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Sample records for affect fracture healing

  1. HOW DO BISPHOSPHONATES AFFECT FRACTURE HEALING?

    PubMed Central

    KATES, STEPHEN L.; ACKERT-BICKNELL, CHERYL L.

    2016-01-01

    Bisphosphonates (BPs) have been in use for many years for the treatment of osteoporosis, multiple myeloma, Paget's disease, as well as a variety of other diseases in which there is reduced bone mineral density. Given that bisphosphonates inhibit bone resorption, an important stage of fracture healing; this class of compounds has been widely studied in preclinical models regarding their influence on fracture healing. In animal models, bisphosphonate treatment is associated with a larger fracture callus, coincident with a delay in remodeling from primary woven bone to lamellar bone, but there is no delay in formation of the fracture callus. In humans, de novo use of bisphosphonate therapy after fracture does not appear to have a significant effect on fracture healing. Rarely, patients with long term use of Bisphosphonates may develop an atypical fracture and delay in fracture healing has been observed. In summary, bisphosphonates appear safe for use in the setting of acute fracture management in the upper and lower extremity in humans. While much remains unknown about the effects on healing of long-term bisphosphonates, use prior to “typical” fracture, in the special case of atypical fracture, evidence suggests that bisphosphonates negatively influence healing. PMID:26768295

  2. Clinical factors affecting pathological fracture and healing of unicameral bone cysts

    PubMed Central

    2014-01-01

    Background Unicameral bone cyst (UBC) is the most common benign lytic bone lesion seen in children. The aim of this study is to investigate clinical factors affecting pathological fracture and healing of UBC. Methods We retrospectively reviewed 155 UBC patients who consulted Nagoya musculoskeletal oncology group hospitals in Japan. Sixty of the 155 patients had pathological fracture at presentation. Of 141 patients with follow-up periods exceeding 6 months, 77 were followed conservatively and 64 treated by surgery. Results The fracture risk was significantly higher in the humerus than other bones. In multivariate analysis, ballooning of bone, cyst in long bone, male sex, thin cortical thickness and multilocular cyst were significant adverse prognostic factors for pathological fractures at presentation. The healing rates were 30% and 83% with observation and surgery, respectively. Multivariate analysis revealed that fracture at presentation and history of biopsy were good prognostic factors for healing of UBC in patients under observation. Conclusion The present results suggest that mechanical disruption of UBC such as fracture and biopsy promotes healing, and thus watchful waiting is indicated in these patients, whereas patients with poor prognostic factors for fractures should be considered for surgery. PMID:24884661

  3. The Role of Oxygen during Fracture Healing

    PubMed Central

    Lu, Chuanyong; Saless, Neema; Wang, Xiaodong; Sinha, Arjun; Decker, Sebastian; Kazakia, Galateia; Hou, Huagang; Williams, Benjamin; Swartz, Harold M.; Hunt, Thomas K.; Miclau, Theodore; Marcucio, Ralph S.

    2016-01-01

    Oxygen affects the activity of multiple skeletogenic cells and is involved in many processes that are important for fracture healing. However, the role of oxygen in fracture healing has not been fully studied. Here we systematically examine the effects of oxygen tension on fracture healing and test the ability of hyperoxia to rescue healing defects in a mouse model of ischemic fracture healing. Mice with tibia fracture were housed in custom-built gas chambers and groups breathed a constant atmosphere of 13% oxygen (hypoxia), 21% oxygen (normoxia), or 50% oxygen (hyperoxia). The influx of inflammatory cells to the fracture site, stem cell differentiation, tissue vascularization, and fracture healing were analyzed. In addition, the efficacy of hyperoxia (50% breathing oxygen) as a treatment regimen for fracture nonunion was tested. Hypoxic animals had decreased tissue vascularity, decreased bone formation, and delayed callus remodeling. Hyperoxia increased tissue vascularization, altered fracture healing in un-complicated fractures, and improved bone repair in ischemia-induced delayed fracture union. However, neither hypoxia nor hyperoxia significantly altered chondrogenesis or osteogenesis during early stages of fracture healing, and infiltration of macrophages and neutrophils was not affected by environmental oxygen after bone injury. In conclusion, our results indicate that environmental oxygen levels affect tissue vascularization and fracture healing, and that providing oxygen to patients with fractures accompanied by ischemia may be beneficial. PMID:23063782

  4. Fracture healing in osteoporotic bone.

    PubMed

    Cheung, Wing Hoi; Miclau, Theodore; Chow, Simon Kwoon-Ho; Yang, Frank F; Alt, Volker

    2016-06-01

    As the world population rises, osteoporotic fracture is an emerging global threat to the well-being of elderly patients. The process of fracture healing by intramembranous ossification or/and endochondral ossification involve many well-orchestrated events including the signaling, recruitment and differentiation of mesenchymal stem cells (MSCs) during the early phase; formation of a hard callus and extracellular matrix, angiogenesis and revascularization during the mid-phase; and finally callus remodeling at the late phase of fracture healing. Through clinical and animal research, many of these factors are shown to be impaired in osteoporotic bone. Animal studies related to post-menopausal estrogen deficient osteoporosis (type I) have shown healing to be prolonged with decreased levels of MSCs and decreased levels of angiogenesis. Moreover, the expression of estrogen receptor (ER) was shown to be delayed in ovariectomy-induced osteoporotic fracture. This might be related to the observed difference in mechanical sensitivity between normal and osteoporotic bones, which requires further experiments to elucidate. In mice fracture models related to senile osteoporosis (type II), it was observed that chondrocyte and osteoblast differentiation were impaired; and that transplantation of juvenile bone marrow would result in enhanced callus formation. Other factors related to angiogenesis and vasculogenesis have also been noted to be impaired in aged models, affecting the degradation of cartilaginous matrixes and vascular invasion; the result is changes in matrix composition and growth factors concentrations that ultimately impairs healing during age-related osteoporosis. Most osteoporotic related fractures occur at metaphyseal sites clinically, and reports have indicated that differences exist between diaphyseal and metaphyseal fractures. An animal model that satisfies three main criteria (metaphyseal region, plate fixation, osteoporosis) is suggested for future research for

  5. Hypochlorhydria‐induced calcium malabsorption does not affect fracture healing but increases post‐traumatic bone loss in the intact skeleton

    PubMed Central

    Haffner‐Luntzer, Melanie; Heilmann, Aline; Heidler, Verena; Liedert, Astrid; Schinke, Thorsten; Amling, Michael; Yorgan, Timur Alexander; vom Scheidt, Annika

    2016-01-01

    ABSTRACT Efficient calcium absorption is essential for skeletal health. Patients with impaired gastric acidification display low bone mass and increased fracture risk because calcium absorption is dependent on gastric pH. We investigated fracture healing and post‐traumatic bone turnover in mice deficient in Cckbr, encoding a gastrin receptor that affects acid secretion by parietal cells. Cckbr−/− mice display hypochlorhydria, calcium malabsorption, and osteopenia. Cckbr−/− and wildtype (WT) mice received a femur osteotomy and were fed either a standard or calcium‐enriched diet. Healed and intact bones were assessed by biomechanical testing, histomorphometry, micro‐computed tomography, and quantitative backscattering. Parathyroid hormone (PTH) serum levels were determined by enzyme‐linked immunosorbent assay. Fracture healing was unaffected in Cckbr−/− mice. However, Cckbr−/− mice displayed increased calcium mobilization from the intact skeleton during bone healing, confirmed by significantly elevated PTH levels and osteoclast numbers compared to WT mice. Calcium supplementation significantly reduced secondary hyperparathyroidism and bone resorption in the intact skeleton in both genotypes, but more efficiently in WT mice. Furthermore, calcium administration improved bone healing in WT mice, indicated by significantly increased mechanical properties and bone mineral density of the fracture callus, whereas it had no significant effect in Cckbr−/− mice. Therefore, under conditions of hypochlorhydria‐induced calcium malabsorption, calcium, which is essential for callus mineralization, appears to be increasingly mobilized from the intact skeleton in favor of fracture healing. Calcium supplementation during fracture healing prevented systemic calcium mobilization, thereby maintaining bone mass and improving fracture healing in healthy individuals whereas the effect was limited by gastric hypochlorhydria. © 2016 Orthopaedic Research Society

  6. Biologic adjuvants for fracture healing

    PubMed Central

    2012-01-01

    Bone tissue has an exceptional quality to regenerate to native tissue in response to injury. However, the fracture repair process requires mechanical stability or a viable biological microenvironment or both to ensure successful healing to native tissue. An improved understanding of the molecular and cellular events that occur during bone repair and remodeling has led to the development of biologic agents that can augment the biological microenvironment and enhance bone repair. Orthobiologics, including stem cells, osteoinductive growth factors, osteoconductive matrices, and anabolic agents, are available clinically for accelerating fracture repair and treatment of compromised bone repair situations like delayed unions and nonunions. Preclinical and clinical studies using biologic agents like recombinant bone morphogenetic proteins have demonstrated an efficacy similar or better than that of autologous bone graft in acute fracture healing. A lack of standardized outcome measures for comparison of biologic agents in clinical fracture repair trials, frequent off-label use, and a limited understanding of the biological activity of these agents at the bone repair site have limited their efficacy in clinical applications. PMID:23198865

  7. Black bone disease in a healing fracture.

    PubMed

    Thiam, Desmond; Teo, Tse Yean; Malhotra, Rishi; Tan, Kong Bing; Chee, Yu Han

    2016-01-28

    Black bone disease refers to the hyperpigmentation of bone secondary to prolonged usage of minocycline. We present a report of a 34-year-old man who underwent femoral shaft fracture fixation complicated by deep infection requiring debridement. The implants were removed 10 months later after long-term treatment with minocycline and fracture union. A refracture of the femoral shaft occurred 2 days after implant removal and repeat fixation was required. Intraoperatively, abundant heavily pigmented and dark brown bone callus was noted over the old fracture site. There was no evidence of other bony pathology and the appearance was consistent with minocycline-associated pigmentation. As far as we are aware, this is the first case of black bone disease affecting callus within the interval period of bone healing. We also discuss the relevant literature on black bone disease to bring light on this rare entity that is an unwelcomed surprise to operating orthopaedic surgeons.

  8. Impaired Fracture Healing after Hemorrhagic Shock.

    PubMed

    Lichte, Philipp; Kobbe, Philipp; Pfeifer, Roman; Campbell, Graeme C; Beckmann, Rainer; Tohidnezhad, Mersedeh; Bergmann, Christian; Kadyrov, Mamed; Fischer, Horst; Glüer, Christian C; Hildebrand, Frank; Pape, Hans-Christoph; Pufe, Thomas

    2015-01-01

    Impaired fracture healing can occur in severely injured patients with hemorrhagic shock due to decreased soft tissue perfusion after trauma. We investigated the effects of fracture healing in a standardized pressure controlled hemorrhagic shock model in mice, to test the hypothesis that bleeding is relevant in the bone healing response. Male C57/BL6 mice were subjected to a closed femoral shaft fracture stabilized by intramedullary nailing. One group was additionally subjected to pressure controlled hemorrhagic shock (HS, mean arterial pressure (MAP) of 35 mmHg for 90 minutes). Serum cytokines (IL-6, KC, MCP-1, and TNF-α) were analyzed 6 hours after shock. Fracture healing was assessed 21 days after fracture. Hemorrhagic shock is associated with a significant increase in serum inflammatory cytokines in the early phase. Histologic analysis demonstrated a significantly decreased number of osteoclasts, a decrease in bone quality, and more cartilage islands after hemorrhagic shock. μCT analysis showed a trend towards decreased bone tissue mineral density in the HS group. Mechanical testing revealed no difference in tensile failure. Our results suggest a delay in fracture healing after hemorrhagic shock. This may be due to significantly diminished osteoclast recruitment. The exact mechanisms should be studied further, particularly during earlier stages of fracture healing.

  9. Biomechanical Characteristics of Osteoporotic Fracture Healing in Ovariectomized Rats: A Systematic Review.

    PubMed

    Chen, Lin; Yang, Long; Yao, Min; Cui, Xue-Jun; Xue, Chun-Chun; Wang, Yong-Jun; Shu, Bing

    2016-01-01

    Biomechanical tests are widely used in animal studies on osteoporotic fracture healing. However, the biomechanical recovery process is still unknown, leading to difficulty in choosing time points for biomechanical tests and in correctly assessing osteoporotic fracture healing. To determine the biomechanical recovery process during osteoporotic fracture healing, studies on osteoporotic femur fracture healing with biomechanical tests in ovariectomized rat (OVX) models were collected from PUBMED, EMBASE, and Chinese databases. Quadratic curves of fracture healing time and maximum load were fitted with data from the analyzed studies. In the fitted curve for normal fractures, the predicted maximum load was 145.56 N, and the fracture healing time was 88.0 d. In the fitted curve for osteoporotic fractures, the predicted maximum load was 122.30 N, and the fracture healing time was 95.2 d. The maximum load of fractured femurs in OVX rats was also lower than that in sham rats at day 84 post-fracture (D84 PF). The fracture healing time was prolonged and maximum load at D84 PF decreased in OVX rats with closed fractures. The maximum load of Wister rats was higher than that of Sprague-Dawley (SD) rats, but the fracture healing time of SD and Wister rats was similar. Osteoporotic fracture healing was delayed in rats that were < = 12 weeks old when ovariectomized, and at D84 PF, the maximum load of rats < = 12 weeks old at ovariectomy was lower than that of rats >12 weeks old at ovariectomy. There was no significant difference in maximum load at D84 PF between rats with an osteoporosis modeling time <12 weeks and > = 12 weeks. In conclusion, fracture healing was delayed and biomechanical property decreased by osteoporosis. Time points around D95.2 PF should be considered for biomechanical tests of osteoporotic femur fracture healing in OVX rat models. Osteoporotic fracture healing in OVX rats was affected by the fracture type but not by the strain of the rat.

  10. Healing of patellar fractures in two kittens.

    PubMed

    Hermer, J V; Bush, M A; Whiting, C; Langley-Hobbs, S J

    2012-01-01

    Two kittens aged between four and five months were presented having sustained patellar fractures. In both cases, healing was subsequently documented radiographically; this has not been reported previously in the literature. One kitten had bilateral patellar fractures - the symptomatic right stifle was treated with a pin and tension-band-wire which later failed, at which point partial patellectomy was performed. The fracture of the left patella was minimally displaced and was treated conservatively. A radiograph of the left patella taken eleven months after initial presentation showed complete healing of the fracture. The second case was treated surgically with a circumferential wire; healing of the fracture was demonstrated radiographically at twelve weeks postoperatively. Radiographic images taken five weeks postoperatively had shown some narrowing of the fracture gap. These two cases demonstrate that bony union of patellar fractures can be documented, given a long enough duration of radiographic follow-up; circumferential wire was an effective treatment in a displaced fracture, and conservative treatment resulted in complete healing of a minimally displaced fracture.

  11. Computational characterization of fracture healing under reduced gravity loading conditions.

    PubMed

    Gadomski, Benjamin C; Lerner, Zachary F; Browning, Raymond C; Easley, Jeremiah T; Palmer, Ross H; Puttlitz, Christian M

    2016-07-01

    The literature is deficient with regard to how the localized mechanical environment of skeletal tissue is altered during reduced gravitational loading and how these alterations affect fracture healing. Thus, a finite element model of the ovine hindlimb was created to characterize the local mechanical environment responsible for the inhibited fracture healing observed under experimental simulated hypogravity conditions. Following convergence and verification studies, hydrostatic pressure and strain within a diaphyseal fracture of the metatarsus were evaluated for models under both 1 and 0.25 g loading environments and compared to results of a related in vivo study. Results of the study suggest that reductions in hydrostatic pressure and strain of the healing fracture for animals exposed to reduced gravitational loading conditions contributed to an inhibited healing process, with animals exposed to the simulated hypogravity environment subsequently initiating an intramembranous bone formation process rather than the typical endochondral ossification healing process experienced by animals healing in a 1 g gravitational environment. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1206-1215, 2016.

  12. Does human immunodeficiency virus status affect early wound healing in open surgically stabilised tibial fractures?: A prospective study.

    PubMed

    Howard, N E; Phaff, M; Aird, J; Wicks, L; Rollinson, P

    2013-12-01

    We compared early post-operative rates of wound infection in HIV-positive and -negative patients presenting with open tibial fractures managed with surgical fixation. The wounds of 84 patients (85 fractures), 28 of whom were HIV positive and 56 were HIV negative, were assessed for signs of infection using the ASEPIS wound score. There were 19 women and 65 men with a mean age of 34.8 years. A total of 57 fractures (17 HIV-positive, 40 HIV-negative) treated with external fixation were also assessed using the Checkett score for pin-site infection. The remaining 28 fractures were treated with internal fixation. No significant difference in early post-operative wound infection between the two groups of patients was found (10.7% (n = 3) vs 19.6% (n = 11); relative risk (RR) 0.55 (95% confidence interval (CI) 0.17 to 1.8); p = 0.32). There was also no significant difference in pin-site infection rates (17.6% (n = 3) vs 12.5% (n = 5); RR 1.62 (95% CI 0.44 to 6.07); p = 0.47). The study does not support the hypothesis that HIV significantly increases the rate of early wound or pin-site infection in open tibial fractures. We would therefore suggest that a patient's HIV status should not alter the management of open tibial fractures in patients who have a CD4 count > 350 cells/μl.

  13. Diabetes and Its Effect on Bone and Fracture Healing

    PubMed Central

    Jiao, Hongli; Xiao, E.; Graves, Dana T.

    2015-01-01

    Diabetes mellitus is a metabolic disorder that increases fracture risk and interferes with bone formation and impairs fracture healing. Type 1 diabetes mellitus (T1DM) and Type 2 diabetes mellitus (T2DM) both increase fracture risk and have several common features that affect bone including hyperglycemia and increased AGE formation, ROS generation, and inflammation. These factors affect both osteoblasts and osteoclasts lead to increased osteoclasts and reduced numbers of osteoblasts and bone formation. In addition to fracture healing, T1DM and T2DM impair bone formation under conditions of perturbation such as bacteria induced periodontal bone loss, which reduces expression of factors that stimulate osteoblasts such as BMPs and growth factors and increase osteoblast apoptosis. PMID:26254939

  14. Role of Wnt signaling in fracture healing.

    PubMed

    Xu, Huiyun; Duan, Jing; Ning, Dandan; Li, Jingbao; Liu, Ruofei; Yang, Ruixin; Jiang, Jean X; Shang, Peng

    2014-12-01

    The Wnt signaling pathway is well known to play major roles in skeletal development and homeostasis. In certain aspects, fracture repair mimics the process of bone embryonic development. Thus, the importance of Wnt signaling in fracture healing has become more apparent in recent years. Here, we summarize recent research progress in the area, which may be conducive to the development of Wnt-based therapeutic strategies for bone repair.

  15. Do Capacity Coupled Electric Fields Accelerate Tibial Stress Fracture Healing

    DTIC Science & Technology

    2006-12-01

    DAMD17-98-1-8519 TITLE: Do Capacity Coupled Electric Fields Accelerate Tibial Stress Fracture Healing PRINCIPAL INVESTIGATOR...2006 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Do Capacity Coupled Electric Fields Accelerate Tibial Stress Fracture Healing 5b. GRANT NUMBER...To determine the effect of capacitively coupled electric field stimulation on tibial stress fracture healing in men and women. Methods: A

  16. Inhibition of Midkine Augments Osteoporotic Fracture Healing

    PubMed Central

    Haffner-Luntzer, Melanie; Kemmler, Julia; Heidler, Verena; Prystaz, Katja; Schinke, Thorsten; Amling, Michael; Kovtun, Anna; Rapp, Anna E.; Ignatius, Anita; Liedert, Astrid

    2016-01-01

    The heparin-binding growth and differentiation factor midkine (Mdk) is proposed to negatively regulate osteoblast activity and bone formation in the adult skeleton. As Mdk-deficient mice were protected from ovariectomy (OVX)-induced bone loss, this factor may also play a role in the pathogenesis of postmenopausal osteoporosis. We have previously demonstrated that Mdk negatively influences bone regeneration during fracture healing. Here, we investigated whether the inhibition of Mdk using an Mdk-antibody (Mdk-Ab) improves compromised bone healing in osteoporotic OVX-mice. Using a standardized femur osteotomy model, we demonstrated that Mdk serum levels were significantly enhanced after fracture in both non-OVX and OVX-mice, however, the increase was considerably greater in osteoporotic mice. Systemic treatment with the Mdk-Ab significantly improved bone healing in osteoporotic mice by increasing bone formation in the fracture callus. On the molecular level, we demonstrated that the OVX-induced reduction of the osteoanabolic beta-catenin signaling in the bony callus was abolished by Mdk-Ab treatment. Furthermore, the injection of the Mdk-Ab increased trabecular bone mass in the skeleton of the osteoporotic mice. These results implicate that antagonizing Mdk may be useful for the therapy of osteoporosis and osteoporotic fracture-healing complications. PMID:27410432

  17. Fracture and healing cycles in glass

    NASA Astrophysics Data System (ADS)

    Lavallee, Yan; Wadsworth, Fabian; Vasseur, Jeremie; Kendrick, Jackie; von Aulock, Felix

    2014-05-01

    The repeated occurrence of fracture and healing occurs in a variety of geological, biological, metallurgical and engineering processes. In geology, it is most common in active tectonic regions, earthquake settings and volcanic conduits, where healing is thought to be intrinsically related to diffusional processes, aided by catalytic fluids. In this study, cycles of compression, healing by contact and tension are performed on standard soda-lime silicate liquids at high temperatures (500 to 700 ° C; i.e., in the diffusive regime of the viscoelastic body). The flat ends of two cylinders are brought in contact at relatively low strain rates (10-3 s-1) until a target normal stress is reached (1, 2.5, 5 and 10 MPa). The specimens are then held in contact whilst the normal stress is left to viscously dissipate for a different portion of Maxwell's relaxation timescale for the liquid (0.25, 0.5, 1, 2.5, 5, 10, 20, 40, 80, 160, 320) in order to achieve different degrees of fracture healing. Strength recovery is assessed by subjecting the healed sample to a rapid tension event at 10-1 s-1 (to ensure a purely brittle response). We note that healing becomes efficient when allowed to operate for at least 5 times the relaxation timescale of the material. From this point onward, we observe an exponential increase in strength as a function of healing time. A small component of heat is generated during failure, monitored using a high-speed infrared thermographic camera. We find that fracture-healing dynamics has similarities with sintering, whereby the kinetics of the process is viscosity and diffusion dependent. Here we aim to expand this definition with normal applied stress constraints and link fracture and healing cycles to seismic swarms. Seismicity is perceived as a first order constraint on the mechanics of magma ascent and facilitates assessment of the real-time rheological state of magma in conduits. The processes presented here may be equally applicable to the strength

  18. 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.

  19. Can a fractured caprock self-heal?

    NASA Astrophysics Data System (ADS)

    Elkhoury, Jean E.; Detwiler, Russell L.; Ameli, Pasha

    2015-05-01

    The ability of geologic seals to prevent leakage of fluids injected into the deep subsurface is critical for mitigating risks associated with greenhouse-gas sequestration and natural-gas production. Fractures caused by tectonic or injection-induced stresses create potential leakage pathways that may be further enhanced by mineral dissolution. We present results from reactive-flow experiments in fractured caprock (dolomitic anhydrite), where additional dissolution occurs in the rock matrix adjacent to the fracture surfaces. Preferential dissolution of anhydrite left a compacted layer of dolomite in the fractures. At lower flow rate, rock-fluid reactions proceeded to near equilibrium within the fracture with preferential flow paths persisting over the 6-month duration of the experiment and a negligible change in permeability. At higher flow rate, permeability decreased by a dramatic two orders of magnitude. This laboratory-scale observation of self-healing argues against the likelihood of runaway permeability growth in fractured porous caprock composed of minerals with different solubilities and reaction kinetics. However, scaling arguments suggest that at larger length scales this self-healing process may be offset by the formation of dissolution channels. Our results have relevance beyond the greenhouse-gas sequestration problem. Chemical disequilibrium at waste injection sites and in hydrothermal reservoirs will lead to reactive flows that may also significantly alter formation permeability.

  20. Remote ischemic preconditioning enhances fracture healing

    PubMed Central

    Çatma, Mehmet Faruk; Şeşen, Hakan; Aydın, Aytekin; Ünlü, Serhan; Demirkale, İsmail; Altay, Murat

    2015-01-01

    Purpose We hypothesized that RIP accelerates fracture healing. Methods Rats (n = 48) were used for the technique of ischemic preconditioning involved applying 35 min of intermittent pneumatic tourniquet for 7 cycles of 5 min each to the fractured hind limb. Results We observed greater callus maturity in RIP group at first week after fracture when compared to controls (p < 0,0001). The serum MDA levels demonstrated statistically lower values at the RIP group at the first week after fracture; however, there were not significant differences at 3rd and 5th weeks (p = 0.0001, p = 0.725, p = 0.271, respectively). Conclusions Greater callus maturity was obtained in RIP group. PMID:26566314

  1. Indium-111 leukocyte scanning and fracture healing

    SciTech Connect

    Mead, L.P.; Scott, A.C.; Bondurant, F.J.; Browner, B.D. )

    1990-01-01

    This study was undertaken to determine the specificity of indium-111 leukocyte scans for osteomyelitis when fractures are present. Midshaft tibial osteotomies were performed in 14 New Zealand white rabbits, seven of which were infected postoperatively with Staphylococcus aureus per Norden's protocol. All 14 rabbits were scanned following injection with 75 microCi of indium 111 at 72 h after osteotomy and at weekly intervals for 4 weeks. Before the rabbits were killed, the fracture sites were cultured to document the presence or absence of infection. The results of all infected osteotomy sites were positive, whereas no positive scans were found in the noninfected osteotomies. We concluded from this study that uncomplicated fracture healing does not result in a positive indium-111 leukocyte scan.

