growth defects or developmental alterations in juvenile bones, but also for forensically relevant applications such as the dating of fractures in cases of child abuse or maltreatment. PMID:27832068

The role of hesperetin on osteogenesis of human mesenchymal stem cells and its function in bone regeneration.

PubMed

Xue, Deting; Chen, Erman; Zhang, Wei; Gao, Xiang; Wang, Shengdong; Zheng, Qiang; Pan, Zhijun; Li, Hang; Liu, Ling

2017-03-28

Hesperetin has been suggested to be involved in bone strength. We aimed to investigate the effects of hesperetin on the osteogenic differentiation of human mesenchymal stem cells and its related mechanisms. We showed that hesperetin promoted osteogenic differentiation of human mesenchymal stem cells in vitro. It potentially exerts its effects via the ERK and Smad signaling pathways. Using a rat osteotomy model, we showed that human mesenchymal stem cells combined with a hesperetin/gelatin sponge scaffold resulted in accelerated fracture healing in vivo. Due to the low cost of hesperetin, it could be used as a growth factor for bone tissue engineering or surgical fracture treatment.

Targeting Transforming Growth Factor Beta to Enhance the Fracture Resistance of Bone

DTIC Science & Technology

2013-01-01

Transforming Growth Factor Beta to Enhance the Fracture Resistance of Bone is to determine whether the suppression of TGF-β activity improves the fracture...effect primarily occurred in the old rats. Effect of TGF-β suppression on fracture resistance in female mice Since the suppression of TGF-β activity by...treated mice. This suggests that 1D11 treatment depleted the osteoprogenitor pool to some extent as inhibition of TGF-β activity in vivo may favor

Cortical Bone Mechanical Properties Are Altered in an Animal Model of Progressive Chronic Kidney Disease

PubMed Central

Newman, Christopher L.; Moe, Sharon M.; Chen, Neal X.; Hammond, Max A.; Wallace, Joseph M.; Nyman, Jeffry S.; Allen, Matthew R.

2014-01-01

Chronic kidney disease (CKD), which leads tocortical bone loss and increasedporosity,increases therisk of fracture. Animal models have confirmed that these changes compromise whole bone mechanical properties. Estimates from whole bone testing suggest that material properties are negatively affected, though tissue-level assessmentshavenot been conducted. Therefore, the goal of the present study was to examine changes in cortical bone at different length scales using a rat model with theprogressive development of CKD. At 30 weeks of age (∼75% reduction in kidney function), skeletally mature male Cy/+ rats were compared to their normal littermates. Cortical bone material propertieswere assessed with reference point indentation (RPI), atomic force microscopy (AFM), Raman spectroscopy,and high performance liquid chromatography (HPLC). Bones from animals with CKD had higher (+18%) indentation distance increase and first cycle energy dissipation (+8%) as measured by RPI.AFM indentation revealed a broader distribution of elastic modulus values in CKD animals witha greater proportion of both higher and lower modulus values compared to normal controls. Yet, tissue composition, collagen morphology, and collagen cross-linking fail to account for these differences. Though the specific skeletal tissue alterations responsible for these mechanical differences remain unclear, these results indicate that cortical bone material properties are altered in these animals and may contribute to the increased fracture risk associated with CKD. PMID:24911162

The effects of honey (Apis dorsata) supplements on increased bone strength in ovariectomized rat as animal model of osteoporosis

NASA Astrophysics Data System (ADS)

Yudaniayanti, Ira Sari; Primarizky, Hardany; Nangoi, Lianny

2018-04-01

Osteoporosis is a chronic skeletal disease characterized by low bone mass and microarchitectural deterioration with a consequent increase in bone fragility and fracture risk. The aim of the study was to evaluate the effects of honey (Apis dorsata) supplements on increased bone strength in ovariectomized rat as animal models of osteoporosis. Twenty female rats at 3 months of age, weighing 150-200 g were used in the study. The rats were divided into five groups (n=4) : Sham operation group (SH); ovariectomy group no treatment(OVX); ovariectomy with treatment Apis dorsata 1g/Kg BW (AD-1); ovariectomy with treatment Apis dorsata 2g/Kg BW (AD-2); ovariectomy with treatment Apis dorsata 4g/Kg BW (AD-3). The treatment started to be given the next day after ovariectomy operation for 12 weeks. The Rats were sacrified within 12 weeks, and then the right femur were taken bone strength test. Based on the statistical analysis of the bone strength test, the greatest score belongs to the Sham operation group (SH) that have significant difference (p<0.05) with OVX group and AD-1 group, but there was no significant difference with AD-2 and AD-3 (p>0,05). In conclusion, honey (Apis dorsata) supplements has the effect of increasing bone strength in ovariectomized rat as animal models of osteoporosis, so that honey (Apis dorsata) supplements has the potential to be used as an alternative treatment for osteoporosis.

Piper sarmentosum enhances fracture healing in ovariectomized osteoporotic rats: a radiological study.

PubMed

Estai, Mohamed Abdalla; Suhaimi, Farihah Haji; Das, Srijit; Fadzilah, Fazalina Mohd; Alhabshi, Sharifah Majedah Idrus; Shuid, Ahmad Nazrun; Soelaiman, Ima-Nirwana

2011-01-01

Osteoporotic fractures are common during osteoporotic states. Piper sarmentosum extract is known to possess antioxidant and anti-inflammatory properties. To observe the radiological changes in fracture calluses following administration of a Piper sarmentosum extract during an estrogen-deficient state. A total of 24 female Sprague-Dawley rats (200-250 g) were randomly divided into 4 groups: (i) the sham-operated group; (ii) the ovariectomized-control group; (iii) the ovariectomized + estrogen-replacement therapy (ovariectomized-control + estrogen replacement therapy) group, which was supplemented with estrogen (100 μg/kg/day); and (iv) the ovariectomized + Piper sarmentosum (ovariectomized + Piper sarmentosum) group, which was supplemented with a water-based Piper sarmentosum extract (125 mg/kg). Six weeks after an ovariectomy, the right femora were fractured at the mid-diaphysis, and a K-wire was inserted. Each group of rats received their respective treatment for 6 weeks. Following sacrifice, the right femora were subjected to radiological assessment. The mean axial callus volume was significantly higher in the ovariectomized-control group (68.2 ± 11.74 mm³) than in the sham-operated, estrogen-replacement-therapy and Piper sarmentosum groups (20.4 ± 4.05, 22.4 ± 4.14 and 17.5 ± 3.68 mm³, respectively). The median callus scores for the sham-operated, estrogen-replacement-therapy and Piper sarmentosum groups had median (range, minimum - maximum value) as 1.0 (0 - 2), 1.0 (1 - 2) and 1.0 (1 - 2), respectively, which were significantly lower than the ovariectomized-control group score of 2.0 (2 - 3). The median fracture scores for the sham-operated, estrogen-replacement-therapy and Piper sarmentosum groups were 3.0 (3 - 4), 3.0 (2 - 3) and 3.0 (2 - 3), respectively, which were significantly higher than the ovariectomized-control group score of 2.0 (1 - 2) (p<0.05). The Piper sarmentosum extract improved fracture healing, as assessed by the reduced callus volumes and reduced callus scores. This extract is beneficial for fractures in osteoporotic states.

Evaluation of the Effects of Photobiomodulation on Partial Osteotomy in Streptozotocin-Induced Diabetes in Rats.

PubMed

Mostafavinia, Ataroalsadat; Masteri Farahani, Reza; Abdollahifar, Mohammad-Amin; Ghatrehsamani, Mahdi; Ghoreishi, Seyed Kamran; Hajihossainlou, Behnam; Chien, Sufan; Dadras, Sara; Rezaei, Fatemehalsadat; Bayat, Mohammad

2018-05-31

We examined the effects of photobiomodulation (PBM) on stereological parameters, and gene expression of Runt-related transcription factor 2 (RUNX2), osteocalcin, and receptor activator of nuclear factor kappa-B ligand (RANKL) in repairing tissue of tibial bone defect in streptozotocin (STZ)-induced type 1 diabetes mellitus (TIDM) in rats during catabolic response of fracture healing. There were conflicting results regarding the efficacy of PBM on bone healing process in healthy and diabetic animals. Forty-eight rats have been distributed into four groups: group 1 (healthy control, no TIDM and no PBM), group 2 (healthy test, no TIDM and PBM), group 3 (diabetic control, TIDM and no PBM), and group 4 (diabetic test, no TIDM and PBM). TIDM was induced in the groups 3 and 4. A partial bone defect in tibia was made in all groups. The bone defects of groups second and fourth were irradiated by a laser (890 nm, 80 Hz, 1.5 J/cm 2 ). Thirty days after the surgery, all bone defects were extracted and were submitted to stereological examination and real-time polymerase chain reaction (RT-PCR). PBM significantly increased volumes of total callus, total bone, bone marrow, trabecular bone, and cortical bone, and the numbers of osteocytes and osteoblasts of callus in TIDM rats compared to those of callus in diabetic control. In addition, TIDM increased RUNX2, and osteocalcin in callus of tibial bone defect compared to healthy group. PBM significantly decreased osteocalcin gene expression in TIDM rats. PBM significantly increased many stereological parameters of bone repair in an STZ-induced TIDM during catabolic response of fracture healing. Further RT-PCR test demonstrated that bone repair was modulated in diabetic rats during catabolic response of fracture healing by significant increase in mRNA expression of RUNX2, and osteocalcin compared to healthy control rats. PBM also decreased osteocalcin mRNA expression in TIDM rats.

Protective Effect of Chokeberry (Aronia melanocarpa L.) Extract against Cadmium Impact on the Biomechanical Properties of the Femur: A Study in a Rat Model of Low and Moderate Lifetime Women Exposure to This Heavy Metal

PubMed Central

Brzóska, Małgorzata M.; Roszczenko, Alicja; Rogalska, Joanna; Gałażyn-Sidorczuk, Małgorzata; Mężyńska, Magdalena

2017-01-01

The hypothesis that the consumption of Aronia melanocarpa berries (chokeberries) extract, recently reported by us to improve bone metabolism in female rats at low-level and moderate chronic exposure to cadmium (1 and 5 mg Cd/kg diet for up to 24 months), may increase the bone resistance to fracture was investigated. Biomechanical properties of the neck (bending test with vertical head loading) and diaphysis (three-point bending test) of the femur of rats administered 0.1% aqueous chokeberry extract (65.74% of polyphenols) or/and Cd in the diet (1 and 5 mg Cd/kg) for 3, 10, 17, and 24 months were evaluated. Moreover, procollagen I was assayed in the bone tissue. The low-level and moderate exposure to Cd decreased the procollagen I concentration in the bone tissue and weakened the biomechanical properties of the femoral neck and diaphysis. Chokeberry extract administration under the exposure to Cd improved the bone collagen biosynthesis and femur biomechanical properties. The results allow for the conclusion that the consumption of chokeberry products under exposure to Cd may improve the bone biomechanical properties and protect from fracture. This study provides support for Aronia melanocarpa berries being a promising natural agent for skeletal protection under low-level and moderate chronic exposure to Cd. PMID:28587093

Protective Effect of Chokeberry (Aronia melanocarpa L.) Extract against Cadmium Impact on the Biomechanical Properties of the Femur: A Study in a Rat Model of Low and Moderate Lifetime Women Exposure to This Heavy Metal.

PubMed

Brzóska, Małgorzata M; Roszczenko, Alicja; Rogalska, Joanna; Gałażyn-Sidorczuk, Małgorzata; Mężyńska, Magdalena

2017-05-25

The hypothesis that the consumption of Aronia melanocarpa berries (chokeberries) extract, recently reported by us to improve bone metabolism in female rats at low-level and moderate chronic exposure to cadmium (1 and 5 mg Cd/kg diet for up to 24 months), may increase the bone resistance to fracture was investigated. Biomechanical properties of the neck (bending test with vertical head loading) and diaphysis (three-point bending test) of the femur of rats administered 0.1% aqueous chokeberry extract (65.74% of polyphenols) or/and Cd in the diet (1 and 5 mg Cd/kg) for 3, 10, 17, and 24 months were evaluated. Moreover, procollagen I was assayed in the bone tissue. The low-level and moderate exposure to Cd decreased the procollagen I concentration in the bone tissue and weakened the biomechanical properties of the femoral neck and diaphysis. Chokeberry extract administration under the exposure to Cd improved the bone collagen biosynthesis and femur biomechanical properties. The results allow for the conclusion that the consumption of chokeberry products under exposure to Cd may improve the bone biomechanical properties and protect from fracture. This study provides support for Aronia melanocarpa berries being a promising natural agent for skeletal protection under low-level and moderate chronic exposure to Cd.

Bone mineral density, chemical composition and biomechanical properties of the tibia of female rats exposed to cadmium since weaning up to skeletal maturity.

PubMed

Brzóska, M M; Majewska, K; Moniuszko-Jakoniuk, J

2005-10-01

The influence of exposure to cadmium (Cd) during skeletal development on the risk of bone fractures at the stage of skeletal maturity was investigated on a female rat model of human exposure. The tibias of rats treated with 1, 5 or 50 mg Cd/l in drinking water for 3, 6, 9 and 12 months (since weaning) were used. The exposure to Cd dose- and time-dependently influenced the tibia bone mineral density (BMD) and chemical composition. In skeletally matured animals, at each level of the exposure to Cd, the BMD at the whole tibia and its diaphysis as well as the percentage of minerals content in the bone, including the content of zinc, copper and iron, were decreased compared to control. Moreover, in the 50 mg Cd/l group, the percentage of organic components content increased. The Cd-induced changes, at all levels of exposure, resulted in weakening in the yield strength and fracture strength of the tibia (a three-point bending test of the diaphysis and compression test with vertical loading) of the skeletally matured females. A very important and clinically useful finding of this study is that a decrease (even by several percent) in the tibia BMD results in weakness in the bone biomechanical properties and that the BMD may predict the risk of its fracture at the exposure to Cd. Moreover, the results together with our previous findings seem to suggest that tibia, due to higher vulnerability of its diaphysis, compared to the femoral diaphysis, to damage by Cd may be more useful than femur to investigate the effect of Cd on the cortical bone. The present study revealed that a low exposure to Cd (1 mg Cd/l), corresponding to low human environmental exposure, during the skeletal development affects the tibia mineral status leading to weakening in its mechanical properties at the skeletal maturity. The findings allow for the conclusion that environmental exposure to Cd during childhood and adolescence may enhance the risk of low BMD and fractures at adulthood.

Estimating the Potential Toxicity of Chemicals Associated with Hydraulic Fracturing Operations Using Quantitative Structure-Activity Relationship Modeling.

PubMed

Yost, Erin E; Stanek, John; DeWoskin, Robert S; Burgoon, Lyle D

2016-07-19

The United States Environmental Protection Agency (EPA) identified 1173 chemicals associated with hydraulic fracturing fluids, flowback, or produced water, of which 1026 (87%) lack chronic oral toxicity values for human health assessments. To facilitate the ranking and prioritization of chemicals that lack toxicity values, it may be useful to employ toxicity estimates from quantitative structure-activity relationship (QSAR) models. Here we describe an approach for applying the results of a QSAR model from the TOPKAT program suite, which provides estimates of the rat chronic oral lowest-observed-adverse-effect level (LOAEL). Of the 1173 chemicals, TOPKAT was able to generate LOAEL estimates for 515 (44%). To address the uncertainty associated with these estimates, we assigned qualitative confidence scores (high, medium, or low) to each TOPKAT LOAEL estimate, and found 481 to be high-confidence. For 48 chemicals that had both a high-confidence TOPKAT LOAEL estimate and a chronic oral reference dose from EPA's Integrated Risk Information System (IRIS) database, Spearman rank correlation identified 68% agreement between the two values (permutation p-value =1 × 10(-11)). These results provide support for the use of TOPKAT LOAEL estimates in identifying and prioritizing potentially hazardous chemicals. High-confidence TOPKAT LOAEL estimates were available for 389 of 1026 hydraulic fracturing-related chemicals that lack chronic oral RfVs and OSFs from EPA-identified sources, including a subset of chemicals that are frequently used in hydraulic fracturing fluids.

Differences of bone healing in metaphyseal defect fractures between osteoporotic and physiological bone in rats.

PubMed

Thormann, Ulrich; El Khawassna, Thaqif; Ray, Seemun; Duerselen, Lutz; Kampschulte, Marian; Lips, Katrin; von Dewitz, Helena; Heinemann, Sascha; Heiss, Christian; Szalay, Gabor; Langheinrich, Alexander C; Ignatius, Anita; Schnettler, Reinhard; Alt, Volker

2014-03-01

Discrepancies in bone healing between osteoporotic and non-osteoporotic bone remain uncertain. The focus of the current work is to evaluate potential healing discrepancies in a metaphyseal defect model in rat femora. Female Sprague-Dawley rats were either ovariectomized (OVX, n=14) and combined with a calcium-, phosphorus- and vitamin D3-, soy- and phytoestrogen-free diet or received SHAM operation with standard diet rat (SHAM, n=14). Three months post-ovariectomy, DEXA measurement showed a reduction of bone mineral density reflecting an osteoporotic bone status in OVX rats. Rats then underwent a 3 mm wedge-shaped osteotomy at the distal metaphyseal area of the left femur stabilized with a T-shaped mini-plate and allowed to heal for 6 weeks. Biomechanical competence by means of a non-destructive three-point bending test showed significant lower flexural rigidity in the OVX rats at 3 mm lever span compared to SHAM animals (p=0.048) but no differences at 10 mm lever span. Microcomputer tomography (μCT) showed bridging cortices and consolidation of the defect in both groups, however, no measurable differences were found in either total ossified tissue or vascular volume fraction. Furthermore, histology showed healing discrepancies that were characterized by cartilaginous remnant and more unmineralized tissue presence in the OVX rats compared to more mature consolidation appearance in the SHAM group. In summary, bone defect healing in metaphyseal bone slightly differs between osteoporotic and non-osteoporotic bone in the current 3 mm defect model in both 3mm lever span biomechanical testing and histology. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Reparative Osteogenesis and Angiogenesis in Low Intensity Electromagnetic Radiation of Ultra-High Frequency].

PubMed

Iryanov, Y M; Kiryanov, N A

2015-01-01

Non-drug correction of reparative bone tissue regeneration in different pathological states - one of the most actual problems of modern medicine. Our aim was to conduct morphological analysis of the influence of electromagnetic radiation of ultra-high frequency and low intensity on reparative osteogenesis and angiogenesis in fracture treatment under transosseous osteosynthesis. A controlled nonrandomized study was carried out. In the experiment conducted on rats we modeled tibial fracture with reposition and fixation of the bone fragments both in control and experimental groups. In the animals of the experimental group the fracture zone was exposed to low intensity electromagnetic radiation of ultra-high frequency. Exposure simulation was performed in the control group. The operated bones were examined using radiography, light and electronic microscopy, X-ray electronic probe microanalysis. It has been established that electromagnetic radiation of ultra-high frequency sessions in fracture treatment stimulate secretory activity and degranulation of mast cells, produce microcirculatory bed vascular permeability increase, endotheliocyte migration phenotype expression, provide endovascular endothelial outgrowth formation, activate reparative osteogenesis and angiogenesis while fracture reparation becomes the one of the primary type. The full periosteal, intermediary and intraosteal bone union was defined in 28 days. Among the therapeutic benefits of electromagnetic radiation of ultra-high frequency in fracture treatment we can detect mast cell secretorv activity stimulation and endovascular anziozenesis activation.

The effect of Amifostine prophylaxis on bone densitometry, biomechanical strength and union in mandibular pathologic fracture repair.

PubMed

Tchanque-Fossuo, Catherine N; Donneys, Alexis; Sarhaddi, Deniz; Poushanchi, Behdod; Deshpande, Sagar S; Weiss, Daniela M; Buchman, Steven R

2013-11-01

Pathologic fractures (Fx) of the mandibles are severely debilitating consequences of radiation (XRT) in the treatment of craniofacial malignancy. We have previously demonstrated Amifostine's effect (AMF) in the remediation of radiation-induced cellular damage. We posit that AMF prophylaxis will preserve bone strength and drastically reverse radiotherapy-induced non-union in a murine mandibular model of pathologic fracture repair. Twenty-nine rats were randomized into 3 groups: Fx, XRT/Fx, and AMF/XRT/Fx. A fractionated human equivalent dose of radiation was delivered to the left hemimandibles of XRT/Fx and AMF/XRT/Fx. AMF/XRT/Fx was pre-treated with AMF. All groups underwent left mandibular osteotomy with external fixation and setting of a 2.1mm fracture gap post-operatively. Utilizing micro-computed tomography and biomechanical testing, the healed fracture was evaluated for strength. All radiomorphometrics and biomechanical properties were significantly diminished in XRT/Fx compared to both Fx and AMF/XRT/Fx. No difference was demonstrated between Fx and AMF/XRT/Fx in both outcomes. Our investigation establishes the significant and substantial capability of AMF prophylaxis to preserve and enhance bone union, quality and strength in the setting of human equivalent radiotherapy. Such novel discoveries establish the true potential to utilize pharmacotherapy to prevent and improve the treatment outcomes of radiation-induced late pathologic fractures. © 2013.

Amifostine Prophylaxis on Bone Densitometry, Biomechanical Strength and Union in Mandibular Pathologic Fracture Repair

PubMed Central

Tchanque-Fossuo, Catherine N.; Donneys, Alexis; Sarhaddi, Deniz; Poushanchi, Behdod; Deshpande, Sagar S.; Weiss, Daniela M.

2013-01-01

Background Pathologic fractures (Fx) of the mandibles are severely debilitating consequences of radiation (XRT) in the treatment of craniofacial malignancy. We have previously demonstrated Amifostine’s effect (AMF) in the remediation of radiation-induced cellular damage. We posit that AMF prophylaxis will preserve bone strength and drastically reverse radiotherapy-induced non-union in a murine mandibular model of pathologic fracture repair. Materials and Methods Twenty-nine rats were randomized into 3 groups: Fx, XRT/Fx, and AMF/XRT/Fx. A fractionated human equivalent dose of radiation was delivered to the left hemimandibles of XRT/Fx and AMF/XRT/Fx. AMF/XRT/Fx was pre-treated with AMF. All groups underwent left mandibular osteotomy with external fixation and setting of a 2.1mm fracture gap post-operatively. Utilizing micro-computed tomography and biomechanical testing, the healed fracture was evaluated for strength. Results All radiomorphometrics and biomechanical properties were significantly diminished in XRT/Fx compared to both Fx and AMF/XRT/Fx. No difference was demonstrated between Fx and AMF/XRT/Fx in both outcomes. Conclusion Our investigation establishes the significant and substantial capability of AMF prophylaxis to preserve and enhance bone union, quality and strength in the setting of human equivalent radiotherapy. Such novel discoveries establish the true potential to utilize pharmacotherapy to prevent and improve the treatment outcomes of radiation-induced late pathologic fractures. PMID:23860272

Effect of strontium ranelate on fracture healing in rat tibia.

PubMed

Cebesoy, Oguz; Tutar, Ediz; Kose, Kamil Cagri; Baltaci, Yasemin; Bagci, Cahit

2007-12-01

Various anti-osteoporotic agents are available for clinical use. In contrast to other anti-osteoporotic drugs, strontium ranelate has anti-resorptive and bone-forming effects (dual action). Our objective in the present study is to investigate the efficacy of strontium ranelate (SR) on fracture healing in rat tibia. Forty-two male Wistar rats randomized into two groups (groups 1 and 2, n=21 for each). Left tibiae of all animals were broken in a closed manner using a manual three-point bending technique through mid-tibia following deep anesthesia with ketamine. The animals in group 1 were fed 25g/day specially produced food containing 450mg/kg SR starting from the first post-operative day. Group 2 were given 25g/day normal food. The animals were sacrificed on the 2nd, 3rd and 4th post-operative weeks (each week 7 animals were sacrificed from each group) and the broken tibiae were removed. The tibiae were examined first radiographically and second, histopathologically. Radiologically, callus maturity and bone union increased with time in both groups. But no significant differences were found regarding callus maturity and bone union in weekly comparisons (p=0.52, p=0.19, p=0.74). Histopathologically, it was seen that the fractures remarkably healed steadily in both groups on the 2nd, 3rd and 4th post-operative weeks. But no significant differences were found regarding the progression of fracture callus in weekly comparison (p=1.0, p=0.52, p=1.0). In the present study, we were unable to find any beneficial or harmful effects of strontium ranelate on fracture healing.

An Efficient and Reproducible Protocol for Distraction Osteogenesis in a Rat Model Leading to a Functional Regenerated Femur.

PubMed

Pithioux, Martine; Roseren, Flavy; Jalain, Christian; Launay, Franck; Charpiot, Philippe; Chabrand, Patrick; Roffino, Sandrine; Lamy, Edouard

2017-10-23

This protocol describes the use of a newly developed external fixator for distraction osteogenesis in a rat femoral model. Distraction osteogenesis (DO) is a surgical technique leading to bone regeneration after an osteotomy. The osteotomized extremities are moved away from each other by gradual distraction to reach the desired elongation. This procedure is widely used in humans for lower and upper limb lengthening, treatment after a bone nonunion, or the regeneration of a bone defect following surgery for bone tumor excision, as well as in maxillofacial reconstruction. Only a few studies clearly demonstrate the efficiency of their protocol in obtaining a functional regenerated bone, i.e., bone that will support physiological weight-bearing without fracture after removal of the external fixator. Moreover, protocols for DO vary and reproducibility is limited by lack of information, making comparison between studies difficult. The aim of this study was to develop a reproducible protocol comprising an appropriate external fixator design for rat limb lengthening, with a detailed surgical technique that permits physiological weight-bearing by the animal after removal of the external fixator.

Evaluation of the effects of pulsed wave LLLT on tibial diaphysis in two rat models of experimental osteoporosis, as examined by stereological and real-time PCR gene expression analyses.

PubMed

Mohsenifar, Zhaleh; Fridoni, Mohammadjavad; Ghatrehsamani, Mahdi; Abdollahifar, Mohammad-amin; Abbaszadeh, Hojjatallah; Mostafavinia, Atarodalsadat; Fallahnezhad, Somaye; Asghari, Mohammadali; Bayat, Saba; Bayat, Mohammad

2016-05-01

Osteoporosis (OP) and osteoporotic fracture are major public health issues for society; the burden for the affected individual is also high. Previous studies have shown that pulsed wave low-level laser therapy (PW LLLT) has osteogenic effects. This study intended to evaluate the impacts of PW LLLT on the cortical bone of osteoporotic rats' tibias in two experimental models, ovariectomized and dexamethasone-treated. We divided the rats into four ovariectomized induced OP (OVX-d) and four dexamethasone-treated (glucocorticoid-induced OP, GIOP) groups. A healthy (H) group of rats was considered for baseline evaluations. At 14 weeks following ovariectomy, we subdivided the OVX-d rats into the following groups: (i) control which had OP, (ii) OVX-d rats treated with alendronate (1 mg/kg), (iii) OVX-d rats treated with LLLT, and (iv) OVX-d rats treated with alendronate and PW LLLT. The remaining rats received dexamethasone over a 5-week period and were also subdivided into four groups: (i) control rats treated with intramuscular (i.m.) injections of distilled water (vehicle), (ii) rats treated with subcutaneous alendronate injections (1 mg/kg), (iii) laser-treated rats, and (iv) rats simultaneously treated with laser and alendronate. The rats received alendronate for 30 days and underwent PW LLLT (890 nm, 80 Hz, 0.972 J/cm(2)) three times per week during 8 weeks. Then, the right tibias were extracted and underwent a stereological analysis of histological parameters and real-time polymerase chain reaction (RT-PCR). A significant increase in cortical bone volume (mm(3)) existed in all study groups compared to the healthy rats. There were significant decreases in trabecular bone volume (mm(3)) in all study groups compared to the group of healthy rats. The control rats with OP and rats from the vehicle group showed significantly increased osteoclast numbers compared to most other groups. Alendronate significantly decreased osteoclast numbers in osteoporotic rats. Concurrent treatments (compounded by PW LLLT and alendronate) produce the same effect on osteoporotic bone.

Parallel Human and Animal Models of Blast- and Concussion-Induced Tinnitus and Related Traumatic Brain Injury (TBI)

DTIC Science & Technology

2013-01-01

supportive apparatus with a locking mechanism . The blast was delivered at approximately 14 and 22 PSI, which generated a noise of 10 ms duration at ~194...Rats were sacrificed two weeks after TBI for histological observations of axonal injury. Data. No skull fractures , respiratory depression or...Mark Haacke, and Pamela VandeVord (2012) Mechanisms and Treatment Strategies of Blast-Induced Tinnitus and Its Related TBI. Military Health 62 | P a

Combined Use of Mesenchymal Stromal Cell Sheet Transplantation and Local Injection of SDF-1 for Bone Repair in a Rat Nonunion Model.

PubMed

Chen, Guangnan; Fang, Tingting; Qi, Yiying; Yin, Xiaofan; Di, Tuoyu; Feng, Gang; Lei, Zhong; Zhang, Yuxiang; Huang, Zhongming

2016-10-01

Bone nonunion treatments pose a challenge in orthopedics. This study investigated the joint effects of using mesenchymal stem cell (MSC) sheets with local injection of stromal cell-derived factor-1 (SDF-1) on bone formation. In vitro, we found that migration of MSCs was mediated by SDF-1 in a dose-dependent manner. Moreover, stimulation with SDF-1 had no direct effect on the proliferation or osteogenic differentiation of MSCs. Furthermore, the results indicated elevated expression levels of bone morphogenetic protein 2, alkaline phosphatase, osteocalcin, and vascular endothelial growth factor in MSC sheets compared with MSCs cultured in medium. New bone formation in fractures was evaluated by X-ray, micro-computed tomography (micro-CT), hematoxylin and eosin (H&E) staining, Safranin-O staining, and immunohistochemistry in vivo. In the rat bone fracture model, the MSC sheets transplanted into the injured site along with injection of SDF-1 showed significantly more new bone formation within the gap. Moreover, at 8 weeks, complete bone union was obtained in this group. In contrast, the control group showed nonunion of the bone. Our study suggests a new strategy involving the use of MSC sheets with a local injection of SDF-1 for hard tissue reconstruction, such as the healing of nonunions and bone defects.

12. Influence of Wound Dressing on the Fracture Healing Effect of Low-Intensity Pulsed Ultrasound (LIPUS).

PubMed

Naruse, Koji; Uchino, Masataka; Hirakawa, Noriko; Toyama, Masahiro; Miyajima, Genyo; Mukai, Manabu; Urabe, Ken; Uchida, Kentaro; Itoman, Moritoshi

2016-08-01

We have conducted a basic study on the influences on ultrasonic properties when LIPUS is applied through wound dressing. According to the results of ex vivo experiments conducted to date, LIPUS showed ultrasonic properties such as transmittance, coefficient of transmission, and a non-uniformity ratio through film wound dressing better than other wound dressing, and it was considered that LIPUS's effect for fracture healing was not influenced by film wound dressing. Then, we discussed the influence on the effect of LIPUS through film wound dressing. Thirty male 8-week-old Sprague-Dawley rats were used for the trial. After creating close transverse femoral fractures on the right legs of these 30 rats, they were divided into 3 groups of 10; LIPUS through wound dressing (Group A), LIPUS without wound dressing (Group B), and No LIPUS treatment (Group C). OPSITE Wound, which was thought to have the least influence on ultrasound properties, was used for this trial. Group A and B received LIPUS for 20 minutes a day from the first day after the fractures. LIPUS was generated from Teijin Pharma's device for a basic experiment. When treating Group A, the wound dressing was pasted on the ultrasound terminal in order to apply LIPUS through the dressing. We assessed the time-oriented morphological change of each group in anesthetized condition using simple radiographs on the 8th, 16th, and 24th day after the fractures. Six rats in Group A, 2 in Group B, and 1 in Group C died in anesthesia, and we discussed the remaining 4 rats in Group A, 8 in Group B, and 9 in Group C. We defined more than one teleost callus bridging as bone-union. We also counted a bone remodeling when we recognized the absorption of existing cortical bone and the transformation of new bone to cortical bone in simple radiographs. As a result, compared with Group C, we recognized that both bone union and remodeling accelerated remarkably in Group B, but not in Group A. It suggested that LIPUS through wound dressing had negative influences on both period shorting of fracture healing and bone remodeling. When LIPUS was conducted through film wound dressing, transmittance and coefficient of transmission were unchanged; however, the non-uniformity ratio changed slightly. The non-uniformity ratio of the ultrasound transducer had a significant influence on the effect of LIPUS on fracture healing.

Exercise Prevents Enhanced Postoperative Neuroinflammation and Cognitive Decline and Rectifies the Gut Microbiome in a Rat Model of Metabolic Syndrome.

PubMed

Feng, Xiaomei; Uchida, Yosuke; Koch, Lauren; Britton, Steve; Hu, Jun; Lutrin, David; Maze, Mervyn

2017-01-01

Postoperative cognitive decline (PCD) can affect in excess of 10% of surgical patients and can be considerably higher with risk factors including advanced age, perioperative infection, and metabolic conditions such as obesity and insulin resistance. To define underlying pathophysiologic processes, we used animal models including a rat model of metabolic syndrome generated by breeding for a trait of low aerobic exercise tolerance. After 35 generations, the low capacity runner (LCR) rats differ 10-fold in their aerobic exercise capacity from high capacity runner (HCR) rats. The LCR rats respond to surgical procedure with an abnormal phenotype consisting of exaggerated and persistent PCD and failure to resolve neuroinflammation. We determined whether preoperative exercise can rectify the abnormal surgical phenotype. Following institutional approval of the protocol each of male LCR and male HCR rats were randomly assigned to four groups and subjected to isoflurane anesthesia and tibia fracture with internal fixation (surgery) or anesthesia alone (sham surgery) and to a preoperative exercise regimen that involved walking for 10 km on a treadmill over 6 weeks (exercise) or being placed on a stationary treadmill (no exercise). Feces were collected before and after exercise for assessment of gut microbiome. Three days following surgery or sham surgery the rats were tested for ability to recall a contextual aversive stimulus in a trace fear conditioning paradigm. Thereafter some rats were euthanized and the hippocampus harvested for analysis of inflammatory mediators. At 3 months, the remainder of the rats were tested for memory recall by the probe test in a Morris Water Maze. Postoperatively, LCR rats exhibited exaggerated cognitive decline both at 3 days and at 3 months that was prevented by preoperative exercise. Similarly, LCR rats had excessive postoperative neuroinflammation that was normalized by preoperative exercise. Diversity of the gut microbiome in the LCR rats improved after exercise. Preoperative exercise eliminated the metabolic syndrome risk for the abnormal surgical phenotype and was associated with a more diverse gut microbiome. Prehabilitation with exercise should be considered as a possible intervention to prevent exaggerated and persistent PCD in high-risk settings.

Effects of Spaceflight on Bone: The Rat as an Animal Model for Human Bone Loss

NASA Technical Reports Server (NTRS)

Halloran, B.; Weider, T.; Morey-Holton, E.

1999-01-01

The loss of weight bearing during spaceflight results in osteopenia in humans. Decrements in bone mineral reach 3-10% after as little as 75-184 days in space. Loss of bone mineral during flight decreases bone strength and increases fracture risk. The mechanisms responsible for, and the factors contributing to, the changes in bone induced by spaceflight are poorly understood. The rat has been widely used as an animal model for human bone loss during spaceflight. Despite its potential usefulness, the results of bone studies performed in the rat in space have been inconsistent. In some flights bone formation is decreased and cancellous bone volume reduced, while in others no significant changes in bone occur. In June of 1996 Drs. T. Wronski, S. Miller and myself participated in a flight experiment (STS 78) to examine the effects of glucocorticoids on bone during weightlessness. Technically the 17 day flight experiment was flawless. The results, however, were surprising. Cancellous bone volume and osteoblast surface in the proximal tibial metaphysis were the same in flight and ground-based control rats. Normal levels of cancellous bone mass and bone formation were also detected in the lumbar vertebrae and femoral neck of flight rats. Furthermore, periosteal bone formation rate was found to be identical in flight and ground-based control rats. Spaceflight had little or no effect on bone metabolism! These results prompted us to carefully review the changes in bone observed in, and the flight conditions of previous spaceflight missions.

Treatment of Radix Dipsaci extract prevents long bone loss induced by modeled microgravity in hindlimb unloading rats.

PubMed

Niu, Yinbo; Li, Chenrui; Pan, Yalei; Li, Yuhua; Kong, Xianghe; Wang, Shuo; Zhai, YuanKun; Wu, Xianglong; Fan, Wutu; Mei, Qibing

2015-01-01

Radix Dipsaci is a kidney tonifying herbal medicine with a long history of safe use for treatment of bone fractures and joint diseases in China. Previous studies have shown that Radix Dipsaci extract (RDE) could prevent bone loss in ovariectomized rats. This study investigates the effect of RDE against bone loss induced by simulated microgravity. A hindlimb unloading rat model was established to determine the effect of RDE on bone mineral density and bone microarchitecture. Twenty-four male Sprague-Dawley rats were divided into four groups (n = 6 per group): control (CON), hindlimb unloading with vehicle (HLU), hindlimb unloading treated with alendronate (HLU-ALN, 2.0 mg/kg/d), and hindlimb unloading treated with RDE (HLU-RDE, 500 mg/kg/d). RDE or ALN was administrated orally for 4 weeks. Treatment with RDE had a positive effect on mechanical strength, BMD, BMC, bone turnover markers, and the changes in urinary calcium and phosphorus excretion. MicroCT analysis showed that RDE significantly prevented the reduction of the bone volume fraction, connectivity density, trabecular number, thickness, tissue mineral density, and tissue mineral content as well as improved the trabecular separation and structure model index. RDE was demonstrated to prevent the loss of bone mass induced by HLU treatment, which suggests the potential application of RDE in the treatment of microgravity-induced bone loss.

Cannabidiol, a Major Non-Psychotropic Cannabis Constituent Enhances Fracture Healing and Stimulates Lysyl Hydroxylase Activity in Osteoblasts.

PubMed

Kogan, Natalya M; Melamed, Eitan; Wasserman, Elad; Raphael, Bitya; Breuer, Aviva; Stok, Kathryn S; Sondergaard, Rachel; Escudero, Ana V Villarreal; Baraghithy, Saja; Attar-Namdar, Malka; Friedlander-Barenboim, Silvina; Mathavan, Neashan; Isaksson, Hanna; Mechoulam, Raphael; Müller, Ralph; Bajayo, Alon; Gabet, Yankel; Bab, Itai

2015-10-01

Cannabinoid ligands regulate bone mass, but skeletal effects of cannabis (marijuana and hashish) have not been reported. Bone fractures are highly prevalent, involving prolonged immobilization and discomfort. Here we report that the major non-psychoactive cannabis constituent, cannabidiol (CBD), enhances the biomechanical properties of healing rat mid-femoral fractures. The maximal load and work-to-failure, but not the stiffness, of femurs from rats given a mixture of CBD and Δ(9) -tetrahydrocannabinol (THC) for 8 weeks were markedly increased by CBD. This effect is not shared by THC (the psychoactive component of cannabis), but THC potentiates the CBD stimulated work-to-failure at 6 weeks postfracture followed by attenuation of the CBD effect at 8 weeks. Using micro-computed tomography (μCT), the fracture callus size was transiently reduced by either CBD or THC 4 weeks after fracture but reached control level after 6 and 8 weeks. The callus material density was unaffected by CBD and/or THC. By contrast, CBD stimulated mRNA expression of Plod1 in primary osteoblast cultures, encoding an enzyme that catalyzes lysine hydroxylation, which is in turn involved in collagen crosslinking and stabilization. Using Fourier transform infrared (FTIR) spectroscopy we confirmed the increase in collagen crosslink ratio by CBD, which is likely to contribute to the improved biomechanical properties of the fracture callus. Taken together, these data show that CBD leads to improvement in fracture healing and demonstrate the critical mechanical role of collagen crosslinking enzymes. © 2015 American Society for Bone and Mineral Research.

Improved Healing of Large, Osseous, Segmental Defects by Reverse Dynamization: Evaluation in a Sheep Model

DTIC Science & Technology

2015-10-01

IFM ) through the separated bone cortices (fracture gap). In research funded by a CDMRP Idea Development Award, we used a rat segmental defect...491, 2011. [3] V. Glatt, M . Miller, a Ivkovic, F. Liu, N. Parry, D. Griffin, M . Vrahas, and C. Evans, “Improved healing of large segmental defects...2012. [4] M . Mehta, S . Checa, J. Lienau, D. Hutmacher, and G. N. Duda, “In vivo tracking of segmental bone defect healing reveals that callus

Fracture bone healing and biodegradation of AZ31 implant in rats.

PubMed

Iglesias, C; Bodelón, O G; Montoya, R; Clemente, C; Garcia-Alonso, M C; Rubio, J C; Escudero, M L

2015-04-17

The ideal temporary implant should offer enough mechanical support to allow healing of the fracture and then biodegrade and be resorbed by metabolic mechanisms without causing any toxic effect. The aim of this research has been to simultaneously study in situ bone healing and the biodegradation of AZ31 Mg alloy as an osteosynthesis material. The in vivo study was carried out in AZ31 implants with and without Mg-fluoride coating inserted in un-fractured and fractured femurs of Wistar rats for long experimentation time, from 1 to 13 months, by means of computed tomography, histological and histomorphometric analysis. Tomography analysis showed the bone healing and biodegradation of AZ31 implants. The fracture is healed in 100% of the animals, and AZ31 maintains its mechanical integrity throughout the healing process. Biodegradation was monitored, quantifying the evolution of gas over time by 3D composition of tomography images. In all the studied groups, gas pockets disappear with time as a result of the diffusion process through soft tissues. Histomorphometric studies reveal that after 13 months the 46.32% of AZ31 alloy has been resorbed. The resorption of the coated and uncoated AZ31 implants inserted in fractured femurs after 1, 9 and 13 months does not have statistically significant differences. There is a balance between the biodegradation of AZ31 and bone healing which allows the use of AZ31 to be proposed as an osteosynthesis material.

Fibroblast growth factor-21 restores insulin sensitivity but induces aberrant bone microstructure in obese insulin-resistant rats.

PubMed

Charoenphandhu, Narattaphol; Suntornsaratoon, Panan; Krishnamra, Nateetip; Sa-Nguanmoo, Piangkwan; Tanajak, Pongpun; Wang, Xiaojie; Liang, Guang; Li, Xiaokun; Jiang, Chao; Chattipakorn, Nipon; Chattipakorn, Siriporn

2017-03-01

Fibroblast growth factor (FGF)-21 is a potent endocrine factor that improves insulin resistance and obesity-associated metabolic disorders. However, concomitant activation of peroxisome proliferator-activated receptor-γ by FGF-21 makes bone susceptible to osteopenia and fragility fracture. Since an increase in body weight often induced adaptive change in bone by making it resistant to fracture, it was unclear whether FGF-21 would still induce bone defects in overweight rats. Therefore, the present study aimed to investigate bone microstructure and its mechanical properties in high fat diet (HF)-fed rats treated with 0.1 mg/kg/day FGF-21. Eighteen male rats were divided into two groups to receive either a normal diet or HF for 12 weeks. HF rats were then divided into two subgroups to receive either vehicle or FGF-21 for 4 weeks. The results showed that HF led to obesity, dyslipidemia and insulin resistance, as indicated by hyperinsulinemia with euglycemia. In HF rats, there was an increase in tibial yield displacement (an indicator of ability to be deformed without losing toughness, as determined by 3-point bending) without changes in tibial trabecular volumetric bone mineral density (vBMD) or cortical bone parameters, e.g., cortical thickness and bone area. FGF-21 treatment strongly improved the metabolic parameters and increased insulin sensitivity in HF rats. However, FGF-21-treated HF rats showed lower yield displacement, trabecular vBMD, trabecular bone volume, trabecular thickness, and osteoblast surface compared with vehicle-treated HF rats. These findings suggest that, despite being a potent antagonist of insulin resistance and visceral fat accumulation, FGF-21 is associated with bone defects in HF rats.

Effect of human vascular endothelial growth factor gene transfer on endogenous vascular endothelial growth factor mRNA expression in a rat fibroblast and osteoblast culture model.

PubMed

Li, Ru; Li, Claire H; Nauth, Aaron; McKee, Michael D; Schemitsch, Emil H

2010-09-01

Vascular endothelial growth factor (VEGF) plays an important role in promoting angiogenesis and osteogenesis during fracture repair. Our previous studies have shown that cell-based VEGF gene therapy enhances bone healing of a rabbit tibia segmental bone defect in vivo. The aim of this project was to examine the effect of exogenous human VEGF on the endogenous rat VEGF messenger RNA (mRNA) expression in a cell-based gene transfer model. Rat fibroblasts and osteoblasts were harvested from the dermal tissue and periosteum, respectively, of Fisher 344 rats. The cells were then cultured and transfected with pcDNA-human VEGF using Superfect reagent (Qiagen). Four experimental groups were created: 1) fibroblast-VEGF; 2) osteoblast-VEGF; 3) nontransfected fibroblast controls; and 4) nontransfected osteoblast controls. The cultured cells were harvested at 1, 3, and 7 days after the gene transfection. The total mRNA was extracted (Trizol; Invitrogen); both human VEGF and rat VEGF mRNA were measured by reverse transcriptase-polymerase chain reaction and quantified by VisionWorksLS. The human VEGF165 mRNA was detected by reverse transcriptase-polymerase chain reaction from transfected fibroblasts and osteoblasts at 1, 3, and 7 days after gene transfection. The human VEGF165 levels peaked at Day 1 and then gradually reduced expression in both transfected fibroblasts and osteoblasts. Two endogenous rat VEGF isoforms were detected in this cell culture model: rat VEGF120 and rat VEGF164. We compared the rat VEGF120 and rat VEGF164 expression level of the fibroblasts or osteoblasts that were transfected with human VEGF165, with nontransfected control cells. Both the transfected fibroblasts and osteoblasts showed greater expression of rat VEGF164 than nontransfected controls at Day 1 (peak level) and Day 3, but not at Day 7. The expression of rat VEGF120 was lower in transfected fibroblasts, but higher in transfected osteoblasts, than the relevant control groups at any time point after transfection. In addition, human VEGF gene transfection increased osteoblast cell proliferation after 3 days. These in vitro results suggest that cell-based human VEGF gene therapy is not only effective at causing human VEGF expression, but also enhances endogenous rat VEGF mRNA expression in both fibroblasts and osteoblasts, particularly the rat VEGF164 isoform.

Osteotomy models - the current status on pain scoring and management in small rodents.

PubMed

Lang, Annemarie; Schulz, Anja; Ellinghaus, Agnes; Schmidt-Bleek, Katharina

2016-12-01

Fracture healing is a complex regeneration process which produces new bone tissue without scar formation. However, fracture healing disorders occur in approximately 10% of human patients and cause severe pain and reduced quality of life. Recently, the development of more standardized, sophisticated and commercially available osteosynthesis techniques reflecting clinical approaches has increased the use of small rodents such as rats and mice in bone healing research dramatically. Nevertheless, there is no standard for pain assessment, especially in these species, and consequently limited information regarding the welfare aspects of osteotomy models. Moreover, the selection of analgesics is restricted for osteotomy models since non-steroidal anti-inflammatory drugs (NSAIDs) are known to affect the initial, inflammatory phase of bone healing. Therefore, opioids such as buprenorphine and tramadol are often used. However, dosage data in the literature are varied. Within this review, we clarify the background of osteotomy models, explain the current status and challenges of animal welfare assessment, and provide an example score sheet including model specific parameters. Furthermore, we summarize current refinement options and present a brief outlook on further 3R research. © The Author(s) 2016.

Sex-Specific Genetic Loci for Femoral Neck Bone Mass and Strength Identified in Inbred COP and DA Rats

PubMed Central

Alam, Imranul; Sun, Qiwei; Liu, Lixiang; Koller, Daniel L; Carr, Lucinda G; Econs, Michael J; Foroud, Tatiana; Turner, Charles H

2008-01-01

Introduction Hip fracture is the most devastating osteoporotic fracture type with significant morbidity and mortality. Several studies in humans identified chromosomal regions linked to hip size and bone mass. Animal models, particularly the inbred rat, serve as complementary approaches for studying the genetic influence on hip fragility. The purpose of this study is to identify sex-independent and sex-specific quantitative trait loci (QTLs) for femoral neck density, structure, and strength in inbred Copenhagen 2331 (COP) and Dark Agouti (DA) rats. Materials and Methods A total of 828 (405 males and 423 females) F2 progeny derived from the inbred COP and DA strains of rats were phenotyped for femoral neck volumetric BMD (vBMD), cross-sectional area, polar moment of inertia (Ip), neck width, ultimate force, and energy to break. A whole genome screen was performed using 93 microsatellite markers with an average intermarker distance of 20 cM. Recombination-based marker maps were generated using MAPMAKER/EXP from the COP × DA F2 data and compared with published Rat Genome Database (RGD) maps. These maps were used for genome-wide linkage analyses to detect sex-independent and sex-specific QTLs. Results Significant evidence of linkage (p < 0.01) for sex-independent QTLs were detected for (1) femoral neck vBMD on chromosomes (Chrs) 1, 6, 10, and 12, (2) femoral neck structure on Chrs 5, 7, 10, and 18, and (3) biomechanical properties on Chrs 1 and 4. Male-specific QTLs were discovered on Chrs 2, 9, and 18 for total vBMD, on Chr 17 for trabecular vBMD, on Chr 9 for total bone area, and on Chr 15 for ultimate force. A female-specific QTL was discovered on Chr 2 for ultimate force. The effect size of the individual QTL varied between 1% and 4%. Conclusions We detected evidence that sex-independent and sex-specific QTLs contribute to hip fragility in the inbred rat. Several QTLs regions identified in this study are homologous to human chromosomal regions previously linked to QTLs contributing to femoral neck and related phenotypes. PMID:18282130

Therapeutic effect of icariin combined with stem cells on postmenopausal osteoporosis in rats.

PubMed

Tang, Dao; Ju, Cuiling; Liu, Yanjie; Xu, Fei; Wang, Zhengguang; Wang, Dongbo

2018-03-01

Osteoporosis is characterized by skeletal fragility and microarchitectural deterioration. The side effects of drugs to treat osteoporosis will negatively affect the health of patients. This study aimed to investigate the therapeutic effects of icariin combined with adipose-derived stem cells on osteoporosis in a postmenopausal osteoporosis model after ovariectomy in rats. After ovariectomy the rats were treated with icariin combined with adipose-derived stem cell transplantation. The levels of alkaline phosphatase, tartrate-resistant acid phosphatase, osteoprotegerin, and bone γ-carboxyglutamate protein in serum were determined by ELISA. The bone mineral density was measured by dual-energy X-ray absorptiometry. The mechanical properties were determined by a three-point bending test. The kidney functions were evaluated by an automatic analyzer and a diagnostic kit. Icariin combined with stem cells significantly reduced body weight gain caused by ovariectomy, significantly decreased alkaline phosphatase, tartrate-resistant acid phosphatase, and bone γ-carboxyglutamate protein content in serum, significantly increased osteoprotegerin content, significantly elevated bone mineral density of the lumbar spine, left femur, and right femur, and enhanced bone biomechanical properties of the femur, including maximum bending load, bending rigidity, and fracture energy, in osteoporotic rats. In addition, icariin combined with stem cells substantially decreased the damage to the liver and kidney in osteoporotic rats. Icariin combined with stem cells can not only ameliorate reduction of bone mass and disruption of the microarchitectural structure of bone tissue caused by osteoporosis in a rat model but can also have a beneficial effect on organ functions, such as those of the liver and kidney.

Low-intensity pulsed ultrasound treatment improved the rate of autograft peripheral nerve regeneration in rat

PubMed Central

Jiang, Wenli; Wang, Yuexiang; Tang, Jie; Peng, Jiang; Wang, Yu; Guo, Quanyi; Guo, Zhiyuan; Li, Pan; Xiao, Bo; Zhang, Jinxing

2016-01-01

Low intensity pulsed ultrasound (LIPUS) has been widely used in clinic for the treatment of repairing pseudarthrosis, bone fractures and of healing in various soft tissues. Some reports indicated that LIPUS accelerated peripheral nerve regeneration including Schwann cells (SCs) and injured nerves. But little is known about its appropriate intensities on autograft nerves. This study was to investigate which intensity of LIPUS improved the regeneration of gold standard postsurgical nerves in experimental rat model. Sprague-Dawley rats were made into 10 mm right side sciatic nerve reversed autologous nerve transplantation and randomly treated with 250 mW/cm2, 500 mW/cm2 or 750 mW/cm2 LIPUS for 2–12 weeks after operation. Functional and pathological results showed that LIPUS of 250 mW/cm2 significantly induced faster rate of axonal regeneration. This suggested that autograft nerve regeneration was improved. PMID:27102358

Low Intensity Pulsed Ultrasound (LIPUS) for the treatment of intervertebral disc degeneration

NASA Astrophysics Data System (ADS)

Horne, Devante; Jones, Peter; Salgaonkar, Vasant; Adams, Matt; Ozilgen, B. Arda; Zahos, Peter; Tang, Xinyan; Liebenberg, Ellen; Coughlin, Dezba; Lotz, Jeffrey; Diederich, Chris

2017-02-01

Discogenic back pain presents a major public health issue, with current therapeutic interventions limited to short-term symptom relief without providing regenerative remedies for diseased intervertebral discs (IVD). Many of these interventions are invasive and can diminish the biomechanical integrity of the IVDs. Low intensity pulsed ultrasound (LIPUS) is a potential treatment option that is both non-invasive and regenerative. LIPUS has been shown to be a clinically effective method for the enhancement of wound and fracture healing. Recent in vitro studies have shown that LIPUS stimulation induces an upregulation functional matrix proteins and downregulation of inflammatory factors in cultured IVD cells. However, we do not know the effects of LIPUS on an in vivo model for intervertebral disc degeneration. The objective of this study was to show technical feasibility of building a LIPUS system that can target the rat tail IVD and apply this setup to a model for acute IVD degeneration. A LIPUS exposimetry system was built using a 1.0 MHz planar transducer and custom housing. Ex vivo intensity measurements demonstrated LIPUS delivery to the center of the rat tail IVD. Using an established stab-incision model for disc degeneration, LIPUS was applied for 20 minutes daily for five days. For rats that displayed a significant injury response, LIPUS treatment caused significant upregulation of Collagen II and downregulation of Tumor Necrosis Factor - α gene expression. Our preliminary studies indicate technical feasibility of targeted delivery of ultrasound to a rat tail IVD for studies of LIPUS biological effects.

Ethanol extract of Peperomia pellucida (Piperaceae) promotes fracture healing by an anabolic effect on osteoblasts.

PubMed

Ngueguim, Florence Tsofack; Khan, Mohd Parvez; Donfack, Jean Hubert; Tewari, Deepshikha; Dimo, Theophile; Kamtchouing, Pierre; Maurya, Rakesh; Chattopadhyay, Naibedya

2013-06-21

The whole plant or some part of Peperomia pellucida (L.) HBK is used in some parts of Cameroon as a treatment for fracture healing. To evaluate the effect of ethanolic extracts of Peperomia pellucida (L.), a Cameroonian medicinal plant on bone regeneration following bone and marrow injury, and determine the mode of action. Ethanol extract of Peperomia pellucida was administered at 100 and 200mg/kg doses orally to adult female Sprague-Dawley rats having a drill hole injury (0.8mm) in the femur diaphysis. Vehicle (gum-acacia in distilled water) was given to the control group. After 12 days of treatment, animals were euthanized and femur bones collected. Confocal microscopy of calcein labeling at the drill hole site was performed to evaluate bone regeneration. 3-D microarchitecture of drill hole site was analyzed by micorocomputed tomography. Osteogenic effects of the extract were evaluated by assessing mineralized nodule formation of bone marrow stromal cells and expression of osteogenic genes (mRNA level of type-1 collagen, bone morphogenetic protein-2 and osteocalcin genes) in the femur. Ethanol extract from Peperomia Pellucida (L.) dose-dependently induced bone regeneration at the fracture site. At 200mg/kg dose, the extract significantly increased mineral deposition compared to controls. The extract also improved microarchitecture of the regenerating bone evident from increased bone volume fraction, trabecular thickness, trabecular number, and decreased trabecular separation and structure model index. In addition, the extract increased the formation of mineralized nodules from the bone marrow stromal cells. Furthermore, the extract induced the expression of osteogenic genes in the femur including type 1 collagen, osteocalcin and BMP-2, compared to control. Ethanolic extract of P. pellucid (L.) accelerates fracture repair in rats via stimulatory effects on osteoblast differentiation and mineralization, thereby justifying its traditional use. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Evaluation of injectable silica-embedded nanohydroxyapatite bone substitute in a rat tibia defect model

PubMed Central

Xu, Weiguo; Ganz, Cornelia; Weber, Ulf; Adam, Martin; Holzhüter, Gerd; Wolter, Daniel; Frerich, Bernhard; Vollmar, Brigitte; Gerber, Thomas

2011-01-01

In clinical practice, vertebral compression fractures occur after trauma and osteoporosis. Kyphoplasty is a minimally invasive procedure using bone filler material for the treatment of such fractures. A full synthetic injectable bone substitute (SIBS) was manufactured by means of spray drying. The aim of this study was to characterize the SIBS and to analyze the remodelling process during degradation of the biomaterial and new bone formation after implantation. SIBS is an aqueous suspension of donut-like microparticles. These microparticles consist of nanocrystallites of synthetic hydroxyapatite embedded in amorphous silica gel. After implantation of SIBS in a proximal tibial diaphyseal defect in 52 rats, grafts were harvested for subsequent analysis on different days. Newly formed bone originating from endosteum was observed on day 6. Hematomas in the medullary space and cortical wounds disappeared on day 12. The wound region was completely replaced by a composite of newly formed cancellous bone, extracellular matrix, and SIBS. At day 63 the cortical defect was fully healed by bone, while newly formed bone in the medullary space almost disappeared and was replaced with bone marrow. In conclusion, SIBS demonstrated a unique structure with osteoinductive and bioresorbable properties, which induced fast bone regeneration. Therefore, a clinical application of SIBS for kyphoplasty is promising. PMID:21845044

Changes in chemical composition of bone matrix in ovariectomized (OVX) rats detected by Raman spectroscopy and multivariate analysis

NASA Astrophysics Data System (ADS)

Oshima, Yusuke; Iimura, Tadahiro; Saitou, Takashi; Imamura, Takeshi

2015-02-01

Osteoporosis is a major bone disease that connotes the risk of fragility fractures resulting from alterations to bone quantity and/or quality to mechanical competence. Bone strength arises from both bone quantity and quality. Assessment of bone quality and bone quantity is important for prediction of fracture risk. In spite of the two factors contribute to maintain the bone strength, only one factor, bone mineral density is used to determine the bone strength in the current diagnosis of osteoporosis. On the other hand, there is no practical method to measure chemical composition of bone tissue including hydroxyapatite and collagen non-invasively. Raman spectroscopy is a powerful technique to analyze chemical composition and material properties of bone matrix non-invasively. Here we demonstrated Raman spectroscopic analysis of the bone matrix in osteoporosis model rat. Ovariectomized (OVX) rat was made and the decalcified sections of tibias were analyzed by a Raman microscope. In the results, Raman bands of typical collagen appeared in the obtained spectra. Although the typical mineral bands at 960 cm-1 (Phosphate) was absent due to decalcified processing, we found that Raman peak intensities of amide I and C-C stretching bands were significantly different between OVX and sham-operated specimens. These differences on the Raman spectra were statistically compared by multivariate analyses, principal component analysis (PCA) and liner discrimination analysis (LDA). Our analyses suggest that amide I and C-C stretching bands can be related to stability of bone matrix which reflects bone quality.

Nano-copper-bearing stainless steel promotes fracture healing by accelerating the callus evolution process.

PubMed

Wang, Lei; Li, Guoyuan; Ren, Ling; Kong, Xiangdong; Wang, Yugang; Han, Xiuguo; Jiang, Wenbo; Dai, Kerong; Yang, Ke; Hao, Yongqiang

2017-01-01

Treatment for fractures requires internal fixation devices, which are mainly produced from stainless steel or titanium alloy without biological functions. Therefore, we developed a novel nano-copper-bearing stainless steel with nano-sized copper-precipitation (317L-Cu SS). Based on previous studies, this work explores the effect of 317L-Cu SS on fracture healing; that is, proliferation, osteogenic differentiation, osteogenesis-related gene expression, and lysyl oxidase activity of human bone mesenchymal stem cells were detected in vitro. Sprague-Dawley rats were used to build an animal fracture model, and fracture healing and callus evolution were investigated by radiology (X-ray and micro-CT), histology (H&E, Masson, and safranin O/fast green staining), and histomorphometry. Further, the Cu 2+ content and Runx2 level in the callus were determined, and local mechanical test of the fracture was performed to assess the healing quality. Our results revealed that 317L-Cu SS did not affect the proliferation of human bone mesenchymal stem cells, but promoted osteogenic differentiation and the expression of osteogenesis-related genes. In addition, 317L-Cu SS upregulated the lysyl oxidase activity. The X-ray and micro-CT results showed that the callus evolution efficiency and fracture healing speed were superior for 317L-Cu SS. Histological staining displayed large amounts of fibrous tissues at 3 weeks, and cartilage and new bone at 6 weeks. Further, histomorphometric analysis indicated that the callus possessed higher osteogenic efficiency at 6 weeks, and a high Cu 2+ content and increased Runx2 expression were observed in the callus for 317L-Cu SS. Besides, the mechanical strength of the fracture site was much better than that of the control group. Overall, we conclude that 317L-Cu SS possesses the ability to increase Cu 2+ content and promote osteogenesis in the callus, which could accelerate the callus evolution process and bone formation to provide faster and better fracture healing.

Nano-copper-bearing stainless steel promotes fracture healing by accelerating the callus evolution process

PubMed Central

Kong, Xiangdong; Wang, Yugang; Han, Xiuguo; Jiang, Wenbo; Dai, Kerong; Yang, Ke; Hao, Yongqiang

2017-01-01

Treatment for fractures requires internal fixation devices, which are mainly produced from stainless steel or titanium alloy without biological functions. Therefore, we developed a novel nano-copper-bearing stainless steel with nano-sized copper-precipitation (317L-Cu SS). Based on previous studies, this work explores the effect of 317L-Cu SS on fracture healing; that is, proliferation, osteogenic differentiation, osteogenesis-related gene expression, and lysyl oxidase activity of human bone mesenchymal stem cells were detected in vitro. Sprague–Dawley rats were used to build an animal fracture model, and fracture healing and callus evolution were investigated by radiology (X-ray and micro-CT), histology (H&E, Masson, and safranin O/fast green staining), and histomorphometry. Further, the Cu2+ content and Runx2 level in the callus were determined, and local mechanical test of the fracture was performed to assess the healing quality. Our results revealed that 317L-Cu SS did not affect the proliferation of human bone mesenchymal stem cells, but promoted osteogenic differentiation and the expression of osteogenesis-related genes. In addition, 317L-Cu SS upregulated the lysyl oxidase activity. The X-ray and micro-CT results showed that the callus evolution efficiency and fracture healing speed were superior for 317L-Cu SS. Histological staining displayed large amounts of fibrous tissues at 3 weeks, and cartilage and new bone at 6 weeks. Further, histomorphometric analysis indicated that the callus possessed higher osteogenic efficiency at 6 weeks, and a high Cu2+ content and increased Runx2 expression were observed in the callus for 317L-Cu SS. Besides, the mechanical strength of the fracture site was much better than that of the control group. Overall, we conclude that 317L-Cu SS possesses the ability to increase Cu2+ content and promote osteogenesis in the callus, which could accelerate the callus evolution process and bone formation to provide faster and better fracture healing. PMID:29225463

Low Intensity Pulsed Ultrasound Enhanced Mesenchymal Stem Cell Recruitment through Stromal Derived Factor-1 Signaling in Fracture Healing

PubMed Central

Wei, Fang-Yuan; Leung, Kwok-Sui; Li, Gang; Qin, Jianghui; Chow, Simon Kwoon-Ho; Huang, Shuo; Sun, Ming-Hui; Qin, Ling; Cheung, Wing-Hoi

2014-01-01

Low intensity pulsed ultrasound (LIPUS) has been proven effective in promoting fracture healing but the underlying mechanisms are not fully depicted. We examined the effect of LIPUS on the recruitment of mesenchymal stem cells (MSCs) and the pivotal role of stromal cell-derived factor-1/C-X-C chemokine receptor type 4 (SDF-1/CXCR4) pathway in response to LIPUS stimulation, which are essential factors in bone fracture healing. For in vitro study, isolated rat MSCs were divided into control or LIPUS group. LIPUS treatment was given 20 minutes/day at 37°C for 3 days. Control group received sham LIPUS treatment. After treatment, intracellular CXCR4 mRNA, SDF-1 mRNA and secreted SDF-1 protein levels were quantified, and MSCs migration was evaluated with or without blocking SDF-1/CXCR4 pathway by AMD3100. For in vivo study, fractured 8-week-old young rats received intracardiac administration of MSCs were assigned to LIPUS treatment, LIPUS+AMD3100 treatment or vehicle control group. The migration of transplanted MSC to the fracture site was investigated by ex vivo fluorescent imaging. SDF-1 protein levels at fracture site and in serum were examined. Fracture healing parameters, including callus morphology, micro-architecture of the callus and biomechanical properties of the healing bone were investigated. The in vitro results showed that LIPUS upregulated SDF-1 and CXCR4 expressions in MSCs, and elevated SDF-1 protein level in the conditioned medium. MSCs migration was promoted by LIPUS and partially inhibited by AMD3100. In vivo study demonstrated that LIPUS promoted MSCs migration to the fracture site, which was associated with an increase of local and serum SDF-1 level, the changes in callus formation, and the improvement of callus microarchitecture and mechanical properties; whereas the blockade of SDF-1/CXCR4 signaling attenuated the LIPUS effects on the fractured bones. These results suggested SDF-1 mediated MSCs migration might be one of the crucial mechanisms through which LIPUS exerted influence on fracture healing. PMID:25181476

Inhibition of fetal bone development through epigenetic down- regulation of HoxA10 in obese rats fed high fat diet

USDA-ARS?s Scientific Manuscript database

Epidemiological studies show that maternal obesity during intrauterine and early postnatal life increases the risk of low bone mass and fracture later in life. Here, we show that bone development is inhibited in GED 18.5 embryos from rat dams made obese by feeding a high fat diet (HFD). Moreover, fe...

Osteogenic efficacy of strontium hydroxyapatite micro-granules in osteoporotic rat model.

PubMed

Chandran, Sunitha; Babu S, Suresh; Vs, Hari Krishnan; Varma, H K; John, Annie

2016-10-01

Excessive demineralization in osteoporotic bones impairs its self-regeneration potential following a defect/fracture and is of great concern among the aged population. In this context, implants with inherent osteogenic ability loaded with therapeutic ions like Strontium (Sr 2+ ) may bring forth promising outcomes. Micro-granular Strontium incorporated Hydroxyapatite scaffolds have been synthesized and in vivo osteogenic efficacy was evaluated in a long-term osteoporosis-induced aged (LOA) rat model. Micro-granules with improved surface area are anticipated to resorb faster and together with the inherent bioactive properties of Hydroxyapatite with the leaching of Strontium ions from the scaffold, osteoporotic bone healing may be promoted. Long-term osteoporosis-induced aged rat model was chosen to extrapolate the results to clinical osteoporotic condition in the aged. Micro-granular 10% Strontium incorporated Hydroxyapatite synthesized by wet precipitation method exhibited increased in vitro dissolution rate and inductively coupled plasma studies confirmed Strontium ion release of 0.01 mM, proving its therapeutic potential for osteoporotic applications. Wistar rats were induced to long-term osteoporosis-induced aged model by ovariectomy along with a prolonged induction period of 10 months. Thereafter, osteogenic efficacy of Strontium incorporated Hydroxyapatite micro-granules was evaluated in femoral bone defects in the long-term osteoporosis-induced aged model. Post eight weeks of implantation in vivo regeneration efficacy ratio was highest in the Strontium incorporated Hydroxyapatite implanted group (0.92 ± 0.04) compared to sham and Hydroxyapatite implanted group. Micro CT evaluation further substantiated the improved osteointegration of Strontium incorporated Hydroxyapatite implants from the density histograms. Thus, the therapeutical potential of micro-granular Strontium incorporated Hydroxyapatite scaffolds becomes relevant, especially as bone void fillers in osteoporotic cases of tumor resection or trauma. © The Author(s) 2016.

Pulsed electromagnetic field therapy improves tendon-to-bone healing in a rat rotator cuff repair model.

PubMed

Tucker, Jennica J; Cirone, James M; Morris, Tyler R; Nuss, Courtney A; Huegel, Julianne; Waldorff, Erik I; Zhang, Nianli; Ryaby, James T; Soslowsky, Louis J

2017-04-01

Rotator cuff tears are common musculoskeletal injuries often requiring surgical intervention with high failure rates. Currently, pulsed electromagnetic fields (PEMFs) are used for treatment of long-bone fracture and lumbar and cervical spine fusion surgery. Clinical studies examining the effects of PEMF on soft tissue healing show promising results. Therefore, we investigated the role of PEMF on rotator cuff healing using a rat rotator cuff repair model. We hypothesized that PEMF exposure following rotator cuff repair would improve tendon mechanical properties, tissue morphology, and alter in vivo joint function. Seventy adult male Sprague-Dawley rats were assigned to three groups: bilateral repair with PEMF (n = 30), bilateral repair followed by cage activity (n = 30), and uninjured control with cage activity (n = 10). Rats in the surgical groups were sacrificed at 4, 8, and 16 weeks. Control group was sacrificed at 8 weeks. Passive joint mechanics and gait analysis were assessed over time. Biomechanical analysis and μCT was performed on left shoulders; histological analysis on right shoulders. Results indicate no differences in passive joint mechanics and ambulation. At 4 weeks the PEMF group had decreased cross-sectional area and increased modulus and maximum stress. At 8 weeks the PEMF group had increased modulus and more rounded cells in the midsubstance. At 16 weeks the PEMF group had improved bone quality. Therefore, results indicate that PEMF improves early tendon healing and does not alter joint function in a rat rotator cuff repair model. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:902-909, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Gene Therapy for Fracture Repair

DTIC Science & Technology

2007-05-01

Methods: We have adopted the Agilent rat oligomer chip to analyze our fracture RNA in our microarray analysis. This chip has 20,046 unique gene...signal during fluorescent labeling of the cDNA. This approach is highly advantageous for reducing the RNA input into the system, minimizing the numbers...perform the analysis on these extremely limited samples without pooling the RNA from multiple individuals. We are therefore able to analyze the

[CHANGES OF SEMAPHORIN 3A EXPRESSION IN HEALING OF TIBIA FRACTURE AFTER TRAUMATIC BRAIN INJURY].

PubMed

Li, Zhengzheng; Zhao, Junwei; Yi, Zhigang; Luo, Wei; Li, Kang; Wang, Yuliang; Wang, Jing; An, Liping; Ma, Jinglin

2016-10-08

To investigate the mechanism of Semaphorin 3A (Sema3A) in fracture healing after nerve injury by observing the expression of Sema3A in the tibia fracture healing after traumatic brain injury (TBI). A total of 192 Wistar female rats, 8-10 weeks old and weighing 220-250 g, were randomly divided into tibia fracture group (group A, n =48), TBI group (group B, n =48), TBI with tibia fracture group (group C, n =48), and control group (group D, n =48). The tibia fracture model was established at the right side of group A; TBI model was made in group B by the improved Feeney method; the TBI and tibia fracture model was made in group C; no treatment was given in group D. The tissue samples were respectively collected at 3, 5, 7, 14, 21, and 28 days after operation; HE staining, immunohistochemistry staining, and Western blot method were used for the location and quantitative detection of Sema3A in callus tissue. HE staining showed that no obvious changes were observed at each time point in groups B and D. At 3 and 5 days, there was no obvious callus growth at fracture site with inflammatory cells and fibrous tissue filling in groups A and C. At 7 and 14 days, fibrous tissue grew from periosteum to fracture site in groups A and C; the proliferation of chondrocytes in exterior periosteum gradually formed osteoid callus at fracture site in groups A and C. The chondrocyte had bigger size, looser arrangement, and more osteoid in group C than group A. Group B had disorder periosteum, slight subperiosteal bone hyperplasia, and no obvious change of bone trabecula in group B when compared with group D. At 21 and 28 days, cartilage callus was gradually replaced by new bone trabecula in groups A and C. Group C had loose arrange, disorder structure, and low density of bone trabecula, big callus area and few chondrocyte and osteoid when compared with group A; group B was similar to Group D. Immunohistochemistry staining showed that Sema3A expression in chondrocytes in group C was higher than that in group A, particularly at 7, 14, and 21 day. Sema3A was significantly higher in osteoblasts of new bone trabecula in group A than group C, especially at 14 and 21 days ( P <0.05). Western blot results showed that the Sema3A had the same expression trend during fracture healing in groups A and C. However, the expression of Sema3A protein was significantly higher in group C than group A ( P <0.05) and in group B than group D ( P <0.05) at 7, 14, 21, and 28 days. Abnormal expression of Sema3A may play a role in fracture healing after nerve injury by promoting the chondrocytes proliferation and reducing the distribution of sensory nerve fibers and osteoblast differentiation.

Effect of nicotine and tobacco administration method on the mechanical properties of healing bone following closed fracture.

PubMed

Hastrup, Sidsel Gaarn; Chen, Xinqian; Bechtold, Joan E; Kyle, Richard F; Rahbek, Ole; Keyler, Daniel E; Skoett, Martin; Soeballe, Kjeld

2010-09-01

We previously showed different effects of tobacco and nicotine on fracture healing, but due to pump reservoir limits, maximum exposure period was 4 weeks. To allow flexibility in pre- and post-fracture exposure periods, the objective of this study was to compare a new oral administration route for nicotine to the established pump method. Four groups were studied: (1) pump saline, (2) pump saline + oral tobacco, (3) pump saline/nicotine + oral tobacco, and (4) pump saline + oral nicotine/tobacco. Sprague-Dawley rats (n = 84) received a transverse femoral fracture stabilized with an intramedullary pin 1 week after initiating dosing. After 3 weeks, no difference was found in torsional strength or stiffness between oral nicotine/tobacco or pump nicotine + tobacco, while energy absorption with oral nicotine/tobacco was greater than pump nicotine + tobacco (p < 0.05). Compared to saline control, strength for oral nicotine/tobacco was higher than control (p < 0.05), and stiffnesses for pump nicotine + tobacco and oral nicotine/tobacco were higher than control (p < 0.05). No differences in energy were found for either nicotine-tobacco group compared to saline control. Mean serum cotinine (stable nicotine metabolite) was different between pump and oral nicotine at 1 and 4 weeks, but all groups were in the range of 1-2 pack/day smokers. In summary, relevant serum cotinine levels can be reached in rats with oral nicotine, and, in the presence of tobacco, nicotine can influence mechanical aspects of fracture healing, dependent on administration method. Caution should be exercised when comparing results of fracture healing studies using different methods of nicotine administration. (c) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Alleviating anastrozole induced bone toxicity by selenium nanoparticles in SD rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vekariya, Kiritkumar K.; Kaur, Jasmine; Tikoo, Kulbhushan, E-mail: tikoo.k@gmail.com

Aromatase inhibitors like anastrozole play an undisputed key role in the treatment of breast cancer, but on the other hand, various side effects like osteoporosis and increased risk of bone fracture accompany the chronic administration of these drugs. Here we show for the first time that selenium nanoparticles, when given in conjugation to anastrozole, lower the bone toxicity caused by anastrozole and thus reduce the probable damage to the bone. Selenium nanoparticles at a dose of 5 μg/ml significantly reduced the cell death caused by anastrozole (1 μM) in HOS (human osteoblast) cells. In addition, our results also highlighted thatmore » in female SD rat model, SeNPs (0.25, 0.5, 1 mg/kg/day) significantly prevented the decrease in bone density and increase in biochemical markers of bone resorption induced by anastrozole (0.2 mg/kg/day) treatment. Histopathological examination of the femurs of SeNP treated group revealed ossification, mineralization, calcified cartilaginous deposits and a marginal osteoclastic activity, all of which indicate a marked restorative action, suggesting the protective action of the SeNPs. Interestingly, SeNPs (1 mg/kg/day) also exhibited protective effect in ovariectomized rat model, by preventing osteoporosis, which signifies that bone loss due to estrogen deficiency can be effectively overcome by using SeNPs. - Highlights: ► SeNPs significantly reduce bone toxicity in anastrozole treated rats. ► SeNPs successfully prevented osteoporosis in ovariectomized rats. ► SeNP treatment lowered the levels of TRAP and increased the levels of ALKP.« less

Pharmacological activation of aldehyde dehydrogenase 2 promotes osteoblast differentiation via bone morphogenetic protein-2 and induces bone anabolic effect

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mittal, Monika; Pal, Subhashis; China, Shyamsundar

Aldehyde dehydrogenases (ALDHs) are a family of enzymes involved in detoxifying aldehydes. Previously, we reported that an ALDH inhibitor, disulfiram caused bone loss in rats and among ALDHs, osteoblast expressed only ALDH2. Loss-of-function mutation in ALDH2 gene is reported to cause bone loss in humans which suggested its importance in skeletal homeostasis. We thus studied whether activating ALDH2 by N-(1, 3-benzodioxol-5-ylmethyl)-2, 6-dichlorobenzamide (alda-1) had osteogenic effect. We found that alda-1 increased and acetaldehyde decreased the differentiation of rat primary osteoblasts and expressions of ALDH2 and bone morphogenetic protein-2 (BMP-2). Silencing ALDH2 in osteoblasts abolished the alda-1 effects. Further, alda-1 attenuatedmore » the acetaldehyde-induced lipid-peroxidation and oxidative stress. BMP-2 is essential for bone regeneration and alda-1 increased its expression in osteoblasts. We then showed that alda-1 (40 mg/kg dose) augmented bone regeneration at the fracture site with concomitant increase in BMP-2 protein compared with control. The osteogenic dose (40 mg/kg) of alda-1 attained a bone marrow concentration that was stimulatory for osteoblast differentiation, suggesting that the tissue concentration of alda-1 matched its pharmacologic effect. In addition, alda-1 promoted modeling-directed bone growth and peak bone mass achievement, and increased bone mass in adult rats which reiterated its osteogenic effect. In osteopenic ovariectomized (OVX) rats, alda-1 reversed trabecular osteopenia with attendant increase in serum osteogenic marker (procollagen type I N-terminal peptide) and decrease in oxidative stress. Alda-1 has no effect on liver and kidney function. We conclude that activating ALDH2 by alda-1 had an osteoanabolic effect involving increased osteoblastic BMP-2 production and decreased OVX-induced oxidative stress. - Highlights: • Alda-1 induced osteoblast differentiation that involved upregulation of ALDH2 and BMP-2 • Alda-1 attenuated acetaldehyde-induced inhibition of osteoblast differentiation • Alda-1 enhanced bone regeneration at the fracture site and peak bone mass achievement • Alda-1 reversed trabecular osteopenia in OVX rats via an osteoanabolic mechanism.« less

Combined local and systemic antibiotic delivery improves eradication of wound contamination: An animal experimental model of contaminated fracture.