  2. Microgrooved Polymer Substrates Promote Collective Cell Migration To Accelerate Fracture Healing in an in Vitro Model.

    PubMed

    Zhang, Qing; Dong, Hua; Li, Yuli; Zhu, Ye; Zeng, Lei; Gao, Huichang; Yuan, Bo; Chen, Xiaofeng; Mao, Chuanbin

    2015-10-21

    Surface topography can affect cell adhesion, morphology, polarity, cytoskeleton organization, and osteogenesis. However, little is known about the effect of topography on the fracture healing in repairing nonunion and large bone defects. Microgrooved topography on the surface of bone implants may promote cell migration into the fracture gap to accelerate fracture healing. To prove this hypothesis, we used an in vitro fracture (wound) healing assay on the microgrooved polycaprolactone substrates to study the effect of microgroove widths and depths on the osteoblast-like cell (MG-63) migration and the subsequent healing. We found that the microgrooved substrates promoted MG-63 cells to migrate collectively into the wound gap, which serves as a fracture model, along the grooves and ridges as compared with the flat substrates. Moreover, the groove widths did not show obvious influence on the wound healing whereas the smaller groove depths tended to favor the collective cell migration and thus subsequent healing. The microgrooved substrates accelerated the wound healing by facilitating the collective cell migration into the wound gaps but not by promoting the cell proliferation. Furthermore, microgrooves were also found to promote the migration of human mesenchymal stem cells (hMSCs) to heal the fracture model. Though osteogenic differentiation of hMSCs was not improved on the microgrooved substrate, collagen I and minerals deposited by hMSCs were organized in a way similar to those in the extracellular matrix of natural bone. These findings suggest the necessity in using microgrooved implants in enhancing fracture healing in bone repair.

  3. Muscle-bone Interactions During Fracture Healing

    DTIC Science & Technology

    2015-03-01

    equal vascu- larization in healed bone and non-unions in animal studies as well as in human patients20,24-26. In a murine open tibial fracture model...the periosteum is intact, repair occurs largely through endochondral ossification driven by a periosteal supply of cells10,47-50. Indeed, in open...activated to serve as a secondary supply of cells when the periosteal supply becomes compro- mised52,53. These recent findings of muscle’s ability to

  4. Stem cells in orthopaedics and fracture healing.

    PubMed

    Alwattar, Basil J; Schwarzkopf, Ran; Kirsch, Thorsten

    2011-01-01

    Stem cell application is a burgeoning field of medicine that is likely to influence the future of orthopaedic surgery. Stem cells are associated with great promise and great controversy. For the orthopaedic surgeon, stem cells may change the way that orthopaedic surgery is practiced and the overall approach of the treatment of musculoskeletal disease. Stem cells may change the field of orthopaedics from a field dominated by surgical replacements and reconstructions to a field of regeneration and prevention. This review will introduce the basic concepts of stem cells pertinent to the orthopaedic surgeon and proceed with a more in depth discussion of current developments in the study of stem cells in fracture healing.

  5. Tibia Fracture Healing Prediction Using First-Order Mathematical Model

    PubMed Central

    Sridevi, M.; Prakasam, P.; Kumaravel, S.; Madhava Sarma, P.

    2015-01-01

    The prediction of healing period of a tibia fracture in humans across limb using first-order mathematical model is demonstrated. At present, fracture healing is diagnosed using X-rays. Recent studies have demonstrated electric stimulation as a diagnostic tool in fracture healing. A DC electric voltage of 0.7 V was applied across the fracture and stabilized with Teflon coated carbon rings and the data was recorded at different time intervals until the fracture heals. The experimental data fitted a first-order plus dead time zero model (FOPDTZ) that coincided with the mathematical model of electrical simulated tibia fracture limb. Fracture healing diagnosis was proposed using model parameter process gain. Current stabilization in terms of process gain parameter becoming constant indicates that the healing of fracture is a new finding in the work. An error analysis was performed and it was observed that the measured data correlated to the FOPDTZ model with an error of less than 2 percent. Prediction of fracture healing period was done by one of the identified model parameters, namely, process gain. Moreover, mathematically, it is justified that once the fracture is completely united there is no capacitance present across the fracture site, which is a novelty of the work. PMID:26495032

  6. Strongly enhanced levels of sclerostin during human fracture healing.

    PubMed

    Sarahrudi, Kambiz; Thomas, Anita; Albrecht, Christian; Aharinejad, Seyedhossin

    2012-10-01

    Sclerostin (SOST), an antagonist of Wnt signaling, is an important negative regulator of bone formation. However, no data on the role of SOST in the human fracture healing have been published so far. This study addressed this issue. Seventy-five patients with long bone fractures were included into the study and divided in two groups. The first group contained 69 patients with normal fracture healing. Six patients with impaired fracture healing formed the second group. Thirty-four volunteers donated blood samples as control. Serum samples were collected over a period of 1 year following a standardized time schedule. In addition, SOST levels were measured in fracture hematoma and serum of 16 patients with bone fractures. Fracture hematoma contained significantly higher SOST concentrations compared to patient's serum. SOST levels in fracture hematoma and in patient's serum were both significantly higher than in the serum of controls. Highly elevated SOST serum concentrations were found in patients with physiological fracture healing. SOST levels were decreased in patients with impaired fracture healing. However, this difference was not statistically significant. This is the first study to provide evidence of strongly enhanced SOST levels in patients with bone fracture. The results indicate local and systemic involvement of SOST in humans during fracture healing.

  7. Nrf2 deficiency impairs fracture healing in mice.

    PubMed

    Lippross, Sebastian; Beckmann, Rainer; Streubesand, Nadine; Ayub, Ferda; Tohidnezhad, Mersedeh; Campbell, Graeme; Kan, Yuet Wai; Horst, Fischer; Sönmez, Tolga Taha; Varoga, Deike; Lichte, Philipp; Jahr, Holger; Pufe, Thomas; Wruck, Christoph Jan

    2014-10-01

    Oxidative stress plays an important role in wound healing but data relating oxidative stress to fracture healing are scarce. Nuclear factor erythroid 2-related factor 2 (Nrf2) is the major transcription factor that controls the cellular defence essential to combat oxidative stress by regulating the expression of antioxidative enzymes. This study examined the impact of Nrf2 on fracture healing using a standard closed femoral shaft fracture model in wild-type (WT) and Nrf2-knockout (Nrf2-KO)-mice. Healing was evaluated by histology, real-time RT-PCR, µCT and biomechanical measurements. We showed that Nrf2 expression is activated during fracture healing. Bone healing and remodelling were retarded in the Nrf2-KO compared to the WT-mice. Nrf2-KO-mice developed significantly less callus tissue compared to WT-mice. In addition, biomechanical testing demonstrated lower strength against shear stress in the Nrf2-KO-group compared to WT. The expression of vascular endothelial growth factor (VEGF) and osteocalcin is reduced during fracture healing in Nrf2-KO-mice. Taken together, our results demonstrate that Nrf2 deficiency in mice results in impaired fracture healing suggesting that Nrf2 plays an essential role in bone regeneration. Pharmacological activation of Nrf2 may have therapeutic potential for the enhancement of fracture healing.

  8. New Opportunities for Fracture Healing Detection: Impedance Spectroscopy Measurements Correlate to Tissue Composition in Fractures.

    PubMed

    Lin, Monica C; Yang, Frank; Herfat, Safa T; Bahney, Chelsea S; Marmor, Meir; Maharbiz, Michel M

    2017-04-06

    Accurate evaluation of fracture healing is important for clinical decisions on when to begin weight-bearing and when early intervention is necessary in cases of fracture nonunion. While the stages of healing involving hematoma, cartilage, trabecular bone, and cortical bone have been well characterized histologically, physicians typically track fracture healing by using subjective physical examinations and radiographic techniques that are only able to detect mineralized stages of bone healing. This exposes the need for a quantitative, reliable technique to monitor fracture healing, and particularly to track healing progression during the early stages of repair. The goal of this study was to validate the use of impedance spectroscopy to monitor fracture healing and perform comprehensive evaluation comparing measurements with histological evidence. Here we show that impedance spectroscopy not only can distinguish between cadaver tissues involved throughout fracture repair, but also correlates to fracture callus composition over the middle stages of healing in wild-type C57BL/6 mice. Specifically, impedance magnitude has a positive relationship with % trabecular bone and a negative relationship with % cartilage, and the opposite relationships are found when comparing phase angle to these same volume fractions of tissues. With this information, we can quantitatively evaluate how far a fracture has progressed through the healing stages. Our results demonstrate the feasibility of impedance spectroscopy for detection of fracture callus composition and reveals its potential as a method for early detection of bone healing and fracture nonunion. This article is protected by copyright. All rights reserved.

  9. [Bone fracture and the healing mechanisms. The mechanical stress for fracture healing in view of distraction osteogenesis].

    PubMed

    Yukata, Kiminori; Takahashi, Mitsuhiko; Yasui, Natsuo

    2009-05-01

    It is generally accepted that moderate mechanical stress influences the course of fracture healing. A flexible fixation of the fractured site can induce fracture callus formation, whereas an unstable fixation can lead to a nonunion. The relationship between mechanical stress and the process of bone regeneration or healing remains incompletely understood. Distraction osteogenesis is a surgical technique that, using appropriate mechanical tension-stress, does not break the callus but rather it stimulates and maintains osteogenesis. The common principles of distraction osteogenesis are osteotomy and slow progressive distraction by an external fixation device. Interest in bone regeneration associated with mechanical stress might lead to better understanding of the fracture healing process.

  10. A finite element inverse analysis to assess functional improvement during the fracture healing process.

    PubMed

    Weis, Jared A; Miga, Michael I; Granero-Moltó, Froilán; Spagnoli, Anna

    2010-02-10

    Assessment of the restoration of load-bearing function is the central goal in the study of fracture healing process. During the fracture healing, two critical aspects affect its analysis: (1) material properties of the callus components, and (2) the spatio-temporal architecture of the callus with respect to cartilage and new bone formation. In this study, an inverse problem methodology is used which takes into account both features and yields material property estimates that can analyze the healing changes. Six stabilized fractured mouse tibias are obtained at two time points during the most active phase of the healing process, respectively 10 days (n=3), and 14 days (n=3) after fracture. Under the same displacement conditions, the inverse procedure estimations of the callus material properties are generated and compared to other fracture healing metrics. The FEA estimated property is the only metric shown to be statistically significant (p=0.0194) in detecting the changes in the stiffness that occur during the healing time points. In addition, simulation studies regarding sensitivity to initial guess and noise are presented; as well as the influence of callus architecture on the FEA estimated material property metric. The finite element model inverse analysis developed can be used to determine the effects of genetics or therapeutic manipulations on fracture healing in rodents.

  11. The SERM raloxifene improves diaphyseal fracture healing in mice.

    PubMed

    Spiro, Alexander S; Khadem, Shahram; Jeschke, Anke; Marshall, Robert Percy; Pogoda, Pia; Ignatius, Anita; Amling, Michael; Beil, Frank Timo

    2013-11-01

    Although several studies reported that raloxifene treatment improves postmenopausal osteoporotic bone structure and reduces fracture risk, only a few animal and no human studies have examined its effects on the fracture healing process. Thus the aim of the present study was to determine, whether systemic application of the selective estrogen receptor modulator raloxifene promotes fracture healing compared to untreated control-, estrogen-deficient-, as well as estrogen-treated mice using a standardized femoral osteotomy model (n = 60 mice). Ten days after surgery, contact radiography and undecalcified histomorphometric analysis revealed that raloxifene administration significantly improved the early stage of fracture healing compared to all other groups. At day 20, raloxifene and estrogen treatment led to a significant increase in callus mineralization and trabecular thickness compared to control mice. μCT analyses revealed no evidence of complete bony bridging of the fracture site in any control-, nor estrogen-deficient mouse after 20 days, while all femoral fractures in the raloxifene and estrogen group already healed adequately at this time. These data indicate that raloxifene treatment significantly improves all phases of fracture healing at least in mice. Therefore, raloxifene could be a possible pharmaceutical to enhance fracture healing in women, without the known side effects of estrogen.

  12. Accelerated fracture healing in mice lacking the 5-lipoxygenase gene

    PubMed Central

    2010-01-01

    Background and purpose Cyclooxygenase-2 (COX-2) promotes inflammation by synthesizing pro-inflammatory prostaglandins from arachidonic acid. Inflammation is an early response to bone fracture, and ablation of COX-2 activity impairs fracture healing. Arachidonic acid is also converted into leukotrienes by 5-lipoxygenase (5-LO). We hypothesized that 5-LO is a negative regulator of fracture healing and that in the absence of COX-2, excess leukotrienes synthesized by 5-LO will impair fracture healing. Methods Fracture healing was assessed in mice with a targeted 5-LO mutation (5-LOKO mice) and control mice by radiographic and histological observations, and measured by histomorphometry and torsional mechanical testing. To assess effects on arachidonic acid metabolism, prostaglandin E2, F2α, and leukotriene B4 levels were measured in the fracture calluses of control, 5-LOKO COX-1KO, and COX-2KO mice by enzyme linked immunoassays. Results Femur fractures in 5-LOKO mice rapidly developed a cartilaginous callus that was replaced with bone to heal fractures faster than in control mice. Femurs from 5-LOKO mice had substantially better mechanical properties after 1 month of healing than did control mice. Callus leukotriene levels were 4-fold higher in mice homozygous for a targeted mutation in the COX-2 gene (COX-2KO), which indicated that arachidonic acid was shunted into the 5-LO pathway in the absence of COX-2. Interpretation These experiments show that 5-LO negatively regulates fracture healing and that shunting of arachidonic acid into the 5-LO pathway may account, at least in part, for the impaired fracture healing response observed in COX-2KO mice. PMID:21067431

  13. Influence of Early Bisphosphonate Administration for Fracture Healing in Patients with Osteoporotic Proximal Humerus Fractures

    PubMed Central

    Yoo, Jae-Sung; Ryu, Jee-Won; Yu, Kun-Woong

    2016-01-01

    Background Bisphosphonates are generally known to adversely affect fracture healing because they inhibit osteoclastic bone resorption. However, some authors argue that bisphosphonates have no adverse effect on the restoration of the mechanical integrity of long bones after fractures. It is unclear whether bisphosphonates can be initiated safely in patients with acute proximal humerus fractures. The aim of this study was to determine whether the early use of a bisphosphonate affects healing and outcomes of osteoporotic proximal humerus fractures treated with a locking compression plate. Methods Between August 2004 and June 2013, a total of 82 osteoporotic patients who underwent locking plate fixation of proximal humerus fractures were enrolled retrospectively. The patients were divided into two groups according to the timing of the commencement of treatment with alendronate after surgery: group A (n = 34, initiation of the bisphosphonate treatment within two weeks after surgery) and group B (n = 48, control group, initiation of the treatment three months after surgery). Patients were assessed for radiographic union at 2, 6, 10, and 16 weeks, 6 months, and 1 year after surgery. Clinical assessments were performed using the Constant score and American Shoulder and Elbow Surgeons (ASES) score at 1 year after surgery. Results No significant differences were observed between the two groups with respect to radiographic and clinical outcomes after locking plate fixation. All patients obtained fracture union, and the mean time to radiographic union was similar in group A and group B (6.3 and 6.6 weeks, respectively; p = 0.67). Conclusions This study shows that the early initiation of bisphosphonate treatment does not affect bone union or clinical outcomes in patients with an osteoporotic proximal humerus fracture treated by locking compression plate fixation. PMID:27904727

  14. Fracture healing physiology and the quest for therapies for delayed healing and nonunion.

    PubMed

    Kostenuik, Paul; Mirza, Faisal M

    2017-02-01

    Delayed healing and nonunion of fractures represent enormous burdens to patients and healthcare systems. There are currently no approved pharmacological agents for the treatment of established nonunions, or for the acceleration of fracture healing, and no pharmacological agents are approved for promoting the healing of closed fractures. Yet several pharmacologic agents have the potential to enhance some aspects of fracture healing. In preclinical studies, various agents working across a broad spectrum of molecular pathways can produce larger, denser and stronger fracture calluses. However, untreated control animals in most of these studies also demonstrate robust structural and biomechanical healing, leaving unclear how these interventions might alter the healing of recalcitrant fractures in humans. This review describes the physiology of fracture healing, with a focus on aspects of natural repair that may be pharmacologically augmented to prevent or treat delayed or nonunion fractures (collectively referred to as DNFs). The agents covered in this review include recombinant BMPs, PTH/PTHrP receptor agonists, activators of Wnt/β-catenin signaling, and recombinant FGF-2. Agents from these therapeutic classes have undergone extensive preclinical testing and progressed to clinical fracture healing trials. Each can promote bone formation, which is important for the stability of bridged calluses, and some but not all can also promote cartilage formation, which may be critical for the initial bridging and subsequent stabilization of fractures. Appropriately timed stimulation of chondrogenesis and osteogenesis in the fracture callus may be a more effective approach for preventing or treating DNFs compared with stimulation of osteogenesis alone. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:213-223, 2017.

  15. Optimization of intramedullary nailing by numerical simulation of fracture healing.

    PubMed

    Wehner, Tim; Claes, Lutz; Ignatius, Anita; Simon, Ulrich

    2012-04-01

    Due to the annular gap between intramedullary (IM) nails and the endosteal surface, high interfragmentary movement can occur under loading. This could prolong the healing time, particularly for thin IM nails that are often used for unreamed IM nailing. The aims of our study were to determine the influence of the nail diameter on the healing time of human tibial shaft fractures and to investigate whether the healing time could be shortened by increasing the stiffness of the implant material. Therefore, a corroborated numerical model for simulating the fracture healing process in humans was used to simulate the healing process of human tibial fractures treated with IM nails. The calculated healing time (up to 71 weeks) was longest for transverse fractures treated with thin IM nails made of titanium. That the healing time was disproportionately long depended on the nail diameter, and could be greatly reduced by using a thicker nail or using steel instead of titanium. To avoid a prolonged healing time, the nail should be thick, and the annular gap should be as narrow as possible. Alternatively, using steel instead of titanium may also help to avoid a prolonged healing time.

  16. Disruption of thrombospondin-2 accelerates ischemic fracture healing.

    PubMed

    Miedel, Emily; Dishowitz, Michael I; Myers, Marc H; Dopkin, Derek; Yu, Yan-Yiu; Miclau, Ted S; Marcucio, Ralph; Ahn, Jaimo; Hankenson, Kurt D

    2013-06-01

    Thrombospondin-2 (TSP2) is a matricellular protein that is highly up-regulated during fracture healing. TSP2 negatively regulates vascularity, vascular reperfusion following ischemia, and cutaneous wound healing. As well, TSP2-null mice show increased endocortical bone formation due to an enhanced number of mesenchymal progenitor cells and show increased cortical thickness. Mice deficient in TSP2 (TSP2-null) show an alteration in fracture healing, that is unrelated to their cortical bone phenotype, which is characterized by enhanced vascularization with a shift towards an intramembranous healing phenotype; thus, we hypothesized that there would be enhanced ischemic fracture healing in the absence of TSP2. We investigated whether an absence of TSP2 would enhance ischemic fracture healing utilizing Laser doppler, µCT and histological analysis. Ischemic tibial fractures were created in wildtype (WT) and TSP2-null mice and harvested 10, 20, or 40 days post-fracture. TSP2-null mice show enhanced vascular perfusion following ischemic fracture. At day 10 post-fracture, TSP2-null mice have 115% greater bone volume than WT mice. This is associated with a 122% increase in vessel density, 20% increase in cell proliferation, and 15% decrease in apoptosis compared to WT. At day 20, TSP2-null mice have 34% more bone volume, 51% greater bone volume fraction, and 37% more bone tissue mineral density than WT. By 40 days after fracture the TSP2-null mice have a 24% increase in bone volume fraction, but other parameters show no significant differences. These findings indicate TSP2 is a negative regulator of ischemic fracture healing and that in the absence of TSP2 bone regeneration is enhanced.

  17. In silico design of treatment strategies in wound healing and bone fracture healing.

    PubMed

    Geris, L; Schugart, R; Van Oosterwyck, H

    2010-06-13

    Wound and bone fracture healing are natural repair processes initiated by trauma. Over the last decade, many mathematical models have been established to investigate the healing processes in silico, in addition to ongoing experimental work. In recent days, the focus of the mathematical models has shifted from simulation of the healing process towards simulation of the impaired healing process and the in silico design of treatment strategies. This review describes the most important causes of failure of the wound and bone fracture healing processes and the experimental models and methods used to investigate and treat these impaired healing cases. Furthermore, the mathematical models that are described address these impaired healing cases and investigate various therapeutic scenarios in silico. Examples are provided to illustrate the potential of these in silico experiments. Finally, limitations of the models and the need for and ability of these models to capture patient specificity and variability are discussed.

  18. Effects of foot posture on fifth metatarsal fracture healing: a finite element study.

    PubMed

    Brilakis, Emmanuel; Kaselouris, Evaggelos; Xypnitos, Frank; Provatidis, Christopher G; Efstathopoulos, Nicolas

    2012-01-01

    The goal of this study was to evaluate the effects of maintaining different foot postures during healing of proximal fifth metatarsal fractures for each of 3 common fracture types. A 3-dimensional (3D) finite element model of a human foot was developed and 3 loading situations were evaluated, including the following: (1) normal weightbearing, (2) standing with the affected foot in dorsiflexion at the ankle, and (3) standing with the affected foot in eversion. Three different stages of the fracture-healing process were studied, including: stage 1, wherein the material interposed between the fractured edges was the initial connective tissue; stage 2, wherein connective tissue had been replaced by soft callus; and stage 3, wherein soft callus was replaced by mature bone. Thus, 30 3D finite element models were analyzed that took into account fracture type, foot posture, and healing stage. Different foot postures did not statistically significantly affect the peak-developed strains on the fracture site. When the fractured foot was everted or dorsiflexed, it developed a slightly higher strain within the fracture than when it was in the normal weightbearing position. In Jones fractures, eversion of the foot caused further torsional strain and we believe that this position should be avoided during foot immobilization during the treatment of fifth metatarsal base fractures. Tuberosity avulsion fractures and Jones fractures seem to be biomechanically stable fractures, as compared with shaft fractures. Our understanding of the literature and experience indicate that current clinical observations and standard therapeutic options are in accordance with the results that we observed in this investigation, with the exception of Jones fractures.

  19. The Effect of Osteoporosis on Healing of Distal Radius Fragility Fractures.

    PubMed

    Tulipan, Jacob; Jones, Christopher M; Ilyas, Asif M

    2015-10-01

    Although the decision for operative versus nonoperative treatment of distal radius fractures remains subjective and is performed on a case-by-case basis, evaluation and treatment of patients with concomitant osteoporosis requires understanding of the behavior of this injury as a distinct subset of distal radius fractures. Age, infirmity, and osteoporosis affect every aspect of the fracture. Understanding what makes these fractures unique assists surgeons in more effective and efficient treatment. The authors present the current understanding of osteoporotic fragility fractures of the distal radius, focusing on epidemiology, biomechanics of bone healing, and its implication on strategies for management.

  20. Micromotion in the fracture healing of closed distal metaphyseal tibial fractures: A multicentre prospective study.

    PubMed

    Vicenti, G; Pesce, V; Tartaglia, N; Abate, A; Mori, C M; Moretti, B

    2014-12-01

    The dynamic locking screw (DLS) in association with minimally invasive plate osteosynthesis (MIPO) in a bridging construct for simple metadiaphyseal long bone fractures enables modulation of the rigidity of the system and facilitates the development of early and triplanar bone callus. Twenty patients affected by distal tibial fracture were treated with MIPO bridging technique and DLS at the proximal side of the fracture. Time of consolidation, quality of the reduction, complications and American Orthopaedic Foot and Ankle Society (AOFAS) score were monitored and the results compared with those from a control group treated with only standard screws on both fracture sides. Student t-test for independent samples was used for the comparison of means between the two groups. Chi-square test was used for the comparison of proportions. A multiple logistic regression model was constructed to assess the possible confounding effects. Performance was considered significant for p<0.05. The mean healing time was 17.6 ± 2.8 weeks in the group treated with standard screws and 13.5 ± 1.8 weeks in the group treated with DLS (t=5.5, p<0.0001). The DLS was associated with early healing and triplanar bone callus.

  1. TRPV1 deletion impaired fracture healing and inhibited osteoclast and osteoblast differentiation

    PubMed Central

    He, Lin-Hai; Liu, Meng; He, Yang; Xiao, E.; Zhao, Lu; Zhang, Ting; Yang, Hua-Qian; Zhang, Yi

    2017-01-01

    Fracture healing, in which osteoclasts and osteoblasts play important roles, has drawn much clinical attention. Osteoclast deficiency or decreased osteoblast activity will impair fracture healing. TRPV1 is a member of the Ca2+ permeable cation channel subfamily, and pharmacological inhibition of TRPV1 prevents ovariectomy-induced bone loss, which makes TRPV1 a potential target for osteoporosis. However, whether long term TRPV1 inhibition or TRPV1 deletion will affect the fracture healing process is unclear. In this study, we found that the wild-type mice showed a well-remodeled fracture callus, whereas TRPV1 knockout mice still had an obvious fracture gap with unresorbed soft-callus 4 weeks post-fracture. The number of osteoclasts was reduced in the TRPV1 knockout fracture callus, and osteoclast formation and resorption activity were also impaired in vitro. TRPV1 deletion decreased the calcium oscillation frequency and peak cytoplasmic concentration in osteoclast precursors, subsequently reducing the expression and nuclear translocation of NFATc1 and downregulating DC-stamp, cathepsin K, and ATP6V. In addition, TRPV1 deletion caused reduced mRNA and protein expression of Runx2 and ALP in bone marrow stromal cells (BMSCs) and reduced calcium deposition in vitro. Our results suggest that TRPV1 deletion impairs fracture healing, and inhibited osteoclastogenesis and osteogenesis. PMID:28225019

  2. TRPV1 deletion impaired fracture healing and inhibited osteoclast and osteoblast differentiation.

    PubMed

    He, Lin-Hai; Liu, Meng; He, Yang; Xiao, E; Zhao, Lu; Zhang, Ting; Yang, Hua-Qian; Zhang, Yi

    2017-02-22

    Fracture healing, in which osteoclasts and osteoblasts play important roles, has drawn much clinical attention. Osteoclast deficiency or decreased osteoblast activity will impair fracture healing. TRPV1 is a member of the Ca(2+) permeable cation channel subfamily, and pharmacological inhibition of TRPV1 prevents ovariectomy-induced bone loss, which makes TRPV1 a potential target for osteoporosis. However, whether long term TRPV1 inhibition or TRPV1 deletion will affect the fracture healing process is unclear. In this study, we found that the wild-type mice showed a well-remodeled fracture callus, whereas TRPV1 knockout mice still had an obvious fracture gap with unresorbed soft-callus 4 weeks post-fracture. The number of osteoclasts was reduced in the TRPV1 knockout fracture callus, and osteoclast formation and resorption activity were also impaired in vitro. TRPV1 deletion decreased the calcium oscillation frequency and peak cytoplasmic concentration in osteoclast precursors, subsequently reducing the expression and nuclear translocation of NFATc1 and downregulating DC-stamp, cathepsin K, and ATP6V. In addition, TRPV1 deletion caused reduced mRNA and protein expression of Runx2 and ALP in bone marrow stromal cells (BMSCs) and reduced calcium deposition in vitro. Our results suggest that TRPV1 deletion impairs fracture healing, and inhibited osteoclastogenesis and osteogenesis.

  3. The early fracture hematoma and its potential role in fracture healing.

    PubMed

    Kolar, Paula; Schmidt-Bleek, Katharina; Schell, Hanna; Gaber, Timo; Toben, Daniel; Schmidmaier, Gerhard; Perka, Carsten; Buttgereit, Frank; Duda, Georg N

    2010-08-01

    Research regarding the potency and potential of the fracture hematoma has begun to receive increasing attention. However, currently there is a paucity of relevant literature on the capability and composition of the fracture hematoma. This review briefly summarizes the regenerative fracture healing process and the close interplay between the skeletal and immune systems. The role of immune cells in wound healing is also discussed to clarify their involvement in immunological processes during regeneration. We attempt to describe the current state of knowledge regarding the fracture hematoma as the initial stage of the regenerative process of fracture healing. The review discusses how a better understanding of immune reactions in the hematoma may have implications for bone tissue engineering strategies. We conclude the review by emphasizing how additional investigations of the initial phase of healing will allow us to better differentiate between deleterious and beneficial aspects of inflammation, thereby facilitating improved fracture treatment strategies.

  4. Basic concepts regarding fracture healing and the current options and future directions in managing bone fractures.

    PubMed

    Bigham-Sadegh, Amin; Oryan, Ahmad

    2015-06-01

    Fracture healing is a complex physiological process, which involves a well-orchestrated series of biological events. Repair of large bone defects resulting from trauma, tumours, osteitis, delayed unions, non-unions, osteotomies, arthrodesis and multifragmentary fractures is a current challenge of surgeons and investigators. Different therapeutic modalities have been developed to enhance the healing response and fill the bone defects. Different types of growth factors, stem cells, natural grafts (autografts, allografts or xenografts) and biologic- and synthetic-based tissue-engineered scaffolds are some of the examples. Nevertheless, these organic and synthetic materials and therapeutic agents have some significant limitations, and there are still no well-approved treatment modalities to meet all the expected requirements. Bone tissue engineering is a newer option than the traditional grafts and may overcome many limitations of the bone graft. To select an appropriate treatment strategy in achieving a successful and secure healing, more information concerning injuries of bones, their healing process and knowledge of the factors involved are required. The main goals of this work are to present different treatment modalities of the fractured bones and to explain how fractures normally heal and what factors interfere with fracture healing. This study provides an overview of the processes of fracture healing and discusses the current therapeutic strategies that have been claimed to be effective in accelerating fracture healing.

  5. Distal radial fractures heal by direct woven bone formation

    PubMed Central

    2013-01-01

    Background Descriptions of fracture healing almost exclusively deal with shaft fractures and they often emphasize endochondral bone formation. In reality, most fractures occur in metaphyseal cancellous bone. Apart from a study of vertebral fractures, we have not found any histological description of cancellous bone healing in humans. Patients and methods We studied histological biopsies from the central part of 12 distal radial fractures obtained during surgery 6–28 days after the injury, using routine hematoxylin and eosin staining. Results New bone formation was seen in 6 cases. It was always in the form of fetal-like, disorganized woven bone. It seldom had contact with old trabeculae and appeared to have formed directly in the marrow. Cartilage was scarce or absent. The samples without bone formation showed only necrosis, scar, or old cancellous bone. Interpretation The histology suggests that cells in the midst of the marrow respond to the trauma by direct formation of bone, independently of trabecular surfaces. PMID:23570338

  6. Radiation-induced alterations of fracture healing biomechanics

    SciTech Connect

    Pelker, R.R.; Friedlaender, G.E.; Panjabi, M.M.; Kapp, D.; Doganis, A.

    1984-01-01

    The effects of irradiation on the normal temporal progression of the physical properties of healing fractures were studied in a rat model. Fractures were surgically produced in the femur, stabilized with an intramedullary pin, and irradiated. One group of rats was exposed to 2,500 rads in divided doses over 2 weeks, beginning 3 days after fracture, and compared to a control group with fractures which were not irradiated. Animals were sacrificed at periodic intervals and the bones were tested to failure in torsion. The torque, stiffness, and energy increased and the angle decreased for the nonirradiated specimens in the expected fashion. This progression was deleteriously altered in the irradiated femurs.

  7. Retardation of fracture healing by cerclage wire near the elbow in radius fracture models.

    PubMed

    Liu, Fangning; Li, Bin; Wang, Haiyu; Han, Qinghe; Shao, Guoxi; Gao, Yingjie; Xie, Guanghong

    2016-02-01

    Cerclage wire is widely used in the treatment of fracture internal fixation and is shown effective in clinic. But a report by S.L. has pointed that the wire loop delayed the growth of bone. We have established a radius fracture model to study the possible detrimental effects of cerclage wire on fracture healing and the potential mechanism. By high-resolution CT analysis cerclage wire is found to delay fracture healing, by histological assessment cerclage wire is found to extended the time of hematoma and the marrow cavity appearing, by confocal microscopy cerclage wire decreased the content of calcium and the expression of alkaline phosphatase (ALP), and by RT-PCR analysis cerclage wire decreased the mRNA levels of bone sialoprotein and ALP. These results suggest that the cerclage wire near the elbow delayed the fracture healing in radius fracture models.

  8. Assessment of the Genetic Variation in Bone Fracture Healing

    DTIC Science & Technology

    2004-10-01

    variations in both structural and material properties of bone development will be recapitulated in the developmental mechanism(s) that controls the bone’s... structural geometry and material properties during fracture healing. Two goals were set out in the proposal to test this hypothesis. The first was to...determine how variations in basic bone structure and material properties in three in bred strains of mice is translated into the healing process of

  9. Different effects of indomethacin on healing of shaft and metaphyseal fractures

    PubMed Central

    Sandberg, Olof; Aspenberg, Per

    2015-01-01

    Background and purpose NSAIDs are commonly used in the clinic, and there is a general perception that this does not influence healing in common types of human fractures. Still, NSAIDs impair fracture healing dramatically in animal models. These models mainly pertain to fractures of cortical bone in shafts, whereas patients more often have corticocancellous fractures in metaphyses. We therefore tested the hypothesis that the effect of an NSAID is different in shaft healing and metaphyseal healing. Methods 26 mice were given an osteotomy of their left femur with an intramedullary nail. 13 received injections of indomethacin, 1 mg/kg twice daily. After 17 days of healing, the femurs were analyzed with 3-point bending and microCT. 24 other mice had holes drilled in both proximal tibias, to mimic a stable metaphyseal injury. A screw was inserted in the right tibial hole only. After 7 days of indomethacin injections or control injections, screw fixation was measured with mechanical pull-out testing and the side without a screw was analyzed with microCT. Results In the shaft model, indomethacin led to a 35% decrease in force at failure (95% CI: 14–54). Callus size was reduced to a similar degree, as seen by microCT. Metaphyseal healing was less affected by indomethacin, as no effect on pull-out force could be seen (95% CI: –27 to 17) and there was only a small drop in new bone volume inside the drill hole. The difference in the relative effect of indomethacin between the 2 models was statistically significant (p = 0.006). Interpretation Indomethacin had a minimal effect on stable metaphyseal fractures, but greatly impaired healing of unstable shaft fractures. This could explain some of the differences found between animal models and clinical experience. PMID:25323801

  10. Effect of zoledronic acid on fracture healing in osteoporotic patients with intertrochanteric fractures

    PubMed Central

    Hayer, Prabhnoor Singh; Deane, Anit Kumar Samuel; Agrawal, Atul; Maheshwari, Rajesh; Juyal, Anil

    2017-01-01

    Aims: To assess the effect of zoledronic acid (ZOL) on fracture healing in osteoporotic patients with intertrochanteric fracture based on radiological evaluation and to study the correlations between severity of osteoporosis, age, gender, and time taken to fracture union. Settings and Design: An open label study was conducted on 43 patients at a tertiary care center. Subjects and Methods: The osteoporosis status of all the included patients was documented using a double-energy X-ray absorptiometry scan. A single dose of injection ZOL 5 mg was administered intravenously to all the patients after fixation during their hospital stay. Follow-up of the patients was done at 1, 3, and 6 months after surgery until union was seen radiologically. Statistical Analysis Used: Data were entered into Microsoft Office Excel version 2007, and interpretation and analysis of obtained data were done using summary statistics. Pearson correlation between age, gender, bone mineral density (BMD), and time taken to fracture union was done using the IBM SPSS Version 22.0 (IBM Corp. Released 2013. IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY: IBM Corp.). Results: The average age of the patients included in the study was 71.27 ± 11.48 and the average BMD was -4.58±1.42. All the fractures united by the 6th month of follow-up, which was similar to the union rate in comparison with the literature. The correlations between the gender, BMD, age, and time to union were calculated, and all the r values obtained showed very low correlation and the P values in all the variables were not significant. Conclusion: The bisphosphonate therapy did not adversely affect radiologically determined fracture union, and no correlations between severity of osteoporosis, age, gender, and time taken to fracture union were found to be significant. PMID:28251108

  11. Osteogenic Differentiation of Periosteal Cells During Fracture Healing.

    PubMed

    Wang, Tao; Zhang, Xinping; Bikle, Daniel D

    2017-05-01

    Five to ten percent of fractures fail to heal normally leading to additional surgery, morbidity, and altered quality of life. Fracture healing involves the coordinated action of stem cells primarily coming from the periosteum which differentiate into the chondrocytes and osteoblasts, forming first the soft (cartilage) callus followed by the hard (bone) callus. These stem cells are accompanied by a vascular invasion that appears critical for the differentiation process and which may enable the entry of osteoclasts necessary for the remodeling of the callus into mature bone. However, more research is needed to clarify the signaling events that activate the osteochondroprogenitor cells of periosteum and stimulate their differentiation into chondrocytes and osteoblasts. Ultimately a thorough understanding of the mechanisms for differential regulation of these osteochondroprogenitors will aid in the treatment of bone healing and the prevention of delayed union and nonunion of fractures. In this review, evidence supporting the concept that the periosteal cells are the major cell sources of skeletal progenitors for the fracture callus will be discussed. The osteogenic differentiation of periosteal cells manipulated by Wnt/β-catenin, TGF/BMP, Ihh/PTHrP, and IGF-1/PI3K-Akt signaling in fracture repair will be examined. The effect of physical (hypoxia and hyperoxia) and chemical factors (reactive oxygen species) as well as the potential coordinated regulatory mechanisms in the periosteal progenitor cells promoting osteogenic differentiation will also be discussed. Understanding the regulation of periosteal osteochondroprogenitors during fracture healing could provide insight into possible therapeutic targets and thereby help to enhance future fracture healing and bone tissue engineering approaches. J. Cell. Physiol. 232: 913-921, 2017. © 2016 Wiley Periodicals, Inc.

  12. Microstructures Induced in Porous Limestone by Dynamic Loading, and Fracture Healing: An Experimental Approach

    NASA Astrophysics Data System (ADS)

    Richard, Julie; Doan, Mai-Linh; Gratier, Jean-Pierre; Renard, François

    2015-05-01

    Fracturing and healing are crucial processes inducing changes in the permeability and mechanical behavior of fault zones. Fracturing increases the permeability of fault rocks, creating flow-channels for fluid circulation and enhancing the kinetics of such fluid-rock processes as pressure solution or metamorphism. Conversely, healing processes reduce permeability by closing the fractures and lead to rock strengthening. Consequently, the timescales of these two processes are important in determining the strength of fault zones and their ability to rupture during earthquakes. This article reports observations of the microstructure of porous limestone samples subjected to rapid dynamic loading, and long-term healing as a result of fluid percolation. Dynamic loading was performed by impacting the samples with steel bars inside a split Hopkinson pressure bar apparatus. Healing was performed by leaving the samples for three months within a triaxial machine with percolation of supersaturated fluids for five weeks. Two kinds of fracture network were observed in samples damaged at high strain rate: a series of radial and circular macrofractures and an incipient pulverization zone at the center of the sample loaded at the highest strain rate. Fracture density determined microscopically from X-ray images correlates with dissipated energy computed from macro-mechanical data. X-ray images enable good quantification of the damaged state of the samples. Percolation experiments under stress with high-solubility fluid at room temperature show that the main healing processes promoting closure of the fractures in the sample are a combination of mechanical and chemical compaction. Microfracturing networks were found to heal faster than the largest fractures, leading to heterogeneous strengthening of the rock. This feature affects the processes of earthquake nucleation and rupture propagation.

  13. Anti-IL-20 monoclonal antibody promotes bone fracture healing through regulating IL-20-mediated osteoblastogenesis

    PubMed Central

    Hsu, Yu-Hsiang; Chiu, Yi-Shu; Chen, Wei-Yu; Huang, Kuo-Yuan; Jou, I-Ming; Wu, Po-Tin; Wu, Chih-Hsing; Chang, Ming-Shi

    2016-01-01

    Bone loss and skeletal fragility in bone fracture are caused by an imbalance in bone remodeling. The current challenge in bone fracture healing is to promote osteoblastogenesis and bone formation. We aimed to explore the role of IL-20 in osteoblastogenesis, osteoblast differentiation and bone fracture. Serum IL-20 was significantly correlated with serum sclerostin in patients with bone fracture. In a mouse model, anti-IL-20 monoclonal antibody (mAb) 7E increased bone formation during fracture healing. In vitro, IL-20 inhibited osteoblastogenesis by upregulating sclerostin, and downregulating osterix (OSX), RUNX2, and osteoprotegerin (OPG). IL-20R1 deficiency attenuated IL-20-mediated inhibition of osteoblast differentiation and maturation and reduced the healing time after a bone fracture. We conclude that IL-20 affects bone formation and downregulates osteoblastogenesis by modulating sclerostin, OSX, RUNX2, and OPG on osteoblasts. Our results demonstrated that IL-20 is involved in osteoregulation and anti-IL-20 mAb is a potential therapeutic for treating bone fracture or metabolic bone diseases. PMID:27075747

  14. The effect of immunonutrition (glutamine, alanine) on fracture healing

    PubMed Central

    Küçükalp, Abdullah; Durak, Kemal; Bayyurt, Sarp; Sönmez, Gürsel; Bilgen, Muhammed S.

    2014-01-01

    Background There have been various studies related to fracture healing. Glutamine is an amino acid with an important role in many cell and organ functions. This study aimed to make a clinical, radiological, and histopathological evaluation of the effects of glutamine on fracture healing. Methods Twenty rabbits were randomly allocated into two groups of control and immunonutrition. A fracture of the fibula was made to the right hind leg. All rabbits received standard food and water. From post-operative first day for 30 days, the study group received an additional 2 ml/kg/day 20% L-alanine L-glutamine solution via a gastric catheter, and the control group received 2 ml/kg/day isotonic via gastric catheter. At the end of 30 days, the rabbits were sacrificed and the fractures were examined clinically, radiologically, and histopathologically in respect to the degree of union. Results Radiological evaluation of the control group determined a mean score of 2.5 according to the orthopaedists and 2.65 according to the radiologists. In the clinical evaluation, the mean score was 1.875 for the control group and 2.0 for the study group. Histopathological evaluation determined a mean score of 8.5 for the control group and 9.0 for the study group. Conclusion One month after orally administered glutamine–alanine, positive effects were observed on fracture healing radiologically, clinically, and histopathologically, although no statistically significant difference was determined.

  15. The Effect of Low Molecular Weight Heparins on Fracture Healing

    PubMed Central

    Kapetanakis, Stylianos; Nastoulis, Evangelos; Demesticha, Theano; Demetriou, Thespis

    2015-01-01

    Venous Thromboembolism is a serious complication in the trauma patient. The most commonly studied and used anticoagulant treatment in prophylaxis of thrombosis is heparin. The prolonged use of unfractionated heparin has been connected with increased incidence of osteoporotic fractures. Low molecular-weight-heparins (LMWHs) have been the golden rule in antithrombotic therapy during the previous two decades as a way to overcome the major drawbacks of unfractioned heparin. However there are few studies reporting the effects of LMWHs on bone repair after fractures. This review presents the studies about the effects of LMWHs on bone biology (bone cells and bone metabolism) and underlying the mechanisms by which LMWHs may impair fracture healing process. The authors’ research based on literature concluded that there are no facts and statistics for the role of LMWHs on fracture healing process in humans and the main body of evidence of their role comes from in vitro and animal studies. Further large clinical studies designed to compare different types of LMWHs, in different dosages and in different patient or animal models are needed for exploring the effects of LMWHs on fracture healing process. PMID:26161162

  16. Fracture and Healing of Rock Salt Related to Salt Caverns

    SciTech Connect

    Chan, K.S.; Fossum, A.F.; Munson, D.E.

    1999-03-01

    In recent years, serious investigations of potential extension of the useful life of older caverns or of the use of abandoned caverns for waste disposal have been of interest to the technical community. All of the potential applications depend upon understanding the reamer in which older caverns and sealing systems can fail. Such an understanding will require a more detailed knowledge of the fracture of salt than has been necessary to date. Fortunately, the knowledge of the fracture and healing of salt has made significant advances in the last decade, and is in a position to yield meaningful insights to older cavern behavior. In particular, micromechanical mechanisms of fracture and the concept of a fracture mechanism map have been essential guides, as has the utilization of continuum damage mechanics. The Multimechanism Deformation Coupled Fracture (MDCF) model, which is summarized extensively in this work was developed specifically to treat both the creep and fracture of salt, and was later extended to incorporate the fracture healing process known to occur in rock salt. Fracture in salt is based on the formation and evolution of microfractures, which may take the form of wing tip cracks, either in the body or the boundary of the grain. This type of crack deforms under shear to produce a strain, and furthermore, the opening of the wing cracks produce volume strain or dilatancy. In the presence of a confining pressure, microcrack formation may be suppressed, as is often the case for triaxial compression tests or natural underground stress situations. However, if the confining pressure is insufficient to suppress fracture, then the fractures will evolve with time to give the characteristic tertiary creep response. Two first order kinetics processes, closure of cracks and healing of cracks, control the healing process. Significantly, volume strain produced by microfractures may lead to changes in the permeability of the salt, which can become a major concern in

  17. Leptin Influences Healing in the Sprague Dawley Rat Fracture Model

    PubMed Central

    Liu, Pengcheng; Cai, Ming

    2017-01-01

    Background Leptin plays a crucial role in bone metabolism, and its level is related to bone callus formation in the fracture repair process. The objective of this study was to evaluate the effect of recombinant leptin on the healing process of femoral fractures in rats. Material/Methods Forty-eight male Sprague Dawley (SD) rats with an average body weight of 389 g (range: 376–398 g) and an average age of 10 weeks were included in this animal research, and all rats were randomly divided into two major groups. Then standardized femur fracture models were implemented in all SD rats. Rats in the control group were treated with only 0.5 mL of physiological saline, and rats in the experimental group were treated with recombinant leptin 5 μg/kg/d along with the same 0.5 mL of physiological saline for 42 days intraperitoneally. At the same time, each major group was evenly divided into three parallel subgroups for each parallel bone evaluation separately at the second, fourth, and sixth weeks. Each subgroup included eight rats. Results The total radiological evaluation results showed that the healing progress of femoral fracture in the experimental group was superior to that in the control group from the fourth week. At the sixth week, experimental group rats began to present significantly better femoral fracture healing progress than that of the control group rats. Results of biomechanics show the ultimate load (N) and deflection ultimate load (mm) of the experimental group rats was significantly increased compared with that of the control group rats from the fourth week. Conclusions Our results suggest that leptin may have a positive effect on SD rat femur fracture healing. PMID:28088810

  18. PREVALENCE OF HEALED LONG-BONE FRACTURES IN WILD CARNIVORES FROM THE NORTHEASTERN UNITED STATES.

    PubMed

    Argyros, George C; Roth, Aaron J

    2016-09-01

    Museum specimens representing 12 species of terrestrial carnivores from the northeastern United States were inspected for evidence of healed long-bone fractures. Of 413 individuals, 18 (4.4%) exhibited healed fractures. Thirteen (72.2%) occurred in hind limbs; five (27.8%) occurred in forelimbs. Mustelids had the highest prevalence of healed long-bone fractures (38.8%) of all observed fractures. Within family, 5.6% of Canidae and 2.8% of Mustelidae exhibited healed fractures. Bobcats had the highest taxon prevalence of fractures, 18%. Observational data to assess use of and behavior near roads could provide insight to causes of fracture. Capture in combination with noninvasive examination techniques could be employed to determine incidence of healed fractures in wild populations. Individuals with healed fractures could then be tracked via radio telemetry to determine if these animals behave differently than uninjured conspecifics, and assess long-term survivability and fitness.

  19. [The effect of polylactide screws on fracture healing].

    PubMed

    Duan, H; Song, Y; Peng, Z; Liu, L; Xiong, C; Zhang, X; Luo, F; Zhu, X; Lin, D

    2000-12-01

    This experiment aimed at investigating the effect of a kind of home-bred poly-DL-lactide screws on fracture healing. An operation was performed so as to make bilateral lateral condylar fractures of the femur in 8 dogs. The left sides were fixed with 2 home-bred PDLLA(Mv = 43 x 10(4)) screws, and the contralateral sides were fixed with 2 metalic screws to be used as controls. The animals were sacrificed at 2, 4, 8, and 12 weeks after surgery. Optic microscopy and SEM photography were done. The results of optic microscopy showed that fibrous callus formed already in both groups by 2 weeks after surgery, and bilateral fractures united uneventfully by 12 weeks. Although the course of fracture healing in experimental group was slower than that in control group, the osteogenesis in experimental group appeared to be normal. The SEM examination demonstrated that collagenous fibers arranged regularly and calcified normally in both groups at 12 weeks. And many square and rhomboid granules produced from the degradation of PDLLA material were found in experimental group at 12 weeks. Therefore, it is suggested that this kind of home-bred PDLLA screws should be applicable to fractures where the tissues are rich in blood supply.

  20. Immature myeloid cells are critical for enhancing bone fracture healing through angiogenic cascade.

    PubMed

    Levy, Seth; Feduska, Joseph M; Sawant, Anandi; Gilbert, Shawn R; Hensel, Jonathan A; Ponnazhagan, Selvarangan

    2016-12-01

    Bone fractures heal with overlapping phases of inflammation, cell proliferation, and bone remodeling. Osteogenesis and angiogenesis work in concert to control many stages of this process, and when one is impaired it leads to failure of bone healing, termed a nonunion. During fracture repair, there is an infiltration of immune cells at the fracture site that not only mediate the inflammatory responses, but we hypothesize they also exert influence on neovasculature. Thus, further understanding the effects of immune cell participation throughout fracture healing will reveal additional knowledge as to why some fractures heal while others form nonunions, and lead to development of novel therapeutics modulating immune cells, to increase fracture healing and prevent nonunions. Using novel femoral segmental and critical-size defect models in mice, we identified a systemic and significant increase in immature myeloid cell (IMC) infiltration during the initial phase of fracture healing until boney union is complete. Using gemcitabine to specifically ablate the IMC population, we confirmed delayed bone healing. Further, adoptive transfer of IMC increased bone growth in a nonunion model, signifying the role of this unique cell population in fracture healing. We also identified IMC post-fracture have the ability to increase endothelial cell migration, and tube formation, signaling the essential communication between the immune system and angiogenesis as a requirement for proper bone healing. Based on this data we propose that IMC may play a significant role in fracture healing and therapeutic targeting of IMC after fracture would minimize the chances of eventual nonunion pathology.