PubMed

Rand, B C C; Penn-Barwell, J G; Wenke, J C

2015-10-01

Systemic antibiotics reduce infection in open fractures. Local delivery of antibiotics can provide higher doses to wounds without toxic systemic effects. This study investigated the effect on infection of combining systemic with local antibiotics via polymethylmethacrylate (PMMA) beads or gel delivery. An established Staphylococcus aureus contaminated fracture model in rats was used. Wounds were debrided and irrigated six hours after contamination and animals assigned to one of three groups, all of which received systemic antibiotics. One group had local delivery via antibiotic gel, another PMMA beads and the control group received no local antibiotics. After two weeks, bacterial levels were quantified. Combined local and systemic antibiotics were superior to systemic antibiotics alone at reducing the quantity of bacteria recoverable from each group (p = 0.002 for gel; p = 0.032 for beads). There was no difference in the bacterial counts between bead and gel delivery (p = 0.62). These results suggest that local antibiotics augment the antimicrobial effect of systemic antibiotics. Although no significant difference was found between vehicles, gel delivery offers technical advantages with its biodegradable nature, ability to conform to wound shape and to deliver increased doses. Further study is required to see if the gel delivery system has a clinical role. ©2015 The British Editorial Society of Bone & Joint Surgery.

Numerical Simulation of Shock Wave Propagation in Fractured Cortical Bone

NASA Astrophysics Data System (ADS)

Padilla, Frédéric; Cleveland, Robin

2009-04-01

Shock waves (SW) are considered a promising method to treat bone non unions, but the associated mechanisms of action are not well understood. In this study, numerical simulations are used to quantify the stresses induced by SWs in cortical bone tissue. We use a 3D FDTD code to solve the linear lossless equations that describe wave propagation in solids and fluids. A 3D model of a fractured rat femur was obtained from micro-CT data with a resolution of 32 μm. The bone was subject to a plane SW pulse with a peak positive pressure of 40 MPa and peak negative pressure of -8 MPa. During the simulations the principal tensile stress and maximum shear stress were tracked throughout the bone. It was found that the simulated stresses in a transverse plane relative to the bone axis may reach values higher than the tensile and shear strength of the bone tissue (around 50 MPa). These results suggest that the stresses induced by the SW may be large enough to initiate local micro-fractures, which may in turn trigger the start of bone healing for the case of a non union.

Severe diffuse axon injury in chronic alcoholic rat medulla oblongata following a concussion blow.

PubMed

Luo, Jianming; Chen, Guang; Wei, Lai; Qian, Hong; Lai, Xiaoping; Wang, Dian; Lv, Junyao; Yu, Xiaojun

2014-01-01

We investigated the axonal morphological changes and expression of both tau protein and β-APP following concussion to the medulla oblongata, in a rat model of chronic alcoholism. Fifty-nine male Sprague-Dawley rats were randomly divided into EtOH, EtOH-TBI and control groups (water group, water-TBI group). To establish chronic alcoholic rats, rats were intragastrically given edible spirituous liquor twice daily. Rats also received a blow on the occipital tuberosity with an iron pendulum. Morphological changes and expression of tau and β-APP proteins in the medulla oblongata were examined. (a) Nerve fibre thickening and twisting were observed in alcoholic rats, with nerve fibre changes becoming more significant following a concussion blow, which leads to some nerve fibres fracturing. (b) Transmission electron microscopy revealed that the nerve fibre myelin became loosened and displayed lamellar separation, which became more significant following concussion. (c) The integral optical density (IOD) sum value of β-APP of the EtOH-TBI group was lower than that in the EtOH group (P < 0.05); the Tau IOD sum value of the EtOH-TBI group was higher than that in the EtOH group (P < 0.05). (a) Chronic alcoholism caused nerve fibre and neuronal morphology damage in the rat medulla oblongata, with structural damage becoming more significant following concussion. (b) Concussion changed the expression of β-APP and tau protein in chronic alcoholic rat medulla oblongata, suggesting that chronic alcoholism can lead to severe axonal injury following a concussion blow. (c) The effect of chronic alcoholism may be synergistic the concussion blow to promote animal injury and death.

Dysfunction of Inflammation-Resolving Pathways Is Associated with Exaggerated Postoperative Cognitive Decline in a Rat Model of the Metabolic Syndrome

PubMed Central

Su, Xiao; Feng, Xiaomei; Terrando, Niccolo; Yan, Yan; Chawla, Ajay; Koch, Lauren G; Britton, Steven L; Matthay, Michael A; Maze, Mervyn

2012-01-01

The cholinergic antiinflammatory pathway (CAP), which terminates in the spleen, attenuates postoperative cognitive decline (PCD) in rodents. Surgical patients with metabolic syndrome exhibit exaggerated and persistent PCD that is reproduced in postoperative rats selectively bred for easy fatigability and that contain all features of metabolic syndrome (low-capacity runners [LCRs]). We compared the CAP and lipoxin A4 (LXA4), another inflammation-resolving pathway in LCR, with its counterpart high-capacity runner (HCR) rats. Isoflurane-anesthetized LCR and HCR rats either underwent aseptic trauma involving tibial fracture (surgery) or not (sham). At postoperative d 3 (POD3), compared with HCR, LCR rats exhibited significantly exaggerated PCD (trace fear conditioning freezing time 43% versus 57%). Separate cohorts were killed at POD3 to collect plasma for LXA4 and to isolate splenic mononuclear cells (MNCs) to analyze CAP signaling, regulatory T cells (Tregs) and M2 macrophages (M2 Mφ). Under lipopolysaccharide (LPS) stimulation, tumor necrosis factor (TNF)-α produced by splenic MNCs was 117% higher in LCR sham and 52% higher in LCR surgery compared with HCR sham and surgery rats; LPS-stimulated TNF-α production could not be inhibited by an α7 nicotinic acetylcholine receptor agonist, whereas inhibition by the β2 adrenergic agonist, salmeterol, was significantly less (−35%) than that obtained in HCR rats. Compared to HCR, sham and surgery LCR rats had reduced β2 adrenergic receptor–expressing T lymphocytes (59%, 44%), Tregs (47%, 54%) and M2 Mφ (45%, 39%); surgical LCR rats’ hippocampal M2 Mφ was 66% reduced, and plasma LXA4 was decreased by 120%. Rats with the metabolic syndrome have ineffective inflammation-resolving mechanisms that represent plausible reasons for the exaggerated and persistent PCD. PMID:23296426

Synergistic antiosteoporotic effect of Lepidium sativum and alendronate in glucocorticoid-induced osteoporosis in Wistar rats.

PubMed

Elshal, Mohamed F; Almalki, Abdulrahman L; Hussein, Hussein K; Khan, Jalal A

2013-01-01

Alendronate belongs to a class of drugs called bisphosphonates. Bisphosphonates (BP) therapy is a vital option to reduce the risk of bone fracture in people who suffer from osteoporosis. Yet, bisphosphonate have displayed several side effects. Lepidium sativum (LS) seeds have been used in traditional folk medicine to heal fractured bones. However, there is a dearth of information on the impact of LS on bone metabolism especially in cases of glucocorticoids induced osteoporosis. Therefore, the aim of the study was to compare the biochemical bone markers and histological responses of LS alone (6 g of LS seeds in diet daily, n=8), ALD (alendronate, 70 mg/kg s.c.; n=8) alone, or LS and ALD combined in a rat model of glucocorticoid-induced osteoporosis (GIO) by injecting rats with methylprednisolone 3.5 mg/kg per day for 4 weeks. Serum calcium (Ca), albumin, phosphorus (P), bone-specific alkaline phosphatase (b-ALP), and tartrate-resistant acid phosphatase (TRAP) were measured 4 weeks after induction of GIO. GIO-group showed significantly increased serum TRAP and decreased b-ALP. GIO-group also showed significantly decreased serum P and unaltered Ca concentrations. Histological examination of GIO-group tibia bones indicated an osteoporotic change and a concomitant decrease in percentage of trabecular area or bone marrow area (PTB) in the proximal femoral epiphysis. Treatment with either LS and/or ALD ameliorated the above mentioned changes with variable degrees, with a net results of enhanced serum calcium, bone architecture, PTB, b-ALP and decreased TRAP in LS and LS+ALD groups compared to that of animals treated with alendronate alone. In conclusion, our findings present evidence supporting the potential benefits of LS in reducing the burden of GCs on bone health.

Mechanical and structural properties of bone in non-critical and critical healing in rat.

PubMed

Hoerth, Rebecca M; Seidt, Britta M; Shah, Miheer; Schwarz, Carolin; Willie, Bettina M; Duda, Georg N; Fratzl, Peter; Wagermaier, Wolfgang

2014-09-01

A fracture in bone results in a dramatic change of mechanical loading conditions at the site of injury. Usually, bone injuries heal normally but with increasing fracture gaps, healing is retarded, eventually leading to non-unions. The clinical situation of these two processes with different outcomes is well described. However, the exact relation between the mechanical environment and characteristics of the tissues at all levels of structural hierarchy remains unclear. Here we studied the differences in material formation of non-critical (1mm) and critical (5mm gap) healing. We employed a rat osteotomy model to explore bone material structure depending upon the different mechanical conditions. In both cases, primary bone formation was followed by secondary bone deposition with mineral particle sizes changing from on average short and thick to long and thin particles. Bony bridging occurred at first in the endosteal callus and the nanostructure and microstructure developed towards cortical ordered material organization. In contrast, in critical healing, instead of bridging, a marrow cavity closure was formed endosteal, exhibiting tissue structure oriented along the curvature and a periosteal callus with less mature material structure. The two healing processes separated between 4 and 6 weeks post-osteotomy. The outcome of healing was determined by the varied geometrical conditions in critical and non-critical healing, inducing completely different mechanical situations. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Prevention of Trauma/Hemorrhagic Shock-Induced Mortality,Apoptosis, Inflammation and Mitochondrial Dysfunction

DTIC Science & Technology

2013-12-01

suggesting another mechanism for the apoptosis-reduction benefit of IL-6 signaling, and 7) Stat3. can substitute for Stat3. to restore mitochondrial...Rats subjected to femur fracture and T-HS (AIM 2) and 3) Swine subjected to laparotomy, splenectomy, tissue injury and controlled HS (AIM 3). Aim...unacceptable mortality during the shock phase, the second was that there was variable amounts of bleeding from the femoral fracture site. We opted based on

Adjustable stiffness, external fixator for the rat femur osteotomy and segmental bone defect models.

PubMed

Glatt, Vaida; Matthys, Romano

2014-10-09

The mechanical environment around the healing of broken bone is very important as it determines the way the fracture will heal. Over the past decade there has been great clinical interest in improving bone healing by altering the mechanical environment through the fixation stability around the lesion. One constraint of preclinical animal research in this area is the lack of experimental control over the local mechanical environment within a large segmental defect as well as osteotomies as they heal. In this paper we report on the design and use of an external fixator to study the healing of large segmental bone defects or osteotomies. This device not only allows for controlled axial stiffness on the bone lesion as it heals, but it also enables the change of stiffness during the healing process in vivo. The conducted experiments have shown that the fixators were able to maintain a 5 mm femoral defect gap in rats in vivo during unrestricted cage activity for at least 8 weeks. Likewise, we observed no distortion or infections, including pin infections during the entire healing period. These results demonstrate that our newly developed external fixator was able to achieve reproducible and standardized stabilization, and the alteration of the mechanical environment of in vivo rat large bone defects and various size osteotomies. This confirms that the external fixation device is well suited for preclinical research investigations using a rat model in the field of bone regeneration and repair.

Effects of Strontium Ranelate on Spinal Interbody Fusion Surgery in an Osteoporotic Rat Model

PubMed Central

Tsai, Tsung-Ting; Ho, Natalie Yi-Ju; Lai, Po-Liang; Fu, Tsai-Sheng; Niu, Chi-Chien; Chen, Lih-Huei; Chen, Wen-Jer

2017-01-01

Osteoporosis is a bone disease that afflicts millions of people around the world, and a variety of spinal integrity issues, such as degenerative spinal stenosis and spondylolisthesis, are frequently concomitant with osteoporosis and are sometimes treated with spinal interbody fusion surgery. Previous studies have demonstrated the efficacy of strontium ranelate (SrR) treatment of osteoporosis in improving bone strength, promoting bone remodeling, and reducing the risk of fractures, but its effects on interbody fusion surgery have not been adequately investigated. SrR-treated rats subjected to interbody fusion surgery exhibited significantly higher lumbar vertebral bone mineral density after 12 weeks of treatment than rats subjected to the same surgery but not treated with SrR. Furthermore, histological and radiographic assessments showed that a greater amount of newly formed bone tissue was present and that better fusion union occurred in the SrR-treated rats than in the untreated rats. Taken together, these results show significant differences in bone mineral density, PINP level, histological score, SrR content and mechanical testing, which demonstrate a relatively moderate effect of SrR treatment on bone strength and remodeling in the specific context of recovery after an interbody fusion surgery, and suggest the potential of SrR treatment as an effective adjunct to spinal interbody fusion surgery for human patients. PMID:28052066

New concept of 3D printed bone clip (polylactic acid/hydroxyapatite/silk composite) for internal fixation of bone fractures.

PubMed

Yeon, Yeung Kyu; Park, Hae Sang; Lee, Jung Min; Lee, Ji Seung; Lee, Young Jin; Sultan, Md Tipu; Seo, Ye Bin; Lee, Ok Joo; Kim, Soon Hee; Park, Chan Hum

Open reduction with internal fixation is commonly used for the treatment of bone fractures. However, postoperative infection associated with internal fixation devices (intramedullary nails, plates, and screws) remains a significant complication, and it is technically difficult to fix multiple fragmented bony fractures using internal fixation devices. In addition, drilling in the bone to install devices can lead to secondary fracture, bone necrosis associated with postoperative infection. In this study, we developed bone clip type internal fixation device using three- dimensional (3D) printing technology. Standard 3D model of the bone clip was generated based on computed tomography (CT) scan of the femur in the rat. Polylacticacid (PLA), hydroxyapatite (HA), and silk were used for bone clip material. The purpose of this study was to characterize 3D printed PLA, PLA/HA, and PLA/HA/Silk composite bone clip and evaluate the feasibility of these bone clips as an internal fixation device. Based on the results, PLA/HA/Silk composite bone clip showed similar mechanical property, and superior biocompatibility compared to other types of the bone clip. PLA/HA/Silk composite bone clip demonstrated excellent alignment of the bony segments across the femur fracture site with well-positioned bone clip in an animal study. Our 3D printed bone clips have several advantages: (1) relatively noninvasive (drilling in the bone is not necessary), (2) patient-specific design (3) mechanically stable device, and (4) it provides high biocompatibility. Therefore, we suggest that our 3D printed PLA/HA/Silk composite bone clip is a possible internal fixation device.

Glabridin and glycyrrhizic acid show no beneficial effect on the chemical composition and mechanical properties of bones in ovariectomized rats, when administered in moderate dose.

PubMed

Kaczmarczyk-Sedlak, Ilona; Klasik-Ciszewska, Sylwia; Wojnar, Weronika

2016-10-01

One of the major causes of osteoporosis and bone fracture in postmenopausal women is estrogen deficiency. To prevent the fractures, and avoid the side effects of hormone replacement therapy, phytoestrogens including the isoflavonoids are used. In the presented study two constituents occurring in the licorice root-the isoflavane glabridin and triterpenoid saponin glycyrrhizic acid were examined on the skeletal system of ovariectomized rats. The female Wistar rats were divided into five groups: control group, ovariectomized group as well as three ovariectomized groups treated with estradiol (0.2mg/kg), glabridin (5mg/kg) or glycyrrhizic acid (15mg/kg). All substances were administered orally for 4 weeks. The estradiol served as a positive control. The mechanical properties of femoral diaphysis, tibial metaphysis and femoral neck were assessed using bending and compression tests. Moreover the chemical composition of the femur, tibia and L-4 vertebra - content of water, organic substances and minerals - was determined. Ovariectomy induced unfavorable changes in the skeletal system of the rats. Administration of glabridin and glycyrrhizic acid to the ovariectomized rats did not improve analyzed parameters of the bones. Obtained results indicate, that the tested substances revealed no beneficial effect on the mechanical properties and chemical composition of the tested bones, thus they cannot be used as the osteoporosis protective agents. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

An Equivalent Fracture Modeling Method

NASA Astrophysics Data System (ADS)

Li, Shaohua; Zhang, Shujuan; Yu, Gaoming; Xu, Aiyun

2017-12-01

3D fracture network model is built based on discrete fracture surfaces, which are simulated based on fracture length, dip, aperture, height and so on. The interesting area of Wumishan Formation of Renqiu buried hill reservoir is about 57 square kilometer and the thickness of target strata is more than 2000 meters. In addition with great fracture density, the fracture simulation and upscaling of discrete fracture network model of Wumishan Formation are very intense computing. In order to solve this problem, a method of equivalent fracture modeling is proposed. First of all, taking the fracture interpretation data obtained from imaging logging and conventional logging as the basic data, establish the reservoir level model, and then under the constraint of reservoir level model, take fault distance analysis model as the second variable, establish fracture density model by Sequential Gaussian Simulation method. Increasing the width, height and length of fracture, at the same time decreasing its density in order to keep the similar porosity and permeability after upscaling discrete fracture network model. In this way, the fracture model of whole interesting area can be built within an accepted time.

Electroacupuncture stimulation at CV4 prevents ovariectomy-induced osteoporosis in rats via Wnt-β-catenin signaling.

PubMed

Fan, Huailing; Ji, Feng; Lin, Ying; Zhang, Mulan; Qin, Wei; Zhou, Qi; Wu, Qiang

2016-03-01

The present study aimed to investigate the effect of electroacupuncture stimulation at CV4 (also termed Guanyuan) on femoral osteocalcin also termed bone gla protein (BGP), alkaline phosphatase (ALP), bone mineral density (BMD) and biomechanics, as well as the Wnt‑β‑catenin signaling pathway in rats with postmenopausal osteoporosis. Female Sprague‑Dawley rats (4.5‑months old) were randomly divided into sham, Ovx, CV4 and mock groups (n=10/group). With the exception of those in the sham group, the rats were ovariectomized to induce postmenopausal osteoporosis. The rats in the CV4 and mock groups were given electroacupuncture at CV4 and non‑acupoint, respectively. The rats in the Ovx model and sham groups underwent identical fixing procedures, but did not undergo electroacupuncture. Following treatment, hematoxylin and eosin staining was used to observe morphological changes in the left femoral trabecular bone, and a three‑point‑bending test was used to analyze femur biomechanics and determine the BMD. In addition, an enzyme‑linked immunosorbent assay was used to measure the serum levels of ALP/BGP and reverse transcription‑quantitative polymerase chain reaction was used detect the expression levels of Wnt3a, β‑catenin and Runx2. In the present study, it was demonstrated that electroacupuncture at CV4 significantly improved the osteoporotic morphological changes that occurred in the ovariectomized rats, increased serum ALP and BGP levels, enhanced the maximum and fracture loads, increased BMD (P<0.01), and activated the Wnt‑β‑catenin signaling pathway. These findings demonstrated that electroacupuncture stimulation at CV4 affected bone formation and promoted bone metabolism in rats with postmenopausal osteoporosis, possibly by activating the Wnt‑β‑catenin signaling pathway.

Electroacupuncture stimulation at CV4 prevents ovariectomy-induced osteoporosis in rats via Wnt-β-catenin signaling

PubMed Central

FAN, HUAILING; JI, FENG; LIN, YING; ZHANG, MULAN; QIN, WEI; ZHOU, QI; WU, QIANG

2016-01-01

The present study aimed to investigate the effect of electroacupuncture stimulation at CV4 (also termed Guanyuan) on femoral osteocalcin also termed bone gla protein (BGP), alkaline phosphatase (ALP), bone mineral density (BMD) and biomechanics, as well as the Wnt-β-catenin signaling pathway in rats with postmenopausal osteoporosis. Female Sprague-Dawley rats (4.5-months old) were randomly divided into sham, Ovx, CV4 and mock groups (n=10/group). With the exception of those in the sham group, the rats were ovariectomized to induce postmenopausal osteoporosis. The rats in the CV4 and mock groups were given electroacupuncture at CV4 and non-acupoint, respectively. The rats in the Ovx model and sham groups underwent identical fixing procedures, but did not undergo electroacupuncture. Following treatment, hematoxylin and eosin staining was used to observe morphological changes in the left femoral trabecular bone, and a three-point-bending test was used to analyze femur biomechanics and determine the BMD. In addition, an enzyme-linked immunosorbent assay was used to measure the serum levels of ALP/BGP and reverse transcription-quantitative polymerase chain reaction was used detect the expression levels of Wnt3a, β-catenin and Runx2. In the present study, it was demonstrated that electroacupuncture at CV4 significantly improved the osteoporotic morphological changes that occurred in the ovariectomized rats, increased serum ALP and BGP levels, enhanced the maximum and fracture loads, increased BMD (P<0.01), and activated the Wnt-β-catenin signaling pathway. These findings demonstrated that electroacupuncture stimulation at CV4 affected bone formation and promoted bone metabolism in rats with postmenopausal osteoporosis, possibly by activating the Wnt-β-catenin signaling pathway. PMID:26846191

Fully Coupled 3D Finite Element Model of Hydraulic Fracturing in a Permeable Rock Formation

NASA Astrophysics Data System (ADS)

Salimzadeh, S.; Paluszny, A.; Zimmerman, R. W.

2015-12-01

Hydraulic fracturing in permeable rock formations is a complex three-dimensional multi-physics phenomenon. Numerous analytical models of hydraulic fracturing processes have been proposed that typically simplify the physical processes, or somehow reduce the problem from three dimensions to two dimensions. Moreover, although such simplified models are able to model the growth of a single hydraulic fracture into an initially intact, homogeneous rock mass, they are generally not able to model fracturing of heterogeneous rock formations, or to account for interactions between multiple induced fractures, or between an induced fracture and pre-existing natural fractures. We have developed a numerical finite-element model for hydraulic fracturing that does not suffer from any of the limitations mentioned above. The model accounts for fluid flow within a fracture, the propagation of the fracture, and the leak-off of fluid from the fracture into the host rock. Fluid flow through the permeable rock matrix is modelled using Darcy's law, and is coupled with the laminar flow within the fracture. Fractures are discretely modelled in the three-dimensional mesh. Growth of a fracture is modelled using the concepts of linear elastic fracture mechanics (LEFM), with the onset and direction of growth based on stress intensity factors that are computed for arbitrary tetrahedral meshes. The model has been verified against several analytical solutions available in the literature for plane-strain (2D) and penny-shaped (3D) fractures, for various regimes of domination: viscosity, toughness, storage and leak-off. The interaction of the hydraulically driven fracture with pre-existing fractures and other fluid-driven fractures in terms of fluid leak-off, stress interaction and fracture arrest is investigated and the results are presented. Finally, some preliminary results are presented regarding the interaction of a hydraulically-induced fracture with a set of pre-existing natural fractures.

Citrus juice modulates bone strength in male senescent rat model of osteoporosis.

PubMed

Deyhim, Farzad; Garica, Kristy; Lopez, Erica; Gonzalez, Julia; Ino, Sumiyo; Garcia, Michelle; Patil, Bhimanagouda S

2006-05-01

An experiment evaluated the effect of citrus juice on enhancing serum antioxidant status and on osteoporosis prevention in orchidectomized rats. Thirty-six 1-y-old male rats were randomized to two groups: a sham-control group (n = 9) and an orchidectomized group (n = 27). The orchidectomized group was divided into three groups of nine and assigned to one of the following treatments: orchidectomy, orchidectomy plus orange juice, and orchidectomy plus grapefruit juice. Sixty days after initiation of the study, all rats were killed, blood was collected, and serum was harvested for total antioxidant status and indices of bone formation and resorption. Femoral density and biomechanical properties were monitored. Orchidectomy decreased (P < 0.05) total antioxidant capacity, femoral density, and biomechanical properties and increased (P < 0.05) alkaline phosphatase, acid phosphatase, and urinary excretion of hydroxyproline compared with the sham-control group. In contrast to orchidectomy, orchidectomy plus orange juice and orchidectomy plus grapefruit juice reversed (P < 0.05) orchidectomy-induced antioxidant suppression, decreased (P < 0.05) alkaline phosphatase and acid phosphatase activities, moderately restored (P = 0.07) femoral density, increased (P < 0.05) femoral strength, significantly delayed time-induced femoral fracture, and decreased (P < 0.05) urinary excretion of hydroxyproline. The present study supports the supposition in that drinking citrus juice positively affects serum antioxidant status and bone strength.

TOUGH-RBSN simulator for hydraulic fracture propagation within fractured media: Model validations against laboratory experiments

NASA Astrophysics Data System (ADS)

Kim, Kunhwi; Rutqvist, Jonny; Nakagawa, Seiji; Birkholzer, Jens

2017-11-01

This paper presents coupled hydro-mechanical modeling of hydraulic fracturing processes in complex fractured media using a discrete fracture network (DFN) approach. The individual physical processes in the fracture propagation are represented by separate program modules: the TOUGH2 code for multiphase flow and mass transport based on the finite volume approach; and the rigid-body-spring network (RBSN) model for mechanical and fracture-damage behavior, which are coupled with each other. Fractures are modeled as discrete features, of which the hydrological properties are evaluated from the fracture deformation and aperture change. The verification of the TOUGH-RBSN code is performed against a 2D analytical model for single hydraulic fracture propagation. Subsequently, modeling capabilities for hydraulic fracturing are demonstrated through simulations of laboratory experiments conducted on rock-analogue (soda-lime glass) samples containing a designed network of pre-existing fractures. Sensitivity analyses are also conducted by changing the modeling parameters, such as viscosity of injected fluid, strength of pre-existing fractures, and confining stress conditions. The hydraulic fracturing characteristics attributed to the modeling parameters are investigated through comparisons of the simulation results.

Animal models for glucocorticoid-induced postmenopausal osteoporosis: An updated review.

PubMed

Zhang, Zhida; Ren, Hui; Shen, Gengyang; Qiu, Ting; Liang, De; Yang, Zhidong; Yao, Zhensong; Tang, Jingjing; Jiang, Xiaobing; Wei, Qiushi

2016-12-01

Glucocorticoid-induced postmenopausal osteoporosis is a severe osteoporosis, with high risk of major osteoporotic fractures. This severe osteoporosis urges more extensive and deeper basic study, in which suitable animal models are indispensable. However, no relevant review is available introducing this model systematically. Based on the recent studies on GI-PMOP, this brief review introduces the GI-PMOP animal model in terms of its establishment, evaluation of bone mass and discuss its molecular mechanism. Rat, rabbit and sheep with their respective merits were chosen. Both direct and indirect evaluation of bone mass help to understand the bone metabolism under different intervention. The crucial signaling pathways, miRNAs, osteogenic- or adipogenic- related factors and estrogen level may be the predominant contributors to the development of glucocorticoid-induced postmenopausal osteoporosis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rybicki, E.F.; Luiskutty, C.T.; Sutrick, J.S.

This User's Manual contains information for four fracture/proppant models. TUPROP1 contains a Geertsma and de Klerk type fracture model. The section of the program utilizing the proppant fracture geometry data from the pseudo three-dimensional highly elongated fracture model is called TUPROPC. The analogous proppant section of the program that was modified to accept fracture shape data from SA3DFRAC is called TUPROPS. TUPROPS also includes fracture closure. Finally there is the penny fracture and its proppant model, PENNPROP. In the first three chapters, the proppant sections are based on the same theory for determining the proppant distribution but have modifications tomore » support variable height fractures and modifications to accept fracture geometry from three different fracture models. Thus, information about each proppant model in the User's Manual builds on information supplied in the previous chapter. The exception to the development of combined treatment models is the penny fracture and its proppant model. In this case, a completely new proppant model was developed. A description of how to use the combined treatment model for the penny fracture is contained in Chapter 4. 2 refs.« less

Recent Advances and Future of Gene Therapy for Bone Regeneration.

PubMed

Shapiro, Galina; Lieber, Raphael; Gazit, Dan; Pelled, Gadi

2018-06-16

The purpose of this review is to discuss the recent advances in gene therapy as a treatment for bone regeneration. While most fractures heal spontaneously, patients who present with fracture nonunion suffer from prolonged pain, disability, and often require additional operations to regain musculoskeletal function. In the last few years, BMP gene delivery by means of electroporation and sonoporation resulted in repair of nonunion bone defects in mice, rats, and minipigs. Ex vivo transfection of porcine mesenchymal stem cells (MSCs) resulted in bone regeneration following implantation in vertebral defects of minipigs. Sustained release of VEGF gene from a collagen-hydroxyapatite scaffold to the mandible of a human patient was shown to be safe and osteoinductive. In conclusion, gene therapy methods for bone regeneration are systematically becoming more efficient and show proof-of-concept in clinically relevant animal models. Yet, on the pathway to clinical use, more investigation is needed to determine the safety aspects of the various techniques in terms of biodistribution, toxicity, and tumorigenicity.

An efficient hydro-mechanical model for coupled multi-porosity and discrete fracture porous media

NASA Astrophysics Data System (ADS)

Yan, Xia; Huang, Zhaoqin; Yao, Jun; Li, Yang; Fan, Dongyan; Zhang, Kai

2018-02-01

In this paper, a numerical model is developed for coupled analysis of deforming fractured porous media with multiscale fractures. In this model, the macro-fractures are modeled explicitly by the embedded discrete fracture model, and the supporting effects of fluid and fillings in these fractures are represented explicitly in the geomechanics model. On the other hand, matrix and micro-fractures are modeled by a multi-porosity model, which aims to accurately describe the transient matrix-fracture fluid exchange process. A stabilized extended finite element method scheme is developed based on the polynomial pressure projection technique to address the displacement oscillation along macro-fracture boundaries. After that, the mixed space discretization and modified fixed stress sequential implicit methods based on non-matching grids are applied to solve the coupling model. Finally, we demonstrate the accuracy and application of the proposed method to capture the coupled hydro-mechanical impacts of multiscale fractures on fractured porous media.

Empirically Based Composite Fracture Prediction Model From the Global Longitudinal Study of Osteoporosis in Postmenopausal Women (GLOW)

PubMed Central

Compston, Juliet E.; Chapurlat, Roland D.; Pfeilschifter, Johannes; Cooper, Cyrus; Hosmer, David W.; Adachi, Jonathan D.; Anderson, Frederick A.; Díez-Pérez, Adolfo; Greenspan, Susan L.; Netelenbos, J. Coen; Nieves, Jeri W.; Rossini, Maurizio; Watts, Nelson B.; Hooven, Frederick H.; LaCroix, Andrea Z.; March, Lyn; Roux, Christian; Saag, Kenneth G.; Siris, Ethel S.; Silverman, Stuart; Gehlbach, Stephen H.

2014-01-01

Context: Several fracture prediction models that combine fractures at different sites into a composite outcome are in current use. However, to the extent individual fracture sites have differing risk factor profiles, model discrimination is impaired. Objective: The objective of the study was to improve model discrimination by developing a 5-year composite fracture prediction model for fracture sites that display similar risk profiles. Design: This was a prospective, observational cohort study. Setting: The study was conducted at primary care practices in 10 countries. Patients: Women aged 55 years or older participated in the study. Intervention: Self-administered questionnaires collected data on patient characteristics, fracture risk factors, and previous fractures. Main Outcome Measure: The main outcome is time to first clinical fracture of hip, pelvis, upper leg, clavicle, or spine, each of which exhibits a strong association with advanced age. Results: Of four composite fracture models considered, model discrimination (c index) is highest for an age-related fracture model (c index of 0.75, 47 066 women), and lowest for Fracture Risk Assessment Tool (FRAX) major fracture and a 10-site model (c indices of 0.67 and 0.65). The unadjusted increase in fracture risk for an additional 10 years of age ranges from 80% to 180% for the individual bones in the age-associated model. Five other fracture sites not considered for the age-associated model (upper arm/shoulder, rib, wrist, lower leg, and ankle) have age associations for an additional 10 years of age from a 10% decrease to a 60% increase. Conclusions: After examining results for 10 different bone fracture sites, advanced age appeared the single best possibility for uniting several different sites, resulting in an empirically based composite fracture risk model. PMID:24423345

Discrete Fracture Network Characterization of Fractured Shale Reservoirs with Implications to Hydraulic Fracturing Optimization

NASA Astrophysics Data System (ADS)

Jin, G.

2016-12-01

Shales are important petroleum source rocks and reservoir seals. Recent developments in hydraulic fracturing technology have facilitated high gas production rates from shale and have had a strong impact on the U.S. gas supply and markets. Modeling of effective permeability for fractured shale reservoirs has been challenging because the presence of a fracture network significantly alters the reservoir hydrologic properties. Due to the frequent occurrence of fracture networks, it is of vital importance to characterize fracture networks and to investigate how these networks can be used to optimize the hydraulic fracturing. We have conducted basic research on 3-D fracture permeability characterization and compartmentization analyses for fractured shale formations, which takes the advantages of the discrete fracture networks (DFN). The DFN modeling is a stochastic modeling approach using the probabilistic density functions of fractures. Three common scenarios of DFN models have been studied for fracture permeability mapping using our previously proposed techniques. In DFN models with moderately to highly concentrated fractures, there exists a representative element volume (REV) for fracture permeability characterization, which indicates that the fractured reservoirs can be treated as anisotropic homogeneous media. Hydraulic fracturing will be most effective if the orientation of the hydraulic fracture is perpendicular to the mean direction of the fractures. A DFN model with randomized fracture orientations, on the other hand, lacks an REV for fracture characterization. Therefore, a fracture permeability tensor has to be computed from each element. Modeling of fracture interconnectivity indicates that there exists no preferred direction for hydraulic fracturing to be most effective oweing to the interconnected pathways of the fracture network. 3-D fracture permeability mapping has been applied to the Devonian Chattanooga Shale in Alabama and the results suggest that an REV exist for fluid flow and transport modeling at element sizes larger than 200 m. Fracture pathway analysis indicates that hydraulic fracturing can be equally effective for hydrocarbon fluid/gas exploration as long as its orientation is not aligned with that of the regional system fractures.

Microarray profiling of diaphyseal bone of rats suffering from hypervitaminosis A.

PubMed

Lind, Thomas; Hu, Lijuan; Lind, P Monica; Sugars, Rachael; Andersson, Göran; Jacobson, Annica; Melhus, Håkan

2012-03-01

Vitamin A is the only known compound that produces spontaneous fractures in rats. In an effort to resolve the molecular mechanism behind this effect, we fed young male rats high doses of vitamin A and performed microarray analysis of diaphyseal bone with and without marrow after 1 week, i.e., just before the first fractures appeared. Of the differentially expressed genes in cortical bone, including marrow, 98% were upregulated. In contrast, hypervitaminotic cortical bone without marrow showed reduced expression of 37% of differentially expressed genes. Gene ontology (GO) analysis revealed that only samples containing bone marrow were associated with a GO term, which principally represented extracellular matrix. This is consistent with the histological findings of increased endosteal/marrow osteoblast number. Fourteen genes, including Cyp26b1, which is known to be upregulated by vitamin A, were selected and verified by real-time PCR. In addition, immunohistochemical staining of bone sections confirmed that the bone-specific molecule osteoadherin was upregulated. Further analysis of the major gene-expression changes revealed apparent augmented Wnt signaling in the sample containing bone marrow but reduced Wnt signaling in cortical bone. Moreover, induced expression of hypoxia-associated genes was found only in samples containing bone marrow. Together, these results highlight the importance of compartment-specific analysis of bone and corroborate previous observations of compartment-specific effects of vitamin A, with reduced activity in cortical bone but increased activity in the endosteal/marrow compartment. We specifically identify potential key osteoblast-, Wnt signaling-, and hypoxia-associated genes in the processes leading to spontaneous fractures.

Effect of formononetin on mechanical properties and chemical composition of bones in rats with ovariectomy-induced osteoporosis.

PubMed

Kaczmarczyk-Sedlak, Ilona; Wojnar, Weronika; Zych, Maria; Ozimina-Kamińska, Ewa; Taranowicz, Joanna; Siwek, Agata

2013-01-01

Formononetin is a naturally occurring isoflavone, which can be found in low concentrations in many dietary products, but the greatest sources of this substance are Astragalus membranaceus, Trifolium pratense, Glycyrrhiza glabra, and Pueraria lobata, which all belong to Fabaceae family. Due to its structural similarity to 17 β -estradiol, it can mimic estradiol's effect and therefore is considered as a "phytoestrogen." The aim of this study was to examine the effect of formononetin on mechanical properties and chemical composition of bones in rats with ovariectomy-induced osteoporosis. 12-week-old female rats were divided into 4 groups: sham-operated, ovariectomized, ovariectomized treated with estradiol (0.2 mg/kg) and ovariectomized treated with formononetin (10 mg/kg). Analyzed substances were administered orally for 4 weeks. Ovariectomy caused osteoporotic changes, which can be observed in bone biomechanical features (decrease of maximum load and fracture load and increase of displacements for maximum and fracture loads) and bone chemical composition (increase of water and organic fraction content, while a decrease of minerals takes place). Supplementation with formononetin resulted in slightly enhanced bone mechanical properties and bone chemistry improvement (significantly lower water content and insignificantly higher mineral fraction content). To summarize, administration of formononetin to ovariectomized rats shows beneficial effect on bone biomechanical features and chemistry; thus, it can prevent osteoporosis development.

Effect of Formononetin on Mechanical Properties and Chemical Composition of Bones in Rats with Ovariectomy-Induced Osteoporosis

PubMed Central

Kaczmarczyk-Sedlak, Ilona; Wojnar, Weronika; Zych, Maria; Ozimina-Kamińska, Ewa; Taranowicz, Joanna; Siwek, Agata

2013-01-01

Formononetin is a naturally occurring isoflavone, which can be found in low concentrations in many dietary products, but the greatest sources of this substance are Astragalus membranaceus, Trifolium pratense, Glycyrrhiza glabra, and Pueraria lobata, which all belong to Fabaceae family. Due to its structural similarity to 17β-estradiol, it can mimic estradiol's effect and therefore is considered as a “phytoestrogen.” The aim of this study was to examine the effect of formononetin on mechanical properties and chemical composition of bones in rats with ovariectomy-induced osteoporosis. 12-week-old female rats were divided into 4 groups: sham-operated, ovariectomized, ovariectomized treated with estradiol (0.2 mg/kg) and ovariectomized treated with formononetin (10 mg/kg). Analyzed substances were administered orally for 4 weeks. Ovariectomy caused osteoporotic changes, which can be observed in bone biomechanical features (decrease of maximum load and fracture load and increase of displacements for maximum and fracture loads) and bone chemical composition (increase of water and organic fraction content, while a decrease of minerals takes place). Supplementation with formononetin resulted in slightly enhanced bone mechanical properties and bone chemistry improvement (significantly lower water content and insignificantly higher mineral fraction content). To summarize, administration of formononetin to ovariectomized rats shows beneficial effect on bone biomechanical features and chemistry; thus, it can prevent osteoporosis development. PMID:23762138

Implications of combined Ovariectomy/Multi-Deficiency Diet on rat bone with age-related variation in Bone Parameters and Bone Loss at Multiple Skeletal Sites by DEXA

PubMed Central

Govindarajan, Parameswari; Schlewitz, Gudrun; Schliefke, Nathalie; Weisweiler, David; Alt, Volker; Thormann, Ulrich; Lips, Katrin Susanne; Wenisch, Sabine; Langheinrich, Alexander C.; Zahner, Daniel; Hemdan, Nasr Y.; Böcker, Wolfgang; Schnettler, Reinhard; Heiss, Christian

2013-01-01

Background Osteoporosis is a multi-factorial, chronic, skeletal disease highly prevalent in post-menopausal women and is influenced by hormonal and dietary factors. Because animal models are imperative for disease diagnostics, the present study establishes and evaluates enhanced osteoporosis obtained through combined ovariectomy and deficient diet by DEXA (dual-energy X-ray absorptiometry) for a prolonged time period. Material/Methods Sprague-Dawley rats were randomly divided into sham (laparotomized) and OVX-diet (ovariectomized and fed with deficient diet) groups. Different skeletal sites were scanned by DEXA at the following time points: M0 (baseline), M12 (12 months post-surgery), and M14 (14 months post-surgery). Parameters analyzed included BMD (bone mineral density), BMC (bone mineral content), bone area, and fat (%). Regression analysis was performed to determine the interrelationships between BMC, BMD, and bone area from M0 to M14. Results BMD and BMC were significantly lower in OVX-diet rats at M12 and M14 compared to sham rats. The Z-scores were below −5 in OVX-diet rats at M12, but still decreased at M14 in OVX-diet rats. Bone area and percent fat were significantly lower in OVX-diet rats at M14 compared to sham rats. The regression coefficients for BMD vs. bone area, BMC vs. bone area, and BMC vs. BMD of OVX-diet rats increased with time. This is explained by differential percent change in BMD, BMC, and bone area with respect to time and disease progression. Conclusions Combined ovariectomy and deficient diet in rats caused significant reduction of BMD, BMC, and bone area, with nearly 40% bone loss after 14 months, indicating the development of severe osteoporosis. An increasing regression coefficient of BMD vs. bone area with disease progression emphasizes bone area as an important parameter, along with BMD and BMC, for prediction of fracture risk. PMID:23446183

Implications of combined ovariectomy/multi-deficiency diet on rat bone with age-related variation in bone parameters and bone loss at multiple skeletal sites by DEXA.

PubMed

Govindarajan, Parameswari; Schlewitz, Gudrun; Schliefke, Nathalie; Weisweiler, David; Alt, Volker; Thormann, Ulrich; Lips, Katrin Susanne; Wenisch, Sabine; Langheinrich, Alexander C; Zahner, Daniel; Hemdan, Nasr Y; Böcker, Wolfgang; Schnettler, Reinhard; Heiss, Christian

2013-02-28

Osteoporosis is a multi-factorial, chronic, skeletal disease highly prevalent in post-menopausal women and is influenced by hormonal and dietary factors. Because animal models are imperative for disease diagnostics, the present study establishes and evaluates enhanced osteoporosis obtained through combined ovariectomy and deficient diet by DEXA (dual-energy X-ray absorptiometry) for a prolonged time period. Sprague-Dawley rats were randomly divided into sham (laparotomized) and OVX-diet (ovariectomized and fed with deficient diet) groups. Different skeletal sites were scanned by DEXA at the following time points: M0 (baseline), M12 (12 months post-surgery), and M14 (14 months post-surgery). Parameters analyzed included BMD (bone mineral density), BMC (bone mineral content), bone area, and fat (%). Regression analysis was performed to determine the interrelationships between BMC, BMD, and bone area from M0 to M14. BMD and BMC were significantly lower in OVX-diet rats at M12 and M14 compared to sham rats. The Z-scores were below -5 in OVX-diet rats at M12, but still decreased at M14 in OVX-diet rats. Bone area and percent fat were significantly lower in OVX-diet rats at M14 compared to sham rats. The regression coefficients for BMD vs. bone area, BMC vs. bone area, and BMC vs. BMD of OVX-diet rats increased with time. This is explained by differential percent change in BMD, BMC, and bone area with respect to time and disease progression. Combined ovariectomy and deficient diet in rats caused significant reduction of BMD, BMC, and bone area, with nearly 40% bone loss after 14 months, indicating the development of severe osteoporosis. An increasing regression coefficient of BMD vs. bone area with disease progression emphasizes bone area as an important parameter, along with BMD and BMC, for prediction of fracture risk.

Hydraulic Fracturing and Production Optimization in Eagle Ford Shale Using Coupled Geomechanics and Fluid Flow Model

NASA Astrophysics Data System (ADS)

Suppachoknirun, Theerapat; Tutuncu, Azra N.

2017-12-01

With increasing production from shale gas and tight oil reservoirs, horizontal drilling and multistage hydraulic fracturing processes have become a routine procedure in unconventional field development efforts. Natural fractures play a critical role in hydraulic fracture growth, subsequently affecting stimulated reservoir volume and the production efficiency. Moreover, the existing fractures can also contribute to the pressure-dependent fluid leak-off during the operations. Hence, a reliable identification of the discrete fracture network covering the zone of interest prior to the hydraulic fracturing design needs to be incorporated into the hydraulic fracturing and reservoir simulations for realistic representation of the in situ reservoir conditions. In this research study, an integrated 3-D fracture and fluid flow model have been developed using a new approach to simulate the fluid flow and deliver reliable production forecasting in naturally fractured and hydraulically stimulated tight reservoirs. The model was created with three key modules. A complex 3-D discrete fracture network model introduces realistic natural fracture geometry with the associated fractured reservoir characteristics. A hydraulic fracturing model is created utilizing the discrete fracture network for simulation of the hydraulic fracture and flow in the complex discrete fracture network. Finally, a reservoir model with the production grid system is used allowing the user to efficiently perform the fluid flow simulation in tight formations with complex fracture networks. The complex discrete natural fracture model, the integrated discrete fracture model for the hydraulic fracturing, the fluid flow model, and the input dataset have been validated against microseismic fracture mapping and commingled production data obtained from a well pad with three horizontal production wells located in the Eagle Ford oil window in south Texas. Two other fracturing geometries were also evaluated to optimize the cumulative production and for the three wells individually. Significant reduction in the production rate in early production times is anticipated in tight reservoirs regardless of the fracturing techniques implemented. The simulations conducted using the alternating fracturing technique led to more oil production than when zipper fracturing was used for a 20-year production period. Yet, due to the decline experienced, the differences in cumulative production get smaller, and the alternating fracturing is not practically implementable while field application of zipper fracturing technique is more practical and widely used.

High-Dose α-Tocopherol Supplementation Does Not Induce Bone Loss in Normal Rats

PubMed Central

Kasai, Shunji; Ito, Akemi; Shindo, Kaori; Toyoshi, Tohru; Bando, Masahiro

2015-01-01

Oxidative stress affects bone turnover. Preventative effects of antioxidants such as vitamin E on reduced bone mineral density and fractures associated with aging, osteoporosis, and smoking have been examined in animals and humans. The effects of vitamin E (α-tocopherol; αT) on bone health have yielded conflicting and inconclusive results from animal studies. In this study, to determine the bone effects of αT, we investigated the in vivo effects of αT on the bone mineral density, bone mass, bone microstructure, bone resorption, and osteogenesis through peripheral quantitative computed tomography (pQCT) measurements, micro-computed tomography (micro-CT) analyses, and bone histomorphometry of lumbar vertebrae and femurs in normal female Wistar rats fed diets containing αT in different quantities (0, 30, 120, or 600 mg/kg diet) for 8 weeks. To validate our hypotheses regarding bone changes, we examined ovariectomized rats as an osteoporosis model and control sham-operated rats in parallel. As expected, ovariectomized rats had reduced bone mineral density in lumbar vertebrae and the distal metaphyses of their femurs, reduced bone mass and deteriorated microstructure of cancellous bones in the vertebral body and distal femur metaphyses, and reduced bone mass due to resorption-dominant enhanced bone turnover in secondary cancellous bones in these sites. In comparison, αT administered to normal rats, even at the highest dose, did not induce reduced bone mineral density of lumbar vertebrae and femurs or a reduced bone mass or fragile microstructure of cancellous bones of the vertebral body and distal femur metaphyses. Instead, αT-fed rats showed a tendency for an osteogenesis-dominant bone mass increase in secondary cancellous bones in the vertebral body, in which active bone remodeling occurs. Thus, αT consumption may have beneficial effects on bone health. PMID:26147575

Ulmus davidiana extract improves lumbar vertebral parameters in ovariectomized osteopenic rats

PubMed Central

Zhuang, Xinming; Fu, Changfeng; Liu, Wanguo; Wang, Yuanyi; Xu, Feng; Zhang, Qi; Liu, Yadong; Liu, Yi

2016-01-01

The aim of this study was to determine the skeletal effect of total ethanolic extract from the stem-bark of Ulmus davidiana (UDE) in a rat model of postmenopausal bone loss. Effective dose of UDE was determined in adult female Sprague-Dawley (SD) rats by measuring bone regeneration at fracture site. UDE (250 mg/kg p.o.) was administered to ovariectomized (OVX) osteopenic SD rats for 12 weeks. OVX rats treated with vehicle or 17β-estradiol, and sham-operated rats treated with vehicle served as various controls. Bone mineral density (BMD), microarchitecture, biomechanical strength, turnover markers, and uterotrophic effect were studied. Bioactive markers in UDE were analyzed by HPLC. Human osteoblasts was used to study the effect of compounds on differentiation by alkaline phosphase assay. One-way ANOVA was used to test significance of effects. OVX+UDE group showed BMD, microarchitectural parameters and compressive strength at lumbar vertebra (L5) comparable to sham. At proximal femur, OVX+UDE group exhibited significantly higher BMD, better microarchitecture and compressive strength compared with OVX+vehicle. OVX-induced decrease in Ca/P ratio was completely restored at both skeletal sites by UDE treatment. Serum procollagen N-terminal propeptide and carboxy-terminal collagen crosslinks were respectively higher and lower in OVX+UDE group compared with OVX+vehicle group. Osteogenic genes were upregulated in L5 and anti-resorptive genes were suppressed in proximal femur of OVX+UDE group compared with OVX+vehicle. UDE had no uterine estrogenicity. Analysis of markers yielded two osteogenic isoforms of catechin. In conclusion, UDE completely restored vertebral trabecular bones and strength in osteopenic rats by an osteogenic mechanism and prevented bone loss at proximal femur. PMID:27158327

Hydroxyapatite-nanotube composites and coatings for orthopedic applications

NASA Astrophysics Data System (ADS)

Lahiri, Debrupa

Hydroxyapatite (HA) has received wide attention in orthopedics, due to its biocompatibility and osseointegration ability. Despite these advantages, the brittle nature and low fracture toughness of HA often results in rapid wear and premature fracture of implant. Hence, there is a need to improve the fracture toughness and wear resistance of HA without compromising its biocompatibility. The aim of the current research is to explore the potential of nanotubes as reinforcement to HA for orthopedic implants. HA- 4 wt.% carbon nanotube (CNT) composites and coatings are synthesized by spark plasma sintering and plasma spraying respectively, and investigated for their mechanical, tribological and biological behavior. CNT reinforcement improves the fracture toughness (>90%) and wear resistance (>66%) of HA for coating and free standing composites. CNTs have demonstrated a positive influence on the proliferation, differentiation and matrix mineralization activities of osteoblasts, during in-vitro biocompatibility studies. In-vivo exposure of HA-CNT coated titanium implant in animal model (rat) shows excellent histocompatibility and neobone integration on the implant surface. The improved osseointegration due to presence of CNTs in HA is quantified by the adhesion strength measurement of single osteoblast using nano-scratch technique. Considering the ongoing debate about cytotoxicity of CNTs in the literature, the present study also suggests boron nitride nanotube (BNNT) as an alternative reinforcement. BNNT with the similar elastic modulus and strength as CNT, were added to HA. The resulting composite having 4 wt.% BNNTs improved the fracture toughness (˜85%) and wear resistance (˜75%) of HA in the similar range as HA-CNT composites. BNNTs were found to be non-cytotoxic for osteoblasts and macrophages. In-vitro evaluation shows positive role of BNNT in osteoblast proliferation and viability. Apatite formability of BNNT surface in ˜4 days establishes its osseointegration ability.

Simulation of Hydraulic and Natural Fracture Interaction Using a Coupled DFN-DEM Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, J.; Huang, H.; Deo, M.

2016-03-01

The presence of natural fractures will usually result in a complex fracture network due to the interactions between hydraulic and natural fracture. The reactivation of natural fractures can generally provide additional flow paths from formation to wellbore which play a crucial role in improving the hydrocarbon recovery in these ultra-low permeability reservoir. Thus, accurate description of the geometry of discrete fractures and bedding is highly desired for accurate flow and production predictions. Compared to conventional continuum models that implicitly represent the discrete feature, Discrete Fracture Network (DFN) models could realistically model the connectivity of discontinuities at both reservoir scale andmore » well scale. In this work, a new hybrid numerical model that couples Discrete Fracture Network (DFN) and Dual-Lattice Discrete Element Method (DL-DEM) is proposed to investigate the interaction between hydraulic fracture and natural fractures. Based on the proposed model, the effects of natural fracture orientation, density and injection properties on hydraulic-natural fractures interaction are investigated.« less

Simulation of Hydraulic and Natural Fracture Interaction Using a Coupled DFN-DEM Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

J. Zhou; H. Huang; M. Deo

The presence of natural fractures will usually result in a complex fracture network due to the interactions between hydraulic and natural fracture. The reactivation of natural fractures can generally provide additional flow paths from formation to wellbore which play a crucial role in improving the hydrocarbon recovery in these ultra-low permeability reservoir. Thus, accurate description of the geometry of discrete fractures and bedding is highly desired for accurate flow and production predictions. Compared to conventional continuum models that implicitly represent the discrete feature, Discrete Fracture Network (DFN) models could realistically model the connectivity of discontinuities at both reservoir scale andmore » well scale. In this work, a new hybrid numerical model that couples Discrete Fracture Network (DFN) and Dual-Lattice Discrete Element Method (DL-DEM) is proposed to investigate the interaction between hydraulic fracture and natural fractures. Based on the proposed model, the effects of natural fracture orientation, density and injection properties on hydraulic-natural fractures interaction are investigated.« less

External validation of the Garvan nomograms for predicting absolute fracture risk: the Tromsø study.

PubMed

Ahmed, Luai A; Nguyen, Nguyen D; Bjørnerem, Åshild; Joakimsen, Ragnar M; Jørgensen, Lone; Størmer, Jan; Bliuc, Dana; Center, Jacqueline R; Eisman, John A; Nguyen, Tuan V; Emaus, Nina

2014-01-01

Absolute risk estimation is a preferred approach for assessing fracture risk and treatment decision making. This study aimed to evaluate and validate the predictive performance of the Garvan Fracture Risk Calculator in a Norwegian cohort. The analysis included 1637 women and 1355 aged 60+ years from the Tromsø study. All incident fragility fractures between 2001 and 2009 were registered. The predicted probabilities of non-vertebral osteoporotic and hip fractures were determined using models with and without BMD. The discrimination and calibration of the models were assessed. Reclassification analysis was used to compare the models performance. The incidence of osteoporotic and hip fracture was 31.5 and 8.6 per 1000 population in women, respectively; in men the corresponding incidence was 12.2 and 5.1. The predicted 5-year and 10-year probability of fractures was consistently higher in the fracture group than the non-fracture group for all models. The 10-year predicted probabilities of hip fracture in those with fracture was 2.8 (women) to 3.1 times (men) higher than those without fracture. There was a close agreement between predicted and observed risk in both sexes and up to the fifth quintile. Among those in the highest quintile of risk, the models over-estimated the risk of fracture. Models with BMD performed better than models with body weight in correct classification of risk in individuals with and without fracture. The overall net decrease in reclassification of the model with weight compared to the model with BMD was 10.6% (p = 0.008) in women and 17.2% (p = 0.001) in men for osteoporotic fractures, and 13.3% (p = 0.07) in women and 17.5% (p = 0.09) in men for hip fracture. The Garvan Fracture Risk Calculator is valid and clinically useful in identifying individuals at high risk of fracture. The models with BMD performed better than those with body weight in fracture risk prediction.

[Analysis of a three-dimensional finite element model of atlas and axis complex fracture].

PubMed

Tang, X M; Liu, C; Huang, K; Zhu, G T; Sun, H L; Dai, J; Tian, J W

2018-05-22

Objective: To explored the clinical application of the three-dimensional finite element model of atlantoaxial complex fracture. Methods: A three-dimensional finite element model of cervical spine (FEM/intact) was established by software of Abaqus6.12.On the basis of this model, a three-dimensional finite element model of four types of atlantoaxial complex fracture was established: C(1) fracture (Jefferson)+ C(2) fracture (type Ⅱfracture), Jefferson+ C(2) fracture(type Ⅲfracture), Jefferson+ C(2) fracture(Hangman), Jefferson+ stable C(2) fracture (FEM/fracture). The range of motion under flexion, extension, lateral bending and axial rotation were measured and compared with the model of cervical spine. Results: The three-dimensional finite element model of four types of atlantoaxial complex fracture had the same similarity and profile.The range of motion (ROM) of different segments had different changes.Compared with those in the normal model, the ROM of C(0/1) and C(1/2) in C(1) combined Ⅱ odontoid fracture model in flexion/extension, lateral bending and rotation increased by 57.45%, 29.34%, 48.09% and 95.49%, 88.52%, 36.71%, respectively.The ROM of C(0/1) and C(1/2) in C(1) combined Ⅲodontoid fracture model in flexion/extension, lateral bending and rotation increased by 47.01%, 27.30%, 45.31% and 90.38%, 27.30%, 30.0%.The ROM of C(0/1) and C(1/2) in C(1) combined Hangman fracture model in flexion/extension, lateral bending and rotation increased by 32.68%, 79.34%, 77.62% and 60.53%, 81.20%, 21.48%, respectively.The ROM of C(0/1) and C(1/2) in C(1) combined axis fracture model in flexion/extension, lateral bending and rotation increased by 15.00%, 29.30%, 8.47% and 37.87%, 75.57%, 8.30%, respectively. Conclusions: The three-dimensional finite element model can be used to simulate the biomechanics of atlantoaxial complex fracture.The ROM of atlantoaxial complex fracture is larger than nomal model, which indicates that surgical treatment should be performed.

A new approach to fracture modelling in reservoirs using deterministic, genetic and statistical models of fracture growth

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rawnsley, K.; Swaby, P.

1996-08-01

It is increasingly acknowledged that in order to understand and forecast the behavior of fracture influenced reservoirs we must attempt to reproduce the fracture system geometry and use this as a basis for fluid flow calculation. This article aims to present a recently developed fracture modelling prototype designed specifically for use in hydrocarbon reservoir environments. The prototype {open_quotes}FRAME{close_quotes} (FRActure Modelling Environment) aims to provide a tool which will allow the generation of realistic 3D fracture systems within a reservoir model, constrained to the known geology of the reservoir by both mechanical and statistical considerations, and which can be used asmore » a basis for fluid flow calculation. Two newly developed modelling techniques are used. The first is an interactive tool which allows complex fault surfaces and their associated deformations to be reproduced. The second is a {open_quotes}genetic{close_quotes} model which grows fracture patterns from seeds using conceptual models of fracture development. The user defines the mechanical input and can retrieve all the statistics of the growing fractures to allow comparison to assumed statistical distributions for the reservoir fractures. Input parameters include growth rate, fracture interaction characteristics, orientation maps and density maps. More traditional statistical stochastic fracture models are also incorporated. FRAME is designed to allow the geologist to input hard or soft data including seismically defined surfaces, well fractures, outcrop models, analogue or numerical mechanical models or geological {open_quotes}feeling{close_quotes}. The geologist is not restricted to {open_quotes}a priori{close_quotes} models of fracture patterns that may not correspond to the data.« less

Systemic and Local Administration of Antimicrobial and Cell Therapies to Prevent Methicillin-Resistant Staphylococcus epidermidis-Induced Femoral Nonunions in a Rat Model

PubMed Central

Drago, Lorenzo; Bottagisio, Marta; Bongio, Matilde; Ferrario, Marzia; Perego, Silvia; Sansoni, Veronica; De Vecchi, Elena; Romanò, Carlo L.

2016-01-01

S. epidermidis is responsible for biofilm-related nonunions. This study compares the response to S. epidermidis-infected fractures in rats systemically or locally injected with vancomycin or bone marrow mesenchymal stem cells (BMSCs) in preventing the nonunion establishment. The 50% of rats receiving BMSCs intravenously (s-rBMSCs) died after treatment. A higher cytokine trend was measured in BMSCs locally injected rats (l-rBMSCs) at day 3 and in vancomycin systemically injected rats (l-VANC) at day 7 compared to the other groups. At day 14, the highest cytokine values were measured in l-VANC and in l-rBMSCs for IL-10. µCT showed a good bony bridging in s-VANC and excellent both in l-VANC and in l-rBMSCs. The bacterial growth was lower in s-VANC and l-VANC than in l-rBMSCs. Histology demonstrated the presence of new woven bone in s-VANC and a more mature bony bridging was found in l-VANC. The l-rBMSCs showed a poor bony bridging of fibrovascular tissue. Our results could suggest the synergic use of systemic and local injection of vancomycin as an effective treatment to prevent septic nonunions. This study cannot sustain the systemic injection of BMSCs due to high risks, while a deeper insight into local BMSCs immunomodulatory effects is mandatory before developing cell therapies in clinics. PMID:27478310

Investigation of the Effect of Cemented Fractures on Fracturing Network Propagation in Model Block with Discrete Orthogonal Fractures

NASA Astrophysics Data System (ADS)

Wang, Y.; Li, C. H.

2017-07-01

Researchers have recently realized that the natural fractures in shale reservoirs are often cemented or sealed with various minerals. However, the influence of cement characteristics of natural fracture on fracturing network propagation is still not well understood. In this work, laboratory-scaled experiments are proposed to prepare model blocks with discrete orthogonal fractures network with different strength of natural fracture, in order to reveal the influence of cemented natural fractures on the interactions between hydraulic fractures and natural fractures. A series of true triaxial hydraulic fracturing experiments were conducted to investigate the mechanism of hydraulic fracture initiation and propagation in model blocks with natural fractures of different cement strength. The results present different responses of interactions between hydraulic and natural fractures, which can be reflected on the pump pressure profiles and block failure morphology. For model blocks with fluctuated pump pressure curves, the communication degree of hydraulic and natural fractures is good, which is confirmed by a proposed new index of "P-SRV." The most significant finding is that too high and too low strength properties of cemented natural fracture are adverse to generate complex fracturing network. This work can help us better understand how cemented natural fractures affect the fracturing network propagation subsurface and give us reference to develop more accurate hydraulic fracturing models.

Evaluation of Cameroonian plants towards experimental bone regeneration.

PubMed

Ngueguim, Florence Tsofack; Khan, Mohd Parvez; Donfack, Jean Hubert; Siddiqui, Jawed Akhtar; Tewari, Deepshikha; Nagar, Geet K; Tiwari, Satish C; Theophile, Dimo; Maurya, Rakesh; Chattopadhyay, Naibedya

2012-05-07

Elephantopus mollis, Spilanthes africana, Urena lobata, Momordica multiflora, Asystasia gangetica and Brillantaisia ovariensis are used in Cameroonian traditional medicine for the treatment of bone diseases and fracture repair. The aim of this study was to evaluate the effect of ethanolic extracts of six Cameroonian medicinal plants on bone regeneration following bone and marrow injury. Ethanol extract of Cameroonian medicinal plants were administered (each extract at 250, 500 and 750mg/kg doses) orally to adult female Sprague-Dawley rats having a drill hole injury (0.8mm) in the femur diaphysis. Vehicle (gum-acacia in distilled water) was given to the control group. After 12 days of treatment, animals were euthanized and femur bones collected. Confocal microscopy of fractured bone was performed to evaluate bone regeneration (calcein labeling). Only active plant extracts were used for further experiments. Thus, callus was analyzed by microcomputed tomography. Osteogenic effects of the extracts were evaluated by assessing mineralized nodules formation of bone marrow stromal cells and osteoblast recruitment at drill hole site by immunohistochemistry. Ethanolic extract of the leaves and twigs of Elephantopus mollis (EM) and whole plant of Spilanthes africana (SA) dose-dependently stimulated bone regeneration at the drill hole site. EM at 250 and 750mg/kg doses and SA at 750mg/kg dose significantly increased mineral deposition compared to controls. Both extracts at 500 and 750mg/kg doses improved microarchitecture of the regenerating bone evident from increased bone volume fraction, trabecular thickness, trabecular number, and decreased trabecular separation and structure model index. EM and SA extracts increased the formation of mineralized nodules from the bone marrow stromal cells. In addition, EM and SA extracts increased osteoblast recruitment at the drill hole site evident from increased Runx-2 positive cells following their treatments compared to control. Ethanolic extracts of EM and SA accelerate fracture repair in rats via stimulatory effects on osteoblast differentiation and mineralization, thereby justifying their traditional use. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

A rat model of concurrent combined injuries (polytrauma)

PubMed Central

Akscyn, Robert M; Franklin, J Lee; Gavrikova, Tatyana A; Schwacha, Martin G; Messina, Joseph L

2015-01-01

Polytrauma, a combination of injuries to more than one body part or organ system, is common in modern warfare and in automobile and industrial accidents. The combination of injuries can include burn injury, fracture, hemorrhage, trauma to the extremities, and trauma to specific organ systems. To investigate the effects of combined injuries, we have developed a new and highly reproducible model of polytrauma. This model combines burn injury with soft tissue and gastrointestinal (GI) tract trauma. Male Sprague Dawley rats were subjected to a 15-20% total body surface area scald burn, or a single puncture of the cecum with a G30 needle, or the combination of both injuries (polytrauma). Unlike many ‘double hit’ models, the injuries in our model were performed simultaneously. We asked whether multiple minor injuries, when combined, would result in a distinct phenotype, different from single minor injuries or a more severe single injury. There were differences between the single injuries and polytrauma in the maintenance of blood glucose, body temperature, body weight, hepatic mRNA and circulating levels of TNF-α, IL-1β and IL-6, and hepatic ER-stress. It has been suggested that models utilizing combinatorial injuries may be needed to more accurately model the human condition. We believe our model is ideal for studying the complex sequelae of polytrauma, which differs from single injuries. Insights gained from this model may suggest better treatment options to improve patient outcomes. PMID:26884923

Developing a Fracture Model of the Granite Rocks Around the Research Tunnel at the Mizunami Underground Research Laboratory in Central Japan

NASA Astrophysics Data System (ADS)

Kalinina, E.; Hadgu, T.; Wang, Y.

2017-12-01

The Mizunami Underground Research Laboratory (MIU) is located in Tono area in Central Japan. It is operated by the Japan Atomic Energy Agency (JAEA) with the main purpose of providing scientific basis for the research and development of technologies needed for deep geological disposal of radioactive waste in fractured crystalline rocks. The current work is focused on the research and experiments in the tunnel located at 500 m depth. The data collected in the tunnel and exploratory boreholes were shared with the participants of the DEvelopment of COupled models and their VALidation against EXperiments (DECOVALEX), an international research and model comparison collaboration. This study describes the development of the fracture model representing granite rocks around the research tunnel. The model domain is 100x150x100m with the main experimental part of the tunnel, Closure Test Drift, located approximately in the center. The major input data were the fracture traces measured on the tunnel walls (total of 2,023 fractures), fractures observed in the horizontal borehole parallel to the tunnel, and the packer tests conducted in this borehole and one vertical borehole located within the modeling domain. 78 fractures (the ones with the inflow) in the tunnel were incorporated in the development of the fracture model. Fracture size was derived from the fracture trace analysis. It was shown that the fracture radius followed lognormal distributions. Fracture transmissivity was estimated from an analytical solution of inflow into the tunnel through an individual fracture and the total measured inflow into the tunnel. 16 fractures were incorporated in the model along the horizontal borehole. The packer test data in the different well intervals were used to estimate the range in fracture transmissivity. A relationship between the fracture transmissivity and fracture radius was developed. The fractures in the tunnel and borehole were used to derive fracture orientation and fracture intensity distributions. These distributions were used to generate stochastic fractures outside the tunnel and horizontal borehole. The fracture model was upscaled to an orthogonal continuum mesh with 1x1x1 m3 cell size using Oda's method.

An Embedded 3D Fracture Modeling Approach for Simulating Fracture-Dominated Fluid Flow and Heat Transfer in Geothermal Reservoirs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnston, Henry; Wang, Cong; Winterfeld, Philip

An efficient modeling approach is described for incorporating arbitrary 3D, discrete fractures, such as hydraulic fractures or faults, into modeling fracture-dominated fluid flow and heat transfer in fractured geothermal reservoirs. This technique allows 3D discrete fractures to be discretized independently from surrounding rock volume and inserted explicitly into a primary fracture/matrix grid, generated without including 3D discrete fractures in prior. An effective computational algorithm is developed to discretize these 3D discrete fractures and construct local connections between 3D fractures and fracture/matrix grid blocks of representing the surrounding rock volume. The constructed gridding information on 3D fractures is then added tomore » the primary grid. This embedded fracture modeling approach can be directly implemented into a developed geothermal reservoir simulator via the integral finite difference (IFD) method or with TOUGH2 technology This embedded fracture modeling approach is very promising and computationally efficient to handle realistic 3D discrete fractures with complicated geometries, connections, and spatial distributions. Compared with other fracture modeling approaches, it avoids cumbersome 3D unstructured, local refining procedures, and increases computational efficiency by simplifying Jacobian matrix size and sparsity, while keeps sufficient accuracy. Several numeral simulations are present to demonstrate the utility and robustness of the proposed technique. Our numerical experiments show that this approach captures all the key patterns about fluid flow and heat transfer dominated by fractures in these cases. Thus, this approach is readily available to simulation of fractured geothermal reservoirs with both artificial and natural fractures.« less

Effects of voluntary running exercise on bone histology in type 2 diabetic rats.

PubMed

Takamine, Yuri; Ichinoseki-Sekine, Noriko; Tsuzuki, Takamasa; Yoshihara, Toshinori; Naito, Hisashi

2018-01-01

The incidence of obesity in children and adolescents, which may lead to type 2 diabetes, is increasing. Exercise is recommended to prevent and improve diabetes. However, little is known about the bone marrow environment at the onset of diabetes in the young, and it is unclear whether exercise training is useful for maintaining bone homeostasis, such as mechanical and histological properties. Thus, this study clarified the histological properties of bone and whether exercise contributes to maintaining bone homeostasis at the onset of type 2 diabetes in rats. Four-week-old male Otsuka Long-Evans Tokushima Fatty (OLETF; n = 21) rats as a diabetic model and Long-Evans Tokushima Otsuka (LETO; n = 18) rats as a control were assigned randomly to four groups: the OLETF sedentary group (O-Sed; n = 11), OLETF exercise group (O-Ex; n = 10), LETO sedentary group (L-Sed; n = 9), and LETO exercise group (L-Ex; n = 9). All rats in the exercise group were allowed free access to a steel running wheel for 20 weeks (5-25 weeks of age). In the glucose tolerance test, blood glucose level was higher in the O-Sed group than that in the L-Sed and L-Ex groups, and was markedly suppressed by the voluntary running exercise of O-Ex rats. The energy to fracture and the two-dimensional bone volume at 25 weeks of age did not differ significantly among the groups, though the maximum breaking force and stiffness were lower in OLETF rats. However, bone marrow fat volume was greater in O-Sed than that in L-Sed and L-Ex rats, and was markedly suppressed by wheel running in the O-Ex rats. Our results indicate that exercise has beneficial effects not only for preventing diabetes but also on normal bone remodeling at an early age.

An analytical model for hydraulic fracturing in shallow bedrock formations.

PubMed

dos Santos, José Sérgio; Ballestero, Thomas Paul; Pitombeira, Ernesto da Silva

2011-01-01

A theoretical method is proposed to estimate post-fracturing fracture size and transmissivity, and as a test of the methodology, data collected from two wells were used for verification. This method can be employed before hydrofracturing in order to obtain estimates of the potential hydraulic benefits of hydraulic fracturing. Five different pumping test analysis methods were used to evaluate the well hydraulic data. The most effective methods were the Papadopulos-Cooper model (1967), which includes wellbore storage effects, and the Gringarten-Ramey model (1974), known as the single horizontal fracture model. The hydraulic parameters resulting from fitting these models to the field data revealed that as a result of hydraulic fracturing, the transmissivity increased more than 46 times in one well and increased 285 times in the other well. The model developed by dos Santos (2008), which considers horizontal radial fracture propagation from the hydraulically fractured well, was used to estimate potential fracture geometry after hydrofracturing. For the two studied wells, their fractures could have propagated to distances of almost 175 m or more and developed maximum apertures of about 2.20 mm and hydraulic apertures close to 0.30 mm. Fracturing at this site appears to have expanded and propagated existing fractures and not created new fractures. Hydraulic apertures calculated from pumping test analyses closely matched the results obtained from the hydraulic fracturing model. As a result of this model, post-fracturing geometry and resulting post-fracturing well yield can be estimated before the actual hydrofracturing. Copyright © 2010 The Author(s). Journal compilation © 2010 National Ground Water Association.

External Validation of the Garvan Nomograms for Predicting Absolute Fracture Risk: The Tromsø Study

PubMed Central

Ahmed, Luai A.; Nguyen, Nguyen D.; Bjørnerem, Åshild; Joakimsen, Ragnar M.; Jørgensen, Lone; Størmer, Jan; Bliuc, Dana; Center, Jacqueline R.; Eisman, John A.; Nguyen, Tuan V.; Emaus, Nina

2014-01-01

Background Absolute risk estimation is a preferred approach for assessing fracture risk and treatment decision making. This study aimed to evaluate and validate the predictive performance of the Garvan Fracture Risk Calculator in a Norwegian cohort. Methods The analysis included 1637 women and 1355 aged 60+ years from the Tromsø study. All incident fragility fractures between 2001 and 2009 were registered. The predicted probabilities of non-vertebral osteoporotic and hip fractures were determined using models with and without BMD. The discrimination and calibration of the models were assessed. Reclassification analysis was used to compare the models performance. Results The incidence of osteoporotic and hip fracture was 31.5 and 8.6 per 1000 population in women, respectively; in men the corresponding incidence was 12.2 and 5.1. The predicted 5-year and 10-year probability of fractures was consistently higher in the fracture group than the non-fracture group for all models. The 10-year predicted probabilities of hip fracture in those with fracture was 2.8 (women) to 3.1 times (men) higher than those without fracture. There was a close agreement between predicted and observed risk in both sexes and up to the fifth quintile. Among those in the highest quintile of risk, the models over-estimated the risk of fracture. Models with BMD performed better than models with body weight in correct classification of risk in individuals with and without fracture. The overall net decrease in reclassification of the model with weight compared to the model with BMD was 10.6% (p = 0.008) in women and 17.2% (p = 0.001) in men for osteoporotic fractures, and 13.3% (p = 0.07) in women and 17.5% (p = 0.09) in men for hip fracture. Conclusions The Garvan Fracture Risk Calculator is valid and clinically useful in identifying individuals at high risk of fracture. The models with BMD performed better than those with body weight in fracture risk prediction. PMID:25255221

Linear Elastic and Cohesive Fracture Analysis to Model Hydraulic Fracture in Brittle and Ductile Rocks

NASA Astrophysics Data System (ADS)

Yao, Yao

2012-05-01

Hydraulic fracturing technology is being widely used within the oil and gas industry for both waste injection and unconventional gas production wells. It is essential to predict the behavior of hydraulic fractures accurately based on understanding the fundamental mechanism(s). The prevailing approach for hydraulic fracture modeling continues to rely on computational methods based on Linear Elastic Fracture Mechanics (LEFM). Generally, these methods give reasonable predictions for hard rock hydraulic fracture processes, but still have inherent limitations, especially when fluid injection is performed in soft rock/sand or other non-conventional formations. These methods typically give very conservative predictions on fracture geometry and inaccurate estimation of required fracture pressure. One of the reasons the LEFM-based methods fail to give accurate predictions for these materials is that the fracture process zone ahead of the crack tip and softening effect should not be neglected in ductile rock fracture analysis. A 3D pore pressure cohesive zone model has been developed and applied to predict hydraulic fracturing under fluid injection. The cohesive zone method is a numerical tool developed to model crack initiation and growth in quasi-brittle materials considering the material softening effect. The pore pressure cohesive zone model has been applied to investigate the hydraulic fracture with different rock properties. The hydraulic fracture predictions of a three-layer water injection case have been compared using the pore pressure cohesive zone model with revised parameters, LEFM-based pseudo 3D model, a Perkins-Kern-Nordgren (PKN) model, and an analytical solution. Based on the size of the fracture process zone and its effect on crack extension in ductile rock, the fundamental mechanical difference of LEFM and cohesive fracture mechanics-based methods is discussed. An effective fracture toughness method has been proposed to consider the fracture process zone effect on the ductile rock fracture.