  1. CaMKK2 Inhibition in Enhancing Bone Fracture Healing

    DTIC Science & Technology

    2016-05-01

    Einhorn, 1986) in the right femurs of 10- week old anesthetized male mice after first inserting an intramedullary pin (25 gauge needle, approx. 0.5...intraperitoneal (i.p.) injections of saline or STO-609 (10 µmol/kg mouse body weight) were performed for 6 weeks . Progression of fracture healing was...permeable inhibitor STO-609 protects from ovariectomy-induced osteoporosis. Moreover, treatment of 32 week old male mice with STO-609 reverses age

  2. Simvastatin Prodrug Micelles Target Fracture and Improve Healing

    PubMed Central

    Dusad, Anand; Yuan, Hongjiang; Ren, Ke; Li, Fei; Fehringer, Edward V.; Purdue, P. Edward; Goldring, Steven R.; Daluiski, Aaron; Wang, Dong

    2014-01-01

    Simvastatin (SIM), a widely used anti-lipidaemic drug, has been identified as a bone anabolic agent. Its poor water solubility and the lack of distribution to the skeleton, however, have limited its application in the treatment of bone metabolic diseases. In this study, an amphiphilic macromolecular prodrug of SIM was designed and synthesized to overcome these limitations. The polyethylene glycol (PEG)-based prodrug can spontaneously self-assemble to form micelles. The use of SIM trimer as the prodrug’s hydrophobic segment allows easy encapsulation of additional free SIM. The in vitro studies showed that SIM/SIM-mPEG micelles were internalized by MC3T3 cells via lysosomal trafficking and consistently induced expression of both BMP2 and DKK1 mRNA, suggesting that the prodrug micelle retains the biological functions of SIM. After systemic administration, optical imaging suggests that the micelles would passively target to bone fracture sites associated with hematoma and inflammation. Furthermore, flow cytometry study revealed that SIM/SIM-mPEG micelles had preferred cellular uptake by inflammatory and resident cells within the fracture callus tissue. The treatment study using a mouse osteotomy model validated the micelles’ therapeutic efficacy in promoting bone fracture healing as demonstrated by micro-CT and histological analyses. Collectively, these data suggest that the macromolecular prodrug-based micelle formulation of SIM may have great potential for clinical management of impaired fracture healing. PMID:25542644

  3. Molecular signaling in bone fracture healing and distraction osteogenesis.

    PubMed

    Liu, Z; Luyten, F P; Lammens, J; Dequeker, J

    1999-04-01

    The process of fracture healing has been described in detail in many histological studies. Recent work has focused on the mechanisms by which growth and differentiation factors regulate the fracture healing process. Rapid progress in skeletal cellular and molecular biology has led to the identification of many signaling molecules associated with the formation of skeletal tissues, including members of the transforming growth factor-beta (TGF-beta) superfamily and the insulin-like growth factor (IGF) family. Increasing evidence indicates that they are critical regulators of cellular proliferation, differentiation, extracellular matrix biosynthesis and mineralization. Limb lengthening procedure (distraction osteogenesis) is a relevant model to investigate the in vivo correlation between mechanical stimulation and biological responses as the callus is stretched by a proper rate and rhythm of mechanical strain. This model also provides additional insights into the molecular and cellular events during bone fracture repair. TGF-beta 1 was significantly increased in both the distracted callus and the fracture callus. The increased level of TGF-beta 1, together with a low concentration of calcium and an enhanced level of collagen synthesis, was maintained in the distracted callus as long as mechanical strain was applied. Less mineralization is also associated with a low level of osteocalcin production. These observations provide further insights into the molecular basis for the cellular events during distraction osteogenesis.

  4. Simvastatin prodrug micelles target fracture and improve healing.

    PubMed

    Jia, Zhenshan; Zhang, Yijia; Chen, Yen Hsun; Dusad, Anand; Yuan, Hongjiang; Ren, Ke; Li, Fei; Fehringer, Edward V; Purdue, P Edward; Goldring, Steven R; Daluiski, Aaron; Wang, Dong

    2015-02-28

    Simvastatin (SIM), a widely used anti-lipidemic drug, has been identified as a bone anabolic agent. Its poor water solubility and the lack of distribution to the skeleton, however, have limited its application in the treatment of bone metabolic diseases. In this study, an amphiphilic macromolecular prodrug of SIM was designed and synthesized to overcome these limitations. The polyethylene glycol (PEG)-based prodrug can spontaneously self-assemble to form micelles. The use of SIM trimer as the prodrug's hydrophobic segment allows easy encapsulation of additional free SIM. The in vitro studies showed that SIM/SIM-mPEG micelles were internalized by MC3T3 cells via lysosomal trafficking and consistently induced expression of both BMP2 and DKK1 mRNA, suggesting that the prodrug micelle retains the biological functions of SIM. After systemic administration, optical imaging suggests that the micelles would passively target to bone fracture sites associated with hematoma and inflammation. Furthermore, flow cytometry study revealed that SIM/SIM-mPEG micelles had preferred cellular uptake by inflammatory and resident cells within the fracture callus tissue. The treatment study using a mouse osteotomy model validated the micelles' therapeutic efficacy in promoting bone fracture healing as demonstrated by micro-CT and histological analyses. Collectively, these data suggest that the macromolecular prodrug-based micelle formulation of SIM may have great potential for clinical management of impaired fracture healing.

  5. 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.

  6. Optimal Treatment of Malignant Long Bone Fracture: Influence of Method of Repair and External Beam Irradiation on the Pathway and Efficacy of Fracture Healing

    DTIC Science & Technology

    2014-10-01

    Long Bone Fracture: Influence of Method of Repair and External Beam Irradiation on the Pathway and Efficacy of Fracture Healing 5a. CONTRACT NUMBER...in the fifth quarter of the award. 15. SUBJECT TERMS Fracture healing , bone healing , endochondral ossification, intramembranous ossification...irradiation, radiotherapy, pathologic fractures, bony metastasis, bone cancer, animal model , rat model 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF

  7. Laboratory investigation of crushed salt consolidation and fracture healing

    SciTech Connect

    Not Available

    1987-01-01

    A laboratory test program was conducted to investigate the consolidation behavior of crushed salt and fracture healing in natural and artificial salt. Crushed salt is proposed for use as backfill in a nuclear waste repository in salt. Artificial block salt is proposed for use in sealing a repository. Four consolidation tests were conducted in a hydrostatic pressure vessel at a maximum pressure of 2500 psi (17.2 MPa) and at room temperature. Three 1-month tests were conducted on salt obtained from the Waste Isolation Pilot Plant and one 2-month test was conducted on salt from Avery Island. Permeability was obtained using argon and either a steady-state or transient method. Initial porosities ranged from 0.26 to 0.36 and initial permeabilities from 2000 to 50,000 md. Final porosities and permeabilities ranged from 0.05 to 0.19 and from <10/sup -5/ md to 110 md, respectively. The lowest final porosity (0.05) and permeability (<10/sup -5/ md) were obtained in a 1-month test in which 2.3% moisture was added to the salt at the beginning of the test. The consolidation rate was much more rapid than in any of the dry salt tests. The fracture healing program included 20 permeability tests conducted on fractured and unfractured samples. The tests were conducted in a Hoek cell at hydrostatic pressures up to 3000 psi (20.6 MPa) with durations up to 8 days. For the natural rock salt tested, permeability was strongly dependent on confining pressure and time. The effect of confining pressure was much weaker in the artificial salt. In most cases the combined effects of time and pressure were to reduce the permeability of fractured samples to the same order of magnitude (or less) as the permeability measured prior to fracturing.

  8. Exposure to 100% Oxygen Abolishes the Impairment of Fracture Healing after Thoracic Trauma

    PubMed Central

    Kemmler, Julia; Bindl, Ronny; McCook, Oscar; Wagner, Florian; Gröger, Michael; Wagner, Katja; Scheuerle, Angelika; Radermacher, Peter; Ignatius, Anita

    2015-01-01

    In polytrauma patients a thoracic trauma is one of the most critical injuries and an important trigger of post-traumatic inflammation. About 50% of patients with thoracic trauma are additionally affected by bone fractures. The risk for fracture malunion is considerably increased in such patients, the pathomechanisms being poorly understood. Thoracic trauma causes regional alveolar hypoxia and, subsequently, hypoxemia, which in turn triggers local and systemic inflammation. Therefore, we aimed to unravel the role of oxygen in impaired bone regeneration after thoracic trauma. We hypothesized that short-term breathing of 100% oxygen in the early post-traumatic phase ameliorates inflammation and improves bone regeneration. Mice underwent a femur osteotomy alone or combined with blunt chest trauma 100% oxygen was administered immediately after trauma for two separate 3 hour intervals. Arterial blood gas tensions, microcirculatory perfusion and oxygenation were assessed at 3, 9 and 24 hours after injury. Inflammatory cytokines and markers of oxidative/nitrosative stress were measured in plasma, lung and fracture hematoma. Bone healing was assessed on day 7, 14 and 21. Thoracic trauma induced pulmonary and systemic inflammation and impaired bone healing. Short-term exposure to 100% oxygen in the acute post-traumatic phase significantly attenuated systemic and local inflammatory responses and improved fracture healing without provoking toxic side effects, suggesting that hyperoxia could induce anti-inflammatory and pro-regenerative effects after severe injury. These results suggest that breathing of 100% oxygen in the acute post-traumatic phase might reduce the risk of poorly healing fractures in severely injured patients. PMID:26147725

  9. Exposure to 100% Oxygen Abolishes the Impairment of Fracture Healing after Thoracic Trauma.

    PubMed

    Kemmler, Julia; Bindl, Ronny; McCook, Oscar; Wagner, Florian; Gröger, Michael; Wagner, Katja; Scheuerle, Angelika; Radermacher, Peter; Ignatius, Anita

    2015-01-01

    In polytrauma patients a thoracic trauma is one of the most critical injuries and an important trigger of post-traumatic inflammation. About 50% of patients with thoracic trauma are additionally affected by bone fractures. The risk for fracture malunion is considerably increased in such patients, the pathomechanisms being poorly understood. Thoracic trauma causes regional alveolar hypoxia and, subsequently, hypoxemia, which in turn triggers local and systemic inflammation. Therefore, we aimed to unravel the role of oxygen in impaired bone regeneration after thoracic trauma. We hypothesized that short-term breathing of 100% oxygen in the early post-traumatic phase ameliorates inflammation and improves bone regeneration. Mice underwent a femur osteotomy alone or combined with blunt chest trauma 100% oxygen was administered immediately after trauma for two separate 3 hour intervals. Arterial blood gas tensions, microcirculatory perfusion and oxygenation were assessed at 3, 9 and 24 hours after injury. Inflammatory cytokines and markers of oxidative/nitrosative stress were measured in plasma, lung and fracture hematoma. Bone healing was assessed on day 7, 14 and 21. Thoracic trauma induced pulmonary and systemic inflammation and impaired bone healing. Short-term exposure to 100% oxygen in the acute post-traumatic phase significantly attenuated systemic and local inflammatory responses and improved fracture healing without provoking toxic side effects, suggesting that hyperoxia could induce anti-inflammatory and pro-regenerative effects after severe injury. These results suggest that breathing of 100% oxygen in the acute post-traumatic phase might reduce the risk of poorly healing fractures in severely injured patients.

  10. VEGF serum concentrations in patients with long bone fractures: a comparison between impaired and normal fracture healing.

    PubMed

    Sarahrudi, Kambiz; Thomas, Anita; Braunsteiner, Tomas; Wolf, Harald; Vécsei, Vilmos; Aharinejad, Seyedhossein

    2009-10-01

    Vascular endothelial growth factor (VEGF) plays an important role in the bone repair process as a potent mediator of angiogenesis and it influences directly osteoblast differentiation. Inhibiting VEGF suppresses angiogenesis and callus mineralization in animals. However, no data exist so far on systemic expression of VEGF with regard to delayed or failed fracture healing in humans. One hundred fourteen patients with long bone fractures were included in the study. Serum samples were collected over a period of 6 months following a standardized time schedule. VEGF serum concentrations were measured. Patients were assigned to one of two groups according to their course of fracture healing. The first group contained 103 patients with physiological fracture healing. Eleven patients with delayed or nonunions formed the second group of the study. In addition, 33 healthy volunteers served as controls. An increase of VEGF serum concentration within the first 2 weeks after fracture in both groups with a following decrease within 6 months after trauma was observed. Serum VEGF concentrations in patients with impaired fracture healing were higher compared to the patients with physiological healing during the entire observation period. However, statistically significant differences were not observed at any time point between both groups. VEGF concentrations in both groups were significantly higher than those in controls. The present results show significantly elevated serum concentrations of VEGF in patients after fracture of long bones especially at the initial healing phase, indicating the importance of VEGF in the process of fracture healing in humans.

  11. Osthole Promotes Endochondral Ossification and Accelerates Fracture Healing in Mice.

    PubMed

    Zhang, Zhongrong; Leung, Wing Nang; Li, Gang; Lai, Yau Ming; Chan, Chun Wai

    2016-12-01

    Osthole has been found to restore bone mass in preclinical osteoporotic models. In the present study, we investigated the effects of osthole on bone fracture repair in mice. Adult C57BL/6 mice were subjected to transverse femoral fractures and administrated orally with 20 mg/kg osthole and vehicle solvent daily from week 1 post-operation. Fracture callus were analyzed by plain radiography, micro-computed tomography, histology, molecular imaging and immunohistochemistry and tartrate-resistant acid phosphatase staining. Results demonstrated that osthole treatment enhanced removal of cartilage and bony union during reparative stage without significant interfering on remodeling process. In vivo molecular imaging showed bone formation rate of the treatment group was almost twofold of control group at week 2 post-operation. Osthole augmented the expression of alkaline phosphatase and collagen type X in hypertrophic chondrocytes as well as expression of bone morphogenetic protein-2, osteocalcin and alkaline phosphatase in osteoblastic cells, indicating it promoted mineralization of hypertrophic cartilage and woven bone growth simultaneously during endochondral healing. In summary, osthole promotes endochondral ossification via upregulation of maturation osteogenic marker genes in chondrocytes and subsequently accelerates fracture repair and bony fusion.

  12. Mobilization of Endogenous Stem Cell Populations Enhances Fracture Healing in a Murine Femoral Fracture Model

    PubMed Central

    Toupadakis, Chrisoula A.; Granick, Jennifer L.; Sagy, Myrrh; Wong, Alice; Ghassemi, Ehssan; Chung, Dai-Jung; Borjesson, Dori L.; Yellowley, Clare E.

    2013-01-01

    Background Delivery of bone marrow derived stem and progenitor cells to the site of injury is an effective strategy to enhance bone healing. An alternate approach is to mobilize endogenous, heterogeneous stem cells that will home to the site of injury. AMD3100 is an antagonist of the chemokine receptor 4 (CXCR4) that rapidly mobilizes stem cell populations into peripheral blood. Our hypothesis was that increasing circulating numbers of stem and progenitor cells using AMD3100 will improve bone fracture healing. Methods A transverse femoral fracture was induced in C57BL/6 mice, after which they were subcutaneously injected for 3 days with AMD3100 or saline control. Mesenchymal stem cells (MSCs), hematopoietic stem and progenitor cells (HSPCs), and endothelial progenitor cells (EPCs) in the peripheral blood and bone marrow were evaluated via flow cytometry, automated hematology analysis, and cell culture 24 hours after injection and/or fracture. Healing was assessed up to 84 days after fracture by histomorphometry and µCT. Results AMD3100 injection resulted in higher numbers of circulating MSCs, HSCs, and EPCs. µCT data demonstrated that the fracture callus was significantly larger compared to the saline controls at day 21 and significantly smaller (remodeled) at day 84. AMD3100-treated mice have a significantly higher bone mineral density than saline-treated counterparts at day 84. Discussion Our data demonstrate that early cell mobilization had significant positive effects on healing throughout the regenerative process. Rapid mobilization of endogenous stem cells could provide an effective alternative strategy to cell transplantation for enhancing tissue regeneration. PMID:23831362

  13. Spontaneous healing responses detected by cone-beam computed tomography of horizontal root fractures: a report of two cases.

    PubMed

    Fagundes, Dyana Dos Santos; de Mendonça, Isabela Lima; de Albuquerque, Maria Tereza Pedrosa; Inojosa, Inês de Fátima de Azevedo Jacinto

    2014-12-01

    Horizontal root fractures (HRF) usually affect the anterior teeth as a result of trauma, and generally heal spontaneously, depending on the vitality of the pulp. Diagnosis based on clinical findings, sensitivity tests, and radiographic examination is important to determine the presence of a root fracture and to prevent a root fracture from passing unnoticed. Cone-beam computed tomography (CBCT) has been used successfully for diagnosis and prognosis imaging of root fractures and has proved to be superior to other radiographic methods. This study reports two cases of dental trauma caused by a collision and a sports accident. The patients suffered horizontal root fractures in the maxillary left central incisor and in the mandibular left central incisor. The diagnosis of root fracture was confirmed by cone-beam computed tomography (CBCT) images, which also demonstrated spontaneous healing of the fracture line. The repair occurred by interposition of connective tissue in the former case and by interposition of bone and connective tissue in the latter case. The final diagnoses of both cases were based on CBCT images, indicating the importance of a CBCT examination to reach a firm diagnosis and to follow the healing process of root fracture cases, avoiding unnecessary radical endodontic treatment.

  14. Outcomes assessment in fracture healing trials: a primer.

    PubMed

    Kooistra, Bauke W; Sprague, Sheila; Bhandari, Mohit; Schemitsch, Emil H

    2010-03-01

    The measurement of clinical outcomes in trauma research is often problematic in that it is subjective and currently no feasible gold standard evaluation is available. Consequently, observed trial results are partly dependent on which outcome measure is used. Precise and useful estimates of treatment effects can only be obtained when using reliable, valid, and responsive instruments for measuring fracture healing. This overview outlines the concept of the validation of outcome measures and provides a summary of available and frequently used instruments in orthopaedic clinical trials. Outcome instruments can be divided into assessments by the clinician and assessments by the patient. Clinician-assessed measures are frequently used in routine practice but have often not been validated before their use in research. They include clinical and radiographic assessments. In contrast, patient-assessed measures have been designed specifically for investigational purposes and measure health on various domains. Some of them have been validated extensively. Critically evaluating established clinician-based assessments and integrating those found to be valid with patient-assessed outcomes into a composite measure of fracture healing constitute major future challenges.

  15. Finite element analysis of the effect of medullary contact on fracture healing and remodeling in the intramedullary interlocking nail-fixed tibia fracture.

    PubMed

    Wang, Haosen; Hao, Zhixiu; Wen, Shizhu

    2017-04-01

    Intramedullary interlocking nail is an effective treatment for tibial diaphyseal fracture. The contact between medullary rod and diaphyseal cortex is able to enhance fracture stability. However, how and to what degree the contact affects fracture healing and subsequent bone remodeling is still unclear. To investigate this, fracture healing and remodeling algorithms were combined, improved, and used to simulate the healing and remodeling processes in a transverse tibial diaphyseal fracture fixed with an intramedullary interlocking nail device. Two different diaphyseal fracture statuses, three different initial loading levels, and two nail materials were considered. The results showed that the medullary contact could significantly enhance the fixation stability; the strain reduction was up to 80% in the initial granulation callus. However, low initial loading level was found to be a more potential risk factor for the insufficient loading-induced nonunion other than medullary contact and stiffer nail material. Furthermore, the stabilizing effect of medullary contact diminished when stiff bone tissue formed in the callus; thus, the remodeling in the long-term was not affected by medullary contact. Copyright © 2016 John Wiley & Sons, Ltd.

  16. Effectiveness of Teriparatide on Fracture Healing: A Systematic Review and Meta-Analysis

    PubMed Central

    Shi, Zhongju; Zhou, Hengxing; Pan, Bin; Lu, Lu; Liu, Jun; Kang, Yi; Yao, Xue; Feng, Shiqing

    2016-01-01

    Purpose Nowadays, the efficacy of teriparatide in treating osteoporosis was widely accepted, but the discussion about using teriparatide to enhance fracture healing hasn’t come to an agreement. This meta-analysis was conducted to evaluate the effectiveness of teriparatide for fracture healing. Methods We searched PubMed, the Cochrane Library, and Embase in August 2016 for randomized controlled trials (RCTs) which concerned the treatment of teriparatide for fracture healing. Results Finally, a total of 380 patients were randomly assigned in the 5 trials included in this meta-analysis. There was a significant effectiveness with regards to function improvement in patients following fracture, however, there was no significant effectiveness with regards to time of radiographic fracture healing, fracture healing rate and reduction in pain. Conclusions This analysis showed that administration of teriparatide following fracture lacked the effectiveness for fracture healing. Moreover, teriparatide administration had no apparent adverse effects. These results should be interpreted with caution because of some clear limitations. If we want to confirm whether teriparatide improves fracture healing, more high-quality randomized controlled trials are needed. PMID:27997614

  17. Systemic Inhibition of Canonical Notch Signaling Results in Sustained Callus Inflammation and Alters Multiple Phases of Fracture Healing

    PubMed Central

    Dishowitz, Michael I.; Mutyaba, Patricia L.; Takacs, Joel D.; Barr, Andrew M.; Engiles, Julie B.; Ahn, Jaimo; Hankenson, Kurt D.

    2013-01-01

    The Notch signaling pathway is an important regulator of embryological bone development, and many aspects of development are recapitulated during bone repair. We have previously reported that Notch signaling components are upregulated during bone fracture healing. However, the significance of the Notch pathway in bone regeneration has not been described. Therefore, the objective of this study was to determine the importance of Notch signaling in regulating bone fracture healing by using a temporally controlled inducible transgenic mouse model (Mx1-Cre;dnMAMLf/-) to impair RBPjκ-mediated canonical Notch signaling. The Mx1 promoter was synthetically activated resulting in temporally regulated systemic dnMAML expression just prior to creation of bilateral tibial fractures. This allowed for mice to undergo unaltered embryological and post-natal skeletal development. Results showed that systemic Notch inhibition prolonged expression of inflammatory cytokines and neutrophil cell inflammation, and reduced the proportion of cartilage formation within the callus at 10 days-post-fracture (dpf) Notch inhibition did not affect early bone formation at 10dpf, but significantly altered bone maturation and remodeling at 20dpf. Increased bone volume fraction in dnMAML fractures, which was due to a moderate decrease in callus size with no change in bone mass, coincided with increased trabecular thickness but decreased connectivity density, indicating that patterning of bone was altered. Notch inhibition decreased total osteogenic cell density, which was comprised of more osteocytes rather than osteoblasts. dnMAML also decreased osteoclast density, suggesting that osteoclast activity may also be important for altered fracture healing. It is likely that systemic Notch inhibition had both direct effects within cell types as well as indirect effects initiated by temporally upstream events in the fracture healing cascade. Surprisingly, Notch inhibition did not alter cell proliferation

  18. 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.

  19. Modeling of an initial stage of bone fracture healing

    NASA Astrophysics Data System (ADS)

    Lu, Yanfei; Lekszycki, Tomasz

    2015-09-01

    In case of the secondary bone fracture healing, four characteristic steps are often distinguished. The first stage, hematoma and clot formation, which is an object of our study, is important because it prepares the environment for the following stages. In this work, a new mathematical model describing basic effects present short after the injury is proposed. The main idea is based on the assumption that blood leaking from the ruptured blood vessels propagates into a poroelastic saturated tissue close to the fracture and mixes with the interstitial liquid present in pores. After certain time period from the first contact with surrounding tissue, the solidification of blood in the fluid mixture starts. This results in clot formation. By assuming the time necessary to initiate solidification and critical saturation of blood in the mixture, the shape and the structure of blood clot could be determined. In numerical example, proposed mathematical formulas were used to study the size of the gap between fractured parts and its effect in blood clot formation.

  20. Elevated levels of macrophage colony-stimulating factor in human fracture healing.

    PubMed

    Sarahrudi, Kambiz; Mousavi, Mehdi; Thomas, Anita; Eipeldauer, Stefan; Vécsei, Vilmos; Pietschmann, Peter; Aharinejad, Seyedhossein

    2010-05-01

    Macrophage colony-stimulating factor (M-CSF) plays a unique role in bone remodeling. However, to our knowledge, no data on the role of M-CSF in fracture healing in humans have been published so far. This study addressed this issue. One hundred and thirteen patients with long-bone fractures were included in the study and divided into two groups, according to their course of fracture healing. The first group contained 103 patients with normal fracture healing. Ten patients with impaired fracture healing formed the second group of the study. Volunteers donated blood samples as control. Serum samples were collected over a period of 6 months, following a standardized time schedule. In addition, M-CSF levels were measured in fracture hematoma and serum of 11 patients with bone fractures. M-CSF concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Fracture hematoma contained significantly higher M-CSF concentrations compared to M-CSF concentrations in patient's serum. M-CSF levels in fracture hematoma and in patient's serum were both significantly higher than M-CSF concentrations measured in serum of healthy controls. Highly elevated M-CSF serum concentrations were found in patients with physiological fracture healing over the entire observation period. Significant differences in the M-CSF serum concentration between patients with normal fracture healing and patients with impaired fracture healing were not observed. This study indicates, for the first time, to our knowledge, a possible local and systemic involvement of M-CSF in humans during fracture healing.

  1. Three-dimensional evaluation of healing joint morphology after closed treatment of condylar fractures.

    PubMed

    Yamashita, Y; Inoue, M; Aijima, R; Danjo, A; Goto, M

    2016-03-01

    Closed treatment for condylar fractures has long been widely accepted. With closed treatment, the deviated bone fragments heal in their new positions, and this may subsequently cause a range of functional impairments. The association between healing morphology and post-treatment functional impairment is unclear. In this study, computed tomography images of 26 patients (35 sides) who had undergone closed treatment for condylar fractures were used to perform a comparative investigation of three-dimensional (3D) bone morphology before and after treatment. As a result, the morphology of the condylar process after treatment was classified into four different patterns: unchanged, spherical, L-shaped, and detached. In terms of the association between fracture types and healing morphology, fractures of the condylar head healed in the spherical pattern, simple fractures of the condylar neck healed in the spherical or L-shaped pattern, and comminuted fractures of the condylar neck healed in the spherical, L-shaped, or detached pattern. The association between mandibular deviation and healing morphology was also investigated, and it was found that deviation was greater for the spherical and detached patterns than for the L-shaped pattern. The present findings indicate that 3D evaluation of the fractured condylar process is required to elucidate the association with functional impairment after healing.

  2. Elements affecting wound healing time: An evidence based analysis.

    PubMed

    Khalil, Hanan; Cullen, Marianne; Chambers, Helen; Carroll, Matthew; Walker, Judi

    2015-01-01

    The purpose of this study was to identify the predominant client factors and comorbidities that affected the time taken for wounds to heal. A prospective study design used the Mobile Wound Care (MWC) database to capture and collate detailed medical histories, comorbidities, healing times and consumable costs for clients with wounds in Gippsland, Victoria. There were 3,726 wounds documented from 2,350 clients, so an average of 1.6 wounds per client. Half (49.6%) of all clients were females, indicating that there were no gender differences in terms of wound prevalence. The clients were primarily older people, with an average age of 64.3 years (ranging between 0.7 and 102.9 years). The majority of the wounds (56%) were acute and described as surgical, crush and trauma. The MWC database categorized the elements that influenced wound healing into 3 groups--factors affecting healing (FAH), comorbidities, and medications known to affect wound healing. While there were a multitude of significant associations, multiple linear regression identified the following key elements: age over 65 years, obesity, nonadherence to treatment plan, peripheral vascular disease, specific wounds associated with pressure/friction/shear, confirmed infection, and cerebrovascular accident (stroke). Wound healing is a complex process that requires a thorough understanding of influencing elements to improve healing times.© 2015 by the Wound Healing Society.

  3. Low dose of propranolol does not affect rat osteotomy healing and callus strength

    PubMed Central

    Smitham, Peter; Crossfield, Lawrence; Hughes, Gillian; Goodship, Allen; Blunn, Gordon; Chenu, Chantal

    2014-01-01

    Experimental studies suggest that the β-blocker propranolol stimulates bone formation but little work has investigated its effect on fracture healing. In this study, we examined if a low dose of propranolol, previously shown to be preventive against bone loss in rats, improves bone repair. Female Wistar rats were injected with saline or propranolol (0.1 mg/kg/day) (n = 20/group), 5 days a week for 8 weeks. Three weeks after the beginning of treatment, all rats underwent a mid-diaphyseal transverse osteotomy in the left femur. Radiographic analysis of ostetomy healing was performed 2 and 5 weeks after osteotomy. Rats were sacrificed at 5 weeks and femora collected for measurements of fracture strength by torsional testing, callus volume, and mineral content by micro-CT analysis and histology of fracture callus. Eighty nine percent of osteotomies achieved apparent radiological union by 5 weeks in both groups. Propranolol treatment did not significantly alter the torsional strength of the fractured femur compared with controls. The volume and mineralization of fracture callus at 5 weeks were not significantly different in both groups. Histology showed that endochondral ossification was not affected by propranolol. Altogether, our results demonstrate that propranolol using the regimen described does not significantly improve or inhibit rat osteotomy healing and mechanical strength. PMID:24710688

  4. Biomechanical analysis of fracture healing in guinea-pigs.

    PubMed

    Kdolsky, Richard; Reihsner, Roland; Beer, Rudolf

    2008-01-01

    To validate the hypothesis that healing of fractures can be accelerated by oral administered L-arginine a guinea-pig model was chosen. A diaphyseal defect fracture was established in the right femur of each of the 32 small animals and stabilized. According to randomization groups the oral administration was realized (2 or 4 weeks medication / solvent). The following biomechanical variables were measured after 4 weeeks in 32 right femora and the corresponding uninjured left femora. The measurement for the healed femur was individually compared with that of the uninjured femur in each animal; bending, force (necessary for refracture) and energy (necessary for refracture). To apply the bending moment in a measurable and reproducible way each end of the femur was secured using a special device. For each femur a strain/momentum graph of the measurements and the essential parameters were drawn (stiffness, end of the linear range, and failure-point). The bending moment was always applied with the same loading rate. The following three variables were used for the biomechanical evaluation; bending stiffness, force until failure and energy necessary for refracture. The bending stiffness reached 73% by the control group and 88% by the 4-week treatment group. The force necessary for refracture was 52% in the control compared with 65% in the 4-week treatment group. The energy necessary for refracture was 36% in the control compared with 73% in the group treated for 4 weeks. The 2 week treatment group showed no statistical significant differences to the control, but the femora from the 4 week treatment group required statistically significant higher energy for refracture than the femora from the control.

  5. A PTH-responsive circadian clock operates in ex vivo mouse femur fracture healing site.

    PubMed

    Kunimoto, Tatsuya; Okubo, Naoki; Minami, Yoichi; Fujiwara, Hiroyoshi; Hosokawa, Toshihiro; Asada, Maki; Oda, Ryo; Kubo, Toshikazu; Yagita, Kazuhiro

    2016-02-29

    The circadian clock contains clock genes including Bmal1 and Period2, and it maintains an interval rhythm of approximately 24 hours (the circadian rhythm) in various organs including growth plate and articular cartilage. As endochondral ossification is involved not only in growth plate but also in fracture healing, we investigated the circadian clock functions in fracture sites undergoing healing. Our fracture models using external fixation involved femurs of Period2::Luciferase knock-in mice which enables the monitoring of endogenous circadian clock state via bioluminescence. Organ culture was performed by collecting femurs, and fracture sites were observed using bioluminescence imaging systems. Clear bioluminescence rhythms of 24-hour intervals were revealed in fracture healing sites. When parathyroid hormone (PTH) was administered to fractured femurs in organ culture, peak time of Period2::Luciferase activity in fracture sites and growth plates changed, indicating that PTH-responsive circadian clock functions in the mouse femur fracture healing site. While PTH is widely used in treating osteoporosis, many studies have reported that it contributes to improvement of fracture healing. Future studies of the role of this local clock in wound healing may reveal a novel function of the circadian timing mechanism in skeletal cells.

  6. Mice with a heterozygous Lrp6 deletion have impaired fracture healing

    PubMed Central

    Burgers, Travis A; Vivanco, Juan F; Zahatnansky, Juraj; Moren, Andrew J Vander; Mason, James J; Williams, Bart O

    2016-01-01

    Bone fracture non-unions, the failure of a fracture to heal, occur in 10%–20% of fractures and are a costly and debilitating clinical problem. The Wnt/β-catenin pathway is critical in bone development and fracture healing. Polymorphisms of linking low-density lipoprotein receptor-related protein 6 (LRP6), a Wnt-binding receptor, have been associated with decreased bone mineral density and fragility fractures, although this remains controversial. Mice with a homozygous deletion of Lrp6 have severe skeletal abnormalities and are not viable, whereas mice with a heterozygous deletion have a combinatory effect with Lrp5 to decrease bone mineral density. As fracture healing closely models embryonic skeletal development, we investigated the process of fracture healing in mice heterozygous for Lrp6 (Lrp6 +/−) and hypothesized that the heterozygous deletion of Lrp6 would impair fracture healing. Mid-diaphyseal femur fractures were induced in Lrp6 +/− mice and wild-type controls (Lrp6 +/+). Fractures were analyzed using micro-computed tomography (μCT) scans, biomechanical testing, and histological analysis. Lrp6 +/− mice had significantly decreased stiffness and strength at 28 days post fracture (PF) and significantly decreased BV/TV, total density, immature bone density, and mature area within the callus on day-14 and -21 PF; they had significantly increased empty callus area at days 14 and 21 PF. Our results demonstrate that the heterozygous deletion of Lrp6 impairs fracture healing, which suggests that Lrp6 has a role in fracture healing. PMID:27635281

  7. The importance of fracture-healing on the deformation of fluid-filled layered systems

    NASA Astrophysics Data System (ADS)

    Vass, Anna; Koehn, Daniel; Toussaint, Renaud; Ghani, Irfan; Piazolo, Sandra

    2014-10-01

    Understanding the fracturing-healing-refracturing cycle is a fundamental part of studying the deformation dynamics and the permeability evolution of rock systems. Previous studies, however, have not examined the influence of healing i.e. fracture-closure through vein formation and the mechanical properties of the "healed" fractures (veins) on the rock deformation. We present results from a two-dimensional coupled hydro-mechanical model which simulates large time and spatial scale dynamic fracturing and healing of a porous medium under the influence of gravity, tectonic stretching and elevated fluid pressures. Our results show that healing decreases the local porosity, and that the veins' strength is more important than their elastic modulus in influencing the deformation and the evolving patterns. Hard veins make the aggregate progressively stronger, results in an overall healing of the system, limited fracturing and thus fluid flow, greater stresses and delayed fracture saturation. Weak veins make the system weaker in which refracturing of the healed bonds is the dominant process that creates more open fractures and thus increases the permeability. These results provide clues for the importance of the veins' mechanical properties and can enhance our understanding of the deformation dynamics and the permeability evolution of the rock systems.

  8. The development of a novel model of direct fracture healing in the rat

    PubMed Central

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

    2012-01-01

    Objectives Small animal models of fracture repair primarily investigate indirect fracture healing via external callus formation. We present the first described rat model of direct fracture healing. Methods A rat tibial osteotomy was created and fixed with compression plating similar to that used in patients. The procedure was evaluated in 15 cadaver rats and then in vivo in ten Sprague-Dawley rats. Controls had osteotomies stabilised with a uniaxial external fixator that used the same surgical approach and relied on the same number and diameter of screw holes in bone. Results Fracture healing occurred without evidence of external callus on plain radiographs. At six weeks after fracture fixation, the mean stress at failure in a four-point bending test was 24.65 N/mm2 (sd 6.15). Histology revealed ‘cutting-cones’ traversing the fracture site. In controls where a uniaxial external fixator was used, bone healing occurred via external callus formation. Conclusions A simple, reproducible model of direct fracture healing in rat tibia that mimics clinical practice has been developed for use in future studies of direct fracture healing. PMID:23610660

  9. Distinct frequency dependent effects of whole-body vibration on non-fractured bone and fracture healing in mice.

    PubMed

    Wehrle, Esther; Wehner, Tim; Heilmann, Aline; Bindl, Ronny; Claes, Lutz; Jakob, Franz; Amling, Michael; Ignatius, Anita

    2014-08-01

    Low-magnitude high-frequency vibration (LMHFV) provokes anabolic effects in non-fractured bone; however, in fracture healing, inconsistent results were reported and optimum vibration conditions remain unidentified. Here, we investigated frequency dependent effects of LMHFV on fracture healing. Twelve-week-old, female C57BL/6 mice received a femur osteotomy stabilized using an external fixator. The mice received whole-body vibrations (20 min/day) with 0.3g peak-to-peak acceleration and a frequency of either 35 or 45 Hz. After 10 and 21 days, the osteotomized femurs and intact bones (contra-lateral femurs, lumbar spine) were evaluated using bending-testing, µ-computed tomography, and histomorphometry. In non-fractured trabecular bone, vibration with 35 Hz significantly increased the relative amount of bone (+28%) and the trabecular number (+29%), whereas cortical bone was not influenced. LMHFV with 45 Hz failed to provoke anabolic effects in trabecular or cortical bone. Fracture healing was not significantly influenced by whole-body vibration with 35 Hz, whereas 45 Hz significantly reduced bone formation (-64%) and flexural rigidity (-34%) of the callus. Although the exact mechanisms remain open, our results suggest that small vibration setting changes could considerably influence LMHFV effects on bone formation in remodeling and repair, and even disrupt fracture healing, implicating caution when treating patients with impaired fracture healing.

  10. Teriparatide Improves Fracture Healing and Early Functional Recovery in Treatment of Osteoporotic Intertrochanteric Fractures

    PubMed Central

    Huang, Tsan-Wen; Chuang, Po-Yao; Lin, Shih-Jie; Lee, Chien-Yin; Huang, Kuo-Chin; Shih, Hsin-Nung; Lee, Mel S.; Hsu, Robert Wen-Wei; Shen, Wun-Jer

    2016-01-01

    Abstract Osteoporotic intertrochanteric fractures result in serious health problems and decrease health-related quality of life (HRQoL). Faster time-to-union is important for early return to daily activities and reduction of complications. Teriparatide has been shown to accelerate fracture healing, but the literature is sparse on this topic. The aim of this study is to assess whether teriparatide accelerates fracture healing. Between 2008 and 2014, patients with osteoporotic intertrochanteric fractures who underwent surgical interventions were enrolled in this retrospective cohort study. Group 1 included patients who were not on any osteoporosis medication prior to fracture and who postoperatively received only calcium and vitamin D; patients in Group 2 were not on any osteoporosis medication prior to fracture, and received teriparatide and calcium and vitamin D postoperatively. Patients in Group 3 were those who were on alendronate prior to fracture and postfracture received teriparatide as well as calcium and vitamin D. Demographics, time-to-union, HRQoL (short-form health survey [SF]-12 physical component summary [PCS] and SF-12 mental component summary [MCS]), morbidities, mortalities, and radiographic and functional outcomes between groups were compared. A total of 189 patients were enrolled in this study. There were 83 patients in Group 1, 47 patients in Group 2, and 59 patients in Group 3. A significantly shorter time-to-union was found in the teriparatide-treated groups (mean, 13.6, 12.3, and 10.6 weeks, respectively [P = 0.002]). With regard to SF-12 PCS, the scores were significantly better in teriparatide-treated groups at 3 months (mean, 19, 28, and 29, respectively [P = 0.002]) and 6 months (mean, 28, 37, and 38, respectively [P = 0.008]). Similar inter-group differences were noted when comparing the pain scores, the ability to get around the house, the ability to get out of the house, and the ability to go shopping at 3 and 6 months

  11. A constitutive model for representing coupled creep, fracture, and healing in rock salt

    SciTech Connect

    Chan, K.S.; Bodner, S.R.; Munson, D.E.; Fossum, A.F.

    1996-03-01

    The development of a constitutive model for representing inelastic flow due to coupled creep, damage, and healing in rock salt is present in this paper. This model, referred to as Multimechanism Deformation Coupled Fracture model, has been formulated by considering individual mechanisms that include dislocation creep, shear damage, tensile damage, and damage healing. Applications of the model to representing the inelastic flow and fracture behavior of WIPP salt subjected to creep, quasi-static loading, and damage healing conditions are illustrated with comparisons of model calculations against experimental creep curves, stress-strain curves, strain recovery curves, time-to-rupture data, and fracture mechanism maps.

  12. Fracture induced mobilization and incorporation of bone marrow-derived endothelial progenitor cells for bone healing.

    PubMed

    Matsumoto, Tomoyuki; Mifune, Yutaka; Kawamoto, Atsuhiko; Kuroda, Ryosuke; Shoji, Taro; Iwasaki, Hiroto; Suzuki, Takahiro; Oyamada, Akira; Horii, Miki; Yokoyama, Ayumi; Nishimura, Hiromi; Lee, Sang Yang; Miwa, Masahiko; Doita, Minoru; Kurosaka, Masahiro; Asahara, Takayuki

    2008-04-01

    We recently reported that systemic administration of peripheral blood (PB) CD34+ cells, an endothelial progenitor cell (EPC)-enriched population, contributed to fracture healing via vasculogenesis/angiogenesis. However, pathophysiological role of EPCs in fracture healing process has not been fully clarified. Therefore, we investigated the hypothesis whether mobilization and incorporation of bone marrow (BM)-derived EPCs may play a pivotal role in appropriate fracture healing. Serial examinations of Laser doppler perfusion imaging and histological capillary density revealed that neovascularization activity at the fracture site peaked at day 7 post-fracture, the early phase of endochondral ossifification. Fluorescence-activated cell sorting (FACS) analysis demonstrated that the frequency of BM cKit+Sca1+Lineage- (Lin-) cells and PB Sca1+Lin- cells, which are EPC-enriched fractions, significantly increased post-fracture. The Sca1+ EPC-derived vasuculogenesis at the fracture site was confirmed by double immunohistochemistry for CD31 and Sca1. BM transplantation from transgenic donors expressing LacZ transcriptionally regulated by endothelial cell-specific Tie-2 promoter into wild type also provided direct evidence that EPCs contributing to enhanced neovascularization at the fracture site were specifically derived from BM. Animal model of systemic administration of PB Sca1+Lin- Green Fluorescent Protein (GFP)+ cells further confirmed incorporation of the mobilized EPCs into the fracture site for fracture healing. These findings indicate that fracture may induce mobilization of EPCs from BM to PB and recruitment of the mobilized EPCs into fracture sites, thereby augment neovascularization during the process of bone healing. EPCs may play an essential role in fracture healing by promoting a favorable environment through neovascularization in damaged skeletal tissue.

  13. 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.

  14. Dynamic Stabilization of Simple Fractures With Active Plates Delivers Stronger Healing Than Conventional Compression Plating

    PubMed Central

    Tsai, Stanley; Bliven, Emily K.; von Rechenberg, Brigitte; Kindt, Philipp; Augat, Peter; Henschel, Julia; Fitzpatrick, Daniel C.; Madey, Steven M.

    2017-01-01

    Objectives: Active plates dynamize a fracture by elastic suspension of screw holes within the plate. We hypothesized that dynamic stabilization with active plates delivers stronger healing relative to standard compression plating. Methods: Twelve sheep were randomized to receive either a standard compression plate (CP) or an active plate (ACTIVE) for stabilization of an anatomically reduced tibial osteotomy. In the CP group, absolute stabilization was pursued by interfragmentary compression with 6 cortical screws. In the ACTIVE group, dynamic stabilization after bony apposition was achieved with 6 elastically suspended locking screws. Fracture healing was analyzed weekly on radiographs. After sacrifice 9 weeks postsurgery, the torsional strength of healed tibiae and contralateral tibiae was measured. Finally, computed tomography was used to assess fracture patterns and healing modes. Results: Healing in both groups included periosteal callus formation. ACTIVE specimens had almost 6 times more callus area by week 9 (P < 0.001) than CP specimens. ACTIVE specimens recovered on average 64% of their native strength by week 9, and were over twice as strong as CP specimens, which recovered 24% of their native strength (P = 0.008). Microcomputed tomography demonstrated that compression plating induced a combination of primary bone healing and gap healing. Active plating consistently stimulated biological bone healing by periosteal callus formation. Conclusions: Compared with compression plating, dynamic stabilization of simple fractures with active plates delivers significantly stronger healing. PMID:27861456

  15. Joint loading modality: its application to bone formation and fracture healing.

    PubMed

    Zhang, P; Malacinski, G M; Yokota, H

    2008-07-01

    Sports-related injuries such as impact and stress fractures often require a rehabilitation programme to stimulate bone formation and accelerate fracture healing. This review introduces a recently developed joint loading modality and evaluates its potential applications to bone formation and fracture healing in post-injury rehabilitation. Bone is a dynamic tissue whose structure is constantly altered in response to its mechanical environments. Indeed, many loading modalities can influence the bone remodelling process. The joint loading modality is, however, able to enhance anabolic responses and accelerate wound healing without inducing significant in situ strain at the site of bone formation or fracture healing. This review highlights the unique features of this loading modality and discusses its potential underlying mechanisms as well as possible clinical applications.

  16. Is there a relationship between fracture healing and mean platelet volume?

    PubMed Central

    Serbest, Sancar; Tiftikci, Ugur; Tosun, Haci Bayram; Gumustas, Seyit Ali; Uludag, Abuzer

    2016-01-01

    Objectives Platelet volume has been defined to be a marker that shows thrombocyte activation and function and it is measured as mean platelet volume (MPV). MPV shows the mean volume of circulating thrombocytes and it is one of the routine parameters in complete blood count. Increased thrombocyte volume is associated with thrombocyte activation. Patients and methods This study included 76 patients who were operated on due to fractures of long tubular bones. Patients who had union without any additional interventions were defined as group I, and patients who needed additional interventions due to nonunion or inadequate union were defined as group II. The control group included healthy volunteers who did not have a fracture. Hematologic test values of the patients that were obtained at admission to emergency ward were recorded. Results The groups were not statistically different in terms of age, sex, and the affected extremity. There were significant differences between group I and group II in terms of mean erythrocyte sedimentation rate, C-reactive protein, and MPV values (P<0.001), but there were no significant differences between group I and the control group. There was also no statistically significant difference among groups in terms of hematologic and biochemical variables. Conclusion In our study, fractures in patients who had lower MPV values than controls during the inflammation process healed without any problem, but fractures in patients with high MPV values more frequently needed additional surgical interventions. PMID:27471388

  17. Impairment of wound healing after operative treatment of mandibular fractures, and the influence of dexamethasone.

    PubMed

    Snäll, Johanna; Kormi, Eeva; Lindqvist, Christian; Suominen, Anna Liisa; Mesimäki, Karri; Törnwall, Jyrki; Thorén, Hanna

    2013-12-01

    Our aim was to clarify the incidence of impaired wound healing after open reduction and ostheosynthesis of mandibular fractures, and to find out whether the use of dexamethasone during the operation increased the risk. Patients were drawn from a larger group of healthy adult dentate patients who had participated in a single-blind, randomised study, the aim of which was to clarify the benefits of operative dexamethasone after treatment of facial fractures. The present analysis comprised 41 patients who had had open reduction and fixation of mandibular fractures with titanium miniplates and monocortical screws through one or 2 intraoral approaches. The outcome variable was impaired healing of the wound. The primary predictive variable was the perioperative use of dexamethasone; other potential predictive variables were age, sex, smoking habit, type of fracture, delay in treatment, and duration of operation. Wound healing was impaired in 13/41 patients (32%) (13/53 of all fractures). The incidence among patients who were given dexamethasone and those who were not did not differ significantly. Only age over 25 was significantly associated with delayed healing (p=0.02). The use of dexamethasone 30 mg perioperatively did not significantly increase the risk of impaired wound healing in healthy patients with clinically uninfected mandibular fractures fixed with titanium miniplates through an intraoral approach. Older age is a significant predictor of impaired healing, which emphasises the importance of thorough anti-infective care in these patients during and after the operation.

  18. Severe muscle trauma triggers heightened and prolonged local musculoskeletal inflammation and impairs adjacent tibia fracture healing

    PubMed Central

    Hurtgen, B.J.; Ward, C.L.; Garg, K.; Pollot, B.E.; Goldman, S.M.; McKinley, T.O.; Wenke, J.C.; Corona, B.T.

    2016-01-01

    Objectives: Complicated fracture healing is often associated with the severity of surrounding muscle tissue trauma. Since inflammation is a primary determinant of musculoskeletal health and regeneration, it is plausible that delayed healing and non-unions are partly caused by compounding local inflammation in response to concomitant muscle trauma. Methods and results: To investigate this possibility, a Lewis rat open fracture model [tibia osteotomy with adjacent tibialis anterior (TA) muscle volumetric muscle loss (VML) injury] was interrogated. We observed that VML injury impaired tibia healing, as indicated by diminished mechanical strength and decreased mineralized bone within the fracture callus, as well as continued presence of cartilage instead of woven bone 28 days post-injury. The VML injured muscle presented innate and adaptive immune responses that were atypical of canonical muscle injury healing. Additionally, the VML injury resulted in a perturbation of the inflammatory phase of fracture healing, as indicated by elevations of CD3+ lymphocytes and CD68+ macrophages in the fracture callus at 3 and 14d post-injury, respectively. Conclusions: These data indicate that heightened and sustained innate and adaptive immune responses to traumatized muscle are associated with impaired fracture healing and may be targeted for the prevention of delayed and non-union following musculoskeletal trauma. PMID:27282456

  19. Role of medicinal plants and natural products on osteoporotic fracture healing.

    PubMed

    Abd Jalil, Mohd Azri; Shuid, Ahmad Nazrun; Muhammad, Norliza

    2012-01-01

    Popularly known as "the silent disease" since early symptoms are usually absent, osteoporosis causes progressive bone loss, which renders the bones susceptible to fractures. Bone fracture healing is a complex process consisting of four overlapping phases-hematoma formation, inflammation, repair, and remodeling. The traditional use of natural products in bone fractures means that phytochemicals can be developed as potential therapy for reducing fracture healing period. Located closely near the equator, Malaysia has one of the world's largest rainforests, which are homes to exotic herbs and medicinal plants. Eurycoma longifolia (Tongkat Ali), Labisia pumila (Kacip Fatimah), and Piper sarmentosum (Kaduk) are some examples of the popular ethnic herbs, which have been used in the Malay traditional medicine. This paper focuses on the use of natural products for treating fracture as a result of osteoporosis and expediting its healing.