The impact of in-situ stress and outcrop-based fracture geometry on hydraulic aperture and upscaled permeability in fractured reservoirs

NASA Astrophysics Data System (ADS)

Bisdom, Kevin; Bertotti, Giovanni; Nick, Hamidreza M.

2016-10-01

Aperture has a controlling impact on porosity and permeability and is a source of uncertainty in modeling of naturally fractured reservoirs. This uncertainty results from difficulties in accurately quantifying aperture in the subsurface and from a limited fundamental understanding of the mechanical and diagenetic processes that control aperture. In the absence of cement bridges and high pore pressure, fractures in the subsurface are generally considered to be closed. However, experimental work, outcrop analyses and subsurface data show that some fractures remain open, and that aperture varies even along a single fracture. However, most fracture flow models consider constant apertures for fractures. We create a stress-dependent heterogeneous aperture by combining Finite Element modeling of discrete fracture networks with an empirical aperture model. Using a modeling approach that considers fractures explicitly, we quantify equivalent permeability, i.e. combined matrix and stress-dependent fracture flow. Fracture networks extracted from a large outcropping pavement form the basis of these models. The results show that the angle between fracture strike and σ1 has a controlling impact on aperture and permeability, where hydraulic opening is maximum for an angle of 15°. At this angle, the fracture experiences a minor amount of shear displacement that allows the fracture to remain open even when fluid pressure is lower than the local normal stress. Averaging the heterogeneous aperture to scale up permeability probably results in an underestimation of flow, indicating the need to incorporate full aperture distributions rather than simplified aperture models in reservoir-scale flow models.

Ductile fracture theories for pressurised pipes and containers

NASA Technical Reports Server (NTRS)

Erdogan, F.

1976-01-01

Two mechanisms of fracture are distinguished. Plane strain fractures occur in materials which do not undergo large-scale plastic deformations prior to and during a possible fracture deformation. Plane stress or high energy fractures are generally accompanied by large inelastic deformations. Theories for analyzing plane stress are based on the concepts of critical crack opening stretch, K(R) characterization, J-integral, and plastic instability. This last is considered in some detail. The ductile fracture process involves fracture initiation followed by a stable crack growth and the onset of unstable fracture propagation. The ductile fracture propagation process may be characterized by either a multiparameter (discrete) model, or some type of a resistance curve which may be considered as a continuous model expressed graphically. These models are studied and an alternative model is also proposed for ductile fractures which cannot be modeled as progressive crack growth phenomena.

Modeling of Propagation of Interacting Cracks Under Hydraulic Pressure Gradient

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Hai; Mattson, Earl Douglas; Podgorney, Robert Karl

A robust and reliable numerical model for fracture initiation and propagation, which includes the interactions among propagating fractures and the coupling between deformation, fracturing and fluid flow in fracture apertures and in the permeable rock matrix, would be an important tool for developing a better understanding of fracturing behaviors of crystalline brittle rocks driven by thermal and (or) hydraulic pressure gradients. In this paper, we present a physics-based hydraulic fracturing simulator based on coupling a quasi-static discrete element model (DEM) for deformation and fracturing with conjugate lattice network flow model for fluid flow in both fractures and porous matrix. Fracturingmore » is represented explicitly by removing broken bonds from the network to represent microcracks. Initiation of new microfractures and growth and coalescence of the microcracks leads to the formation of macroscopic fractures when external and/or internal loads are applied. The coupled DEM-network flow model reproduces realistic growth pattern of hydraulic fractures. In particular, simulation results of perforated horizontal wellbore clearly demonstrate that elastic interactions among multiple propagating fractures, fluid viscosity, strong coupling between fluid pressure fluctuations within fractures and fracturing, and lower length scale heterogeneities, collectively lead to complicated fracturing patterns.« less

The subsurface impact of hydraulic fracturing in shales- Perspectives from the well and reservoir

NASA Astrophysics Data System (ADS)

ter Heege, Jan; Coles, Rhys

2017-04-01

It has been identified that the main risks of subsurface shale gas operations in the U.S.A. and Canada are associated with (1) drilling and well integrity, (2) hydraulic fracturing, and (3) induced seismicity. Although it is unlikely that hydraulic fracturing operations result in direct pathways of enhanced migration between stimulated fracture disturbed rock volume and shallow aquifers, operations may jeopardize well integrity or induce seismicity. From the well perspective, it is often assumed that fluid injection leads to the initiation of tensile (mode I) fractures at different perforation intervals along the horizontal sections of shale gas wells if pore pressure exceeds the minimum principal stress. From the reservoir perspective, rise in pore pressure resulting from fluid injection may lead to initiation of tensile fractures, reactivation of shear (mode II) fractures if the criterion for failure in shear is exceeded, or combinations of different fracturing modes. In this study, we compare tensile fracturing simulations using conventional well-based models with shear fracturing simulations using a fractured shale model with characteristic fault populations. In the fractured shale model, stimulated permeability is described by an analytical model that incorporates populations of reactivated faults and that combines 3D permeability tensors for layered shale matrix, damage zone and fault core. Well-based models applied to wells crosscutting the Posidonia Shale Formation are compared to generic fractured shale models, and fractured shale models are compared to micro-seismic data from the Marcellus Shale. Focus is on comparing the spatial distribution of permeability, stimulated reservoir volume and seismicity, and on differences in fracture initiation pressure and fracture orientation for tensile and shear fracturing end-members. It is shown that incorporation of fault populations (for example resulting from analysis of 3D seismics or outcrops) in hydraulic fracturing models provides better constraints on well pressures, stimulated fracture disturbed volume and induced seismicity. Thereby, it helps assessing the subsurface impact of hydraulic fracturing in shales and mitigating risks associated with loss of loss of well integrity, loss of fracture containment, and induced seismicity.

Discrete fracture modeling of multiphase flow and hydrocarbon production in fractured shale or low permeability reservoirs

NASA Astrophysics Data System (ADS)

Hao, Y.; Settgast, R. R.; Fu, P.; Tompson, A. F. B.; Morris, J.; Ryerson, F. J.

2016-12-01

It has long been recognized that multiphase flow and transport in fractured porous media is very important for various subsurface applications. Hydrocarbon fluid flow and production from hydraulically fractured shale reservoirs is an important and complicated example of multiphase flow in fractured formations. The combination of horizontal drilling and hydraulic fracturing is able to create extensive fracture networks in low permeability shale rocks, leading to increased formation permeability and enhanced hydrocarbon production. However, unconventional wells experience a much faster production decline than conventional hydrocarbon recovery. Maintaining sustainable and economically viable shale gas/oil production requires additional wells and re-fracturing. Excessive fracturing fluid loss during hydraulic fracturing operations may also drive up operation costs and raise potential environmental concerns. Understanding and modeling processes that contribute to decreasing productivity and fracturing fluid loss represent a critical component for unconventional hydrocarbon recovery analysis. Towards this effort we develop a discrete fracture model (DFM) in GEOS (LLNL multi-physics computational code) to simulate multiphase flow and transfer in hydraulically fractured reservoirs. The DFM model is able to explicitly account for both individual fractures and their surrounding rocks, therefore allowing for an accurate prediction of impacts of fracture-matrix interactions on hydrocarbon production. We apply the DFM model to simulate three-phase (water, oil, and gas) flow behaviors in fractured shale rocks as a result of different hydraulic stimulation scenarios. Numerical results show that multiphase flow behaviors at the fracture-matrix interface play a major role in controlling both hydrocarbon production and fracturing fluid recovery rates. The DFM model developed in this study will be coupled with the existing hydro-fracture model to provide a fully integrated geomechanical and reservoir simulation capability for an accurate prediction and assessment of hydrocarbon production and hydraulic fracturing performance. This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

Laboratory research of fracture geometry in multistage HFF in triaxial state

NASA Astrophysics Data System (ADS)

Bondarenko, T. M.; Hou, B.; Chen, M.; Yan, L.

2017-05-01

Multistage hydraulic fracturing of formation (HFF) in wells with horizontal completion is an efficientmethod for intensifying oil extraction which, as a rule, is used to develop nontraditional collectors. It is assumed that the complicated character of HFF fractures significantly influences the fracture geometry in the rock matrix. Numerous theoretical models proposed to predict the fracture geometry and the character of interaction of mechanical stresses in the multistage HFF have not been proved experimentally. In this paper, we present the results of laboratory modeling of the multistage HFF performed on a contemporary laboratory-scale plant in the triaxial stress state by using a gel-solution as the HFF agent. As a result of the experiment, a fracturing pattern was formed in the cubic specimen of the model material. The laboratory results showed that a nearly plane fracture is formed at the firstHFF stage, while a concave fracture is formed at the second HFF stage. The interaction of the stress fields created by the two principal HFF fractures results in the growth of secondary fractures whose directions turned out to be parallel to the modeled well bore. But this stress interference leads to a decrease in the width of the second principal fracture. It is was discovered that the penny-shaped fracture model is more appropriate for predicting the geometry of HFF fractures in horizontal wells than the two-dimensional models of fracture propagation (PKN model, KGD model). A computational experiment based on the boundary element method was carried out to obtain the qualitative description of the multistage HFF processes. As a result, a mechanical model of fracture propagation was constructed,which was used to obtain the mechanical stress field (the stress contrast) and the fracture opening angle distribution over fracture length and fracture orientation direction. The conclusions made in the laboratory modeling of the multistage HFF technology agree well with the conclusions made in the computational experiment. Special attention must be paid to the design of the HFF stage spacing density in the implementation of the multistage HFF in wells with horizontal completion.

The effects of axial displacement on fracture callus morphology and MSC homing depend on the timing of application.

PubMed

Weaver, Aaron S; Su, Yu-Ping; Begun, Dana L; Miller, Joshua D; Alford, Andrea I; Goldstein, Steven A

2010-07-01

The local mechanical environment and the availability of mesenchymal stem cells (MSC) have both been shown to be important factors in bone fracture healing. This study was designed to investigate how the timing of an applied axial displacement across a healing fracture affects callus properties as well as the migration of systemically introduced MSC. Bilateral osteotomies were created in male, Sprague-Dawley rats. Exogenous MSC were injected via the tail vein, and a controlled micro-motion was applied to one defect starting 0, 3, 10, or 24 days after surgery. The results showed that fractures stimulated 10 days after surgery had more mineral, less cartilage, and greater mechanical properties at 48 days than other groups. Populations of MSC were found in osteotomies 48 days after surgery, with the exception of the group that was stimulated 10 days after surgery. These results demonstrate that the timing of mechanical stimulation affects the physical properties of the callus and the migration of MSC to the fracture site. Published by Elsevier Inc.

Mathematical algorithm development and parametric studies with the GEOFRAC three-dimensional stochastic model of natural rock fracture systems

NASA Astrophysics Data System (ADS)

Ivanova, Violeta M.; Sousa, Rita; Murrihy, Brian; Einstein, Herbert H.

2014-06-01

This paper presents results from research conducted at MIT during 2010-2012 on modeling of natural rock fracture systems with the GEOFRAC three-dimensional stochastic model. Following a background summary of discrete fracture network models and a brief introduction of GEOFRAC, the paper provides a thorough description of the newly developed mathematical and computer algorithms for fracture intensity, aperture, and intersection representation, which have been implemented in MATLAB. The new methods optimize, in particular, the representation of fracture intensity in terms of cumulative fracture area per unit volume, P32, via the Poisson-Voronoi Tessellation of planes into polygonal fracture shapes. In addition, fracture apertures now can be represented probabilistically or deterministically whereas the newly implemented intersection algorithms allow for computing discrete pathways of interconnected fractures. In conclusion, results from a statistical parametric study, which was conducted with the enhanced GEOFRAC model and the new MATLAB-based Monte Carlo simulation program FRACSIM, demonstrate how fracture intensity, size, and orientations influence fracture connectivity.

Expression of CD44v6 as matrix-associated ectodomain in the bone development.

PubMed

Nakajima, Kosei; Taniguchi, Kazumi; Mutoh, Ken-ichiro

2010-08-01

This study describes the expression of CD44v6 in the bone development and is the first study of its kind to the authors' best knowledge. The CD44 family is a family of transmembrane glycoproteins that acts as cell adhesion molecules binding cells to other cells as well as cells to the extracellular matrix. It has been suggested that the CD44v6, a family member of CD44, is closely related to the osteosarcoma metastasis. In general, when cancer cells metastasize, they revert to their immature forms. In the present study, therefore, we have investigated CD44v6 and the standard form of CD44 (CD44st) in two types of immature forms of bone tissues: developmentally immature stages from fetuses to adults as well as experimentally immature stages using fracture models. CD44st expression was identified in osteoblasts, osteocytes, and in the peripheral portion of the bone matrix from the fetal to young ages of rats. Many more intense reactions for CD44v6 were observed in the bone matrix than CD44st in fetal stages. In experimental fracture models, positive immunoreactions to CD44st were clearly observed in the osteoblasts and osteocytes. CD44v6-positive immunoreactivity, however, was not detected in either osteoblasts or the bone matrix. In conclusion, CD44v6 is expressed in the embryonic stages and may be involved in the bone matrix formation as a matrix-associated ectodomain during normal ontogenetic development but not involved in the process of fracture healing.

Fracture strength of the particulate-reinforced ultra-high temperature ceramics based on a temperature dependent fracture toughness model

NASA Astrophysics Data System (ADS)

Wang, Ruzhuan; Li, Weiguo; Ji, Baohua; Fang, Daining

2017-10-01

The particulate-reinforced ultra-high temperature ceramics (pUHTCs) have been particularly developed for fabricating the leading edge and nose cap of hypersonic vehicles. They have drawn intensive attention of scientific community for their superior fracture strength at high temperatures. However, there is no proper model for predicting the fracture strength of the ceramic composites and its dependency on temperature. In order to account for the effect of temperature on the fracture strength, we proposed a concept called energy storage capacity, by which we derived a new model for depicting the temperature dependent fracture toughness of the composites. This model gives a quantitative relationship between the fracture toughness and temperature. Based on this temperature dependent fracture toughness model and Griffith criterion, we developed a new fracture strength model for predicting the temperature dependent fracture strength of pUHTCs at different temperatures. The model takes into account the effects of temperature, flaw size and residual stress without any fitting parameters. The predictions of the fracture strength of pUHTCs in argon or air agreed well with the experimental measurements. Additionally, our model offers a mechanism of monitoring the strength of materials at different temperatures by testing the change of flaw size. This study provides a quantitative tool for design, evaluation and monitoring of the fracture properties of pUHTCs at high temperatures.

Modeling CO2 Storage in Fractured Reservoirs: Fracture-Matrix Interactions of Free-Phase and Dissolved CO2

NASA Astrophysics Data System (ADS)

Oldenburg, C. M.; Zhou, Q.; Birkholzer, J. T.

2017-12-01

The injection of supercritical CO2 (scCO2) in fractured reservoirs has been conducted at several storage sites. However, no site-specific dual-continuum modeling for fractured reservoirs has been reported and modeling studies have generally underestimated the fracture-matrix interactions. We developed a conceptual model for enhanced CO2 storage to take into account global scCO2 migration in the fracture continuum, local storage of scCO2 and dissolved CO2 (dsCO2) in the matrix continuum, and driving forces for scCO2 invasion and dsCO2 diffusion from fractures. High-resolution discrete fracture-matrix models were developed for a column of idealized matrix blocks bounded by vertical and horizontal fractures and for a km-scale fractured reservoir. The column-scale simulation results show that equilibrium storage efficiency strongly depends on matrix entry capillary pressure and matrix-matrix connectivity while the time scale to reach equilibrium is sensitive to fracture spacing and matrix flow properties. The reservoir-scale modeling results shows that the preferential migration of scCO2 through fractures is coupled with bulk storage in the rock matrix that in turn retards the fracture scCO2 plume. We also developed unified-form diffusive flux equations to account for dsCO2 storage in brine-filled matrix blocks and found solubility trapping is significant in fractured reservoirs with low-permeability matrix.

Mathematical modeling and simulation analysis of hydraulic fracture propagation in three-layered poro-elastic media

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moon, H.Y.; Advani, S.H.; Lee, T.S.

1992-11-01

Hydraulic fracturing plays a pivotal role in the enhancement of oil and gas production recovery from low permeability reservoirs. The process of hydraulic fracturing entails the generation of a fracture by pumping fluids blended with special chemicals and proppants into the payzone at high injection rates and pressures to extend and wedge fractures. The mathematical modeling of hydraulically induced fractures generally incorporates coupling between the formation elasticity, fracture fluid flow, and fracture mechanics equations governing the formation structural responses, fluid pressure profile, and fracture growth. Two allied unsymmetric elliptic fracture models are developed for fracture configuration evolutions in three-layered rockmore » formations. The first approach is based on a Lagrangian formulation incorporating pertinent energy components associated with the formation structural responses and fracture fluid flow. The second model is based on a generalized variational principle, introducing an energy rate related functional. These models initially simulate a penny-shaped fracture, which becomes elliptic if the crack tips encounters (upper and/or lower) barriers with differential reservoir properties (in situ stresses, 16 elastic moduli, and fracture toughness-contrasts and fluid leak-off characteristics). The energy rate component magnitudes are determined to interpret the governing hydraulic fracture mechanisms during fracture evolution. The variational principle is extended to study the phenomenon and consequences of fluid lag in fractures. Finally, parametric sensitivity and energy rate investigations to evaluate the roles of controllable hydraulic treatment variables and uncontrollable reservoir property characterization parameters are performed. The presented field applications demonstrate the overall capabilities of the developed models. These studies provide stimulation treatment guidelines for fracture configuration design, control, and optimization.« less

Effects of fracture surface roughness and shear displacement on geometrical and hydraulic properties of three-dimensional crossed rock fracture models

NASA Astrophysics Data System (ADS)

Huang, Na; Liu, Richeng; Jiang, Yujing; Li, Bo; Yu, Liyuan

2018-03-01

While shear-flow behavior through fractured media has been so far studied at single fracture scale, a numerical analysis of the shear effect on the hydraulic response of 3D crossed fracture model is presented. The analysis was based on a series of crossed fracture models, in which the effects of fracture surface roughness and shear displacement were considered. The rough fracture surfaces were generated using the modified successive random additions (SRA) algorithm. The shear displacement was applied on one fracture, and at the same time another fracture shifted along with the upper and lower surfaces of the sheared fracture. The simulation results reveal the development and variation of preferential flow paths through the model during the shear, accompanied by the change of the flow rate ratios between two flow planes at the outlet boundary. The average contact area accounts for approximately 5-27% of the fracture planes during shear, but the actual calculated flow area is about 38-55% of the fracture planes, which is much smaller than the noncontact area. The equivalent permeability will either increase or decrease as shear displacement increases from 0 to 4 mm, depending on the aperture distribution of intersection part between two fractures. When the shear displacement continuously increases by up to 20 mm, the equivalent permeability increases sharply first, and then keeps increasing with a lower gradient. The equivalent permeability of rough fractured model is about 26-80% of that calculated from the parallel plate model, and the equivalent permeability in the direction perpendicular to shear direction is approximately 1.31-3.67 times larger than that in the direction parallel to shear direction. These results can provide a fundamental understanding of fluid flow through crossed fracture model under shear.

Nerve growth factor and associated nerve sprouting contribute to local mechanical hyperalgesia in a rat model of bone injury.

PubMed

Yasui, M; Shiraishi, Y; Ozaki, N; Hayashi, K; Hori, K; Ichiyanagi, M; Sugiura, Y

2012-08-01

To clarify the mechanism of tenderness after bone injury, we investigated changes in the withdrawal threshold to mechanical stimuli, nerve distribution and nerve growth factor (NGF)-expression in a rat model of bone injury without immobilization for bone injury healing. Rats were divided into three groups as follows: (1) rats incised in the skin and periosteum, followed by drilling a hole in the tibia [bone lesion group (BLG)]; (2) those incised in the skin and periosteum without bone drilling [periosteum lesion group (PLG)]; and (3) those incised in the skin [skin lesion group (SLG)]. Mechanical hyperalgesia continued for 28 days at a lesion in the BLG, 21 days in PLG and 5 days in SLG after treatments, respectively. Endochondral ossification was observed on days 5-28 in BLG and on days 5-21 in PLG. Nerve growth appeared in deep connective tissue (DCT) at day 28 in BLG. Nerve fibres increased in both cutaneous tissue and DCT at day 7 in PLG, but they were not found at day 28. Mechanical hyperalgesia accompanied with endochondral ossification and nerve fibres increasing at the lesion in both BLG and PLG. NGF was expressed in bone-regenerating cells during the bone injury healing. Anti-NGF and trk inhibitor K252a inhibited hyperalgesia in the different time course. This study shows that localized tenderness coincides with the bone healing and involves NGF expression and nerve sprouting after bone injury. The findings present underlying mechanisms and provide pathophysiological relevance of local tenderness to determination of bone fracture and its healing. © 2011 European Federation of International Association for the Study of Pain Chapters.

a Fractal Network Model for Fractured Porous Media

NASA Astrophysics Data System (ADS)

Xu, Peng; Li, Cuihong; Qiu, Shuxia; Sasmito, Agus Pulung

2016-04-01

The transport properties and mechanisms of fractured porous media are very important for oil and gas reservoir engineering, hydraulics, environmental science, chemical engineering, etc. In this paper, a fractal dual-porosity model is developed to estimate the equivalent hydraulic properties of fractured porous media, where a fractal tree-like network model is used to characterize the fracture system according to its fractal scaling laws and topological structures. The analytical expressions for the effective permeability of fracture system and fractured porous media, tortuosity, fracture density and fraction are derived. The proposed fractal model has been validated by comparisons with available experimental data and numerical simulation. It has been shown that fractal dimensions for fracture length and aperture have significant effect on the equivalent hydraulic properties of fractured porous media. The effective permeability of fracture system can be increased with the increase of fractal dimensions for fracture length and aperture, while it can be remarkably lowered by introducing tortuosity at large branching angle. Also, a scaling law between the fracture density and fractal dimension for fracture length has been found, where the scaling exponent depends on the fracture number. The present fractal dual-porosity model may shed light on the transport physics of fractured porous media and provide theoretical basis for oil and gas exploitation, underground water, nuclear waste disposal and geothermal energy extraction as well as chemical engineering, etc.

Numerical simulation and fracture identification of dual laterolog in organic shale

NASA Astrophysics Data System (ADS)

Maojin, Tan; Peng, Wang; Qiong, Liu

2012-09-01

Fracture is one of important spaces in shale oil and shale gas reservoirs, and fractures identification and evaluation are an important part in organic shale interpretation. According to the fractured shale gas reservoir, a physical model is set up to study the dual laterolog logging responses. First, based on the principle of dual laterolog, three-dimensional finite element method (FEM) is used to simulate the dual laterolog responses in various formation models with different fractures widths, different fracture numbers, different fractures inclination angle. All the results are extremely important for the fracture identification and evaluation in shale reservoirs. Appointing to different base rock resistivity models, the fracture models are constructed respectively through a number of numerical simulation, and the fracture porosity can be calculated by solving the corresponding formulas. A case study about organic shale formation is analyst and discussed, and the fracture porosity is calculated from dual laterolog. The fracture evaluation results are also be validated right by Full borehole Micro-resistivity Imaging (FMI). So, in case of the absence of borehole resistivity imaging log, the dual laterolog resistivity can be used to estimate the fracture development.

Specimen-specific modeling of hip fracture pattern and repair.

PubMed

Ali, Azhar A; Cristofolini, Luca; Schileo, Enrico; Hu, Haixiang; Taddei, Fulvia; Kim, Raymond H; Rullkoetter, Paul J; Laz, Peter J

2014-01-22

Hip fracture remains a major health problem for the elderly. Clinical studies have assessed fracture risk based on bone quality in the aging population and cadaveric testing has quantified bone strength and fracture loads. Prior modeling has primarily focused on quantifying the strain distribution in bone as an indicator of fracture risk. Recent advances in the extended finite element method (XFEM) enable prediction of the initiation and propagation of cracks without requiring a priori knowledge of the crack path. Accordingly, the objectives of this study were to predict femoral fracture in specimen-specific models using the XFEM approach, to perform one-to-one comparisons of predicted and in vitro fracture patterns, and to develop a framework to assess the mechanics and load transfer in the fractured femur when it is repaired with an osteosynthesis implant. Five specimen-specific femur models were developed from in vitro experiments under a simulated stance loading condition. Predicted fracture patterns closely matched the in vitro patterns; however, predictions of fracture load differed by approximately 50% due to sensitivity to local material properties. Specimen-specific intertrochanteric fractures were induced by subjecting the femur models to a sideways fall and repaired with a contemporary implant. Under a post-surgical stance loading, model-predicted load sharing between the implant and bone across the fracture surface varied from 59%:41% to 89%:11%, underscoring the importance of considering anatomic and fracture variability in the evaluation of implants. XFEM modeling shows potential as a macro-level analysis enabling fracture investigations of clinical cohorts, including at-risk groups, and the design of robust implants. © 2013 Published by Elsevier Ltd.

The effects of photobiomodulation and low-amplitude high-frequency vibration on bone healing process: a comparative study.

PubMed

Rajaei Jafarabadi, M; Rouhi, G; Kaka, G; Sadraie, S H; Arum, J

2016-12-01

This study aimed at investigating the effects of photobiomodulation (PBM) and low-amplitude high-frequency (LAHF) whole body mechanical vibration on bone fracture healing process when metallic plates are implanted in rats' femurs. Forty male rats weighing between 250 and 350 g, 12 weeks old, were employed in this study. A transverse critical size defect (CSD) was made in their right femurs that were fixed by stainless steel plates. After the surgery, the rats were divided equally into four groups: low-level laser therapy group (GaAlAs laser, 830 nm, 40 mW, 4 J/cm 2 , 0.35 cm beam diameter, LLLT), whole body vibration group (60 Hz, 0.1 mm amplitude, 1.5 g, WBV), a combination of laser and vibration group (LV), and the control group (C). Each group was divided into two subgroups based on sacrifice dates. The rats were sacrificed at intervals of 3 and 6 weeks after the surgery to extract their right femurs for radiography and biomechanical and histological analyses, and the results were analyzed using standard statistical methods. Radiographic analyses showed greater callus formation in the LLLT and WBV groups than in control group at both 3 (P < 0.05 and P < 0.001, respectively) and 6 weeks after surgery (P < 0.05 and P < 0.05, respectively). Histological evaluations showed a higher amount of new bone formation and better maturity in the LLLT and WBV groups than the control groups at 3 and 6 weeks after surgery. Biomechanical tests showed that the maximum force at fracture in the LLLT (P < 0.05 in 3 weeks and P < 0.05 in 6 weeks) and WBV (P < 0.001 in 3 weeks and P < 0.05 in 6 weeks) groups was greater than that in the control groups at both time intervals. But a combination of laser and vibration therapy, LV, did not show a positive interaction on bone fracture healing process. The biostimulation effects of PBM or LLLT and of low-amplitude high-frequency WBV both had a positive impact on bone healing process, for critical size defects in the presence of a stainless steel implant. But their combination, i.e., low-level laser therapy and low-amplitude high-frequency whole body vibration (LV), interestingly did not accelerate the fractured bone healing process.

Tuning Fractures With Dynamic Data

NASA Astrophysics Data System (ADS)

Yao, Mengbi; Chang, Haibin; Li, Xiang; Zhang, Dongxiao

2018-02-01

Flow in fractured porous media is crucial for production of oil/gas reservoirs and exploitation of geothermal energy. Flow behaviors in such media are mainly dictated by the distribution of fractures. Measuring and inferring the distribution of fractures is subject to large uncertainty, which, in turn, leads to great uncertainty in the prediction of flow behaviors. Inverse modeling with dynamic data may assist to constrain fracture distributions, thus reducing the uncertainty of flow prediction. However, inverse modeling for flow in fractured reservoirs is challenging, owing to the discrete and non-Gaussian distribution of fractures, as well as strong nonlinearity in the relationship between flow responses and model parameters. In this work, building upon a series of recent advances, an inverse modeling approach is proposed to efficiently update the flow model to match the dynamic data while retaining geological realism in the distribution of fractures. In the approach, the Hough-transform method is employed to parameterize non-Gaussian fracture fields with continuous parameter fields, thus rendering desirable properties required by many inverse modeling methods. In addition, a recently developed forward simulation method, the embedded discrete fracture method (EDFM), is utilized to model the fractures. The EDFM maintains computational efficiency while preserving the ability to capture the geometrical details of fractures because the matrix is discretized as structured grid, while the fractures being handled as planes are inserted into the matrix grids. The combination of Hough representation of fractures with the EDFM makes it possible to tune the fractures (through updating their existence, location, orientation, length, and other properties) without requiring either unstructured grids or regridding during updating. Such a treatment is amenable to numerous inverse modeling approaches, such as the iterative inverse modeling method employed in this study, which is capable of dealing with strongly nonlinear problems. A series of numerical case studies with increasing complexity are set up to examine the performance of the proposed approach.

Fracture simulation of restored teeth using a continuum damage mechanics failure model.

PubMed

Li, Haiyan; Li, Jianying; Zou, Zhenmin; Fok, Alex Siu-Lun

2011-07-01

The aim of this paper is to validate the use of a finite-element (FE) based continuum damage mechanics (CDM) failure model to simulate the debonding and fracture of restored teeth. Fracture testing of plastic model teeth, with or without a standard Class-II MOD (mesial-occusal-distal) restoration, was carried out to investigate their fracture behavior. In parallel, 2D FE models of the teeth are constructed and analyzed using the commercial FE software ABAQUS. A CDM failure model, implemented into ABAQUS via the user element subroutine (UEL), is used to simulate the debonding and/or final fracture of the model teeth under a compressive load. The material parameters needed for the CDM model to simulate fracture are obtained through separate mechanical tests. The predicted results are then compared with the experimental data of the fracture tests to validate the failure model. The failure processes of the intact and restored model teeth are successfully reproduced by the simulation. However, the fracture parameters obtained from testing small specimens need to be adjusted to account for the size effect. The results indicate that the CDM model is a viable model for the prediction of debonding and fracture in dental restorations. Copyright © 2011 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athymic Rats

PubMed Central

Curtis, Ryan C.; Custis, James T.; Ehrhart, Nicole P.; Ehrhart, E. J.; Condon, Keith W.; Gookin, Sara E.; Donahue, Seth W.

2016-01-01

Clinical studies using definitive-intent stereotactic radiation therapy (SRT) for the local treatment of canine osteosarcoma (OSA) have shown canine patients achieving similar median survival times as the current standard of care (amputation and adjuvant chemotherapy). Despite this, there remains an unacceptable high risk of pathologic fracture following radiation treatment. Zoledronic acid (ZA) and parathyroid hormone (PTH) are therapeutic candidates for decreasing this fracture risk post-irradiation. Due to differing mechanisms, we hypothesized that the combined treatment with ZA and PTH would significantly improve bone healing more than ZA or PTH treatment alone. Using an orthotopic model of canine osteosarcoma in athymic rats, we evaluated bone healing following clinically-relevant doses of radiation therapy (12 Gy x 3 fractions, 36 Gy total). Groups included 36 Gy SRT only, 36 Gy SRT plus ZA, 36 Gy SRT plus ZA and PTH, 36 Gy SRT plus PTH, and 36 Gy SRT plus localized PTH treatment. Our study showed significant increases in bone volume and increased polar moments of inertia (in the distal femoral metaphysis) 8 weeks after radiation in the combined (ZA/PTH) treatment group as compared to radiation treatment alone. Histomorphometric analysis revealed evidence of active mineralization at the study endpoint as well as successful tumor-cell kill across all treatment groups. This work provides further evidence for the expanding potential indications for ZA and PTH therapy, including post-irradiated bone disease due to osteosarcoma. PMID:27332712

Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athymic Rats.

PubMed

Curtis, Ryan C; Custis, James T; Ehrhart, Nicole P; Ehrhart, E J; Condon, Keith W; Gookin, Sara E; Donahue, Seth W

2016-01-01

Clinical studies using definitive-intent stereotactic radiation therapy (SRT) for the local treatment of canine osteosarcoma (OSA) have shown canine patients achieving similar median survival times as the current standard of care (amputation and adjuvant chemotherapy). Despite this, there remains an unacceptable high risk of pathologic fracture following radiation treatment. Zoledronic acid (ZA) and parathyroid hormone (PTH) are therapeutic candidates for decreasing this fracture risk post-irradiation. Due to differing mechanisms, we hypothesized that the combined treatment with ZA and PTH would significantly improve bone healing more than ZA or PTH treatment alone. Using an orthotopic model of canine osteosarcoma in athymic rats, we evaluated bone healing following clinically-relevant doses of radiation therapy (12 Gy x 3 fractions, 36 Gy total). Groups included 36 Gy SRT only, 36 Gy SRT plus ZA, 36 Gy SRT plus ZA and PTH, 36 Gy SRT plus PTH, and 36 Gy SRT plus localized PTH treatment. Our study showed significant increases in bone volume and increased polar moments of inertia (in the distal femoral metaphysis) 8 weeks after radiation in the combined (ZA/PTH) treatment group as compared to radiation treatment alone. Histomorphometric analysis revealed evidence of active mineralization at the study endpoint as well as successful tumor-cell kill across all treatment groups. This work provides further evidence for the expanding potential indications for ZA and PTH therapy, including post-irradiated bone disease due to osteosarcoma.

Numerical modelling of single-phase flow in rough fractures with contacts

NASA Astrophysics Data System (ADS)

Olkiewicz, Piotr; Dabrowski, Marcin

2017-04-01

Fracture flow may dominate in rocks with low porosity and it can accompany both industrial and natural processes. Typical examples of such processes are natural flows in crystalline rocks and industrial flows in oil and gas production systems or hydraulic fracturing. Fracture flow provides an important mechanism for transporting mass and energy. The distribution of the apertures of fracture and contact area are the key parameters with regard to the fracture transmissivity. We use the method of correlated random fields [Mourzenko, 1996] to generate synthetic fracture geometry in 3D. The flow of an incompressible Newtonian viscous fluid in geological formation can be approximated by the Stokes, the Stokes-Brinkman or the Reynolds models. We use our own implementation of the finite element method based on MILAMIN [Dabrowski, 2008] to solve governing partial differential equation over domain. We compare the Stokes, the Stokes-Brinkamn and the Reynolds models for fracture flow based on systematic numerical simulations for a wide range of geometric parameters. Mismatch between the Reynolds and the Stokes models becomes significant with increasing fracture roughness or contact area. The Stokes-Brinkman model is more accurate than Reynolds models due to additional Laplacian term, which allows to fulfil no-slip boundary condition. We present condition when the Reynolds and the Stokes-Brinkman models are valid. In the last three decades many authors used the Reynolds equation for studying fracture flow because of its simplicity. We recommend using the Stokes-Brinkman model for fracture flow, which allows to fulfil no-slip boundary condition on asperities boundary and is more accurate for rough fractures than the Reynolds model.

Kefir improves bone mass and microarchitecture in an ovariectomized rat model of postmenopausal osteoporosis.

PubMed

Chen, H-L; Tung, Y-T; Chuang, C-H; Tu, M-Y; Tsai, T-C; Chang, S-Y; Chen, C-M

2015-02-01

Kefir treatment in ovariectomized (OVX) rats could significantly decrease the levels of bone turnover markers and prevent OVX-induced bone loss, deterioration of trabecular microarchitecture, and biomechanical dysfunction that may be due to increase intracellular calcium uptake through the TRPV6 calcium channel. Osteoporosis is a disease characterized by low bone mass and structural deterioration of bone tissue, leading to an increased fracture risk. The incidence of osteoporosis increases with age and occurs most frequently in postmenopausal women due to estrogen deficiency, as the balance between bone resorption and bone formation shifts towards increased levels of bone resorption. Among various methods of prevention and treatment for osteoporosis, an increase in calcium intake is the most commonly recommended preventive measure. Kefir is a fermented milk product made with kefir grains that degrade milk proteins into various peptides with health-promoting effects, including immunomodulating-, antithrombotic-, antimicrobial-, and calcium-absorption-enhancing bioactivities. The aim of this study is to investigate the effect of kefir on osteoporosis prophylaxis in an ovariectomized rat model. A total of 56 16-week-old female Sprague-Dawley (SD) rats were divided into 7 experimental groups: sham (normal), OVX/Mock, OVX/1X kefir (164 mg/kg BW/day), OVX/2X kefir (328 mg/kg BW/day), OVX/4X kefir (656 mg/kg BW/day), OVX/ALN (2.5 mg/kg BW/day), and OVX/REBONE (800 mg/kg BW/day). After 12-week treatment with kefir, the bone physiology in the OVX rat model was investigated. Accordingly, the aim of this study was to investigate the possible transport mechanism involved in calcium absorption using the Caco-2 human cell line. A 12-week treatment with kefir on the OVX-induced osteoporosis model reduced the levels of C-terminal telopeptides of type I collagen (CTx), bone turnover markers, and trabecular separation (Tb. Sp.). Additionally, treatment with kefir increased trabecular bone mineral density (BMD), bone volume (BV/TV), trabecular thickness (Tb. Th), trabecular number (Tb. N), and the biomechanical properties (hardness and modulus) of the distal femur with a dose-dependent efficacy. In addition, in in vitro assay, we found that kefir increased intracellular calcium uptake in Caco-2 cell through TRPV6 calcium channels and not through L-type voltage-operated calcium channels. The protective effect of kefir in the OVX rat model may occur through increasing intracellular calcium uptake through the TRPV6 calcium channel.

Role of geomechanically grown fractures on dispersive transport in heterogeneous geological formations.

PubMed

Nick, H M; Paluszny, A; Blunt, M J; Matthai, S K

2011-11-01

A second order in space accurate implicit scheme for time-dependent advection-dispersion equations and a discrete fracture propagation model are employed to model solute transport in porous media. We study the impact of the fractures on mass transport and dispersion. To model flow and transport, pressure and transport equations are integrated using a finite-element, node-centered finite-volume approach. Fracture geometries are incrementally developed from a random distributions of material flaws using an adoptive geomechanical finite-element model that also produces fracture aperture distributions. This quasistatic propagation assumes a linear elastic rock matrix, and crack propagation is governed by a subcritical crack growth failure criterion. Fracture propagation, intersection, and closure are handled geometrically. The flow and transport simulations are separately conducted for a range of fracture densities that are generated by the geomechanical finite-element model. These computations show that the most influential parameters for solute transport in fractured porous media are as follows: fracture density and fracture-matrix flux ratio that is influenced by matrix permeability. Using an equivalent fracture aperture size, computed on the basis of equivalent permeability of the system, we also obtain an acceptable prediction of the macrodispersion of poorly interconnected fracture networks. The results hold for fractures at relatively low density.

Systemic administration of mesenchymal stem cells combined with parathyroid hormone therapy synergistically regenerates multiple rib fractures.

PubMed

Cohn Yakubovich, Doron; Sheyn, Dmitriy; Bez, Maxim; Schary, Yeshai; Yalon, Eran; Sirhan, Afeef; Amira, May; Yaya, Alin; De Mel, Sandra; Da, Xiaoyu; Ben-David, Shiran; Tawackoli, Wafa; Ley, Eric J; Gazit, Dan; Gazit, Zulma; Pelled, Gadi

2017-03-09

A devastating condition that leads to trauma-related morbidity, multiple rib fractures, remain a serious unmet clinical need. Systemic administration of mesenchymal stem cells (MSCs) has been shown to regenerate various tissues. We hypothesized that parathyroid hormone (PTH) therapy would enhance MSC homing and differentiation, ultimately leading to bone formation that would bridge rib fractures. The combination of human MSCs (hMSCs) and a clinically relevant PTH dose was studied using immunosuppressed rats. Segmental defects were created in animals' fifth and sixth ribs. The rats were divided into four groups: a negative control group, in which animals received vehicle alone; the PTH-only group, in which animals received daily subcutaneous injections of 4 μg/kg teriparatide, a pharmaceutical derivative of PTH; the hMSC-only group, in which each animal received five injections of 2 × 10 6 hMSCs; and the hMSC + PTH group, in which animals received both treatments. Longitudinal in vivo monitoring of bone formation was performed biweekly using micro-computed tomography (μCT), followed by histological analysis. Fluorescently-dyed hMSCs were counted using confocal microscopy imaging of histological samples harvested 8 weeks after surgery. PTH significantly augmented the number of hMSCs that homed to the fracture site. Immunofluorescence of osteogenic markers, osteocalcin and bone sialoprotein, showed that PTH induced cell differentiation in both exogenously administered cells and resident cells. μCT scans revealed a significant increase in bone volume only in the hMSC + PTH group, beginning by the 4 th week after surgery. Eight weeks after surgery, 35% of ribs in the hMSC + PTH group had complete bone bridging, whereas there was complete bridging in only 6.25% of ribs (one rib) in the PTH-only group and in none of the ribs in the other groups. Based on the μCT scans, biomechanical analysis using the micro-finite element method demonstrated that the healed ribs were stiffer than intact ribs in torsion, compression, and bending simulations, as expected when examining bone callus composed of woven bone. Administration of both hMSCs and PTH worked synergistically in rib fracture healing, suggesting this approach may pave the way to treat multiple rib fractures as well as additional fractures in various anatomical sites.

3D Numerical Modeling of the Propagation of Hydraulic Fracture at Its Intersection with Natural (Pre-existing) Fracture

NASA Astrophysics Data System (ADS)

Dehghan, Ali Naghi; Goshtasbi, Kamran; Ahangari, Kaveh; Jin, Yan; Bahmani, Aram

2017-02-01

A variety of 3D numerical models were developed based on hydraulic fracture experiments to simulate the propagation of hydraulic fracture at its intersection with natural (pre-existing) fracture. Since the interaction between hydraulic and pre-existing fractures is a key condition that causes complex fracture patterns, the extended finite element method was employed in ABAQUS software to simulate the problem. The propagation of hydraulic fracture in a fractured medium was modeled in two horizontal differential stresses (Δ σ) of 5e6 and 10e6 Pa considering different strike and dip angles of pre-existing fracture. The rate of energy release was calculated in the directions of hydraulic and pre-existing fractures (G_{{frac}} /G_{{rock}}) at their intersection point to determine the fracture behavior. Opening and crossing were two dominant fracture behaviors during the hydraulic and pre-existing fracture interaction at low and high differential stress conditions, respectively. The results of numerical studies were compared with those of experimental models, showing a good agreement between the two to validate the accuracy of the models. Besides the horizontal differential stress, strike and dip angles of the natural (pre-existing) fracture, the key finding of this research was the significant effect of the energy release rate on the propagation behavior of the hydraulic fracture. This effect was more prominent under the influence of strike and dip angles, as well as differential stress. The obtained results can be used to predict and interpret the generation of complex hydraulic fracture patterns in field conditions.

Stochastic Ground Water Flow Simulation with a Fracture Zone Continuum Model

USGS Publications Warehouse

Langevin, C.D.

2003-01-01

A method is presented for incorporating the hydraulic effects of vertical fracture zones into two-dimensional cell-based continuum models of ground water flow and particle tracking. High hydraulic conductivity features are used in the model to represent fracture zones. For fracture zones that are not coincident with model rows or columns, an adjustment is required for the hydraulic conductivity value entered into the model cells to compensate for the longer flowpath through the model grid. A similar adjustment is also required for simulated travel times through model cells. A travel time error of less than 8% can occur for particles moving through fractures with certain orientations. The fracture zone continuum model uses stochastically generated fracture zone networks and Monte Carlo analysis to quantify uncertainties with simulated advective travel times. An approach is also presented for converting an equivalent continuum model into a fracture zone continuum model by establishing the contribution of matrix block transmissivity to the bulk transmissivity of the aquifer. The methods are used for a case study in west-central Florida to quantify advective travel times from a potential wetland rehydration site to a municipal supply wellfield. Uncertainties in advective travel times are assumed to result from the presence of vertical fracture zones, commonly observed on aerial photographs as photolineaments.

Upscaling permeability for three-dimensional fractured porous rocks with the multiple boundary method

NASA Astrophysics Data System (ADS)

Chen, Tao; Clauser, Christoph; Marquart, Gabriele; Willbrand, Karen; Hiller, Thomas

2018-02-01

Upscaling permeability of grid blocks is crucial for groundwater models. A novel upscaling method for three-dimensional fractured porous rocks is presented. The objective of the study was to compare this method with the commonly used Oda upscaling method and the volume averaging method. First, the multiple boundary method and its computational framework were defined for three-dimensional stochastic fracture networks. Then, the different upscaling methods were compared for a set of rotated fractures, for tortuous fractures, and for two discrete fracture networks. The results computed by the multiple boundary method are comparable with those of the other two methods and fit best the analytical solution for a set of rotated fractures. The errors in flow rate of the equivalent fracture model decrease when using the multiple boundary method. Furthermore, the errors of the equivalent fracture models increase from well-connected fracture networks to poorly connected ones. Finally, the diagonal components of the equivalent permeability tensors tend to follow a normal or log-normal distribution for the well-connected fracture network model with infinite fracture size. By contrast, they exhibit a power-law distribution for the poorly connected fracture network with multiple scale fractures. The study demonstrates the accuracy and the flexibility of the multiple boundary upscaling concept. This makes it attractive for being incorporated into any existing flow-based upscaling procedures, which helps in reducing the uncertainty of groundwater models.

AN INTEGRATED VIEW OF GROUNDWATER FLOW CHARACTERIZATION AND MODELING IN FRACTURED GEOLOGIC MEDIA

EPA Science Inventory

The particular attributes of fractured geologic media pertaining to groundwater flow characterization and modeling are presented. These cover the issues of fracture network and hydraulic control of fracture geometry parameters, major and minor fractures, heterogeneity, anisotrop...

Use of the Fracture Continuum Model for Numerical Modeling of Flow and Transport of Deep Geologic Disposal of Nuclear Waste in Crystalline Rock

NASA Astrophysics Data System (ADS)

Hadgu, T.; Kalinina, E.; Klise, K. A.; Wang, Y.

2015-12-01

Numerical modeling of disposal of nuclear waste in a deep geologic repository in fractured crystalline rock requires robust characterization of fractures. Various methods for fracture representation in granitic rocks exist. In this study we used the fracture continuum model (FCM) to characterize fractured rock for use in the simulation of flow and transport in the far field of a generic nuclear waste repository located at 500 m depth. The FCM approach is a stochastic method that maps the permeability of discrete fractures onto a regular grid. The method generates permeability fields using field observations of fracture sets. The original method described in McKenna and Reeves (2005) was designed for vertical fractures. The method has since then been extended to incorporate fully three-dimensional representations of anisotropic permeability, multiple independent fracture sets, and arbitrary fracture dips and orientations, and spatial correlation (Kalinina et al. 20012, 2014). For this study the numerical code PFLOTRAN (Lichtner et al., 2015) has been used to model flow and transport. PFLOTRAN solves a system of generally nonlinear partial differential equations describing multiphase, multicomponent and multiscale reactive flow and transport in porous materials. The code is designed to run on massively parallel computing architectures as well as workstations and laptops (e.g. Hammond et al., 2011). Benchmark tests were conducted to simulate flow and transport in a specified model domain. Distributions of fracture parameters were used to generate a selected number of realizations. For each realization, the FCM method was used to generate a permeability field of the fractured rock. The PFLOTRAN code was then used to simulate flow and transport in the domain. Simulation results and analysis are presented. The results indicate that the FCM approach is a viable method to model fractured crystalline rocks. The FCM is a computationally efficient way to generate realistic representation of complex fracture systems. This approach is of interest for nuclear waste disposal models applied over large domains.

Analysis of metallic traces from the biodegradation of endomedullary AZ31 alloy temporary implants in rat organs after long implantation times.

PubMed

Bodelón, O G; Iglesias, C; Garrido, J; Clemente, C; Garcia-Alonso, M C; Escudero, M L

2015-08-04

AZ31 alloy has been tested as a biodegradable material in the form of endomedullary implants in female Wistar rat femurs. In order to evaluate the accumulation of potentially toxic elements from the biodegradation of the implant, magnesium (Mg), aluminium (Al), zinc (Zn), manganese (Mn) and fluorine (F) levels have been measured in different organs such as kidneys, liver, lungs, spleen and brain. Several factors that may influence accumulation have been taken into account: how long the implant has been in place, whether or not the bone is fractured, and the presence of an MgF2 protective coating on the implant. The main conclusions and the clinical relevance of the study have been that AZ31 endomedullary implants have a degradation rate of about 60% after 13 months, which is fully compatible with fracture consolidation. Neither bone fracture nor an MgF2 coating seems to influence the accumulation of trace elements in the studied organs. Aluminium is the only alloying element in this study that requires special attention. The increase in Al recovered from the sampled organs represents 3.95% of the amount contained in the AZ31 implant. Al accumulates in a statistically significant way in all the organs except the brain. All of this suggests that in long-term tests AZ31 may be a suitable material for osteosynthesis.

Accuracy of specimen-specific nonlinear finite element analysis for evaluation of distal radius strength in cadaver material.

PubMed

Matsuura, Yusuke; Kuniyoshi, Kazuki; Suzuki, Takane; Ogawa, Yasufumi; Sukegawa, Koji; Rokkaku, Tomoyuki; Takahashi, Kazuhisa

2014-11-01

Distal radius fracture, which often occurs in the setting of osteoporosis, can lead to permanent deformity and disability. Great effort has been directed toward developing noninvasive methods for evaluating the distal radius strength, with the goal of assessing fracture risk. The aim of this study was to evaluate distal radius strength using a finite element model and to gauge the accuracy of finite element model measurement using cadaver material. Ten wrists were obtained from cadavers with a mean age of 89.5 years at death. CT images of each wrist in an extended position were obtained. CT-based finite element models were prepared with Mechanical Finder software. Fracture on the models was simulated by applying a mechanical load to the palm in a direction parallel to the forearm axis, after which the fracture load and the site at which the fracture began were identified. For comparison, the wrists were fractured using a universal testing machine and the fracture load and the site of fracture were identified. The fracture load was 970.9 N in the finite element model group and 990.0 N in the actual measurement group. The site of the initial fracture was extra-articular to the distal radius in both groups. The finite element model was predictive for distal radius fracture when compared to the actual measurement. In this study, a finite element model for evaluation of distal radius strength was validated and can be used to predict fracture risk. We conclude that a finite element model is useful for the evaluation of distal radius strength. Knowing distal radius strength might avoid distal radius fracture because appropriate antiosteoporotic treatment can be initiated.

Effect of maternal obesity on fetal bone development in the rat

USDA-ARS?s Scientific Manuscript database

Epidemiological studies show that quality of nutrition during intrauterine and postnatal early life impact the risk of low bone mass and fracture later in life. Maternal consumption of high-fat diets has been demonstrated to affect health outcomes, such as: brain development; obesity; insulin resist...

Epigenetic control of fetal bone development through HoxA10 in the rat

USDA-ARS?s Scientific Manuscript database

Epidemiological studies show that quality of nutrition during intrauterine and early postnatal life impact the risk of low bone mass and fracture later in life. Maternal consumption of high-fat diets has been demonstrated to affect health outcomes, such as: brain development; obesity; insulin resist...

Physiological Challenges of Bone Repair

DTIC Science & Technology

2012-12-01

expression, in general, followed the same pattern in both groups, but significantly, lower levels of mRNA for Indian Hedgehog (ihh) and BMP-2 were detected in...the fracture calluses of the older rats. Indian Hedgehog is thought to be involved in chondrogenesis and bone repair, whereas BMP-2 stimulates bone

Small-scale electrical resistivity tomography of wet fractured rocks.

PubMed

LaBrecque, Douglas J; Sharpe, Roger; Wood, Thomas; Heath, Gail

2004-01-01

This paper describes a series of experiments that tested the ability of the electrical resistivity tomography (ERT) method to locate correctly wet and dry fractures in a meso-scale model. The goal was to develop a method of monitoring the flow of water through a fractured rock matrix. The model was a four by six array of limestone blocks equipped with 28 stainless steel electrodes. Dry fractures were created by placing pieces of vinyl between one or more blocks. Wet fractures were created by injecting tap water into a joint between blocks. In electrical terms, the dry fractures are resistive and the wet fractures are conductive. The quantities measured by the ERT system are current and voltage around the outside edge of the model. The raw ERT data were translated to resistivity values inside the model using a three-dimensional Occam's inversion routine. This routine was one of the key components of ERT being tested. The model presented several challenges. First, the resistivity of both the blocks and the joints was highly variable. Second, the resistive targets introduced extreme changes the software could not precisely quantify. Third, the abrupt changes inherent in a fracture system were contrary to the smoothly varying changes expected by the Occam's inversion routine. Fourth, the response of the conductive fractures was small compared to the background variability. In general, ERT was able to locate correctly resistive fractures. Problems occurred, however, when the resistive fracture was near the edges of the model or when multiple fractures were close together. In particular, ERT tended to position the fracture closer to the model center than its true location. Conductive fractures yielded much smaller responses than the resistive case. A difference-inversion method was able to correctly locate these targets.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahmad Ghassemi

Geothermal energy is recovered by circulating water through heat exchange areas within a hot rock mass. Geothermal reservoir rock masses generally consist of igneous and metamorphic rocks that have low matrix permeability. Therefore, cracks and fractures play a significant role in extraction of geothermal energy by providing the major pathways for fluid flow and heat exchange. Therefore, knowledge of the conditions leading to formation of fractures and fracture networks is of paramount importance. Furthermore, in the absence of natural fractures or adequate connectivity, artificial fractures are created in the reservoir using hydraulic fracturing. Multiple fractures are preferred because of themore » large size necessary when using only a single fracture. Although the basic idea is rather simple, hydraulic fracturing is a complex process involving interactions of high pressure fluid injections with a stressed hot rock mass, mechanical interaction of induced fractures with existing natural fractures, and the spatial and temporal variations of in-situ stress. As a result, it is necessary to develop tools that can be used to study these interactions as an integral part of a comprehensive approach to geothermal reservoir development, particularly enhanced geothermal systems. In response to this need we have developed advanced poro-thermo-chemo-mechanical fracture models for rock fracture research in support of EGS design. The fracture propagation models are based on a regular displacement discontinuity formulation. The fracture propagation studies include modeling interaction of induced fractures. In addition to the fracture propagation studies, two-dimensional solution algorithms have been developed and used to estimate the impact of pro-thermo-chemical processes on fracture permeability and reservoir pressure. Fracture permeability variation is studied using a coupled thermo-chemical model with quartz reaction kinetics. The model is applied to study quartz precipitation/dissolution, as well as the variation in fracture aperture and pressure. Also, a three-dimensional model of injection/extraction has been developed to consider the impact poro- and thermoelastic stresses on fracture slip and injection pressure. These investigations shed light on the processes involved in the observed phenomenon of injection pressure variation (e.g., in Coso), and allow the assessment of the potential of thermal and chemical stimulation strategies.« less

Spacing of bending-induced fractures at saturation: Numerical models and approximate analytical solution

NASA Astrophysics Data System (ADS)

Schöpfer, Martin; Lehner, Florian; Grasemann, Bernhard; Kaserer, Klemens; Hinsch, Ralph

2017-04-01

John G. Ramsay's sketch of structures developed in a layer progressively folded and deformed by tangential longitudinal strain (Figure 7-65 in Folding and Fracturing of Rocks) and the associated strain pattern analysis have been reproduced in many monographs on Structural Geology and are referred to in numerous publications. Although the origin of outer-arc extension fractures is well-understood and documented in many natural examples, geomechanical factors controlling their (finite or saturation) spacing are hitherto unexplored. This study investigates the formation of bending-induced fractures during constant-curvature forced folding using Distinct Element Method (DEM) numerical modelling. The DEM model comprises a central brittle layer embedded within weaker (low modulus) elastic layers; the layer interfaces are frictionless (free slip). Folding of this three-layer system is enforced by a velocity boundary condition at the model base, while a constant overburden pressure is maintained at the model top. The models illustrate several key stages of fracture array development: (i) Prior to the onset of fracture, the neutral surface is located midway between the layer boundaries; (ii) A first set of regularly spaced fractures develops once the tensile stress in the outer-arc equals the tensile strength of the layer. Since the layer boundaries are frictionless, these bending-induced fractures propagate through the entire layer; (iii) After the appearance of the first fracture set, the rate of fracture formation decreases rapidly and so-called infill fractures develop approximately midway between two existing fractures (sequential infilling); (iv) Eventually no new fractures form, irrespective of any further increase in fold curvature (fracture saturation). Analysis of the interfacial normal stress distributions suggests that at saturation the fracture-bound blocks are subjected to a loading condition similar to three-point bending. Using classical beam theory an analytical solution is derived for the critical fracture spacing, i.e. the spacing below which the maximum tensile stress cannot reach the layer strength. The model results are consistent with an approximate analytical solution, and illustrate that the spacing of bending-induced fractures is proportional to layer thickness and a square root function of the ratio of layer tensile strength to confining pressure. Although highly idealised, models and analysis presented in this study offer an explanation for fracture saturation during folding and point towards certain key factors that may control fracture spacing in natural systems.

Brittle fracture phase-field modeling of a short-rod specimen

DOE Office of Scientific and Technical Information (OSTI.GOV)

Escobar, Ivana; Tupek, Michael R.; Bishop, Joseph E.

2015-09-01

Predictive simulation capabilities for modeling fracture evolution provide further insight into quantities of interest in comparison to experimental testing. Based on the variational approach to fracture, the advent of phase-field modeling achieves the goal to robustly model fracture for brittle materials and captures complex crack topologies in three dimensions.

Effect of hydro mechanical coupling on natural fracture network formation in sedimentary basins

NASA Astrophysics Data System (ADS)

Ouraga, Zady; Guy, Nicolas; Pouya, Amade

2018-05-01

In sedimentary basin context, numerous phenomena, depending on the geological time span, can result in natural fracture network formation. In this paper, fracture network and dynamic fracture spacing triggered by significant sedimentation rate are studied considering mode I fracture propagation using a coupled hydro-mechanical numerical methods. The focus is put on synthetic geological structure under a constant sedimentation rate on its top. This model contains vertical fracture network initially closed and homogeneously distributed. The fractures are modelled with cohesive zone model undergoing damage and the flow is described by Poiseuille's law. The effect of the behaviour of the rock is studied and the analysis leads to a pattern of fracture network and fracture spacing in the geological layer.

Predicting grid-size-dependent fracture strains of DP980 with a microstructure-based post-necking model

DOE PAGES

Cheng, G.; Hu, X. H.; Choi, K. S.; ...

2017-07-08

Ductile fracture is a local phenomenon, and it is well established that fracture strain levels depend on both stress triaxiality and the resolution (grid size) of strain measurements. Two-dimensional plane strain post-necking models with different model sizes are used in this paper to predict the grid-size-dependent fracture strain of a commercial dual-phase steel, DP980. The models are generated from the actual microstructures, and the individual phase flow properties and literature-based individual phase damage parameters for the Johnson–Cook model are used for ferrite and martensite. A monotonic relationship is predicted: the smaller the model size, the higher the fracture strain. Thus,more » a general framework is developed to quantify the grid-size-dependent fracture strains for multiphase materials. In addition to the grid-size dependency, the influences of intrinsic microstructure features, i.e., the flow curve and fracture strains of the two constituent phases, on the predicted fracture strains also are examined. Finally, application of the derived fracture strain versus model size relationship is demonstrated with large clearance trimming simulations with different element sizes.« less

Predicting grid-size-dependent fracture strains of DP980 with a microstructure-based post-necking model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, G.; Hu, X. H.; Choi, K. S.

Ductile fracture is a local phenomenon, and it is well established that fracture strain levels depend on both stress triaxiality and the resolution (grid size) of strain measurements. Two-dimensional plane strain post-necking models with different model sizes are used in this paper to predict the grid-size-dependent fracture strain of a commercial dual-phase steel, DP980. The models are generated from the actual microstructures, and the individual phase flow properties and literature-based individual phase damage parameters for the Johnson–Cook model are used for ferrite and martensite. A monotonic relationship is predicted: the smaller the model size, the higher the fracture strain. Thus,more » a general framework is developed to quantify the grid-size-dependent fracture strains for multiphase materials. In addition to the grid-size dependency, the influences of intrinsic microstructure features, i.e., the flow curve and fracture strains of the two constituent phases, on the predicted fracture strains also are examined. Finally, application of the derived fracture strain versus model size relationship is demonstrated with large clearance trimming simulations with different element sizes.« less

Modeling Responses of Naturally Fractured Geothermal Reservoir to Low-Pressure Stimulation

DOE Data Explorer

Fu, Pengcheng; Carrigan, Charles R.

2012-01-01

Hydraulic shearing is an appealing reservoir stimulation strategy for Enhanced Geothermal Systems. It is believed that hydro-shearing is likely to simulate a fracture network that covers a relatively large volume of the reservoir whereas hydro-fracturing tends to create a small number of fractures. In this paper, we examine the geomechanical and hydraulic behaviors of natural fracture systems subjected to hydro-shearing stimulation and develop a coupled numerical model within the framework of discrete fracture network modeling. We found that in the low pressure hydro-shearing regime, the coupling between the fluid phase and the rock solid phase is relatively simple, and the numerical model is computationally efficient. Using this modified model, we study the behavior of a random fracture network subjected to hydro-shearing stimulation.

Coupled Hydro-mechanical process of natural fracture network formation in sedimentary basin

NASA Astrophysics Data System (ADS)

Ouraga, zady; Guy, Nicolas; Pouya, amade

2017-04-01

In sedimentary basin numerous phenomenon depending on the geological time span and its history can lead to a decrease in effective stress and therefore result in fracture initiation. Thus, during its formation, under certain conditions, natural fracturing and fracture network formation can occur in various context such as under erosion, tectonic loading and the compaction disequilibrium due to significant sedimentation rate. In this work, natural fracture network and fracture spacing induced by significant sedimentation rate is studied considering mode I fracture propagation, using a coupled hydro-mechanical numerical methods. Assumption of vertical fracture can be considered as a relevant hypothesis in our case of low ratio of horizontal total stress to vertical stress. A particular emphasis is put on synthetic geological structure on which a constant sedimentation rate is imposed on its top. This synthetic geological structure contains defects initially closed and homogeneously distributed. The Fractures are modeled with a constitutive model undergoing damage and the flow is described by poiseuille's law. The damage parameter affects both the mechanical and the hydraulic opening of the fracture. For the numerical simulations, the code Porofis based on finite element modeling is used, fractures are taken into account by cohesive model and the flow is described by Poiseuille's law. The effect of several parameters is also studied and the analysis lead to a fracture network and fracture spacing criterion for basin modeling.

Phase field model of fluid-driven fracture in elastic media: Immersed-fracture formulation and validation with analytical solutions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Santillán, David; Juanes, Ruben; Cueto-Felgueroso, Luis

Propagation of fluid-driven fractures plays an important role in natural and engineering processes, including transport of magma in the lithosphere, geologic sequestration of carbon dioxide, and oil and gas recovery from low-permeability formations, among many others. The simulation of fracture propagation poses a computational challenge as a result of the complex physics of fracture and the need to capture disparate length scales. Phase field models represent fractures as a diffuse interface and enjoy the advantage that fracture nucleation, propagation, branching, or twisting can be simulated without ad hoc computational strategies like remeshing or local enrichment of the solution space. Heremore » we propose a new quasi-static phase field formulation for modeling fluid-driven fracturing in elastic media at small strains. The approach fully couples the fluid flow in the fracture (described via the Reynolds lubrication approximation) and the deformation of the surrounding medium. The flow is solved on a lower dimensionality mesh immersed in the elastic medium. This approach leads to accurate coupling of both physics. We assessed the performance of the model extensively by comparing results for the evolution of fracture length, aperture, and fracture fluid pressure against analytical solutions under different fracture propagation regimes. Thus, the excellent performance of the numerical model in all regimes builds confidence in the applicability of phase field approaches to simulate fluid-driven fracture.« less

Phase field model of fluid-driven fracture in elastic media: Immersed-fracture formulation and validation with analytical solutions

DOE PAGES

Santillán, David; Juanes, Ruben; Cueto-Felgueroso, Luis

2017-04-20

Propagation of fluid-driven fractures plays an important role in natural and engineering processes, including transport of magma in the lithosphere, geologic sequestration of carbon dioxide, and oil and gas recovery from low-permeability formations, among many others. The simulation of fracture propagation poses a computational challenge as a result of the complex physics of fracture and the need to capture disparate length scales. Phase field models represent fractures as a diffuse interface and enjoy the advantage that fracture nucleation, propagation, branching, or twisting can be simulated without ad hoc computational strategies like remeshing or local enrichment of the solution space. Heremore » we propose a new quasi-static phase field formulation for modeling fluid-driven fracturing in elastic media at small strains. The approach fully couples the fluid flow in the fracture (described via the Reynolds lubrication approximation) and the deformation of the surrounding medium. The flow is solved on a lower dimensionality mesh immersed in the elastic medium. This approach leads to accurate coupling of both physics. We assessed the performance of the model extensively by comparing results for the evolution of fracture length, aperture, and fracture fluid pressure against analytical solutions under different fracture propagation regimes. Thus, the excellent performance of the numerical model in all regimes builds confidence in the applicability of phase field approaches to simulate fluid-driven fracture.« less

Complementary hydro-mechanical coupled finite/discrete element and microseismic modelling to predict hydraulic fracture propagation in tight shale reservoirs

NASA Astrophysics Data System (ADS)

Profit, Matthew; Dutko, Martin; Yu, Jianguo; Cole, Sarah; Angus, Doug; Baird, Alan

2016-04-01

This paper presents a novel approach to predict the propagation of hydraulic fractures in tight shale reservoirs. Many hydraulic fracture modelling schemes assume that the fracture direction is pre-seeded in the problem domain discretisation. This is a severe limitation as the reservoir often contains large numbers of pre-existing fractures that strongly influence the direction of the propagating fracture. To circumvent these shortcomings, a new fracture modelling treatment is proposed where the introduction of discrete fracture surfaces is based on new and dynamically updated geometrical entities rather than the topology of the underlying spatial discretisation. Hydraulic fracturing is an inherently coupled engineering problem with interactions between fluid flow and fracturing when the stress state of the reservoir rock attains a failure criterion. This work follows a staggered hydro-mechanical coupled finite/discrete element approach to capture the key interplay between fluid pressure and fracture growth. In field practice, the fracture growth is hidden from the design engineer and microseismicity is often used to infer hydraulic fracture lengths and directions. Microseismic output can also be computed from changes of the effective stress in the geomechanical model and compared against field microseismicity. A number of hydraulic fracture numerical examples are presented to illustrate the new technology.

Disuse exaggerates the detrimental effects of alcohol on cortical bone

NASA Technical Reports Server (NTRS)

Hefferan, Theresa E.; Kennedy, Angela M.; Evans, Glenda L.; Turner, Russell T.

2003-01-01

BACKGROUND: Alcohol abuse is associated with an increased risk for osteoporosis. However, comorbidity factors may play an important role in the pathogenesis of alcohol-related bone fractures. Suboptimal mechanical loading of the skeleton, an established risk factor for bone loss, may occur in some alcohol abusers due to reduced physical activity, muscle atrophy, or both. The effect of alcohol consumption and reduced physical activity on bone metabolism has not been well studied. The purpose of this study was to determine whether mechanical disuse alters bone metabolism in a rat model for chronic alcohol abuse. METHODS: Alcohol was administered in the diet (35% caloric intake) of 6-month-old male rats for 4 weeks. Rats were hindlimb-unloaded the final 2 weeks of the experiment to prevent dynamic weight bearing. Afterward, cortical bone histomorphometry was evaluated at the tibia-fibula synostosis. RESULTS: At the periosteal surface of the tibial diaphysis, alcohol and hindlimb unloading independently decreased the mineralizing perimeter, mineral apposition rate, and bone formation rate. In addition, alcohol, but not hindlimb unloading, increased endocortical bone resorption. The respective detrimental effects of alcohol and hindlimb unloading to inhibit bone formation were additive; there was no interaction between the two variables. CONCLUSIONS: Reduced weight bearing accentuates the detrimental effects of alcohol on cortical bone in adult male rats by further inhibiting bone formation. This finding suggests that reduced physical activity may be a comorbidity factor for osteoporosis in alcohol abusers.

Consequences of Fluid Lag in Three-Dimensional Hydraulic Fractures

NASA Astrophysics Data System (ADS)

Advani (Deceased), S. H.; Lee, T. S.; Dean, R. H.; Pak, C. K.; Avasthi, J. M.

1997-04-01

Research investigations on three-dimensional (3-D) rectangular hydraulic fracture configurations with varying degrees of fluid lag are reported. This paper demonstrates that a 3-D fracture model coupled with fluid lag (a small region of reduced pressure) at the fracture tip can predict very large excess pressure measurements for hydraulic fracture processes. Predictions of fracture propagation based on critical stress intensity factors are extremely sensitive to the pressure profile at the tip of a propagating fracture. This strong sensitivity to the pressure profile at the tip of a hydraulic fracture is more strongly pronounced in 3-D models versus 2-D models because 3-D fractures are clamped at the top and bottom, and pressures in the 3-D fractures that are far removed from the fracture tip have little effect on the stress intensity factor at the fracture tip. This rationale for the excess pressure mechanism is in marked contrast to the crack tip process damage zone assumptions and attendant high rock fracture toughness value hypotheses advanced in the literature. A comparison with field data is presented to illustrate the proposed fracture fluid pressure sensitivity phenomenon. This paper does not attempt to calculate the length of the fluid lag region in a propagating fracture but instead attempts to show that the pressure profile at the tip of the propagating fracture plays a major role in fracture propagation, and this role is magnified in 3-D models. Int. J. Numer. Anal. Meth. Geomech., vol. 21, 229-240 (1997).

A nonequilibrium model for reactive contaminant transport through fractured porous media: Model development and semianalytical solution

NASA Astrophysics Data System (ADS)

Joshi, Nitin; Ojha, C. S. P.; Sharma, P. K.

2012-10-01

In this study a conceptual model that accounts for the effects of nonequilibrium contaminant transport in a fractured porous media is developed. Present model accounts for both physical and sorption nonequilibrium. Analytical solution was developed using the Laplace transform technique, which was then numerically inverted to obtain solute concentration in the fracture matrix system. The semianalytical solution developed here can incorporate both semi-infinite and finite fracture matrix extent. In addition, the model can account for flexible boundary conditions and nonzero initial condition in the fracture matrix system. The present semianalytical solution was validated against the existing analytical solutions for the fracture matrix system. In order to differentiate between various sorption/transport mechanism different cases of sorption and mass transfer were analyzed by comparing the breakthrough curves and temporal moments. It was found that significant differences in the signature of sorption and mass transfer exists. Applicability of the developed model was evaluated by simulating the published experimental data of Calcium and Strontium transport in a single fracture. The present model simulated the experimental data reasonably well in comparison to the model based on equilibrium sorption assumption in fracture matrix system, and multi rate mass transfer model.

Three-dimensional DFN Model Development and Calibration: A Case Study for Pahute Mesa, Nevada National Security Site

NASA Astrophysics Data System (ADS)

Pham, H. V.; Parashar, R.; Sund, N. L.; Pohlmann, K.

2017-12-01

Pahute Mesa, located in the north-western region of the Nevada National Security Site, is an area where numerous underground nuclear tests were conducted. The mesa contains several fractured aquifers that can potentially provide high permeability pathways for migration of radionuclides away from testing locations. The BULLION Forced-Gradient Experiment (FGE) conducted on Pahute Mesa injected and pumped solute and colloid tracers from a system of three wells for obtaining site-specific information about the transport of radionuclides in fractured rock aquifers. This study aims to develop reliable three-dimensional discrete fracture network (DFN) models to simulate the BULLION FGE as a means for computing realistic ranges of important parameters describing fractured rock. Multiple conceptual DFN models were developed using dfnWorks, a parallelized computational suite developed by Los Alamos National Laboratory, to simulate flow and conservative particle movement in subsurface fractured rocks downgradient from the BULLION test. The model domain is 100x200x100 m and includes the three tracer-test wells of the BULLION FGE and the Pahute Mesa Lava-flow aquifer. The model scenarios considered differ from each other in terms of boundary conditions and fracture density. For each conceptual model, a number of statistically equivalent fracture network realizations were generated using data from fracture characterization studies. We adopt the covariance matrix adaptation-evolution strategy (CMA-ES) as a global local stochastic derivative-free optimization method to calibrate the DFN models using groundwater levels and tracer breakthrough data obtained from the three wells. Models of fracture apertures based on fracture type and size are proposed and the values of apertures in each model are estimated during model calibration. The ranges of fracture aperture values resulting from this study are expected to enhance understanding of radionuclide transport in fractured rocks and support development of improved large-scale flow and transport models for Pahute Mesa.

Adaptive Multiscale Modeling of Geochemical Impacts on Fracture Evolution

NASA Astrophysics Data System (ADS)

Molins, S.; Trebotich, D.; Steefel, C. I.; Deng, H.

2016-12-01

Understanding fracture evolution is essential for many subsurface energy applications, including subsurface storage, shale gas production, fracking, CO2 sequestration, and geothermal energy extraction. Geochemical processes in particular play a significant role in the evolution of fractures through dissolution-driven widening, fines migration, and/or fracture sealing due to precipitation. One obstacle to understanding and exploiting geochemical fracture evolution is that it is a multiscale process. However, current geochemical modeling of fractures cannot capture this multi-scale nature of geochemical and mechanical impacts on fracture evolution, and is limited to either a continuum or pore-scale representation. Conventional continuum-scale models treat fractures as preferential flow paths, with their permeability evolving as a function (often, a cubic law) of the fracture aperture. This approach has the limitation that it oversimplifies flow within the fracture in its omission of pore scale effects while also assuming well-mixed conditions. More recently, pore-scale models along with advanced characterization techniques have allowed for accurate simulations of flow and reactive transport within the pore space (Molins et al., 2014, 2015). However, these models, even with high performance computing, are currently limited in their ability to treat tractable domain sizes (Steefel et al., 2013). Thus, there is a critical need to develop an adaptive modeling capability that can account for separate properties and processes, emergent and otherwise, in the fracture and the rock matrix at different spatial scales. Here we present an adaptive modeling capability that treats geochemical impacts on fracture evolution within a single multiscale framework. Model development makes use of the high performance simulation capability, Chombo-Crunch, leveraged by high resolution characterization and experiments. The modeling framework is based on the adaptive capability in Chombo which not only enables mesh refinement, but also refinement of the model-pore scale or continuum Darcy scale-in a dynamic way such that the appropriate model is used only when and where it is needed. Explicit flux matching provides coupling betwen the scales.

The Effect of Vibration Treatments Combined with Teriparatide or Strontium Ranelate on Bone Healing and Muscle in Ovariectomized Rats.

PubMed

Komrakova, M; Hoffmann, D B; Nuehnen, V; Stueber, H; Wassmann, M; Wicke, M; Tezval, M; Stuermer, K M; Sehmisch, S

2016-10-01

The aim of the present study was to study the effect of combined therapy of teriparatide (PTH) or strontium ranelate (SR) with whole-body vibration (WBV) on bone healing and muscle properties in an osteopenic rat model. Seventy-two rats (3 months old) were bilaterally ovariectomized (Ovx), and 12 rats were left intact (Non-Ovx). After 8 weeks, bilateral transverse osteotomy was performed at the tibia metaphysis in all rats. Thereafter, Ovx rats were divided into six groups (n = 12): (1) Ovx-no treatment, (2) Ovx + vibration (Vib), (3) SR, (4) SR + Vib, (5) PTH, and (6) PTH + Vib. PTH (40 μg/kg BW sc. 5×/week) and SR (613 mg/kg BW in food daily) were applied on the day of ovariectomy, vibration treatments 5 days later (vertical, 70 Hz, 0.5 mm, 2×/day for 15 min) for up to 6 weeks. In the WBV + SR group, the callus density, trabecular number, and Alp and Oc gene expression were decreased compared to SR alone. In the WBV + PTH group, the cortical and callus widths, biomechanical properties, Opg gene expression, and Opg/Rankl ratio were increased; the cortical and callus densities were decreased compared to PTH alone. A case of non-bridging was found in both vibrated groups. Vibration alone did not change the bone parameters; PTH possessed a stronger effect than SR therapy. In muscles, combined therapies improved the fiber size of Ovx rats. WBV could be applied alone or in combination with anti-osteoporosis drug therapy to improve muscle tissue. However, in patients with fractures, anti-osteoporosis treatments and the application of vibration could have an adverse effect on bone healing.

Distinct Element Method modelling of fold-related fractures in a multilayer sequence

NASA Astrophysics Data System (ADS)

Kaserer, Klemens; Schöpfer, Martin P. J.; Grasemann, Bernhard

2017-04-01

Natural fractures have a significant impact on the performance of hydrocarbon systems/reservoirs. In a multilayer sequence, both the fracture density within the individual layers and the type of fracture intersection with bedding contacts are key parameters controlling fluid pathways. In the present study the influence of layer stacking and interlayer friction on fracture density and connectivity within a folded sequence is systematically investigated using 2D Distinct Element Method modelling. Our numerical approach permits forward modelling of both fracture nucleation/propagation/arrest and (contemporaneous) frictional slip along bedding planes in a robust and mechanically sound manner. Folding of the multilayer sequence is achieved by enforcing constant curvature folding by means of a velocity boundary condition at the model base, while a constant overburden pressure is maintained at the model top. The modelling reveals that with high bedding plane friction the multilayer stack behaves mechanically as a single layer so that the neutral surface develops in centre of the sequence and fracture spacing is controlled by the total thickness of the folded sequence. In contrast, low bedding plane friction leads to decoupling of the individual layers (flexural slip folding) so that a neutral surface develops in the centre of each layer and fracture spacing is controlled by the thickness of the individual layers. The low interfacial friction models illustrate that stepping of fractures across bedding planes is a common process, which can however have two contrasting origins: The mechanical properties of the interface cause fracture stepping during fracture propagation. Originally through-going fractures are later offset by interfacial slip during folding. A combination of these two different origins may lead to (apparently) inconsistent fracture offsets across bedding planes within a flexural slip fold.