  20. Role of Medicinal Plants and Natural Products on Osteoporotic Fracture Healing

    PubMed Central

    Abd Jalil, Mohd Azri; Shuid, Ahmad Nazrun; Muhammad, Norliza

    2012-01-01

    Popularly known as “the silent disease” since early symptoms are usually absent, osteoporosis causes progressive bone loss, which renders the bones susceptible to fractures. Bone fracture healing is a complex process consisting of four overlapping phases—hematoma formation, inflammation, repair, and remodeling. The traditional use of natural products in bone fractures means that phytochemicals can be developed as potential therapy for reducing fracture healing period. Located closely near the equator, Malaysia has one of the world's largest rainforests, which are homes to exotic herbs and medicinal plants. Eurycoma longifolia (Tongkat Ali), Labisia pumila (Kacip Fatimah), and Piper sarmentosum (Kaduk) are some examples of the popular ethnic herbs, which have been used in the Malay traditional medicine. This paper focuses on the use of natural products for treating fracture as a result of osteoporosis and expediting its healing. PMID:22973405

  1. The effects of alpha-tocopherol supplementation on fracture healing in a postmenopausal osteoporotic rat model

    PubMed Central

    Mohamad, Sharlina; Shuid, Ahmad Nazrun; Mohamed, Norazlina; Fadzilah, Fazalina Mohd; Mokhtar, Sabarul Afian; Abdullah, Shahrum; Othman, Faizah; Suhaimi, Farihah; Muhammad, Norliza; Soelaiman, Ima Nirwana

    2012-01-01

    OBJECTIVE: Osteoporosis increases the risk of bone fractures and may impair fracture healing. The aim of this study was to investigate whether alpha-tocopherol can improve the late-phase fracture healing of osteoporotic bones in ovariectomized rats. METHOD: In total, 24 female Sprague-Dawley rats were divided into three groups. The first group was sham-operated, and the other two groups were ovariectomized. After two months, the right femora of the rats were fractured under anesthesia and internally repaired with K-wires. The sham-operated and ovariectomized control rat groups were administered olive oil (a vehicle), whereas 60 mg/kg of alpha-tocopherol was administered via oral gavage to the alpha-tocopherol group for six days per week over the course of 8 weeks. The rats were sacrificed, and the femora were dissected out. Computed tomography scans and X-rays were performed to assess fracture healing and callus staging, followed by the assessment of callus strengths through the biomechanical testing of the bones. RESULTS: Significantly higher callus volume and callus staging were observed in the ovariectomized control group compared with the sham-operated and alpha-tocopherol groups. The ovariectomized control group also had significantly lower fracture healing scores than the sham-operated group. There were no differences between the alpha-tocopherol and sham-operated groups with respect to the above parameters. The healed femora of the ovariectomized control group demonstrated significantly lower load and strain parameters than the healed femora of the sham-operated group. Alpha-tocopherol supplementation was not able to restore these biomechanical properties. CONCLUSION: Alpha-tocopherol supplementation appeared to promote bone fracture healing in osteoporotic rats but failed to restore the strength of the fractured bone. PMID:23018307

  2. The Pathobiology of Diabetes Mellitus in Bone Metabolism, Fracture Healing, and Complications.

    PubMed

    Forslund, Johan M; Archdeacon, Michael T

    2015-10-01

    Complications and inferior outcomes of fractures in the setting of diabetes mellitus (DM) are well documented. The incidence of DM is increasing rapidly, particularly in an aging and obese population. Thus, the combination of DM and fracture is becoming a serious health problem worldwide. As many fractures are relatively uncomplicated in the healthy patient population, a concerted effort to improve outcomes of fractures in patients with DM is warranted. In this article, we review relevant studies and examine the pathobiological mechanisms influencing fracture outcomes, including complications related to bone and soft-tissue healing, and infection.

  3. Thrombospondin-2 influences the proportion of cartilage and bone during fracture healing.

    PubMed

    Taylor, Douglas K; Meganck, Jeffrey A; Terkhorn, Shawn; Rajani, Rajiv; Naik, Amish; O'Keefe, Regis J; Goldstein, Steven A; Hankenson, Kurt D

    2009-06-01

    Thrombospondin-2 (TSP2) is a matricellular protein with increased expression during growth and regeneration. TSP2-null mice show accelerated dermal wound healing and enhanced bone formation. We hypothesized that bone regeneration would be enhanced in the absence of TSP2. Closed, semistabilized transverse fractures were created in the tibias of wildtype (WT) and TSP2-null mice. The fractures were examined 5, 10, and 20 days after fracture using microCT, histology, immunohistochemistry, quantitative RT-PCR, and torsional mechanical testing. Ten days after fracture, TSP2-null mice showed 30% more bone by microCT and 40% less cartilage by histology. Twenty days after fracture, TSP2-null mice showed reduced bone volume fraction and BMD. Mice were examined 5 days after fracture during the stage of neovascularization and mesenchymal cell influx to determine a cellular explanation for the phenotype. TSP2-null mice showed increased cell proliferation with no difference in apoptosis in the highly cellular fracture callus. Although mature bone and cartilage is minimal 5 days after fracture, TSP2-null mice had reduced expression of collagen IIa and Sox9 (chondrocyte differentiation markers) but increased expression of osteocalcin and osterix (osteoblast differentiation markers). Importantly, TSP2-null mice had a 2-fold increase in vessel density that corresponded with a reduction in vascular endothelial growth factor (VEGF) and Glut-1 (markers of hypoxia inducible factor [HIF]-regulated transcription). Finally, by expressing TSP2 using adenovirus starting 3 days after fracture, chondrogenesis was restored in TSP2-null mice. We hypothesize that TSP2 expressed by cells in the fracture mesenchyme regulates callus vascularization. The increase in vascularity increases tissue oxemia and decreases HIF; thus, undifferentiated cells in the callus develop into osteoblasts rather than chondrocytes. This leads to an alternative strategy for achieving fracture healing with reduced

  4. Analyzing the cellular contribution of bone marrow to fracture healing using bone marrow transplantation in mice

    SciTech Connect

    Colnot, C. . E-mail: colnotc@orthosurg.ucsf.edu; Huang, S.; Helms, J.

    2006-11-24

    The bone marrow is believed to play important roles during fracture healing such as providing progenitor cells for inflammation, matrix remodeling, and cartilage and bone formation. Given the complex nature of bone repair, it remains difficult to distinguish the contributions of various cell types. Here we describe a mouse model based on bone marrow transplantation and genetic labeling to track cells originating from bone marrow during fracture healing. Following lethal irradiation and engraftment of bone marrow expressing the LacZ transgene constitutively, wild type mice underwent tibial fracture. Donor bone marrow-derived cells, which originated from the hematopoietic compartment, did not participate in the chondrogenic and osteogenic lineages during fracture healing. Instead, the donor bone marrow contributed to inflammatory and bone resorbing cells. This model can be exploited in the future to investigate the role of inflammation and matrix remodeling during bone repair, independent from osteogenesis and chondrogenesis.

  5. Potential Role of Local Estrogen in Enhancement of Fracture Healing: Preclinical Study in Rabbits

    PubMed Central

    Tahami, Mohammad; Haddad, Behrooz; Abtahian, Armin; Hashemi, Ali; Aminian, Amir; Konan, Sujith

    2016-01-01

    Background: Effects of estrogen on bone metabolism and its protective role on prevention of osteoporosis are well documented. However, the efficacy of estrogen treatment on bone healing is not well investigated. The drug can be delivered both systemically or locally to the bone with differences in concentrations and side effects. The aim of this study was to investigate the effect of local and systemic administration of estrogen on the fracture healing process. Methods: Standardized tibial fractures with 4 millimeter gaps were created in twenty four adult male Dutch rabbits. Fractures were fixed using intramedullary wires and long leg casts. Rabbits were randomly divided into three groups. Group A was treated with twice a week administration of long acting systemic estrogen; group B was treated with a similar regimen given locally at the fracture gap; and group C received sham normal saline injections (control). Fracture healing was assessed at six weeks post fracture by gross examination, radiographic and histomorphometric analysis. Results: Group B had significantly higher gross stability, radiographic union and gap reduction than the two other groups. Histomorphometric analysis showed higher cartilaginous proportion of periosteal callus area in the control group. Conclusions: Our results showed that estrogen may enhance fracture healing of long bone in rabbits. Furthermore, local estrogen treatment might have better effect than systemic treatment. PMID:27847844

  6. What is the role of bosentan in healing of femur fractures in a rat model?

    PubMed

    Aydin, Ali; Halici, Zekai; Akpinar, Erol; Aksakal, A Murat; Saritemur, Murat; Yayla, Muhammed; Kunak, C Semih; Cadirci, Elif; Atmaca, H Tarik; Karcioglu, S Sena

    2015-09-01

    The purpose of this study was to examine the effects bosentan (which is a strong vasoconstrictor) on bone fracture pathophysiology, and investigate the roles of the nonselective endothelin 1 receptor blocker bosentan on the bone fractures formed in rats through radiographic, histopathologic, and immunohistochemical methods. The rats were divided into three groups (six rats in each group): a femoral fracture control group, a femoral fracture plus bosentan at 50 mg/kg group, and a femoral fracture plus bosentan at 100 mg/kg group. The femoral fracture model was established by transversely cutting the femur at the midsection. After manual reduction, the fractured femur was fixed with intramedullary Kirschner wires. The radiographic healing scores of the bosentan 100 and 50 mg/kg groups were significantly better that those of the fracture control group. The fracture callus percent of new bone in the bosentan 100 mg/kg group was significantly greater than that in the control group. Also, semiquantitative analysis showed higher positive vascular endothelial growth factor and osteocalcin staining and lower positive endothelin receptor type A staining in the treatment groups than in the control group. Bosentan treatment also decreased tissue endothelin 1 expression relative to that in the fracture control group. As a result of our study, the protective effect of bosentan was shown in experimental femoral fracture healing in rats by radiographic, histopathologic, and molecular analyses.

  7. Loss of B cell regulatory function is associated with delayed healing in patients with tibia fracture.

    PubMed

    Yang, Shufeng; Ding, Wei; Feng, Dapeng; Gong, Haiyang; Zhu, Dongmei; Chen, Bin; Chen, Jianmin

    2015-11-01

    The process of bone regeneration after fracture is a complex and well-orchestrated process usually requiring 3-12 weeks. A subset of patients, however, exhibit delayed healing time and even incomplete restoration of the normal bone structure. Although the precise mechanism is unknown, studies have shown that smurf1 may play a role during the process. Here, we sought to determine the involvement of the immune system in impaired bone healing. We found that immediately after fracture, the B-cell composition was shifted toward increased frequency of plasmablasts and decreased frequency of naïve B cells, reflecting higher inflammatory status. The percentage of CD19(+) CD24(+) CD38(+) regulatory B cells was also upregulated in response to bone fracture. The production of IL-10, a pivotal cytokine in regulatory B-cell function, was upregulated in all patients. Interestingly, the increase in IL-10 production was only sustained throughout the healing course in normal healing patients but not in delayed healing patients. Rather, delayed healing patients downregulated B-cell IL-10 secretion early and had reduced level of regulatory B-cell activity. Together, these data revealed a role of regulatory B cells in the endogenous bone regeneration process and an alternation in B-cell-mediated regulation in delayed healing patients.

  8. Supplementary vitamin C does not accelerate bone healing in a rat tibia fracture model

    PubMed Central

    Giordano, Vincenzo; Albuquerque, Rodrigo Pires e; do Amaral, Ney Pecegueiro; Chame, Cristiano Curcio; de Souza, Fabio; Apfel, Mara Íbis Rodrigues

    2012-01-01

    Objective To investigate the role of ascorbic acid supplementation on bone healing after rat tibia fracture. Methods Thirty male Wistar rats were randomly divided into Vitamin C (Group A) and sham (Group B) groups (15 rats each). Group A received 200 mg intraperitoneally per kg per day of ascorbic acid and Group B was given saline 5 ml per kg per day intraperitoneally once a day. The animals were caged in pairs and allowed free access to tap water and a standard rodent chow ad libitum. Fractures were produced manually, they were not stabilized, and unprotected weight-bearing was allowed. At two, four, and six weeks post-fracture, the rats in both groups were anesthetized and sacrificed by cervical dislocation. Callus tissue was dissected, prepared, and analyzed histologically. Histomorphological analysis was performed at six weeks post-fracture and the extent of fracture healing was determined using a five-point scale. Results There were no histological and histomorphological differences between drug-treated animals and the sham in the three different stages studied. By six weeks post-fracture, the five animals of each group had a complete bone union. Conclusion Under the studied conditions, intraperitoneal Vitamin C supplementation does not accelerate the fracture healing process after experimental tibia fracture in rats. Level of evidence: Level 2, individual study with experimental design. PMID:24453572

  9. Hedgehog signaling mediates woven bone formation and vascularization during stress fracture healing

    PubMed Central

    Kazmers, Nikolas H.; McKenzie, Jennifer A.; Shen, Tony S.; Long, Fanxin; Silva, Matthew J.

    2015-01-01

    Hedgehog (Hh) signaling is critical in developmental osteogenesis, and recent studies suggest it may also play a role in regulating osteogenic gene expression in the post-natal setting. However, there is a void of studies directly assessing the effect of Hh inhibition on post-natal osteogenesis. This study utilized a cyclic loading-induced ulnar stress fracture model to evaluate the hypothesis that Hh signaling contributes to osteogenesis and angiogenesis during stress fracture healing. Immediately prior to loading, adult rats were given GDC-0449 (Vismodegib - a selective Hh pathway inhibitor; 50mg/kg orally twice daily), or vehicle. Hh signaling was upregulated in response to stress fracture at 3d (Ptch1, Gli1 expression), and was markedly inhibited by GDC-0449 at 1d and 3d in the loaded and non-loaded ulnae. GDC-0449 did not affect Hh ligand expression (Shh, Ihh, Dhh) at 1d, but decreased Shh expression by 37% at 3d. GDC-0449 decreased woven bone volume (−37%) and mineral density (−17%) at 7d. Dynamic histomorphometry revealed that the 7d callus was composed predominantly of woven bone in both groups. The observed reduction in woven bone occurred concomitantly with decreased expression of Alpl and Ibsp, but was not associated with differences in early cellular proliferation (as determined by callus PCNA staining at 3d), osteoblastic differentiation (Osx expression at 1d and 3d), chondrogenic gene expression (Acan, Sox9, and Col2α1 expression at 1d and 3d), or bone resorption metrics (callus TRAP staining at 3d, Rankl and Opg expression at 1d and 3d). To evaluate angiogenesis, vWF immunohistochemistry showed that GDC-0449 reduced fracture callus blood vessel density by 55% at 3d, which was associated with increased Hif1α gene expression (+30%). Dynamic histomorphometric analysis demonstrated that GDC-0449 also inhibited lamellar bone formation. Lamellar bone analysis of the loaded limb (directly adjacent to the woven bone callus) showed that GDC-0449

  10. Hedgehog signaling mediates woven bone formation and vascularization during stress fracture healing.

    PubMed

    Kazmers, Nikolas H; McKenzie, Jennifer A; Shen, Tony S; Long, Fanxin; Silva, Matthew J

    2015-12-01

    Hedgehog (Hh) signaling is critical in developmental osteogenesis, and recent studies suggest it may also play a role in regulating osteogenic gene expression in the post-natal setting. However, there is a void of studies directly assessing the effect of Hh inhibition on post-natal osteogenesis. This study utilized a cyclic loading-induced ulnar stress fracture model to evaluate the hypothesis that Hh signaling contributes to osteogenesis and angiogenesis during stress fracture healing. Immediately prior to loading, adult rats were given GDC-0449 (Vismodegib - a selective Hh pathway inhibitor; 50mg/kg orally twice daily), or vehicle. Hh signaling was upregulated in response to stress fracture at 3 days (Ptch1, Gli1 expression), and was markedly inhibited by GDC-0449 at 1 day and 3 days in the loaded and non-loaded ulnae. GDC-0449 did not affect Hh ligand expression (Shh, Ihh, Dhh) at 1 day, but decreased Shh expression by 37% at 3 days. GDC-0449 decreased woven bone volume (-37%) and mineral density (-17%) at 7 days. Dynamic histomorphometry revealed that the 7 day callus was composed predominantly of woven bone in both groups. The observed reduction in woven bone occurred concomitantly with decreased expression of Alpl and Ibsp, but was not associated with differences in early cellular proliferation (as determined by callus PCNA staining at 3 days), osteoblastic differentiation (Osx expression at 1 day and 3 days), chondrogenic gene expression (Acan, Sox9, and Col2α1 expression at 1 day and 3 days), or bone resorption metrics (callus TRAP staining at 3 days, Rankl and Opg expression at 1 day and 3 days). To evaluate angiogenesis, vWF immunohistochemistry showed that GDC-0449 reduced fracture callus blood vessel density by 55% at 3 days, which was associated with increased Hif1α gene expression (+30%). Dynamic histomorphometric analysis demonstrated that GDC-0449 also inhibited lamellar bone formation. Lamellar bone analysis of the loaded limb (directly adjacent

  11. Strontium ranelate enhances callus strength more than PTH 1-34 in an osteoporotic rat model of fracture healing.

    PubMed

    Habermann, Bjoern; Kafchitsas, Konstantinos; Olender, Gavin; Augat, Peter; Kurth, Andreas

    2010-01-01

    Treatment of an underlying disease is often initiated after the occurrence of an osteoporotic fracture. Our aim was to investigate whether teriparatide (PTH 1-34) and strontium ranelate affect fracture healing in ovariectomized (OVX) rats when provided for the first time after the occurrence of an osteoporotic fracture. We combined the model of an OVX rat with a closed diaphyseal fracture. Sixty Sprague Dawley rats were randomly assigned to four groups. Fracture healing in OVX rats after treatment with pharmacological doses of strontium ranelate and PTH 1-34 was compared with OVX and sham-treated control groups. After 28 days, the femur was excised and scanned by micro computed tomography and the callus evaluated, after which biomechanical torsional testing was performed and torque and toughness until reaching the yield point were analyzed. Only treatment with strontium ranelate led to a significant increase in callus resistance compared to the OVX control rats, whereas both PTH 1-34 and strontium ranelate increased the bone volume/tissue volume ratio of the callus. The PTH 1-34-increased trabecular bone volume within the callus was even higher compared to sham. As for the callus tissue volume, the increase induced by strontium ranelate was significant, contrary to the changes induced by PTH. Callus in strontium ranelate-treated animals is more resistant to torsion compared with OVX control rats. To our knowledge, this is the first report of the enhancement of fracture healing by strontium ranelate. Because both treatments enhance bone and tissue volume within the callus, there may be a qualitative difference between the calluses of PTH 1-34- and strontium ranelate-treated OVX rats. The superior results obtained with strontium ranelate compared to PTH in terms of callus resistance could be the consequence of a better quality of the new bone formed within the callus.

  12. Current Role and Application of Teriparatide in Fracture Healing of Osteoporotic Patients: A Systematic Review

    PubMed Central

    Kim, Sang-Min; Kang, Kyung-Chung; Kim, Ji Wan; Lim, Seung-Jae

    2017-01-01

    Background The use of osteoanabolic agents to facilitate fracture healing has been of heightened interest to the field of orthopaedic trauma. This study aimed to evaluate the evidence of teriparatide for fracture healing and functional recovery in osteoporotic patients. Methods We performed a literature search in PubMed, EMBASE, Web of Science, and the Cochrane Library using terms including “Fracture” [tiab] AND “Teriparatide [tiab] OR “PTH” [tiab]. Results This systematic review included 6 randomized clinical trials, 4 well-controlled retrospective studies, and 1 retrospective post hoc subgroup analysis. Fracture location was 2 in pelvis, 3 in proximal femur, 1 in distal femur, 1 in shoulder, 2 in wrist and 2 in spine. The use of teriparatide yielded positive effects on radiographic bone healing in 6 studies, but was not associated with better radiographic outcome in 3. In terms of functional recovery, teriparatide injection was related with decrease in pain or shorter time to mobilization in 6 studies, but not related with pain numerical scale and mobility in 3. Conclusions Our findings suggest that teriparatide provide selective advantages to fracture healing or functional recovery in the management of osteoporotic fractures. A better understanding of the role of teriparatide on osteoporotic fractures requires greater evidences from large volume prospective trials. PMID:28326303

  13. Effect of nonsteroidal antiinflammatory drugs on fracture healing: a laboratory study in rats.

    PubMed

    Altman, R D; Latta, L L; Keer, R; Renfree, K; Hornicek, F J; Banovac, K

    1995-01-01

    We studied the effects of two nonsteroidal antiinflammatory drugs (NSAIDs) on fracture healing in rats: ibuprofen (30 mg/kg/day) and indomethacin (1 mg/kg/day). Femoral fractures were induced via a three-point bending technique. NSAIDs were administered orally for 4 or 12 weeks. Control animals received no medication. In each group a minimum of six animals were killed at the following intervals: 2, 4, 6, 8, 10, and 12 weeks postfracture. Fracture healing was determined by mechanical testing and histologic evaluation. The bending strength of each fractured femur was expressed as a percentage of the strength of the intact, contralateral femur. Histologic evaluation was performed on serial longitudinal sections stained with hematoxylin and eosin using a qualitative score of maturity of the callus. Ibuprofen and indomethacin both retarded fracture healing, with significant differences in "mechanical healing" found between the control and experimental groups after 10 weeks of drug administration. Both drugs also induced qualitative histologic changes manifested by delayed maturation of callus, which was noticeable earlier than the difference found by mechanical testing of bone. Our data suggest that NSAIDs have an inhibitory effect on fracture repair that is reversible after cessation of indomethacin but not ibuprofen.

  14. Clinician's ability to evaluate the strength of healing fractures from plain radiographs

    SciTech Connect

    Panjabi, M.M.; Lindsey, R.W.; Walter, S.D.; White, A.A. 3d.

    1989-01-01

    The present study was designed to analyze the usefulness of plain radiographs in evaluating bone healing. Rabbit tibiae were osteotomized, externally fixed, and allowed to heal for 3-8 weeks. Bones were harvested, x-rayed, and tested to failure in a dynamic torsion tester. AP and lateral radiographs of 10 rabbit tibia pairs and 10 individual rabbit tibiae were selected randomly for use in a questionnaire, given to 93 physicians who routinely assess fracture healing to evaluate clinicians' ability to assess bone strength. The results indicated that clinicians can differentiate the relative strength of bones by comparing two sets of radiographs. However, the strength determination from a single set of radiographs of a fracture is unreliable, the tendency being to evaluate the fracture to be weaker than it actually is.

  15. The effect of HIV on early wound healing in open fractures treated with internal and external fixation.

    PubMed

    Aird, J; Noor, S; Lavy, C; Rollinson, P

    2011-05-01

    There are 33 million people worldwide currently infected with human immunodeficiency virus (HIV). This complex disease affects many of the processes involved in wound and fracture healing, and there is little evidence available to guide the management of open fractures in these patients. Fears of acute and delayed infection often inhibit the use of fixation, which may be the most effective way of achieving union. This study compared fixation of open fractures in HIV-positive and -negative patients in South Africa, a country with very high rates of both HIV and high-energy trauma. A total of 133 patients (33 HIV-positive) with 135 open fractures fulfilled the inclusion criteria. This cohort is three times larger than in any similar previously published study. The results suggest that HIV is not a contraindication to internal or external fixation of open fractures in this population, as HIV is not a significant risk factor for acute wound/implant infection. However, subgroup analysis of grade I open fractures in patients with advanced HIV and a low CD4 count (< 350) showed an increased risk of infection; we suggest that grade I open fractures in patients with advanced HIV should be treated by early debridement followed by fixation at an appropriate time.

  16. Anti-DKK1 antibody promotes bone fracture healing through activation of β-catenin signaling.

    PubMed

    Jin, Hongting; Wang, Baoli; Li, Jia; Xie, Wanqing; Mao, Qiang; Li, Shan; Dong, Fuqiang; Sun, Yan; Ke, Hua-Zhu; Babij, Philip; Tong, Peijian; Chen, Di

    2015-02-01

    In this study we investigated if Wnt/β-catenin signaling in mesenchymal progenitor cells plays a role in bone fracture repair and if DKK1-Ab promotes fracture healing through activation of β-catenin signaling. Unilateral open transverse tibial fractures were created in CD1 mice and in β-catenin(Prx1ER) conditional knockout (KO) and Cre-negative control mice (C57BL/6 background). Bone fracture callus tissues were collected and analyzed by radiography, micro-CT (μCT), histology, biomechanical testing and gene expression analysis. The results demonstrated that treatment with DKK1-Ab promoted bone callus formation and increased mechanical strength during the fracture healing process in CD1 mice. DKK1-Ab enhanced fracture repair by activation of endochondral ossification. The normal rate of bone repair was delayed when the β-catenin gene was conditionally deleted in mesenchymal progenitor cells during the early stages of fracture healing. DKK1-Ab appeared to act through β-catenin signaling to enhance bone repair since the beneficial effect of DKK1-Ab was abrogated in β-catenin(Prx1ER) conditional KO mice. Further understanding of the signaling mechanism of DKK1-Ab in bone formation and bone regeneration may facilitate the clinical translation of this anabolic agent into therapeutic intervention.