A systematic review of models used in cost-effectiveness analyses of preventing osteoporotic fractures.

PubMed

Si, L; Winzenberg, T M; Palmer, A J

2014-01-01

This review was aimed at the evolution of health economic models used in evaluations of clinical approaches aimed at preventing osteoporotic fractures. Models have improved, with medical continuance becoming increasingly recognized as a contributor to health and economic outcomes, as well as advancements in epidemiological data. Model-based health economic evaluation studies are increasingly used to investigate the cost-effectiveness of osteoporotic fracture preventions and treatments. The objective of this study was to carry out a systematic review of the evolution of health economic models used in the evaluation of osteoporotic fracture preventions. Electronic searches within MEDLINE and EMBASE were carried out using a predefined search strategy. Inclusion and exclusion criteria were used to select relevant studies. References listed of included studies were searched to identify any potential study that was not captured in our electronic search. Data on country, interventions, type of fracture prevention, evaluation perspective, type of model, time horizon, fracture sites, expressed costs, types of costs included, and effectiveness measurement were extracted. Seventy-four models were described in 104 publications, of which 69% were European. Earlier models focused mainly on hip, vertebral, and wrist fracture, but later models included multiple fracture sites (humerus, pelvis, tibia, and other fractures). Modeling techniques have evolved from simple decision trees, through deterministic Markov processes to individual patient simulation models accounting for uncertainty in multiple parameters. Treatment continuance has been increasingly taken into account in the models in the last decade. Models have evolved in their complexity and emphasis, with medical continuance becoming increasingly recognized as a contributor to health and economic outcomes. This evolution may be driven in part by the desire to capture all the important differentiating characteristics of medications under scrutiny, as well as the advancement in epidemiological data relevant to osteoporosis fractures.

Sepsis Reduces Bone Strength Before Morphologic Changes Are Identifiable.

PubMed

Puthucheary, Zudin A; Sun, Yao; Zeng, Kaiyang; Vu, Lien Hong; Zhang, Zhi Wei; Lim, Ryan Z L; Chew, Nicholas S Y; Cove, Matthew E

2017-12-01

Survivors of critical illness have an increased prevalence of bone fractures. However, early changes in bone strength, and their relationship to structural changes, have not been described. We aimed to characterize early changes in bone functional properties in critical illness and their relationship to changes in bone structure, using a sepsis rodent model. Experimental study. Animal research laboratory. Adult Sprague-Dawley rats. Forty Sprague-Dawley rats were randomized to cecal ligation and puncture or sham surgery. Twenty rodents (10 cecal ligation and puncture, 10 sham) were killed at 24 hours, and 20 more at 96 hours. Femoral bones were harvested for strength testing, microCT imaging, histologic analysis, and multifrequency scanning probe microscopy. Fracture loads at the femoral neck were significantly reduced for cecal ligation and puncture-exposed rodents at 24 hours (83.39 ± 10.1 vs 103.1 ± 17.6 N; p = 0.014) and 96 hours (81.60 ± 14.2 vs 95.66 ± 14.3 N; p = 0.047). Using multifrequency scanning probe microscopy, collagen elastic modulus was lower in cecal ligation and puncture-exposed rats at 24 hours (1.37 ± 0.2 vs 6.13 ± 0.3 GPa; p = 0.001) and 96 hours (5.57 ± 0.5 vs 6.13 ± 0.3 GPa; p = 0.006). Bone mineral elastic modulus was similar at 24 hours but reduced in cecal ligation and puncture-exposed rodents at 96 hours (75.34 ± 13.2 vs 134.4 ± 8.2 GPa; p < 0.001). There were no bone architectural or bone mineral density differences by microCT. Similarly, histologic analysis demonstrated no difference in collagen and elastin staining, and C-X-C chemokine receptor type 4, nuclear factor kappa beta, and tartrate-resistant acid phosphatase immunostaining. In a rodent sepsis model, trabecular bone strength is functionally reduced within 24 hours and is associated with a reduction in collagen and mineral elastic modulus. This is likely to be the result of altered biomechanical properties, rather than increased bone mineral turnover. These data offer both mechanistic insights and may potentially guide development of therapeutic interventions.

A multi-scale experimental and simulation approach for fractured subsurface systems

NASA Astrophysics Data System (ADS)

Viswanathan, H. S.; Carey, J. W.; Frash, L.; Karra, S.; Hyman, J.; Kang, Q.; Rougier, E.; Srinivasan, G.

2017-12-01

Fractured systems play an important role in numerous subsurface applications including hydraulic fracturing, carbon sequestration, geothermal energy and underground nuclear test detection. Fractures that range in scale from microns to meters and their structure control the behavior of these systems which provide over 85% of our energy and 50% of US drinking water. Determining the key mechanisms in subsurface fractured systems has been impeded due to the lack of sophisticated experimental methods to measure fracture aperture and connectivity, multiphase permeability, and chemical exchange capacities at the high temperature, pressure, and stresses present in the subsurface. In this study, we developed and use microfluidic and triaxial core flood experiments required to reveal the fundamental dynamics of fracture-fluid interactions. In addition we have developed high fidelity fracture propagation and discrete fracture network flow models to simulate these fractured systems. We also have developed reduced order models of these fracture simulators in order to conduct uncertainty quantification for these systems. We demonstrate an integrated experimental/modeling approach that allows for a comprehensive characterization of fractured systems and develop models that can be used to optimize the reservoir operating conditions over a range of subsurface conditions.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Kyoungsoo, E-mail: kpark16@illinois.ed; Paulino, Glaucio H.; Roesler, Jeffery

A simple, effective, and practical constitutive model for cohesive fracture of fiber reinforced concrete is proposed by differentiating the aggregate bridging zone and the fiber bridging zone. The aggregate bridging zone is related to the total fracture energy of plain concrete, while the fiber bridging zone is associated with the difference between the total fracture energy of fiber reinforced concrete and the total fracture energy of plain concrete. The cohesive fracture model is defined by experimental fracture parameters, which are obtained through three-point bending and split tensile tests. As expected, the model describes fracture behavior of plain concrete beams. Inmore » addition, it predicts the fracture behavior of either fiber reinforced concrete beams or a combination of plain and fiber reinforced concrete functionally layered in a single beam specimen. The validated model is also applied to investigate continuously, functionally graded fiber reinforced concrete composites.« less

Modelling of Local Necking and Fracture in Aluminium Alloys

DOE Office of Scientific and Technical Information (OSTI.GOV)

Achani, D.; Eriksson, M.; Hopperstad, O. S.

2007-05-17

Non-linear Finite Element simulations are extensively used in forming and crashworthiness studies of automotive components and structures in which fracture need to be controlled. For thin-walled ductile materials, the fracture-related phenomena that must be properly represented are thinning instability, ductile fracture and through-thickness shear instability. Proper representation of the fracture process relies on the accuracy of constitutive and fracture models and their parameters that need to be calibrated through well defined experiments. The present study focuses on local necking and fracture which is of high industrial importance, and uses a phenomenological criterion for modelling fracture in aluminium alloys. As anmore » accurate description of plastic anisotropy is important, advanced phenomenological constitutive equations based on the yield criterion YLD2000/YLD2003 are used. Uniaxial tensile tests and disc compression tests are performed for identification of the constitutive model parameters. Ductile fracture is described by the Cockcroft-Latham fracture criterion and an in-plane shear tests is performed to identify the fracture parameter. The reason is that in a well designed in-plane shear test no thinning instability should occur and it thus gives more direct information about the phenomenon of ductile fracture. Numerical simulations have been performed using a user-defined material model implemented in the general-purpose non-linear FE code LS-DYNA. The applicability of the model is demonstrated by correlating the predicted and experimental response in the in-plane shear tests and additional plane strain tension tests.« less

Phase Field Model of Hydraulic Fracturing in Poroelastic Media: Fracture Propagation, Arrest, and Branching Under Fluid Injection and Extraction

NASA Astrophysics Data System (ADS)

Santillán, David; Juanes, Ruben; Cueto-Felgueroso, Luis

2018-03-01

The simulation of fluid-driven fracture propagation in a porous medium is a major computational challenge, with applications in geosciences and engineering. The two main families of modeling approaches are those models that represent fractures as explicit discontinuities and solve the moving boundary problem and those that represent fractures as thin damaged zones, solving a continuum problem throughout. The latter family includes the so-called phase field models. Continuum approaches to fracture face validation and verification challenges, in particular grid convergence, well posedness, and physical relevance in practical scenarios. Here we propose a new quasi-static phase field formulation. The approach fully couples fluid flow in the fracture with deformation and flow in the porous medium, discretizes flow in the fracture on a lower-dimension manifold, and employs the fluid flux between the fracture and the porous solid as coupling variable. We present a numerical assessment of the model by studying the propagation of a fracture in the quarter five-spot configuration. We study the interplay between injection flow rate and rock properties and elucidate fracture propagation patterns under the leak-off toughness dominated regime as a function of injection rate, initial fracture length, and poromechanical properties. For the considered injection scenario, we show that the final fracture length depends on the injection rate, and three distinct patterns are observed. We also rationalize the system response using dimensional analysis to collapse the model results. Finally, we propose some simplifications that alleviate the computational cost of the simulations without significant loss of accuracy.

Modelling CO2 flow in naturally fractured geological media using MINC and multiple subregion upscaling procedure

NASA Astrophysics Data System (ADS)

Tatomir, Alexandru Bogdan A. C.; Flemisch, Bernd; Class, Holger; Helmig, Rainer; Sauter, Martin

2017-04-01

Geological storage of CO2 represents one viable solution to reduce greenhouse gas emission in the atmosphere. Potential leakage of CO2 storage can occur through networks of interconnected fractures. The geometrical complexity of these networks is often very high involving fractures occurring at various scales and having hierarchical structures. Such multiphase flow systems are usually hard to solve with a discrete fracture modelling (DFM) approach. Therefore, continuum fracture models assuming average properties are usually preferred. The multiple interacting continua (MINC) model is an extension of the classic double porosity model (Warren and Root, 1963) which accounts for the non-linear behaviour of the matrix-fracture interactions. For CO2 storage applications the transient representation of the inter-porosity two phase flow plays an important role. This study tests the accuracy and computational efficiency of the MINC method complemented with the multiple sub-region (MSR) upscaling procedure versus the DFM. The two phase flow MINC simulator is implemented in the free-open source numerical toolbox DuMux (www.dumux.org). The MSR (Gong et al., 2009) determines the inter-porosity terms by solving simplified local single-phase flow problems. The DFM is considered as the reference solution. The numerical examples consider a quasi-1D reservoir with a quadratic fracture system , a five-spot radial symmetric reservoir, and a completely random generated fracture system. Keywords: MINC, upscaling, two-phase flow, fractured porous media, discrete fracture model, continuum fracture model

Parameter Prediction of Hydraulic Fracture for Tight Reservoir Based on Micro-Seismic and History Matching

NASA Astrophysics Data System (ADS)

Zhang, Kai; Ma, Xiaopeng; Li, Yanlai; Wu, Haiyang; Cui, Chenyu; Zhang, Xiaoming; Zhang, Hao; Yao, Jun

Hydraulic fracturing is an important measure for the development of tight reservoirs. In order to describe the distribution of hydraulic fractures, micro-seismic diagnostic was introduced into petroleum fields. Micro-seismic events may reveal important information about static characteristics of hydraulic fracturing. However, this method is limited to reflect the distribution area of the hydraulic fractures and fails to provide specific parameters. Therefore, micro-seismic technology is integrated with history matching to predict the hydraulic fracture parameters in this paper. Micro-seismic source location is used to describe the basic shape of hydraulic fractures. After that, secondary modeling is considered to calibrate the parameters information of hydraulic fractures by using DFM (discrete fracture model) and history matching method. In consideration of fractal feature of hydraulic fracture, fractal fracture network model is established to evaluate this method in numerical experiment. The results clearly show the effectiveness of the proposed approach to estimate the parameters of hydraulic fractures.

Protective Effects of Vildagliptin against Pioglitazone-Induced Bone Loss in Type 2 Diabetic Rats

PubMed Central

Kwak, Kyung Min; Kim, Ju-Young; Yu, Seung Hee; Lee, Sihoon; Kim, Yeun Sun; Park, Ie Byung; Kim, Kwang-Won; Lee, Kiyoung

2016-01-01

Long-term use of thiazolidinediones (TZDs) is associated with bone loss and an increased risk of fracture in patients with type 2 diabetes (T2DM). Incretin-based drugs (glucagon-like peptide-1 (GLP-1) agonists and dipeptidylpeptidase-4 (DPP-4) inhibitors) have several benefits in many systems in addition to glycemic control. In a previous study, we reported that exendin-4 might increase bone mineral density (BMD) by decreasing the expression of SOST/sclerostin in osteocytes in a T2DM animal model. In this study, we investigated the effects of a DPP-4 inhibitor on TZD-induced bone loss in a T2DM animal model. We randomly divided 12-week-old male Zucker Diabetic Fatty (ZDF) rats into four groups; control, vildagliptin, pioglitazone, and vildagliptin and pioglitazone combination. Animals in each group received the respective treatments for 5 weeks. We performed an intraperitoneal glucose tolerance test (IPGTT) before and after treatment. BMD and the trabecular micro-architecture were measured by DEXA and micro CT, respectively, at the end of the treatment. The circulating levels of active GLP-1, bone turnover markers, and sclerostin were assayed. Vildagliptin treatment significantly increased BMD and trabecular bone volume. The combination therapy restored BMD, trabecular bone volume, and trabecular bone thickness that were decreased by pioglitazone. The levels of the bone formation marker, osteocalcin, decreased and that of the bone resorption marker, tartrate-resistant acid phosphatase (TRAP) 5b increased in the pioglitazone group. These biomarkers were ameliorated and the pioglitazone-induced increase in sclerostin level was lowered to control values by the addition of vildagliptin. In conclusion, our results indicate that orally administered vildagliptin demonstrated a protective effect on pioglitazone-induced bone loss in a type 2 diabetic rat model. PMID:27997588

Protective Effects of Vildagliptin against Pioglitazone-Induced Bone Loss in Type 2 Diabetic Rats.

PubMed

Eom, Young Sil; Gwon, A-Ryeong; Kwak, Kyung Min; Kim, Ju-Young; Yu, Seung Hee; Lee, Sihoon; Kim, Yeun Sun; Park, Ie Byung; Kim, Kwang-Won; Lee, Kiyoung; Kim, Byung-Joon

2016-01-01

Long-term use of thiazolidinediones (TZDs) is associated with bone loss and an increased risk of fracture in patients with type 2 diabetes (T2DM). Incretin-based drugs (glucagon-like peptide-1 (GLP-1) agonists and dipeptidylpeptidase-4 (DPP-4) inhibitors) have several benefits in many systems in addition to glycemic control. In a previous study, we reported that exendin-4 might increase bone mineral density (BMD) by decreasing the expression of SOST/sclerostin in osteocytes in a T2DM animal model. In this study, we investigated the effects of a DPP-4 inhibitor on TZD-induced bone loss in a T2DM animal model. We randomly divided 12-week-old male Zucker Diabetic Fatty (ZDF) rats into four groups; control, vildagliptin, pioglitazone, and vildagliptin and pioglitazone combination. Animals in each group received the respective treatments for 5 weeks. We performed an intraperitoneal glucose tolerance test (IPGTT) before and after treatment. BMD and the trabecular micro-architecture were measured by DEXA and micro CT, respectively, at the end of the treatment. The circulating levels of active GLP-1, bone turnover markers, and sclerostin were assayed. Vildagliptin treatment significantly increased BMD and trabecular bone volume. The combination therapy restored BMD, trabecular bone volume, and trabecular bone thickness that were decreased by pioglitazone. The levels of the bone formation marker, osteocalcin, decreased and that of the bone resorption marker, tartrate-resistant acid phosphatase (TRAP) 5b increased in the pioglitazone group. These biomarkers were ameliorated and the pioglitazone-induced increase in sclerostin level was lowered to control values by the addition of vildagliptin. In conclusion, our results indicate that orally administered vildagliptin demonstrated a protective effect on pioglitazone-induced bone loss in a type 2 diabetic rat model.

Fractal Analysis of Permeability of Unsaturated Fractured Rocks

PubMed Central

Jiang, Guoping; Shi, Wei; Huang, Lili

2013-01-01

A physical conceptual model for water retention in fractured rocks is derived while taking into account the effect of pore size distribution and tortuosity of capillaries. The formula of calculating relative hydraulic conductivity of fractured rock is given based on fractal theory. It is an issue to choose an appropriate capillary pressure-saturation curve in the research of unsaturated fractured mass. The geometric pattern of the fracture bulk is described based on the fractal distribution of tortuosity. The resulting water content expression is then used to estimate the unsaturated hydraulic conductivity of the fractured medium based on the well-known model of Burdine. It is found that for large enough ranges of fracture apertures the new constitutive model converges to the empirical Brooks-Corey model. PMID:23690746

Fractal analysis of permeability of unsaturated fractured rocks.

PubMed

Jiang, Guoping; Shi, Wei; Huang, Lili

2013-01-01

A physical conceptual model for water retention in fractured rocks is derived while taking into account the effect of pore size distribution and tortuosity of capillaries. The formula of calculating relative hydraulic conductivity of fractured rock is given based on fractal theory. It is an issue to choose an appropriate capillary pressure-saturation curve in the research of unsaturated fractured mass. The geometric pattern of the fracture bulk is described based on the fractal distribution of tortuosity. The resulting water content expression is then used to estimate the unsaturated hydraulic conductivity of the fractured medium based on the well-known model of Burdine. It is found that for large enough ranges of fracture apertures the new constitutive model converges to the empirical Brooks-Corey model.

Novel Model of Frontal Impact Closed Head Injury in the Rat

PubMed Central

Kilbourne, Michael; Kuehn, Reed; Tosun, Cigdem; Caridi, John; Keledjian, Kaspar; Bochicchio, Grant; Scalea, Thomas; Gerzanich, Volodymyr

2009-01-01

Abstract Frontal impact, closed head trauma is a frequent cause of traumatic brain injury (TBI) in motor vehicle and sports accidents. Diffuse axonal injury (DAI) is common in humans and experimental animals, and results from shearing forces that develop within the anisotropic brain. Because the specific anisotropic properties of the brain are axis-dependent, the anatomical site where force is applied as well as the resultant acceleration, be it linear, rotational, or some combination, are important determinants of the resulting pattern of brain injury. Available rodent models of closed head injury do not reproduce the frontal impact commonly encountered in humans. Here we describe a new rat model of closed head injury that is a modification of the impact-acceleration model of Marmarou. In our model (the Maryland model), the impact force is applied to the anterior part of the cranium and produces TBI by causing anterior-posterior plus sagittal rotational acceleration of the brain inside the intact cranium. Skull fractures, prolonged apnea, and mortality were absent. The animals exhibited petechial hemorrhages, DAI marked by a bead-like pattern of β-amyloid precursor protein (β-APP) in damaged axons, and widespread upregulation of β-APP in neurons, with regions affected including the orbitofrontal cortex (coup), corpus callosum, caudate, putamen, thalamus, cerebellum, and brainstem. Activated caspase-3 was prominent in hippocampal neurons and Purkinje cells at the grey-white matter junction of the cerebellum. Neurobehavioral dysfunction, manifesting as reduced spontaneous exploration, lasted more than 1 week. We conclude that the Maryland model produces diffuse injuries that may be relevant to human brain injury. PMID:19929375

Multiporosity flow in fractured low-permeability rocks: Extension to shale hydrocarbon reservoirs

DOE PAGES

Kuhlman, Kristopher L.; Malama, Bwalya; Heath, Jason E.

2015-02-05

We presented a multiporosity extension of classical double and triple-porosity fractured rock flow models for slightly compressible fluids. The multiporosity model is an adaptation of the multirate solute transport model of Haggerty and Gorelick (1995) to viscous flow in fractured rock reservoirs. It is a generalization of both pseudo steady state and transient interporosity flow double-porosity models. The model includes a fracture continuum and an overlapping distribution of multiple rock matrix continua, whose fracture-matrix exchange coefficients are specified through a discrete probability mass function. Semianalytical cylindrically symmetric solutions to the multiporosity mathematical model are developed using the Laplace transform tomore » illustrate its behavior. Furthermore, the multiporosity model presented here is conceptually simple, yet flexible enough to simulate common conceptualizations of double and triple-porosity flow. This combination of generality and simplicity makes the multiporosity model a good choice for flow modelling in low-permeability fractured rocks.« less

Global Sensitivity Applied to Dynamic Combined Finite Discrete Element Methods for Fracture Simulation

NASA Astrophysics Data System (ADS)

Godinez, H. C.; Rougier, E.; Osthus, D.; Srinivasan, G.

2017-12-01

Fracture propagation play a key role for a number of application of interest to the scientific community. From dynamic fracture processes like spall and fragmentation in metals and detection of gas flow in static fractures in rock and the subsurface, the dynamics of fracture propagation is important to various engineering and scientific disciplines. In this work we implement a global sensitivity analysis test to the Hybrid Optimization Software Suite (HOSS), a multi-physics software tool based on the combined finite-discrete element method, that is used to describe material deformation and failure (i.e., fracture and fragmentation) under a number of user-prescribed boundary conditions. We explore the sensitivity of HOSS for various model parameters that influence how fracture are propagated through a material of interest. The parameters control the softening curve that the model relies to determine fractures within each element in the mesh, as well a other internal parameters which influence fracture behavior. The sensitivity method we apply is the Fourier Amplitude Sensitivity Test (FAST), which is a global sensitivity method to explore how each parameter influence the model fracture and to determine the key model parameters that have the most impact on the model. We present several sensitivity experiments for different combination of model parameters and compare against experimental data for verification.

A discrete fracture model for two-phase flow in fractured porous media

NASA Astrophysics Data System (ADS)

Gläser, Dennis; Helmig, Rainer; Flemisch, Bernd; Class, Holger

2017-12-01

A discrete fracture model on the basis of a cell-centered finite volume scheme with multi-point flux approximation (MPFA) is presented. The fractures are included in a d-dimensional computational domain as (d - 1)-dimensional entities living on the element facets, which requires the grid to have the element facets aligned with the fracture geometries. However, the approach overcomes the problem of small cells inside the fractures when compared to equi-dimensional models. The system of equations considered is solved on both the matrix and the fracture domain, where on the prior the fractures are treated as interior boundaries and on the latter the exchange term between fracture and matrix appears as an additional source/sink. This exchange term is represented by the matrix-fracture fluxes, computed as functions of the unknowns in both domains by applying adequate modifications to the MPFA scheme. The method is applicable to both low-permeable as well as highly conductive fractures. The quality of the results obtained by the discrete fracture model is studied by comparison to an equi-dimensional discretization on a simple geometry for both single- and two-phase flow. For the case of two-phase flow in a highly conductive fracture, good agreement in the solution and in the matrix-fracture transfer fluxes could be observed, while for a low-permeable fracture the discrepancies were more pronounced. The method is then applied two-phase flow through a realistic fracture network in two and three dimensions.

Discriminative value of FRAX for fracture prediction in a cohort of Chinese postmenopausal women.

PubMed

Cheung, E Y N; Bow, C H; Cheung, C L; Soong, C; Yeung, S; Loong, C; Kung, A

2012-03-01

We followed 2,266 postmenopausal Chinese women for 4.5 years to determine which model best predicts osteoporotic fracture. A model that contains ethnic-specific risk factors, some of which reflect frailty, performed as well as or better than the well-established FRAX model. Clinical risk assessment, with or without T-score, can predict fractures in Chinese postmenopausal women although it is unknown which combination of clinical risk factors is most effective. This prospective study sought to compare the accuracy for fracture prediction using various models including FRAX, our ethnic-specific clinical risk factors (CRF) and other simple models. This study is part of the Hong Kong Osteoporosis Study. A total of 2,266 treatment naïve postmenopausal women underwent clinical risk factor and bone mineral density assessment. Subjects were followed up for outcome of major osteoporotic fracture and receiver operating characteristic (ROC) curves for different models were compared. The percentage of subjects in different quartiles of risk according to various models who actually fractured was also compared. The mean age at baseline was 62.1 ± 8.5 years and mean follow-up time was 4.5 ± 2.8 years. A total of 106 new major osteoporotic fractures were reported, of which 21 were hip fractures. Ethnic-specific CRF with T-score performed better than FRAX with T-score (based on both Chinese normative and National Health and Nutrition Examination Survey (NHANES) databases) in terms of AUC comparison for prediction of major osteoporotic fracture. The two models were similar in hip fracture prediction. The ethnic-specific CRF model had a 10% higher sensitivity than FRAX at a specificity of 0.8 or above. CRF related to frailty and differences in lifestyle between populations are likely to be important in fracture prediction. Further work is required to determine which and how CRF can be applied to develop a fracture prediction model in our population.

Rate decline curves analysis of multiple-fractured horizontal wells in heterogeneous reservoirs

NASA Astrophysics Data System (ADS)

Wang, Jiahang; Wang, Xiaodong; Dong, Wenxiu

2017-10-01

In heterogeneous reservoir with multiple-fractured horizontal wells (MFHWs), due to the high density network of artificial hydraulic fractures, the fluid flow around fracture tips behaves like non-linear flow. Moreover, the production behaviors of different artificial hydraulic fractures are also different. A rigorous semi-analytical model for MFHWs in heterogeneous reservoirs is presented by combining source function with boundary element method. The model are first validated by both analytical model and simulation model. Then new Blasingame type curves are established. Finally, the effects of critical parameters on the rate decline characteristics of MFHWs are discussed. The results show that heterogeneity has significant influence on the rate decline characteristics of MFHWs; the parameters related to the MFHWs, such as fracture conductivity and length also can affect the rate characteristics of MFHWs. One novelty of this model is to consider the elliptical flow around artificial hydraulic fracture tips. Therefore, our model can be used to predict rate performance more accurately for MFHWs in heterogeneous reservoir. The other novelty is the ability to model the different production behavior at different fracture stages. Compared to numerical and analytic methods, this model can not only reduce extensive computing processing but also show high accuracy.

XFEM modeling of hydraulic fracture in porous rocks with natural fractures

NASA Astrophysics Data System (ADS)

Wang, Tao; Liu, ZhanLi; Zeng, QingLei; Gao, Yue; Zhuang, Zhuo

2017-08-01

Hydraulic fracture (HF) in porous rocks is a complex multi-physics coupling process which involves fluid flow, diffusion and solid deformation. In this paper, the extended finite element method (XFEM) coupling with Biot theory is developed to study the HF in permeable rocks with natural fractures (NFs). In the recent XFEM based computational HF models, the fluid flow in fractures and interstitials of the porous media are mostly solved separately, which brings difficulties in dealing with complex fracture morphology. In our new model the fluid flow is solved in a unified framework by considering the fractures as a kind of special porous media and introducing Poiseuille-type flow inside them instead of Darcy-type flow. The most advantage is that it is very convenient to deal with fluid flow inside the complex fracture network, which is important in shale gas extraction. The weak formulation for the new coupled model is derived based on virtual work principle, which includes the XFEM formulation for multiple fractures and fractures intersection in porous media and finite element formulation for the unified fluid flow. Then the plane strain Kristianovic-Geertsma-de Klerk (KGD) model and the fluid flow inside the fracture network are simulated to validate the accuracy and applicability of this method. The numerical results show that large injection rate, low rock permeability and isotropic in-situ stresses tend to lead to a more uniform and productive fracture network.

Prediction on fracture risk of femur with Osteogenesis Imperfecta using finite element models: Preliminary study

NASA Astrophysics Data System (ADS)

Wanna, S. B. C.; Basaruddin, K. S.; Mat Som, M. H.; Mohamad Hashim, M. S.; Daud, R.; Majid, M. S. Abdul; Sulaiman, A. R.

2017-10-01

Osteogenesis imperfecta (OI) is a genetic disease which affecting the bone geometry. In a severe case, this disease can cause death to patients. The main issue of this disease is the prediction on bone fracture by the orthopaedic surgeons. The resistance of the bone to withstand the force before the bones fracture often become the main concern. Therefore, the objective of the present preliminary study was to investigate the fracture risk associated with OI bone, particularly in femur, when subjected to the self-weight. Finite element (FEA) was employed to reconstruct the OI bone model and analyse the mechanical stress response of femur before it fractures. Ten deformed models with different severity of OI bones were developed and the force that represents patient self-weight was applied to the reconstructed models in static analysis. Stress and fracture risk were observed and analysed throughout the simulation. None of the deformed model were observed experienced fracture. The fracture risk increased with increased severity of the deformed bone. The results showed that all deformed femur models were able to bear the force without experienced fracture when subjected to only the self-weight.

Predicting grid-size-dependent fracture strains of DP980 with a microstructure-based post-necking model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, G.; Hu, X. H.; Choi, K. S.

Ductile fracture is a local phenomenon, and it is well established that fracture strain levels depend on both stress triaxiality and the resolution (grid size) of strain measurements. Two-dimensional plane strain post-necking models with different representative volume element (RVE) sizes are used to predict the size-dependent fracture strain of a commercial dual-phase steel, DP980. The models are generated from the actual microstructures, and the individual phase flow properties and literature-based individual phase damage parameters for the Johnson-Cook model are used for ferrite and martensite. A monotonic relationship is predicted: the smaller the model size, the higher the fracture strain. Thus,more » a general framework is developed to quantify the size-dependent fracture strains for multiphase materials. In addition to the RVE sizes, the influences of intrinsic microstructure features, i.e., the flow curve and fracture strains of the two constituent phases, on the predicted fracture strains also are examined. Application of the derived fracture strain versus RVE size relationship is demonstrated with large clearance trimming simulations with different element sizes.« less

Lean business model and implementation of a geriatric fracture center.

PubMed

Kates, Stephen L

2014-05-01

Geriatric hip fracture is a common event associated with high costs of care and often with suboptimal outcomes for the patients. Ideally, a new care model to manage geriatric hip fractures would address both quality and safety of patient care as well as the need for reduced costs of care. The geriatric fracture center model of care is one such model reported to improve both outcomes and quality of care. It is a lean business model applied to medicine. This article describes basic lean business concepts applied to geriatric fracture care and information needed to successfully implement a geriatric fracture center. It is written to assist physicians and surgeons in their efforts to implement an improved care model for their patients. Copyright © 2014 Elsevier Inc. All rights reserved.

Vibration acceleration promotes bone formation in rodent models

PubMed Central

Uchida, Ryohei; Nakata, Ken; Kawano, Fuminori; Yonetani, Yasukazu; Ogasawara, Issei; Nakai, Naoya; Mae, Tatsuo; Matsuo, Tomohiko; Tachibana, Yuta; Yokoi, Hiroyuki; Yoshikawa, Hideki

2017-01-01

All living tissues and cells on Earth are subject to gravitational acceleration, but no reports have verified whether acceleration mode influences bone formation and healing. Therefore, this study was to compare the effects of two acceleration modes, vibration and constant (centrifugal) accelerations, on bone formation and healing in the trunk using BMP 2-induced ectopic bone formation (EBF) mouse model and a rib fracture healing (RFH) rat model. Additionally, we tried to verify the difference in mechanism of effect on bone formation by accelerations between these two models. Three groups (low- and high-magnitude vibration and control-VA groups) were evaluated in the vibration acceleration study, and two groups (centrifuge acceleration and control-CA groups) were used in the constant acceleration study. In each model, the intervention was applied for ten minutes per day from three days after surgery for eleven days (EBF model) or nine days (RFH model). All animals were sacrificed the day after the intervention ended. In the EBF model, ectopic bone was evaluated by macroscopic and histological observations, wet weight, radiography and microfocus computed tomography (micro-CT). In the RFH model, whole fracture-repaired ribs were excised with removal of soft tissue, and evaluated radiologically and histologically. Ectopic bones in the low-magnitude group (EBF model) had significantly greater wet weight and were significantly larger (macroscopically and radiographically) than those in the other two groups, whereas the size and wet weight of ectopic bones in the centrifuge acceleration group showed no significant difference compared those in control-CA group. All ectopic bones showed calcified trabeculae and maturated bone marrow. Micro-CT showed that bone volume (BV) in the low-magnitude group of EBF model was significantly higher than those in the other two groups (3.1±1.2mm3 v.s. 1.8±1.2mm3 in high-magnitude group and 1.3±0.9mm3 in control-VA group), but BV in the centrifuge acceleration group had no significant difference compared those in control-CA group. Union rate and BV in the low-magnitude group of RFH model were also significantly higher than those in the other groups (Union rate: 60% v.s. 0% in the high-magnitude group and 10% in the control-VA group, BV: 0.69±0.30mm3 v.s. 0.15±0.09mm3 in high-magnitude group and 0.22±0.17mm3 in control-VA group). BV/TV in the low-magnitude group of RFH model was significantly higher than that in control-VA group (59.4±14.9% v.s. 35.8±13.5%). On the other hand, radiographic union rate (10% in centrifuge acceleration group v.s. 20% in control-CA group) and micro-CT parameters in RFH model were not significantly different between two groups in the constant acceleration studies. Radiographic images of non-union rib fractures showed cartilage at the fracture site and poor new bone formation, whereas union samples showed only new bone. In conclusion, low-magnitude vibration acceleration promoted bone formation at the trunk in both BMP-induced ectopic bone formation and rib fracture healing models. However, the micro-CT parameters were not similar between two models, which suggested that there might be difference in the mechanism of effect by vibration between two models. PMID:28264058

Vibration acceleration promotes bone formation in rodent models.

PubMed

Uchida, Ryohei; Nakata, Ken; Kawano, Fuminori; Yonetani, Yasukazu; Ogasawara, Issei; Nakai, Naoya; Mae, Tatsuo; Matsuo, Tomohiko; Tachibana, Yuta; Yokoi, Hiroyuki; Yoshikawa, Hideki

2017-01-01

All living tissues and cells on Earth are subject to gravitational acceleration, but no reports have verified whether acceleration mode influences bone formation and healing. Therefore, this study was to compare the effects of two acceleration modes, vibration and constant (centrifugal) accelerations, on bone formation and healing in the trunk using BMP 2-induced ectopic bone formation (EBF) mouse model and a rib fracture healing (RFH) rat model. Additionally, we tried to verify the difference in mechanism of effect on bone formation by accelerations between these two models. Three groups (low- and high-magnitude vibration and control-VA groups) were evaluated in the vibration acceleration study, and two groups (centrifuge acceleration and control-CA groups) were used in the constant acceleration study. In each model, the intervention was applied for ten minutes per day from three days after surgery for eleven days (EBF model) or nine days (RFH model). All animals were sacrificed the day after the intervention ended. In the EBF model, ectopic bone was evaluated by macroscopic and histological observations, wet weight, radiography and microfocus computed tomography (micro-CT). In the RFH model, whole fracture-repaired ribs were excised with removal of soft tissue, and evaluated radiologically and histologically. Ectopic bones in the low-magnitude group (EBF model) had significantly greater wet weight and were significantly larger (macroscopically and radiographically) than those in the other two groups, whereas the size and wet weight of ectopic bones in the centrifuge acceleration group showed no significant difference compared those in control-CA group. All ectopic bones showed calcified trabeculae and maturated bone marrow. Micro-CT showed that bone volume (BV) in the low-magnitude group of EBF model was significantly higher than those in the other two groups (3.1±1.2mm3 v.s. 1.8±1.2mm3 in high-magnitude group and 1.3±0.9mm3 in control-VA group), but BV in the centrifuge acceleration group had no significant difference compared those in control-CA group. Union rate and BV in the low-magnitude group of RFH model were also significantly higher than those in the other groups (Union rate: 60% v.s. 0% in the high-magnitude group and 10% in the control-VA group, BV: 0.69±0.30mm3 v.s. 0.15±0.09mm3 in high-magnitude group and 0.22±0.17mm3 in control-VA group). BV/TV in the low-magnitude group of RFH model was significantly higher than that in control-VA group (59.4±14.9% v.s. 35.8±13.5%). On the other hand, radiographic union rate (10% in centrifuge acceleration group v.s. 20% in control-CA group) and micro-CT parameters in RFH model were not significantly different between two groups in the constant acceleration studies. Radiographic images of non-union rib fractures showed cartilage at the fracture site and poor new bone formation, whereas union samples showed only new bone. In conclusion, low-magnitude vibration acceleration promoted bone formation at the trunk in both BMP-induced ectopic bone formation and rib fracture healing models. However, the micro-CT parameters were not similar between two models, which suggested that there might be difference in the mechanism of effect by vibration between two models.

The impact of different aperture distribution models and critical stress criteria on equivalent permeability in fractured rocks

NASA Astrophysics Data System (ADS)

Bisdom, Kevin; Bertotti, Giovanni; Nick, Hamidreza M.

2016-05-01

Predicting equivalent permeability in fractured reservoirs requires an understanding of the fracture network geometry and apertures. There are different methods for defining aperture, based on outcrop observations (power law scaling), fundamental mechanics (sublinear length-aperture scaling), and experiments (Barton-Bandis conductive shearing). Each method predicts heterogeneous apertures, even along single fractures (i.e., intrafracture variations), but most fractured reservoir models imply constant apertures for single fractures. We compare the relative differences in aperture and permeability predicted by three aperture methods, where permeability is modeled in explicit fracture networks with coupled fracture-matrix flow. Aperture varies along single fractures, and geomechanical relations are used to identify which fractures are critically stressed. The aperture models are applied to real-world large-scale fracture networks. (Sub)linear length scaling predicts the largest average aperture and equivalent permeability. Barton-Bandis aperture is smaller, predicting on average a sixfold increase compared to matrix permeability. Application of critical stress criteria results in a decrease in the fraction of open fractures. For the applied stress conditions, Coulomb predicts that 50% of the network is critically stressed, compared to 80% for Barton-Bandis peak shear. The impact of the fracture network on equivalent permeability depends on the matrix hydraulic properties, as in a low-permeable matrix, intrafracture connectivity, i.e., the opening along a single fracture, controls equivalent permeability, whereas for a more permeable matrix, absolute apertures have a larger impact. Quantification of fracture flow regimes using only the ratio of fracture versus matrix permeability is insufficient, as these regimes also depend on aperture variations within fractures.

Finite element modeling of the influence of hand position and bone properties on the Colles' fracture load during a fall.

PubMed

Buchanan, Drew; Ural, Ani

2010-08-01

Distal forearm fracture is one of the most frequently observed osteoporotic fractures, which may occur as a result of low energy falls such as falls from a standing height and may be linked to the osteoporotic nature of the bone, especially in the elderly. In order to prevent the occurrence of radius fractures and their adverse outcomes, understanding the effect of both extrinsic and intrinsic contributors to fracture risk is essential. In this study, a nonlinear fracture mechanics-based finite element model is applied to human radius to assess the influence of extrinsic factors (load orientation and load distribution between scaphoid and lunate) and intrinsic bone properties (age-related changes in fracture properties and bone geometry) on the Colles' fracture load. Seven three-dimensional finite element models of radius were created, and the fracture loads were determined by using cohesive finite element modeling, which explicitly represented the crack and the fracture process zone behavior. The simulation results showed that the load direction with respect to the longitudinal and dorsal axes of the radius influenced the fracture load. The fracture load increased with larger angles between the resultant load and the dorsal axis, and with smaller angles between the resultant load and longitudinal axis. The fracture load also varied as a function of the load ratio between the lunate and scaphoid, however, not as drastically as with the load orientation. The fracture load decreased as the load ratio (lunate/scaphoid) increased. Multiple regression analysis showed that the bone geometry and the load orientation are the most important variables that contribute to the prediction of the fracture load. The findings in this study establish a robust computational fracture risk assessment method that combines the effects of intrinsic properties of bone with extrinsic factors associated with a fall, and may be elemental in the identification of high fracture risk individuals as well as in the development of fracture prevention methods including protective falling techniques. The additional information that this study brings to fracture identification and prevention highlights the promise of fracture mechanics-based finite element modeling in fracture risk assessment.

Characterization of fracture aperture for groundwater flow and transport

NASA Astrophysics Data System (ADS)

Sawada, A.; Sato, H.; Tetsu, K.; Sakamoto, K.

2007-12-01

This paper presents experiments and numerical analyses of flow and transport carried out on natural fractures and transparent replica of fractures. The purpose of this study was to improve the understanding of the role of heterogeneous aperture patterns on channelization of groundwater flow and dispersion in solute transport. The research proceeded as follows: First, a precision plane grinder was applied perpendicular to the fracture plane to characterize the aperture distribution on a natural fracture with 1 mm of increment size. Although both time and labor were intensive, this approach provided a detailed, three dimensional picture of the pattern of fracture aperture. This information was analyzed to provide quantitative measures for the fracture aperture distribution, including JRC (Joint Roughness Coefficient) and fracture contact area ratio. These parameters were used to develop numerical models with corresponding synthetic aperture patterns. The transparent fracture replica and numerical models were then used to study how transport is affected by the aperture spatial pattern. In the transparent replica, transmitted light intensity measured by a CCD camera was used to image channeling and dispersion due to the fracture aperture spatial pattern. The CCD image data was analyzed to obtain the quantitative fracture aperture and tracer concentration data according to Lambert-Beer's law. The experimental results were analyzed using the numerical models. Comparison of the numerical models to the transparent replica provided information about the nature of channeling and dispersion due to aperture spatial patterns. These results support to develop a methodology for defining representative fracture aperture of a simplified parallel fracture model for flow and transport in heterogeneous fractures for contaminant transport analysis.

A poisson process model for hip fracture risk.

PubMed

Schechner, Zvi; Luo, Gangming; Kaufman, Jonathan J; Siffert, Robert S

2010-08-01

The primary method for assessing fracture risk in osteoporosis relies primarily on measurement of bone mass. Estimation of fracture risk is most often evaluated using logistic or proportional hazards models. Notwithstanding the success of these models, there is still much uncertainty as to who will or will not suffer a fracture. This has led to a search for other components besides mass that affect bone strength. The purpose of this paper is to introduce a new mechanistic stochastic model that characterizes the risk of hip fracture in an individual. A Poisson process is used to model the occurrence of falls, which are assumed to occur at a rate, lambda. The load induced by a fall is assumed to be a random variable that has a Weibull probability distribution. The combination of falls together with loads leads to a compound Poisson process. By retaining only those occurrences of the compound Poisson process that result in a hip fracture, a thinned Poisson process is defined that itself is a Poisson process. The fall rate is modeled as an affine function of age, and hip strength is modeled as a power law function of bone mineral density (BMD). The risk of hip fracture can then be computed as a function of age and BMD. By extending the analysis to a Bayesian framework, the conditional densities of BMD given a prior fracture and no prior fracture can be computed and shown to be consistent with clinical observations. In addition, the conditional probabilities of fracture given a prior fracture and no prior fracture can also be computed, and also demonstrate results similar to clinical data. The model elucidates the fact that the hip fracture process is inherently random and improvements in hip strength estimation over and above that provided by BMD operate in a highly "noisy" environment and may therefore have little ability to impact clinical practice.

An integrated workflow for stress and flow modelling using outcrop-derived discrete fracture networks

NASA Astrophysics Data System (ADS)

Bisdom, K.; Nick, H. M.; Bertotti, G.

2017-06-01

Fluid flow in naturally fractured reservoirs is often controlled by subseismic-scale fracture networks. Although the fracture network can be partly sampled in the direct vicinity of wells, the inter-well scale network is poorly constrained in fractured reservoir models. Outcrop analogues can provide data for populating domains of the reservoir model where no direct measurements are available. However, extracting relevant statistics from large outcrops representative of inter-well scale fracture networks remains challenging. Recent advances in outcrop imaging provide high-resolution datasets that can cover areas of several hundred by several hundred meters, i.e. the domain between adjacent wells, but even then, data from the high-resolution models is often upscaled to reservoir flow grids, resulting in loss of accuracy. We present a workflow that uses photorealistic georeferenced outcrop models to construct geomechanical and fluid flow models containing thousands of discrete fractures covering sufficiently large areas, that does not require upscaling to model permeability. This workflow seamlessly integrates geomechanical Finite Element models with flow models that take into account stress-sensitive fracture permeability and matrix flow to determine the full permeability tensor. The applicability of this workflow is illustrated using an outcropping carbonate pavement in the Potiguar basin in Brazil, from which 1082 fractures are digitised. The permeability tensor for a range of matrix permeabilities shows that conventional upscaling to effective grid properties leads to potential underestimation of the true permeability and the orientation of principal permeabilities. The presented workflow yields the full permeability tensor model of discrete fracture networks with stress-induced apertures, instead of relying on effective properties as most conventional flow models do.

Epidemiology of hip fracture and the development of FRAX in Ukraine.

PubMed

Povoroznyuk, V V; Grygorieva, N V; Kanis, J A; Ev, McCloskey; Johansson, H; Harvey, N C; Korzh, M O; Strafun, S S; Vaida, V M; Klymovytsky, F V; Vlasenko, R O; Forosenko, V S

2017-12-01

A country-specific FRAX model has been developed for the Ukraine to replace the Austrian model hitherto used. Comparison of the Austrian and Ukrainian models indicated that the former markedly overestimated fracture probability whilst correctly stratifying risk. FRAX has been used to estimate osteoporotic fracture risk since 2009. Rather than using a surrogate model, the Austrian version of FRAX was adopted for clinical practice. Since then, data have become available on hip fracture incidence in the Ukraine. The incidence of hip fracture was computed from three regional estimates and used to construct a country-specific FRAX model for the Ukraine. The model characteristics were compared with those of the Austrian FRAX model, previously used in Ukraine by using all combinations of six risk factors and eight values of BMD (total number of combinations =512). The relationship between the probabilities of a major fracture derived from the two versions of FRAX indicated a close correlation between the two estimates (r > 0.95). The Ukrainian version, however, gave markedly lower probabilities than the Austrian model at all ages. For a major osteoporotic fracture, the median probability was lower by 25% at age 50 years and the difference increased with age. At the age of 60, 70 and 80 years, the median value was lower by 30, 53 and 65%, respectively. Similar findings were observed for men and for hip fracture. The Ukrainian FRAX model should enhance accuracy of determining fracture probability among the Ukrainian population and help to guide decisions about treatment. The study also indicates that the use of surrogate FRAX models or models from other countries, whilst correctly stratifying risk, may markedly over or underestimate the absolute fracture probability.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rybicki, E.F.; Luiskutty, C.T.; Sutrick, J.S.

This research is part of a larger program sponsored by the United States Department of Energy with the objective of developing better methods to produce gas from low permeability formations in western gas sands. This large research program involves several universities and research centers. Each group is involved in a different area of study to answer specific questions. The hydraulic fracturing computer model has three components---a model for fracture geometry, a model for proppant transport, and a computer program that couples the two models. The fracture geometry model was developed at Oral Roberts University and the proppant transport model wasmore » developed at The University of Tulsa prior to the start of the present work. The present work is directed at enhancing the capabilities of these two models and coupling them to obtain a single model for evaluating the final fracture geometry and proppant distribution within the fracture. The report is organized into four parts. Part 1 describes the fracture geometry modeling effort accomplished at Oral Roberts University, NIPER and recently at The University of Tulsa. The proppant transport model, developed for constant height fractures at the University of Tulsa, is contained in Part 2. The coupling of the Proppant Transport Model and the model for the variable height fracture geometry constitutes Part 3 of this report. Part 4 presents a summary of accomplishments and recommendations of this study. 112 refs., 147 figs., 70 tabs.« less

Development of Fracture Mechanics Maps for Composite Materials. Volume 4.

DTIC Science & Technology

1985-12-01

CONSTITUENTS, ETC.) ON NOTCH SENSITIVITY. A LIST OF FRACTURE MODELS AUTHORS REF, ABBRV. CRITERION HOLE SLITS M.E. WADDOUPS J.R. EISENMANN 3 WEK LEFM / / B.E...fracture model) SCF Stress Concentration Factor SIF Stress Intensity Factor WEK Waddoups- Eisenmann -Kaminski (-fracture model) 9 WN Whitney-Nuismer...Technomic Pub. Co., Inc., Stamford, Conn., 1968, pp. 20-43. 3. M.E. Waddoups, J.R. Eisenmann and B.E. Kaminski, "Macroscopic Fracture Mechanics of

Contaminant transport in fractured rocks with significant matrix permeability, using natural fracture geometries

NASA Astrophysics Data System (ADS)

Odling, Noelle E.; Roden, Julie E.

1997-09-01

Some results from numerical models of flow and contaminant transport in fractured permeable rocks, where fractures are more conductive than rock matrix, are described. The 2D flow field in the fractured and permeable rock matrix is calculated using a finite difference, 'conductance mesh' method, and the contaminant transport is simulated by particle tracking methods using an advection-biased, random walk technique. The model is applied to simulated and naturally occurring fracture patterns. The simulated pattern is an en echelon array of unconnected fractures, as an example of a common, naturally occurring fracture geometry. Two natural fracture patterns are used: one of unconnected, sub-parallel fractures and one with oblique fracture sets which is well connected. Commonly occurring matrix permeability and fracture aperture values are chosen. The simulations show that the presence of fractures creates complex and heterogeneous flow fields and contaminant distribution in the permeable rock matrix. The modelling results have shown that some effects are non-intuitive and therefore difficult to foresee without the help of a model. With respect to contaminant transport rates and plume heterogeneity, it was found that fracture connectivity (crucial when the matrix is impermeable) can play a secondary role to fracture orientation and density. Connected fracture systems can produce smooth break-through curves of contaminants summed over, for example, a bore-hole length, whereas in detail the contaminant plume is spatially highly heterogeneous. Close to a constant-pressure boundary (e.g. an extraction bore-hole), flow and contaminants can be channelled by fractures. Thus observations at a bore-hole may suggest that contaminants are largely confined to the fracture system, when, in fact, significant contamination resides in the matrix.

Age-related Changes in the Fracture Resistance of Male Fischer F344 Rat Bone

PubMed Central

Uppuganti, Sasidhar; Granke, Mathilde; Makowski, Alexander J.; Does, Mark D.; Nyman, Jeffry S.

2015-01-01

In addition to the loss in bone volume that occurs with age, there is a decline in material properties. To test new therapies or diagnostic tools that target such properties as material strength and toughness, a pre-clinical model of aging would be useful in which changes in bone are similar to those that occur with aging in humans. Toward that end, we hypothesized that similar to human bone, the estimated toughness and material strength of cortical bone at the apparent-level decreases with age in the male Fischer F344 rat. In addition, we tested whether the known decline in trabecular architecture in rats translated to an age-related decrease in vertebra (VB) strength and whether non-X-ray techniques could quantify tissue changes at micron and sub-micron length scales. Bones were harvested from 6-, 12-, and 24-month (mo.) old rats (n=12 per age). Despite a loss in trabecular bone with age, VB compressive strength was similar among the age groups. Similarly, whole-bone strength (peak force) in bending was maintained (femur) or increased (radius) with aging. There was though an age-related decrease in post-yield toughness (radius) and bending strength (femur). The ability to resist crack initiation was actually higher for the 12-mo. and 24-mo. than for 6-mo. rats (notch femur), but the estimated work to propagate the crack was less for the aged bone. For the femur diaphysis region, porosity increased while bound water decreased with age. For the radius diaphysis, there was an age-related increase in non-enzymatic and mature enzymatic collagen crosslinks. Both Raman spectroscopy and reference point indentation detected differences in tissue properties with age, though the trends did not necessarily match observations from human tissue. PMID:26610688

Age-related changes in the fracture resistance of male Fischer F344 rat bone.

PubMed

Uppuganti, Sasidhar; Granke, Mathilde; Makowski, Alexander J; Does, Mark D; Nyman, Jeffry S

2016-02-01

In addition to the loss in bone volume that occurs with age, there is a decline in material properties. To test new therapies or diagnostic tools that target such properties as material strength and toughness, a pre-clinical model of aging would be useful in which changes in bone are similar to those that occur with aging in humans. Toward that end, we hypothesized that similar to human bone, the estimated toughness and material strength of cortical bone at the apparent-level decreases with age in the male Fischer F344 rat. In addition, we tested whether the known decline in trabecular architecture in rats translated to an age-related decrease in vertebra (VB) strength and whether non-X-ray techniques could quantify tissue changes at micron and sub-micron length scales. Bones were harvested from 6-, 12-, and 24-month (mo.) old rats (n=12 per age). Despite a loss in trabecular bone with age, VB compressive strength was similar among the age groups. Similarly, whole-bone strength (peak force) in bending was maintained (femur) or increased (radius) with aging. There was though an age-related decrease in post-yield toughness (radius) and bending strength (femur). The ability to resist crack initiation was actually higher for the 12-mo. and 24-mo. than for 6-mo. rats (notch femur), but the estimated work to propagate the crack was less for the aged bone. For the femur diaphysis region, porosity increased while bound water decreased with age. For the radius diaphysis, there was an age-related increase in non-enzymatic and mature enzymatic collagen crosslinks. Raman spectroscopy analysis of embedded cross-sections of the tibia mid-shaft detected an increase in carbonate subsitution with advanced aging for both inner and outer tissue. Published by Elsevier Inc.

The Effects of Annatto Tocotrienol on Bone Biomechanical Strength and Bone Calcium Content in an Animal Model of Osteoporosis Due to Testosterone Deficiency

PubMed Central

Chin, Kok-Yong; Gengatharan, Dhivakaran; Mohd Nasru, Fadlin Sakina; Khairussam, Rehan Amalia; Ern, Sherlyn Lai Hui; Aminuddin, Siti Aina Wahidah; Ima-Nirwana, Soelaiman

2016-01-01

Osteoporosis reduces the skeletal strength and increases the risk for fracture. It is an underdiagnosed disease in men. Annatto tocotrienol has been shown to improve bone structural indices and increase expression of bone formation genes in orchidectomized rats. This study aimed to evaluate the effects of annatto tocotrienol on biomechanical strength and calcium content of the bone in orchidectomized rats. Thirty three-month-old male Sprague-Dawley rats were randomly assigned to five groups. The baseline control (BC) group was sacrificed at the onset of the study. The sham-operated group (SHAM) received olive oil (the vehicle of tocotrienol) orally daily and peanut oil (the vehicle of testosterone) intramuscularly weekly. The remaining rats were orchidectomized and treated with three different regimens, i.e., (1) daily oral olive oil plus weekly intramuscular peanut oil injection; (2) daily oral annatto tocotrienol at 60 mg/kg plus weekly intramuscular peanut oil injection; (3) daily oral olive oil plus weekly intramuscular testosterone enanthate injection at 7 mg/kg. Blood, femur and tibia of the rats were harvested at the end of the two-month treatment period for the evaluation of serum total calcium and inorganic phosphate levels, bone biomechanical strength test and bone calcium content. Annatto-tocotrienol treatment improved serum calcium level and tibial calcium content (p < 0.05) but it did not affect femoral biomechanical strength (p > 0.05). In conclusion, annatto-tocotrienol at 60 mg/kg augments bone calcium level by preventing calcium mobilization into the circulation. A longer treatment period is needed for annatto tocotrienol to exert its effects on bone strength. PMID:27983628

The Effects of Annatto Tocotrienol on Bone Biomechanical Strength and Bone Calcium Content in an Animal Model of Osteoporosis Due to Testosterone Deficiency.

PubMed

Chin, Kok-Yong; Gengatharan, Dhivakaran; Mohd Nasru, Fadlin Sakina; Khairussam, Rehan Amalia; Ern, Sherlyn Lai Hui; Aminuddin, Siti Aina Wahidah; Ima-Nirwana, Soelaiman

2016-12-14

Osteoporosis reduces the skeletal strength and increases the risk for fracture. It is an underdiagnosed disease in men. Annatto tocotrienol has been shown to improve bone structural indices and increase expression of bone formation genes in orchidectomized rats. This study aimed to evaluate the effects of annatto tocotrienol on biomechanical strength and calcium content of the bone in orchidectomized rats. Thirty three-month-old male Sprague-Dawley rats were randomly assigned to five groups. The baseline control (BC) group was sacrificed at the onset of the study. The sham-operated group (SHAM) received olive oil (the vehicle of tocotrienol) orally daily and peanut oil (the vehicle of testosterone) intramuscularly weekly. The remaining rats were orchidectomized and treated with three different regimens, i.e., (1) daily oral olive oil plus weekly intramuscular peanut oil injection; (2) daily oral annatto tocotrienol at 60 mg/kg plus weekly intramuscular peanut oil injection; (3) daily oral olive oil plus weekly intramuscular testosterone enanthate injection at 7 mg/kg. Blood, femur and tibia of the rats were harvested at the end of the two-month treatment period for the evaluation of serum total calcium and inorganic phosphate levels, bone biomechanical strength test and bone calcium content. Annatto-tocotrienol treatment improved serum calcium level and tibial calcium content ( p < 0.05) but it did not affect femoral biomechanical strength ( p > 0.05). In conclusion, annatto-tocotrienol at 60 mg/kg augments bone calcium level by preventing calcium mobilization into the circulation. A longer treatment period is needed for annatto tocotrienol to exert its effects on bone strength.

An efficient numerical model for multicomponent compressible flow in fractured porous media

NASA Astrophysics Data System (ADS)

Zidane, Ali; Firoozabadi, Abbas

2014-12-01

An efficient and accurate numerical model for multicomponent compressible single-phase flow in fractured media is presented. The discrete-fracture approach is used to model the fractures where the fracture entities are described explicitly in the computational domain. We use the concept of cross flow equilibrium in the fractures. This will allow large matrix elements in the neighborhood of the fractures and considerable speed up of the algorithm. We use an implicit finite volume (FV) scheme to solve the species mass balance equation in the fractures. This step avoids the use of Courant-Freidricks-Levy (CFL) condition and contributes to significant speed up of the code. The hybrid mixed finite element method (MFE) is used to solve for the velocity in both the matrix and the fractures coupled with the discontinuous Galerkin (DG) method to solve the species transport equations in the matrix. Four numerical examples are presented to demonstrate the robustness and efficiency of the proposed model. We show that the combination of the fracture cross-flow equilibrium and the implicit composition calculation in the fractures increase the computational speed 20-130 times in 2D. In 3D, one may expect even a higher computational efficiency.

Influence of Regional Difference in Bone Mineral Density on Hip Fracture Site in Elderly Females by Finite Element Analysis.

PubMed

Lin, Z L; Li, P F; Pang, Z H; Zheng, X H; Huang, F; Xu, H H; Li, Q L

2015-11-01

Hip fracture is a kind of osteoporotic fractures in elderly patients. Its important monitoring indicator is to measure bone mineral density (BMD) using DXA. The stress characteristics and material distribution in different parts of the bones can be well simulated by three-dimensional finite element analysis. Our previous studies have demonstrated a linear positive correlation between clinical BMD and the density of three-dimensional finite element model of the femur. However, the correlation between the density variation between intertrochanteric region and collum femoris region of the model and the fracture site has not been studied yet. The present study intends to investigate whether the regional difference in the density of three-dimensional finite element model of the femur can be used to predict hip fracture site in elderly females. The CT data of both hip joints were collected from 16 cases of elderly female patients with hip fractures. Mimics 15.01 software was used to reconstruct the model of proximal femur on the healthy side. Ten kinds of material properties were assigned. In Abaqus 6.12 software, the collum femoris region and intertrochanteric region were, respectively, drawn for calculating the corresponding regional density of the model, followed by prediction of hip fracture site and final comparison with factual fracture site. The intertrochanteric region/collum femoris region density was [(1.20 ± 0.02) × 10(6)] on the fracture site and [(1.22 ± 0.03) × 10(6)] on the non-fracture site, and the difference was statistically significant (P = 0.03). Among 16 established models of proximal femur on the healthy side, 14 models were consistent with the actual fracture sites, one model was inconsistent, and one model was unpredictable, with the coincidence rate of 87.5 %. The intertrochanteric region or collum femoris region with lower BMD is more prone to hip fracture of the type on the corresponding site.

Effect of medium chain triglycerides (MCT) on jejunal mucosa mass and protein synthesis.

PubMed Central

Schwartz, S; Farriol, M; Garcia-Arumi, E; Andreu, A L; López Hellín, J; Arbós, M A

1994-01-01

The effects of medium chain triglycerides (MCT) on jejunal mucosa mass and protein synthesis were compared with results from previous experiments with rats fed by parenteral nutrition or enteral nutrition. Other published studies have also been analysed. Three experimental models were studied. In the traumatic model, production of a femoral fracture was followed by Kirschner pin insertion into the medullary canal of both fragments at reduction. (Forty ras were fed enteral nutrition and 93 were given parenteral nutrition.) A second model entailed resection under ether anaesthesia using the technique described by Higgins. (Fifty five rats were fed enteral nutrition and 28 with parenteral nutrition.) A third model entailed a terminolateral portocaval shunt under anaesthesia with pentobarbital. (Sixty nine rats were treated this way and then given enteral nutrition.) Proportions of medium chain/long chain triglycerides (LCT) were as follows: 0/100, 20/80, 40/60, 50/50, and 92/8 for enteral nutrition and 0/100, 30/70, 50/50, and 70/30 for parenteral nutrition. Faecal losses of alpha amino nitrogen, protein, total fats, and free fatty acids were analysed together with the quantitative intake, weight gain of the rats, jejunal mucosal mass, and protein synthesis in relation to the MCT proportion ingested or given by enteral nutrition or parenteral nutrition. From analysis of our results and those of others, several conclusions could be drawn. Firstly, the route of administration of MCT is extremely important and enterocytes might be considered one of the main target sites. Secondly, a high proportion of MCT (more than 80%) offers no advantage for jejunal mucosa and produces undesirable side effects. Thirdly, the effect of MCT on jejunal mucosal protein synthesis depends on the metabolic state. Finally, an increase in jejunal mucosal mass directly correlated with MCT concentrations, but no correlation was found between mass and protein synthesis. A positive correlation, however, between MCT proportion and enzyme activity (alkaline phosphatase and sucrase) in the brush border membrane was seen as well as a positive correlation with the concentration of phospholipids in the microvilli. PMID:8125388

Transient pressure analysis of a volume fracturing well in fractured tight oil reservoirs

NASA Astrophysics Data System (ADS)

Lu, Cheng; Wang, Jiahang; Zhang, Cong; Cheng, Minhua; Wang, Xiaodong; Dong, Wenxiu; Zhou, Yingfang

2017-12-01

This paper presents a semi-analytical model to simulate transient pressure curves for a vertical well with a reconstructed fracture network in fractured tight oil reservoirs. In the proposed model, the reservoir is a composite system and contains two regions. The inner region is described as a formation with a finite conductivity hydraulic fracture network and the flow in the fracture is assumed to be linear, while the outer region is modeled using the classical Warren-Root model where radial flow is applied. The transient pressure curves of a vertical well in the proposed reservoir model are calculated semi-analytically using the Laplace transform and Stehfest numerical inversion. As shown in the type curves, the flow is divided into several regimes: (a) linear flow in artificial main fractures; (b) coupled boundary flow; (c) early linear flow in a fractured formation; (d) mid radial flow in the semi-fractures of the formation; (e) mid radial flow or pseudo steady flow; (f) mid cross-flow; (g) closed boundary flow. Based on our newly proposed model, the effects of some sensitive parameters, such as elastic storativity ratio, cross-flow coefficient, fracture conductivity and skin factor, on the type curves were also analyzed extensively. The simulated type curves show that for a vertical fractured well in a tight reservoir, the elastic storativity ratios and crossflow coefficients affect the time and the degree of crossflow respectively. The pressure loss increases with an increase in the fracture conductivity. To a certain extent, the effect of the fracture conductivity is more obvious than that of the half length of the fracture on improving the production effect. With an increase in the wellbore storage coefficient, the fluid compressibility is so large that it might cover the early stage fracturing characteristics. Linear or bilinear flow may not be recognized, and the pressure and pressure derivative gradually shift to the right. With an increase in the skin effect, the pressure loss increases gradually.

Use of a real-size 3D-printed model as a preoperative and intraoperative tool for minimally invasive plating of comminuted midshaft clavicle fractures.

PubMed

Kim, Hyong Nyun; Liu, Xiao Ning; Noh, Kyu Cheol

2015-06-10

Open reduction and plate fixation is the standard operative treatment for displaced midshaft clavicle fracture. However, sometimes it is difficult to achieve anatomic reduction by open reduction technique in cases with comminution. We describe a novel technique using a real-size three dimensionally (3D)-printed clavicle model as a preoperative and intraoperative tool for minimally invasive plating of displaced comminuted midshaft clavicle fractures. A computed tomography (CT) scan is taken of both clavicles in patients with a unilateral displaced comminuted midshaft clavicle fracture. Both clavicles are 3D printed into a real-size clavicle model. Using the mirror imaging technique, the uninjured side clavicle is 3D printed into the opposite side model to produce a suitable replica of the fractured side clavicle pre-injury. The 3D-printed fractured clavicle model allows the surgeon to observe and manipulate accurate anatomical replicas of the fractured bone to assist in fracture reduction prior to surgery. The 3D-printed uninjured clavicle model can be utilized as a template to select the anatomically precontoured locking plate which best fits the model. The plate can be inserted through a small incision and fixed with locking screws without exposing the fracture site. Seven comminuted clavicle fractures treated with this technique achieved good bone union. This technique can be used for a unilateral displaced comminuted midshaft clavicle fracture when it is difficult to achieve anatomic reduction by open reduction technique. Level of evidence V.

Influence of patchy saturation on seismic dispersion and attenuation in fractured porous media

NASA Astrophysics Data System (ADS)

Jinwei, Zhang; Handong, Huang; Chunhua, Wu; Sheng, Zhang; Gang, Wu; Fang, Chen

2018-04-01

Wave induced fluid flow due to mesoscopic heterogeneity can explain seismic dispersion and attenuation in the seismic frequency band. The mesoscopic heterogeneity mainly contains lithological variations, patchy saturation and mesoscopic fractures. The patchy saturation models which are locally based on Biot theory for porous media have been deeply studied, but the patchy saturation model for fractured porous media is rarely studied. In this paper, we develop a model to describe the poroelastic characteristics in fractured porous media where the background and fractures are filled with different fluids based on two scales of squirt flow. The seismic dispersion and attenuation in fractured porous media occur in two scales, the microscale due to fluid flow between pores and micro-cracks and mesoscale due to fluid flow between background and heterogeneities. We derive the complex stiffness tensor through the solution of stress equivalence and fluid conservation. Two new parameters embodying the fluid effects are introduced into the model compared with the single fluid phase model. The model is consistent with Gassmann-Wood equation at low frequency limit and consistent with the isolated fracture model at high frequency limit. After the frequency dependent stiffness tensor is obtained, the variations of velocities and inverse quality factors with frequency are analyzed through several numerical examples. We investigated three poroelastic cases: medium including pores and micro-cracks, media including pores, micro-cracks and fractures, media including pores and fractures. The frequency dependent characteristics of patchy saturation model are different with those of single fluid model not only in characteristic frequency but also in the magnitude of the attenuation. Finally, we discuss the results obtained and the special case where the fractures are saturated with gas or dry and the background is filled with water. We also compare our results with those of patchy saturation model and double porosity model. The results will contribute to the actual exploration work to a certain extent, such as the fluid identification in fractured reservoirs.

Influence of patchy saturation on seismic dispersion and attenuation in fractured porous media

NASA Astrophysics Data System (ADS)

Zhang, Jinwei; Huang, Handong; Wu, Chunhua; Zhang, Sheng; Wu, Gang; Chen, Fang

2018-07-01

Wave-induced fluid flow due to mesoscopic heterogeneity can explain seismic dispersion and attenuation in the seismic frequency band. The mesoscopic heterogeneity mainly contains lithological variations, patchy saturation and mesoscopic fractures. The patchy saturation models which are locally based on Biot theory for porous media have been deeply studied, but the patchy saturation model for fractured porous media is rarely studied. In this paper, we develop a model to describe the poroelastic characteristics in fractured porous media where the background and fractures are filled with different fluids based on two scales of squirt flow. The seismic dispersion and attenuation in fractured porous media occur in two scales, the microscale due to fluid flow between pores and microcracks and mesoscale due to fluid flow between background and heterogeneities. We derive the complex stiffness tensor through the solution of stress equivalence and fluid conservation. Two new parameters embodying the fluid effects are introduced into the model compared with the single fluid phase model. The model is consistent with Gassmann-Wood equation at low-frequency limit and consistent with the isolated fracture model at high-frequency limit. After the frequency-dependent stiffness tensor is obtained, the variations of velocities and inverse quality factors with frequency are analysed through several numerical examples. We investigated three poroelastic cases: medium including pores and microcracks; media including pores, microcracks and fractures; media including pores and fractures. The frequency-dependent characteristics of patchy saturation model are different with those of single fluid model not only in characteristic frequency but also in the magnitude of the attenuation. Finally, we discuss the results obtained and the special case where the fractures are saturated with gas or dry and the background is filled with water. We also compare our results with those of patchy saturation model and double porosity model. The results will contribute to the actual exploration work to a certain extent, such as the fluid identification in fractured reservoirs.

Ibandronate treatment for osteoporosis: rationale, preclinical, and clinical development of extended dosing regimens.

PubMed

Epstein, Solomon

2006-03-01

Ibandronate is a potent nitrogen-containing bisphosphonate available as a once-monthly oral formulation for the treatment and prevention of osteoporosis. Preclinical experiments with estrogen-depleted rats, dogs, and monkeys demonstrated the efficacy of daily and intermittent ibandronate dosing. Initial clinical trials explored the optimal dosing regimens for oral administration in humans. The Oral Ibandronate Osteoporosis Vertebral Fracture Trial in North America and Europe (BONE) and Monthly Oral Ibandronate in Ladies (MOBILE) trials demonstrated that long-term daily and intermittent administration of ibandronate was efficacious for increasing bone mineral density, reducing markers of bone turnover, and preventing fractures, while maintaining bone quality. These preclinical and clinical ibandronate trials provided progressive evidence that a simple, long interval dosing regimen could offer efficacy and safety comparable with currently available bisphosphonates. It is anticipated that once-monthly ibandronate may have a positive impact on patient adherence, and ultimately, on fracture protection in osteoporotic women.

On the temperature independence of statistical model parameters for cleavage fracture in ferritic steels

NASA Astrophysics Data System (ADS)

Qian, Guian; Lei, Wei-Sheng; Niffenegger, M.; González-Albuixech, V. F.

2018-04-01

The work relates to the effect of temperature on the model parameters in local approaches (LAs) to cleavage fracture. According to a recently developed LA model, the physical consensus of plastic deformation being a prerequisite to cleavage fracture enforces any LA model of cleavage fracture to observe initial yielding of a volume element as its threshold stress state to incur cleavage fracture in addition to the conventional practice of confining the fracture process zone within the plastic deformation zone. The physical consistency of the new LA model to the basic LA methodology and the differences between the new LA model and other existing models are interpreted. Then this new LA model is adopted to investigate the temperature dependence of LA model parameters using circumferentially notched round tensile specimens. With the published strength data as input, finite element (FE) calculation is conducted for elastic-perfectly plastic deformation and the realistic elastic-plastic hardening, respectively, to provide stress distributions for model calibration. The calibration results in temperature independent model parameters. This leads to the establishment of a 'master curve' characteristic to synchronise the correlation between the nominal strength and the corresponding cleavage fracture probability at different temperatures. This 'master curve' behaviour is verified by strength data from three different steels, providing a new path to calculate cleavage fracture probability with significantly reduced FE efforts.

Scaling Laws of Discrete-Fracture-Network Models

NASA Astrophysics Data System (ADS)

Philippe, D.; Olivier, B.; Caroline, D.; Jean-Raynald, D.

2006-12-01

The statistical description of fracture networks through scale still remains a concern for geologists, considering the complexity of fracture networks. A challenging task of the last 20-years studies has been to find a solid and rectifiable rationale to the trivial observation that fractures exist everywhere and at all sizes. The emergence of fractal models and power-law distributions quantifies this fact, and postulates in some ways that small-scale fractures are genetically linked to their larger-scale relatives. But the validation of these scaling concepts still remains an issue considering the unreachable amount of information that would be necessary with regards to the complexity of natural fracture networks. Beyond the theoretical interest, a scaling law is a basic and necessary ingredient of Discrete-Fracture-Network models (DFN) that are used for many environmental and industrial applications (groundwater resources, mining industry, assessment of the safety of deep waste disposal sites, ..). Indeed, such a function is necessary to assemble scattered data, taken at different scales, into a unified scaling model, and to interpolate fracture densities between observations. In this study, we discuss some important issues related to scaling laws of DFN: - We first describe a complete theoretical and mathematical framework that takes account of both the fracture- size distribution and the fracture clustering through scales (fractal dimension). - We review the scaling laws that have been obtained, and we discuss the ability of fracture datasets to really constrain the parameters of the DFN model. - And finally we discuss the limits of scaling models.

Models of tibial fracture healing in normal and Nf1-deficient mice.

PubMed

Schindeler, Aaron; Morse, Alyson; Harry, Lorraine; Godfrey, Craig; Mikulec, Kathy; McDonald, Michelle; Gasser, Jürg A; Little, David G

2008-08-01

Delayed union and nonunion are common complications associated with tibial fractures, particularly in the distal tibia. Existing mouse tibial fracture models are typically closed and middiaphyseal, and thus poorly recapitulate the prevailing conditions following surgery on a human open distal tibial fracture. This report describes our development of two open tibial fracture models in the mouse, where the bone is broken either in the tibial midshaft (mid-diaphysis) or in the distal tibia. Fractures in the distal tibial model showed delayed repair compared to fractures in the tibial midshaft. These tibial fracture models were applied to both wild-type and Nf1-deficient (Nf1+/-) mice. Bone repair has been reported to be exceptionally problematic in human NF1 patients, and these patients can also spontaneously develop tibial nonunions (known as congenital pseudarthrosis of the tibia), which are recalcitrant to even vigorous intervention. pQCT analysis confirmed no fundamental differences in cortical or cancellous bone in Nf1-deficient mouse tibiae compared to wild-type mice. Although no difference in bone healing was seen in the tibial midshaft fracture model, the healing of distal tibial fractures was found to be impaired in Nf1+/- mice. The histological features associated with nonunited Nf1+/- fractures were variable, but included delayed cartilage removal, disproportionate fibrous invasion, insufficient new bone anabolism, and excessive catabolism. These findings imply that the pathology of tibial pseudarthrosis in human NF1 is complex and likely to be multifactorial.

A Comprehensive Numerical Model for Simulating Fluid Transport in Nanopores

PubMed Central

Zhang, Yuan; Yu, Wei; Sepehrnoori, Kamy; Di, Yuan

2017-01-01

Since a large amount of nanopores exist in tight oil reservoirs, fluid transport in nanopores is complex due to large capillary pressure. Recent studies only focus on the effect of nanopore confinement on single-well performance with simple planar fractures in tight oil reservoirs. Its impacts on multi-well performance with complex fracture geometries have not been reported. In this study, a numerical model was developed to investigate the effect of confined phase behavior on cumulative oil and gas production of four horizontal wells with different fracture geometries. Its pore sizes were divided into five regions based on nanopore size distribution. Then, fluid properties were evaluated under different levels of capillary pressure using Peng-Robinson equation of state. Afterwards, an efficient approach of Embedded Discrete Fracture Model (EDFM) was applied to explicitly model hydraulic and natural fractures in the reservoirs. Finally, three fracture geometries, i.e. non-planar hydraulic fractures, non-planar hydraulic fractures with one set natural fractures, and non-planar hydraulic fractures with two sets natural fractures, are evaluated. The multi-well performance with confined phase behavior is analyzed with permeabilities of 0.01 md and 0.1 md. This work improves the analysis of capillarity effect on multi-well performance with complex fracture geometries in tight oil reservoirs. PMID:28091599

A Comprehensive Numerical Model for Simulating Fluid Transport in Nanopores

NASA Astrophysics Data System (ADS)

Zhang, Yuan; Yu, Wei; Sepehrnoori, Kamy; di, Yuan

2017-01-01

Since a large amount of nanopores exist in tight oil reservoirs, fluid transport in nanopores is complex due to large capillary pressure. Recent studies only focus on the effect of nanopore confinement on single-well performance with simple planar fractures in tight oil reservoirs. Its impacts on multi-well performance with complex fracture geometries have not been reported. In this study, a numerical model was developed to investigate the effect of confined phase behavior on cumulative oil and gas production of four horizontal wells with different fracture geometries. Its pore sizes were divided into five regions based on nanopore size distribution. Then, fluid properties were evaluated under different levels of capillary pressure using Peng-Robinson equation of state. Afterwards, an efficient approach of Embedded Discrete Fracture Model (EDFM) was applied to explicitly model hydraulic and natural fractures in the reservoirs. Finally, three fracture geometries, i.e. non-planar hydraulic fractures, non-planar hydraulic fractures with one set natural fractures, and non-planar hydraulic fractures with two sets natural fractures, are evaluated. The multi-well performance with confined phase behavior is analyzed with permeabilities of 0.01 md and 0.1 md. This work improves the analysis of capillarity effect on multi-well performance with complex fracture geometries in tight oil reservoirs.

Fracture characterization by hybrid enumerative search and Gauss-Newton least-squares inversion methods

NASA Astrophysics Data System (ADS)

Alkharji, Mohammed N.