  17. Haploinsufficiency of endogenous parathyroid hormone-related peptide impairs bone fracture healing.

    PubMed

    Wang, Yin-He; Qiu, Yong; Han, Xiao-Dong; Xiong, Jin; Chen, Yi-Xin; Shi, Hong-Fei; Karaplis, Andrew

    2013-11-01

    Previous studies have demonstrated that endogenous parathyroid hormone-related peptide (PTHrP) plays a central role in the physiological regulation of bone formation. However, it is unclear whether endogenous PTHrP plays an important function in enhancing bone fracture healing. To determine whether endogenous PTHrP haploinsufficiency impaired bone fracture healing, closed mid-diaphyseal femur fractures were created in 8-week-old wild-type and Pthrp(+/-) mice. Callus tissue properties were analysed 1, 2 and 4 weeks after fracture by radiography, histology, histochemistry, immunohistochemistry and molecular biology. The size of the calluses was reduced 2 weeks after fracture, and the fracture repairs were poor 4 weeks after fractures, in Pthrp(+/-) compared with wild-type mice. Cartilaginous callus areas were reduced 1 week after fracture, but were increased 2 weeks after fracture in Pthrp(+/-) mice. There was a reduction in the number of ostoblasts, alkaline phosphatase (ALP)-positive areas, Type I collagen immunopositive areas, mRNA levels of ALP, Runt-related transcription factor 2 (Runx2) and Type I collagen, Runx2 and insulin-like growth factor-1 protein levels, the number of osteoclasts and the surface in callus tissues in Pthrp(+/-) compared with wild-type mice. These results demonstrate that endogenous PTHrP haploinsufficiency impairs the fracture repair process by reducing cartilaginous and bony callus formation, with downregulation of osteoblastic gene and protein expression and a reduction in endochondral bone formation, osteoblastic bone formation and osteoclastic bone resorption. Together, the results indicate that endogenous PTHrP plays an important role in fracture healing.

  18. Extracorporeal shock wave therapy for non-unions and delayed fracture healing

    NASA Astrophysics Data System (ADS)

    Schaden, Wolfgang; Fischer, Andreas; Sailler, Andreas; Karadas, Ender

    2005-04-01

    Although the primary management of fractures is highly developed in Central Europe 1% of fractures develop a non-union. After successful pilot studies the Traumacenter Meidling started in December 1998 to treat non-unions regularly with shock wave therapy. From December 1998 to August 2004, 1153 patients with non-union and delayed healing fractures were treated. The results of 755 patients are available up to September 2004. The patients consisted of 250 (33%) female and 505 (67%) male. The mean age was 44.1 years (10; 90). The mean age of the non-union was 15.5 months. In 74 (10%) osteomyelitis was present before shockwave therapy. Out of 755 non-unions 593 (79%) achieved bony healing. As expected, the subgroup of 284 delayed unions (shockwave therapy 3-6 months after the trauma or the last surgery concerning the bone) showed the best results. 245 (86%) healed. Out of 471 non-unions being older than 6 months 348 (72%) achieved bony healing. Because of the efficacy and the lack of complications as well as the economic advantage in comparison to surgery, shockwave therapy is considered as therapy of first choice in the treatment of non-union and delayed healing fractures.

  19. Vitamin E and the Healing of Bone Fracture: The Current State of Evidence

    PubMed Central

    Borhanuddin, Boekhtiar; Mohd Fozi, Nur Farhana; Naina Mohamed, Isa

    2012-01-01

    Background. The effect of vitamin E on health-related conditions has been extensively researched, with varied results. However, to date, there was no published review of the effect of vitamin E on bone fracture healing. Purpose. This paper systematically audited past studies of the effect of vitamin E on bone fracture healing. Methods. Related articles were identified from Medline, CINAHL, and Scopus databases. Screenings were performed based on the criteria that the study must be an original study that investigated the independent effect of vitamin E on bone fracture healing. Data were extracted using standardised forms, followed by evaluation of quality of reporting using ARRIVE Guidelines, plus recalculation procedure for the effect size and statistical power of the results. Results. Six animal studies fulfilled the selection criteria. The study methods were heterogeneous with mediocre reporting quality and focused on the antioxidant-related mechanism of vitamin E. The metasynthesis showed α-tocopherol may have a significant effect on bone formation during the normal bone remodeling phase of secondary bone healing. Conclusion. In general, the effect of vitamin E on bone fracture healing remained inconclusive due to the small number of heterogeneous and mediocre studies included in this paper. PMID:23304211

  20. Is Sonic Hedgehog Involved in Human Fracture Healing? - A Prospective Study on Local and Systemic Concentrations of SHH

    PubMed Central

    Eipeldauer, Stefan; Thomas, Anita; Hoechtl-Lee, Leonard; Kecht, Mathias; Binder, Harald; Koettstorfer, Julia; Gregori, Markus; Sarahrudi, Kambiz

    2014-01-01

    Introduction Sonic Hedgehog (SHH) is a new signalling pathway in bone repair. Evidence exist that SHH pathway plays a significant role in vasculogenesis and limb development during embryogenesis. Some in vitro and animal studies has already proven its potential for bone regeneration. However, no data on the role of SHH in the human fracture healing have been published so far. Methods Seventy-five patients with long bone fractures were included into the study and divided in 2 groups. First group contained 69 patients with normal fracture healing. Four patients with impaired fracture healing formed the second group. 34 volunteers donated blood samples as control. Serum samples were collected over a period of 1 year following a standardized time schedule. In addition, SHH levels were measured in fracture haematoma and serum of 16 patients with bone fractures. Results Fracture haematoma and patients serum both contained lower SHH concentrations compared to control serum. The comparison between the patients' serum SHH level and the control serum revealed lower levels for the patients at all measurement time points. Significantly lower concentrations were observed at weeks 1 and 2 after fracture. SHH levels were slightly decreased in patients with impaired fracture healing without statistical significance. Conclusion This is the first study to report local and systemic concentration of SHH in human fracture healing and SHH serum levels in healthy adults. A significant reduction of the SHH levels during the inflammatory phase of fracture healing was found. SHH concentrations in fracture haematoma and serum were lower than the concentration in control serum for the rest of the healing period. Our findings indicate that there is no relevant involvement of SHH in human fracture healing. Fracture repair process seem to reduce the SHH level in human. Further studies are definitely needed to clarify the underlying mechanisms. PMID:25501422

  1. [Bone fracture and the healing mechanisms. Pathophysiology and classification of osteoporotic fractures].

    PubMed

    Kishimoto, Hideaki

    2009-05-01

    Bone provides momentary strength and fatigue strength, and bone strength decreases with age. In elderly men and women with fragile bones osteoporotic fractures frequently occur. Fragility fracture occurs as a consequence of the decrease in momentary strength, and fragility fracture is one of the pathological fractures. In patients with the decrease in fatigue strength, insufficiency fractures frequently occurs. Insufficiency fracture is the same term as stress or fatigue fracture.

  2. Naringin promotes fracture healing through stimulation of angiogenesis by regulating the VEGF/VEGFR-2 signaling pathway in osteoporotic rats.

    PubMed

    Song, Nan; Zhao, Zhihu; Ma, Xinlong; Sun, Xiaolei; Ma, Jianxiong; Li, Fengbo; Sun, Lei; Lv, Jianwei

    2017-01-05

    Postmenopausal osteoporosis is characterized by a reduction in the number of sinusoidal and arterial capillaries in the bone marrow and reduced bone perfusion. Thus, osteogenesis and angiogenesis are coupled in the process of osteoporosis formation and fracture healing. Naringin is the main ingredient of the root Rhizoma Drynariae, a traditional Chinese medicine, and it has potential effects on promoting fracture healing. However, whether naringin stimulates angiogenesis in the process of bone healing is unclear. Here, we show that naringin promotes fracture healing through stimulating angiogenesis by regulating the VEGF/VEGFR-2 signaling pathway in osteoporotic rats.

  3. Influence of mechanical rock properties and fracture healing rate on crustal fluid flow dynamics

    NASA Astrophysics Data System (ADS)

    Sachau, Till; Bons, Paul; Gomez-Rivas, Enrique; Koehn, Daniel; de Riese, Tamara

    2016-04-01

    Fluid flow in the Earth's crust is very slow over extended periods of time, during which it occurs within the connected pore space of rocks. If the fluid production rate exceeds a certain threshold, matrix permeability alone is insufficient to drain the fluid volume and fluid pressure builds up, thereby reducing the effective stress supported by the rock matrix. Hydraulic fractures form once the effective pressure exceeds the tensile strength of the rock matrix and act subsequently as highly effective fluid conduits. Once local fluid pressure is sufficiently low again, flow ceases and fractures begin to heal. Since fluid flow is controlled by the alternation of fracture permeability and matrix permeability, the flow rate in the system is strongly discontinuous and occurs in intermittent pulses. Resulting hydraulic fracture networks are largely self-organized: opening and subsequent healing of hydraulic fractures depends on the local fluid pressure and on the time-span between fluid pulses. We simulate this process with a computer model and describe the resulting dynamics statistically. Special interest is given to a) the spatially and temporally discontinuous formation and closure of fractures and fracture networks and b) the total flow rate over time. The computer model consists of a crustal-scale dual-porosity setup. Control parameters are the pressure- and time-dependent fracture healing rate, and the strength and the permeability of the intact rock. Statistical analysis involves determination of the multifractal properties and of the power spectral density of the temporal development of the total drainage rate and hydraulic fractures. References Bons, P. D. (2001). The formation of large quartz veins by rapid ascent of fluids in mobile hydrofractures. Tectonophysics, 336, 1-17. Miller, S. a., & Nur, A. (2000). Permeability as a toggle switch in fluid-controlled crustal processes. Earth and Planetary Science Letters, 183(1-2), 133-146. Sachau, T., Bons, P. D

  4. The Difference between Growth Factor Expression after Single and Multiple Fractures: Preliminary Results in Human Fracture Healing

    PubMed Central

    Binder, Harald; Eipeldauer, Stefan; Gregori, Markus; Höchtl-Lee, Leonard; Thomas, Anita; Tiefenboeck, Thomas M.; Hajdu, Stefan; Sarahrudi, Kambiz

    2015-01-01

    Objectives. Circulating levels of VEGF-A (Vascular Endothelia Growth Factor-A), TGF-β1 (Transforming Growth Factor-beta 1), and M-CSF (Macrophage-Colony Stimulating Factor) were found to be predictors of bone healing and therefore prognostic criteria of delayed bone healing or nonunion. The aim of this study was to evaluate a potential rise of these markers in patients with multiple fractures of long bones compared to patients with single fractured long bone. Methods. 92 patients were included in the study and finally after excluding all female patients 45 male patients were left for final analysis and divided into the single or multiple fracture group. TGF-β1, M-CSF, and VEGF-A serum levels were analysed over a time period of two weeks. Results. MCSF serum concentrations were higher in the group with multiple fractures as also TGF-β1 serum concentrations were at one and two weeks after trauma. No statistically significant difference was observed in the VEGF-A serum concentrations of both groups at either measurement point. Conclusion. We did observe a correlation between the quantity of the M-CSF and TGF-β1 expressions in serum and the number of fractured bones; surprisingly there was no statistically significant difference in the serum levels between patients with single and multiple fractures of long bones. PMID:26246654

  5. Exogenous PTHrP Repairs the Damaged Fracture Healing of PTHrP+/− Mice and Accelerates Fracture Healing of Wild Mice

    PubMed Central

    Wang, Yinhe; Fang, Xin; Wang, Chun; Ding, Congzhu; Lin, Hua; Liu, Anlong; Wang, Lei; Cao, Yang

    2017-01-01

    Bone fracture healing is a complicated physiological regenerative process initiated in response to injury and is similar to bone development. To demonstrate whether an exogenous supply of parathyroid hormone–related protein (PTHrP) helps in bone fracture healing, closed mid-diaphyseal femur fractures were created and stabilized with intramedullary pins in eight-week-old wild-type (WT) PTHrP+/+ and PTHrP+/− mice. After administering PTHrP for two weeks, callus tissue properties were analyzed at one, two, and four weeks post-fracture (PF) by various methods. Bone formation–related genes and protein expression levels were evaluated by real-time reverse transcriptase–polymerase chain reaction and Western blots. At two weeks PF, mineral density of callus, bony callus areas, mRNA levels of alkaline phosphatase (ALP), type I collagen, Runt-related transcription factor 2 (Runx-2), and protein levels of Runx-2 and insulin-like growth factor-1 decreased in PTHrP+/− mice compared with WT mice. At four weeks PF, total collagen-positive bony callus areas, osteoblast number, ALP-positive areas, and type I collagen-positive areas all decreased in PTHrP+/− mice. At both two and four weeks PF, tartrate-resistant acid phosphatase–positive osteoclast number and surface decreased a little in PTHrP+/− mice. The study indicates that exogenous PTHrP provided by subcutaneous injection could redress impaired bone fracture healing, leading to mutation of activated PTHrP by influencing callus areas, endochondral bone formation, osteoblastic bone formation, and bone turnover. PMID:28178186

  6. CaMKK2 Inhibition in Enhancing Bone Fracture Healing

    DTIC Science & Technology

    2014-08-01

    study to establish the following: (1) Reliable and reproducible surgical procedures for creating a transverse femoral fracture and fixing it with an...Reliable and reproducible surgical procedures for creating a transverse femoral fracture and fixing it with an intramedullary device. 2) The treatment...disinfected with alternating scrubs of betadine and alcohol. Sterile instruments were used to make a small incision (approximately 2 mm). A 25 gauge

  7. [Bone fracture and the healing mechanisms. Fragility fracture and bone quality].

    PubMed

    Mawatari, Taro; Iwamoto, Yukihide

    2009-05-01

    Fracture occurs in bone having less than normal elastic resistance without any violence. Numerous terms have been used to classify various types of fractures from low trauma events; "fragility fracture", "stress fracture", "insufficiency fracture", "fatigue fracture", "pathologic fracture", etc. The definitions of these terms and clinical characteristics of these fractures are discussed. Also state-of-the-art bone quality assessments; Finite element analysis of clinical CT scans, assessments of the Microdamage, and the Cross-links of Collagen are introduced in this review.

  8. Treatment with Carnitine Enhances Bone Fracture Healing under Osteoporotic and/or Inflammatory Conditions.

    PubMed

    Aydin, Ali; Halici, Zekai; Albayrak, Abdulmecit; Polat, Beyzagul; Karakus, Emre; Yildirim, Omer Selim; Bayir, Yasin; Cadirci, Elif; Ayan, Arif Kursad; Aksakal, Ahmet Murat

    2015-09-01

    The aim of this study was to examine the effects of carnitine on bone healing in ovariectomy (OVX) and inflammation (INF)-induced osteoporotic rats. The rats were randomly divided into nine groups (n = 8 animals per group): sham-operated (Group 1: SHAM); sham + magnesium silicate (Mg-silicate) (Group 2: SHAM + INF); ovariectomy (Group 3: OVX); ovariectomy + femoral fracture (Group 4: OVX + FRC); ovariectomy + femoral fracture + Mg-silicate (Group 5: OVX + FRC + INF); ovariectomy + femoral fracture + carnitine 50 mg/kg (Group 6: OVX + FRC + CAR50); ovariectomy + femoral fracture + carnitine 100 mg/kg (Group 7: OVX + FRC + CAR100); ovariectomy + femoral fracture + Mg-silicate + carnitine 50 mg/kg (Group 8: OVX + FRC + INF + CAR50); and ovariectomy + femoral fracture + Mg-silicate + carnitine 100 mg/kg (Group 9: OVX + FRC + INF + CAR100). Eight weeks after OVX, which allowed for osteoporosis to develop, INF was induced with subcutaneous Mg-silicate. On day 80, all of the rats in groups 4-9 underwent fracture operation on the right femur. Bone mineral density (BMD) showed statistically significant improvements in the treatment groups. The serum markers of bone turnover (osteocalcin and osteopontin) and pro-inflammatory cytokines (tumour necrosis factor α, interleukin 1β and interleukin 6) were decreased in the treatment group. The X-ray images showed significantly increased callus formation and fracture healing in the groups treated with carnitine. The present results show that in a rat model with osteoporosis induced by ovariectomy and Mg-silicate, treatment with carnitine improves the healing of femur fractures.

  9. Erythropoietin (EPO): EPO-receptor signaling improves early endochondral ossification and mechanical strength in fracture healing.

    PubMed

    Holstein, Joerg H; Menger, Michael D; Scheuer, Claudia; Meier, Christoph; Culemann, Ulf; Wirbel, Rainer J; Garcia, Patric; Pohlemann, Tim

    2007-02-13

    Beyond its role in the regulation of red blood cell proliferation, the glycoprotein erythropoietin (EPO) has been shown to promote cell regeneration and angiogenesis in a variety of different tissues. In addition, EPO has been indicated to share significant functional and structural homologies with the vascular endothelial growth factor (VEGF), a cytokine essential in the process of fracture healing. However, there is complete lack of information on the action of EPO in bone repair and fracture healing. Therefore, we investigated the effect of EPO treatment on bone healing in a murine closed femur fracture model using radiological, histomorphometric, immunohistochemical, biomechanical and protein biochemical analysis. Thirty-six SKH1-hr mice were treated with daily i.p. injections of 5000 U/kg EPO from day 1 before fracture until day 4 after fracture. Controls received equivalent amounts of the vehicle. After 2 weeks of fracture healing, we could demonstrate expression of the EPO-receptor (EPOR) in terminally differentiating chondrocytes within the callus. At this time point EPO-treated animals showed a higher torsional stiffness (biomechanical analysis: 39.6+/-19.4% of the contralateral unfractured femur) and an increased callus density (X-ray analysis (callus density/spongiosa density): 110.5+/-7.1%) when compared to vehicle-treated controls (14.3+/-8.2% and 105.9+/-6.6%; p<0.05). Accordingly, the histomorphometric examination revealed an increased fraction of mineralized bone and osteoid (33.0+/-3.0% versus 28.5+/-3.6%; p<0.05). Of interest, this early effect of the initial 6-day EPO treatment had vanished at 5 weeks after fracture. We conclude that EPO-EPOR signaling is involved in the process of early endochondral ossification, enhancing the transition of soft callus to hard callus.

  10. A small interfering RNA targeting Lnk accelerates bone fracture healing with early neovascularization.

    PubMed

    Kawakami, Yohei; Ii, Masaaki; Matsumoto, Tomoyuki; Kawamoto, Atsuhiko; Kuroda, Ryosuke; Akimaru, Hiroshi; Mifune, Yutaka; Shoji, Taro; Fukui, Tomoaki; Asahi, Michio; Kurosaka, Masahiro; Asahara, Takayuki

    2013-09-01

    Lnk, an intracellular adapter protein, is expressed in hematopoietic cell lineages, which has recently been proved as an essential inhibitory signaling molecule for stem cell self-renewal in the stem cell factor-c-Kit signaling pathway with enhanced hematopoietic and osteogenic reconstitution in Lnk-deficient mice. Moreover, the therapeutic potential of hematopoietic stem/endothelial progenitor cells (EPCs) for fracture healing has been demonstrated with mechanistic insight into vasculogenesis/angiogenesis and osteogenesis enhancement in the fracture sites. We report here, Lnk siRNA-transfected endothelial commitment of c-kit+/Sca-1+/lineage- subpopulations of bone marrow cells have high EPC colony-forming capacity exhibiting endothelial markers, VE-Cad, VEGF and Ang-1. Lnk siRNA-transfected osteoblasts also show highly osteoblastic capacity. In vivo, locally transfected Lnk siRNA could successfully downregulate the expression of Lnk at the fracture site up to 1 week, and radiological and histological examination showed extremely accelerated fracture healing in Lnk siRNA-transfected mice. Moreover, Lnk siRNA-transfected mice exhibited sufficient therapeutic outcomes with intrinstic enhancement of angiogenesis and osteogenesis, specifically, the mice demonstrated better blood flow recovery in the sites of fracture. In our series of experiments, we clarified that a negatively regulated Lnk system contributed to a favorable circumstance for fracture healing by enhancing vasculogenesis/angiogenesis and osteogenesis. These findings suggest that downregulation of Lnk system may have the clinical potential for faster fracture healing, which contributes to the reduction of delayed unions or non-unions.

  11. PTH 1-34 (teriparatide) may not improve healing in proximal humerus fractures

    PubMed Central

    2016-01-01

    Background and purpose There is solid evidence from animal experiments that parathyroid hormone (PTH) improves fracture healing. So far, only 3 papers on PTH and fracture repair in humans have been published. They suggest that PTH may enhance fracture healing, but the results do not appear to justify specific clinical recommendations. This study was carried out to determine whether teriparatide enhances fracture healing of proximal humerus fractures. Patients and methods 40 post-menopausal women with a proximal humerus fracture were randomized to either daily injections with 20 µg teriparatide (PTH 1-34 (Forteo)) for 4 weeks or control treatment. At randomization, the patients were asked to assess how their pain at rest and during activity (visual analog scale (VAS)) and also function (DASH score) had been prior to the fracture. At 7 weeks and again at 3 months, their current state was assessed and the tests were repeated, including radiographs. 2 radiologists performed a blind qualitative scoring of the callus at 7 weeks. Callus formation was arbitrarily classified as ”normal” or “better”. Results 39 patients completed the follow-up. The radiographic assessment showed a correct correlation, “better” in the teriparatide group and “normal” in the control group, in 21 of the 39 cases. There were no statistically significant differences in pain, in use of strong analgesics, or in function between the groups at the follow-up examinations. Interpretation There were no radiographic signs of enhanced healing or improved clinical results in the group treated with teriparatide PMID:26179771

  12. Systemic application of growth hormone for enhancement of secondary and intramembranous fracture healing.

    PubMed

    Bail, Hermann J; Kolbeck, Stefan; Krummrey, Gert; Schmidmaier, Gerhard; Haas, Norbert P; Raschke, Michael J

    2002-01-01

    Hormones are known to influence bone metabolism and cellular mechanisms of fracture healing. Recent technologies in molecular biology offer recombinant production of hormones, which makes them applicable for pharmacological use. To investigate the effect of systemic growth hormone (GH) application experiments were performed in micropig animal models. Systemic daily subcutaneous injection of species-specific recombinant GH was investigated in Yucatan micropigs to evaluate the effect on secondary fracture healing in a standardized gap model (1 cm) and on intramembranous bone formation in distraction osteogenesis (DO). Quantitative computed tomography (qCT), biomechanical testing, measurement of systemic insulin-like growth factor 1 (IGF-1) levels as well as histomorphometric analyses were performed to investigate differences in regenerate formation. Systemic GH administration significantly increased the torsional stability of the regenerate in comparison to the contralateral side in both experiments. qCT showed accelerated fracture bridging in the GH-treated animals in bone defect healing, while in DO histomorphometry elicited larger callus areas in the case of GH application. Systemic IGF-1 levels were significantly increased in both GH-treated groups. These experiments show that the systemic administration of recombinant GH accelerates fracture healing in standardized animal models. Clinical studies have now been initiated in order to prove the safety and the effectiveness of this therapeutical option.

  13. Relationship between microstructure, material distribution, and mechanical properties of sheep tibia during fracture healing process.

    PubMed

    Gao, Jiazi; Gong, He; Huang, Xing; Fang, Juan; Zhu, Dong; Fan, Yubo

    2013-01-01

    The aim of this study was to investigate the relationship between microstructural parameters, material distribution, and mechanical properties of sheep tibia at the apparent and tissue levels during the fracture healing process. Eighteen sheep underwent tibial osteotomy and were sacrificed at 4, 8, and 12 weeks. Radiographs and micro-computed tomography (micro-CT) scanning were taken for microstructural assessment, material distribution evaluation, and micro-finite element analysis. A displacement of 5% compressive strain on the longitudinal direction was applied to the micro-finite element model, and apparent and tissue-level mechanical properties were calculated. Principle component analysis and linear regression were used to establish the relationship between principle components (PCs) and mechanical parameters. Visible bony callus formation was observed throughout the healing process from radiographic assessment. Apparent mechanical property increased at 8 weeks, but tissue-level mechanical property did not increase significantly until 12 weeks. Three PCs were extracted from microstructural parameters and material distribution, which accounted for 87.592% of the total variation. The regression results showed a significant relationship between PCs and mechanical parameters (R>0.8, P<0.05). Results of this study show that microstructure and material distribution based on micro-CT imaging could efficiently predict bone strength and reflect the bone remodeling process during fracture healing, which provides a basis for exploring the fracture healing mechanism and may be used as an approach for fractured bone strength assessment.

  14. The association between healed skeletal fractures indicative of interpersonal violence and alcoholic liver disease in a cadaver cohort from the Western Cape, South Africa.

    PubMed

    Geldenhuys, Elsje-Márie; Burger, Elsie H; Alblas, Amanda; Greyling, Linda M; Kotzé, Sanet H

    2016-05-01

    Interpersonal violence (IPV) and heavy alcohol consumption are major problems in the Western Cape Province of South Africa. Cranio-maxillofacial fractures, particularly nasal and zygomatic bone fractures, as well as isolated radial fractures (Colles fractures) and ulnar shaft fractures (parry fractures), are indicative of IPV, while alcoholic liver disease (ALD) is the consequence of chronic alcohol abuse. We therefore aim to investigate whether a significant association exists between the prevalence of cranio-maxillofacial fractures and parry fractures and ALD in a Western Cape population. Embalmed cadavers (n = 124) used for medical students' anatomy training at the Division of Anatomy and Histology, Faculty of Medicine and Health Sciences, Stellenbosch University were studied. The cadavers were dissected according to departmental protocol. The liver of each cadaver was investigated for macroscopic pathology lesions. Tissue samples were removed, processed to wax, and sectioned and stained with hematoxylin and eosin (H&E). All soft tissue was removed from the skulls, radii, and ulnae, which were then investigated for healed skeletal trauma. The results showed 37/124 (29.8%) cadavers had healed cranio-maxillofacial fractures and 24/124 (19.4%) cadavers had morphologic features of ALD. A total of 12/124 (9.7%) cadavers showed signs of both ALD and healed cranio-maxillofacial trauma. More males were affected than females, and left-sided facial fractures were statistically more common compared to the right side. This study illustrated a significant trend between alcohol abuse and cranio-maxillofacial fractures in individuals from communities with a low socio-economic status (SES) where IPV is a major problem.