Most fracture characterization methods provide a general description of the fracture parameters as part of the reservoirs parameters; the fracture interaction and geometry within the reservoir is given less attention. T-Matrix and Linear Slip effective medium fracture models are implemented to invert the elastic tensor for the parameters and geometries of the fractures within the reservoir. The fracture inverse problem has an ill-posed, overdetermined, underconstrained rank-deficit system of equations. Least-squares inverse methods are used to solve the problem. A good starting initial model for the parameters is a key factor in the reliability of the inversion. Most methods assume that the starting parameters are close to the solution to avoid inaccurate local minimum solutions. The prior knowledge of the fracture parameters and their geometry is not available. We develop a hybrid, enumerative and Gauss-Newton, method that estimates the fracture parameters and geometry from the elastic tensor with no prior knowledge of the initial parameter values. The fracture parameters are separated into two groups. The first group contains the fracture parameters with no prior information, and the second group contains the parameters with known prior information. Different models are generated from the first group parameters by sampling the solution space over a predefined range of possible solutions for each parameter. Each model generated by the first group is fixed and used as a starting model to invert for the second group of parameters using the Gauss-Newton method. The least-squares residual between the observed elastic tensor and the estimated elastic tensor is calculated for each model. The model parameters that yield the least-squares residual corresponds to the correct fracture reservoir parameters and geometry. Two synthetic examples of fractured reservoirs with oil and gas saturations were inverted with no prior information about the fracture properties. The results showed that the hybrid algorithm successfully predicted the fracture parametrization, geometry, and the fluid content within the modeled reservoir. The method was also applied on an elastic tensor extracted from the Weyburn field in Saskatchewan, Canada. The solution suggested no presence of fractures but only a VTI system caused by the shale layering in the targeted reservoir, this interpretation is supported by other Weyburn field data.

Multiphase flow models for hydraulic fracturing technology

NASA Astrophysics Data System (ADS)

Osiptsov, Andrei A.

2017-10-01

The technology of hydraulic fracturing of a hydrocarbon-bearing formation is based on pumping a fluid with particles into a well to create fractures in porous medium. After the end of pumping, the fractures filled with closely packed proppant particles create highly conductive channels for hydrocarbon flow from far-field reservoir to the well to surface. The design of the hydraulic fracturing treatment is carried out with a simulator. Those simulators are based on mathematical models, which need to be accurate and close to physical reality. The entire process of fracture placement and flowback/cleanup can be conventionally split into the following four stages: (i) quasi-steady state effectively single-phase suspension flow down the wellbore, (ii) particle transport in an open vertical fracture, (iii) displacement of fracturing fluid by hydrocarbons from the closed fracture filled with a random close pack of proppant particles, and, finally, (iv) highly transient gas-liquid flow in a well during cleanup. The stage (i) is relatively well described by the existing hydralics models, while the models for the other three stages of the process need revisiting and considerable improvement, which was the focus of the author’s research presented in this review paper. For stage (ii), we consider the derivation of a multi-fluid model for suspension flow in a narrow vertical hydraulic fracture at moderate Re on the scale of fracture height and length and also the migration of particles across the flow on the scale of fracture width. At the stage of fracture cleanaup (iii), a novel multi-continua model for suspension filtration is developed. To provide closure relationships for permeability of proppant packings to be used in this model, a 3D direct numerical simulation of single phase flow is carried out using the lattice-Boltzmann method. For wellbore cleanup (iv), we present a combined 1D model for highly-transient gas-liquid flow based on the combination of multi-fluid and drift-flux approaches. The derivation of the drift-flux model from conservation olaws is criticall revisited in order to define the list of underlying assumptions and to mark the applicability margins of the model. All these fundamental problems share the same technological application (hydraulic fracturing) and the same method of research, namely, the multi-fluid approach to multiphase flow modeling and the consistent use of asymptotic methods. Multi-fluid models are then discussed in comparison with semi-empirical (often postulated) models widely used in the industry.

Application of Discrete Fracture Modeling and Upscaling Techniques to Complex Fractured Reservoirs

NASA Astrophysics Data System (ADS)

Karimi-Fard, M.; Lapene, A.; Pauget, L.

2012-12-01

During the last decade, an important effort has been made to improve data acquisition (seismic and borehole imaging) and workflow for reservoir characterization which has greatly benefited the description of fractured reservoirs. However, the geological models resulting from the interpretations need to be validated or calibrated against dynamic data. Flow modeling in fractured reservoirs remains a challenge due to the difficulty of representing mass transfers at different heterogeneity scales. The majority of the existing approaches are based on dual continuum representation where the fracture network and the matrix are represented separately and their interactions are modeled using transfer functions. These models are usually based on idealized representation of the fracture distribution which makes the integration of real data difficult. In recent years, due to increases in computer power, discrete fracture modeling techniques (DFM) are becoming popular. In these techniques the fractures are represented explicitly allowing the direct use of data. In this work we consider the DFM technique developed by Karimi-Fard et al. [1] which is based on an unstructured finite-volume discretization. The mass flux between two adjacent control-volumes is evaluated using an optimized two-point flux approximation. The result of the discretization is a list of control-volumes with the associated pore-volumes and positions, and a list of connections with the associated transmissibilities. Fracture intersections are simplified using a connectivity transformation which contributes considerably to the efficiency of the methodology. In addition, the method is designed for general purpose simulators and any connectivity based simulator can be used for flow simulations. The DFM technique is either used standalone or as part of an upscaling technique. The upscaling techniques are required for large reservoirs where the explicit representation of all fractures and faults is not possible. Karimi-Fard et al. [2] have developed an upscaling technique based on DFM representation. The original version of this technique was developed to construct a dual-porosity model from a discrete fracture description. This technique has been extended and generalized so it can be applied to a wide range of problems from reservoirs with a few or no fracture to highly fractured reservoirs. In this work, we present the application of these techniques to two three-dimensional fractured reservoirs constructed using real data. The first model contains more than 600 medium and large scale fractures. The fractures are not always connected which requires a general modeling technique. The reservoir has 50 wells (injectors and producers) and water flooding simulations are performed. The second test case is a larger reservoir with sparsely distributed faults. Single-phase simulations are performed with 5 producing wells. [1] Karimi-Fard M., Durlofsky L.J., and Aziz K. 2004. An efficient discrete-fracture model applicable for general-purpose reservoir simulators. SPE Journal, 9(2): 227-236. [2] Karimi-Fard M., Gong B., and Durlofsky L.J. 2006. Generation of coarse-scale continuum flow models from detailed fracture characterizations. Water Resources Research, 42(10): W10423.

Modeling of the fracture behavior of spot welds using advanced micro-mechanical damage models

NASA Astrophysics Data System (ADS)

Sommer, Silke

2010-06-01

This paper presents the modeling of deformation and fracture behavior of resistance spot welded joints in DP600 steel sheets. Spot welding is still the most commonly used joining technique in automotive engineering. In overloading situations like crash joints are often the weakest link in a structure. For those reasons, crash simulations need reliable and applicable tools to predict the load bearing capacity of spot welded components. Two series of component tests with different spot weld diameters have shown that the diameter of the weld nugget is the main influencing factor affecting fracture mode (interfacial or pull-out fracture), load bearing capacity and energy absorption. In order to find a correlation between nugget diameter, load bearing capacity and fracture mode, the spot welds are simulated with detailed finite element models containing base metal, heat affected zone and weld metal in lap-shear loading conditions. The change in fracture mode from interfacial to pull-out or peel-out fracture with growing nugget diameter under lap-shear loading was successfully modeled using the Gologanu-Leblond model in combination with the fracture criteria of Thomason and Embury. A small nugget diameter is identified to be the main cause for interfacial fracture. In good agreement with experimental observations, the calculated pull-out fracture initiates in the base metal at the boundary to the heat affected zone.

Inverse modeling of hydraulic tests in fractured crystalline rock based on a transition probability geostatistical approach

NASA Astrophysics Data System (ADS)

Blessent, Daniela; Therrien, René; Lemieux, Jean-Michel

2011-12-01

This paper presents numerical simulations of a series of hydraulic interference tests conducted in crystalline bedrock at Olkiluoto (Finland), a potential site for the disposal of the Finnish high-level nuclear waste. The tests are in a block of crystalline bedrock of about 0.03 km3 that contains low-transmissivity fractures. Fracture density, orientation, and fracture transmissivity are estimated from Posiva Flow Log (PFL) measurements in boreholes drilled in the rock block. On the basis of those data, a geostatistical approach relying on a transitional probability and Markov chain models is used to define a conceptual model based on stochastic fractured rock facies. Four facies are defined, from sparsely fractured bedrock to highly fractured bedrock. Using this conceptual model, three-dimensional groundwater flow is then simulated to reproduce interference pumping tests in either open or packed-off boreholes. Hydraulic conductivities of the fracture facies are estimated through automatic calibration using either hydraulic heads or both hydraulic heads and PFL flow rates as targets for calibration. The latter option produces a narrower confidence interval for the calibrated hydraulic conductivities, therefore reducing the associated uncertainty and demonstrating the usefulness of the measured PFL flow rates. Furthermore, the stochastic facies conceptual model is a suitable alternative to discrete fracture network models to simulate fluid flow in fractured geological media.

Epidemiological burden of postmenopausal osteoporosis in Italy from 2010 to 2020: estimations from a disease model.

PubMed

Piscitelli, P; Brandi, M; Cawston, H; Gauthier, A; Kanis, J A; Compston, J; Borgström, F; Cooper, C; McCloskey, E

2014-11-01

The article describes the adaptation of a model to estimate the burden of postmenopausal osteoporosis in women aged 50 years and over in Italy between 2010 and 2020. For this purpose, a validated postmenopausal osteoporosis disease model developed for Sweden was adapted to Italy. For each year of the study, the 'incident cohort' (women experiencing a first osteoporotic fracture) was identified and run through a Markov model using 1-year cycles until 2020. Health states were based on the number of fractures and deaths. Fracture by site (hip, clinical vertebral, non-hip non-vertebral) was tracked for each health state. Transition probabilities reflected fracture site-specific risk of death and subsequent fractures. Model inputs specific to Italy included population size and life tables from 1970 to 2020, incidence of hip fracture and BMD by age in the general population (mean and standard deviation). The model estimated that the number of postmenopausal osteoporotic women would increase from 3.3 million to 3.7 million between 2010 and 2020 (+14.3%). Assuming unchanged incidence rates by age group over time, the model predicted the overall number of osteoporotic fractures to increase from 285.0 to 335.8 thousand fractures between 2010 and 2020 (+17.8%). The estimated expected increases in hip, vertebral and non-hip non-vertebral fractures were 22.3, 17.2 and 16.3%, respectively. Due to demographic changes, the burden of fractures is expected to increase markedly by 2020.

Simulating Fragmentation and Fluid-Induced Fracture in Disordered Media Using Random Finite-Element Meshes

DOE PAGES

Bishop, Joseph E.; Martinez, Mario J.; Newell, Pania

2016-11-08

Fracture and fragmentation are extremely nonlinear multiscale processes in which microscale damage mechanisms emerge at the macroscale as new fracture surfaces. Numerous numerical methods have been developed for simulating fracture initiation, propagation, and coalescence. In this paper, we present a computational approach for modeling pervasive fracture in quasi-brittle materials based on random close-packed Voronoi tessellations. Each Voronoi cell is formulated as a polyhedral finite element containing an arbitrary number of vertices and faces. Fracture surfaces are allowed to nucleate only at the intercell faces. Cohesive softening tractions are applied to new fracture surfaces in order to model the energy dissipatedmore » during fracture growth. The randomly seeded Voronoi cells provide a regularized discrete random network for representing fracture surfaces. The potential crack paths within the random network are viewed as instances of realizable crack paths within the continuum material. Mesh convergence of fracture simulations is viewed in a weak, or distributional, sense. The explicit facet representation of fractures within this approach is advantageous for modeling contact on new fracture surfaces and fluid flow within the evolving fracture network. Finally, applications of interest include fracture and fragmentation in quasi-brittle materials and geomechanical applications such as hydraulic fracturing, engineered geothermal systems, compressed-air energy storage, and carbon sequestration.« less

Simulating Fragmentation and Fluid-Induced Fracture in Disordered Media Using Random Finite-Element Meshes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bishop, Joseph E.; Martinez, Mario J.; Newell, Pania

Fracture and fragmentation are extremely nonlinear multiscale processes in which microscale damage mechanisms emerge at the macroscale as new fracture surfaces. Numerous numerical methods have been developed for simulating fracture initiation, propagation, and coalescence. In this paper, we present a computational approach for modeling pervasive fracture in quasi-brittle materials based on random close-packed Voronoi tessellations. Each Voronoi cell is formulated as a polyhedral finite element containing an arbitrary number of vertices and faces. Fracture surfaces are allowed to nucleate only at the intercell faces. Cohesive softening tractions are applied to new fracture surfaces in order to model the energy dissipatedmore » during fracture growth. The randomly seeded Voronoi cells provide a regularized discrete random network for representing fracture surfaces. The potential crack paths within the random network are viewed as instances of realizable crack paths within the continuum material. Mesh convergence of fracture simulations is viewed in a weak, or distributional, sense. The explicit facet representation of fractures within this approach is advantageous for modeling contact on new fracture surfaces and fluid flow within the evolving fracture network. Finally, applications of interest include fracture and fragmentation in quasi-brittle materials and geomechanical applications such as hydraulic fracturing, engineered geothermal systems, compressed-air energy storage, and carbon sequestration.« less

Sri Lankan FRAX model and country-specific intervention thresholds.

PubMed

Lekamwasam, Sarath

2013-01-01

There is a wide variation in fracture probabilities estimated by Asian FRAX models, although the outputs of South Asian models are concordant. Clinicians can choose either fixed or age-specific intervention thresholds when making treatment decisions in postmenopausal women. Cost-effectiveness of such approach, however, needs to be addressed. This study examined suitable fracture probability intervention thresholds (ITs) for Sri Lanka, based on the Sri Lankan FRAX model. Fracture probabilities were estimated using all Asian FRAX models for a postmenopausal woman of BMI 25 kg/m² and has no clinical risk factors apart from a fragility fracture, and they were compared. Age-specific ITs were estimated based on the Sri Lankan FRAX model using the method followed by the National Osteoporosis Guideline Group in the UK. Using the age-specific ITs as the reference standard, suitable fixed ITs were also estimated. Fracture probabilities estimated by different Asian FRAX models varied widely. Japanese and Taiwan models showed higher fracture probabilities while Chinese, Philippine, and Indonesian models gave lower fracture probabilities. Output of remaining FRAX models were generally similar. Age-specific ITs of major osteoporotic fracture probabilities (MOFP) based on the Sri Lankan FRAX model varied from 2.6 to 18% between 50 and 90 years. ITs of hip fracture probabilities (HFP) varied from 0.4 to 6.5% between 50 and 90 years. In finding fixed ITs, MOFP of 11% and HFP of 3.5% gave the lowest misclassification and highest agreement. Sri Lankan FRAX model behaves similar to other Asian FRAX models such as Indian, Singapore-Indian, Thai, and South Korean. Clinicians may use either the fixed or age-specific ITs in making therapeutic decisions in postmenopausal women. The economical aspects of such decisions, however, need to be considered.

Modeling of orthotropic plate fracture under impact load using various strength criteria

NASA Astrophysics Data System (ADS)

Radchenko, Andrey; Krivosheina, Marina; Kobenko, Sergei; Radchenko, Pavel; Grebenyuk, Grigory

2017-01-01

The paper presents the comparative analysis of various tensor multinomial criteria of strength for modeling of orthotropic organic plastic plate fracture under impact load. Ashkenazi, Hoffman and Wu strength criteria were used. They allowed fracture modeling of orthotropic materials with various compressive and tensile strength properties. The modeling of organic plastic fracture was performed numerically within the impact velocity range of 700-1500 m/s.

Nuclear Graphite - Fracture Behavior and Modeling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burchell, Timothy D; Battiste, Rick; Strizak, Joe P

2011-01-01

Evidence for the graphite fracture mechanism is reviewed and discussed. The roles of certain microstructural features in the graphite fracture process are reported. The Burchell fracture model is described and its derivation reported. The successful application of the fracture model to uniaxial tensile data from several graphites with widely ranging structure and texture is reported. The extension of the model to multiaxial loading scenarios using two criteria is discussed. Initially, multiaxial strength data for H-451 graphite were modeled using the fracture model and the Principle of Independent Action. The predicted 4th stress quadrant failure envelope was satisfactory but the 1stmore » quadrant predictions were not conservative and thus were unsatisfactory. Multiaxial strength data from the 1st and 4th stress quadrant for NBG-18 graphite are reported. To improve the conservatism of the predicted 1st quadrant failure envelope for NBG-18 the Shetty criterion has been applied to obtain the equivalent critical stress intensity factor, KIc (Equi), for each applied biaxial stress ratio. The equivalent KIc value is used in the Burchell fracture model to predict the failure envelope. The predicted 1st stress quadrant failure envelope is conservative and thus more satisfactory than achieved previously using the fracture model combined with the Principle of Independent Action.« less

Discrete Dual Porosity Modeling of Electrical Current Flow in Fractured Media

NASA Astrophysics Data System (ADS)

Roubinet, D.; Irving, J.

2013-12-01

The study of fractured rocks is highly important in a variety of research fields and applications such as hydrogeology, geothermal energy, hydrocarbon extraction, and the long-term storage of toxic waste. Fractured media are characterized by a large contrast in permeability between the fractures and the rock matrix. For hydrocarbon extraction, the presence of highly conductive fractures is an advantage as they allow for quick and easy access to the resource. For toxic waste storage, however, the fractures represent a significant drawback as there is an increased risk of leakage and migration of pollutants deep into the subsurface. In both cases, the identification of fracture network characteristics is a critical, challenging, and required step. A number of previous studies have indicated that the presence of fractures in geological materials can have a significant impact on geophysical electrical resistivity measurements. It thus appears that, in some cases, geoelectrical surveys might be used to obtain useful information regarding fracture network characteristics. However, existing geoelectrical modeling tools and inversion methods are not properly adapted to deal with the specific challenges of fractured media. This prevents us from fully exploring the potential of the method to characterize fracture network properties. We thus require, as a first step, the development of accurate and efficient numerical modeling tools specifically designed for fractured domains. Building on the discrete fracture network (DFN) approach that has been widely used for modeling groundwater flow in fractured rocks, we have developed a discrete dual-porosity model for electrical current flow in fractured media. Our novel approach combines an explicit representation of the fractures with fracture-matrix electrical flow exchange at the block-scale. Tests in two dimensions show the ability of our method to deal with highly heterogeneous fracture networks in a highly computationally efficient manner, which permits us to study the impact of fractures and their properties on the electrical response of the domain. With additional development, the method will be extended to three dimensions and used in the context of geoelectrical field investigations.

Application of Fracture Distribution Prediction Model in Xihu Depression of East China Sea

NASA Astrophysics Data System (ADS)

Yan, Weifeng; Duan, Feifei; Zhang, Le; Li, Ming

2018-02-01

There are different responses on each of logging data with the changes of formation characteristics and outliers caused by the existence of fractures. For this reason, the development of fractures in formation can be characterized by the fine analysis of logging curves. The well logs such as resistivity, sonic transit time, density, neutron porosity and gamma ray, which are classified as conventional well logs, are more sensitive to formation fractures. In view of traditional fracture prediction model, using the simple weighted average of different logging data to calculate the comprehensive fracture index, are more susceptible to subjective factors and exist a large deviation, a statistical method is introduced accordingly. Combining with responses of conventional logging data on the development of formation fracture, a prediction model based on membership function is established, and its essence is to analyse logging data with fuzzy mathematics theory. The fracture prediction results in a well formation in NX block of Xihu depression through two models are compared with that of imaging logging, which shows that the accuracy of fracture prediction model based on membership function is better than that of traditional model. Furthermore, the prediction results are highly consistent with imaging logs and can reflect the development of cracks much better. It can provide a reference for engineering practice.

Detection of Natural Fractures from Observed Surface Seismic Data Based on a Linear-Slip Model

NASA Astrophysics Data System (ADS)

Chen, Huaizhen; Zhang, Guangzhi

2018-03-01

Natural fractures play an important role in migration of hydrocarbon fluids. Based on a rock physics effective model, the linear-slip model, which defines fracture parameters (fracture compliances) for quantitatively characterizing the effects of fractures on rock total compliance, we propose a method to detect natural fractures from observed seismic data via inversion for the fracture compliances. We first derive an approximate PP-wave reflection coefficient in terms of fracture compliances. Using the approximate reflection coefficient, we derive azimuthal elastic impedance as a function of fracture compliances. An inversion method to estimate fracture compliances from seismic data is presented based on a Bayesian framework and azimuthal elastic impedance, which is implemented in a two-step procedure: a least-squares inversion for azimuthal elastic impedance and an iterative inversion for fracture compliances. We apply the inversion method to synthetic and real data to verify its stability and reasonability. Synthetic tests confirm that the method can make a stable estimation of fracture compliances in the case of seismic data containing a moderate signal-to-noise ratio for Gaussian noise, and the test on real data reveals that reasonable fracture compliances are obtained using the proposed method.

Robust QCT/FEA Models of Proximal Femur Stiffness and Fracture Load During a Sideways Fall on the Hip

PubMed Central

Dragomir-Daescu, Dan; Buijs, Jorn Op Den; McEligot, Sean; Dai, Yifei; Entwistle, Rachel C.; Salas, Christina; Melton, L. Joseph; Bennet, Kevin E.; Khosla, Sundeep; Amin, Shreyasee

2013-01-01

Clinical implementation of quantitative computed tomography-based finite element analysis (QCT/FEA) of proximal femur stiffness and strength to assess the likelihood of proximal femur (hip) fractures requires a unified modeling procedure, consistency in predicting bone mechanical properties, and validation with realistic test data that represent typical hip fractures, specifically, a sideways fall on the hip. We, therefore, used two sets (n = 9, each) of cadaveric femora with bone densities varying from normal to osteoporotic to build, refine, and validate a new class of QCT/FEA models for hip fracture under loading conditions that simulate a sideways fall on the hip. Convergence requirements of finite element models of the first set of femora led to the creation of a new meshing strategy and a robust process to model proximal femur geometry and material properties from QCT images. We used a second set of femora to cross-validate the model parameters derived from the first set. Refined models were validated experimentally by fracturing femora using specially designed fixtures, load cells, and high speed video capture. CT image reconstructions of fractured femora were created to classify the fractures. The predicted stiffness (cross-validation R2 = 0.87), fracture load (cross-validation R2 = 0.85), and fracture patterns (83% agreement) correlated well with experimental data. PMID:21052839

Experimental and statistical study on fracture boundary of non-irradiated Zircaloy-4 cladding tube under LOCA conditions

NASA Astrophysics Data System (ADS)

Narukawa, Takafumi; Yamaguchi, Akira; Jang, Sunghyon; Amaya, Masaki

2018-02-01

For estimating fracture probability of fuel cladding tube under loss-of-coolant accident conditions of light-water-reactors, laboratory-scale integral thermal shock tests were conducted on non-irradiated Zircaloy-4 cladding tube specimens. Then, the obtained binary data with respect to fracture or non-fracture of the cladding tube specimen were analyzed statistically. A method to obtain the fracture probability curve as a function of equivalent cladding reacted (ECR) was proposed using Bayesian inference for generalized linear models: probit, logit, and log-probit models. Then, model selection was performed in terms of physical characteristics and information criteria, a widely applicable information criterion and a widely applicable Bayesian information criterion. As a result, it was clarified that the log-probit model was the best among the three models to estimate the fracture probability in terms of the degree of prediction accuracy for both next data to be obtained and the true model. Using the log-probit model, it was shown that 20% ECR corresponded to a 5% probability level with a 95% confidence of fracture of the cladding tube specimens.

Subject specific finite element modeling of periprosthetic femoral fracture using element deactivation to simulate bone failure.

PubMed

Miles, Brad; Kolos, Elizabeth; Walter, William L; Appleyard, Richard; Shi, Angela; Li, Qing; Ruys, Andrew J

2015-06-01

Subject-specific finite element (FE) modeling methodology could predict peri-prosthetic femoral fracture (PFF) for cementless hip arthoplasty in the early postoperative period. This study develops methodology for subject-specific finite element modeling by using the element deactivation technique to simulate bone failure and validate with experimental testing, thereby predicting peri-prosthetic femoral fracture in the early postoperative period. Material assignments for biphasic and triphasic models were undertaken. Failure modeling with the element deactivation feature available in ABAQUS 6.9 was used to simulate a crack initiation and propagation in the bony tissue based upon a threshold of fracture strain. The crack mode for the biphasic models was very similar to the experimental testing crack mode, with a similar shape and path of the crack. The fracture load is sensitive to the friction coefficient at the implant-bony interface. The development of a novel technique to simulate bone failure by element deactivation of subject-specific finite element models could aid prediction of fracture load in addition to fracture risk characterization for PFF. Copyright © 2015 IPEM. Published by Elsevier Ltd. All rights reserved.

A quasi steady state method for solving transient Darcy flow in complex 3D fractured networks accounting for matrix to fracture flow

NASA Astrophysics Data System (ADS)

Nœtinger, B.

2015-02-01

Modeling natural Discrete Fracture Networks (DFN) receives more and more attention in applied geosciences, from oil and gas industry, to geothermal recovery and aquifer management. The fractures may be either natural, or artificial in case of well stimulation. Accounting for the flow inside the fracture network, and accounting for the transfers between the matrix and the fractures, with the same level of accuracy is an important issue for calibrating the well architecture and for setting up optimal resources recovery strategies. Recently, we proposed an original method allowing to model transient pressure diffusion in the fracture network only [1]. The matrix was assumed to be impervious. A systematic approximation scheme was built, allowing to model the initial DFN by a set of N unknowns located at each identified intersection between fractures. The higher N, the higher the accuracy of the model. The main assumption was using a quasi steady state hypothesis, that states that the characteristic diffusion time over one single fracture is negligible compared with the characteristic time of the macroscopic problem, e.g. change of boundary conditions. In that context, the lowest order approximation N = 1 has the form of solving a transient problem in a resistor/capacitor network, a so-called pipe network. Its topology is the same as the network of geometrical intersections between fractures. In this paper, we generalize this approach in order to account for fluxes from matrix to fractures. The quasi steady state hypothesis at the fracture level is still kept. Then, we show that in the case of well separated time scales between matrix and fractures, the preceding model needs only to be slightly modified in order to incorporate these fluxes. The additional knowledge of the so-called matrix to fracture transfer function allows to modify the mass matrix that becomes a time convolution operator. This is reminiscent of existing space averaged transient dual porosity models.

Field investigation into unsaturated flow and transport in a fault: Model analyses

USGS Publications Warehouse

Liu, H.-H.; Salve, R.; Wang, J.-S.; Bodvarsson, G.S.; Hudson, D.

2004-01-01

Results of a fault test performed in the unsaturated zone of Yucca Mountain, Nevada, were analyzed using a three-dimensional numerical model. The fault was explicitly represented as a discrete feature and the surrounding rock was treated as a dual-continuum (fracture-matrix) system. Model calibration against seepage and water-travel-velocity data suggests that lithophysal cavities connected to fractures can considerably enhance the effective fracture porosity and therefore retard water flow in fractures. Comparisons between simulation results and tracer concentration data also indicate that matrix diffusion is an important mechanism for solute transport in unsaturated fractured rock. We found that an increased fault-matrix and fracture-matrix interface areas were needed to match the observed tracer data, which is consistent with previous studies. The study results suggest that the current site-scale model for the unsaturated zone of Yucca Mountain may underestimate radionuclide transport time within the unsaturated zone, because an increased fracture-matrix interface area and the increased effective fracture porosity arising from lithophysal cavities are not considered in the current site-scale model. ?? 2004 Published by Elsevier B.V.

A Theoretical Model for Predicting Fracture Strength and Critical Flaw Size of the ZrB2-ZrC Composites at High Temperatures

NASA Astrophysics Data System (ADS)

Wang, Ruzhuan; Li, Xiaobo; Wang, Jing; Jia, Bi; Li, Weiguo

2018-06-01

This work shows a new rational theoretical model for quantitatively predicting fracture strength and critical flaw size of the ZrB2-ZrC composites at different temperatures, which is based on a new proposed temperature dependent fracture surface energy model and the Griffith criterion. The fracture model takes into account the combined effects of temperature and damage terms (surface flaws and internal flaws) with no any fitting parameters. The predictions of fracture strength and critical flaw size of the ZrB2-ZrC composites at high temperatures agree well with experimental data. Then using the theoretical method, the improvement and design of materials are proposed. The proposed model can be used to predict the fracture strength, find the critical flaw and study the effects of microstructures on the fracture mechanism of the ZrB2-ZrC composites at high temperatures, which thus could become a potential convenient, practical and economical technical means for predicting fracture properties and material design.

Integrated workflow for characterizing and modeling fracture network in unconventional reservoirs using microseismic data

NASA Astrophysics Data System (ADS)

Ayatollahy Tafti, Tayeb

We develop a new method for integrating information and data from different sources. We also construct a comprehensive workflow for characterizing and modeling a fracture network in unconventional reservoirs, using microseismic data. The methodology is based on combination of several mathematical and artificial intelligent techniques, including geostatistics, fractal analysis, fuzzy logic, and neural networks. The study contributes to scholarly knowledge base on the characterization and modeling fractured reservoirs in several ways; including a versatile workflow with a novel objective functions. Some the characteristics of the methods are listed below: 1. The new method is an effective fracture characterization procedure estimates different fracture properties. Unlike the existing methods, the new approach is not dependent on the location of events. It is able to integrate all multi-scaled and diverse fracture information from different methodologies. 2. It offers an improved procedure to create compressional and shear velocity models as a preamble for delineating anomalies and map structures of interest and to correlate velocity anomalies with fracture swarms and other reservoir properties of interest. 3. It offers an effective way to obtain the fractal dimension of microseismic events and identify the pattern complexity, connectivity, and mechanism of the created fracture network. 4. It offers an innovative method for monitoring the fracture movement in different stages of stimulation that can be used to optimize the process. 5. Our newly developed MDFN approach allows to create a discrete fracture network model using only microseismic data with potential cost reduction. It also imposes fractal dimension as a constraint on other fracture modeling approaches, which increases the visual similarity between the modeled networks and the real network over the simulated volume.

Numerical model of water flow in a fractured basalt vadose zone: Box Canyon Site, Idaho

NASA Astrophysics Data System (ADS)

Doughty, Christine

2000-12-01

A numerical model of a fractured basalt vadose zone has been developed on the basis of the conceptual model described by Faybishenko et al. [[his issue]. The model has been used to simulate a ponded infiltration test in order to investigate infiltration through partially saturated fractured basalt. A key question addressed is how the fracture pattern geometry and fracture connectivity within a single basalt flow of the Snake River Plain basalt affect water infiltration. The two-dimensional numerical model extends from the ground surface to a perched water body 20 m below and uses an unconventional quasi-deterministic approach with explicit but highly simplified representation of major fractures and other important hydrogeologic features. The model adequately reproduces the majority of the field observation and provides insights into the infiltration process that cannot be obtained by data collection alone, demonstrating its value as a component of field studies.

Numerical Modelling of Femur Fracture and Experimental Validation Using Bone Simulant.

PubMed

Marco, Miguel; Giner, Eugenio; Larraínzar-Garijo, Ricardo; Caeiro, José Ramón; Miguélez, María Henar

2017-10-01

Bone fracture pattern prediction is still a challenge and an active field of research. The main goal of this article is to present a combined methodology (experimental and numerical) for femur fracture onset analysis. Experimental work includes the characterization of the mechanical properties and fracture testing on a bone simulant. The numerical work focuses on the development of a model whose material properties are provided by the characterization tests. The fracture location and the early stages of the crack propagation are modelled using the extended finite element method and the model is validated by fracture tests developed in the experimental work. It is shown that the accuracy of the numerical results strongly depends on a proper bone behaviour characterization.

A statistical model of brittle fracture by transgranular cleavage

NASA Astrophysics Data System (ADS)

Lin, Tsann; Evans, A. G.; Ritchie, R. O.

A MODEL for brittle fracture by transgranular cleavage cracking is presented based on the application of weakest link statistics to the critical microstructural fracture mechanisms. The model permits prediction of the macroscopic fracture toughness, KI c, in single phase microstructures containing a known distribution of particles, and defines the critical distance from the crack tip at which the initial cracking event is most probable. The model is developed for unstable fracture ahead of a sharp crack considering both linear elastic and nonlinear elastic ("elastic/plastic") crack tip stress fields. Predictions are evaluated by comparison with experimental results on the low temperature flow and fracture behavior of a low carbon mild steel with a simple ferrite/grain boundary carbide microstructure.

Analytic crack solutions for tilt fields around hydraulic fractures

NASA Astrophysics Data System (ADS)

Warpinski, Norman R.

2000-10-01

The recent development of downhole tiltmeter arrays for monitoring hydraulic fractures has provided new information on fracture growth and geometry. These downhole arrays offer the significant advantages of being close to the fracture (large signal) and being unaffected by the free surface. As with surface tiltmeter data, analysis of these measurements requires the inversion of a crack or dislocation model. To supplement the dislocation models of Davis [1983], Okada [1992], and others, this work has extended several elastic crack solutions to provide tilt calculations. The solutions include constant-pressure two-dimensional (2-D), penny-shaped, and 3-D-elliptic cracks and a 2-D-variable-pressure crack. Equations are developed for an arbitrary inclined fracture in an infinite elastic space. Effects of fracture height, fracture length, fracture dip, fracture azimuth, fracture width, and monitoring distance on the tilt distribution are given, as well as comparisons with the dislocation model. The results show that the tilt measurements are very sensitive to the fracture dimensions but also that it is difficult to separate the competing effects of the various parameters.

Analytic crack solutions for tilt fields around hydraulic fractures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Warpinski, N.R.

The recent development of downhole tiltmeter arrays for monitoring hydraulic fractures has provided new information on fracture growth and geometry. These downhole arrays offer the significant advantages of being close to the fracture (large signal) and being unaffected by the free surface. As with surface tiltmeter data, analysis of these measurements requires the inversion of a crack or dislocation model. To supplement the dislocation models of Davis [1983], Okada [1992] and others, this work has extended several elastic crack solutions to provide tilt calculations. The solutions include constant-pressure 2D, penny-shaped, and 3D-elliptic cracks and a 2D-variable-pressure crack. Equations are developedmore » for an arbitrary inclined fracture in an infinite elastic space. Effects of fracture height, fracture length, fracture dip, fracture azimuth, fracture width and monitoring distance on the tilt distribution are given, as well as comparisons with the dislocation model. The results show that the tilt measurements are very sensitive to the fracture dimensions, but also that it is difficult to separate the competing effects of the various parameters.« less

Numerical modeling of flow and transport in the far-field of a generic nuclear waste repository in fractured crystalline rock using updated fracture continuum model

NASA Astrophysics Data System (ADS)

Hadgu, T.; Kalinina, E.; Klise, K. A.; Wang, Y.

2016-12-01

Disposal of high-level radioactive waste in a deep geological repository in crystalline host rock is one of the potential options for long term isolation. Characterization of the natural barrier system is an important component of the disposal option. In this study we present numerical modeling of flow and transport in fractured crystalline rock using an updated fracture continuum model (FCM). The FCM is a stochastic method that maps the permeability of discrete fractures onto a regular grid. The original method by McKenna and Reeves (2005) has been updated to provide capabilities that enhance representation of fractured rock. As reported in Hadgu et al. (2015) the method was first modified to include fully three-dimensional representations of anisotropic permeability, multiple independent fracture sets, and arbitrary fracture dips and orientations, and spatial correlation. More recently the FCM has been extended to include three different methods. (1) The Sequential Gaussian Simulation (SGSIM) method uses spatial correlation to generate fractures and define their properties for FCM (2) The ELLIPSIM method randomly generates a specified number of ellipses with properties defined by probability distributions. Each ellipse represents a single fracture. (3) Direct conversion of discrete fracture network (DFN) output. Test simulations were conducted to simulate flow and transport using ELLIPSIM and direct conversion of DFN methods. The simulations used a 1 km x 1km x 1km model domain and a structured with grid block of size of 10 m x 10m x 10m, resulting in a total of 106 grid blocks. Distributions of fracture parameters were used to generate a selected number of realizations. For each realization, the different methods were applied to generate representative permeability fields. The PFLOTRAN (Hammond et al., 2014) code was used to simulate flow and transport in the domain. Simulation results and analysis are presented. The results indicate that the FCM approach is a viable method to model fractured crystalline rocks. The FCM is a computationally efficient way to generate realistic representation of complex fracture systems. This approach is of interest for nuclear waste disposal models applied over large domains. SAND2016-7509 A

Well test mathematical model for fractures network in tight oil reservoirs

NASA Astrophysics Data System (ADS)

Diwu, Pengxiang; Liu, Tongjing; Jiang, Baoyi; Wang, Rui; Yang, Peidie; Yang, Jiping; Wang, Zhaoming

2018-02-01

Well test, especially build-up test, has been applied widely in the development of tight oil reservoirs, since it is the only available low cost way to directly quantify flow ability and formation heterogeneity parameters. However, because of the fractures network near wellbore, generated from artificial fracturing linking up natural factures, traditional infinite and finite conductivity fracture models usually result in significantly deviation in field application. In this work, considering the random distribution of natural fractures, physical model of fractures network is proposed, and it shows a composite model feature in the large scale. Consequently, a nonhomogeneous composite mathematical model is established with threshold pressure gradient. To solve this model semi-analytically, we proposed a solution approach including Laplace transform and virtual argument Bessel function, and this method is verified by comparing with existing analytical solution. The matching data of typical type curves generated from semi-analytical solution indicates that the proposed physical and mathematical model can describe the type curves characteristic in typical tight oil reservoirs, which have up warping in late-term rather than parallel lines with slope 1/2 or 1/4. It means the composite model could be used into pressure interpretation of artificial fracturing wells in tight oil reservoir.

Evaluating the effect of internal aperture variability on transport in kilometer scale discrete fracture networks

DOE PAGES

Makedonska, Nataliia; Hyman, Jeffrey D.; Karra, Satish; ...

2016-08-01

The apertures of natural fractures in fractured rock are highly heterogeneous. However, in-fracture aperture variability is often neglected in flow and transport modeling and individual fractures are assumed to have uniform aperture distribution. The relative importance of in-fracture variability in flow and transport modeling within kilometer-scale fracture networks has been under debate for a long time, since the flow in each single fracture is controlled not only by in-fracture variability but also by boundary conditions. Computational limitations have previously prohibited researchers from investigating the relative importance of in-fracture variability in flow and transport modeling within large-scale fracture networks. We addressmore » this question by incorporating internal heterogeneity of individual fractures into flow simulations within kilometer scale three-dimensional fracture networks, where fracture intensity, P 32 (ratio between total fracture area and domain volume) is between 0.027 and 0.031 [1/m]. The recently developed discrete fracture network (DFN) simulation capability, dfnWorks, is used to generate kilometer scale DFNs that include in-fracture aperture variability represented by a stationary log-normal stochastic field with various correlation lengths and variances. The Lagrangian transport parameters, non-reacting travel time, , and cumulative retention, , are calculated along particles streamlines. As a result, it is observed that due to local flow channeling early particle travel times are more sensitive to in-fracture aperture variability than the tails of travel time distributions, where no significant effect of the in-fracture aperture variations and spatial correlation length is observed.« less

Evaluating the effect of internal aperture variability on transport in kilometer scale discrete fracture networks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Makedonska, Nataliia; Hyman, Jeffrey D.; Karra, Satish

The apertures of natural fractures in fractured rock are highly heterogeneous. However, in-fracture aperture variability is often neglected in flow and transport modeling and individual fractures are assumed to have uniform aperture distribution. The relative importance of in-fracture variability in flow and transport modeling within kilometer-scale fracture networks has been under debate for a long time, since the flow in each single fracture is controlled not only by in-fracture variability but also by boundary conditions. Computational limitations have previously prohibited researchers from investigating the relative importance of in-fracture variability in flow and transport modeling within large-scale fracture networks. We addressmore » this question by incorporating internal heterogeneity of individual fractures into flow simulations within kilometer scale three-dimensional fracture networks, where fracture intensity, P 32 (ratio between total fracture area and domain volume) is between 0.027 and 0.031 [1/m]. The recently developed discrete fracture network (DFN) simulation capability, dfnWorks, is used to generate kilometer scale DFNs that include in-fracture aperture variability represented by a stationary log-normal stochastic field with various correlation lengths and variances. The Lagrangian transport parameters, non-reacting travel time, , and cumulative retention, , are calculated along particles streamlines. As a result, it is observed that due to local flow channeling early particle travel times are more sensitive to in-fracture aperture variability than the tails of travel time distributions, where no significant effect of the in-fracture aperture variations and spatial correlation length is observed.« less

A Discrete Fracture Network Model with Stress-Driven Nucleation and Growth

NASA Astrophysics Data System (ADS)

Lavoine, E.; Darcel, C.; Munier, R.; Davy, P.

2017-12-01

The realism of Discrete Fracture Network (DFN) models, beyond the bulk statistical properties, relies on the spatial organization of fractures, which is not issued by purely stochastic DFN models. The realism can be improved by injecting prior information in DFN from a better knowledge of the geological fracturing processes. We first develop a model using simple kinematic rules for mimicking the growth of fractures from nucleation to arrest, in order to evaluate the consequences of the DFN structure on the network connectivity and flow properties. The model generates fracture networks with power-law scaling distributions and a percentage of T-intersections that are consistent with field observations. Nevertheless, a larger complexity relying on the spatial variability of natural fractures positions cannot be explained by the random nucleation process. We propose to introduce a stress-driven nucleation in the timewise process of this kinematic model to study the correlations between nucleation, growth and existing fracture patterns. The method uses the stress field generated by existing fractures and remote stress as an input for a Monte-Carlo sampling of nuclei centers at each time step. Networks so generated are found to have correlations over a large range of scales, with a correlation dimension that varies with time and with the function that relates the nucleation probability to stress. A sensibility analysis of input parameters has been performed in 3D to quantify the influence of fractures and remote stress field orientations.

Flow and fracture behavior of aluminum alloy 6082-T6 at different tensile strain rates and triaxialities.

PubMed

Chen, Xuanzhen; Peng, Yong; Peng, Shan; Yao, Song; Chen, Chao; Xu, Ping

2017-01-01

This study aims to investigate the flow and fracture behavior of aluminum alloy 6082-T6 (AA6082-T6) at different strain rates and triaxialities. Two groups of Charpy impact tests were carried out to further investigate its dynamic impact fracture property. A series of tensile tests and numerical simulations based on finite element analysis (FEA) were performed. Experimental data on smooth specimens under various strain rates ranging from 0.0001~3400 s-1 shows that AA6082-T6 is rather insensitive to strain rates in general. However, clear rate sensitivity was observed in the range of 0.001~1 s-1 while such a characteristic is counteracted by the adiabatic heating of specimens under high strain rates. A Johnson-Cook constitutive model was proposed based on tensile tests at different strain rates. In this study, the average stress triaxiality and equivalent plastic strain at facture obtained from numerical simulations were used for the calibration of J-C fracture model. Both of the J-C constitutive model and fracture model were employed in numerical simulations and the results was compared with experimental results. The calibrated J-C fracture model exhibits higher accuracy than the J-C fracture model obtained by the common method in predicting the fracture behavior of AA6082-T6. Finally, the Scanning Electron Microscope (SEM) of fractured specimens with different initial stress triaxialities were analyzed. The magnified fractographs indicate that high initial stress triaxiality likely results in dimple fracture.

Anisotropic composite human skull model and skull fracture validation against temporo-parietal skull fracture.

PubMed

Sahoo, Debasis; Deck, Caroline; Yoganandan, Narayan; Willinger, Rémy

2013-12-01

A composite material model for skull, taking into account damage is implemented in the Strasbourg University finite element head model (SUFEHM) in order to enhance the existing skull mechanical constitutive law. The skull behavior is validated in terms of fracture patterns and contact forces by reconstructing 15 experimental cases. The new SUFEHM skull model is capable of reproducing skull fracture precisely. The composite skull model is validated not only for maximum forces, but also for lateral impact against actual force time curves from PMHS for the first time. Skull strain energy is found to be a pertinent parameter to predict the skull fracture and based on statistical (binary logistical regression) analysis it is observed that 50% risk of skull fracture occurred at skull strain energy of 544.0mJ. © 2013 Elsevier Ltd. All rights reserved.

The Development of a new Numerical Modelling Approach for Naturally Fractured Rock Masses

NASA Astrophysics Data System (ADS)

Pine, R. J.; Coggan, J. S.; Flynn, Z. N.; Elmo, D.

2006-11-01

An approach for modelling fractured rock masses has been developed which has two main objectives: to maximise the quality of representation of the geometry of existing rock jointing and to use this within a loading model which takes full account of this style of jointing. Initially the work has been applied to the modelling of mine pillars and data from the Middleton Mine in the UK has been used as a case example. However, the general approach is applicable to all aspects of rock mass behaviour including the stress conditions found in hangingwalls, tunnels, block caving, and slopes. The rock mass fracture representation was based on a combination of explicit mapping of rock faces and the synthesis of this data into a three-dimensional model, based on the use of the FracMan computer model suite. Two-dimensional cross sections from this model were imported into the finite element computer model, ELFEN, for loading simulation. The ELFEN constitutive model for fracture simulation includes the Rotating Crack, and Rankine material models, in which fracturing is controlled by tensile strength and fracture energy parameters. For tension/compression stress states, the model is complemented with a capped Mohr-Coulomb criterion in which the softening response is coupled to the tensile model. Fracturing due to dilation is accommodated by introducing an explicit coupling between the inelastic strain accrued by the Mohr-Coulomb yield surface and the anisotropic degradation of the mutually orthogonal tensile yield surfaces of the rotating crack model. Pillars have been simulated with widths of 2.8, 7 and 14 m and a height of 7 m (the Middleton Mine pillars are typically 14 m wide and 7 m high). The evolution of the pillar failure under progressive loading through fracture extension and creation of new fractures is presented, and pillar capacities and stiffnesses are compared with empirical models. The agreement between the models is promising and the new model provides useful insights into the influence of pre-existing fractures. Further work is needed to consider the effects of three-dimensional loading and other boundary condition problems.

A nondestructive technique for predicting the strength remaining in filament wound composites subjected to low-level impact

NASA Technical Reports Server (NTRS)

Madaras, E. I.; Poe, C. C.; Heyman, J. S.

1987-01-01

A model for predicting the fracture strength of homogeneous materials is proposed. Impacted FWC samples were evaluated using ultrasonic testing and an X-ray dye penetration method. The ability of the model to measure fracture strength was also examined. The relation between attenuation and velocity measurements is studied. It is observed that the X-ray method is not useful for predicting fracture strength because the dye could not penetrate the matrix. It is noted that fracture strength predictions derived from the fracture mechanical model and the ultrasonic measurements correlate well with actual measured fracture strengths.

Measurement of Function Post Hip Fracture: Testing a Comprehensive Measurement Model of Physical Function

PubMed Central

Gruber-Baldini, Ann L.; Hicks, Gregory; Ostir, Glen; Klinedinst, N. Jennifer; Orwig, Denise; Magaziner, Jay

2015-01-01

Background Measurement of physical function post hip fracture has been conceptualized using multiple different measures. Purpose This study tested a comprehensive measurement model of physical function. Design This was a descriptive secondary data analysis including 168 men and 171 women post hip fracture. Methods Using structural equation modeling, a measurement model of physical function which included grip strength, activities of daily living, instrumental activities of daily living and performance was tested for fit at 2 and 12 months post hip fracture and among male and female participants and validity of the measurement model of physical function was evaluated based on how well the model explained physical activity, exercise and social activities post hip fracture. Findings The measurement model of physical function fit the data. The amount of variance the model or individual factors of the model explained varied depending on the activity. Conclusion Decisions about the ideal way in which to measure physical function should be based on outcomes considered and participant Clinical Implications The measurement model of physical function is a reliable and valid method to comprehensively measure physical function across the hip fracture recovery trajectory. Practical but useful assessment of function should be considered and monitored over the recovery trajectory post hip fracture. PMID:26492866

Assessment of a novel biomechanical fracture model for distal radius fractures

PubMed Central

2012-01-01

Background Distal radius fractures (DRF) are one of the most common fractures and often need surgical treatment, which has been validated through biomechanical tests. Currently a number of different fracture models are used, none of which resemble the in vivo fracture location. The aim of the study was to develop a new standardized fracture model for DRF (AO-23.A3) and compare its biomechanical behavior to the current gold standard. Methods Variable angle locking volar plates (ADAPTIVE, Medartis) were mounted on 10 pairs of fresh-frozen radii. The osteotomy location was alternated within each pair (New: 10 mm wedge 8 mm / 12 mm proximal to the dorsal / volar apex of the articular surface; Gold standard: 10 mm wedge 20 mm proximal to the articular surface). Each specimen was tested in cyclic axial compression (increasing load by 100 N per cycle) until failure or −3 mm displacement. Parameters assessed were stiffness, displacement and dissipated work calculated for each cycle and ultimate load. Significance was tested using a linear mixed model and Wald test as well as t-tests. Results 7 female and 3 male pairs of radii aged 74 ± 9 years were tested. In most cases (7/10), the two groups showed similar mechanical behavior at low loads with increasing differences at increasing loads. Overall the novel fracture model showed a significant different biomechanical behavior than the gold standard model (p < 0,001). The average final loads resisted were significantly lower in the novel model (860 N ± 232 N vs. 1250 N ± 341 N; p = 0.001). Conclusion The novel biomechanical fracture model for DRF more closely mimics the in vivo fracture site and shows a significantly different biomechanical behavior with increasing loads when compared to the current gold standard. PMID:23244634

A biomechanical comparison of four different fixation methods for midshaft clavicle fractures.

PubMed

Chen, Yang; Yang, Yang; Ma, Xinlong; Xu, Weiguo; Ma, Jianxiong; Zhu, Shaowen; Ma, Baoyi; Xing, Dan

2016-01-01

Clavicle fractures may occur in all age groups, and 70%-80% of clavicle fractures occur in the midshaft. Many methods for treating midshaft clavicular fractures have been reported and remain controversial. To provide some guidance for clinical treatment, 30 artificial polymethyl methacrylate models of the clavicle were sewn obliquely at the midshaft to simulate the most common type of clavicular fractures, and the fracture models were divided into five groups randomly and were fixed as follows: the reconstruction plates were placed at the superior position of the fracture model (R-S group), the reconstruction plates were placed at the anteroinferior position of the fracture model (R-AI group), the locking plates were placed at the superior position (L-S group), the locking plates were placed at the anteroinferior position (L-AI group); and the control models were unfixed (control group). The strain gauges were attached to the bone surface near the fracture fragments, and then, the biomechanical properties of the specimens were measured using the compression test, torsion test and three-point bending test. The results showed that plate fixation can provide a stable construct to help with fracture healing and is the preferred method in the treatment of clavicle fractures. The locking plate provides the best biomechanical stability when placed at the anteroinferior position, and this surgical method can reduce the operation time and postoperative complications; thus, it would be a better choice in clinical practice. © IMechE 2015.

A systematic review of current osteoporotic metaphyseal fracture animal models.

PubMed

Wong, R M Y; Choy, M H V; Li, M C M; Leung, K-S; K-H Chow, S; Cheung, W-H; Cheng, J C Y

2018-01-01

The treatment of osteoporotic fractures is a major challenge, and the enhancement of healing is critical as a major goal in modern fracture management. Most osteoporotic fractures occur at the metaphyseal bone region but few models exist and the healing is still poorly understood. A systematic review was conducted to identify and analyse the appropriateness of current osteoporotic metaphyseal fracture animal models. A literature search was performed on the Pubmed, Embase, and Web of Science databases, and relevant articles were selected. A total of 19 studies were included. Information on the animal, induction of osteoporosis, fracture technique, site and fixation, healing results, and utility of the model were extracted. Fracture techniques included drill hole defects (3 of 19), bone defects (3 of 19), partial osteotomy (1 of 19), and complete osteotomies (12 of 19). Drill hole models and incomplete osteotomy models are easy to perform and allow the study of therapeutic agents but do not represent the usual clinical setting. Additionally, biomaterials can be filled into drill hole defects for analysis. Complete osteotomy models are most commonly used and are best suited for the investigation of therapeutic drugs or noninvasive interventions. The metaphyseal defect models allow the study of biomaterials, which are associated with complex and comminuted osteoporotic fractures. For a clinically relevant model, we propose that an animal model should satisfy the following criteria to study osteoporotic fracture healing: 1) induction of osteoporosis, 2) complete osteotomy or defect at the metaphysis unilaterally, and 3) internal fixation. Cite this article : R. M. Y. Wong, M. H. V. Choy, M. C. M. Li, K-S. Leung, S. K-H. Chow, W-H. Cheung, J. C. Y. Cheng. A systematic review of current osteoporotic metaphyseal fracture animal models. Bone Joint Res 2018;7:6-11. DOI: 10.1302/2046-3758.71.BJR-2016-0334.R2. © 2018 Wong et al.

Modeling folding related multi-scale deformation of sedimentary rock using ALSM and fracture characterization at Raplee Ridge, UT

NASA Astrophysics Data System (ADS)

Mynatt, I.; Hilley, G. E.; Pollard, D. D.

2006-12-01

Understanding and predicting the characteristics of folding induced fracturing is an important and intriguing structural problem. Folded sequences of sedimentary rock at depth are common traps for hydrocarbons and water and fractures can strongly effect (both positively and negatively) this trapping capability. For these reasons fold-fracture relationships are well studied, but due to the complex interactions between the remote tectonic stress, rheologic properties, underlying fault geometry and slip, and pre-existing fractures, fracture characteristics can vary greatly from fold to fold. Additionally, examination of the relationships between fundamental characteristics such as fold geometry and fracture density are difficult even in thoroughly studied producing fields as measurements of fold shape are hampered by the low resolution of seismic surveying and measurements of fractures are limited to sparse well-bore locations. Due to the complexity of the system, the limitations of available data and small number of detailed case studies, prediction of fracture characteristics, e.g. the distribution of fracture density, are often difficult to make for a particular fold. We suggest a combination of mechanical and numerical modeling and analysis combined with detailed field mapping can lead to important insights into fold-fracture relationships. We develop methods to quantify both fold geometry and fracture characteristics, and summarize their relationships for an exhumed analogue reservoir case study. The field area is Raplee Monocline, a Laramide aged, N-S oriented, ~14-km long fold exposed in the Monument Upwarp of south-eastern Utah and part of the larger Colorado Plateau geologic province. The investigation involves three distinct parts: 1) Field based characterization and mapping of the fractures on and near the fold; 2) Development of accurate models of the fold geometry using high resolution data including ~3.5x107 x, y, z topographic points collected using Airborne Laser Swath Mapping (ALSM); and 3) Analysis of the fold shape and fracture patterns using the concepts of differential geometry and fracture mechanics. Field documentation of fracture characteristics enables the classification of distinct pre- and syn- folding fracture sets and the development of conceptual models of multiple stages of fracture evolution. Numerical algorithms, visual methods and field mapping techniques are used to extract the geometry of specific stratigraphic bedding surfaces and interpolate fold geometry between topographic exposures, thereby creating models of the fold geometry at several stratigraphic levels. Geometric characteristics of the fold models, such as magnitudes and directions of maximum and minimum normal curvature and fold limb dip, are compared to the observed fracture characteristics to identify the following relationships: 1) Initiation of folding related fractures at ten degrees of limb dip and increasing fracture density with increasing dip and 2) No correlation between absolute maximum fold curvature and fracture density.

Cola beverage consumption delays alveolar bone healing: a histometric study in rats.

PubMed

Teófilo, Juliana Mazzonetto; Leonel, Daniel Vilela; Lamano, Teresa

2010-01-01

Epidemiological studies have suggested that cola beverage consumption may affect bone metabolism and increase bone fracture risk. Experimental evidence linking cola beverage consumption to deleterious effects on bone is lacking. Herein, we investigated whether cola beverage consumption from weaning to early puberty delays the rate of reparative bone formation inside the socket of an extracted tooth in rats. Twenty male Wistar rats received cola beverage (cola group) or tap water (control group) ad libitum from the age of 23 days until tooth extraction at 42 days and euthanasia 2 and 3 weeks later. The neoformed bone volume inside the alveolar socket was estimated in semi-serial longitudinal sections using a quantitative differential point-counting method. Histological examination suggested a decrease in the osteogenic process within the tooth sockets of rats from both cola groups, which had thinner and sparser new bone trabeculae. Histometric data confirmed that alveolar bone healing was significantly delayed in cola-fed rats at three weeks after tooth extraction (ANOVA, p = 0.0006, followed by Tukey's test, p < 0.01). Although the results of studies in rats cannot be extrapolated directly to human clinical dentistry, the present study provides evidence that cola beverage consumption negatively affect maxillary bone formation.

Origin of Permeability and Structure of Flows in Fractured Media

NASA Astrophysics Data System (ADS)

De Dreuzy, J.; Darcel, C.; Davy, P.; Erhel, J.; Le Goc, R.; Maillot, J.; Meheust, Y.; Pichot, G.; Poirriez, B.

2013-12-01

After more than three decades of research, flows in fractured media have been shown to result from multi-scale geological structures. Flows result non-exclusively from the damage zone of the large faults, from the percolation within denser networks of smaller fractures, from the aperture heterogeneity within the fracture planes and from some remaining permeability within the matrix. While the effect of each of these causes has been studied independently, global assessments of the main determinisms is still needed. We propose a general approach to determine the geological structures responsible for flows, their permeability and their organization based on field data and numerical modeling [de Dreuzy et al., 2012b]. Multi-scale synthetic networks are reconstructed from field data and simplified mechanical modeling [Davy et al., 2010]. High-performance numerical methods are developed to comply with the specificities of the geometry and physical properties of the fractured media [Pichot et al., 2010; Pichot et al., 2012]. And, based on a large Monte-Carlo sampling, we determine the key determinisms of fractured permeability and flows (Figure). We illustrate our approach on the respective influence of fracture apertures and fracture correlation patterns at large scale. We show the potential role of fracture intersections, so far overlooked between the fracture and the network scales. We also demonstrate how fracture correlations reduce the bulk fracture permeability. Using this analysis, we highlight the need for more specific in-situ characterization of fracture flow structures. Fracture modeling and characterization are necessary to meet the new requirements of a growing number of applications where fractures appear both as potential advantages to enhance permeability and drawbacks for safety, e.g. in energy storage, stimulated geothermal energy and non-conventional gas productions. References Davy, P., et al. (2010), A likely universal model of fracture scaling and its consequence for crustal hydromechanics, Journal of Geophysical Research-Solid Earth, 115, 13. de Dreuzy, J.-R., et al. (2012a), Influence of fracture scale heterogeneity on the flow properties of three-dimensional Discrete Fracture Networks (DFN), J. Geophys. Res.-Earth Surf., 117(B11207), 21 PP. de Dreuzy, J.-R., et al. (2012b), Synthetic benchmark for modeling flow in 3D fractured media, Computers and Geosciences(0). Pichot, G., et al. (2010), A Mixed Hybrid Mortar Method for solving flow in Discrete Fracture Networks, Applicable Analysis, 89(10), 1729-1643. Pichot, G., et al. (2012), Flow simulation in 3D multi-scale fractured networks using non-matching meshes, SIAM Journal on Scientific Computing (SISC), 34(1). Figure: (a) Fracture network with a broad-range of fracture lengths. (b) Flows (log-scale) with homogeneous fractures. (c) Flows (log-scale) with heterogeneous fractures [de Dreuzy et al., 2012a]. The impact of the fracture apertures (c) is illustrated on the organization of flows.

Piper sarmentosum Effects on 11β-Hydroxysteroid Dehydrogenase Type 1 Enzyme in Serum and Bone in Rat Model of Glucocorticoid-Induced Osteoporosis.

PubMed

Mohamad Asri, Siti Fadziyah; Mohd Ramli, Elvy Suhana; Soelaiman, Ima Nirwana; Mat Noh, Muhamad Alfakry; Abdul Rashid, Abdul Hamid; Suhaimi, Farihah

2016-11-15

Glucocorticoid-induced osteoporosis is one of the common causes of secondary osteoporosis. Piper sarmentosum ( Ps ) extract possesses antioxidant and anti-inflammatory activities. In this study, we determined the correlation between the effects of Ps leaf water extract with the regulation of 11β-hydroxysteroid dehydrogenase (HSD) type 1 enzyme activity in serum and bone of glucocorticoid-induced osteoporotic rats. Twenty-four Sprague-Dawley rats were grouped into following: G1: sham-operated group administered with intramuscular vehicle olive oil and vehicle normal saline orally; G2: adrenalectomized (adrx) control group given intramuscular dexamethasone (120 μg/kg/day) and vehicle normal saline orally; G3: adrx group given intramuscular dexamethasone (120 μg/kg/day) and water extract of Piper sarmentosum (125 mg/kg/day) orally. After two months, the femur and serum were taken for ELISA analysis. Results showed that Ps leaf water extract significantly reduced the femur corticosterone concentration ( p < 0.05). This suggests that Ps leaf water extract was able to prevent bone loss due to long-term glucocorticoid therapy by acting locally on the bone cells by increasing the dehydrogenase action of 11β-HSD type 1. Thus, Ps may have the potential to be used as an alternative medicine against osteoporosis and osteoporotic fracture in patients on long-term glucocorticoid treatment.

Low dose PTH improves metaphyseal bone healing more when muscles are paralyzed.

PubMed

Sandberg, Olof; Macias, Brandon R; Aspenberg, Per

2014-06-01

Stimulation of bone formation by PTH is related to mechanosensitivity. The response to PTH treatment in intact bone could therefore be blunted by unloading. We studied the effects of mechanical loading on the response to PTH treatment in bone healing. Most fractures occur in the metaphyses, therefor we used a model for metaphyseal bone injury. One hind leg of 20 male SD rats was unloaded via intramuscular botulinum toxin injections. Two weeks later, the proximal unloaded tibia had lost 78% of its trabecular contents. At this time-point, the rats received bilateral proximal tibiae screw implants. Ten of the 20 rats were given daily injections of 5 μg/kg PTH (1-34). After two weeks of healing, screw fixation was measured by pull-out, and microCT of the distal femur cancellous compartment was performed. Pull-out force provided an estimate for cancellous bone formation after trauma. PTH more than doubled the pull-out force in the unloaded limbs (from 14 to 30 N), but increased it by less than half in the loaded ones (from 30 to 44 N). In relative terms, PTH had a stronger effect on pull-out force in unloaded bone than in loaded bone (p=0.03). The results suggest that PTH treatment for stimulation of bone healing does not require simultaneous mechanical stimulation. Copyright © 2014 Elsevier Inc. All rights reserved.

Osteogenic actions of metoprolol in an ovariectomized rat model of menopause.

PubMed

Zang, Yuan; Tan, Quanchang; Ma, Xiangyu; Zhao, Xiong; Lei, Wei

2016-09-01

Osteoporosis and hypertension are age-related chronic diseases with increased morbidity rates among postmenopausal women. Clinical epidemiological investigations have demonstrated that hypertensive patients treated with β1-selective β-blockers have a higher bone mineral density (BMD) and lower fracture risk. Nevertheless, no fundamental studies have examined the relationships between β1-selective β-blockers and these effects. The present study explored the effects and mechanisms of metoprolol in the in vitro treatment of osteoblasts and the in vivo treatment of ovariectomy-induced osteoporosis in rats. Primary osteoblasts were obtained by digestion of the cranial bones of 24-hour-old Sprague-Dawley rats. After metoprolol treatment, cell proliferation and differentiation capacities were assessed at the corresponding time points. In addition, 3-month-old female Sprague-Dawley rats (200-220 g) were divided into a sham-operated group (n = 8) and three ovariectomized (OVX) (bilateral removal of ovaries) groups as follows: vehicle (OVX; n = 8), low-dose metoprolol (L-M, oral, 120 mg/kg/d; n = 8), and high-dose metoprolol (H-M, oral, 240 mg/kg/d; n = 8). After 12 weeks of metoprolol treatment, BMD, microarchitecture, and biomechanical properties were evaluated. The results indicated that the treatments with 0.01 to 0.1 μM metoprolol increased osteoblast proliferation, alkaline phosphatase activity, and calcium mineralization, and promoted the expression of osteogenic genes. The in vivo study indicated that administration of metoprolol to OVX rats resulted in maintenance of the BMDs of the L4 vertebrae. Moreover, amelioration of trabecular microarchitecture deterioration and preservation of bone biomechanical properties were detected in the trabecular bones of the OVX rats. Our findings indicate that metoprolol prevents estrogen deficiency-induced bone loss by increasing the number and enhancing the biological functions of osteoblasts, implying its potential use as an alternative treatment for postmenopausal osteoporosis in hypertensive patients.

Phase Field Modeling of Directional Fracture in Anisotropic Polycrystals

DTIC Science & Technology

2015-02-01

include [35–37]. The phase field description of fracture should be con- trasted with continuum damage mechanics descriptions such as [38,39] that do not...ARL-RP-0518 ● FEBRUARY 2015 US Army Research Laboratory Phase Field Modeling of Directional Fracture in Anisotropic Polycrystals...0518 ● FEBRUARY 2015 US Army Research Laboratory Phase Field Modeling of Directional Fracture in Anisotropic Polycrystals by JD Clayton

A simplified model to evaluate the effect of fluid rheology on non-Newtonian flow in variable aperture fractures

NASA Astrophysics Data System (ADS)

Felisa, Giada; Ciriello, Valentina; Longo, Sandro; Di Federico, Vittorio

2017-04-01

Modeling of non-Newtonian flow in fractured media is essential in hydraulic fracturing operations, largely used for optimal exploitation of oil, gas and thermal reservoirs. Complex fluids interact with pre-existing rock fractures also during drilling operations, enhanced oil recovery, environmental remediation, and other natural phenomena such as magma and sand intrusions, and mud volcanoes. A first step in the modeling effort is a detailed understanding of flow in a single fracture, as the fracture aperture is typically spatially variable. A large bibliography exists on Newtonian flow in single, variable aperture fractures. Ultimately, stochastic modeling of aperture variability at the single fracture scale leads to determination of the flowrate under a given pressure gradient as a function of the parameters describing the variability of the aperture field and the fluid rheological behaviour. From the flowrate, a flow, or 'hydraulic', aperture can then be derived. The equivalent flow aperture for non-Newtonian fluids of power-law nature in single, variable aperture fractures has been obtained in the past both for deterministic and stochastic variations. Detailed numerical modeling of power-law fluid flow in a variable aperture fracture demonstrated that pronounced channelization effects are associated to a nonlinear fluid rheology. The availability of an equivalent flow aperture as a function of the parameters describing the fluid rheology and the aperture variability is enticing, as it allows taking their interaction into account when modeling flow in fracture networks at a larger scale. A relevant issue in non-Newtonian fracture flow is the rheological nature of the fluid. The constitutive model routinely used for hydro-fracturing modeling is the simple, two-parameter power-law. Yet this model does not characterize real fluids at low and high shear rates, as it implies, for shear-thinning fluids, an apparent viscosity which becomes unbounded for zero shear rate and tends to zero for infinite shear rate. On the contrary, the four-parameter Carreau constitutive equation includes asymptotic values of the apparent viscosity at those limits; in turn, the Carreau rheological equation is well approximated by the more tractable truncated power-law model. Results for flow of such fluids between parallel walls are already available. This study extends the adoption of the truncated power-law model to variable aperture fractures, with the aim of understanding the joint influence of rheology and aperture spatial variability. The aperture variation, modeled within a stochastic or deterministic framework, is taken to be one-dimensional and perpendicular to the flow direction; for stochastic modeling, the influence of different distribution functions is examined. Results are then compared with those obtained for pure power-law fluids for different combinations of model parameters. It is seen that the adoption of the pure power law model leads to significant overestimation of the flowrate with respect to the truncated model, more so for large external pressure gradient and/or aperture variability.

Parallel numerical modeling of hybrid-dimensional compositional non-isothermal Darcy flows in fractured porous media

NASA Astrophysics Data System (ADS)

Xing, F.; Masson, R.; Lopez, S.

2017-09-01

This paper introduces a new discrete fracture model accounting for non-isothermal compositional multiphase Darcy flows and complex networks of fractures with intersecting, immersed and non-immersed fractures. The so called hybrid-dimensional model using a 2D model in the fractures coupled with a 3D model in the matrix is first derived rigorously starting from the equi-dimensional matrix fracture model. Then, it is discretized using a fully implicit time integration combined with the Vertex Approximate Gradient (VAG) finite volume scheme which is adapted to polyhedral meshes and anisotropic heterogeneous media. The fully coupled systems are assembled and solved in parallel using the Single Program Multiple Data (SPMD) paradigm with one layer of ghost cells. This strategy allows for a local assembly of the discrete systems. An efficient preconditioner is implemented to solve the linear systems at each time step and each Newton type iteration of the simulation. The numerical efficiency of our approach is assessed on different meshes, fracture networks, and physical settings in terms of parallel scalability, nonlinear convergence and linear convergence.

Micromechanics based simulation of ductile fracture in structural steels

NASA Astrophysics Data System (ADS)

Yellavajjala, Ravi Kiran

The broader aim of this research is to develop fundamental understanding of ductile fracture process in structural steels, propose robust computational models to quantify the associated damage, and provide numerical tools to simplify the implementation of these computational models into general finite element framework. Mechanical testing on different geometries of test specimens made of ASTM A992 steels is conducted to experimentally characterize the ductile fracture at different stress states under monotonic and ultra-low cycle fatigue (ULCF) loading. Scanning electron microscopy studies of the fractured surfaces is conducted to decipher the underlying microscopic damage mechanisms that cause fracture in ASTM A992 steels. Detailed micromechanical analyses for monotonic and cyclic loading are conducted to understand the influence of stress triaxiality and Lode parameter on the void growth phase of ductile fracture. Based on monotonic analyses, an uncoupled micromechanical void growth model is proposed to predict ductile fracture. This model is then incorporated in to finite element program as a weakly coupled model to simulate the loss of load carrying capacity in the post microvoid coalescence regime for high triaxialities. Based on the cyclic analyses, an uncoupled micromechanics based cyclic void growth model is developed to predict the ULCF life of ASTM A992 steels subjected to high stress triaxialities. Furthermore, a computational fracture locus for ASTM A992 steels is developed and incorporated in to finite element program as an uncoupled ductile fracture model. This model can be used to predict the ductile fracture initiation under monotonic loading in a wide range of triaxiality and Lode parameters. Finally, a coupled microvoid elongation and dilation based continuum damage model is proposed, implemented, calibrated and validated. This model is capable of simulating the local softening caused by the various phases of ductile fracture process under monotonic loading for a wide range of stress states. Novel differentiation procedures based on complex analyses along with existing finite difference methods and automatic differentiation are extended using perturbation techniques to evaluate tensor derivatives. These tensor differentiation techniques are then used to automate nonlinear constitutive models into implicit finite element framework. Finally, the efficiency of these automation procedures is demonstrated using benchmark problems.

Coupled Effects of non-Newtonian Rheology and Aperture Variability on Flow in a Single Fracture

NASA Astrophysics Data System (ADS)

Di Federico, V.; Felisa, G.; Lauriola, I.; Longo, S.

2017-12-01

Modeling of non-Newtonian flow in fractured media is essential in hydraulic fracturing and drilling operations, EOR, environmental remediation, and to understand magma intrusions. An important step in the modeling effort is a detailed understanding of flow in a single fracture, as the fracture aperture is spatially variable. A large bibliography exists on Newtonian and non-Newtonian flow in variable aperture fractures. Ultimately, stochastic or deterministic modeling leads to the flowrate under a given pressure gradient as a function of the parameters describing the aperture variability and the fluid rheology. Typically, analytical or numerical studies are performed adopting a power-law (Oswald-de Waele) model. Yet the power-law model, routinely used e.g. for hydro-fracturing modeling, does not characterize real fluids at low and high shear rates. A more appropriate rheological model is provided by e.g. the four-parameter Carreau constitutive equation, which is in turn approximated by the more tractable truncated power-law model. Moreover, fluids of interest may exhibit yield stress, which requires the Bingham or Herschel-Bulkely model. This study employs different rheological models in the context of flow in variable aperture fractures, with the aim of understanding the coupled effect of rheology and aperture spatial variability with a simplified model. The aperture variation, modeled within a stochastic or deterministic framework, is taken to be one-dimensional and i) perpendicular; ii) parallel to the flow direction; for stochastic modeling, the influence of different distribution functions is examined. Results for the different rheological models are compared with those obtained for the pure power-law. The adoption of the latter model leads to overestimation of the flowrate, more so for large aperture variability. The presence of yield stress also induces significant changes in the resulting flowrate for assigned external pressure gradient.

Fracture Propagation, Fluid Flow, and Geomechanics of Water-Based Hydraulic Fracturing in Shale Gas Systems and Electromagnetic Geophysical Monitoring of Fluid Migration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Jihoon; Um, Evan; Moridis, George

2014-12-01

We investigate fracture propagation induced by hydraulic fracturing with water injection, using numerical simulation. For rigorous, full 3D modeling, we employ a numerical method that can model failure resulting from tensile and shear stresses, dynamic nonlinear permeability, leak-off in all directions, and thermo-poro-mechanical effects with the double porosity approach. Our numerical results indicate that fracture propagation is not the same as propagation of the water front, because fracturing is governed by geomechanics, whereas water saturation is determined by fluid flow. At early times, the water saturation front is almost identical to the fracture tip, suggesting that the fracture is mostlymore » filled with injected water. However, at late times, advance of the water front is retarded compared to fracture propagation, yielding a significant gap between the water front and the fracture top, which is filled with reservoir gas. We also find considerable leak-off of water to the reservoir. The inconsistency between the fracture volume and the volume of injected water cannot properly calculate the fracture length, when it is estimated based on the simple assumption that the fracture is fully saturated with injected water. As an example of flow-geomechanical responses, we identify pressure fluctuation under constant water injection, because hydraulic fracturing is itself a set of many failure processes, in which pressure consistently drops when failure occurs, but fluctuation decreases as the fracture length grows. We also study application of electromagnetic (EM) geophysical methods, because these methods are highly sensitive to changes in porosity and pore-fluid properties due to water injection into gas reservoirs. Employing a 3D finite-element EM geophysical simulator, we evaluate the sensitivity of the crosswell EM method for monitoring fluid movements in shaly reservoirs. For this sensitivity evaluation, reservoir models are generated through the coupled flow-geomechanical simulator and are transformed via a rock-physics model into electrical conductivity models. It is shown that anomalous conductivity distribution in the resulting models is closely related to injected water saturation, but not closely related to newly created unsaturated fractures. Our numerical modeling experiments demonstrate that the crosswell EM method can be highly sensitive to conductivity changes that directly indicate the migration pathways of the injected fluid. Accordingly, the EM method can serve as an effective monitoring tool for distribution of injected fluids (i.e., migration pathways) during hydraulic fracturing operations« less

A Comprehensive Model for Real Gas Transport in Shale Formations with Complex Non-planar Fracture Networks

PubMed Central

Yang, Ruiyue; Huang, Zhongwei; Yu, Wei; Li, Gensheng; Ren, Wenxi; Zuo, Lihua; Tan, Xiaosi; Sepehrnoori, Kamy; Tian, Shouceng; Sheng, Mao

2016-01-01

A complex fracture network is generally generated during the hydraulic fracturing treatment in shale gas reservoirs. Numerous efforts have been made to model the flow behavior of such fracture networks. However, it is still challenging to predict the impacts of various gas transport mechanisms on well performance with arbitrary fracture geometry in a computationally efficient manner. We develop a robust and comprehensive model for real gas transport in shales with complex non-planar fracture network. Contributions of gas transport mechanisms and fracture complexity to well productivity and rate transient behavior are systematically analyzed. The major findings are: simple planar fracture can overestimate gas production than non-planar fracture due to less fracture interference. A “hump” that occurs in the transition period and formation linear flow with a slope less than 1/2 can infer the appearance of natural fractures. The sharpness of the “hump” can indicate the complexity and irregularity of the fracture networks. Gas flow mechanisms can extend the transition flow period. The gas desorption could make the “hump” more profound. The Knudsen diffusion and slippage effect play a dominant role in the later production time. Maximizing the fracture complexity through generating large connected networks is an effective way to increase shale gas production. PMID:27819349

A Comprehensive Model for Real Gas Transport in Shale Formations with Complex Non-planar Fracture Networks.

PubMed

Yang, Ruiyue; Huang, Zhongwei; Yu, Wei; Li, Gensheng; Ren, Wenxi; Zuo, Lihua; Tan, Xiaosi; Sepehrnoori, Kamy; Tian, Shouceng; Sheng, Mao

2016-11-07

A complex fracture network is generally generated during the hydraulic fracturing treatment in shale gas reservoirs. Numerous efforts have been made to model the flow behavior of such fracture networks. However, it is still challenging to predict the impacts of various gas transport mechanisms on well performance with arbitrary fracture geometry in a computationally efficient manner. We develop a robust and comprehensive model for real gas transport in shales with complex non-planar fracture network. Contributions of gas transport mechanisms and fracture complexity to well productivity and rate transient behavior are systematically analyzed. The major findings are: simple planar fracture can overestimate gas production than non-planar fracture due to less fracture interference. A "hump" that occurs in the transition period and formation linear flow with a slope less than 1/2 can infer the appearance of natural fractures. The sharpness of the "hump" can indicate the complexity and irregularity of the fracture networks. Gas flow mechanisms can extend the transition flow period. The gas desorption could make the "hump" more profound. The Knudsen diffusion and slippage effect play a dominant role in the later production time. Maximizing the fracture complexity through generating large connected networks is an effective way to increase shale gas production.

In situ measurements of hydraulic fracture behavior, PTE-3. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Warpinski, N.R.

Measurements of width and pressure in a propagating hydraulic fracture have been made in tests conducted at DOE`s Nevada Test Site. This was accomplished by creating an "instrumented fracture" at a tunnel complex (at a depth of 1400 ft) where realistic in situ conditions prevail, particularly with respect to stress and geologic features such as natural fractures and material anisotropy. Analyses of these data show that the pressure drop along the fracture length is much larger than predicted by viscous theory currently in use in models today. This is apparently due to the tortuosity of the fracture path, multiple fracturemore » strands, roughness, and sharp turns (corners) in the flow path due to natural fractures and rock property variations. It suggests that fracture design models need to be updated to include a more realistic friction factor so that fracture lengths are not overestimated. The width and pressure profiles near the crack tip have been investigated in some detail, including the length of the unwetted region and the tapering of the crack tip. The overall fracture behavior has been compared with published fracture models. Mineback of the fracture provided evidence of the geometry of the fracture and details of surface features. 35 refs., 89 figs., 30 tabs.« less

Sodium selenate treatment mitigates reduction of bone volume following traumatic brain injury in rats.

PubMed

Brady, R D; Grills, B L; Romano, T; Wark, J D; O'Brien, T J; Shultz, S R; McDonald, S J

2016-12-14

Administration of sodium selenate to rats given traumatic brain injury (TBI) attenuates brain damage and improves long-term behavioural outcomes. We have previously provided evidence that TBI causes bone loss in rats, however the effect of sodium selenate treatment on bone quantity following TBI is unknown. Rats were randomly assigned into sham injury or fluid percussion injury (FPI) groups and administered saline or sodium selenate for 12 weeks post-injury. Femora were analysed using histomorphometry, peripheral quantitative computed tomography (pQCT) and biomechanical testing. Distal metaphyseal trabecular bone volume fraction of FPI-selenate rats was higher than FPI-vehicle rats (41.8%; p<0.01), however, femora from selenate-treated groups were shorter in length (4.3%; p<0.01) and had increased growth plate width (22.1%; p<0.01), indicating that selenate impaired long bone growth. pQCT analysis demonstrated that distal metaphyseal cortical thickness was decreased in TBI rats compared to shams (11.7%; p<0.05), however selenate treatment to TBI animals offset this reduction (p<0.05). At the midshaft we observed no differences in biomechanical measures. These are the first findings to indicate that mitigating TBI-induced neuropathology may have the added benefit of preventing osteoporosis and associated fracture risk following TBI.

A new computer code for discrete fracture network modelling

NASA Astrophysics Data System (ADS)

Xu, Chaoshui; Dowd, Peter

2010-03-01

The authors describe a comprehensive software package for two- and three-dimensional stochastic rock fracture simulation using marked point processes. Fracture locations can be modelled by a Poisson, a non-homogeneous, a cluster or a Cox point process; fracture geometries and properties are modelled by their respective probability distributions. Virtual sampling tools such as plane, window and scanline sampling are included in the software together with a comprehensive set of statistical tools including histogram analysis, probability plots, rose diagrams and hemispherical projections. The paper describes in detail the theoretical basis of the implementation and provides a case study in rock fracture modelling to demonstrate the application of the software.

Three-Dimensional Modeling of Fracture Clusters in Geothermal Reservoirs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ghassemi, Ahmad

The objective of this is to develop a 3-D numerical model for simulating mode I, II, and III (tensile, shear, and out-of-plane) propagation of multiple fractures and fracture clusters to accurately predict geothermal reservoir stimulation using the virtual multi-dimensional internal bond (VMIB). Effective development of enhanced geothermal systems can significantly benefit from improved modeling of hydraulic fracturing. In geothermal reservoirs, where the temperature can reach or exceed 350oC, thermal and poro-mechanical processes play an important role in fracture initiation and propagation. In this project hydraulic fracturing of hot subsurface rock mass will be numerically modeled by extending the virtual multiplemore » internal bond theory and implementing it in a finite element code, WARP3D, a three-dimensional finite element code for solid mechanics. The new constitutive model along with the poro-thermoelastic computational algorithms will allow modeling the initiation and propagation of clusters of fractures, and extension of pre-existing fractures. The work will enable the industry to realistically model stimulation of geothermal reservoirs. The project addresses the Geothermal Technologies Office objective of accurately predicting geothermal reservoir stimulation (GTO technology priority item). The project goal will be attained by: (i) development of the VMIB method for application to 3D analysis of fracture clusters; (ii) development of poro- and thermoelastic material sub-routines for use in 3D finite element code WARP3D; (iii) implementation of VMIB and the new material routines in WARP3D to enable simulation of clusters of fractures while accounting for the effects of the pore pressure, thermal stress and inelastic deformation; (iv) simulation of 3D fracture propagation and coalescence and formation of clusters, and comparison with laboratory compression tests; and (v) application of the model to interpretation of injection experiments (planned by our industrial partner) with reference to the impact of the variations in injection rate and temperature, rock properties, and in-situ stress.« less

Inclusion-based effective medium models for the field-scale permeability of 3D fractured rock masses

NASA Astrophysics Data System (ADS)

Ebigbo, Anozie; Lang, Philipp S.; Paluszny, Adriana; Zimmerman, Robert W.

2016-04-01

Fractures that are more permeable than their host rock can act as preferential, or at least additional, pathways for fluid to flow through the rock. The additional transmissivity contributed by these fractures will be of great relevance in several areas of earth science and engineering, such as radioactive waste disposal in crystalline rock, exploitation of fractured hydrocarbon and geothermal reservoirs, or hydraulic fracturing. In describing or predicting flow through fractured rock, the effective permeability of the rock mass, comprising both the rock matrix and a network of fractures, is a crucial parameter, and will depend on several geometric properties of the fractures/networks, such as lateral extent, aperture, orientation, and fracture density. This study investigates the ability of classical inclusion-based effective medium models (following the work of Sævik et al., Transp. Porous Media, 2013) to predict this permeability. In these models, the fractures are represented as thin, spheroidal inclusions, the interiors of which are treated as porous media having a high (but finite) permeability. The predictions of various effective medium models, such as the symmetric and asymmetric self-consistent schemes, the differential scheme, and Maxwell's method, are tested against the results of explicit numerical simulations of mono- and polydisperse isotropic fracture networks embedded in a permeable rock matrix. Comparisons are also made with the Hashin-Shrikman bounds, Snow's model, and Mourzenko's heuristic model (Mourzenko et al., Phys. Rev. E, 2011). This problem is characterised mathematically by two small parameters, the aspect ratio of the spheroidal fractures, α, and the ratio between matrix and fracture permeability, κ. Two different regimes can be identified, corresponding to α/κ < 1 and α/κ > 1. The lower the value of α/κ, the more significant is flow through the matrix. Due to differing flow patterns, the dependence of effective permeability on fracture density differs in the two regimes. When α/κ > 1, a distinct percolation threshold is observed, whereas for α/κ < 1, the matrix is sufficiently transmissive that a percolation-like transition is not observed. The self-consistent effective medium methods show good accuracy for both mono- and polydisperse isotropic fracture networks. Mourzenko's equation is also found to be very accurate, particularly for monodisperse networks. Finally, it is shown that Snow's model essentially coincides with the Hashin-Shtrikman upper bound.

Hybrid-dimensional modelling of two-phase flow through fractured porous media with enhanced matrix fracture transmission conditions

NASA Astrophysics Data System (ADS)

Brenner, Konstantin; Hennicker, Julian; Masson, Roland; Samier, Pierre

2018-03-01

In this work, we extend, to two-phase flow, the single-phase Darcy flow model proposed in [26], [12] in which the (d - 1)-dimensional flow in the fractures is coupled with the d-dimensional flow in the matrix. Three types of so called hybrid-dimensional two-phase Darcy flow models are proposed. They all account for fractures acting either as drains or as barriers, since they allow pressure jumps at the matrix-fracture interfaces. The models also permit to treat gravity dominated flow as well as discontinuous capillary pressure at the material interfaces. The three models differ by their transmission conditions at matrix fracture interfaces: while the first model accounts for the nonlinear two-phase Darcy flux conservations, the second and third ones are based on the linear single phase Darcy flux conservations combined with different approximations of the mobilities. We adapt the Vertex Approximate Gradient (VAG) scheme to this problem, in order to account for anisotropy and heterogeneity aspects as well as for applicability on general meshes. Several test cases are presented to compare our hybrid-dimensional models to the generic equi-dimensional model, in which fractures have the same dimension as the matrix, leading to deep insight about the quality of the proposed reduced models.

On Subsurface Fracture Opening and Closure

NASA Astrophysics Data System (ADS)

Wang, Y.

2016-12-01

Mechanistic understanding of fracture opening and closure in geologic media is of significant importance to nature resource extraction and waste management, such as geothermal energy extraction, oil/gas production, radioactive waste disposal, and carbon sequestration and storage). A dynamic model for subsurface fracture opening and closure has been formulated. The model explicitly accounts for the stress concentration around individual aperture channels and the stress-activated mineral dissolution and precipitation. A preliminary model analysis has demonstrated the importance of the stress-activated dissolution mechanism in the evolution of fracture aperture in a stressed geologic medium. The model provides a reasonable explanation for some key features of fracture opening and closure observed in laboratory experiments, including a spontaneous switch from a net permeability reduction to a net permeability increase with no changes in a limestone fracture experiment.

Modeling of Hydraulic Fracture Propagation at the kISMET Site Using a Fully Coupled 3D Network-Flow and Quasi- Static Discrete Element Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Jing; Huang, Hai; Mattson, Earl

Aimed at supporting the design of hydraulic fracturing experiments at the kISMET site, ~1500 m below ground in a deep mine, we performed pre-experimental hydraulic fracturing simulations in order to estimate the breakdown pressure, propagation pressure, fracture geometry, and the magnitude of induced seismicity using a newly developed fully coupled three-dimensional (3D) network flow and quasi-static discrete element model (DEM). The quasi-static DEM model, which is constructed by Delaunay tessellation of the rock volume, considers rock fabric heterogeneities by using the “disordered” DEM mesh and adding random perturbations to the stiffness and tensile/shear strengths of individual DEM elements and themore » elastic beams between them. A conjugate 3D flow network based on the DEM lattice is constructed to calculate the fluid flow in both the fracture and porous matrix. One distinctive advantage of the model is that fracturing is naturally described by the breakage of elastic beams between DEM elements. It is also extremely convenient to introduce mechanical anisotropy into the model by simply assigning orientation-dependent tensile/shear strengths to the elastic beams. In this paper, the 3D hydraulic fracturing model was verified against the analytic solution for a penny-shaped crack model. We applied the model to simulate fracture propagation from a vertical open borehole based on initial estimates of rock mechanical properties and in-situ stress conditions. The breakdown pressure and propagation pressure are directly obtained from the simulation. In addition, the released elastic strain energies of individual fracturing events were calculated and used as a conservative estimate for the magnitudes of the potential induced seismic activities associated with fracturing. The comparisons between model predictions and experimental results are still ongoing.« less

Experiments and Simulations of Fully Hydro-Mechanically Coupled Response of Rough Fractures Exposed to High-Pressure Fluid Injection

NASA Astrophysics Data System (ADS)

Vogler, D.; Settgast, R. R.; Annavarapu, C.; Madonna, C.; Bayer, P.; Amann, F.

2018-02-01

In this work, we present the application of a fully coupled hydro-mechanical method to investigate the effect of fracture heterogeneity on fluid flow through fractures at the laboratory scale. Experimental and numerical studies of fracture closure behavior in the presence of heterogeneous mechanical and hydraulic properties are presented. We compare the results of two sets of laboratory experiments on granodiorite specimens against numerical simulations in order to investigate the mechanical fracture closure and the hydro-mechanical effects, respectively. The model captures fracture closure behavior and predicts a nonlinear increase in fluid injection pressure with loading. Results from this study indicate that the heterogeneous aperture distributions measured for experiment specimens can be used as model input for a local cubic law model in a heterogeneous fracture to capture fracture closure behavior and corresponding fluid pressure response.

Adaptive mixed finite element methods for Darcy flow in fractured porous media

NASA Astrophysics Data System (ADS)

Chen, Huangxin; Salama, Amgad; Sun, Shuyu

2016-10-01

In this paper, we propose adaptive mixed finite element methods for simulating the single-phase Darcy flow in two-dimensional fractured porous media. The reduced model that we use for the simulation is a discrete fracture model coupling Darcy flows in the matrix and the fractures, and the fractures are modeled by one-dimensional entities. The Raviart-Thomas mixed finite element methods are utilized for the solution of the coupled Darcy flows in the matrix and the fractures. In order to improve the efficiency of the simulation, we use adaptive mixed finite element methods based on novel residual-based a posteriori error estimators. In addition, we develop an efficient upscaling algorithm to compute the effective permeability of the fractured porous media. Several interesting examples of Darcy flow in the fractured porous media are presented to demonstrate the robustness of the algorithm.

Three-dimensional modeling of flow through fractured tuff at Fran Ridge

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eaton, R.R.; Ho, C.K.; Glass, RJ.

1996-09-01

Numerical studies have been made of an infiltration experiment at Fran Ridge using the TOUGH2 code to aid in the selection of computational models for performance assessment. The exercise investigates the capabilities of TOUGH2 to model transient flows through highly fractured tuff and provides a possible means of calibration. Two distinctly different conceptual models were used in the TOUGH2 code, the dual permeability model and the equivalent continuum model. The infiltration test modeled involved the infiltration of dyed ponded water for 36 minutes. The 205 gallon infiltration of water observed in the experiment was subsequently modeled using measured Fran Ridgemore » fracture frequencies, and a specified fracture aperture of 285 {micro}m. The dual permeability formulation predicted considerable infiltration along the fracture network, which was in agreement with the experimental observations. As expected, al fracture penetration of the infiltrating water was calculated using the equivalent continuum model, thus demonstrating that this model is not appropriate for modeling the highly transient experiment. It is therefore recommended that the dual permeability model be given priority when computing high-flux infiltration for use in performance assessment studies.« less

Three-dimensional modeling of flow through fractured tuff at Fran Ridge

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eaton, R.R.; Ho, C.K.; Glass, R.J.

1996-01-01

Numerical studies have been made of an infiltration experiment at Fran Ridge using the TOUGH2 code to aid in the selection of computational models for performance assessment. The exercise investigates the capabilities of TOUGH2 to model transient flows through highly fractured tuff and provides a possible means of calibration. Two distinctly different conceptual models were used in the TOUGH2 code, the dual permeability model and the equivalent continuum model. The infiltration test modeled involved the infiltration of dyed ponded water for 36 minutes. The 205 gallon filtration of water observed in the experiment was subsequently modeled using measured Fran Ridgemore » fracture frequencies, and a specified fracture aperture of 285 {mu}m. The dual permeability formulation predicted considerable infiltration along the fracture network, which was in agreement with the experimental observations. As expected, minimal fracture penetration of the infiltrating water was calculated using the equivalent continuum model, thus demonstrating that this model is not appropriate for modeling the highly transient experiment. It is therefore recommended that the dual permeability model be given priority when computing high-flux infiltration for use in performance assessment studies.« less

Preferential flow and pesticide transport in a clay-rich till: Field, laboratory, and modeling analysis

NASA Astrophysics Data System (ADS)

JøRgensen, Peter R.; Hoffmann, Martin; Kistrup, Jens P.; Bryde, Claus; Bossi, Rossana; Villholth, Karen G.

2002-11-01

This study investigates vertical flow and pesticide transport along fractures in water saturated unoxidized clayey till. From two experimental fields, each 40 m2, 96% and 98%, respectively, of total vertical flow was conducted along fractures in the till, while the remaining 2-4% of flow occurred in the clay matrix at very slow flow rate. An applied dye tracer was observed only along 10-26% of the total fracture length measured on the horizontal surface of the experimental fields. In vertical sections the dyed fracture portions constituted root channels, which penetrated the till vertically along the fractures into the local aquifer at 5 m depth. No dye tracer was observed in the fractures without root channels or in the unfractured clay matrix, suggesting that root growth along the fracture surfaces was the principal agent of fracture aperture enhancement. Using hydraulic fracture aperture values determined from large undisturbed column (LUC) collected from one of the experimental fields, it was estimated that 94% of flow in the fractures was conducted along the fracture root channels, while only 6% of flow was conducted along the fracture sections without root channels. For natural vertical hydraulic gradients (0.8-2.3 at the site), flow rates of 0.8-2 km/d were determined for a fracture root channel, while fracture sections without root channels revealed flow rates of 9-22 m/d. Corresponding flow rates in the unfractured matrix were 7-19 mm/yr. For infiltrated bromide (nonreactive tracer) and mobile pesticides mecoprop (MCPP) and metsulfuron, very rapid migration (0.28-0.5 m/d) and high relative breakthrough concentrations (30-60%) into the aquifer were observed to occur along the fracture root channels using a constant hydraulic gradient of 1. Only traces were measured from infiltration of the strongly sorbed pesticide prochloraz. The concentrations of the bromide and pesticides in the monitoring wells were modeled with a discrete fracture matrix diffusion (DFDM) model coupled with a single porosity model (SP) for the till and aquifer, respectively. Using effective fracture spacings and mean fracture apertures for the fracture channel sections as modeling input parameters for the till, the concentrations observed in the wells of the aquifer could be reasonably approximated.

Evaluation of ground-penetrating radar to detect free-phase hydrocarbons in fractured rocks - Results of numerical modeling and physical experiments

USGS Publications Warehouse

Lane, J.W.; Buursink, M.L.; Haeni, F.P.; Versteeg, R.J.

2000-01-01

The suitability of common-offset ground-penetrating radar (GPR) to detect free-phase hydrocarbons in bedrock fractures was evaluated using numerical modeling and physical experiments. The results of one- and two-dimensional numerical modeling at 100 megahertz indicate that GPR reflection amplitudes are relatively insensitive to fracture apertures ranging from 1 to 4 mm. The numerical modeling and physical experiments indicate that differences in the fluids that fill fractures significantly affect the amplitude and the polarity of electromagnetic waves reflected by subhorizontal fractures. Air-filled and hydrocarbon-filled fractures generate low-amplitude reflections that are in-phase with the transmitted pulse. Water-filled fractures create reflections with greater amplitude and opposite polarity than those reflections created by air-filled or hydrocarbon-filled fractures. The results from the numerical modeling and physical experiments demonstrate it is possible to distinguish water-filled fracture reflections from air- or hydrocarbon-filled fracture reflections, nevertheless subsurface heterogeneity, antenna coupling changes, and other sources of noise will likely make it difficult to observe these changes in GPR field data. This indicates that the routine application of common-offset GPR reflection methods for detection of hydrocarbon-filled fractures will be problematic. Ideal cases will require appropriately processed, high-quality GPR data, ground-truth information, and detailed knowledge of subsurface physical properties. Conversely, the sensitivity of GPR methods to changes in subsurface physical properties as demonstrated by the numerical and experimental results suggests the potential of using GPR methods as a monitoring tool. GPR methods may be suited for monitoring pumping and tracer tests, changes in site hydrologic conditions, and remediation activities.The suitability of common-offset ground-penetrating radar (GPR) to detect free-phase hydrocarbons in bedrock fractures was evaluated using numerical modeling and physical experiments. The results of one- and two-dimensional numerical modeling at 100 megahertz indicate that GPR reflection amplitudes are relatively insensitive to fracture apertures ranging from 1 to 4 mm. The numerical modeling and physical experiments indicate that differences in the fluids that fill fractures significantly affect the amplitude and the polarity of electromagnetic waves reflected by subhorizontal fractures. Air-filled and hydrocarbon-filled fractures generate low-amplitude reflections that are in-phase with the transmitted pulse. Water-filled fractures create reflections with greater amplitude and opposite polarity than those reflections created by air-filled or hydrocarbon-filled fractures. The results from the numerical modeling and physical experiments demonstrate it is possible to distinguish water-filled fracture reflections from air- or hydrocarbon-filled fracture reflections, nevertheless subsurface heterogeneity, antenna coupling changes, and other sources of noise will likely make it difficult to observe these changes in GPR field data. This indicates that the routine application of common-offset GPR reflection methods for detection of hydrocarbon-filled fractures will be problematic. Ideal cases will require appropriately processed, high-quality GPR data, ground-truth information, and detailed knowledge of subsurface physical properties. Conversely, the sensitivity of GPR methods to changes in subsurface physical properties as demonstrated by the numerical and experimental results suggests the potential of using GPR methods as a monitoring tool. GPR methods may be suited for monitoring pumping and tracer tests, changes in site hydrologic conditions, and remediation activities.

Onset of mandible and tibia osteoradionecrosis – a comparative pilot study in the rat

PubMed Central

Damek-Poprawa, Monika; Both, Stefan; Wright, Alexander C.; Maity, Amit; Akintoye, Sunday O.

2012-01-01

Objectives Osteoradionecrosis (ORN) is common in the jaws following radiotherapy. We hypothesized that mandible is more susceptible to ORN than tibia based on site-disparity in hypoxic-hypocellular-hypovascular tissue breakdown. Study Design Twelve rats received 50 Gy irradiation to mandible or tibia; 4 of 12 rats further received minor surgical trauma to the irradiated sites. Structural and cellular skeletal changes were assessed with computer tomography, histology and immunostaining. Results Mandible developed ORN with 70% mean bone loss 10 weeks post-irradiation (p < 0.05) while tibia was structurally and radiological intact for 20 weeks post-irradiation. Hypocellularity, hypoxia and oxidative stress were higher in irradiated mandible (p < 0.001) than tibia (p < 0.01) but vascular damage was similar at both skeletal sites. Combined effects of radiation and minor trauma promoted mandibular alveolar bone loss and tibial fracture Conclusion ORN has a more rapid onset in mandible relative to tibia in the rat PMID:23254371

Sensitivity Analysis of the Bone Fracture Risk Model

NASA Technical Reports Server (NTRS)

Lewandowski, Beth; Myers, Jerry; Sibonga, Jean Diane

2017-01-01

Introduction: The probability of bone fracture during and after spaceflight is quantified to aid in mission planning, to determine required astronaut fitness standards and training requirements and to inform countermeasure research and design. Probability is quantified with a probabilistic modeling approach where distributions of model parameter values, instead of single deterministic values, capture the parameter variability within the astronaut population and fracture predictions are probability distributions with a mean value and an associated uncertainty. Because of this uncertainty, the model in its current state cannot discern an effect of countermeasures on fracture probability, for example between use and non-use of bisphosphonates or between spaceflight exercise performed with the Advanced Resistive Exercise Device (ARED) or on devices prior to installation of ARED on the International Space Station. This is thought to be due to the inability to measure key contributors to bone strength, for example, geometry and volumetric distributions of bone mass, with areal bone mineral density (BMD) measurement techniques. To further the applicability of model, we performed a parameter sensitivity study aimed at identifying those parameter uncertainties that most effect the model forecasts in order to determine what areas of the model needed enhancements for reducing uncertainty. Methods: The bone fracture risk model (BFxRM), originally published in (Nelson et al) is a probabilistic model that can assess the risk of astronaut bone fracture. This is accomplished by utilizing biomechanical models to assess the applied loads; utilizing models of spaceflight BMD loss in at-risk skeletal locations; quantifying bone strength through a relationship between areal BMD and bone failure load; and relating fracture risk index (FRI), the ratio of applied load to bone strength, to fracture probability. There are many factors associated with these calculations including environmental factors, factors associated with the fall event, mass and anthropometric values of the astronaut, BMD characteristics, characteristics of the relationship between BMD and bone strength and bone fracture characteristics. The uncertainty in these factors is captured through the use of parameter distributions and the fracture predictions are probability distributions with a mean value and an associated uncertainty. To determine parameter sensitivity, a correlation coefficient is found between the sample set of each model parameter and the calculated fracture probabilities. Each parameters contribution to the variance is found by squaring the correlation coefficients, dividing by the sum of the squared correlation coefficients, and multiplying by 100. Results: Sensitivity analyses of BFxRM simulations of preflight, 0 days post-flight and 365 days post-flight falls onto the hip revealed a subset of the twelve factors within the model which cause the most variation in the fracture predictions. These factors include the spring constant used in the hip biomechanical model, the midpoint FRI parameter within the equation used to convert FRI to fracture probability and preflight BMD values. Future work: Plans are underway to update the BFxRM by incorporating bone strength information from finite element models (FEM) into the bone strength portion of the BFxRM. Also, FEM bone strength information along with fracture outcome data will be incorporated into the FRI to fracture probability.

Residual lifetime and 10 year absolute risks of osteoporotic fractures in Chinese men and women.

PubMed

Si, Lei; Winzenberg, Tania M; Chen, Mingsheng; Jiang, Qicheng; Palmer, Andrew J

2015-06-01

To determine the residual lifetime and 10 year absolute risks of osteoporotic fractures in Chinese men and women. A validated state-transition microsimulation model was used. Microsimulation and probabilistic sensitivity analyses were performed to address the uncertainties in the model. All parameters including fracture incidence rates and mortality rates were retrieved from published literature. Simulated subjects were run through the model until they died to estimate the residual lifetime fracture risks. A 10 year time horizon was used to determine the 10 year fracture risks. We estimated the risk of only the first osteoporotic fracture during the simulation time horizon. The residual lifetime and 10 year risks of having the first osteoporotic (hip, clinical vertebral or wrist) fracture for Chinese women aged 50 years were 40.9% (95% CI: 38.3-44.0%) and 8.2% (95% CI: 6.8-9.3%) respectively. For men, the residual lifetime and 10 year fracture risks were 8.7% (95% CI: 7.5-9.8%) and 1.2% (95% CI: 0.8-1.7%) respectively. The residual lifetime fracture risks declined with age, whilst the 10 year fracture risks increased with age until the short-term mortality risks outstripped the fracture risks. Residual lifetime and 10 year clinical vertebral fracture risks were higher than those of hip and wrist fractures in both sexes. More than one third of the Chinese women and approximately one tenth of the Chinese men aged 50 years are expected to sustain a major osteoporotic fracture in their remaining lifetimes. Due to increased fracture risks and a rapidly ageing population, osteoporosis will present a great challenge to the Chinese healthcare system. While national data was used wherever possible, regional Chinese hip and clinical vertebral fracture incidence rates were used, wrist fracture rates were taken from a Norwegian study and calibrated to the Chinese population. Other fracture sites like tibia, humerus, ribs and pelvis were not included in the analysis, thus these risks are likely to be underestimates. Fracture risk factors other than age and sex were not included in the model. Point estimates were used for fracture incidence rates, osteoporosis prevalence and mortality rates for the general population.

The Israeli elite infantry recruit: a model for understanding the biomechanics of stress fractures.

PubMed

Milgrom, C

1989-01-01

In a series of prospective studies among infantry recruits the biomechanics of stress fractures have been studied. In this recruit model bone geometry and the natural shock absorbers of the body have been found to be related to stress fracture morbidity. Using the technique of accelerometry in this model, it has been shown that in the fatigue state shock absorption decreases, resulting in an increase in the amplitude of vertical accelerations that propagate up the skeleton at heel strike. Experiments to study the possibility of lowering stress fracture morbidity in this model by means of viscoelastic orthotics have been successful only in the case of femoral and metatarsal stress fractures among certain subpopulations. Stress fracture management in this model has been improved by early detection and by treatment regimens according to a protocol that emphasizes limited rest periods to allow healing to take place rather than judging recovery by pain levels.

Attempting to bridge the gap between laboratory and seismic estimates of fracture energy

USGS Publications Warehouse

McGarr, A.; Fletcher, Joe B.; Beeler, N.M.

2004-01-01

To investigate the behavior of the fracture energy associated with expanding the rupture zone of an earthquake, we have used the results of a large-scale, biaxial stick-slip friction experiment to set the parameters of an equivalent dynamic rupture model. This model is determined by matching the fault slip, the static stress drop and the apparent stress. After confirming that the fracture energy associated with this model earthquake is in reasonable agreement with corresponding laboratory values, we can use it to determine fracture energies for earthquakes as functions of stress drop, rupture velocity and fault slip. If we take account of the state of stress at seismogenic depths, the model extrapolation to larger fault slips yields fracture energies that agree with independent estimates by others based on dynamic rupture models for large earthquakes. For fixed stress drop and rupture speed, the fracture energy scales linearly with fault slip.

Percolation Theory and Modern Hydraulic Fracturing

NASA Astrophysics Data System (ADS)

Norris, J. Q.; Turcotte, D. L.; Rundle, J. B.

2015-12-01

During the past few years, we have been developing a percolation model for fracking. This model provides a powerful tool for understanding the growth and properties of the complex fracture networks generated during a modern high volume hydraulic fracture stimulations of tight shale reservoirs. The model can also be used to understand the interaction between the growing fracture network and natural reservoir features such as joint sets and faults. Additionally, the model produces a power-law distribution of bursts which can easily be compared to observed microseismicity.

Streaming potential modeling in fractured rock: Insights into the identification of hydraulically active fractures

NASA Astrophysics Data System (ADS)

Roubinet, D.; Linde, N.; Jougnot, D.; Irving, J.

2016-05-01

Numerous field experiments suggest that the self-potential (SP) geophysical method may allow for the detection of hydraulically active fractures and provide information about fracture properties. However, a lack of suitable numerical tools for modeling streaming potentials in fractured media prevents quantitative interpretation and limits our understanding of how the SP method can be used in this regard. To address this issue, we present a highly efficient two-dimensional discrete-dual-porosity approach for solving the fluid flow and associated self-potential problems in fractured rock. Our approach is specifically designed for complex fracture networks that cannot be investigated using standard numerical methods. We then simulate SP signals associated with pumping conditions for a number of examples to show that (i) accounting for matrix fluid flow is essential for accurate SP modeling and (ii) the sensitivity of SP to hydraulically active fractures is intimately linked with fracture-matrix fluid interactions. This implies that fractures associated with strong SP amplitudes are likely to be hydraulically conductive, attracting fluid flow from the surrounding matrix.

Surrogate-based optimization of hydraulic fracturing in pre-existing fracture networks

NASA Astrophysics Data System (ADS)

Chen, Mingjie; Sun, Yunwei; Fu, Pengcheng; Carrigan, Charles R.; Lu, Zhiming; Tong, Charles H.; Buscheck, Thomas A.

2013-08-01

Hydraulic fracturing has been used widely to stimulate production of oil, natural gas, and geothermal energy in formations with low natural permeability. Numerical optimization of fracture stimulation often requires a large number of evaluations of objective functions and constraints from forward hydraulic fracturing models, which are computationally expensive and even prohibitive in some situations. Moreover, there are a variety of uncertainties associated with the pre-existing fracture distributions and rock mechanical properties, which affect the optimized decisions for hydraulic fracturing. In this study, a surrogate-based approach is developed for efficient optimization of hydraulic fracturing well design in the presence of natural-system uncertainties. The fractal dimension is derived from the simulated fracturing network as the objective for maximizing energy recovery sweep efficiency. The surrogate model, which is constructed using training data from high-fidelity fracturing models for mapping the relationship between uncertain input parameters and the fractal dimension, provides fast approximation of the objective functions and constraints. A suite of surrogate models constructed using different fitting methods is evaluated and validated for fast predictions. Global sensitivity analysis is conducted to gain insights into the impact of the input variables on the output of interest, and further used for parameter screening. The high efficiency of the surrogate-based approach is demonstrated for three optimization scenarios with different and uncertain ambient conditions. Our results suggest the critical importance of considering uncertain pre-existing fracture networks in optimization studies of hydraulic fracturing.

Recombinant human parathyroid hormone (PTH 1-34) and low-intensity pulsed ultrasound have contrasting additive effects during fracture healing.

PubMed

Warden, Stuart J; Komatsu, David E; Rydberg, Johanna; Bond, Julie L; Hassett, Sean M

2009-03-01

Fracture healing is thought to be naturally optimized; however, recent evidence indicates that it may be manipulated to occur at a faster rate. This has implications for the duration of morbidity associated with bone injuries. Two interventions found to accelerate fracture healing processes are recombinant human parathyroid hormone [1-34] (PTH) and low-intensity pulsed ultrasound (LIPUS). This study aimed to investigate the individual and combined effects of PTH and LIPUS on fracture healing. Bilateral midshaft femur fractures were created in Sprague-Dawley rats, and the animals treated 7 days/week with PTH (10 microg/kg) or a vehicle solution. Each animal also had one fracture treated for 20 min/day with active-LIPUS (spatial-averaged, temporal-averaged intensity [I(SATA)]=100 mW/cm(2)) and the contralateral fracture treated with inactive-LIPUS (placebo). Femurs were harvested 35 days following injury to permit micro-computed tomography, mechanical property and histological assessments of the fracture calluses. There were no interactions between PTH and LIPUS indicating that their effects were additive rather than synergistic. These additive effects were contrasting with LIPUS primarily increasing total callus volume (TV) without influencing bone mineral content (BMC), and PTH having the opposite effect of increasing BMC without influencing TV. As a consequence of the effect of LIPUS on TV but not BMC, it decreased volumetric bone mineral density (vBMD) resulting in a less mature callus. The decreased maturity and persistence of cartilage at the fracture site when harvested offset any beneficial mechanical effects of the increased callus size with LIPUS. In contrast, the effect of PTH on callus BMC but not TV resulted in increased callus vBMD and a more mature callus. This resulted in PTH increasing fracture site mechanical strength and stiffness. These data suggest that PTH may have utility in the treatment of acute bone fractures, whereas LIPUS at an I(SATA) of 100 mW/cm(2) does not appear to be indicated in the management of closed, diaphyseal fractures.

Multi-scale modeling of microstructure dependent intergranular brittle fracture using a quantitative phase-field based method

DOE PAGES

Chakraborty, Pritam; Zhang, Yongfeng; Tonks, Michael R.

2015-12-07

In this study, the fracture behavior of brittle materials is strongly influenced by their underlying microstructure that needs explicit consideration for accurate prediction of fracture properties and the associated scatter. In this work, a hierarchical multi-scale approach is pursued to model microstructure sensitive brittle fracture. A quantitative phase-field based fracture model is utilized to capture the complex crack growth behavior in the microstructure and the related parameters are calibrated from lower length scale atomistic simulations instead of engineering scale experimental data. The workability of this approach is demonstrated by performing porosity dependent intergranular fracture simulations in UO 2 and comparingmore » the predictions with experiments.« less

Multi-scale modeling of microstructure dependent intergranular brittle fracture using a quantitative phase-field based method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chakraborty, Pritam; Zhang, Yongfeng; Tonks, Michael R.

In this study, the fracture behavior of brittle materials is strongly influenced by their underlying microstructure that needs explicit consideration for accurate prediction of fracture properties and the associated scatter. In this work, a hierarchical multi-scale approach is pursued to model microstructure sensitive brittle fracture. A quantitative phase-field based fracture model is utilized to capture the complex crack growth behavior in the microstructure and the related parameters are calibrated from lower length scale atomistic simulations instead of engineering scale experimental data. The workability of this approach is demonstrated by performing porosity dependent intergranular fracture simulations in UO 2 and comparingmore » the predictions with experiments.« less

Cubic law with aperture-length correlation: implications for network scale fluid flow

NASA Astrophysics Data System (ADS)

Klimczak, Christian; Schultz, Richard A.; Parashar, Rishi; Reeves, Donald M.

2010-06-01

Previous studies have computed and modeled fluid flow through fractured rock with the parallel plate approach where the volumetric flow per unit width normal to the direction of flow is proportional to the cubed aperture between the plates, referred to as the traditional cubic law. When combined with the square root relationship of displacement to length scaling of opening-mode fractures, total flow rates through natural opening-mode fractures are found to be proportional to apertures to the fifth power. This new relationship was explored by examining a suite of flow simulations through fracture networks using the discrete fracture network model (DFN). Flow was modeled through fracture networks with the same spatial distribution of fractures for both correlated and uncorrelated fracture length-to-aperture relationships. Results indicate that flow rates are significantly higher for correlated DFNs. Furthermore, the length-to-aperture relations lead to power-law distributions of network hydraulic conductivity which greatly influence equivalent permeability tensor values. These results confirm the importance of the correlated square root relationship of displacement to length scaling for total flow through natural opening-mode fractures and, hence, emphasize the role of these correlations for flow modeling.

A novel computer algorithm for modeling and treating mandibular fractures: A pilot study.

PubMed

Rizzi, Christopher J; Ortlip, Timothy; Greywoode, Jewel D; Vakharia, Kavita T; Vakharia, Kalpesh T

2017-02-01

To describe a novel computer algorithm that can model mandibular fracture repair. To evaluate the algorithm as a tool to model mandibular fracture reduction and hardware selection. Retrospective pilot study combined with cross-sectional survey. A computer algorithm utilizing Aquarius Net (TeraRecon, Inc, Foster City, CA) and Adobe Photoshop CS6 (Adobe Systems, Inc, San Jose, CA) was developed to model mandibular fracture repair. Ten different fracture patterns were selected from nine patients who had already undergone mandibular fracture repair. The preoperative computed tomography (CT) images were processed with the computer algorithm to create virtual images that matched the actual postoperative three-dimensional CT images. A survey comparing the true postoperative image with the virtual postoperative images was created and administered to otolaryngology resident and attending physicians. They were asked to rate on a scale from 0 to 10 (0 = completely different; 10 = identical) the similarity between the two images in terms of the fracture reduction and fixation hardware. Ten mandible fracture cases were analyzed and processed. There were 15 survey respondents. The mean score for overall similarity between the images was 8.41 ± 0.91; the mean score for similarity of fracture reduction was 8.61 ± 0.98; and the mean score for hardware appearance was 8.27 ± 0.97. There were no significant differences between attending and resident responses. There were no significant differences based on fracture location. This computer algorithm can accurately model mandibular fracture repair. Images created by the algorithm are highly similar to true postoperative images. The algorithm can potentially assist a surgeon planning mandibular fracture repair. 4. Laryngoscope, 2016 127:331-336, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Flow and fracture behavior of aluminum alloy 6082-T6 at different tensile strain rates and triaxialities

PubMed Central

Chen, Xuanzhen; Peng, Shan; Yao, Song; Chen, Chao; Xu, Ping

2017-01-01

This study aims to investigate the flow and fracture behavior of aluminum alloy 6082-T6 (AA6082-T6) at different strain rates and triaxialities. Two groups of Charpy impact tests were carried out to further investigate its dynamic impact fracture property. A series of tensile tests and numerical simulations based on finite element analysis (FEA) were performed. Experimental data on smooth specimens under various strain rates ranging from 0.0001~3400 s-1 shows that AA6082-T6 is rather insensitive to strain rates in general. However, clear rate sensitivity was observed in the range of 0.001~1 s-1 while such a characteristic is counteracted by the adiabatic heating of specimens under high strain rates. A Johnson-Cook constitutive model was proposed based on tensile tests at different strain rates. In this study, the average stress triaxiality and equivalent plastic strain at facture obtained from numerical simulations were used for the calibration of J-C fracture model. Both of the J-C constitutive model and fracture model were employed in numerical simulations and the results was compared with experimental results. The calibrated J-C fracture model exhibits higher accuracy than the J-C fracture model obtained by the common method in predicting the fracture behavior of AA6082-T6. Finally, the Scanning Electron Microscope (SEM) of fractured specimens with different initial stress triaxialities were analyzed. The magnified fractographs indicate that high initial stress triaxiality likely results in dimple fracture. PMID:28759617

The Shear Mechanisms of Natural Fractures during the Hydraulic Stimulation of Shale Gas Reservoirs.

PubMed

Zhang, Zhaobin; Li, Xiao

2016-08-23

The shearing of natural fractures is important in the permeability enhancement of shale gas reservoirs during hydraulic fracturing treatment. In this work, the shearing mechanisms of natural fractures are analyzed using a newly proposed numerical model based on the displacement discontinuities method. The fluid-rock coupling system of the model is carefully designed to calculate the shearing of fractures. Both a single fracture and a complex fracture network are used to investigate the shear mechanisms. The investigation based on a single fracture shows that the non-ignorable shearing length of a natural fracture could be formed before the natural fracture is filled by pressurized fluid. Therefore, for the hydraulic fracturing treatment of the naturally fractured shale gas reservoirs, the shear strength of shale is generally more important than the tensile strength. The fluid-rock coupling propagation processes of a complex fracture network are simulated under different crustal stress conditions and the results agree well with those of the single fracture. The propagation processes of complex fracture network show that a smaller crustal stress difference is unfavorable to the shearing of natural fractures, but is favorable to the formation of complex fracture network.

The Shear Mechanisms of Natural Fractures during the Hydraulic Stimulation of Shale Gas Reservoirs

PubMed Central

Zhang, Zhaobin; Li, Xiao

2016-01-01

The shearing of natural fractures is important in the permeability enhancement of shale gas reservoirs during hydraulic fracturing treatment. In this work, the shearing mechanisms of natural fractures are analyzed using a newly proposed numerical model based on the displacement discontinuities method. The fluid-rock coupling system of the model is carefully designed to calculate the shearing of fractures. Both a single fracture and a complex fracture network are used to investigate the shear mechanisms. The investigation based on a single fracture shows that the non-ignorable shearing length of a natural fracture could be formed before the natural fracture is filled by pressurized fluid. Therefore, for the hydraulic fracturing treatment of the naturally fractured shale gas reservoirs, the shear strength of shale is generally more important than the tensile strength. The fluid-rock coupling propagation processes of a complex fracture network are simulated under different crustal stress conditions and the results agree well with those of the single fracture. The propagation processes of complex fracture network show that a smaller crustal stress difference is unfavorable to the shearing of natural fractures, but is favorable to the formation of complex fracture network. PMID:28773834

Development of a new semi-analytical model for cross-borehole flow experiments in fractured media

USGS Publications Warehouse

Roubinet, Delphine; Irving, James; Day-Lewis, Frederick D.

2015-01-01

Analysis of borehole flow logs is a valuable technique for identifying the presence of fractures in the subsurface and estimating properties such as fracture connectivity, transmissivity and storativity. However, such estimation requires the development of analytical and/or numerical modeling tools that are well adapted to the complexity of the problem. In this paper, we present a new semi-analytical formulation for cross-borehole flow in fractured media that links transient vertical-flow velocities measured in one or a series of observation wells during hydraulic forcing to the transmissivity and storativity of the fractures intersected by these wells. In comparison with existing models, our approach presents major improvements in terms of computational expense and potential adaptation to a variety of fracture and experimental configurations. After derivation of the formulation, we demonstrate its application in the context of sensitivity analysis for a relatively simple two-fracture synthetic problem, as well as for field-data analysis to investigate fracture connectivity and estimate fracture hydraulic properties. These applications provide important insights regarding (i) the strong sensitivity of fracture property estimates to the overall connectivity of the system; and (ii) the non-uniqueness of the corresponding inverse problem for realistic fracture configurations.

Quartz c-axis orientation patterns in fracture cement as a measure of fracture opening rate and a validation tool for fracture pattern models

DOE PAGES

Ukar, Estibalitz; Laubach, Stephen E.; Marrett, Randall

2016-03-09

Here, we evaluate a published model for crystal growth patterns in quartz cement in sandstone fractures by comparing crystal fracture-spanning predictions to quartz c-axis orientation distributions measured by electron backscatter diffraction (EBSD) of spanning quartz deposits. Samples from eight subvertical opening-mode fractures in four sandstone formations, the Jurassic– Cretaceous Nikanassin Formation, northwestern Alberta Foothills (Canada), Cretaceous Mesaverde Group (USA; Cozzette Sandstone Member of the Iles Formation), Piceance Basin, Colorado (USA), and upper Jurassic–lower Cretaceous Cotton Valley Group (Taylor sandstone) and overlying Travis Peak Formation, east Texas, have similar quartzose composition and grain size but contain fractures with different temperature historiesmore » and opening rates based on fluid inclusion assemblages and burial history. Spherical statistical analysis shows that, in agreement with model predictions, bridging crystals have a preferred orientation with c-axis orientations at a high angle to fracture walls. The second form of validation is for spanning potential that depends on the size of cut substrate grains. Using measured cut substrate grain sizes and c-axis orientations of spanning bridges, we calculated the required orientation for the smallest cut grain to span the maximum gap size and the required orientation of the crystal with the least spanning potential to form overgrowths that span across maximum measured gap sizes. We find that within a 10° error all spanning crystals conform to model predictions. Using crystals with the lowest spanning potential based on crystallographic orientation (c-axis parallel to fracture wall) and a temperature range for fracture opening measured from fluid inclusion assemblages, we calculate maximum fracture opening rates that allow crystals to span. These rates are comparable to those derived independently from fracture temperature histories based on burial history and multiple sequential fluid inclusion assemblages. Results support the R. Lander and S. Laubach model, which predicts that for quartz deposited synchronously with fracture opening, spanning potential, or likelihood of quartz deposits that are thick enough to span between fracture walls, depends on temperature history, fracture opening rate, size of opening increments, and size, mineralogy, and crystallographic orientation of substrates in the fracture wall (transected grains). Results suggest that EBSD maps, which can be more rapidly acquired than measurement of tens to hundreds of fluid inclusion assemblages, can provide a useful measure of relative opening rates within populations of quartz-filled fractures formed under sedimentary basin conditions. Such data are useful for evaluating fracture pattern development models.« less

Quartz c-axis orientation patterns in fracture cement as a measure of fracture opening rate and a validation tool for fracture pattern models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ukar, Estibalitz; Laubach, Stephen E.; Marrett, Randall

Here, we evaluate a published model for crystal growth patterns in quartz cement in sandstone fractures by comparing crystal fracture-spanning predictions to quartz c-axis orientation distributions measured by electron backscatter diffraction (EBSD) of spanning quartz deposits. Samples from eight subvertical opening-mode fractures in four sandstone formations, the Jurassic– Cretaceous Nikanassin Formation, northwestern Alberta Foothills (Canada), Cretaceous Mesaverde Group (USA; Cozzette Sandstone Member of the Iles Formation), Piceance Basin, Colorado (USA), and upper Jurassic–lower Cretaceous Cotton Valley Group (Taylor sandstone) and overlying Travis Peak Formation, east Texas, have similar quartzose composition and grain size but contain fractures with different temperature historiesmore » and opening rates based on fluid inclusion assemblages and burial history. Spherical statistical analysis shows that, in agreement with model predictions, bridging crystals have a preferred orientation with c-axis orientations at a high angle to fracture walls. The second form of validation is for spanning potential that depends on the size of cut substrate grains. Using measured cut substrate grain sizes and c-axis orientations of spanning bridges, we calculated the required orientation for the smallest cut grain to span the maximum gap size and the required orientation of the crystal with the least spanning potential to form overgrowths that span across maximum measured gap sizes. We find that within a 10° error all spanning crystals conform to model predictions. Using crystals with the lowest spanning potential based on crystallographic orientation (c-axis parallel to fracture wall) and a temperature range for fracture opening measured from fluid inclusion assemblages, we calculate maximum fracture opening rates that allow crystals to span. These rates are comparable to those derived independently from fracture temperature histories based on burial history and multiple sequential fluid inclusion assemblages. Results support the R. Lander and S. Laubach model, which predicts that for quartz deposited synchronously with fracture opening, spanning potential, or likelihood of quartz deposits that are thick enough to span between fracture walls, depends on temperature history, fracture opening rate, size of opening increments, and size, mineralogy, and crystallographic orientation of substrates in the fracture wall (transected grains). Results suggest that EBSD maps, which can be more rapidly acquired than measurement of tens to hundreds of fluid inclusion assemblages, can provide a useful measure of relative opening rates within populations of quartz-filled fractures formed under sedimentary basin conditions. Such data are useful for evaluating fracture pattern development models.« less

Human growth hormone may be detrimental when used to accelerate recovery from acute tendon-bone interface injuries.

PubMed

Baumgarten, Keith M; Oliver, Harvey A; Foley, Jack; Chen, Ding-Geng; Autenried, Peter; Duan, Shanzhong; Heiser, Patrick

2013-05-01

There have been few scientific studies that have examined usage of human growth hormone to accelerate recovery from injury. The hypothesis of this study was that human growth hormone would accelerate tendon-to-bone healing compared with control animals treated with placebo in a rat model of acute rotator cuff injury repair. Seventy-two rats underwent repair of acute rotator cuff injuries and were randomized into the following postoperative dosing regimens: placebo, and human growth hormone at 0.1, 1, 2, 5, and 10 mg/kg/day, administered subcutaneously once per day for fourteen days (Protocol 1). An additional twenty-four rats were randomized to receive either (1) placebo or (2) human growth hormone at 5 mg/kg, administered subcutaneously twice per day for seven days preoperatively and twenty-eight days postoperatively (Protocol 2). All rats were killed twenty-eight days postoperatively. Mechanical testing was performed. Ultimate stress, ultimate force, stiffness, energy to failure, and ultimate distension were determined. For Protocol 1, analysis of variance testing showed no significant difference between the groups with regard to ultimate stress, ultimate force, stiffness, energy to failure, or ultimate distension. In Protocol 2, ultimate force to failure was significantly worse in the human growth hormone group compared with the placebo group (21.1 ± 5.85 versus 26.3 ± 5.47 N; p = 0.035). Failure was more likely to occur through the bone than the tendon-bone interface in the human growth hormone group compared with the placebo group (p = 0.001). No significant difference was found for ultimate stress, ultimate force, stiffness, energy to failure, or ultimate distension between the groups in Protocol 2. In this rat model of acute tendon-bone injury repair, daily subcutaneous postoperative human growth hormone treatment for fourteen days failed to demonstrate a significant difference in any biomechanical parameter compared with placebo. Furthermore, subcutaneous administration of 5 mg/kg of human growth hormone twice daily from seven days preoperatively until twenty-eight days postoperatively demonstrated lower loads to ultimate failure and a higher risk of bone fracture failure compared with placebo.

Effects of Trigonelline, an Alkaloid Present in Coffee, on Diabetes-Induced Disorders in the Rat Skeletal System.

PubMed

Folwarczna, Joanna; Janas, Aleksandra; Pytlik, Maria; Cegieła, Urszula; Śliwiński, Leszek; Krivošíková, Zora; Štefíková, Kornélia; Gajdoš, Martin

2016-03-02

Diabetes increases bone fracture risk. Trigonelline, an alkaloid with potential antidiabetic activity, is present in considerable amounts in coffee. The aim of the study was to investigate the effects of trigonelline on experimental diabetes-induced disorders in the rat skeletal system. Effects of trigonelline (50 mg/kg p.o. daily for four weeks) were investigated in three-month-old female Wistar rats, which, two weeks before the start of trigonelline administration, received streptozotocin (60 mg/kg i.p.) or streptozotocin after nicotinamide (230 mg/kg i.p.). Serum bone turnover markers, bone mineralization, and mechanical properties were studied. Streptozotocin induced diabetes, with significant worsening of bone mineralization and bone mechanical properties. Streptozotocin after nicotinamide induced slight glycemia increases in first days of experiment only, however worsening of cancellous bone mechanical properties and decreased vertebral bone mineral density (BMD) were demonstrated. Trigonelline decreased bone mineralization and tended to worsen bone mechanical properties in streptozotocin-induced diabetic rats. In nicotinamide/streptozotocin-treated rats, trigonelline significantly increased BMD and tended to improve cancellous bone strength. Trigonelline differentially affected the skeletal system of rats with streptozotocin-induced metabolic disorders, intensifying the osteoporotic changes in streptozotocin-treated rats and favorably affecting bones in the non-hyperglycemic (nicotinamide/streptozotocin-treated) rats. The results indicate that, in certain conditions, trigonelline may damage bone.

Biomechanical comparison of straight and helical compression plates for fixation of transverse and oblique bone fractures: Modeling and experiments.

PubMed

Sezek, Sinan; Aksakal, Bunyamin; Gürger, Murat; Malkoc, Melih; Say, Y

2016-08-12

Total deformation and stability of straight and helical compression plates were studied by means of the finite element method (FEM) and in vitro biomechanical experiments. Fixations of transverse (TF) and oblique (45°) bone (OF) fractures have been analyzed on sheep tibias by designing the straight compression (SP) and Helical Compression Plate (HP) models. The effects of axial compression, bending and torsion loads on both plating systems were analyzed in terms of total displacements. Numerical models and experimental models suggested that under compression loadings, bone fracture gap closures for both fracture types were found to be in the favor of helical plate designs. The helical plate (HP) fixations provided maximum torsional resistance compared to the (SP) fixations. The fracture gap closure and stability of helical plate fixation for transverse fractures was determined to be higher than that found for the oblique fractures. The comparison of average compression stress, bending and torsion moments showed that the FEM and experimental results are in good agreement and such designs are likely to have a positive impact in future bone fracture fixation designs.

An interface finite element model can be used to predict healing outcome of bone fractures.

PubMed

Alierta, J A; Pérez, M A; García-Aznar, J M

2014-01-01

After fractures, bone can experience different potential outcomes: successful bone consolidation, non-union and bone failure. Although, there are a lot of factors that influence fracture healing, experimental studies have shown that the interfragmentary movement (IFM) is one of the main regulators for the course of bone healing. In this sense, computational models may help to improve the development of mechanical-based treatments for bone fracture healing. Hence, based on this fact, we propose a combined repair-failure mechanistic computational model to describe bone fracture healing. Despite being a simple model, it is able to correctly estimate the time course evolution of the IFM compared to in vivo measurements under different mechanical conditions. Therefore, this mathematical approach is especially suitable for modeling the healing response of bone to fractures treated with different mechanical fixators, simulating realistic clinical conditions. This model will be a useful tool to identify factors and define targets for patient specific therapeutics interventions. © 2013 Published by Elsevier Ltd.

Avalanche weak layer shear fracture parameters from the cohesive crack model

NASA Astrophysics Data System (ADS)

McClung, David

2014-05-01

Dry slab avalanches release by mode II shear fracture within thin weak layers under cohesive snow slabs. The important fracture parameters include: nominal shear strength, mode II fracture toughness and mode II fracture energy. Alpine snow is not an elastic material unless the rate of deformation is very high. For natural avalanche release, it would not be possible that the fracture parameters can be considered as from classical fracture mechanics from an elastic framework. The strong rate dependence of alpine snow implies that it is a quasi-brittle material (Bažant et al., 2003) with an important size effect on nominal shear strength. Further, the rate of deformation for release of an avalanche is unknown, so it is not possible to calculate the fracture parameters for avalanche release from any model which requires the effective elastic modulus. The cohesive crack model does not require the modulus to be known to estimate the fracture energy. In this paper, the cohesive crack model was used to calculate the mode II fracture energy as a function of a brittleness number and nominal shear strength values calculated from slab avalanche fracture line data (60 with natural triggers; 191 with a mix of triggers). The brittleness number models the ratio of the approximate peak value of shear strength to nominal shear strength. A high brittleness number (> 10) represents large size relative to fracture process zone (FPZ) size and the implications of LEFM (Linear Elastic Fracture Mechanics). A low brittleness number (e.g. 0.1) represents small sample size and primarily plastic response. An intermediate value (e.g. 5) implies non-linear fracture mechanics with intermediate relative size. The calculations also implied effective values for the modulus and the critical shear fracture toughness as functions of the brittleness number. The results showed that the effective mode II fracture energy may vary by two orders of magnitude for alpine snow with median values ranging from 0.08 N/m (non-linear) to 0.18 N/m (LEFM) for median slab density around 200 kg/m3. Schulson and Duval (2009) estimated the fracture energy of solid ice (mode I) to be about 0.22-1 N/m which yields rough theoretical limits of about 0.05- 0.2 N/m for density 200 kg/m3 when the ice volume fraction is accounted for. Mode I results from lab tests (Sigrist, 2006) gave 0.1 N/m (200 kg/m3). The median effective mode II shear fracture toughness was calculated between 0.31 to 0.35 kPa(m)1/2 for the avalanche data. All the fracture energy results are much lower than previously calculated from propagation saw tests (PST) results for a weak layer collapse model (1.3 N/m) (Schweizer et al., 2011). The differences are related to model assumptions and estimates of the effective slab modulus. The calculations in this paper apply to quasi-static deformation and mode II weak layer fracture whereas the weak layer collapse model is more appropriate for dynamic conditions which follow fracture initiation (McClung and Borstad, 2012). References: Bažant, Z.P. et al. (2003) Size effect law and fracture mechanics of the triggering of dry snow slab avalanches, J. Geophys. Res. 108(B2): 2119, doi:10.1029/2002JB))1884.2003. McClung, D.M. and C.P. Borstad (2012) Deformation and energy of dry snow slabs prior to fracture propagation, J. Glaciol. 58(209), 2012 doi:10.3189/2012JoG11J009. Schulson, E.M and P. Duval (2009) Creep and fracture of ice, Cambridge University Press, 401 pp. Schweizer, J. et al. (2011) Measurements of weak layer fracture energy, Cold Reg. Sci. and Tech. 69: 139-144. Sigrist, C. (2006) Measurement of fracture mechanical properties of snow and application to dry snow slab avalanche release, Ph.D thesis: 16736, ETH, Zuerich: 139 pp.

Numerical investigations of rib fracture failure models in different dynamic loading conditions.

PubMed

Wang, Fang; Yang, Jikuang; Miller, Karol; Li, Guibing; Joldes, Grand R; Doyle, Barry; Wittek, Adam

2016-01-01

Rib fracture is one of the most common thoracic injuries in vehicle traffic accidents that can result in fatalities associated with seriously injured internal organs. A failure model is critical when modelling rib fracture to predict such injuries. Different rib failure models have been proposed in prediction of thorax injuries. However, the biofidelity of the fracture failure models when varying the loading conditions and the effects of a rib fracture failure model on prediction of thoracic injuries have been studied only to a limited extent. Therefore, this study aimed to investigate the effects of three rib failure models on prediction of thoracic injuries using a previously validated finite element model of the human thorax. The performance and biofidelity of each rib failure model were first evaluated by modelling rib responses to different loading conditions in two experimental configurations: (1) the three-point bending on the specimen taken from rib and (2) the anterior-posterior dynamic loading to an entire bony part of the rib. Furthermore, the simulation of the rib failure behaviour in the frontal impact to an entire thorax was conducted at varying velocities and the effects of the failure models were analysed with respect to the severity of rib cage damages. Simulation results demonstrated that the responses of the thorax model are similar to the general trends of the rib fracture responses reported in the experimental literature. However, they also indicated that the accuracy of the rib fracture prediction using a given failure model varies for different loading conditions.

The role of local stress perturbation on the simultaneous opening of orthogonal fractures

NASA Astrophysics Data System (ADS)

Boersma, Quinten; Hardebol, Nico; Barnhoorn, Auke; Bertotti, Giovanni; Drury, Martyn

2016-04-01

Orthogonal fracture networks (ladder-like networks) are arrangements that are commonly observed in outcrop studies. They form a particularly dense and well connected network which can play an important role in the effective permeability of tight hydrocarbon or geothermal reservoirs. One issue is the extent to which both the long systematic and smaller cross fractures can be simultaneously critically stressed under a given stress condition. Fractures in an orthogonal network form by opening mode-I displacements in which the main component is separation of the two fracture walls. This opening is driven by effective tensile stresses as the smallest principle stress acting perpendicular to the fracture wall, which accords with linear elastic fracture mechanics. What has been well recognized in previous field and modelling studies is how both the systematic fractures and perpendicular cross fractures require the minimum principle stress to act perpendicular to the fracture wall. Thus, these networks either require a rotation of the regional stress field or local perturbations in stress field. Using a mechanical finite element modelling software, a geological case of layer perpendicular systematic mode I opening fractures is generated. New in our study is that we not only address tensile stresses at the boundary, but also address models using pore fluid pressure. The local stress in between systematic fractures is then assessed in order to derive the probability and orientation of micro crack propagation using the theory of sub critical crack growth and Griffith's theory. Under effective tensile conditions, the results indicate that in between critically spaced systematic fractures, local effective tensile stresses flip. Therefore the orientation of the least principle stress will rotate 90°, hence an orthogonal fracture is more likely to form. Our new findings for models with pore fluid pressures instead of boundary tension show that the magnitude of effective tension in between systematic fractures is reduced but does not remove the occurring stress flip. However, putting effective tension on the boundaries will give overestimates in the reduction of the local effective tensile stress perpendicular to the larger systematic fractures and therefore the magnitude of the stress flip. In conclusion, both model approaches indicate that orthogonal fractures can form while experiencing one regional stress regime. This also means that under these specific loading and locally perturbed stress conditions both sets of orthogonal fractures stay open and can provide a pathway for fluid circulation.

Multi-scale Fracture Patterns Associated with a Complex Anticline Structure: Insights from Field Outcrop Analogues of the Jebel Hafit Pericline, Al Ain-UAE

NASA Astrophysics Data System (ADS)

Kokkalas, S.; Jones, R. R.; Long, J. J.; Zampos, M.; Wilkinson, M. W.; Gilment, S.

2017-12-01

The formation of folds and their associated fracture patterns plays an important role in controlling the migration and concentration of fluids within the upper crust. Prediction of fracture patterns from various fold shapes and kinematics still remains poorly understood in terms of spatial and temporal distribution of fracture sets. Thus, a more detailed field-based multi scale approach is required to better constrain 3D models of fold-fracture relationships, which are critical for reservoir characterization studies. In order to generate reservoir-scale fracture models representative fracture properties across a wider range of scales are needed. For this reason we applied modern geospatial technologies, including terrestrial LiDAR, photogrammetry and satellite images in the asymmetric, east verging, four-way closure Jebel Hafit anticline, in the eastern part of the United Arab Emirates. The excellent surface outcrops allowed the rapid acquisition of extensive areas of fracture data from both limbs and fold hinge area of the anticline, even from large areas of steep exposure that are practically inaccessible on foot. The digital outcrops provide longer 1D transects, and 2D or 3D surface datasets and give more robust data, particularly for fracture heights, lengths, spacing, clustering, termination and connectivity. The fracture patterns across the folded structure are more complex than those predicted from conceptual models and geomechanical fracture modeling. Mechanical layering, pre-existing structures and sedimentation during fold growth seem to exert a critical influence in the development of fracture systems within Jebel Hafit anticline and directly affect fracture orientations, spacing/intensity, segmentation and connectivity. Seismic and borehole data provide additional constraints on the sub-surface fold geometry and existence of large-scale thrusting in the core of the anticline. The complexity of the relationship between fold geometry and fracture intensity is presented and the implications for prediction of fracture networks in naturally fractured reservoirs are discussed.

A Fracture-Mechanical Model of Crack Growth and Interaction: Application to Pre-eruptive Seismicity

NASA Astrophysics Data System (ADS)

Matthews, C.; Sammonds, P.; Kilburn, C.

2007-12-01

A greater understanding of the physical processes occurring within a volcano is a key aspect in the success of eruption forecasting. By considering the role of fracture growth, interaction and coalescence in the formation of dykes and conduits as well as the source mechanism for observed seismicity we can create a more general, more applicable model for precursory seismicity. The frequency of volcano-tectonic earthquakes, created by fracturing of volcanic rock, often shows a short-term increase prior to eruption. Using fracture mechanics, the model presented here aims to determine the conditions necessary for the acceleration in fracture events which produces the observed pre-eruptive seismicity. By focusing on the cause of seismic events rather than simply the acceleration patterns observed, the model also highlights the distinction between an accelerating seismic sequence ending with an eruption and a short-term increase which returns to background levels with no activity occurring, an event also observed in the field and an important capability if false alarms are to be avoided. This 1-D model explores the effects of a surrounding stress field and the distribution of multi-scale cracks on the interaction and coalescence of these cracks to form an open pathway for magma ascent. Similarly to seismic observations in the field, and acoustic emissions data from the laboratory, exponential and hyperbolic accelerations in fracturing events are recorded. Crack distribution and inter-crack distance appears to be a significant controlling factor on the evolution of the fracture network, dominating over the effects of a remote stress field. The generality of the model and its basis on fundamental fracture mechanics results makes it applicable to studies of fracture networks in numerous situations. For example looking at the differences between high temperature fracture processes and purely brittle failure the model can be similarly applied to fracture dynamics in the edifice of a long repose volcano and a lava dome.

Predicting bulk permeability using outcrop fracture attributes: The benefits of a Maximum Likelihood Estimator

NASA Astrophysics Data System (ADS)

Rizzo, R. E.; Healy, D.; De Siena, L.

2015-12-01

The success of any model prediction is largely dependent on the accuracy with which its parameters are known. In characterising fracture networks in naturally fractured rocks, the main issues are related with the difficulties in accurately up- and down-scaling the parameters governing the distribution of fracture attributes. Optimal characterisation and analysis of fracture attributes (fracture lengths, apertures, orientations and densities) represents a fundamental step which can aid the estimation of permeability and fluid flow, which are of primary importance in a number of contexts ranging from hydrocarbon production in fractured reservoirs and reservoir stimulation by hydrofracturing, to geothermal energy extraction and deeper Earth systems, such as earthquakes and ocean floor hydrothermal venting. This work focuses on linking fracture data collected directly from outcrops to permeability estimation and fracture network modelling. Outcrop studies can supplement the limited data inherent to natural fractured systems in the subsurface. The study area is a highly fractured upper Miocene biosiliceous mudstone formation cropping out along the coastline north of Santa Cruz (California, USA). These unique outcrops exposes a recently active bitumen-bearing formation representing a geological analogue of a fractured top seal. In order to validate field observations as useful analogues of subsurface reservoirs, we describe a methodology of statistical analysis for more accurate probability distribution of fracture attributes, using Maximum Likelihood Estimators. These procedures aim to understand whether the average permeability of a fracture network can be predicted reducing its uncertainties, and if outcrop measurements of fracture attributes can be used directly to generate statistically identical fracture network models.

Effects of infrared laser on the bone repair assessed by x-ray microtomography (μct) and histomorphometry

NASA Astrophysics Data System (ADS)

Paolillo, Alessandra Rossi; Paolillo, Fernanda Rossi; da Silva, Alessandro M. Hakme; Reiff, Rodrigo Bezerra de Menezes; Bagnato, Vanderlei Salvador; Alves, José Marcos

2015-06-01

The bone fracture is important public health problems. The lasertherapy is used to accelerate tissue healing. Regarding diagnosis, few methods are validated to follow the evolution of bone microarchitecture. The aim of this study was to evaluate the effects of lasertherapy on bone repair with x-ray microtomography (μCT) and histomorphometry. A transverse rat tibia osteotomy with a Kirchner wire and a 2mm width polymeric spacer beads were used to produce a delayed bone union. Twelve rats were divided into two groups: (i) Control Group: untreated fracture and; (ii) Laser Group: fracture treated with laser. Twelve sessions of treatment (808nm laser, 100mW, 125J/cm2, 50seconds) were performed. The μCT scanner parameters were: 100kV, 100μA, Al+Cu filter and 9.92μm resolution. A volume of interest (VOI) was chosen with 300 sections above and below the central region of the fracture, totaling 601sections with a 5.96mm. The softwares CT-Analyzer, NRecon and Mimics were used for 2D and 3D analysis. A histomorphometry analysis was also performed. The connectivity (Conn) showed significant increase for Laser Group than Control Group (32371+/-20689 vs 17216+/-9467, p<0.05). There was no significant difference for bone volume (59+/-19mm3 vs 47+/- 8mm3) and histomorfometric data [Laser and Control Groups showed greater amount of cartilaginous (0.19+/-0.05% vs 0.11+/-0.09%) and fibrotic (0.21+/-0.12% vs 0.09+/-0.11%) tissues]. The negative effect was presence of the cartilaginous and fibrotic tissues which may be related to the Kirchner wire and the non-absorption of the polymeric that may have influenced negatively the light distribution through the bone. However, the positive effect was greater bone connectivity, indicating improvement in bone microarchitecture.

Modelling DC responses of 3D complex fracture networks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beskardes, Gungor Didem; Weiss, Chester Joseph

Here, the determination of the geometrical properties of fractures plays a critical role in many engineering problems to assess the current hydrological and mechanical states of geological media and to predict their future states. However, numerical modeling of geoelectrical responses in realistic fractured media has been challenging due to the explosive computational cost imposed by the explicit discretizations of fractures at multiple length scales, which often brings about a tradeoff between computational efficiency and geologic realism. Here, we use the hierarchical finite element method to model electrostatic response of realistically complex 3D conductive fracture networks with minimal computational cost.

Modelling DC responses of 3D complex fracture networks

DOE PAGES

Beskardes, Gungor Didem; Weiss, Chester Joseph

2018-03-01

Here, the determination of the geometrical properties of fractures plays a critical role in many engineering problems to assess the current hydrological and mechanical states of geological media and to predict their future states. However, numerical modeling of geoelectrical responses in realistic fractured media has been challenging due to the explosive computational cost imposed by the explicit discretizations of fractures at multiple length scales, which often brings about a tradeoff between computational efficiency and geologic realism. Here, we use the hierarchical finite element method to model electrostatic response of realistically complex 3D conductive fracture networks with minimal computational cost.

Vertically-Integrated Dual-Continuum Models for CO2 Injection in Fractured Aquifers

NASA Astrophysics Data System (ADS)

Tao, Y.; Guo, B.; Bandilla, K.; Celia, M. A.

2017-12-01

Injection of CO2 into a saline aquifer leads to a two-phase flow system, with supercritical CO2 and brine being the two fluid phases. Various modeling approaches, including fully three-dimensional (3D) models and vertical-equilibrium (VE) models, have been used to study the system. Almost all of that work has focused on unfractured formations. 3D models solve the governing equations in three dimensions and are applicable to generic geological formations. VE models assume rapid and complete buoyant segregation of the two fluid phases, resulting in vertical pressure equilibrium and allowing integration of the governing equations in the vertical dimension. This reduction in dimensionality makes VE models computationally more efficient, but the associated assumptions restrict the applicability of VE model to formations with moderate to high permeability. In this presentation, we extend the VE and 3D models for CO2 injection in fractured aquifers. This is done in the context of dual-continuum modeling, where the fractured formation is modeled as an overlap of two continuous domains, one representing the fractures and the other representing the rock matrix. Both domains are treated as porous media continua and can be modeled by either a VE or a 3D formulation. The transfer of fluid mass between rock matrix and fractures is represented by a mass transfer function connecting the two domains. We have developed a computational model that combines the VE and 3D models, where we use the VE model in the fractures, which typically have high permeability, and the 3D model in the less permeable rock matrix. A new mass transfer function is derived, which couples the VE and 3D models. The coupled VE-3D model can simulate CO2 injection and migration in fractured aquifers. Results from this model compare well with a full-3D model in which both the fractures and rock matrix are modeled with 3D models, with the hybrid VE-3D model having significantly reduced computational cost. In addition to the VE-3D model, we explore simplifications of the rock matrix domain by using sugar-cube and matchstick conceptualizations and develop VE-dual porosity and VE-matchstick models. These vertically-integrated dual-permeability and dual-porosity models provide a range of computationally efficient tools to model CO2 storage in fractured saline aquifers.

Efficient and robust compositional two-phase reservoir simulation in fractured media

NASA Astrophysics Data System (ADS)

Zidane, A.; Firoozabadi, A.

2015-12-01

Compositional and compressible two-phase flow in fractured media has wide applications including CO2 injection. Accurate simulations are currently based on the discrete fracture approach using the cross-flow equilibrium model. In this approach the fractures and a small part of the matrix blocks are combined to form a grid cell. The major drawback is low computational efficiency. In this work we use the discrete-fracture approach to model the fractures where the fracture entities are described explicitly in the computational domain. We use the concept of cross-flow equilibrium in the fractures (FCFE). This allows using large matrix elements in the neighborhood of the fractures. We solve the fracture transport equations implicitly to overcome the Courant-Freidricks-Levy (CFL) condition in the small fracture elements. Our implicit approach is based on calculation of the derivative of the molar concentration of component i in phase (cαi ) with respect to the total molar concentration (ci ) at constant volume V and temperature T. This contributes to significant speed up of the code. The hybrid mixed finite element method (MFE) is used to solve for the velocity in both the matrix and the fractures coupled with the discontinuous Galerkin (DG) method to solve the species transport equations in the matrix, and a finite volume (FV) discretization in the fractures. In large scale problems the proposed approach is orders of magnitude faster than the existing models.

Hands-On Exercise in Environmental Structural Geology Using a Fracture Block Model.

ERIC Educational Resources Information Center

Gates, Alexander E.

2001-01-01

Describes the use of a scale analog model of an actual fractured rock reservoir to replace paper copies of fracture maps in the structural geology curriculum. Discusses the merits of the model in enabling students to gain experience performing standard structural analyses. (DDR)

A three-dimensional semianalytical model of hydraulic fracture growth through weak barriers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luiskutty, C.T.; Tomutes, L.; Palmer, I.D.

1989-08-01

The goal of this research was to develop a fracture model for length/height ratio {le}4 that includes 2D flow (and a line source corresponding to the perforated interval) but makes approximations that allow a semianalytical solution, with large computer-time savings over the fully numerical mode. The height, maximum width, and pressure at the wellbore in this semianalytical model are calculated and compared with the results of the fully three-dimensional (3D) model. There is reasonable agreement in all parameters, the maximum discrepancy being 24%. Comparisons of fracture volume and leakoff volume also show reasonable agreement in volume and fluid efficiencies. Themore » values of length/height ratio, in the four cases in which agreement is found, vary from 1.5 to 3.7. The model offers a useful first-order (or screening) calculation of fracture-height growth through weak barriers (e.g., low stress contrasts). When coupled with the model developed for highly elongated fractures of length/height ratio {ge}4, which are also found to be in basic agreement with the fully numerical model, this new model provides the capability for approximating fracture-height growth through barriers for vertical fracture shapes that vary from penny to highly elongated. The computer time required is estimated to be less than the time required for the fully numerical model by a factor of 10 or more.« less

A biomechanical comparison of four fixed-angle dorsal plates in a finite element model of dorsally-unstable radius fracture.

PubMed

Knežević, Josip; Kodvanj, Janoš; Čukelj, Fabijan; Pamuković, Frane; Pavić, Arsen

2017-11-01

To compare the finite element models of two different composite radius fracture patterns, reduced and stabilised with four different fixed-angle dorsal plates during axial, dorsal and volar loading conditions. Eight different plastic models representing four AO/ASIF type 23-A3 distal radius fractures and four AO/ASIF 23-C2 distal radius fractures were obtained and fixed each with 1 of 4 methods: a standard dorsal non-anatomical fixed angle T-plate (3.5mm Dorsal T-plate, Synthes), anatomical fixed-angle double plates (2.4mm LCP Dorsal Distal Radius, Synthes), anatomical fixed angle T-plate (2.4mm Acu-Loc Dorsal Plate, Acumed) or anatomical variable-angle dorsal T-plate (3.5mm, Dorsal Plate, Zrinski). Composite radius with plate and screws were scanned with a 3D optical scanner and later processed in Abaqus Software to generate the finite element model. All models were axially loaded at 3 points (centrally, volarly and dorsally) with 50 N forces to avoid the appearance of plastic deformations of the models. Total displacements at the end of the bone and the stresses in the bones and plates were determined and compared. Maximal von Mises stress in bone for 3-part fracture models was very similar to that in 2-part fracture models. The biggest difference between models and the largest displacements were seen during volar loading. The stresses in all models were the highest above the fracture gap. The best performance in all parameters tested was with the Zrinski plate and the most modest results were with the Synthes T-plate. There was no significant difference between 2-part (AO/ASIF type 23-A3) and 3-part (AO/ASIF 23-C2) fracture models. Maximal stresses in the plates appeared above the fracture gap; therefore, it is worth considering the development of plates without screw holes above the gap. © 2017 Elsevier Ltd. All rights reserved.

Impact of Stress on Anomalous Transport in Fractured Rock

NASA Astrophysics Data System (ADS)

Kang, P. K.; Lei, Q.; Lee, S.; Dentz, M.; Juanes, R.

2016-12-01

Fluid flow and transport in fractured rock controls many natural and engineered processes in the subsurface. However, characterizing flow and transport through fractured media is challenging due to the large heterogeneity of fractured rock properties. In addition to these "static" challenges, geologic fractures are always under significant overburden stress, and changes in the stress state can lead to changes in the fracture's ability to conduct fluids. While confining stress has been shown to impact fluid flow through fractures in a fundamental way, the impact of confining stress on transport through fractured rock remains largely unexplored. The link between anomalous (non-Fickian) transport and confining stress has been shown only recently, at the level of a single rough fracture [1]. Here, we investigate the impact of confining stress on flow and transport through discrete fracture networks. We model geomechanical effects in 2D fractured rock by means of a finite-discrete element method (FEMDEM), which can capture the deformation of matrix blocks, reactivation and propagation of cracks. We implement a joint constitutive model within the FEMDEM framework to simulate the effect of fracture roughness. We apply the model to a fracture network extracted from the geological map of an actual outcrop to obtain the aperture field at different stress conditions (Figure 1). We then simulate fluid flow and particle transport through the stressed fracture networks. We observe that anomalous transport emerges in response to confining stress on the fracture networks, and show that this anomalous behavior can be linked to the stress state of the rock. Finally, we develop an effective transport model that captures the anomalous transport through stressed fractures. Our results point to a heretofore unrecognized link between geomechanics and anomalous transport in discrete fractured networks. [1] P. K. Kang, S. Brown, and R. Juanes, Emergence of anomalous transport in stressed rough fractures. Earth and Planetary Science Letters, to appear (2016). Figure (a) Map of maximum principal stress with a vertical normal compressive stress of 3 MPa at top and bottom boundaries, and 1MPa at left and right boundaries. (b) Normal compressive stress of 15 MPa at top and bottom boundaries, and 5MPa at left and right boundaries.

Application of Phase-Field Techniques to Hydraulically- and Deformation-Induced Fracture.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Culp, David; Miller, Nathan; Schweizer, Laura

Phase-field techniques provide an alternative approach to fracture problems which mitigate some of the computational expense associated with tracking the crack interface and the coalescence of individual fractures. The technique is extended to apply to hydraulically driven fracture such as would occur during fracking or CO 2 sequestration. Additionally, the technique is applied to a stainless steel specimen used in the Sandia Fracture Challenge. It was found that the phase-field model performs very well, at least qualitatively, in both deformation-induced fracture and hydraulically-induced fracture, though spurious hourglassing modes were observed during coupled hydralically-induced fracture. Future work would include performing additionalmore » quantitative benchmark tests and updating the model as needed.« less

Measurement of width and pressure in a propagating hydraulic fracture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Warpinski, N.R.

Measurements of width and pressure in a propagating hydraulic fracture have been made in tests conducted at DOE's Nevada Test Site. This was accomplished by creating an instrumented fracture at a tunnel complex (at a depth of 1400 ft) where realistic in situ conditions prevail, particularly with respect to stress and geologic features such as natural fractures and material anisotropy. Analyses of these data show that the pressure drop along the fracture length is much larger than predicted by viscous theory and currently in use in models today. This is apparently due to the tortuosity of the fracture path, multiplemore » fracture strands, roughness and sharp turns (corners) in the flow path due to natural fractures and rock property variations. It suggests that fracture design models need to be updated to include a more realistic friction factor so that fracture lengths are not overestimated.« less

Localized rosuvastatin via implantable bioerodible sponge and its potential role in augmenting bone healing and regeneration.

PubMed

Ibrahim, Howida Kamal; Fahmy, Rania Hassan

2016-11-01

Statins proved potential bone healing properties. Rosuvastatin is a synthetic, hydrophilic, potent and highly efficacious statin. In the current work, an attempt was investigated to develop, evaluate various bioerodible composite sponges enclosing rosuvastatin and explore their potential in augmenting bone healing and regeneration. Twelve lyophilized sponge formulae were prepared adapting a 4 1 .3 1 full factorial design. Xanthan gum, polycarbophil, Carbopol® and sodium alginate were investigated as anionic polymers, each at three chitosan:anionic polymer ratios (1:3, 1:1, 3:1). The formula of choice was implanted in fractured rat femora. Visual and microscopic examination showed flexible homogenous porous structures with considerable bending ability. Polyelectrolyte complex formation was proved by DSC and FT-IR for all chitosan/anionic combinations except with xanthan gum where chitosan probably bound to the drug rather than xanthan gum. Statistical analysis proved that anionic polymer type and chitosan: polymer ratio, as well as, their interactions, exhibited significant effects on the release parameters at p ≤ 0.05. The optimum chitosan/anionic polymer complexation ratios were 3:1 for polycarbophil and 1:1 for Carbopol and alginate. The release at these ratios followed Fiction diffusion while other ratios had anomalous diffusion. Imwitor® 900K and HPMC K100M were added as release retarardants for further release optimization. The formula of choice was implanted in fractured rat femora. Histopathological examination revealed advanced stages of healing in treated femora compared to control ones. Biodegradable sponges for local rosuvastatin delivery proved significantly enhanced wound healing and regeneration properties to fractured bones.

Integration of outcrop and subsurface fracture data for reservoir modeling of the Natih field, north Oman

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mercadier, C.G.L.; Milatz, H.U.C.

1991-03-01

The Natih field reservoir comprises several distinct fractured limestone intervals which contain some 500 {times} 10{sup 6} m{sup 3} STOIIP. The field is being developed by gas-oil gravity drainage. Fracture orientations, dimensions, and spacings are critical to predict the effectiveness of this process. Statistically representative fracture data from Cretaceous Natih outcrop analogs in North Oman, core data, and electrical borehole imagery provided a realistic input for Natih field reservoir modeling and simulation. In the outcrops the fractures trend both cross-axially and longitudinally with dimensions and spacings varying with lithology, bed thickness, and curvature. Dimensions of matrix blocks in clean thicklymore » bedded limestones are an order of magnitude greater than in more argillaceous thinly bedded limestones. Subsurface data from the Natih reservoirs indicate that open cross-axial subvertical northeast-southwest-trending fractures dominate and strongly influence the reservoir flow pattern, but longitudinal fractures could not be identified. This is in line with the orientation of the present day, principal horizontal in situ stress that preferentially keeps open the cross-axial fracture set. Fracture apertures from borehole imagery have a range of 0.1 to 0.3 mm which is consistent with that derived from reservoir pressure behavior. Combining outcrop and well data results in a Natih reservoir fracture model with open cross-axial fractures that have a lithology dependent spacing of 0.1 to 2 m over the entire structure. From these data fracture porosities are calculated for each gridblock in the model. Longitudinal fractures probably exist in the vicinity of faults and in the northern part of the field where rapid down-warping occurs.« less

Mapping of hydraulic fractures from tiltmeter measurements

NASA Astrophysics Data System (ADS)

Lecampion, B.; Jeffrey, R.

2003-12-01

In considering the problem of inverse modeling of tiltmeter data for hydraulic fracture mapping, we address the issues of selecting the elastic model to represent the hydraulic fracture and limitations imposed by distance and fracture size on the information that can be recovered about the fracture. A tiltmeter measures, at its location, the changes in the surface inclination in two orthogonal directions. These inclinations are a direct measure of the horizontal gradient of the vertical component of the displacement field. Since advances in instrumentation in the last two decades, this type of apparatus have become extremely precise and can detect inclination changes down to a nanoradian. The simplicity of tiltmeter measurements has attracted interest not only in geophysics, but also in the petroleum industry. The idea of using tiltmeters to monitor hydraulic fractures can be traced back to the paper of Sun te{S} and is now a commercial service offered to the petroleum industry te{W}. However, the modeling and associated inverse problems required to analyze tiltmeter data raise difficult questions. The object(s) (fault, dyke, fracture) responsible for the recorded tilt are often modeled by finite Displacement Discontinuities, also called dislocation models. The validity of this type of model has been extensively discussed te{O,E} and many solutions for different configurations can be found in the literature. We show that it is possible to construct the solution for any type of dislocation model from the fundamental solution for an infinitesimal Displacement Discontinuity tensor. The eigenstrain theory te{M} is used to obtain this fundamental solution from the Green's function for the desired elastic domain (e.g. full or half space). Comparisons with known solutions demonstrate the flexibility of such method. We then focus on the problem of obtaining information about the orientation and size of an opening mode hydraulic fracture from the measured tilt field. One important problem is the identification of all the dimensions of the fracture model (length, width). The ability to obtain these parameters is controlled by limits, expressed in terms of the distance between the measurements and the fracture compared to the size of the fracture itself. The value of this ratio provides a condition that must be met before the fracture length-scales can be resolved. Determination of the fracture orientation is then investigated using a spatial Fourier Transform on the data set. This procedure highlights the requirement on the measurement array needed for a reliable identification: extension, number of tiltmeters, relative angle between the array and the fracture plane. \\begin{thebibliography}{1} \\bibitem{E} {Evans K.} \

Cost-Effectiveness of Orthogeriatric and Fracture Liaison Service Models of Care for Hip Fracture Patients: A Population-Based Study.

PubMed

Leal, Jose; Gray, Alastair M; Hawley, Samuel; Prieto-Alhambra, Daniel; Delmestri, Antonella; Arden, Nigel K; Cooper, Cyrus; Javaid, M Kassim; Judge, Andrew

2017-02-01

Fracture liaison services are recommended as a model of best practice for organizing patient care and secondary fracture prevention for hip fracture patients, although variation exists in how such services are structured. There is considerable uncertainty as to which model is most cost-effective and should therefore be mandated. This study evaluated the cost- effectiveness of orthogeriatric (OG)- and nurse-led fracture liaison service (FLS) models of post-hip fracture care compared with usual care. Analyses were conducted from a health care and personal social services payer perspective, using a Markov model to estimate the lifetime impact of the models of care. The base-case population consisted of men and women aged 83 years with a hip fracture. The risk and costs of hip and non-hip fractures were derived from large primary and hospital care data sets in the UK. Utilities were informed by a meta-regression of 32 studies. In the base-case analysis, the orthogeriatric-led service was the most effective and cost-effective model of care at a threshold of £30,000 per quality-adjusted life years gained (QALY). For women aged 83 years, the OG-led service was the most cost-effective at £22,709/QALY. If only health care costs are considered, OG-led service was cost-effective at £12,860/QALY and £14,525/QALY for women and men aged 83 years, respectively. Irrespective of how patients were stratified in terms of their age, sex, and Charlson comorbidity score at index hip fracture, our results suggest that introducing an orthogeriatrician-led or a nurse-led FLS is cost-effective when compared with usual care. Although considerable uncertainty remains concerning which of the models of care should be preferred, introducing an orthogeriatrician-led service seems to be the most cost-effective service to pursue. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

Prediction of Fracture Behavior in Rock and Rock-like Materials Using Discrete Element Models

NASA Astrophysics Data System (ADS)

Katsaga, T.; Young, P.

2009-05-01

The study of fracture initiation and propagation in heterogeneous materials such as rock and rock-like materials are of principal interest in the field of rock mechanics and rock engineering. It is crucial to study and investigate failure prediction and safety measures in civil and mining structures. Our work offers a practical approach to predict fracture behaviour using discrete element models. In this approach, the microstructures of materials are presented through the combination of clusters of bonded particles with different inter-cluster particle and bond properties, and intra-cluster bond properties. The geometry of clusters is transferred from information available from thin sections, computed tomography (CT) images and other visual presentation of the modeled material using customized AutoCAD built-in dialog- based Visual Basic Application. Exact microstructures of the tested sample, including fractures, faults, inclusions and void spaces can be duplicated in the discrete element models. Although the microstructural fabrics of rocks and rock-like structures may have different scale, fracture formation and propagation through these materials are alike and will follow similar mechanics. Synthetic material provides an excellent condition for validating the modelling approaches, as fracture behaviours are known with the well-defined composite's properties. Calibration of the macro-properties of matrix material and inclusions (aggregates), were followed with the overall mechanical material responses calibration by adjusting the interfacial properties. The discrete element model predicted similar fracture propagation features and path as that of the real sample material. The path of the fractures and matrix-inclusion interaction was compared using computed tomography images. Initiation and fracture formation in the model and real material were compared using Acoustic Emission data. Analysing the temporal and spatial evolution of AE events, collected during the sample testing, in relation to the CT images allows the precise reconstruction of the failure sequence. Our proposed modelling approach illustrates realistic fracture formation and growth predictions at different loading conditions.

A linearized microstructural model for hydraulic conductivity evolution due to brittle damage: application to Hydraulic Fracturing treatments

NASA Astrophysics Data System (ADS)

Caramiello, G.; Montanino, A.; Della Vecchia, G., Sr.; Pandolfi, A., Sr.

2017-12-01

Among the features of geological structures, fractures and discontinuities play a dominant role, due to their significant influence on both the hydraulic and the mechanical behavior of the rock mass. Despite the current availability of fault and fracture mappings, the understanding of the influence of faults on fluid flow is nowadays not satisfactory, in particular when hydro-mechanical coupling is significant. In engineering technology fracture processes are often exploited. Hydraulic fracturing is one of the most important example. Hydraulic fracturing is a process characterized by the inception and propagation of fractures as a consequence of a hydraulic driven solicitation and it is used to improve the production and optimize well stimulation in low permeability reservoirs. Due to the coupling of several different phenomena (hydro-thermo-chemical coupling) there is not a reliable complete mathematical model able to simulate in a proper way the process. To design hydraulic fracturing treatments, it is necessary to predict the growth of fracture geometry as a function of treatment parameters. In this contribution we present a recently developed model of brittle damage of confined rock masses, with particular emphasis on the influence of mechanical damage on the evolution of porosity and permeability. The model is based on an explicit micromechanical construction of connected patterns of parallel equi-spaced cracks. A relevant feature of the model is that the fracture patterns are not arbitrary, but their inception, orientation and spacing follow from energetic consideration. The model, based on the Terzaghi effective stress concepts, has been then implemented into a coupled hydro-mechanical finite element code, where the linear momentum and the fluid mass balance equations are numerically solved via a staggered approach. The coupled code is used to simulate fracturing processes induced by an increase in pore pressure. The examples show the capability of the model in reproducing three-dimensional multiscale complex fracture patterns and permeability enhancement in the damaged porous medium. The numerical code, has been used to verify the influence of the distance between the different perforation slots as well of the wellbore-deviation from the minimum stress axis on the propagation of multiple.

Mechanical and hydraulic properties of rocks related to induced seismicity

USGS Publications Warehouse

Witherspoon, P.A.; Gale, J.E.

1977-01-01

Witherspoon, P.A. and Gale, J.E., 1977. Mechanical and hydraulic properties of rocks related to induced seismicity. Eng. Geol., 11(1): 23-55. The mechanical and hydraulic properties of fractured rocks are considered with regard to the role they play in induced seismicity. In many cases, the mechanical properties of fractures determine the stability of a rock mass. The problems of sampling and testing these rock discontinuities and interpreting their non-linear behavior are reviewed. Stick slip has been proposed as the failure mechanism in earthquake events. Because of the complex interactions that are inherent in the mechanical behavior of fractured rocks, there seems to be no simple way to combine the deformation characteristics of several sets of fractures when there are significant perturbations of existing conditions. Thus, the more important fractures must be treated as individual components in the rock mass. In considering the hydraulic properties, it has been customary to treat a fracture as a parallel-plate conduit and a number of mathematical models of fracture systems have adopted this approach. Non-steady flow in fractured systems has usually been based on a two-porosity model, which assumes the primary (intergranular) porosity contributes only to storage and the secondary (fracture) porosity contributes only to the overall conductivity. Using such a model, it has been found that the time required to achieve quasi-steady state flow in a fractured reservoir is one or two orders of magnitude greater than it is in a homogeneous system. In essentially all of this work, the assumption has generally been made that the fractures are rigid. However, it is clear from a review of the mechanical and hydraulic properties that not only are fractures easily deformed but they constitute the main flow paths in many rock masses. This means that one must consider the interaction of mechanical and hydraulic effects. A considerable amount of laboratory and field data is now available that clearly demonstrates this stress-flow behavior. Two approaches have been used in attempting to numerically model such behavior: (1) continuum models, and (2) discrete models. The continuum approach only needs information as to average values of fracture spacing and material properties. But because of the inherent complexity of fractured rock masses and the corresponding decrease in symmetry, it is difficult to develop an equivalent continuum that will simulate the behavior of the entire system. The discrete approach, on the other hand, requires details of the fracture geometry and material properties of both fractures and rock matrix. The difficulty in obtaining such information has been considered a serious limitation of discrete models, but improved borehole techniques can enable one to obtain the necessary data, at least in shallow systems. The possibility of extending these methods to deeper fracture systems needs more investigation. Such data must be considered when deciding whether to use a continuum or discrete model to represent the interaction of rock and fluid forces in a fractured rock system, especially with regard to the problem of induced seismicity. When one is attempting to alter the pressure distribution in a fault zone by injection or withdrawal of fluids, the extent to which this can be achieved will be controlled in large measure by the behavior of the fractures that communicate with the borehole. Since this is essentially a point phenomenon, i.e., the changes will propagate from a relatively small region around the borehole, the use of a discrete model would appear to be preferable. ?? 1977.

Modelling Laccoliths: Fluid-Driven Fracturing in the Lab

NASA Astrophysics Data System (ADS)

Ball, T. V.; Neufeld, J. A.

2017-12-01

Current modelling of the formation of laccoliths neglects the necessity to fracture rock layers for propagation to occur [1]. In magmatic intrusions at depth the idea of fracture toughness is used to characterise fracturing, however an analogue for near surface intrusions has yet to be explored [2]. We propose an analytical model for laccolith emplacement that accounts for the energy required to fracture at the tip of an intrusion. For realistic physical parameters we find that a lag region exists between the fluid magma front and the crack tip where large negative pressures in the tip cause volatiles to exsolve from the magma. Crucially, the dynamics of this tip region controls the spreading due to the competition between viscous forces and fracture energy. We conduct a series of complementary experiments to investigate fluid-driven fracturing of adhered layers and confirm the existence of two regimes: viscosity dominant spreading, controlled by the pressure in the lag region, and fracture energy dominant spreading, controlled by the energy required to fracture layers. Our experiments provide the first observations, and evolution, of a vapour tip. These experiments and our simplified model provide insight into the key physical processes in near surface magmatic intrusions with applications to fluid-driven fracturing more generally. Michaut J. Geophys. Res. 116(B5), B05205. Bunger & Cruden J. Geophys. Res. 116(B2), B02203.

Micro-mechanics of hydro-mechanical coupled processes during hydraulic fracturing in sandstone

NASA Astrophysics Data System (ADS)

Caulk, R.; Tomac, I.

2017-12-01

This contribution presents micro-mechanical study of hydraulic fracture initiation and propagation in sandstone. The Discrete Element Method (DEM) Yade software is used as a tool to model fully coupled hydro-mechanical behavior of the saturated sandstone under pressures typical for deep geo-reservoirs. Heterogeneity of sandstone strength tensile and shear parameters are introduced using statistical representation of cathodoluminiscence (CL) sandstone rock images. Weibull distribution of statistical parameter values was determined as a best match of the CL scans of sandstone grains and cement between grains. Results of hydraulic fracturing stimulation from the well bore indicate significant difference between models with the bond strengths informed from CL scans and uniform homogeneous representation of sandstone parameters. Micro-mechanical insight reveals formed hydraulic fracture typical for mode I or tensile cracking in both cases. However, the shear micro-cracks are abundant in the CL informed model while they are absent in the standard model with uniform strength distribution. Most of the mode II cracks, or shear micro-cracks, are not part of the main hydraulic fracture and occur in the near-tip and near-fracture areas. The position and occurrence of the shear micro-cracks is characterized as secondary effect which dissipates the hydraulic fracturing energy. Additionally, the shear micro-crack locations qualitatively resemble acoustic emission cloud of shear cracks frequently observed in hydraulic fracturing, and sometimes interpreted as re-activation of existing fractures. Clearly, our model does not contain pre-existing cracks and has continuous nature prior to fracturing. This observation is novel and interesting and is quantified in the paper. The shear particle contact forces field reveals significant relaxation compared to the model with uniform strength distribution.

Coupling Hydraulic Fracturing Propagation and Gas Well Performance for Simulation of Production in Unconventional Shale Gas Reservoirs

NASA Astrophysics Data System (ADS)

Wang, C.; Winterfeld, P. H.; Wu, Y. S.; Wang, Y.; Chen, D.; Yin, C.; Pan, Z.

2014-12-01

Hydraulic fracturing combined with horizontal drilling has made it possible to economically produce natural gas from unconventional shale gas reservoirs. An efficient methodology for evaluating hydraulic fracturing operation parameters, such as fluid and proppant properties, injection rates, and wellhead pressure, is essential for the evaluation and efficient design of these processes. Traditional numerical evaluation and optimization approaches are usually based on simulated fracture properties such as the fracture area. In our opinion, a methodology based on simulated production data is better, because production is the goal of hydraulic fracturing and we can calibrate this approach with production data that is already known. This numerical methodology requires a fully-coupled hydraulic fracture propagation and multi-phase flow model. In this paper, we present a general fully-coupled numerical framework to simulate hydraulic fracturing and post-fracture gas well performance. This three-dimensional, multi-phase simulator focuses on: (1) fracture width increase and fracture propagation that occurs as slurry is injected into the fracture, (2) erosion caused by fracture fluids and leakoff, (3) proppant subsidence and flowback, and (4) multi-phase fluid flow through various-scaled anisotropic natural and man-made fractures. Mathematical and numerical details on how to fully couple the fracture propagation and fluid flow parts are discussed. Hydraulic fracturing and production operation parameters, and properties of the reservoir, fluids, and proppants, are taken into account. The well may be horizontal, vertical, or deviated, as well as open-hole or cemented. The simulator is verified based on benchmarks from the literature and we show its application by simulating fracture network (hydraulic and natural fractures) propagation and production data history matching of a field in China. We also conduct a series of real-data modeling studies with different combinations of hydraulic fracturing parameters and present the methodology to design these operations with feedback of simulated production data. The unified model aids in the optimization of hydraulic fracturing design, operations, and production.

Simulation Study of CO2-EOR in Tight Oil Reservoirs with Complex Fracture Geometries

PubMed Central

Zuloaga-Molero, Pavel; Yu, Wei; Xu, Yifei; Sepehrnoori, Kamy; Li, Baozhen

2016-01-01

The recent development of tight oil reservoirs has led to an increase in oil production in the past several years due to the progress in horizontal drilling and hydraulic fracturing. However, the expected oil recovery factor from these reservoirs is still very low. CO2-based enhanced oil recovery is a suitable solution to improve the recovery. One challenge of the estimation of the recovery is to properly model complex hydraulic fracture geometries which are often assumed to be planar due to the limitation of local grid refinement approach. More flexible methods like the use of unstructured grids can significantly increase the computational demand. In this study, we introduce an efficient methodology of the embedded discrete fracture model to explicitly model complex fracture geometries. We build a compositional reservoir model to investigate the effects of complex fracture geometries on performance of CO2 Huff-n-Puff and CO2 continuous injection. The results confirm that the appropriate modelling of the fracture geometry plays a critical role in the estimation of the incremental oil recovery. This study also provides new insights into the understanding of the impacts of CO2 molecular diffusion, reservoir permeability, and natural fractures on the performance of CO2-EOR processes in tight oil reservoirs. PMID:27628131

An animal model of co-existing sarcopenia and osteoporotic fracture in senescence accelerated mouse prone 8 (SAMP8).

PubMed

Zhang, Ning; Chow, Simon Kwoon Ho; Leung, Kwok Sui; Lee, Ho Hin; Cheung, Wing Hoi

2017-10-15

Sarcopenia and osteoporotic fracture are common aging-related musculoskeletal problems. Recent evidences report that osteoporotic fracture patients showed high prevalence of sarcopenia; however, current clinical practice basically does not consider sarcopenia in the treatment or rehabilitation of osteoporotic fracture. There is almost no report studying the relationship of the co-existing of sarcopenia and osteoporotic fracture healing. In this study, we validated aged senescence accelerated mouse prone 8 (SAMP8) and senescence accelerated mouse resistant 1 (SAMR1) as animal models of senile osteoporosis with/without sarcopenia. Bone mineral density (BMD) at the 5th lumbar and muscle testing of the two animal strains were measured to confirm the status of osteoporosis and sarcopenia, respectively. Closed fracture was created on the right femur of 8-month-old animals. Radiographs were taken weekly post-fracture. MicroCT and histology of the fractured femur were performed at week 2, 4 and 6 post-fracture, while mechanical test of both femora at week 4 and 6 post-fracture. Results showed that the callus of SAMR1 was significantly larger at week 2 but smaller at week 6 post-fracture than SAMP8. Mechanical properties were significantly better at week 4 post-fracture in SAMR1 than SAMP8, indicating osteoporotic fracture healing was delayed in sarcopenic SAMP8. This study validated an animal model of co-existing sarcopenia and osteoporotic fracture, where a delayed fracture healing might be resulted in the presence of sarcopenia. Copyright © 2017 Elsevier Inc. All rights reserved.

Recovery Act. Development and Validation of an Advanced Stimulation Prediction Model for Enhanced Geothermal System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gutierrez, Marte

The research project aims to develop and validate an advanced computer model that can be used in the planning and design of stimulation techniques to create engineered reservoirs for Enhanced Geothermal Systems. The specific objectives of the proposal are to: 1) Develop a true three-dimensional hydro-thermal fracturing simulator that is particularly suited for EGS reservoir creation. 2) Perform laboratory scale model tests of hydraulic fracturing and proppant flow/transport using a polyaxial loading device, and use the laboratory results to test and validate the 3D simulator. 3) Perform discrete element/particulate modeling of proppant transport in hydraulic fractures, and use the resultsmore » to improve understand of proppant flow and transport. 4) Test and validate the 3D hydro-thermal fracturing simulator against case histories of EGS energy production. 5) Develop a plan to commercialize the 3D fracturing and proppant flow/transport simulator. The project is expected to yield several specific results and benefits. Major technical products from the proposal include: 1) A true-3D hydro-thermal fracturing computer code that is particularly suited to EGS, 2) Documented results of scale model tests on hydro-thermal fracturing and fracture propping in an analogue crystalline rock, 3) Documented procedures and results of discrete element/particulate modeling of flow and transport of proppants for EGS applications, and 4) Database of monitoring data, with focus of Acoustic Emissions (AE) from lab scale modeling and field case histories of EGS reservoir creation.« less

Recovery Act. Development and Validation of an Advanced Stimulation Prediction Model for Enhanced Geothermal Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gutierrez, Marte

2013-12-31

This research project aims to develop and validate an advanced computer model that can be used in the planning and design of stimulation techniques to create engineered reservoirs for Enhanced Geothermal Systems. The specific objectives of the proposal are to; Develop a true three-dimensional hydro-thermal fracturing simulator that is particularly suited for EGS reservoir creation; Perform laboratory scale model tests of hydraulic fracturing and proppant flow/transport using a polyaxial loading device, and use the laboratory results to test and validate the 3D simulator; Perform discrete element/particulate modeling of proppant transport in hydraulic fractures, and use the results to improve understandmore » of proppant flow and transport; Test and validate the 3D hydro-thermal fracturing simulator against case histories of EGS energy production; and Develop a plan to commercialize the 3D fracturing and proppant flow/transport simulator. The project is expected to yield several specific results and benefits. Major technical products from the proposal include; A true-3D hydro-thermal fracturing computer code that is particularly suited to EGS; Documented results of scale model tests on hydro-thermal fracturing and fracture propping in an analogue crystalline rock; Documented procedures and results of discrete element/particulate modeling of flow and transport of proppants for EGS applications; and Database of monitoring data, with focus of Acoustic Emissions (AE) from lab scale modeling and field case histories of EGS reservoir creation.« less

The importance of conceptual models in the reactive transport simulation of oxygen ingress in sparsely fractured crystalline rock.

PubMed

Macquarrie, K T B; Mayer, K U; Jin, B; Spiessl, S M

2010-03-01

Redox evolution in sparsely fractured crystalline rocks is a key, and largely unresolved, issue when assessing the geochemical suitability of deep geological repositories for nuclear waste. Redox zonation created by the influx of oxygenated waters has previously been simulated using reactive transport models that have incorporated a variety of processes, resulting in predictions for the depth of oxygen penetration that may vary greatly. An assessment and direct comparison of the various underlying conceptual models are therefore needed. In this work a reactive transport model that considers multiple processes in an integrated manner is used to investigate the ingress of oxygen for both single fracture and fracture zone scenarios. It is shown that the depth of dissolved oxygen migration is greatly influenced by the a priori assumptions that are made in the conceptual models. For example, the ability of oxygen to access and react with minerals in the rock matrix may be of paramount importance for single fracture conceptual models. For fracture zone systems, the abundance and reactivity of minerals within the fractures and thin matrix slabs between the fractures appear to provide key controls on O(2) attenuation. The findings point to the need for improved understanding of the coupling between the key transport-reaction feedbacks to determine which conceptual models are most suitable and to provide guidance for which parameters should be targeted in field and laboratory investigations. Copyright 2009 Elsevier B.V. All rights reserved.

Risk Assessment of Bone Fracture During Space Exploration Missions to the Moon and Mars

NASA Technical Reports Server (NTRS)

Lewandowski, Beth E.; Myers, Jerry G.; Nelson, Emily S.; Licatta, Angelo; Griffin, Devon

2007-01-01

The possibility of a traumatic bone fracture in space is a concern due to the observed decrease in astronaut bone mineral density (BMD) during spaceflight and because of the physical demands of the mission. The Bone Fracture Risk Module (BFxRM) was developed to quantify the probability of fracture at the femoral neck and lumbar spine during space exploration missions. The BFxRM is scenario-based, providing predictions for specific activities or events during a particular space mission. The key elements of the BFxRM are the mission parameters, the biomechanical loading models, the bone loss and fracture models and the incidence rate of the activity or event. Uncertainties in the model parameters arise due to variations within the population and unknowns associated with the effects of the space environment. Consequently, parameter distributions were used in Monte Carlo simulations to obtain an estimate of fracture probability under real mission scenarios. The model predicts an increase in the probability of fracture as the mission length increases and fracture is more likely in the higher gravitational field of Mars than on the moon. The resulting probability predictions and sensitivity analyses of the BFxRM can be used as an engineering tool for mission operation and resource planning in order to mitigate the risk of bone fracture in space.

Risk Assessment of Bone Fracture During Space Exploration Missions to the Moon and Mars

NASA Technical Reports Server (NTRS)

Lewandowski, Beth E.; Myers, Jerry G.; Nelson, Emily S.; Griffin, Devon

2008-01-01

The possibility of a traumatic bone fracture in space is a concern due to the observed decrease in astronaut bone mineral density (BMD) during spaceflight and because of the physical demands of the mission. The Bone Fracture Risk Module (BFxRM) was developed to quantify the probability of fracture at the femoral neck and lumbar spine during space exploration missions. The BFxRM is scenario-based, providing predictions for specific activities or events during a particular space mission. The key elements of the BFxRM are the mission parameters, the biomechanical loading models, the bone loss and fracture models and the incidence rate of the activity or event. Uncertainties in the model parameters arise due to variations within the population and unknowns associated with the effects of the space environment. Consequently, parameter distributions were used in Monte Carlo simulations to obtain an estimate of fracture probability under real mission scenarios. The model predicts an increase in the probability of fracture as the mission length increases and fracture is more likely in the higher gravitational field of Mars than on the moon. The resulting probability predictions and sensitivity analyses of the BFxRM can be used as an engineering tool for mission operation and resource planning in order to mitigate the risk of bone fracture in space.

Hydraulic fracture propagation modeling and data-based fracture identification

NASA Astrophysics Data System (ADS)

Zhou, Jing

Successful shale gas and tight oil production is enabled by the engineering innovation of horizontal drilling and hydraulic fracturing. Hydraulically induced fractures will most likely deviate from the bi-wing planar pattern and generate complex fracture networks due to mechanical interactions and reservoir heterogeneity, both of which render the conventional fracture simulators insufficient to characterize the fractured reservoir. Moreover, in reservoirs with ultra-low permeability, the natural fractures are widely distributed, which will result in hydraulic fractures branching and merging at the interface and consequently lead to the creation of more complex fracture networks. Thus, developing a reliable hydraulic fracturing simulator, including both mechanical interaction and fluid flow, is critical in maximizing hydrocarbon recovery and optimizing fracture/well design and completion strategy in multistage horizontal wells. A novel fully coupled reservoir flow and geomechanics model based on the dual-lattice system is developed to simulate multiple nonplanar fractures' propagation in both homogeneous and heterogeneous reservoirs with or without pre-existing natural fractures. Initiation, growth, and coalescence of the microcracks will lead to the generation of macroscopic fractures, which is explicitly mimicked by failure and removal of bonds between particles from the discrete element network. This physics-based modeling approach leads to realistic fracture patterns without using the empirical rock failure and fracture propagation criteria required in conventional continuum methods. Based on this model, a sensitivity study is performed to investigate the effects of perforation spacing, in-situ stress anisotropy, rock properties (Young's modulus, Poisson's ratio, and compressive strength), fluid properties, and natural fracture properties on hydraulic fracture propagation. In addition, since reservoirs are buried thousands of feet below the surface, the parameters used in the reservoir flow simulator have large uncertainty. Those biased and uncertain parameters will result in misleading oil and gas recovery predictions. The Ensemble Kalman Filter is used to estimate and update both the state variables (pressure and saturations) and uncertain reservoir parameters (permeability). In order to directly incorporate spatial information such as fracture location and formation heterogeneity into the algorithm, a new covariance matrix method is proposed. This new method has been applied to a simplified single-phase reservoir and a complex black oil reservoir with complex structures to prove its capability in calibrating the reservoir parameters.

Thermodynamically consistent model of brittle oil shales under overpressure

NASA Astrophysics Data System (ADS)

Izvekov, Oleg

2016-04-01

The concept of dual porosity is a common way for simulation of oil shale production. In the frame of this concept the porous fractured media is considered as superposition of two permeable continua with mass exchange. As a rule the concept doesn't take into account such as the well-known phenomenon as slip along natural fractures, overpressure in low permeability matrix and so on. Overpressure can lead to development of secondary fractures in low permeability matrix in the process of drilling and pressure reduction during production. In this work a new thermodynamically consistent model which generalizes the model of dual porosity is proposed. Particularities of the model are as follows. The set of natural fractures is considered as permeable continuum. Damage mechanics is applied to simulation of secondary fractures development in low permeability matrix. Slip along natural fractures is simulated in the frame of plasticity theory with Drucker-Prager criterion.

Tilt and strain deformation induced by hydrologically active natural fractures: application to the tiltmeters installed in Sainte-Croix-aux-Mines observatory (France)

NASA Astrophysics Data System (ADS)

Longuevergne, Laurent; Florsch, Nicolas; Boudin, Frédéric; Oudin, Ludovic; Camerlynck, Christian

2009-08-01

We investigate the deformation induced by water pressure variations in hydrologically active natural fractures, and recorded by tiltmeters and strainmeters. The deformation associated with a single fracture is derived using finite-element modelling (FEM). A range in fracture geometries is explored, first to highlight the sensitivity of each geometrical parameter to the deformation, and secondly to allow transfer to observation sites. Water level variations in the fracture are then derived from a hydrological model, driven by observed rainfall, and calibrated on fracture water flow measurements. The modelling results are explicitly applied to constrain the local hydrological contribution to observations with the 100-m-long hydrostatic tiltmeter installed at Sainte-Croix-aux-Mines (France). Our study shows that well-founded physical modelling of local hydrological effect allows a substantial correction of records in observatories.

Surrogate Modeling of High-Fidelity Fracture Simulations for Real-Time Residual Strength Predictions

NASA Technical Reports Server (NTRS)

Spear, Ashley D.; Priest, Amanda R.; Veilleux, Michael G.; Ingraffea, Anthony R.; Hochhalter, Jacob D.

2011-01-01

A surrogate model methodology is described for predicting, during flight, the residual strength of aircraft structures that sustain discrete-source damage. Starting with design of experiment, an artificial neural network is developed that takes as input discrete-source damage parameters and outputs a prediction of the structural residual strength. Target residual strength values used to train the artificial neural network are derived from 3D finite element-based fracture simulations. Two ductile fracture simulations are presented to show that crack growth and residual strength are determined more accurately in discrete-source damage cases by using an elastic-plastic fracture framework rather than a linear-elastic fracture mechanics-based method. Improving accuracy of the residual strength training data does, in turn, improve accuracy of the surrogate model. When combined, the surrogate model methodology and high fidelity fracture simulation framework provide useful tools for adaptive flight technology.

Analysis of seismic sources for different mechanisms of fracture growth for microseismic monitoring applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duchkov, A. A., E-mail: DuchkovAA@ipgg.sbras.ru; Novosibirsk State University, Novosibirsk, 630090; Stefanov, Yu. P., E-mail: stefanov@ispms.tsc.ru

2015-10-27

We have developed and illustrated an approach for geomechanic modeling of elastic wave generation (microsiesmic event occurrence) during incremental fracture growth. We then derived properties of effective point seismic sources (radiation patterns) approximating obtained wavefields. These results establish connection between geomechanic models of hydraulic fracturing and microseismic monitoring. Thus, the results of the moment tensor inversion of microseismic data can be related to different geomechanic scenarios of hydraulic fracture growth. In future, the results can be used for calibrating hydrofrac models. We carried out a series of numerical simulations and made some observations about wave generation during fracture growth. Inmore » particular when the growing fracture hits pre-existing crack then it generates much stronger microseismic event compared to fracture growth in homogeneous medium (radiation pattern is very close to the theoretical dipole-type source mechanism)« less

Fracture identification based on remote detection acoustic reflection logging

NASA Astrophysics Data System (ADS)

Zhang, Gong; Li, Ning; Guo, Hong-Wei; Wu, Hong-Liang; Luo, Chao

2015-12-01

Fracture identification is important for the evaluation of carbonate reservoirs. However, conventional logging equipment has small depth of investigation and cannot detect rock fractures more than three meters away from the borehole. Remote acoustic logging uses phase-controlled array-transmitting and long sound probes that increase the depth of investigation. The interpretation of logging data with respect to fractures is typically guided by practical experience rather than theory and is often ambiguous. We use remote acoustic reflection logging data and high-order finite-difference approximations in the forward modeling and prestack reverse-time migration to image fractures. First, we perform forward modeling of the fracture responses as a function of the fracture-borehole wall distance, aperture, and dip angle. Second, we extract the energy intensity within the imaging area to determine whether the fracture can be identified as the formation velocity is varied. Finally, we evaluate the effect of the fracture-borehole distance, fracture aperture, and dip angle on fracture identification.

Experimental investigation of heat transport through single synthetic fractures

NASA Astrophysics Data System (ADS)

Pastore, Nicola; Cherubini, Claudia; Giasi, Concetta I.; Redondo, Jose M.

2017-04-01

In fractured geothermal reservoirs, heat transport is highly influenced by the presence of the fractures, so appropriate knowledge of heat behaviour in fractured porous media is essential for accurate prediction of the energy extraction in geothermal reservoirs. The present study focuses on the study of heat transport within single synthetic fractures. In particular manner several tests have been carried out in order to explore the role of fracture roughness, aperture variability and the fracture-matrix ratio on the heat transport dynamics. The Synfrac program together with a 3d printer have been used to build several fracture planes having different geometrical characteristics that have been moulded to generate concrete porous fractured blocks. The tests regard the observation of the thermal breakthrough curves obtained through a continuous flow injection in correspondence of eight thermocouples located uniformly on the fractured blocks. The physical model developed permits to reproduce and understand adequately some features of heat transport dynamics in fractured media. The results give emphasis on the errors of the assumptions commonly used in heat transport modelling.

Simulation of Anisotropic Rock Damage for Geologic Fracturing

NASA Astrophysics Data System (ADS)

Busetti, S.; Xu, H.; Arson, C. F.

2014-12-01

A continuum damage model for differential stress-induced anisotropic crack formation and stiffness degradation is used to study geologic fracturing in rocks. The finite element-based model solves for deformation in the quasi-linear elastic domain and determines the six component damage tensor at each deformation increment. The model permits an isotropic or anisotropic intact or pre-damaged reference state, and the elasticity tensor evolves depending on the stress path. The damage variable, similar to Oda's fabric tensor, grows when the surface energy dissipated by three-dimensional opened cracks exceeds a threshold defined at the appropriate scale of the representative elementary volume (REV). At the laboratory or wellbore scale (<1m) brittle continuum damage reflects microcracking, grain boundary separation, grain crushing, or fine delamination, such as in shale. At outcrop (1m-100m), seismic (10m-1000m), and tectonic (>1000m) scales the damaged REV reflects early natural fracturing (background or tectonic fracturing) or shear strain localization (fault process zone, fault-tip damage, etc.). The numerical model was recently benchmarked against triaxial stress-strain data from laboratory rock mechanics tests. However, the utility of the model to predict geologic fabric such as natural fracturing in hydrocarbon reservoirs was not fully explored. To test the ability of the model to predict geological fracturing, finite element simulations (Abaqus) of common geologic scenarios with known fracture patterns (borehole pressurization, folding, faulting) are simulated and the modeled damage tensor is compared against physical fracture observations. Simulated damage anisotropy is similar to that derived using fractured rock-mass upscaling techniques for pre-determined fracture patterns. This suggests that if model parameters are constrained with local data (e.g., lab, wellbore, or reservoir domain), forward modeling could be used to predict mechanical fabric at the relevant REV scale. This reference fabric also can be used as the starting material property to pre-condition subsequent deformation or fluid flow. Continuing efforts are to expand the present damage model to couple damage evolution with plasticity and with permeability for more geologically realistic simulation.

The Friction Factor in the Forchheimer Equation for Rock Fractures

NASA Astrophysics Data System (ADS)

Zhou, Jia-Qing; Hu, Shao-Hua; Chen, Yi-Feng; Wang, Min; Zhou, Chuang-Bing

2016-08-01

The friction factor is an important dimensionless parameter for fluid flow through rock fractures that relates pressure head loss to average flow velocity; it can be affected by both fracture geometry and flow regime. In this study, a theoretical formula form of the friction factor containing both viscous and inertial terms is formulated by incorporating the Forchheimer equation, and a new friction factor model is proposed based on a recent phenomenological relation for the Forchheimer coefficient. The viscous term in the proposed formula is inversely proportional to Reynolds number and represents the limiting case in Darcy flow regime when the inertial effects diminish, whereas the inertial term is a power function of the relative roughness and represents a limiting case in fully turbulent flow regime when the fracture roughness plays a dominant role. The proposed model is compared with existing friction factor models for fractures through parametric sensitivity analyses and using experimental data on granite fractures, showing that the proposed model has not only clearer physical significance, but also better predictive performance. By accepting proper percentages of nonlinear pressure drop to quantify the onset of Forchheimer flow and fully turbulent flow, a Moody-type diagram with explicitly defined flow regimes is created for rock fractures of varying roughness, indicating that rougher fractures have a large friction factor and are more prone to the Forchheimer flow and fully turbulent flow. These findings may prove useful in better understanding of the flow behaviors in rock fractures and improving the numerical modeling of non-Darcy flow in fractured aquifers.

Scale-Dependent Fracture-Matrix Interactions And Their Impact on Radionuclide Transport - Final Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Detwiler, Russell

Matrix diffusion and adsorption within a rock matrix are widely regarded as important mechanisms for retarding the transport of radionuclides and other solutes in fractured rock (e.g., Neretnieks, 1980; Tang et al., 1981; Maloszewski and Zuber, 1985; Novakowski and Lapcevic, 1994; Jardine et al., 1999; Zhou and Xie, 2003; Reimus et al., 2003a,b). When remediation options are being evaluated for old sources of contamination, where a large fraction of contaminants reside within the rock matrix, slow diffusion out of the matrix greatly increases the difficulty and timeframe of remediation. Estimating the rates of solute exchange between fractures and the adjacentmore » rock matrix is a critical factor in quantifying immobilization and/or remobilization of DOE-relevant contaminants within the subsurface. In principle, the most rigorous approach to modeling solute transport with fracture-matrix interaction would be based on local-scale coupled advection-diffusion/dispersion equations for the rock matrix and in discrete fractures that comprise the fracture network (Discrete Fracture Network and Matrix approach, hereinafter referred to as DFNM approach), fully resolving aperture variability in fractures and matrix property heterogeneity. However, such approaches are computationally demanding, and thus, many predictive models rely upon simplified models. These models typically idealize fracture rock masses as a single fracture or system of parallel fractures interacting with slabs of porous matrix or as a mobile-immobile or multi-rate mass transfer system. These idealizations provide tractable approaches for interpreting tracer tests and predicting contaminant mobility, but rely upon a fitted effective matrix diffusivity or mass-transfer coefficients. However, because these fitted parameters are based upon simplified conceptual models, their effectiveness at predicting long-term transport processes remains uncertain. Evidence of scale dependence of effective matrix diffusion coefficients obtained from tracer tests highlights this point and suggests that the underlying mechanisms and relationship between rock and fracture properties are not fully understood in large complex fracture networks. In this project, we developed a high-resolution DFN model of solute transport in fracture networks to explore and quantify the mechanisms that control transport in complex fracture networks and how these may give rise to observed scale-dependent matrix diffusion coefficients. Results demonstrate that small scale heterogeneity in the flow field caused by local aperture variability within individual fractures can lead to long-tailed breakthrough curves indicative of matrix diffusion, even in the absence of interactions with the fracture matrix. Furthermore, the temporal and spatial scale dependence of these processes highlights the inability of short-term tracer tests to estimate transport parameters that will control long-term fate and transport of contaminants in fractured aquifers.« less

Numerical and Statistical Analysis of Fractures in Mechanically Dissimilar Rocks of Limestone Interbedded with Shale from Nash Point in Bristol Channel, South Wales, UK.

NASA Astrophysics Data System (ADS)

Adeoye-Akinde, K.; Gudmundsson, A.

2017-12-01

Heterogeneity and anisotropy, especially with layered strata within the same reservoir, makes the geometry and permeability of an in-situ fracture network challenging to forecast. This study looks at outcrops analogous to reservoir rocks for a better understanding of in-situ fracture networks and permeability, especially fracture formation, propagation, and arrest/deflection. Here, fracture geometry (e.g. length and aperture) from interbedded limestone and shale is combined with statistical and numerical modelling (using the Finite Element Method) to better forecast fracture network properties and permeability. The main aim is to bridge the gap between fracture data obtained at the core level (cm-scale) and at the seismic level (km-scale). Analysis has been made of geometric properties of over 250 fractures from the blue Lias in Nash Point, UK. As fractures propagate, energy is required to keep them going, and according to the laws of thermodynamics, this energy can be linked to entropy. As fractures grow, entropy increases, therefore, the result shows a strong linear correlation between entropy and the scaling exponent of fracture length and aperture-size distributions. Modelling is used to numerically simulate the stress/fracture behaviour in mechanically dissimilar rocks. Results show that the maximum principal compressive stress orientation changes in the host rock as the fracture-induced stress tip moves towards a more compliant (shale) layer. This behaviour can be related to the three mechanisms of fracture arrest/deflection at an interface, namely: elastic mismatch, stress barrier and Cook-Gordon debonding. Tensile stress concentrates at the contact between the stratigraphic layers, ahead of and around the propagating fracture. However, as shale stiffens with time, the stresses concentrated at the contact start to dissipate into it. This can happen in nature through diagenesis, and with greater depth of burial. This study also investigates how induced fractures propagate and interact with existing discontinuities in layered rocks using analogue modelling. Further work will introduce the Maximum Entropy Method for more accurate statistical modelling. This method is mainly useful to forecast likely fracture-size probability distributions from incomplete subsurface information.

Design and Implementation of Energized Fracture Treatment in Tight Gas Sands

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mukul Sharma; Kyle Friehauf

2009-12-31

Hydraulic fracturing is essential for producing gas and oil at an economic rate from low permeability sands. Most fracturing treatments use water and polymers with a gelling agent as a fracturing fluid. The water is held in the small pore spaces by capillary pressure and is not recovered when drawdown pressures are low. The un-recovered water leaves a water saturated zone around the fracture face that stops the flow of gas into the fracture. This is a particularly acute problem in low permeability formations where capillary pressures are high. Depletion (lower reservoir pressures) causes a limitation on the drawdown pressuremore » that can be applied. A hydraulic fracturing process can be energized by the addition of a compressible, sometimes soluble, gas phase into the treatment fluid. When the well is produced, the energized fluid expands and gas comes out of solution. Energizing the fluid creates high gas saturation in the invaded zone, thereby facilitating gas flowback. A new compositional hydraulic fracturing model has been created (EFRAC). This is the first model to include changes in composition, temperature, and phase behavior of the fluid inside the fracture. An equation of state is used to evaluate the phase behavior of the fluid. These compositional effects are coupled with the fluid rheology, proppant transport, and mechanics of fracture growth to create a general model for fracture creation when energized fluids are used. In addition to the fracture propagation model, we have also introduced another new model for hydraulically fractured well productivity. This is the first and only model that takes into account both finite fracture conductivity and damage in the invaded zone in a simple analytical way. EFRAC was successfully used to simulate several fracture treatments in a gas field in South Texas. Based on production estimates, energized fluids may be required when drawdown pressures are smaller than the capillary forces in the formation. For this field, the minimum CO{sub 2} gas quality (volume % of gas) recommended is 30% for moderate differences between fracture and reservoir pressures (2900 psi reservoir, 5300 psi fracture). The minimum quality is reduced to 20% when the difference between pressures is larger, resulting in additional gas expansion in the invaded zone. Inlet fluid temperature, flow rate, and base viscosity did not have a large impact on fracture production. Finally, every stage of the fracturing treatment should be energized with a gas component to ensure high gas saturation in the invaded zone. A second, more general, sensitivity study was conducted. Simulations show that CO{sub 2} outperforms N{sub 2} as a fluid component because it has higher solubility in water at fracturing temperatures and pressures. In fact, all gas components with higher solubility in water will increase the fluid's ability to reduce damage in the invaded zone. Adding methanol to the fracturing solution can increase the solubility of CO{sub 2}. N{sub 2} should only be used if the gas leaks-off either during the creation of the fracture or during closure, resulting in gas going into the invaded zone. Experimental data is needed to determine if the gas phase leaks-off during the creation of the fracture. Simulations show that the bubbles in a fluid traveling across the face of a porous medium are not likely to attach to the surface of the rock, the filter cake, or penetrate far into the porous medium. In summary, this research has created the first compositional fracturing simulator, a useful tool to aid in energized fracture design. We have made several important and original conclusions about the best practices when using energized fluids in tight gas sands. The models and tools presented here may be used in the future to predict behavior of any multi-phase or multi-component fracturing fluid system.« less

Progress on Discrete Fracture Network models with implications on the predictions of permeability and flow channeling structure

NASA Astrophysics Data System (ADS)

Darcel, C.; Davy, P.; Le Goc, R.; Maillot, J.; Selroos, J. O.

2017-12-01

We present progress on Discrete Fracture Network (DFN) flow modeling, including realistic advanced DFN spatial structures and local fracture transmissivity properties, through an application to the Forsmark site in Sweden. DFN models are a framework to combine fracture datasets from different sources and scales and to interpolate them in combining statistical distributions and stereological relations. The resulting DFN upscaling function - size density distribution - is a model component key to extrapolating fracture size densities between data gaps, from borehole core up to site scale. Another important feature of DFN models lays in the spatial correlations between fractures, with still unevaluated consequences on flow predictions. Indeed, although common Poisson (i.e. spatially random) models are widely used, they do not reflect these geological evidences for more complex structures. To model them, we define a DFN growth process from kinematic rules for nucleation, growth and stopping conditions. It mimics in a simplified way the geological fracturing processes and produces DFN characteristics -both upscaling function and spatial correlations- fully consistent with field observations. DFN structures are first compared for constant transmissivities. Flow simulations for the kinematic and equivalent Poisson DFN models show striking differences: with the kinematic DFN, connectivity and permeability are significantly smaller, down to a difference of one order of magnitude, and flow is much more channelized. Further flow analyses are performed with more realistic transmissivity distribution conditions (sealed parts, relations to fracture sizes, orientations and in-situ stress field). The relative importance of the overall DFN structure in the final flow predictions is discussed.

Compositional Reservoir Simulation of Highly Heterogeneous and Anisotropic Fractured Media in 2D and 3D Unstructured Gridding

NASA Astrophysics Data System (ADS)

Zidane, A.; Firoozabadi, A.

2017-12-01

We present an efficient and accurate numerical model for multicomponent compressible single-phase flow in 2D and 3D fractured media based on higher-order discretization. The numerical model accounts for heterogeneity and anisotropy in unstructured gridding with low mesh dependency. The efficiency of our model is demonstrated by having comparable CPU time between fractured and unfractured media. The fracture cross-flow equilibrium approach (FCFE) is applied on triangular finite elements (FE) in 2D. This allows simulating fractured reservoirs with all possible orientations of fractures as opposed to rectangular FE. In 3D we apply the FCFE approach on the prism FE. The prism FE with FCFE allows simulating realistic fractured domains compared to hexahedron FE. In addition, when using FCFE on triangular and prism FE there is no limitation on the number of intersecting fractures, whereas in rectangular and hexahedron FE the number is limited to 2 in 2D and 3 in 3D. To generate domains with complicated boundaries, we have developed a computer-aided design (CAD) interface in our model. The advances introduced in this work are demonstrated through various examples.

Role of Vascular Endothelial Growth Factor and Transforming Growth Factor-β2 in Rat Bone Tissue after Bone Fracture and Placement of Titanium Implants with Bioactive Bioresorbable Coatings.

PubMed

Kalinichenko, S G; Matveeva, N Yu; Kostiv, R E; Puz', A V

2017-03-01

The study established enhanced expression of vascular endothelial growth factor (VEGF) in the subpopulation of osteoblasts located in the regeneration region of femoral bone fracture near the titanium implants with bioactive calcium phosphate and hydroxyapatite coatings and suppressed activity of transforming growth factor-β2 (TGF-β2) in chondroblasts during the two weeks after surgery. In the delayed posttraumatic period, the distribution of TGF-β2 inversely related to its maximal activity. The data revealed the up-regulating effect of bioresorbable coatings on expression of VEGF and TGF-β2 and their implication in the control over various stages of reparative osteogenesis.

Evaluation of stability of osteosynthesis with K-wires on an artificial model of tibial malleolus fracture.

PubMed

Bumči, Igor; Vlahović, Tomislav; Jurić, Filip; Žganjer, Mirko; Miličić, Gordana; Wolf, Hinko; Antabak, Anko

2015-11-01

Paediatric ankle fractures comprise approximately 4% of all paediatric fractures and 30% of all epiphyseal fractures. Integrity of the ankle "mortise", which consists of tibial and fibular malleoli, is significant for stability and function of the ankle joint. Tibial malleolar fractures are classified as SH III or SH IV intra-articular fractures and, in cases where the fragments are displaced, anatomic reposition and fixation is mandatory. Type SH III-IV fractures of the tibial malleolus are usually treated with open reduction and fixation with cannulated screws that are parallel to the physis. Two K-wires are used for temporary stabilisation of fragments during reduction. A third "guide wire" for the screw is then placed parallel with the physis. Considering the rules of mechanics, it is assumed that the two temporary pins with the additional third pin placed parallel to the physis create a strong triangle and thus provide strong fracture fixation. To prove this hypothesis, an experiment was conducted on the artificial models of the lower end of the tibia from the company "Sawbones". Each model had been sawn in a way that imitates the fracture of medial malleoli and then reattached with 1.8mm pins in various combinations. Prepared models were then tested for tensile and pressure forces. The least stable model was that in which the fractured pieces were attached with only two parallel pins. The most stable model comprised three pins, where two crossed pins were inserted in the opposite compact bone and the third pin was inserted through the epiphysis parallel with and below the growth plate. A potential method of choice for fixation of tibial malleolar fractures comprises three K-wires, where two crossed pins are placed in the opposite compact bone and one is parallel with the growth plate. The benefits associated with this method include shorter operating times and avoidance of a second operation for screw removal. Copyright © 2015 Elsevier Ltd. All rights reserved.

The cost effectiveness of teriparatide as a first-line treatment for glucocorticoid-induced and postmenopausal osteoporosis patients in Sweden.

PubMed

Murphy, Daniel R; Smolen, Lee J; Klein, Timothy M; Klein, Robert W

2012-10-30

This paper presents the model and results to evaluate the use of teriparatide as a first-line treatment of severe postmenopausal osteoporosis (PMO) and glucocorticoid-induced osteoporosis (GIOP). The study's objective was to determine if teriparatide is cost effective against oral bisphosphonates for two large and high risk cohorts. A computer simulation model was created to model treatment, osteoporosis related fractures, and the remaining life of PMO and GIOP patients. Natural mortality and additional mortality from osteoporosis related fractures were included in the model. Costs for treatment with both teriparatide and oral bisphosphonates were included. Drug efficacy was modeled as a reduction to the relative fracture risk for subsequent osteoporosis related fractures. Patient health utilities associated with age, gender, and osteoporosis related fractures were included in the model. Patient costs and utilities were summarized and incremental cost-effectiveness ratios (ICERs) for teriparatide versus oral bisphosphonates and teriparatide versus no treatment were estimated.For each of the PMO and GIOP populations, two cohorts differentiated by fracture history were simulated. The first contained patients with both a historical vertebral fracture and an incident vertebral fracture. The second contained patients with only an incident vertebral fracture. The PMO cohorts simulated had an initial Bone Mineral Density (BMD) T-Score of -3.0. The GIOP cohorts simulated had an initial BMD T-Score of -2.5. The ICERs for teriparatide versus bisphosphonate use for the one and two fracture PMO cohorts were €36,995 per QALY and €19,371 per QALY. The ICERs for teriparatide versus bisphosphonate use for the one and two fracture GIOP cohorts were €20,826 per QALY and €15,155 per QALY, respectively. The selection of teriparatide versus oral bisphosphonates as a first-line treatment for the high risk PMO and GIOP cohorts evaluated is justified at a cost per QALY threshold of €50,000.

Simulation of a multistage fractured horizontal well in a water-bearing tight fractured gas reservoir under non-Darcy flow

NASA Astrophysics Data System (ADS)

Zhang, Rui-Han; Zhang, Lie-Hui; Wang, Rui-He; Zhao, Yu-Long; Huang, Rui

2018-06-01

Reservoir development for unconventional resources such as tight gas reservoirs is in increasing demand due to the rapid decline of production in conventional reserves. Compared with conventional reservoirs, fluid flow in water-bearing tight gas reservoirs is subject to more nonlinear multiphase flow and gas slippage in nano/micro matrix pores because of the strong collisions between rock and gas molecules. Economic gas production from tight gas reservoirs depends on extensive application of water-based hydraulic fracturing of horizontal wells, associated with non-Darcy flow at a high flow rate, geomechanical stress sensitivity of un-propped natural fractures, complex flow geometry and multiscale heterogeneity. How to efficiently and accurately predict the production performance of a multistage fractured horizontal well (MFHW) is challenging. In this paper, a novel multicontinuum, multimechanism, two-phase simulator is established based on unstructured meshes and the control volume finite element method to analyze the production performance of MFHWs. The multiple interacting continua model and discrete fracture model are coupled to integrate the unstimulated fractured reservoir, induced fracture networks (stimulated reservoir volumes, SRVs) and irregular discrete hydraulic fractures. Several simulations and sensitivity analyses are performed with the developed simulator for determining the key factors affecting the production performance of MFHWs. Two widely applied fracturing models, classic hydraulic fracturing which generates long double-wing fractures and the volumetric fracturing aimed at creating large SRVs, are compared to identify which of them can make better use of tight gas reserves.

Post-injection Multiphase Flow Modeling and Risk Assessments for Subsurface CO2 Storage in Naturally Fractured Reservoirs

NASA Astrophysics Data System (ADS)

Jin, G.

2015-12-01

Subsurface storage of carbon dioxide in geological formations is widely regarded as a promising tool for reducing global atmospheric CO2 emissions. Successful geologic storage for sequestrated carbon dioxides must prove to be safe by means of risk assessments including post-injection analysis of injected CO2 plumes. Because fractured reservoirs exhibit a higher degree of heterogeneity, it is imperative to conduct such simulation studies in order to reliably predict the geometric evolution of plumes and risk assessment of post CO2injection. The research has addressed the pressure footprint of CO2 plumes through the development of new techniques which combine discrete fracture network and stochastic continuum modeling of multiphase flow in fractured geologic formations. A subsequent permeability tensor map in 3-D, derived from our preciously developed method, can accurately describe the heterogeneity of fracture reservoirs. A comprehensive workflow integrating the fracture permeability characterization and multiphase flow modeling has been developed to simulate the CO2plume migration and risk assessments. A simulated fractured reservoir model based on high-priority geological carbon sinks in central Alabama has been employed for preliminary study. Discrete fracture networks were generated with an NE-oriented regional fracture set and orthogonal NW-fractures. Fracture permeability characterization revealed high permeability heterogeneity with an order of magnitude of up to three. A multiphase flow model composed of supercritical CO2 and saline water was then applied to predict CO2 plume volume, geometry, pressure footprint, and containment during and post injection. Injection simulation reveals significant permeability anisotropy that favors development of northeast-elongate CO2 plumes, which are aligned with systematic fractures. The diffusive spreading front of the CO2 plume shows strong viscous fingering effects. Post-injection simulation indicates significant upward lateral spreading of CO2 resulting in accumulation of CO2 directly under the seal unit because of its buoyancy and strata-bound vertical fractures. Risk assessment shows that lateral movement of CO2 along interconnected fractures requires widespread seals with high integrity to confine the injected CO2.

Quantifying the Effects of Spatial Uncertainty in Fracture Permeability on CO2 Leakage through Columbia River Basalt Flow Interiors

NASA Astrophysics Data System (ADS)

Gierzynski, A.; Pollyea, R.

2016-12-01

Recent studies suggest that continental flood basalts may be suitable for geologic carbon sequestration, due to fluid-rock reactions that mineralize injected CO2 on relatively short time-scales. Flood basalts also possess a morphological structure conducive to injection, with alternating high-permeability (flow margin) and low-permeability (flow interior) layers. However, little information exists on the behavior of CO2 migration within field-scale fracture networks, particularly within flow interiors and at conditions near the critical point for CO2. In this study, numerical simulation is used to investigate the influence of fracture permeability uncertainty during gravity-driven CO2 migration within a jointed basalt flow interior as CO2 undergoes phase change from supercritical fluid to a subcritical phase. The model domain comprises a 2D fracture network mapped with terrestrial LiDAR scans of Columbia River Basalt acquired near Starbuck, WA. The model domain is 5 m × 5 m with bimodal heterogeneity (fracture and matrix), and initial conditions corresponding to a hydrostatic pressure gradient between 750 and 755 m depth. Under these conditions, the critical point for CO2 occurs 1.5 m above the bottom of the domain. For this model scenario, CO2 enters the base of the fracture network at 0.5 MPa overpressure, and matrix permeability is assumed constant. Fracture permeability follows a lognormal distribution on the basis of fracture aperture values from literature. In order to account for spatial uncertainty, the lognormal fracture permeability distribution is randomly located in the model domain and CO2 migration is simulated within the same fracture network for 50 equally probable realizations. Model results suggest that fracture connectivity, which is independent of permeability distribution, governs the path taken by buoyant CO2 as it rises through the flow interior; however, the permeability distribution strongly governs the CO2 flux magnitude. In particular, this research shows that even where fracture networks are sufficiently connected, CO2 flux is often inhibited by a cell of lower permeability, analogous to an obstruction or asperity in a natural fracture. This impresses the importance of considering spatial uncertainty in fracture apertures when modeling CO2 leakage through a caprock.

Study of sex differences in the association between hip fracture risk and body parameters by DXA-based biomechanical modeling.

PubMed

Nasiri, Masoud; Luo, Yunhua

2016-09-01

There is controversy about whether or not body parameters affect hip fracture in men and women in the same way. In addition, although bone mineral density (BMD) is currently the most important single discriminator of hip fracture, it is unclear if BMD alone is equally effective for men and women. The objective of this study was to quantify and compare the associations of hip fracture risk with BMD and body parameters in men and women using our recently developed two-level biomechanical model that combines a whole-body dynamics model with a proximal-femur finite element model. Sideways fall induced impact force of 130 Chinese clinical cases, including 50 males and 80 females, were determined by subject-specific dynamics modeling. Then, a DXA-based finite element model was used to simulate the femur bone under the fall-induced loading conditions and calculate the hip fracture risk. Body weight, body height, body mass index, trochanteric soft tissue thickness, and hip bone mineral density were determined for each subject and their associations with impact force and hip fracture risk were quantified. Results showed that the association between impact force and hip fracture risk was not strong enough in both men (r=-0.31,p<0.05) and women (r=0.42,p<0.001) to consider the force as a sole indicator of hip fracture risk. The correlation between hip BMD and hip fracture risk in men (r=-0.83,p<0.001) was notably stronger than that in women (r=-0.68,p<0.001). Increased body mass index was not a protective factor against hip fracture in men (r=-0.13,p>0.05), but it can be considered as a protective factor among women (r=-0.28,p<0.05). In contrast to men, trochanteric soft tissue thickness can be considered as a protective factor against hip fracture in women (r=-0.50,p<0.001). This study suggested that the biomechanical risk/protective factors for hip fracture are sex-specific. Therefore, the effect of body parameters should be considered differently for men and women in hip fracture risk assessment tools. These findings support further exploration of sex-specific preventive and protective measurements to reduce the incidence of hip fractures. Copyright © 2016 Elsevier Inc. All rights reserved.

Numerical and Experimental Studies of Particle Settling in Real Fracture Geometries

NASA Astrophysics Data System (ADS)

Roy, Pratanu; Du Frane, Wyatt L.; Kanarska, Yuliya; Walsh, Stuart D. C.

2016-11-01

Proppant is a vital component of hydraulic stimulation operations, improving conductivity by maintaining fracture aperture. While correct placement is a necessary part of ensuring that proppant performs efficiently, the transport behavior of proppant in natural rock fractures is poorly understood. In particular, as companies pursue new propping strategies involving new types of proppant, more accurate models of proppant behavior are needed to help guide their deployment. A major difficulty with simulating reservoir-scale proppant behavior is that continuum models traditionally used to represent large-scale slurry behavior loose applicability in fracture geometries. Particle transport models are often based on representative volumes that are at the same scale or larger than fractures found in hydraulic fracturing operations, making them inappropriate for modeling these types of flows. In the absence of a first-principles approach, empirical closure relations are needed. However, even such empirical closure relationships are difficult to derive without an accurate understanding of proppant behavior on the particle level. Thus, there is a need for experiments and simulations capable of probing phenomena at the sub-fracture scale. In this paper, we present results from experimental and numerical studies investigating proppant behavior at the sub-fracture level, in particular, the role of particle dispersion during proppant settling. In the experimental study, three-dimensional printing techniques are used to accurately reproduce the topology of a fractured Marcellus shale sample inside a particle-flow cell. By recreating the surface in clear plastic resin, proppant movement within the fracture can be tracked directly in real time without the need for X-ray imaging. Particle tracking is further enhanced through the use of mixtures of transparent and opaque proppant analogues. The accompanying numerical studies employ a high-fidelity three-dimensional particle-flow model, capable of explicitly representing the particles, the fracture surface and the interstitial fluid flow. Both studies reveal large-scale vortex motion during particle settling. For the most part, this behavior is independent of the fracture topology, instead driven by interactions between the sinking particles and the upwelling interstitial fluid. This motion results in large amounts of particle dispersion, significantly greater than might be expected from traditional slurry models. The competition between the particles and the fluid also results in a redistribution of particles toward the fracture walls, which has significant implications for the transport of proppant along the fracture.

Additive Effects of Mechanical Marrow Ablation and PTH Treatment on de Novo Bone Formation in Mature Adult Rats

PubMed Central

Zhang, Qing; Miller, Christopher; Bible, Jesse; Li, Jiliang; Xu, Xiaoqing; Mehta, Nozer; Gilligan, James; Vignery, Agnès; Scholz, Jodi A Carlson

2012-01-01

Mechanical ablation of bone marrow in young rats induces rapid but transient bone growth, which can be enhanced and maintained for three weeks by the administration of parathyroid hormone (PTH). Additionally, marrow ablation, followed by PTH treatment for three months leads to increased cortical thickness. In this study, we sought to determine whether PTH enhances bone formation after marrow ablation in aged rats. Aged rats underwent unilateral femoral marrow ablation and treatment with PTH or vehicle for four weeks. Both femurs from each rat were analyzed by X-ray and pQCT, then analyzed either by microCT, histology or biomechanical testing. Marrow ablation alone induced transient bone formation of low abundance that persisted over four weeks, while marrow ablation followed by PTH induced bone formation of high abundance that also persisted over four weeks. Our data confirms that the osteo-inducive effect of marrow ablation and the additive effect of marrow ablation, followed by PTH, occurs in aged rats. Our observations open new avenues of investigations in the field of tissue regeneration. Local marrow ablation, in conjunction with an anabolic agent, might provide a new platform for rapid site-directed bone growth in areas of high bone loss, such as in the hip and wrist, which are subject to fracture. PMID:24710549

Rock deformation models and fluid leak-off in hydraulic fracturing

NASA Astrophysics Data System (ADS)

Yarushina, Viktoriya M.; Bercovici, David; Oristaglio, Michael L.

2013-09-01

Fluid loss into reservoir rocks during hydraulic fracturing is modelled via a poro-elastoplastic pressure diffusion equation in which the total compressibility is a sum of fluid, rock and pore space compressibilities. Inclusion of pore compressibility and porosity-dependent permeability in the model leads to a strong pressure dependence of leak-off (i.e. drainage rate). Dilation of the matrix due to fluid invasion causes higher rates of fluid leak-off. The present model is appropriate for naturally fractured and tight gas reservoirs as well as for soft and poorly consolidated formations whose mechanical behaviour departs from simple elastic laws. Enhancement of the leak-off coefficient by dilation, predicted by the new model, may help explain the low percentage recovery of fracturing fluid (usually between 5 and 50 per cent) in shale gas stimulation by hydraulic fracturing.

Development of the T+M coupled flow–geomechanical simulator to describe fracture propagation and coupled flow–thermal–geomechanical processes in tight/shale gas systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Jihoon; Moridis, George J.

2013-10-01

We developed a hydraulic fracturing simulator by coupling a flow simulator to a geomechanics code, namely T+M simulator. Modeling of the vertical fracture development involves continuous updating of the boundary conditions and of the data connectivity, based on the finite element method for geomechanics. The T+M simulator can model the initial fracture development during the hydraulic fracturing operations, after which the domain description changes from single continuum to double or multiple continua in order to rigorously model both flow and geomechanics for fracture-rock matrix systems. The T+H simulator provides two-way coupling between fluid-heat flow and geomechanics, accounting for thermoporomechanics, treatsmore » nonlinear permeability and geomechanical moduli explicitly, and dynamically tracks changes in the fracture(s) and in the pore volume. We also fully accounts for leak-off in all directions during hydraulic fracturing. We first validate the T+M simulator, matching numerical solutions with the analytical solutions for poromechanical effects, static fractures, and fracture propagations. Then, from numerical simulation of various cases of the planar fracture propagation, shear failure can limit the vertical fracture propagation of tensile failure, because of leak-off into the reservoirs. Slow injection causes more leak-off, compared with fast injection, when the same amount of fluid is injected. Changes in initial total stress and contributions of shear effective stress to tensile failure can also affect formation of the fractured areas, and the geomechanical responses are still well-posed.« less

Proceedings of the International Symposium on Dynamics of Fluids in Fractured Rocks: Concepts and Recent Advances

DOE Office of Scientific and Technical Information (OSTI.GOV)

Faybishenko, B.

1999-02-01

This publication contains extended abstracts of papers presented at the International Symposium ''Dynamics of Fluids in Fractured Rocks: Concepts and Recent Advances'' held at Ernest Orlando Lawrence Berkeley National Laboratory on February 10-12, 1999. This Symposium is organized in Honor of the 80th Birthday of Paul A. Witherspoon, who initiated some of the early investigations on flow and transport in fractured rocks at the University of California, Berkeley, and at Lawrence Berkeley National Laboratory. He is a key figure in the development of basic concepts, modeling, and field measurements of fluid flow and contaminant transport in fractured rock systems. Themore » technical problems of assessing fluid flow, radionuclide transport, site characterization, modeling, and performance assessment in fractured rocks remain the most challenging aspects of subsurface flow and transport investigations. An understanding of these important aspects of hydrogeology is needed to assess disposal of nu clear wastes, development of geothermal resources, production of oil and gas resources, and remediation of contaminated sites. These Proceedings of more than 100 papers from 12 countries discuss recent scientific and practical developments and the status of our understanding of fluid flow and radionuclide transport in fractured rocks. The main topics of the papers are: Theoretical studies of fluid flow in fractured rocks; Multi-phase flow and reactive chemical transport in fractured rocks; Fracture/matrix interactions; Hydrogeological and transport testing; Fracture flow models; Vadose zone studies; Isotopic studies of flow in fractured systems; Fractures in geothermal systems; Remediation and colloid transport in fractured systems; and Nuclear waste disposal in fractured rocks.« less

Application of fracture toughness scaling models to the ductile-to- brittle transition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Link, R.E.; Joyce, J.A.

1996-01-01

An experimental investigation of fracture toughness in the ductile-brittle transition range was conducted. A large number of ASTM A533, Grade B steel, bend and tension specimens with varying crack lengths were tested throughout the transition region. Cleavage fracture toughness scaling models were utilized to correct the data for the loss of constraint in short crack specimens and tension geometries. The toughness scaling models were effective in reducing the scatter in the data, but tended to over-correct the results for the short crack bend specimens. A proposed ASTM Test Practice for Fracture Toughness in the Transition Range, which employs a mastermore » curve concept, was applied to the results. The proposed master curve over predicted the fracture toughness in the mid-transition and a modified master curve was developed that more accurately modeled the transition behavior of the material. Finally, the modified master curve and the fracture toughness scaling models were combined to predict the as-measured fracture toughness of the short crack bend and the tension specimens. It was shown that when the scaling models over correct the data for loss of constraint, they can also lead to non-conservative estimates of the increase in toughness for low constraint geometries.« less

Injection-Sensitive Mechanics of Hydraulic Fracture Interaction with Discontinuities

NASA Astrophysics Data System (ADS)

Chuprakov, D.; Melchaeva, O.; Prioul, R.

2014-09-01

We develop a new analytical model, called OpenT, that solves the elasticity problem of a hydraulic fracture (HF) contact with a pre-existing discontinuity natural fracture (NF) and the condition for HF re-initiation at the NF. The model also accounts for fluid penetration into the permeable NFs. For any angle of fracture intersection, the elastic problem of a blunted dislocation discontinuity is solved for the opening and sliding generated at the discontinuity. The sites and orientations of a new tensile crack nucleation are determined based on a mixed stress- and energy-criterion. In the case of tilted fracture intersection, the finite offset of the new crack initiation point along the discontinuity is computed. We show that aside from known controlling parameters such stress contrast, cohesional and frictional properties of the NFs and angle of intersection, the fluid injection parameters such as the injection rate and the fluid viscosity are of first-order in the crossing behavior. The model is compared to three independent laboratory experiments, analytical criteria of Blanton, extended Renshaw-Pollard, as well as fully coupled numerical simulations. The relative computational efficiency of OpenT model (compared to the numerical models) makes the model attractive for implementation in modern engineering tools simulating hydraulic fracture propagation in naturally fractured environments.

Modeling thermal stress propagation during hydraulic stimulation of geothermal wells

NASA Astrophysics Data System (ADS)

Jansen, Gunnar; Miller, Stephen A.

2017-04-01

A large fraction of the world's water and energy resources are located in naturally fractured reservoirs within the earth's crust. Depending on the lithology and tectonic history of a formation, fracture networks can range from dense and homogeneous highly fractured networks to single large scale fractures dominating the flow behavior. Understanding the dynamics of such reservoirs in terms of flow and transport is crucial to successful application of engineered geothermal systems (also known as enhanced geothermal systems or EGS) for geothermal energy production in the future. Fractured reservoirs are considered to consist of two distinct separate media, namely the fracture and matrix space respectively. Fractures are generally thin, highly conductive containing only small amounts of fluid, whereas the matrix rock provides high fluid storage but typically has much smaller permeability. Simulation of flow and transport through fractured porous media is challenging due to the high permeability contrast between the fractures and the surrounding rock matrix. However, accurate and efficient simulation of flow through a fracture network is crucial in order to understand, optimize and engineer reservoirs. It has been a research topic for several decades and is still under active research. Accurate fluid flow simulations through field-scale fractured reservoirs are still limited by the power of current computer processing units (CPU). We present an efficient implementation of the embedded discrete fracture model, which is a promising new technique in modeling the behavior of enhanced geothermal systems. An efficient coupling strategy is determined for numerical performance of the model. We provide new insight into the coupled modeling of fluid flow, heat transport of engineered geothermal reservoirs with focus on the thermal stress changes during the stimulation process. We further investigate the interplay of thermal and poro-elastic stress changes in the reservoir. Combined with a analytical formulation for the injection temperatures in the open hole section of a geothermal well, the stress changes induced during the injection period of reservoir development can be studied.

Semi-analytical model of cross-borehole flow experiments for fractured medium characterization

NASA Astrophysics Data System (ADS)

Roubinet, D.; Irving, J.; Day-Lewis, F. D.

2014-12-01

The study of fractured rocks is extremely important in a wide variety of research fields where the fractures and faults can represent either rapid access to some resource of interest or potential pathways for the migration of contaminants in the subsurface. Identification of their presence and determination of their properties are critical and challenging tasks that have led to numerous fracture characterization methods. Among these methods, cross-borehole flowmeter analysis aims to evaluate fracture connections and hydraulic properties from vertical-flow-velocity measurements conducted in one or more observation boreholes under forced hydraulic conditions. Previous studies have demonstrated that analysis of these data can provide important information on fracture connectivity, transmissivity, and storativity. Estimating these properties requires the development of analytical and/or numerical modeling tools that are well adapted to the complexity of the problem. Quantitative analysis of cross-borehole flowmeter experiments, in particular, requires modeling formulations that: (i) can be adapted to a variety of fracture and experimental configurations; (ii) can take into account interactions between the boreholes because their radii of influence may overlap; and (iii) can be readily cast into an inversion framework that allows for not only the estimation of fracture hydraulic properties, but also an assessment of estimation error. To this end, we present a new semi-analytical formulation for cross-borehole flow in fractured media that links transient vertical-flow velocities measured in one or a series of observation wells during hydraulic forcing to the transmissivity and storativity of the fractures intersected by these wells. Our model addresses the above needs and provides a flexible and computationally efficient semi-analytical framework having strong potential for future adaptation to more complex configurations. The proposed modeling approach is demonstrated in the context of sensitivity analysis for a relatively simple two-fracture synthetic problem, as well as in the context of field-data analysis for fracture connectivity and estimation of corresponding hydraulic properties.

Understanding how hydrodynamics affects particle transport in saturated fractures using modelling and experimental results

NASA Astrophysics Data System (ADS)

Cianflone, S.; Lakhian, V.; Dickson, S. E.

2013-12-01

Approximately 35% of Canadians and Americans utilize groundwater for drinking water and as such, it is essential to understand the mechanisms which may jeopardize this resource. Porous media aquifers typically provide significant removal of particulate contaminants (eg. viruses, bacteria); however, fractures in fractured rock aquifers and aquitards often provide pathways for particles to move in greater numbers and speed than in porous media. Thus, understanding flow and transport in fractures is important for the preservation and use of groundwater sources. Models based on coupling flow and transport equations can be used in understanding transport in fractures. Both experiments and simulations have shown that there are inconsistencies in current transport, attachment and detachment theory, particularly when particle size is varied. The assumption that hydrodynamic effects do not significantly affect transport of particles is likely untrue. As well, it has been shown that preferential flow paths occur in fractures, but the effects of path specific properties such as fracture geometry have yet to be thoroughly explored. It has been observed that eddies caused by local changes in geometry exist in fractures in the environment and models have demonstrated that such eddies will retard the flow of particles. In this work, two 2D fractures were randomly generated with a mean aperture of approximately 2mm. Finite element software, COMSOL Multiphysics, generated flow fields through the fractures by numerically solving the steady-state Navier-Stokes equation for varied flow rates. Eddies were observed in one of the fractures at both low (~1 m/day) and high (>100 m/day) velocities. A program was written using random walk particle tracking to simulate transport. Theories of attachment, detachment and matrix flow are not included in this model in order to isolate hydrodynamic forces. In combination with the modelling procedure, the two fractures were inscribed into pieces of poly(methyl methacrylate), thus creating a pseudo-2D fracture. Namely, the 2D fracture (x-y coordinates) is cut into the plastic using a laser printer, thus the z-coordinate is constant to a depth of 2.3 mm. Experiments using Acid Yellow 17, as a tracer, as well as fluorescent microspheres (42.5 nm and 525 nm, non-carboxylated to minimize attachment/detachment) will be performed in order to compare simulations and experimental results. Concentrations of the microspheres and tracer were measured at the effluent end of the fracture where the end cap housed an LED (400-470 nm) and an optical fibre attached to a spectrophotometer. Simulations suggest that in fractures where eddies occur, there is retention of smaller particles only when there is sufficient diffusion and a slow enough fluid velocity to allow them to enter the eddy. Otherwise, the particles exit the fracture earlier than typically expected when considering particle size exclusion and average fluid velocity. Further modelling results suggest that using bulk measurements (eg. mean aperture, mean fluid velocity, and measures of fracture roughness) to predict the resultant particulate outflow in a saturated fracture is difficult. We plan to include visualization experiments in order to draw further comparisons to the modelling results.

A new estimation of equivalent matrix block sizes in fractured media with two-phase flow applications in dual porosity models

NASA Astrophysics Data System (ADS)

Jerbi, Chahir; Fourno, André; Noetinger, Benoit; Delay, Frederick

2017-05-01

Single and multiphase flows in fractured porous media at the scale of natural reservoirs are often handled by resorting to homogenized models that avoid the heavy computations associated with a complete discretization of both fractures and matrix blocks. For example, the two overlapping continua (fractures and matrix) of a dual porosity system are coupled by way of fluid flux exchanges that deeply condition flow at the large scale. This characteristic is a key to realistic flow simulations, especially for multiphase flow as capillary forces and contrasts of fluid mobility compete in the extraction of a fluid from a capacitive matrix then conveyed through the fractures. The exchange rate between fractures and matrix is conditioned by the so-called mean matrix block size which can be viewed as the size of a single matrix block neighboring a single fracture within a mesh of a dual porosity model. We propose a new evaluation of this matrix block size based on the analysis of discrete fracture networks. The fundaments rely upon establishing at the scale of a fractured block the equivalence between the actual fracture network and a Warren and Root network only made of three regularly spaced fracture families parallel to the facets of the fractured block. The resulting matrix block sizes are then compared via geometrical considerations and two-phase flow simulations to the few other available methods. It is shown that the new method is stable in the sense it provides accurate sizes irrespective of the type of fracture network investigated. The method also results in two-phase flow simulations from dual porosity models very close to that from references calculated in finely discretized networks. Finally, calculations of matrix block sizes by this new technique reveal very rapid, which opens the way to cumbersome applications such as preconditioning a dual porosity approach applied to regional fractured reservoirs.

Individual risk factors for deep infection and compromised fracture healing after intramedullary nailing of tibial shaft fractures: a single centre experience of 480 patients.

PubMed

Metsemakers, W-J; Handojo, K; Reynders, P; Sermon, A; Vanderschot, P; Nijs, S

2015-04-01

Despite modern advances in the treatment of tibial shaft fractures, complications including nonunion, malunion, and infection remain relatively frequent. A better understanding of these injuries and its complications could lead to prevention rather than treatment strategies. A retrospective study was performed to identify risk factors for deep infection and compromised fracture healing after intramedullary nailing (IMN) of tibial shaft fractures. Between January 2000 and January 2012, 480 consecutive patients with 486 tibial shaft fractures were enrolled in the study. Statistical analysis was performed to determine predictors of deep infection and compromised fracture healing. Compromised fracture healing was subdivided in delayed union and nonunion. The following independent variables were selected for analysis: age, sex, smoking, obesity, diabetes, American Society of Anaesthesiologists (ASA) classification, polytrauma, fracture type, open fractures, Gustilo type, primary external fixation (EF), time to nailing (TTN) and reaming. As primary statistical evaluation we performed a univariate analysis, followed by a multiple logistic regression model. Univariate regression analysis revealed similar risk factors for delayed union and nonunion, including fracture type, open fractures and Gustilo type. Factors affecting the occurrence of deep infection in this model were primary EF, a prolonged TTN, open fractures and Gustilo type. Multiple logistic regression analysis revealed polytrauma as the single risk factor for nonunion. With respect to delayed union, no risk factors could be identified. In the same statistical model, deep infection was correlated with primary EF. The purpose of this study was to evaluate risk factors of poor outcome after IMN of tibial shaft fractures. The univariate regression analysis showed that the nature of complications after tibial shaft nailing could be multifactorial. This was not confirmed in a multiple logistic regression model, which only revealed polytrauma and primary EF as risk factors for nonunion and deep infection, respectively. Future strategies should focus on prevention in high-risk populations such as polytrauma patients treated with EF. Copyright © 2014 Elsevier Ltd. All rights reserved.

Subclinical hypervitaminosis A causes fragile bones in rats.

PubMed

Johansson, S; Lind, P M; Hakansson, H; Oxlund, H; Orberg, J; Melhus, H

2002-12-01

Excessive intake of vitamin A has been associated with an increased risk of hip fracture in humans. This finding has raised the question of whether long-term intake of relatively moderate doses ("subclinical" hypervitaminosis A) contributes to fracture risk. Although it has been known for more than half a century that toxic doses of vitamin A lead to spontaneous fractures in rats, the lowest intake that induces adverse effects is not known, and the result of exposure to excessive doses that do not cause general toxicity has been rarely investigated. In this study, mature female rats were fed a standard diet with 12 IU vitamin A/g pellet (control, C), or standard diet supplemented with either 120 IU ("10 x C") or 600 IU ("50 x C") vitamin A/g pellet for 12 weeks. Fifteen animals were included in each group. The supplemented diets correspond to a vitamin A intake of approximately 1800 IU/day and 9000 IU/day, respectively. The latter dose is about one third of that previously reported to cause skeletal lesions. At the end of the study, serum retinyl esters were elevated 4- (p < 0.01) and 20-fold (p < 0.001) and the total amount of liver retinoid had increased 3- (p < 0.001) and 7-fold (p < 0.001) in the 10 x C and 50 x C group, respectively. The animals showed no clinical signs of general toxicity, and there were no significant bone changes in the 10 x C group. However, in the 50 x C group, a characteristic thinning of the cortex (cortical area -6.5% [p < 0.001]) and reduction of the diameter of the long bones were evident (bone cross-sectional area -7.2% [p < 0.01] at the midshaft and -11.0% [p < 0.01] at the metaphysis), as measured by peripheral quantitative computed tomography. In agreement with these data and a decreased polar strength strain index (-14.0%, p < 0.01), the three-point bending breaking force of the femur was reduced by 10.3% (p < 0.01) in the 50 x C group. These data indicate that the negative skeletal effects appear at a subchronic vitamin A intake of somewhere between 10 and 50 times the standard diet. This level is considerably lower than previously reported. Our results suggest that long-term ingestion of modest excesses of vitamin A may contribute to fracture risk. Copyright 2002 by Elsevier Science Inc.

Fracture properties of concrete specimens made from alkali activated binders

NASA Astrophysics Data System (ADS)

Šimonová, Hana; Kucharczyková, Barbara; Topolář, Libor; Bílek, Vlastimil, Jr.; Keršner, Zbyněk

2017-09-01

The aim of this paper is to quantify crack initiation and other fracture properties - effective fracture toughness and specific fracture energy - of two types of concrete with an alkali activated binder. The beam specimens with a stress concentrator were tested in a three-point bending test after 28, 90, and 365 days of maturing. Records of fracture tests in the form of load versus deflection (P-d) diagrams were evaluated using effective crack model and work-of-fracture method and load versus mouth crack opening displacement (P-CMOD) diagrams were evaluated using the Double-K fracture model. The initiation of cracks during the fracture tests for all ages was also monitored by the acoustic emission method. The higher value of monitored mechanical fracture parameters of concrete with alkali activated blast furnace slag were achieved with substitution blast furnace slag by low calcium fly ash in comparison with substitution by cement kiln dust.

Measurement of width and pressure in a propagating hydraulic fracture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Warpinski, N.R.

Measurements of width and pressure in a propagating hydraulic fracture have been made in tests conducted at the U.S. DOE's Nevada test site. This was accomplished by creating an ''instrumented fracture'' at a tunnel complex (at a depth of 1,400 ft (425 m)) where realistic insitu conditions prevail, particularly with respect to stress and geologic features such as natural fractures and material anisotropy. Analyses of these data show that the pressure drop along the fracture length is much larger than predicted by viscous theory, which currently is used in models. This apparently is caused by the tortuosity of the fracturemore » path, multiple fracture strands, roughness, and sharp turns (corners) in the flow path resulting from natural fractures and rock property variations. It suggests that fracture design models need to be updated to include a more realistic friction factor so that fracture lengths are not overestimated.« less

Measurement of width and pressure in a propagating hydraulic fracture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Warpinski, N.R.

Measurements of width and pressure in a propagating hydraulic fracture have been made in tests conducted at DOE's Nevada Test Site. This was accomplished by creating an ''instrumented fracture'' at a tunnel complex (at a depth of 1400 ft) where realistic in-situ conditions prevail, particularly with respect to stress and geologic features such as natural fractures and material anisotropy. Analyses of these data show that the pressure drop along the fracture length is much larger than predicted by viscous theory and currently in use in models today. This is apparently due to the tortuosity of the fracture path, multiple fracturemore » strands, roughness and sharp turns (corners) in the flow path due to natural fractures and rock property variations. It suggests that fracture design models need to be updated to include a more realistic friction factor so that fracture lengths are not overestimated.« less

Semianalytical solutions for transport in aquifer and fractured clay matrix system

NASA Astrophysics Data System (ADS)

Huang, Junqi; Goltz, Mark N.

2015-09-01

A three-dimensional mathematical model that describes transport of contaminant in a horizontal aquifer with simultaneous diffusion into a fractured clay formation is proposed. A group of semianalytical solutions is derived based on specific initial and boundary conditions as well as various source functions. The analytical model solutions are evaluated by numerical Laplace inverse transformation and analytical Fourier inverse transformation. The model solutions can be used to study the fate and transport in a three-dimensional spatial domain in which a nonaqueous phase liquid exists as a pool atop a fractured low-permeability clay layer. The nonaqueous phase liquid gradually dissolves into the groundwater flowing past the pool, while simultaneously diffusing into the fractured clay formation below the aquifer. Mass transfer of the contaminant into the clay formation is demonstrated to be significantly enhanced by the existence of the fractures, even though the volume of fractures is relatively small compared to the volume of the clay matrix. The model solution is a useful tool in assessing contaminant attenuation processes in a confined aquifer underlain by a fractured clay formation.

Discontinuities in effective permeability due to fracture percolation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hyman, Jeffrey De'Haven; Karra, Satish; Carey, James William

Motivated by a triaxial coreflood experiment with a sample of Utica shale where an abrupt jump in permeability was observed, possibly due to the creation of a percolating fracture network through the sample, we perform numerical simulations based on the experiment to characterize how the effective permeability of otherwise low-permeability porous media depends on fracture formation, connectivity, and the contrast between the fracture and matrix permeabilities. While a change in effective permeability due to fracture formation is expected, the dependence of its magnitude upon the contrast between the matrix permeability and fracture permeability and the fracture network structure is poorlymore » characterized. We use two different high-fidelity fracture network models to characterize how effective permeability changes as percolation occurs. The first is a dynamic two-dimensional fracture propagation model designed to mimic the laboratory settings of the experiment. The second is a static three-dimensional discrete fracture network (DFN) model, whose fracture and network statistics are based on the fractured sample of Utica shale. Once the network connects the inflow and outflow boundaries, the effective permeability increases non-linearly with network density. In most networks considered, a jump in the effective permeability was observed when the embedded fracture network percolated. We characterize how the magnitude of the jump, should it occur, depends on the contrast between the fracture and matrix permeabilities. For small contrasts between the matrix and fracture permeabilities the change is insignificant. However, for larger contrasts, there is a substantial jump whose magnitude depends non-linearly on the difference between matrix and fracture permeabilities. A power-law relationship between the size of the jump and the difference between the matrix and fracture permeabilities is observed. In conclusion, the presented results underscore the importance of fracture network topology on the upscaled properties of the porous medium in which it is embedded.« less

A New Physics-Based Modeling of Multiple Non-Planar Hydraulic Fractures Propagation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Jing; Huang, Hai; Deo, Milind

Because of the low permeability in shale plays, closely spaced hydraulic fractures and multilateral horizontal wells are generally required to improve production. Therefore, understanding the potential fracture interaction and stress evolution is critical in optimizing fracture/well design and completion strategy in multi-stage horizontal wells. In this paper, a novel fully coupled reservoir flow and geomechanics model based on the dual-lattice system is developed to simulate multiple non-planar fractures propagation. The numerical model from Discrete Element Method (DEM) is used to simulate the mechanics of fracture propagations and interactions, while a conjugate irregular lattice network is generated to represent fluid flowmore » in both fractures and formation. The fluid flow in the formation is controlled by Darcy’s law, but within fractures it is simulated by using cubic law for laminar flow through parallel plates. Initiation, growth and coalescence of the microcracks will lead to the generation of macroscopic fractures, which is explicitly mimicked by failure and removal of bonds between particles from the discrete element network. We investigate the fracture propagation path in both homogeneous and heterogeneous reservoirs using the simulator developed. Stress shadow caused by the transverse fracture will change the orientation of principal stress in the fracture neighborhood, which may inhibit or alter the growth direction of nearby fracture clusters. However, the initial in-situ stress anisotropy often helps overcome this phenomenon. Under large in-situ stress anisotropy, the hydraulic fractures are more likely to propagate in a direction that is perpendicular to the minimum horizontal stress. Under small in-situ stress anisotropy, there is a greater chance for fractures from nearby clusters to merge with each other. Then, we examine the differences in fracture geometry caused by fracturing in cemented or uncemented wellbore. Moreover, the impact of intrinsic reservoir heterogeneity caused by the rock fabric and mineralogy on fracture nucleation and propagation paths is examined through a three-layered reservoir. Finally, we apply the method to a realistic heterogeneous dataset.« less

Discontinuities in effective permeability due to fracture percolation

DOE PAGES

Hyman, Jeffrey De'Haven; Karra, Satish; Carey, James William; ...

2018-01-31

Motivated by a triaxial coreflood experiment with a sample of Utica shale where an abrupt jump in permeability was observed, possibly due to the creation of a percolating fracture network through the sample, we perform numerical simulations based on the experiment to characterize how the effective permeability of otherwise low-permeability porous media depends on fracture formation, connectivity, and the contrast between the fracture and matrix permeabilities. While a change in effective permeability due to fracture formation is expected, the dependence of its magnitude upon the contrast between the matrix permeability and fracture permeability and the fracture network structure is poorlymore » characterized. We use two different high-fidelity fracture network models to characterize how effective permeability changes as percolation occurs. The first is a dynamic two-dimensional fracture propagation model designed to mimic the laboratory settings of the experiment. The second is a static three-dimensional discrete fracture network (DFN) model, whose fracture and network statistics are based on the fractured sample of Utica shale. Once the network connects the inflow and outflow boundaries, the effective permeability increases non-linearly with network density. In most networks considered, a jump in the effective permeability was observed when the embedded fracture network percolated. We characterize how the magnitude of the jump, should it occur, depends on the contrast between the fracture and matrix permeabilities. For small contrasts between the matrix and fracture permeabilities the change is insignificant. However, for larger contrasts, there is a substantial jump whose magnitude depends non-linearly on the difference between matrix and fracture permeabilities. A power-law relationship between the size of the jump and the difference between the matrix and fracture permeabilities is observed. In conclusion, the presented results underscore the importance of fracture network topology on the upscaled properties of the porous medium in which it is embedded.« less

Topical Rifampin Powder for Orthopaedic Trauma Part I: Rifampin powder reduces recalcitrant infection in a delayed treatment musculoskeletal trauma model.

PubMed

Shiels, Stefanie M; Tennent, David J; Wenke, Joseph C

2018-05-21

Open fractures become infected despite meticulous debridement and care. Locally applied antibiotics, commonly embedded in polymethylmethacrylate, deliver high doses of drug directly to the fracture site. Direct application of antibiotic powder, which is being applied prophylactically in spine surgery, is a recent interest in the trauma sector, where bacterial biofilms are more prevalent. Traditional antibiotics, such as vancomycin, are poor performers against bacterial biofilms thus are ineffective in delayed treatment. Rifampin is an effective eradicator of Staphylococcal biofilms. Here, a rat model of musculoskeletal trauma was used to evaluate the utility of locally applied rifampin powder for reducing established orthopaedic Staphylococcal infections in a delayed treatment scenario that previously indicated the limited use of local vancomycin. By applying rifampin powder directly to the contaminated segmental defect, the number of bacteria, as well as clinical indications of infection, were significantly reduced compared to vancomycin and daptomycin. Considering the Infectious Disease Society of America's recommendation to use rifampin in combination with another antibiotic to reduce the onset of rifampin resistance, rifampin powder was also applied in combination with vancomycin or daptomycin with insignificant changes in eradication performance. No indications of rifampin resistance were identified. Statement of Clinical Significance: The use of locally applied rifampin is a promising therapy for mature and tolerant musculoskeletal infections. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Calcium Sulphate/Hydroxyapatite Carrier for Bone Formation in the Femoral Neck of Osteoporotic Rats.

PubMed

Sirka, Aurimas; Raina, Deepak Bushan; Isaksson, Hanna; Tanner, K Elizabeth; Smailys, Alfredas; Kumar, Ashok; Tarasevicius, Sarunas; Tägil, Magnus; Lidgren, Lars

2018-06-01

We investigated bone regeneration in the femoral neck canal of osteoporotic rats using a novel animal model. We used a calcium sulphate (CS)/ Hydroxyapatite (HA) carrier to locally deliver a bisphosphonate, zoledronic acid (ZA), with or without added recombinant human bone morphogenic protein-2 (rhBMP-2). Ovariectomized Sprague-Dawley rats of 28 weeks age were used. A 1 mm diameter and 8 mm long defect was created in the femoral neck by drilling from the lateral cortex in the axis of the femoral neck leaving the surrounding cortex intact. Three treatment groups and one control group were used 1) CS/HA alone, 2) CS/HA+ ZA (10 μg) 3) CS/HA+ZA (10 μg)+rhBMP-2 (4 μg) and 4) Empty defect. The bone formation was assessed at 4 weeks post-surgery using in vivo micro computed tomography (micro-CT). At 8 weeks post-surgery, the animals were sacrificed and both defect and contralateral femurs were subjected to micro-CT, mechanical testing and histology. Micro-CT results showed that the combination of CS/HA with ZA or ZA+rhBMP-2 increased the bone formation in the defect when compared to the other groups and to the contralateral hips. Evidence of new dense bone formation in CS/HA+ZA and CS/HA+ZA+rhBMP-2 groups was seen histologically. Mechanical testing results showed no differences in the load to fracture between the treatments in either of the treated or contralateral legs. The CS/HA biomaterial can be used as a carrier for ZA and rhBMP-2 to regenerate bone in the femoral neck canal of osteoporotic rats.

Origins and nature of non-Fickian transport through fractures

NASA Astrophysics Data System (ADS)

Wang, L.; Cardenas, M. B.

2014-12-01

Non-Fickian transport occurs across all scales within fractured and porous geological media. Fundamental understanding and appropriate characterization of non-Fickian transport through fractures is critical for understanding and prediction of the fate of solutes and other scalars. We use both analytical and numerical modeling, including direct numerical simulation and particle tracking random walk, to investigate the origin of non-Fickian transport through both homogeneous and heterogeneous fractures. For the simple homogenous fracture case, i.e., parallel plates, we theoretically derived a formula for dynamic longitudinal dispersion (D) within Poiseuille flow. Using the closed-form expression for the theoretical D, we quantified the time (T) and length (L) scales separating preasymptotic and asymptotic dispersive transport, with T and L proportional to aperture (b) of parallel plates to second and fourth orders, respectively. As for heterogeneous fractures, the fracture roughness and correlation length are closely associated with the T and L, and thus indicate the origin for non-Fickian transport. Modeling solute transport through 2D rough-walled fractures with continuous time random walk with truncated power shows that the degree of deviation from Fickian transport is proportional to fracture roughness. The estimated L for 2D rough-walled fractures is significantly longer than that derived from the formula within Poiseuille flow with equivalent b. Moreover, we artificially generated normally distributed 3D fractures with fixed correlation length but different fracture dimensions. Solute transport through 3D fractures was modeled with a particle tracking random walk algorithm. We found that transport transitions from non-Fickian to Fickian with increasing fracture dimensions, where the estimated L for the studied 3D fractures is related to the correlation length.

Theoretical Analysis of the Mechanism of Fracture Network Propagation with Stimulated Reservoir Volume (SRV) Fracturing in Tight Oil Reservoirs.

PubMed

Su, Yuliang; Ren, Long; Meng, Fankun; Xu, Chen; Wang, Wendong

2015-01-01

Stimulated reservoir volume (SRV) fracturing in tight oil reservoirs often induces complex fracture-network growth, which has a fundamentally different formation mechanism from traditional planar bi-winged fracturing. To reveal the mechanism of fracture network propagation, this paper employs a modified displacement discontinuity method (DDM), mechanical mechanism analysis and initiation and propagation criteria for the theoretical model of fracture network propagation and its derivation. A reasonable solution of the theoretical model for a tight oil reservoir is obtained and verified by a numerical discrete method. Through theoretical calculation and computer programming, the variation rules of formation stress fields, hydraulic fracture propagation patterns (FPP) and branch fracture propagation angles and pressures are analyzed. The results show that during the process of fracture propagation, the initial orientation of the principal stress deflects, and the stress fields at the fracture tips change dramatically in the region surrounding the fracture. Whether the ideal fracture network can be produced depends on the geological conditions and on the engineering treatments. This study has both theoretical significance and practical application value by contributing to a better understanding of fracture network propagation mechanisms in unconventional oil/gas reservoirs and to the improvement of the science and design efficiency of reservoir fracturing.

Theoretical Analysis of the Mechanism of Fracture Network Propagation with Stimulated Reservoir Volume (SRV) Fracturing in Tight Oil Reservoirs

PubMed Central

Su, Yuliang; Ren, Long; Meng, Fankun; Xu, Chen; Wang, Wendong

2015-01-01

Stimulated reservoir volume (SRV) fracturing in tight oil reservoirs often induces complex fracture-network growth, which has a fundamentally different formation mechanism from traditional planar bi-winged fracturing. To reveal the mechanism of fracture network propagation, this paper employs a modified displacement discontinuity method (DDM), mechanical mechanism analysis and initiation and propagation criteria for the theoretical model of fracture network propagation and its derivation. A reasonable solution of the theoretical model for a tight oil reservoir is obtained and verified by a numerical discrete method. Through theoretical calculation and computer programming, the variation rules of formation stress fields, hydraulic fracture propagation patterns (FPP) and branch fracture propagation angles and pressures are analyzed. The results show that during the process of fracture propagation, the initial orientation of the principal stress deflects, and the stress fields at the fracture tips change dramatically in the region surrounding the fracture. Whether the ideal fracture network can be produced depends on the geological conditions and on the engineering treatments. This study has both theoretical significance and practical application value by contributing to a better understanding of fracture network propagation mechanisms in unconventional oil/gas reservoirs and to the improvement of the science and design efficiency of reservoir fracturing. PMID:25966285

Faulting, fracturing and in situ stress prediction in the Ahnet Basin, Algeria — a finite element approach

NASA Astrophysics Data System (ADS)

Beekman, Fred; Badsi, Madjid; van Wees, Jan-Diederik

2000-05-01

Many low-efficiency hydrocarbon reservoirs are productive largely because effective reservoir permeability is controlled by faults and natural fractures. Accurate and low-cost information on basic fault and fracture properties, orientation in particular, is critical in reducing well costs and increasing well recoveries. This paper describes how we used an advanced numerical modelling technique, the finite element method (FEM), to compute site-specific in situ stresses and rock deformation and to predict fracture attributes as a function of material properties, structural position and tectonic stress. Presented are the numerical results of two-dimensional, plane-strain end-member FEM models of a hydrocarbon-bearing fault-propagation-fold structure. Interpretation of the modelling results remains qualitative because of the intrinsic limitations of numerical modelling; however, it still allows comparisons with (the little available) geological and geophysical data. In all models, the weak mechanical strength and flow properties of a thick shale layer (the main seal) leads to a decoupling of the structural deformation of the shallower sediments from the underlying sediments and basement, and results in flexural slip across the shale layer. All models predict rock fracturing to initiate at the surface and to expand with depth under increasing horizontal tectonic compression. The stress regime for the formation of new fractures changes from compressional to shear with depth. If pre-existing fractures exist, only (sub)horizontal fractures are predicted to open, thus defining the principal orientation of effective reservoir permeability. In models that do not include a blind thrust fault in the basement, flexural amplification of the initial fold structure generates additional fracturing in the crest of the anticline controlled by the material properties of the rocks. The folding-induced fracturing expands laterally along the stratigraphic boundaries under enhanced tectonic loading. Models incorporating a blind thrust fault correctly predict the formation of secondary syn- and anti-thetic mesoscale faults in the basement and sediments of the hanging wall. Some of these faults cut reservoir and/or seal layers, and thus may influence effective reservoir permeability and affect seal integrity. The predicted faults divide the sediments across the anticline in several compartments with different stress levels and different rock failure (and proximity to failure). These numerical model outcomes can assist classic interpretation of seismic and well bore data in search of fractured and overpressured hydrocarbon reservoirs.

Influence of Natural Fractures Cohesive Properties on Geometry of Hydraulic Fracture Networks

NASA Astrophysics Data System (ADS)

Gonzalez-Chavez, M. A.; Dahi Taleghani, A.; Puyang, P.

2014-12-01

An integrated modeling methodology is proposed to analyze hydraulic fracturing jobs in the presence of the natural fracture network in the formation. A propagating hydraulic fracture may arrest, cross, or diverts into a preexisting natural crack depending on fracture properties of rock and magnitude and direction of principal rock stresses. Opening of natural fractures during fracturing treatment could define the effectiveness of the stimulation technique. Here, we present an integrated methodology initiated with lab scale fracturing properties using Double Cantilever Beam tests (DCB) to determine cohesive properties of rock and natural fractures. We used cohesive finite element models to reproduce laboratory results to verify the numerical model for the interaction of the hydraulic fracture and individual cemented natural fractures. Based on the initial investigations, we found out that distribution of pre-existing natural fractures could play a significant role in the final geometry of the induced fracture network; however in practice, there is not much information about the distribution of natural fractures in the subsurface due to the limited access. Hence, we propose a special optimization scheme to generate natural fracture geometry from the location of microseismic events. Accordingly, the criteria of evaluating the fitness of natural fracture realizations is defined as the total minimum distance squares of all microseismic events, which is the sum of minimum square distance for all microseismic events. Moreover, an additional constraint in this problem is that we need to set a minimum distance between fracture grids. Using generated natural fracture realizations, forward field-scale simulations are implemented using cohesive finite element analysis to find the best match with the recorded bottomhole pressure. To show the robustness of the proposed workflow for real field problem, we implemented this technique on available data from several well Chicontepec basin to forecast post-treatment production rate. Our results show a constructive approach to integrate microseismic maps with lab mechanical measurements and bottomhole pressure to estimate the geometry of induced fracture network in the subsurface which does not suffer from any limiting assumption about fracture geometries.

Effect of Inflammatory and Noninflammatory Stress on Beta-Hydroxybutyrate and Free Fatty Acids in Rat Blood.

DTIC Science & Technology

fasting plus screen-restraint and fasting plus femoral fracture. Inflammatory stresses caused a marked inhibition of the normal fasting-induced ketosis ...and a reduction in the level of circulating free fatty acids. Noninflammatory stresses caused no inhibition of the normal fasting-induced ketosis but did cause a reduction in the level of circulating free fatty acids. (Author)

Biomechanical comparison of locking plate and crossing metallic and absorbable screws fixations for intra-articular calcaneal fractures.

PubMed

Ni, Ming; Wong, Duo Wai-Chi; Mei, Jiong; Niu, Wenxin; Zhang, Ming

2016-09-01

The locking plate and percutaneous crossing metallic screws and crossing absorbable screws have been used clinically to treat intra-articular calcaneal fractures, but little is known about the biomechanical differences between them. This study compared the biomechanical stability of calcaneal fractures fixed using a locking plate and crossing screws. Three-dimensional finite-element models of intact and fractured calcanei were developed based on the CT images of a cadaveric sample. Surgeries were simulated on models of Sanders type III calcaneal fractures to produce accurate postoperative models fixed by the three implants. A vertical force was applied to the superior surface of the subtalar joint to simulate the stance phase of a walking gait. This model was validated by an in vitro experiment using the same calcaneal sample. The intact calcaneus showed greater stiffness than the fixation models. Of the three fixations, the locking plate produced the greatest stiffness and the highest von Mises stress peak. The micromotion of the fracture fixated with the locking plate was similar to that of the fracture fixated with the metallic screws but smaller than that fixated with the absorbable screws. Fixation with both plate and crossing screws can be used to treat intra-articular calcaneal fractures. In general, fixation with crossing metallic screws is preferable because it provides sufficient stability with less stress shielding.

Implementation of ERDC HEP Geo-Material Model in CTH and Application

DTIC Science & Technology

2011-11-02

used TARDEC JWL inputs for C4 and Johnson- Cook Strength inputs   TARDEC JC fracture model inputs for 5083 plate changed due to problems seen in...fracture inputs from IMD tests -  LS-DYNA C4 JWL and Johnson-Cook strength inputs used in CTH runs -  Results indicate that TARDEC JC fracture model

Impact of eliminating fracture intersection nodes in multiphase compositional flow simulation

NASA Astrophysics Data System (ADS)

Walton, Kenneth M.; Unger, Andre J. A.; Ioannidis, Marios A.; Parker, Beth L.

2017-04-01

Algebraic elimination of nodes at discrete fracture intersections via the star-delta technique has proven to be a valuable tool for making multiphase numerical simulations more tractable and efficient. This study examines the assumptions of the star-delta technique and exposes its effects in a 3-D, multiphase context for advective and dispersive/diffusive fluxes. Key issues of relative permeability-saturation-capillary pressure (kr-S-Pc) and capillary barriers at fracture-fracture intersections are discussed. This study uses a multiphase compositional, finite difference numerical model in discrete fracture network (DFN) and discrete fracture-matrix (DFM) modes. It verifies that the numerical model replicates analytical solutions and performs adequately in convergence exercises (conservative and decaying tracer, one and two-phase flow, DFM and DFN domains). The study culminates in simulations of a two-phase laboratory experiment in which a fluid invades a simple fracture intersection. The experiment and simulations evoke different invading fluid flow paths by varying fracture apertures as oil invades water-filled fractures and as water invades air-filled fractures. Results indicate that the node elimination technique as implemented in numerical model correctly reproduces the long-term flow path of the invading fluid, but that short-term temporal effects of the capillary traps and barriers arising from the intersection node are lost.

Continuum Damage Modeling for Dynamic Fracture Toughness of Metal Matrix Composites

NASA Astrophysics Data System (ADS)

Lee, Intaek; Ochi, Yasuo; Bae, Sungin; Song, Jungil

Short fiber reinforced metal-matrix composites (MMCs) have widely adopted as structural materials and many experimental researches have been performed to study fracture toughness of it. Fracture toughness is often referred as the plane strain(maximum constraint) fracture toughness KIc determined by the well-established standard test method, such as ASTM E399. But the application for dynamic fracture toughness KId has not been popular yet, because of reliance in capturing the crack propagating time. This paper deals with dynamic fracture toughness testing and simulation using finite element method to evaluate fracture behaviors of MMCs manufactured by squeeze casting process when material combination is varied with the type of reinforcement (appearance, size), volume fraction and combination of reinforcements, and the matrix alloy. The instrumented Charphy impact test was used for KId determination and continuum damage model embedded in commercial FE program is used to investigate the dynamic fracture toughness with the influence of elasto-visco-plastic constitutive relation of quasi-brittle fracture that is typical examples of ceramics and some fibre reinforced composites. With Compared results between experimental method and FE simulation, the determination process for KId is presented. FE simulation coupled with continuum damage model is emphasized single shot simulation can predict the dynamic fracture toughness, KId and real time evolution of that directly.

Niobrara Discrete Fracture Network: From Outcrop Surveys to Subsurface Reservoir Models

NASA Astrophysics Data System (ADS)

Grechishnikova, Alena

Heterogeneity of an unconventional reservoir is one of the main factors affecting production. Well performance depends on the size and efficiency of the interconnected fracture "plumbing system", as influenced by multistage hydraulic fracturing. A complex, interconnected natural fracture network can significantly increase the size of stimulated reservoir volume, provide additional surface area contact and enhance permeability. In 2013 the Reservoir Characterization Project (RCP) at the Colorado School of Mines began Phase XV to study Niobrara shale reservoir management. Anadarko Petroleum Corporation and RCP jointly acquired time-lapse multicomponent seismic data in Wattenberg Field, Denver Basin. Anadarko also provided RCP with a regional 3D seismic survey and a rich well dataset. The purpose of this study is to characterize the natural fracture patterns occurring in the unconventional Niobrara reservoir and to determine the drivers that influenced fracture trends and distributions. The findings are integrated into a reservoir model though DFN (Discrete Fracture Network) for further prediction of reservoir performance using reservoir simulations. Aiming to better understand the complexity of the natural fracture system I began my fracture analysis work at an active mine site that provides a Niobrara exposure. Access to a "fresh" outcrop surface created a perfect natural laboratory. Ground-based LIDAR and photogrammetry facilitated construction of a geological model and a DFN model for the mine site. The work was carried into subsurface where the information gained served to improve reservoir characterization at a sub-seismic scale and can be used in well planning. I then embarked on a challenging yet essential task of outcrop-to-subsurface data calibration and application to RCP's Wattenberg Field study site. In this research the surface data was proven to be valid for comparative use in the subsurface. The subsurface fracture information was derived from image logs run within the horizontal wellbores and augmented with microseismic data. Limitations of these datasets included the potential to induce biased interpretations; but the data collected during the outcrop study aided in removing the bias. All four fracture sets observed at the quarry were also interpreted in the subsurface; however there was a limitation on statistical validity for one of the four sets due to a low frequency of observed occurrence potentially caused by wellbore orientation. Microseismic data was used for identification of one of the reactivated natural fracture sets. An interesting phenomenon observed in the microseismic data trends was the low frequency of event occurrence within dense populations of open natural fracture swarms suggesting that zones of higher natural fracture intensities are capable of absorbing and transmitting energy resulting in lower levels of microseismicity. Thus currently open natural fractures could be challenging to detect using microseismic. Through this study I identified a significant variability in fracture intensity at a localized scale due to lithological composition and structural features. The complex faulting styles observed at the outcrop were utilized as an analog and verified by horizontal well log data and seismic volume interpretations creating a high resolution structural model for the subsurface. A lithofacies model was developed based on the well log, core, and seismic inversion analysis. These models combined served to accurately distribute fracture intensity information within the geological model for further use in DFN. As a product of this study, a workflow was developed to aid in fracture network model creation allowing for more intelligent decisions to be made during well planning and completion optimization aiming to improve recovery. A high resolution integrated discrete fracture network model serves to advance dynamic reservoir characterization in the subsurface at a sub-seismic scale resulting in improved reservoir characterization.

Investigation of Stimulation-Response Relationships for Complex Fracture Systems in Enhanced Geothermal Reservoirs

DOE Data Explorer

Fu, Pengcheng; Johnson, Scott M.; Carrigan, Charles R.

2011-01-01

Hydraulic fracturing is currently the primary method for stimulating low-permeability geothermal reservoirs and creating Enhanced (or Engineered) Geothermal Systems (EGS) with improved permeability and heat production efficiency. Complex natural fracture systems usually exist in the formations to be stimulated and it is therefore critical to understand the interactions between existing fractures and newly created fractures before optimal stimulation strategies can be developed. Our study aims to improve the understanding of EGS stimulation-response relationships by developing and applying computer-based models that can effectively reflect the key mechanisms governing interactions between complex existing fracture networks and newly created hydraulic fractures. In this paper, we first briefly describe the key modules of our methodology, namely a geomechanics solver, a discrete fracture flow solver, a rock joint response model, an adaptive remeshing module, and most importantly their effective coupling. After verifying the numerical model against classical closed-form solutions, we investigate responses of reservoirs with different preexisting natural fractures to a variety of stimulation strategies. The factors investigated include: the in situ stress states (orientation of the principal stresses and the degree of stress anisotropy), pumping pressure, and stimulation sequences of multiple wells.

A comparative study of discrete fracture network and equivalent continuum models for simulating flow and transport in the far field of a hypothetical nuclear waste repository in crystalline host rock

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hadgu, Teklu; Karra, Satish; Kalinina, Elena

One of the major challenges of simulating flow and transport in the far field of a geologic repository in crystalline host rock is related to reproducing the properties of the fracture network over the large volume of rock with sparse fracture characterization data. Various approaches have been developed to simulate flow and transport through the fractured rock. The approaches can be broadly divided into Discrete Fracture Network (DFN) and Equivalent Continuum Model (ECM). The DFN explicitly represents individual fractures, while the ECM uses fracture properties to determine equivalent continuum parameters. In this paper, we compare DFN and ECM in termsmore » of upscaled observed transport properties through generic fracture networks. The major effort was directed on making the DFN and ECM approaches similar in their conceptual representations. This allows for separating differences related to the interpretation of the test conditions and parameters from the differences between the DFN and ECM approaches. The two models are compared using a benchmark test problem that is constructed to represent the far field (1 × 1 × 1 km 3) of a hypothetical repository in fractured crystalline rock. The test problem setting uses generic fracture properties that can be expected in crystalline rocks. The models are compared in terms of the: 1) effective permeability of the domain, and 2) nonreactive solute breakthrough curves through the domain. The principal differences between the models are mesh size, network connectivity, matrix diffusion and anisotropy. We demonstrate how these differences affect the flow and transport. Finally, we identify the factors that should be taken in consideration when selecting an approach most suitable for the site-specific conditions.« less

A comparative study of discrete fracture network and equivalent continuum models for simulating flow and transport in the far field of a hypothetical nuclear waste repository in crystalline host rock

DOE PAGES

Hadgu, Teklu; Karra, Satish; Kalinina, Elena; ...

2017-07-28

One of the major challenges of simulating flow and transport in the far field of a geologic repository in crystalline host rock is related to reproducing the properties of the fracture network over the large volume of rock with sparse fracture characterization data. Various approaches have been developed to simulate flow and transport through the fractured rock. The approaches can be broadly divided into Discrete Fracture Network (DFN) and Equivalent Continuum Model (ECM). The DFN explicitly represents individual fractures, while the ECM uses fracture properties to determine equivalent continuum parameters. In this paper, we compare DFN and ECM in termsmore » of upscaled observed transport properties through generic fracture networks. The major effort was directed on making the DFN and ECM approaches similar in their conceptual representations. This allows for separating differences related to the interpretation of the test conditions and parameters from the differences between the DFN and ECM approaches. The two models are compared using a benchmark test problem that is constructed to represent the far field (1 × 1 × 1 km 3) of a hypothetical repository in fractured crystalline rock. The test problem setting uses generic fracture properties that can be expected in crystalline rocks. The models are compared in terms of the: 1) effective permeability of the domain, and 2) nonreactive solute breakthrough curves through the domain. The principal differences between the models are mesh size, network connectivity, matrix diffusion and anisotropy. We demonstrate how these differences affect the flow and transport. Finally, we identify the factors that should be taken in consideration when selecting an approach most suitable for the site-specific conditions.« less

A comparative study of discrete fracture network and equivalent continuum models for simulating flow and transport in the far field of a hypothetical nuclear waste repository in crystalline host rock

NASA Astrophysics Data System (ADS)

Hadgu, Teklu; Karra, Satish; Kalinina, Elena; Makedonska, Nataliia; Hyman, Jeffrey D.; Klise, Katherine; Viswanathan, Hari S.; Wang, Yifeng

2017-10-01

One of the major challenges of simulating flow and transport in the far field of a geologic repository in crystalline host rock is related to reproducing the properties of the fracture network over the large volume of rock with sparse fracture characterization data. Various approaches have been developed to simulate flow and transport through the fractured rock. The approaches can be broadly divided into Discrete Fracture Network (DFN) and Equivalent Continuum Model (ECM). The DFN explicitly represents individual fractures, while the ECM uses fracture properties to determine equivalent continuum parameters. We compare DFN and ECM in terms of upscaled observed transport properties through generic fracture networks. The major effort was directed on making the DFN and ECM approaches similar in their conceptual representations. This allows for separating differences related to the interpretation of the test conditions and parameters from the differences between the DFN and ECM approaches. The two models are compared using a benchmark test problem that is constructed to represent the far field (1 × 1 × 1 km3) of a hypothetical repository in fractured crystalline rock. The test problem setting uses generic fracture properties that can be expected in crystalline rocks. The models are compared in terms of the: 1) effective permeability of the domain, and 2) nonreactive solute breakthrough curves through the domain. The principal differences between the models are mesh size, network connectivity, matrix diffusion and anisotropy. We demonstrate how these differences affect the flow and transport. We identify the factors that should be taken in consideration when selecting an approach most suitable for the site-specific conditions.

The influence of open fracture anisotropy on CO2 movement within geological storage complexes

NASA Astrophysics Data System (ADS)

Bond, C. E.; Wightman, R.; Ringrose, P. S.

2012-12-01

Carbon mitigation through the geological storage of carbon dioxide is dependent on the ability of geological formations to store CO2 trapping it within a geological storage complex. Secure long-term containment needs to be demonstrated, due to both political and social drivers, meaning that this containment must be verifiable over periods of 100-105 years. The effectiveness of sub-surface geological storage systems is dependent on trapping CO2 within a volume of rock and is reliant on the integrity of the surrounding rocks, including their chemical and physical properties, to inhibit migration to the surface. Oil and gas reservoir production data, and field evidence show that fracture networks have the potential to act as focused pathways for fluid movement. Fracture networks can allow large volumes of fluid to migrate to the surface within the time scales of interest. In this paper we demonstrate the importance of predicting the effects of fracture networks in storage, using a case study from the In Salah CO2 storage site, and show how the fracture permeability is closely controlled by the stress regime that determines the open fracture network. Our workflow combines well data of imaged fractures, with a discrete fracture network (DFN) model of tectonically induced fractures, within the horizon of interest. The modelled and observed fractures have been compared and combined with present day stress data to predict the open fracture network and its implications for anisotropic movement of CO2 in the sub-surface. The created fracture network model has been used to calculate the 2D permeability tensor for the reservoir for two scenarios: 1) a model in which all fractures are permeable, based on the whole DFN model and 2) those fractures determined to be in dilatational failure under the present day stress regime, a sub-set of the DFN. The resulting permeability anisotropy tensors show distinct anisotropies for the predicted CO2 movement within the reservoir. These predictions have been compared with InSAR imagery of surface uplift, used as an indicator of fluid pressure and movement in the sub-surface, around the CO2 injection wells. The analysis shows that the permeability tensor with the greatest anisotropy, that for the DFN sub-set of open fractures, matches well with the anisotropy in surface uplift imaged by InSAR. We demonstrate that predicting fracture networks alone does not predict fluid movement in the sub-surface, and that fracture permeability is closely controlled by the stress regime that determines the open fracture network. Our results show that a workflow of fracture network prediction combined with present day stress analysis can be used to successfully predict CO2 movement in the sub-surface at an active injection site.

Seismic determination of saturation in fractured reservoirs

USGS Publications Warehouse

Brown, R.L.; Wiggins, M.L.; Gupta, A.

2002-01-01

Detecting the saturation of a fractured reservoir using shear waves is possible when the fractures have a geometry that induces a component of movement perpendicular to the fractures. When such geometry is present, vertically traveling shear waves can be used to examine the saturation of the fractured reservoir. Tilted, corrugated, and saw-tooth fracture models are potential examples.

3D Modeling and Characterization of Hydraulic Fracture Efficiency Integrated with 4D/9C Time-Lapse Seismic Interpretations in the Niobrara Formation, Wattenberg Field, Denver Basin

NASA Astrophysics Data System (ADS)

Alfataierge, Ahmed

Hydrocarbon recovery rates within the Niobrara Shale are estimated as low as 2-8%. These recovery rates are controlled by the ability to effectively hydraulic fracture stimulate the reservoir using multistage horizontal wells. Subsequent to any mechanical issues that affect production from lateral wells, the variability in production performance and reserve recovery along multistage lateral shale wells is controlled by the reservoir heterogeneity and its consequent effect on hydraulic fracture stimulation efficiency. Using identical stimulation designs on a number of wells that are as close as 600ft apart can yield variable production and recovery rates due to inefficiencies in hydraulic fracture stimulation that result from the variability in elastic rock properties and in-situ stress conditions. As a means for examining the effect of the geological heterogeneity on hydraulic fracturing and production within the Niobrara Formation, a 3D geomechanical model is derived using geostatistical methods and volumetric calculations as an input to hydraulic fracture stimulation. The 3D geomechanical model incorporates the faults, lithological facies changes and lateral variation in reservoir properties and elastic rock properties that best represent the static reservoir conditions pre-hydraulic fracturing. Using a 3D numerical reservoir simulator, a hydraulic fracture predictive model is generated and calibrated to field diagnostic measurements (DFIT) and observations (microseismic and 4D/9C multicomponent time-lapse seismic). By incorporating the geological heterogeneity into the 3D hydraulic fracture simulation, a more representative response is generated that demonstrate the variability in hydraulic fracturing efficiency along the lateral wells that will inevitability influence production performance. Based on the 3D hydraulic fracture simulation results, integrated with microseismic observations and 4D/9C time-lapse seismic analysis (post-hydraulic fracturing & post production), the variability in production performance within the Niobrara Shale wells is shown to significantly be affected by the lateral variability in reservoir quality, well and stage positioning relative to the target interval, and the relative completion efficiency. The variation in reservoir properties, faults, rock strength parameters, and in-situ stress conditions are shown to influence and control the hydraulic fracturing geometry and stimulation efficiency resulting in complex and isolated induced fracture geometries to form within the reservoir. This consequently impacts the effective drainage areas, production performance and recovery rates from inefficiently stimulated horizontal wells. The 3D simulation results coupled with the 4D seismic interpretations illustrate that there is still room for improvement to be made in optimizing well spacing and hydraulic fracturing efficiency within the Niobrara Formation. Integrated analysis show that the Niobrara reservoir is not uniformly stimulated. The vertical and lateral variability in rock properties control the hydraulic fracturing efficiency and geometry. Better production is also correlated to higher fracture conductivity. 4D seismic interpretation is also shown to be essential for the validation and calibration hydraulic fracture simulation models. The hydraulic fracture modeling also demonstrations that there is bypassed pay in the Niobrara B chalk resulting from initial Niobrara C chalk stimulation treatments. Forward modeling also shows that low pressure intervals within the Niobrara reservoir influence hydraulic fracturing and infill drilling during field development.

Potential Effects of Phytoestrogen Genistein in Modulating Acute Methotrexate Chemotherapy-Induced Osteoclastogenesis and Bone Damage in Rats

PubMed Central

King, Tristan J.; Shandala, Tetyana; Lee, Alice M.; Foster, Bruce K.; Chen, Ke-Ming; Howe, Peter R.; Xian, Cory J.

2015-01-01

Chemotherapy-induced bone damage is a frequent side effect which causes diminished bone mineral density and fracture in childhood cancer sufferers and survivors. The intensified use of anti-metabolite methotrexate (MTX) and other cytotoxic drugs has led to the need for a mechanistic understanding of chemotherapy-induced bone loss and for the development of protective treatments. Using a young rat MTX-induced bone loss model, we investigated potential bone protective effects of phytoestrogen genistein. Oral gavages of genistein (20 mg/kg) were administered daily, for seven days before, five days during, and three days after five once-daily injections (sc) of MTX (0.75 mg/kg). MTX treatment reduced body weight gain and tibial metaphyseal trabecular bone volume (p < 0.001), increased osteoclast density on the trabecular bone surface (p < 0.05), and increased the bone marrow adipocyte number in lower metaphyseal bone (p < 0.001). Genistein supplementation preserved body weight gain (p < 0.05) and inhibited ex vivo osteoclast formation of bone marrow cells from MTX-treated rats (p < 0.001). However, MTX-induced changes in bone volume, trabecular architecture, metaphyseal mRNA expression of pro-osteoclastogenic cytokines, and marrow adiposity were not significantly affected by the co-administration of genistein. This study suggests that genistein may suppress MTX-induced osteoclastogenesis; however, further studies are required to examine its potential in protecting against MTX chemotherapy-induced bone damage. PMID:26258775

Multi-Elemental Profiling of Tibial and Maxillary Trabecular Bone in Ovariectomised Rats

PubMed Central

Han, Pingping; Lu, Shifeier; Zhou, Yinghong; Moromizato, Karine; Du, Zhibin; Friis, Thor; Xiao, Yin

2016-01-01

Atomic minerals are the smallest components of bone and the content of Ca, being the most abundant mineral in bone, correlates strongly with the risk of osteoporosis. Postmenopausal women have a far greater risk of suffering from OP due to low Ca concentrations in their bones and this is associated with low bone mass and higher bone fracture rates. However, bone strength is determined not only by Ca level, but also a number of metallic and non-metallic elements in bone. Thus, in this study, the difference of metallic and non-metallic elements in ovariectomy-induced osteoporosis tibial and maxillary trabecular bone was investigated in comparison with sham operated normal bone by laser ablation inductively-coupled plasma mass spectrometry using a rat model. The results demonstrated that the average concentrations of 25Mg, 28Si, 39K, 47Ti, 56Fe, 59Co, 77Se, 88Sr, 137Ba, and 208Pb were generally higher in tibia than those in maxilla. Compared with the sham group, Ovariectomy induced more significant changes of these elements in tibia than maxilla, indicating tibial trabecular bones are more sensitive to changes of circulating estrogen. In addition, the concentrations of 28Si, 77Se, 208Pb, and Ca/P ratios were higher in tibia and maxilla in ovariectomised rats than those in normal bone at all time-points. The present study indicates that ovariectomy could significantly impact the element distribution and concentrations between tibia and maxilla. PMID:27338361

a Predictive Model of Permeability for Fractal-Based Rough Rock Fractures during Shear

NASA Astrophysics Data System (ADS)

Huang, Na; Jiang, Yujing; Liu, Richeng; Li, Bo; Zhang, Zhenyu

This study investigates the roles of fracture roughness, normal stress and shear displacement on the fluid flow characteristics through three-dimensional (3D) self-affine fractal rock fractures, whose surfaces are generated using the modified successive random additions (SRA) algorithm. A series of numerical shear-flow tests under different normal stresses were conducted on rough rock fractures to calculate the evolutions of fracture aperture and permeability. The results show that the rough surfaces of fractal-based fractures can be described using the scaling parameter Hurst exponent (H), in which H = 3 - Df, where Df is the fractal dimension of 3D single fractures. The joint roughness coefficient (JRC) distribution of fracture profiles follows a Gauss function with a negative linear relationship between H and average JRC. The frequency curves of aperture distributions change from sharp to flat with increasing shear displacement, indicating a more anisotropic and heterogeneous flow pattern. Both the mean aperture and permeability of fracture increase with the increment of surface roughness and decrement of normal stress. At the beginning of shear, the permeability increases remarkably and then gradually becomes steady. A predictive model of permeability using the mean mechanical aperture is proposed and the validity is verified by comparisons with the experimental results reported in literature. The proposed model provides a simple method to approximate permeability of fractal-based rough rock fractures during shear using fracture aperture distribution that can be easily obtained from digitized fracture surface information.

The three-zone composite productivity model for a multi-fractured horizontal shale gas well

NASA Astrophysics Data System (ADS)

Qi, Qian; Zhu, Weiyao

2018-02-01

Due to the nano-micro pore structures and the massive multi-stage multi-cluster hydraulic fracturing in shale gas reservoirs, the multi-scale seepage flows are much more complicated than in most other conventional reservoirs, and are crucial for the economic development of shale gas. In this study, a new multi-scale non-linear flow model was established and simplified, based on different diffusion and slip correction coefficients. Due to the fact that different flow laws existed between the fracture network and matrix zone, a three-zone composite model was proposed. Then, according to the conformal transformation combined with the law of equivalent percolation resistance, the productivity equation of a horizontal fractured well, with consideration given to diffusion, slip, desorption, and absorption, was built. Also, an analytic solution was derived, and the interference of the multi-cluster fractures was analyzed. The results indicated that the diffusion of the shale gas was mainly in the transition and Fick diffusion regions. The matrix permeability was found to be influenced by slippage and diffusion, which was determined by the pore pressure and diameter according to the Knudsen number. It was determined that, with the increased half-lengths of the fracture clusters, flow conductivity of the fractures, and permeability of the fracture network, the productivity of the fractured well also increased. Meanwhile, with the increased number of fractures, the distance between the fractures decreased, and the productivity slowly increased due to the mutual interfere of the fractures.

DFN Modeling for the Safety Case of the Final Disposal of Spent Nuclear Fuel in Olkiluoto, Finland

NASA Astrophysics Data System (ADS)

Vanhanarkaus, O.

2017-12-01

Olkiluoto Island is a site in SW Finland chosen to host a deep geological repository for high-level nuclear waste generated by nuclear power plants of power companies TVO and Fortum. Posiva, a nuclear waste management organization, submitted a construction license application for the Olkiluoto repository to the Finnish government in 2012. A key component of the license application was an integrated geological, hydrological and biological description of the Olkiluoto site. After the safety case was reviewed in 2015 by the Radiation and Nuclear Safety Authority in Finland, Posiva was granted a construction license. Posiva is now preparing an updated safety case for the operating license application to be submitted in 2022, and an update of the discrete fracture network (DFN) model used for site characterization is part of that. The first step describing and modelling the network of fractures in the Olkiluoto bedrock was DFN model version 1 (2009), which presented an initial understanding of the relationships between rock fracturing and geology at the site and identified the important primary controls on fracturing. DFN model version 2 (2012) utilized new subsurface data from additional drillholes, tunnels and excavated underground facilities in ONKALO to better understand spatial variability of the geological controls on geological and hydrogeological fracture properties. DFN version 2 connected fracture geometric and hydraulic properties to distinct tectonic domains and to larger-scale hydraulically conductive fault zones. In the version 2 DFN model, geological and hydrogeological models were developed along separate parallel tracks. The version 3 (2017) DFN model for the Olkiluoto site integrates geological and hydrogeological elements into a single consistent model used for geological, rock mechanical, hydrogeological and hydrogeochemical studies. New elements in the version 3 DFN model include a stochastic description of fractures within Brittle Fault Zones (BFZ), integration of geological and hydrostructural interpretations of BFZ, greater use of 3D geological models to better constrain the spatial variability of fracturing and fractures using hydromechanical principles to account for material behavior and in-situ stresses.

Regenerate Healing Outcomes in Unilateral Mandibular Distraction Osteogenesis Using Quantitative Histomorphometry

PubMed Central

Schwarz, Daniel A.; Arman, Krikor G.; Kakwan, Mehreen S.; Jamali, Ameen M.; Elmeligy, Ayman A.; Buchman, Steven R.

2015-01-01

Background The authors’ goal was to ascertain regenerate bone-healing metrics using quantitative histomorphometry at a single consolidation period. Methods Rats underwent either mandibular distraction osteogenesis (n=7) or partially reduced fractures (n=7); their contralateral mandibles were used as controls (n=11). External fixators were secured and unilateral osteotomies performed, followed by either mandibular distraction osteogenesis (4 days’ latency, then 0.3 mm every 12 hours for 8 days; 5.1 mm) or partially reduced fractures (fixed immediately postoperatively; 2.1 mm); both groups underwent 4 weeks of consolidation. After tissue processing, bone volume/tissue volume ratio, osteoid volume/tissue volume ratio, and osteocyte count per high-power field were analyzed by means of quantitative histomorphometry. Results Contralateral mandibles had statistically greater bone volume/tissue volume ratio and osteocyte count per high-power field compared with both mandibular distraction osteogenesis and partially reduced fractures by almost 50 percent, whereas osteoid volume/tissue volume ratio was statistically greater in both mandibular distraction osteogenesis specimens and partially reduced fractures compared with contralateral mandibles. No statistical difference in bone volume/tissue volume ratio, osteoid volume/tissue volume ratio, or osteocyte count per high-power field was found between mandibular distraction osteogenesis specimens and partially reduced fractures. Conclusions The authors’ findings demonstrate significantly decreased bone quantity and maturity in mandibular distraction osteogenesis specimens and partially reduced fractures compared with contralateral mandibles using the clinically analogous protocols. If these results are extrapolated clinically, treatment strategies may require modification to ensure reliable, predictable, and improved outcomes. PMID:20463629

Experimental and theoretical fracture mechanics applied to volcanic conduits and domes

NASA Astrophysics Data System (ADS)

Sammonds, P.; Matthews, C.; Kilburn, C.; Smith, R.; Tuffen, H.; Meredith, P.

2008-12-01

We present an integrated modelling and experimental approach to magma deformation and fracture, which we attempt to validate against field observations of seismicity. The importance of fracture processes in magma ascent dynamics and lava dome growth and collapse are apparent from the associated seismicity. Our laboratory experiments have shown that brittle fracture of magma can occur at high temperature and stress conditions prevalent in the shallow volcanic system. Here, we use a fracture mechanics approach to model seismicity preceding volcanic eruptions. Starting with the fracture mechanics concept of a crack in an elastic body, we model crack growth around the volcanic conduit through the processes of crack interactions, leading either to the propagation and linkage of cracks, or crack avoidance and the inhibition of crack propagation. The nature of that interaction is governed by the temperature and plasticity of the magma. We find that fracture mechanics rules can account for the style of seismicity preceding eruptions. We have derived the changes in seismic b-value predicted by the model and interpret these in terms of the style of fracturing, fluid flow and heat transport. We compare our model with results from our laboratory experiments where we have deformed lava at high temperatures under triaxial stresses. These experiments were conducted in dry and water saturated conditions at effective pressures up to 10 MPa, temperatures up to 1000°C and strain rates from 10-4 s-1 to 10-6 s-1. The behaviour of these magmas was largely brittle under these conditions. We monitored the acoustic emission emitted and calculate the change in micro-seismic b-value with deformation. These we find are in accord with volcano seismicity and our fracture mechanics model.

The biomechanical analysis of three-dimensional distal radius fracture model with different fixed splints.

PubMed

Hua, Zhen; Wang, Jian-Wei; Lu, Zhen-Fei; Ma, Jian-Wei; Yin, Heng

2018-01-01

The distal radius fracture is one of the common clinical fractures. At present, there are no reports regarding application of the finite element method in studying the mechanism of Colles fracture and the biomechanical behavior when using splint fixation. To explore the mechanism of Colles fracture and the biomechanical behavior when using different fixed splints. Based on the CT scanning images of forearm for a young female volunteer, by using model construction technology combined with RPOE and ANSYS software, a 3-D distal radius fracture forearm finite element model with a real shape and bioactive materials is built. The material tests are performed to obtain the mechanical properties of the paper-based splint, the willow splint and the anatomical splint. The numerical results are compared with the experimental results to verify the correctness of the presented model. Based on the verified model, the stress distribution of different tissues are analyzed. Finally, the clinical tests are performed to observe and verify that the anatomical splint is the best fit for human body. Using the three kinds of splints, the transferred bone stress focus on the distal radius and ulna, which is helpful to maintain the stability of fracture. Also the stress is accumulated in the distal radius which may be attributed to flexion position. Such stress distribution may be helpful to maintain the ulnar declination. By comparing the simulation results with the experimental observations, the anatomical splint has the best fitting to the limb, which can effectively avoid the local compression. The anatomical splint is the most effective for fixing and curing the fracture. The presented model can provide theoretical basis and technical guide for further investigating mechanism of distal radius fracture and clinical application of anatomical splint.

Assessment of CO2 Storage Potential in Naturally Fractured Reservoirs With Dual-Porosity Models

NASA Astrophysics Data System (ADS)

March, Rafael; Doster, Florian; Geiger, Sebastian

2018-03-01

Naturally Fractured Reservoirs (NFR's) have received little attention as potential CO2 storage sites. Two main facts deter from storage projects in fractured reservoirs: (1) CO2 tends to be nonwetting in target formations and capillary forces will keep CO2 in the fractures, which typically have low pore volume; and (2) the high conductivity of the fractures may lead to increased spatial spreading of the CO2 plume. Numerical simulations are a powerful tool to understand the physics behind brine-CO2 flow in NFR's. Dual-porosity models are typically used to simulate multiphase flow in fractured formations. However, existing dual-porosity models are based on crude approximations of the matrix-fracture fluid transfer processes and often fail to capture the dynamics of fluid exchange accurately. Therefore, more accurate transfer functions are needed in order to evaluate the CO2 transfer to the matrix. This work presents an assessment of CO2 storage potential in NFR's using dual-porosity models. We investigate the impact of a system of fractures on storage in a saline aquifer, by analyzing the time scales of brine drainage by CO2 in the matrix blocks and the maximum CO2 that can be stored in the rock matrix. A new model to estimate drainage time scales is developed and used in a transfer function for dual-porosity simulations. We then analyze how injection rates should be limited in order to avoid early spill of CO2 (lost control of the plume) on a conceptual anticline model. Numerical simulations on the anticline show that naturally fractured reservoirs may be used to store CO2.

2017 GTO Project review Laboratory Evaluation of EGS Shear Stimulation.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bauer, Stephen J.

The objectives and purpose of this research has been to produce laboratory-based experimental and numerical analyses to provide a physics-based understanding of shear stimulation phenomena (hydroshearing) and its evolution during stimulation. Water was flowed along fractures in hot and stressed fractured rock, to promote slip. The controlled laboratory experiments provide a high resolution/high quality data resource for evaluation of analysis methods developed by DOE to assess EGS “behavior” during this stimulation process. Segments of the experimental program will provide data sets for model input parameters, i.e., material properties, and other segments of the experimental program will represent small scale physicalmore » models of an EGS system, which may be modeled. The coupled lab/analysis project has been a study of the response of a fracture in hot, water-saturated fractured rock to shear stress experiencing fluid flow. Under this condition, the fracture experiences a combination of potential pore pressure changes and fracture surface cooling, resulting in slip along the fracture. The laboratory work provides a means to assess the role of “hydroshearing” on permeability enhancement in reservoir stimulation. Using the laboratory experiments and results to define boundary and input/output conditions of pore pressure, thermal stress, fracture shear deformation and fluid flow, and models were developed and simulations completed by the University of Oklahoma team. The analysis methods are ones used on field scale problems. The sophisticated numerical models developed contain parameters present in the field. The analysis results provide insight into the role of fracture slip on permeability enhancement-“hydroshear” is to be obtained. The work will provide valuable input data to evaluate stimulation models, thus helping design effective EGS.« less

A Relationship Between Constraint and the Critical Crack Tip Opening Angle

NASA Technical Reports Server (NTRS)

Johnston, William M.; James, Mark A.

2009-01-01

Of the various approaches used to model and predict fracture, the Crack Tip Opening Angle (CTOA) fracture criterion has been successfully used for a wide range of two-dimensional thin-sheet and thin plate applications. As thicker structure is considered, modeling the full three-dimensional fracture process will become essential. This paper investigates relationships between the local CTOA evaluated along a three-dimensional crack front and the corresponding local constraint. Previously reported tunneling crack front shapes were measured during fracture by pausing each test and fatigue cycling the specimens to mark the crack surface. Finite element analyses were run to model the tunneling shape during fracture, with the analysis loading conditions duplicating those tests. The results show an inverse relationship between the critical fracture value and constraint which is valid both before maximum load and after maximum load.

Hydromechanical modeling of clay rock including fracture damage

NASA Astrophysics Data System (ADS)

Asahina, D.; Houseworth, J. E.; Birkholzer, J. T.

2012-12-01

Argillaceous rock typically acts as a flow barrier, but under certain conditions significant and potentially conductive fractures may be present. Fracture formation is well-known to occur in the vicinity of underground excavations in a region known as the excavation disturbed zone. Such problems are of particular importance for low-permeability, mechanically weak rock such as clays and shales because fractures can be relatively transient as a result of fracture self-sealing processes. Perhaps not as well appreciated is the fact that natural fractures can form in argillaceous rock as a result of hydraulic overpressure caused by phenomena such as disequlibrium compaction, changes in tectonic stress, and mineral dehydration. Overpressure conditions can cause hydraulic fracturing if the fluid pressure leads to tensile effective stresses that exceed the tensile strength of the material. Quantitative modeling of this type of process requires coupling between hydrogeologic processes and geomechanical processes including fracture initiation and propagation. Here we present a computational method for three-dimensional, hydromechanical coupled processes including fracture damage. Fractures are represented as discrete features in a fracture network that interact with a porous rock matrix. Fracture configurations are mapped onto an unstructured, three-dimensonal, Voronoi grid, which is based on a random set of spatial points. Discrete fracture networks (DFN) are represented by the connections of the edges of a Voronoi cells. This methodology has the advantage that fractures can be more easily introduced in response to coupled hydro-mechanical processes and generally eliminates several potential issues associated with the geometry of DFN and numerical gridding. A geomechanical and fracture-damage model is developed here using the Rigid-Body-Spring-Network (RBSN) numerical method. The hydrogelogic and geomechanical models share the same geometrical information from a 3D Voronoi grid and associated nodes, where the scalar field quantities (e.g. temperature, pressure, and saturation) and the generalized displacements are obtained by an integral finite difference method (e.g., TOUGH2) and RBSN, respectively. Fractures propagate along Voronoi cell boundaries as induced stresses evolve and exceed the material strength. Examples of fracture propagation in clay rock are examined for the excavation disturbed zone and for cases in which hydraulic overpressure leads to hydraulic fracture. Fluid flow behavior in these evolving fracture networks and eventual fracture closing and self-sealing are investigated. Funding for this work was provided by the Used Fuel Disposition Campaign, Office of Nuclear Energy, of the U.S. Department of Energy under Contract NumberDE-AC02-05CH11231 with Berkeley Lab.

The imbalance between regulatory and IL-17-secreting CD4⁺T cells in multiple-trauma rat.

PubMed

Dai, Heling; Sun, Tiansheng; Liu, Zhi; Zhang, Jianzheng; Zhou, Meng

2013-11-01

It has been well recognised that a deficit of numbers and function of CD4(+)CD25(+)Foxp3(+)cells (Treg) is attributed to the development of auto-immune diseases, inflammatory diseases, tumour and rejection of transplanted tissue; however, there are controversial data regarding the suppressive effect of Treg cells on the T-cell response in auto-immune diseases. Additionally, interleukin-17 (IL-17)-producing cells (Th17) have a pro-inflammatory role. The balance between Th17 and Treg may be essential for maintaining immune homeostasis and has long been thought as one of the important factors in the development/prevention of auto-immune diseases, inflammatory diseases, tumour and rejection of transplanted tissue, but their role in multiple trauma remains unclear. This study aims to investigate whether an imbalance of Treg and Th17 effector cells is characteristic of rats suffering from multiple trauma. Sixty Sprague-Dawley (SD) rats were randomly divided into three groups. The control group (n=20, group I) no received procedures (normal). The sham group (n=20, group II) only received anaesthesia, cannulation and observation. The bilateral femoral shaft fractures with haemorrhagic shock groups (n=20, group III). Rats in groups II and III were killed at the end of 4h after models were established. Peripheral blood samples were collected for assessment of Treg cells, Th17 cells and cytokines (IL-17, IL-6, IL-2, transforming growth factor beta (TGF-β)) and intestine tissue was collected for intestine histological analysis. We observed decreased Treg/Th17 ratios in CD4(+)T cells in rats with multiple trauma and a strong inverse correlation with disease activity (intestinal histological scores). We suggest a role for immune imbalance in the pathogenesis and development of multiple trauma. The alteration of the index of Treg/Th17 cells likely indicates the therapeutic response and progress in the clinic. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Application of particle and lattice codes to simulation of hydraulic fracturing

NASA Astrophysics Data System (ADS)

Damjanac, Branko; Detournay, Christine; Cundall, Peter A.

2016-04-01

With the development of unconventional oil and gas reservoirs over the last 15 years, the understanding and capability to model the propagation of hydraulic fractures in inhomogeneous and naturally fractured reservoirs has become very important for the petroleum industry (but also for some other industries like mining and geothermal). Particle-based models provide advantages over other models and solutions for the simulation of fracturing of rock masses that cannot be assumed to be continuous and homogeneous. It has been demonstrated (Potyondy and Cundall Int J Rock Mech Min Sci Geomech Abstr 41:1329-1364, 2004) that particle models based on a simple force criterion for fracture propagation match theoretical solutions and scale effects derived using the principles of linear elastic fracture mechanics (LEFM). The challenge is how to apply these models effectively (i.e., with acceptable models sizes and computer run times) to the coupled hydro-mechanical problems of relevant time and length scales for practical field applications (i.e., reservoir scale and hours of injection time). A formulation of a fully coupled hydro-mechanical particle-based model and its application to the simulation of hydraulic treatment of unconventional reservoirs are presented. Model validation by comparing with available analytical asymptotic solutions (penny-shape crack) and some examples of field application (e.g., interaction with DFN) are also included.

A battery model that enables consideration of realistic anisotropic environment surrounding an active material particle and its application

NASA Astrophysics Data System (ADS)

Lin, Xianke; Lu, Wei

2017-07-01

This paper proposes a model that enables consideration of the realistic anisotropic environment surrounding an active material particle by incorporating both diffusion and migration of lithium ions and electrons in the particle. This model makes it possible to quantitatively evaluate effects such as fracture on capacity degradation. In contrast, the conventional model assumes isotropic environment and only considers diffusion in the active particle, which cannot capture the effect of fracture since it would predict results contradictory to experimental observations. With the developed model we have investigated the effects of active material electronic conductivity, particle size, and State of Charge (SOC) swing window when fracture exists. The study shows that the low electronic conductivity of active material has a significant impact on the lithium ion pattern. Fracture increases the resistance for electron transport and therefore reduces lithium intercalation/deintercalation. Particle size plays an important role in lithium ion transport. Smaller particle size is preferable for mitigating capacity loss when fracture happens. The study also shows that operating at high SOC reduces the impact of fracture.

Tritium and 36Cl as constraints on fast fracture flow and percolation flux in the unsaturated zone at Yucca Mountain

NASA Astrophysics Data System (ADS)

Guerin, Marianne

2001-10-01

An analysis of tritium and 36Cl data collected at Yucca Mountain, Nevada suggests that fracture flow may occur at high velocities through the thick unsaturated zone. The mechanisms and extent of this "fast flow" in fractures at Yucca Mountain are investigated with data analysis, mixing models and several one-dimensional modeling scenarios. The model results and data analysis provide evidence substantiating the weeps model [Gauthier, J.H., Wilson, M.L., Lauffer, F.C., 1992. Proceedings of the Third Annual International High-level Radioactive Waste Management Conference, vol. 1, Las Vegas, NV. American Nuclear Society, La Grange Park, IL, pp. 891-989] and suggest that fast flow in fractures with minimal fracture-matrix interaction may comprise a substantial proportion of the total infiltration through Yucca Mountain. Mixing calculations suggest that bomb-pulse tritium measurements, in general, represent the tail end of travel times for thermonuclear-test-era (bomb-pulse) infiltration. The data analysis shows that bomb-pulse tritium and 36Cl measurements are correlated with discrete features such as horizontal fractures and areas where lateral flow may occur. The results presented here imply that fast flow in fractures may be ubiquitous at Yucca Mountain, occurring when transient infiltration (storms) generates flow in the connected fracture network.

Tritium and 36Cl as constraints on fast fracture flow and percolation flux in the unsaturated zone at Yucca Mountain.

PubMed

Guerin, M

2001-10-01

An analysis of tritium and 36Cl data collected at Yucca Mountain, Nevada suggests that fracture flow may occur at high velocities through the thick unsaturated zone. The mechanisms and extent of this "fast flow" in fractures at Yucca Mountain are investigated with data analysis, mixing models and several one-dimensional modeling scenarios. The model results and data analysis provide evidence substantiating the weeps model [Gauthier, J.H., Wilson, M.L., Lauffer, F.C., 1992. Proceedings of the Third Annual International High-level Radioactive Waste Management Conference, vol. 1, Las Vegas, NV. American Nuclear Society, La Grange Park, IL, pp. 891-989] and suggest that fast flow in fractures with minimal fracture-matrix interaction may comprise a substantial proportion of the total infiltration through Yucca Mountain. Mixing calculations suggest that bomb-pulse tritium measurements, in general, represent the tail end of travel times for thermonuclear-test-era (bomb-pulse) infiltration. The data analysis shows that bomb-pulse tritium and 36Cl measurements are correlated with discrete features such as horizontal fractures and areas where lateral flow may occur. The results presented here imply that fast flow in fractures may be ubiquitous at Yucca Mountain, occurring when transient infiltration (storms) generates flow in the connected fracture network.

Dynamic seismic signatures of saturated porous rocks containing two orthogonal sets of fractures: theory versus numerical simulations

NASA Astrophysics Data System (ADS)

Guo, Junxin; Rubino, J. Germán; Glubokovskikh, Stanislav; Gurevich, Boris

2018-05-01

The dispersion and attenuation of seismic waves are potentially important attributes for the non-invasive detection and characterization of fracture networks. A primary mechanism for these phenomena is wave-induced fluid flow (WIFF), which can take place between fractures and their embedding background (FB-WIFF), as well as within connected fractures (FF-WIFF). In this work, we propose a theoretical approach to quantify seismic dispersion and attenuation related to these two manifestations of WIFF in saturated porous rocks permeated by two orthogonal sets of fractures. The methodology is based on existing theoretical models for rocks with aligned fractures, and we consider three types of fracture geometries, namely, periodic planar fractures, randomly spaced planar fractures and penny-shaped cracks. Synthetic 2-D rock samples with different degrees of fracture intersections are then explored by considering both the proposed theoretical approach and a numerical upscaling procedure that provides the effective seismic properties of generic heterogeneous porous media. The results show that the theoretical predictions are in overall good agreement with the numerical simulations, in terms of both the stiffness coefficients and the anisotropic properties. For the seismic dispersion and attenuation caused by FB-WIFF, the theoretical model for penny-shaped cracks matches the numerical simulations best, whereas for representing the effects due to FF-WIFF the periodic planar fractures model turns out to be the most suitable one. The proposed theoretical approach is easy to apply and is applicable not only to 2-D but also to 3-D fracture systems. Hence, it has the potential to constitute a useful framework for the seismic characterization of fractured reservoirs, especially in the presence of intersecting fractures.

OpenACC directive-based GPU acceleration of an implicit reconstructed discontinuous Galerkin method for compressible flows on 3D unstructured grids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lou, Jialin; Xia, Yidong; Luo, Lixiang

2016-09-01

In this study, we use a combination of modeling techniques to describe the relationship between fracture radius that might be accomplished in a hypothetical enhanced geothermal system (EGS) and drilling distance required to create and access those fractures. We use a combination of commonly applied analytical solutions for heat transport in parallel fractures and 3D finite-element method models of more realistic heat extraction geometries. For a conceptual model involving multiple parallel fractures developed perpendicular to an inclined or horizontal borehole, calculations demonstrate that EGS will likely require very large fractures, of greater than 300 m radius, to keep interfracture drillingmore » distances to ~10 km or less. As drilling distances are generally inversely proportional to the square of fracture radius, drilling costs quickly escalate as the fracture radius decreases. It is important to know, however, whether fracture spacing will be dictated by thermal or mechanical considerations, as the relationship between drilling distance and number of fractures is quite different in each case. Information about the likelihood of hydraulically creating very large fractures comes primarily from petroleum recovery industry data describing hydraulic fractures in shale. Those data suggest that fractures with radii on the order of several hundred meters may, indeed, be possible. The results of this study demonstrate that relatively simple calculations can be used to estimate primary design constraints on a system, particularly regarding the relationship between generated fracture radius and the total length of drilling needed in the fracture creation zone. Comparison of the numerical simulations of more realistic geometries than addressed in the analytical solutions suggest that simple proportionalities can readily be derived to relate a particular flow field.« less