  15. Healed Depressed Parasagittal Skull Fractures-A Feature of Archaic Australian Aboriginal Remains.

    PubMed

    Walshe, Keryn; Brophy, Brian; Cornish, Brian; Byard, Roger W

    2016-11-01

    The skeletal remains of eight Australian Aboriginals with healed depressed skull fractures were examined. Male:female ratio 5:3; age range 20-60 yrs. Burial dates by (14) C dating in three cases were 500 years BP (n = 2) and 1300 BP. There were 13 healed depressed skull fractures manifested by shallow indentations of cortical bone and thinning of diploe, with no significant disturbance of the inner skull tables. Nine (69%) were located within 35 mm of the sagittal suture/midline. These lesions represent another acquired feature that might be helpful in suggesting that a skull is from a tribal Aboriginal individual and may be particularly useful if the remains are represented by only fragments of calvarium. While obviously not a finding specific to this population, these healed injuries would be consistent with the possible results of certain types of conflict behavior reported in traditional Aboriginal groups that involved formalized inflicted blunt head trauma.

  16. Low-dose TNF augments fracture healing in normal and osteoporotic bone by up-regulating the innate immune response.

    PubMed

    Chan, James K; Glass, Graeme E; Ersek, Adel; Freidin, Andrew; Williams, Garry A; Gowers, Kate; Espirito Santo, Ana I; Jeffery, Rosemary; Otto, William R; Poulsom, Richard; Feldmann, Marc; Rankin, Sara M; Horwood, Nicole J; Nanchahal, Jagdeep

    2015-05-01

    The mechanism by which trauma initiates healing remains unclear. Precise understanding of these events may define interventions for accelerating healing that could be translated to the clinical arena. We previously reported that addition of low-dose recombinant human TNF (rhTNF) at the fracture site augmented fracture repair in a murine tibial fracture model. Here, we show that local rhTNF treatment is only effective when administered within 24 h of injury, when neutrophils are the major inflammatory cell infiltrate. Systemic administration of anti-TNF impaired fracture healing. Addition of rhTNF enhanced neutrophil recruitment and promoted recruitment of monocytes through CCL2 production. Conversely, depletion of neutrophils or inhibition of the chemokine receptor CCR2 resulted in significantly impaired fracture healing. Fragility, or osteoporotic, fractures represent a major medical problem as they are associated with permanent disability and premature death. Using a murine model of fragility fractures, we found that local rhTNF treatment improved fracture healing during the early phase of repair. If translated clinically, this promotion of fracture healing would reduce the morbidity and mortality associated with delayed patient mobilization.

  17. Inhibition of beta-catenin signaling by Pb leads to incomplete fracture healing

    PubMed Central

    Beier, Eric E; Buckley, Taylor; Yukata, Kiminori; Sheu, Tzong-Jen; O’Keefe, Regis; Zuscik, Michael J; Puzas, J Edward

    2015-01-01

    There is strong evidence in the clinical literature to suggest that elevated lead (Pb) exposure impairs fracture healing. Since Pb has been demonstrated to inhibit bone formation, and Wnt signaling is an important anabolic pathway in chondrocyte maturation and endochondral ossification, we investigated the impact of Wnt therapy on Pb-exposed mice undergoing bone repair in a mouse tibial fracture model. We established that tibial fracture calluses from Pb-treated mice were smaller and contained less mineralized tissue than vehicle controls. This resulted in the persistence of immature cartilage in the callus and decreased β-catenin levels. Reduction of β-catenin protein was concurrent with systemic elevation of LRP5/6 antagonists DKK1 and sclerostin in Pb-exposed mice throughout fracture healing. β-catenin stimulation by the GSK3 inhibitor BIO reversed these molecular changes and restored the amount of mineralized callus. Overall, Pb is identified as a potent inhibitor of endochondral ossification in vivo with correlated effects on bone healing with noted deficits in β-catenin signaling, suggesting the Wnt/β-catenin as a pivotal pathway in the influence of Pb on fracture repair. PMID:25044211

  18. Inhibition of beta-catenin signaling by Pb leads to incomplete fracture healing.

    PubMed

    Beier, Eric E; Sheu, Tzong-Jen; Buckley, Taylor; Yukata, Kiminori; O'Keefe, Regis; Zuscik, Michael J; Puzas, J Edward

    2014-11-01

    There is strong evidence in the clinical literature to suggest that elevated lead (Pb) exposure impairs fracture healing. Since Pb has been demonstrated to inhibit bone formation, and Wnt signaling is an important anabolic pathway in chondrocyte maturation and endochondral ossification, we investigated the impact of Wnt therapy on Pb-exposed mice undergoing bone repair in a mouse tibial fracture model. We established that tibial fracture calluses from Pb-treated mice were smaller and contained less mineralized tissue than vehicle controls. This resulted in the persistence of immature cartilage in the callus and decreased β-catenin levels. Reduction of β-catenin protein was concurrent with systemic elevation of LRP5/6 antagonists DKK1 and sclerostin in Pb-exposed mice throughout fracture healing. β-catenin stimulation by the GSK3 inhibitor BIO reversed these molecular changes and restored the amount of mineralized callus. Overall, Pb is identified as a potent inhibitor of endochondral ossification in vivo with correlated effects on bone healing with noted deficits in β-catenin signaling, suggesting the Wnt/β-catenin as a pivotal pathway in the influence of Pb on fracture repair.

  19. Ultrasound imaging of long bone fractures and healing with the split-step fourier imaging method.

    PubMed

    Li, Hongjiang; Le, Lawrence H; Sacchi, Mauricio D; Lou, Edmond H M

    2013-08-01

    We applied the split-step Fourier imaging method to back-propagate the ultrasound zero-offset wavefields acquired on the bone surface to the sources of scatterers, which are the reflecting interfaces. The method required, as an input, an estimated slowness (reciprocal of half the velocity) model to map the time-dependent sonogram to the depth image, which provides the geometric properties of the interfaces. The slowness was approximated by a depth-dependent term and a first-order spatially varying perturbation. Simulated data sets were used to validate the method. The reconstructed images show proper mapping of the interfaces and the fracture, and a reasonable cortical thickness measurement with 8.3% error. The images also illustrate clearly the bone fracture healing process of a 1-mm-wide 45° inclined crack with different in-filled tissue velocities for various healing stages. Reconstruction of a fractured bone plate using data from an in vitro experiment is also presented. This study suggests that the proposed imaging method has good potential in quantification of bone fractures and monitoring of the fracture healing process.

  20. Reduced COX-2 Expression in Aged Mice Is Associated With Impaired Fracture Healing

    PubMed Central

    Naik, Amish A; Xie, Chao; Zuscik, Michael J; Kingsley, Paul; Schwarz, Edward M; Awad, Hani; Guldberg, Robert; Drissi, Hicham; Puzas, J Edward; Boyce, Brendan; Zhang, Xinping; O'Keefe, Regis J

    2009-01-01

    The cellular and molecular events responsible for reduced fracture healing with aging are unknown. Cyclooxygenase 2 (COX-2), the inducible regulator of prostaglandin E2 (PGE2) synthesis, is critical for normal bone repair. A femoral fracture repair model was used in mice at either 7–9 or 52–56 wk of age, and healing was evaluated by imaging, histology, and gene expression studies. Aging was associated with a decreased rate of chondrogenesis, decreased bone formation, reduced callus vascularization, delayed remodeling, and altered expression of genes involved in repair and remodeling. COX-2 expression in young mice peaked at 5 days, coinciding with the transition of mesenchymal progenitors to cartilage and the onset of expression of early cartilage markers. In situ hybridization and immunohistochemistry showed that COX-2 is expressed primarily in early cartilage precursors that co-express col-2. COX-2 expression was reduced by 75% and 65% in fractures from aged mice compared with young mice on days 5 and 7, respectively. Local administration of an EP4 agonist to the fracture repair site in aged mice enhanced the rate of chondrogenesis and bone formation to levels observed in young mice, suggesting that the expression of COX-2 during the early inflammatory phase of repair regulates critical subsequent events including chondrogenesis, bone formation, and remodeling. The findings suggest that COX-2/EP4 agonists may compensate for deficient molecular signals that result in the reduced fracture healing associated with aging. PMID:18847332

  1. 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

  2. Expression and Role of Sonic Hedgehog in the Process of Fracture Healing with Aging.

    PubMed

    Matsumoto, Kenichi; Shimo, Tsuyoshi; Kurio, Naito; Okui, Tatsuo; Obata, Kyoichi; Masui, Masanori; Pang, Pai; Horikiri, Yuu; Sasaki, Akira

    2016-01-01

    Aging is one of the risk factors for delayed fracture healing. Sonic hedgehog (SHH) protein, an inducer of embryonic development, has been demonstrated to be activated in osteoblasts at the dynamic remodeling site of a bone fracture. Herein, we compared and examined the distribution patterns of SHH and the functional effect of SHH signaling on osteogenesis and osteoclastogenesis between young (5-week-old) and aged (60-week-old) mice during fracture healing. We found that SHH was expressed in bone marrow cells from the fractured site of the rib of young mice on day 5, but was barely detectable in the corresponding cells from the rib of aged mice. SHH was also detected in osteoblasts and bone marrow cells at the callus remodeling stage on days 14 and 28 in both young and aged mice. The number of alkaline phosphatase (ALP)-positive osteoblasts was significantly higher in young mice on days 5 and 14, whereas the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts was significantly higher in aged mice. SHH stimulated significantly more osteoblast formation in the young compared to old mice. SHH stimulated the osteoclast formation directly in the aged mice and suppressed the formation indirectly through osteoprotegerin expression in the young mice. Results indicate that an aged-related delay of fracture healing may contribute to the unbalanced bone formation and resorption, regulated by hedgehog signaling.

  3. Chondrocyte BMP2 signaling plays an essential role in bone fracture healing.

    PubMed

    Mi, Meng; Jin, Hongting; Wang, Baoli; Yukata, Kiminori; Sheu, Tzong-Jen; Ke, Qiao Han; Tong, Peijian; Im, Hee-Jeong; Xiao, Guozhi; Chen, Di

    2013-01-10

    The specific role of endogenous Bmp2 gene in chondrocytes and in osteoblasts in fracture healing was investigated by generation and analysis of chondrocyte- and osteoblast-specific Bmp2 conditional knockout (cKO) mice. The unilateral open transverse tibial fractures were created in these Bmp2 cKO mice. Bone fracture callus samples were collected and analyzed by X-ray, micro-CT, histology analyses, biomechanical testing and gene expression assays. The results demonstrated that the lack of Bmp2 expression in chondrocytes leads to a prolonged cartilage callus formation and a delayed osteogenesis initiation and progression into mineralization phase with lower biomechanical properties. In contrast, when the Bmp2 gene was deleted in osteoblasts, the mice showed no significant difference in the fracture healing process compared to control mice. These findings suggest that endogenous BMP2 expression in chondrocytes may play an essential role in cartilage callus maturation at an early stage of fracture healing. Our studies may provide important information for clinical application of BMP2.

  4. 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

  5. Self-healing of cement fractures under dynamic flow of CO2-rich brine

    NASA Astrophysics Data System (ADS)

    Cao, Peilin; Karpyn, Zuleima T.; Li, Li

    2015-06-01

    Fractures and defects in wellbore cement can lead to increased possibilities of CO2 leakage from abandoned wells during geological carbon sequestration. To investigate the physicochemical response of defective wellbore cement to CO2-rich brine, we carried out a reactive flow-through experiment using an artificially fractured cement sample at a length of 224.8 mm. A brine solution with dissolved CO2 at a pH of approximately 3.9 was injected through the sample at a constant rate of 0.0083 cm3/s. Surface optical profilometry analysis and 3-D X-ray microtomography imaging confirmed fracture closure and self-healing behavior consistent with the measured permeability decrease. Visual inspection of the reacted fracture surface showed the development of reactive patterns mapping the flow velocity field inside the fracture, as well as restricted flow toward the sample outlet. The postexperiment permeability of the core sample was measured at half of its initial permeability. A reactive transport model was developed with parameters derived from the experiment to further examine property evolution of fractured cement under dynamic flow of CO2-rich brine. Sensitivity analysis showed that residence time and the size of initial fracture aperture are the key factors controlling the tendency to self-healing or fracture opening behavior and therefore determine the long-term integrity of the wellbore cement. Longer residence time and small apertures promote mineral precipitation, fracture closure, and therefore flow restriction. This work also suggests a narrow threshold separating the fracture opening and self-sealing behavior.

  6. A Pronounced Inflammatory Activity Characterizes the Early Fracture Healing Phase in Immunologically Restricted Patients.

    PubMed

    Hoff, Paula; Gaber, Timo; Strehl, Cindy; Jakstadt, Manuela; Hoff, Holger; Schmidt-Bleek, Katharina; Lang, Annemarie; Röhner, Eric; Huscher, Dörte; Matziolis, Georg; Burmester, Gerd-Rüdiger; Schmidmaier, Gerhard; Perka, Carsten; Duda, Georg N; Buttgereit, Frank

    2017-03-08

    Immunologically restricted patients such as those with autoimmune diseases or malignancies often suffer from delayed or insufficient fracture healing. In human fracture hematomas and the surrounding bone marrow obtained from immunologically restricted patients, we analyzed the initial inflammatory phase on cellular and humoral level via flow cytometry and multiplex suspension array. Compared with controls, we demonstrated higher numbers of immune cells like monocytes/macrophages, natural killer T (NKT) cells, and activated T helper cells within the fracture hematomas and/or the surrounding bone marrow. Also, several pro-inflammatory cytokines such as Interleukin (IL)-6 and Tumor necrosis factor α (TNFα), chemokines (e.g., Eotaxin and RANTES), pro-angiogenic factors (e.g., IL-8 and Macrophage migration inhibitory factor: MIF), and regulatory cytokines (e.g., IL-10) were found at higher levels within the fracture hematomas and/or the surrounding bone marrow of immunologically restricted patients when compared to controls. We conclude here that the inflammatory activity on cellular and humoral levels at fracture sites of immunologically restricted patients considerably exceeds that of control patients. The initial inflammatory phase profoundly differs between these patient groups and is probably one of the reasons for prolonged or insufficient fracture healing often occurring within immunologically restricted patients.

  7. A Pronounced Inflammatory Activity Characterizes the Early Fracture Healing Phase in Immunologically Restricted Patients

    PubMed Central

    Hoff, Paula; Gaber, Timo; Strehl, Cindy; Jakstadt, Manuela; Hoff, Holger; Schmidt-Bleek, Katharina; Lang, Annemarie; Röhner, Eric; Huscher, Dörte; Matziolis, Georg; Burmester, Gerd-Rüdiger; Schmidmaier, Gerhard; Perka, Carsten; Duda, Georg N.; Buttgereit, Frank

    2017-01-01

    Immunologically restricted patients such as those with autoimmune diseases or malignancies often suffer from delayed or insufficient fracture healing. In human fracture hematomas and the surrounding bone marrow obtained from immunologically restricted patients, we analyzed the initial inflammatory phase on cellular and humoral level via flow cytometry and multiplex suspension array. Compared with controls, we demonstrated higher numbers of immune cells like monocytes/macrophages, natural killer T (NKT) cells, and activated T helper cells within the fracture hematomas and/or the surrounding bone marrow. Also, several pro-inflammatory cytokines such as Interleukin (IL)-6 and Tumor necrosis factor α (TNFα), chemokines (e.g., Eotaxin and RANTES), pro-angiogenic factors (e.g., IL-8 and Macrophage migration inhibitory factor: MIF), and regulatory cytokines (e.g., IL-10) were found at higher levels within the fracture hematomas and/or the surrounding bone marrow of immunologically restricted patients when compared to controls. We conclude here that the inflammatory activity on cellular and humoral levels at fracture sites of immunologically restricted patients considerably exceeds that of control patients. The initial inflammatory phase profoundly differs between these patient groups and is probably one of the reasons for prolonged or insufficient fracture healing often occurring within immunologically restricted patients. PMID:28282868

  8. Quantifying mechanical properties in a murine fracture healing system using inverse modeling: preliminary work

    NASA Astrophysics Data System (ADS)

    Miga, Michael I.; Weis, Jared A.; Granero-Molto, Froilan; Spagnoli, Anna

    2010-03-01

    Understanding bone remodeling and mechanical property characteristics is important for assessing treatments to accelerate healing or in developing diagnostics to evaluate successful return to function. The murine system whereby mid-diaphaseal tibia fractures are imparted on the subject and fracture healing is assessed at different time points and under different therapeutic conditions is a particularly useful model to study. In this work, a novel inverse geometric nonlinear elasticity modeling framework is proposed that can reconstruct multiple mechanical properties from uniaxial testing data. To test this framework, the Lame' constants were reconstructed within the context of a murine cohort (n=6) where there were no differences in treatment post tibia fracture except that half of the mice were allowed to heal 4 days longer (10 day, and 14 day healing time point, respectively). The properties reconstructed were a shear modulus of G=511.2 +/- 295.6 kPa, and 833.3+/- 352.3 kPa for the 10 day, and 14 day time points respectively. The second Lame' constant reconstructed at λ=1002.9 +/-42.9 kPa, and 14893.7 +/- 863.3 kPa for the 10 day, and 14 day time points respectively. An unpaired Student t-test was used to test for statistically significant differences among the groups. While the shear modulus did not meet our criteria for significance, the second Lame' constant did at a value p<0.0001. Traditional metrics that are commonly used within the bone fracture healing research community were not found to be statistically significant.

  9. Experimental study of high-energy fractures delayed operation in promote bone healing

    PubMed Central

    Pan, Zhi-Jun; Li, Zhong; Li, Jing

    2015-01-01

    To investigate role of delayed operation to stimulate growth of strong external callus in high-energy fractures, and explore a new way for bone healing. Twenty adult dogs were employed, and randomly divided into four groups, including group A-D. The dogs underwent osteotomy by wire saw in middle of femur, electric coagulation damaged surrounding periosteum, forming a 1 cm defect. Group A were internal fixed 14 days after osteotomy (higher-energy fractures delayed operation), Group B and C were internal fixed immediately (no delayed operation), Group D were internal fixed 14 days after osteotomy (delayed operation, but resected granulations around extremities). The results showed that groups of early fixed have no external callus growth and almost no growth in internal callus, these conditions leads to atrophy nonunion. On contrary, the porosis was strong and callus union was steady in group A and D, which have a delayed operation. In conclusion, early surgical fixation of high-energy fracture restrains external callus growth, easily lead to poor callus healing phenomenon of low-quality. Delayed surgical fixation can begin to repair soft tissues injury, stimulate external callus growth and improve fracture healing, so a small incision open reduction produce more robust growth effect than closed reduction. PMID:26379852

  10. Determining the Role of Sost and Sostdc1 During Fracture Healing

    SciTech Connect

    Yee, Cristal Sook Ngei

    2016-01-01

    The bone is a dynamic organ, often changing throughout the course of the human lifespan with its continuous remodeling, laying down new bone and resorbing old bone. With age, the bone becomes increasingly porous and mechanically unstable, leading to the development of osteoporosis in some individuals. Elderly patients with osteoporosis are at an increased risk of fracturing their bones which contributes to a higher mortality rate. Recent studies have revealed that type 1 diabetic mellitus (T1DM) patients also have an osteoporotic bone phenotype and impaired fracture healing, independent of age. Currently, there is a lack of available treatments that can improve impaired healing and directly enhance bone formation. Therefore, there is a great need for developing new therapies that can not only aid type 1 diabetic patients with osteoporosis to improve bone phenotype, but that could also aid patients with difficult or impaired fracture healing. In this thesis, I will be discussing the role of Wnt signaling and Sclerostin, a Wnt antagonist that negatively regulates bone formation, in the content of fracture repair.

  11. Computational simulation of fracture healing: influence of interfragmentary movement on the callus growth.

    PubMed

    García-Aznar, J M; Kuiper, J H; Gómez-Benito, M J; Doblaré, M; Richardson, J B

    2007-01-01

    Bone fractures heal through a complex process involving several cellular events. This healing process can serve to study factors that control tissue growth and differentiation from mesenchymal stem cells. The mechanical environment at the fracture site is one of the factors influencing the healing process and controls size and differentiation patterns in the newly formed tissue. Mathematical models can be useful to unravel the complex relation between mechanical environment and tissue formation. In this study, we present a mathematical model that predicts tissue growth and differentiation patterns from local mechanical signals. Our aim was to investigate whether mechanical stimuli, through their influence on stem cell proliferation and chondrocyte hypertrophy, predict characteristic features of callus size and geometry. We found that the model predicted several geometric features of fracture calluses. For instance, callus size was predicted to increase with increasing movement. Also, increases in size were predicted to occur through increase in callus diameter but not callus length. These features agree with experimental observations. In addition, spatial and temporal tissue differentiation patterns were in qualitative agreement with well-known experimental results. We therefore conclude that local mechanical signals can probably explain the shape and size of fracture calluses.

  12. Analysis of gene expression profiles in healing rat fractures treated with nail and plate fixation.

    PubMed

    Wang, S D; Li, X L; Liu, H P

    2014-10-20

    To compare fracture healing therapies, the gene expression profiles of rat fracture samples treated with nail and plate fixation were analyzed at 1 day, 3 days, 1 week, 2 weeks, 4 weeks, and 6 weeks after surgery. The gene expression profiles GSE1685, which include 19 samples, were downloaded from the Gene Expression Omnibus database. After preprocessing, the gene expression profiles were subjected to time series analysis using the Short Time-series Expression Miner software, and the significantly differentially expressed gene (DEG) sets were selected. Further, the distributions of those DEG sets on the corresponding chromosomes were identified using the functional classification tool. Finally, the DEGs were subjected to function and pathway enrichment analysis. DEG analysis indicated that the number of DEGs (854 genes) from nail fixation was significantly lower than that of DEGs (1029 genes) from plate fixation. The DEGs were mainly enriched in cell proliferation, cellular localization, and response to wounding functions. Several critical DEGs expressed during the fracture healing process were screened, and 2 common pathways were enriched for the DEGs in the nail fixation and plate fixation. These DEGs and pathways may be potential targets or predictive markers during fracture healing.

  13. Modeled Microgravity Affects Fibroblast Functions Related to Wound Healing

    NASA Astrophysics Data System (ADS)

    Cialdai, Francesca; Vignali, Leonardo; Morbidelli, Lucia; Colciago, Alessandra; Celotti, Fabio; Santi, Alice; Caselli, Anna; Cirri, Paolo; Monici, Monica

    2017-02-01

    Wound healing is crucial for the survival of an organism. Therefore, in the perspective of space exploration missions, it is important to understand if and how microgravity conditions affect the behavior of the cell populations involved in wound healing and the evolution of the process. Since fibroblasts are the major players in tissue repair, this study was focused on the behavior of fibroblasts in microgravity conditions, modeled by a RCCS. Cell cytoskeleton was studied by immunofluorescence microscopy, the ability to migrate was assessed by microchemotaxis and scratch assay, and the expression of markers of fibroblast activation, angiogenesis, and inflammation was assessed by western blot. Results revealed that after cell exposure to modeled microgravity conditions, a thorough rearrangement of microtubules occurred and α-SMA bundles were replaced by a tight network of faulty and disorganized filaments. Exposure to modeled microgravity induced a decrease in α-SMA and E-CAD expressions. Also, the expression of the pro-angiogenic protein VEGF decreased, while that of the inflammatory signal COX-2 increased. Fibroblast ability to adhere, migrate, and respond to chemoattractants (PRP), closely related to cytoskeleton integrity and membrane junctions, was significantly impaired. Nevertheless, PRP was able to partially restore fibroblast migration.

  14. Modeled Microgravity Affects Fibroblast Functions Related to Wound Healing

    NASA Astrophysics Data System (ADS)

    Cialdai, Francesca; Vignali, Leonardo; Morbidelli, Lucia; Colciago, Alessandra; Celotti, Fabio; Santi, Alice; Caselli, Anna; Cirri, Paolo; Monici, Monica

    2017-01-01

    Wound healing is crucial for the survival of an organism. Therefore, in the perspective of space exploration missions, it is important to understand if and how microgravity conditions affect the behavior of the cell populations involved in wound healing and the evolution of the process. Since fibroblasts are the major players in tissue repair, this study was focused on the behavior of fibroblasts in microgravity conditions, modeled by a RCCS. Cell cytoskeleton was studied by immunofluorescence microscopy, the ability to migrate was assessed by microchemotaxis and scratch assay, and the expression of markers of fibroblast activation, angiogenesis, and inflammation was assessed by western blot. Results revealed that after cell exposure to modeled microgravity conditions, a thorough rearrangement of microtubules occurred and α-SMA bundles were replaced by a tight network of faulty and disorganized filaments. Exposure to modeled microgravity induced a decrease in α-SMA and E-CAD expressions. Also, the expression of the pro-angiogenic protein VEGF decreased, while that of the inflammatory signal COX-2 increased. Fibroblast ability to adhere, migrate, and respond to chemoattractants (PRP), closely related to cytoskeleton integrity and membrane junctions, was significantly impaired. Nevertheless, PRP was able to partially restore fibroblast migration.

  15. Loss of Gi G-Protein-Coupled Receptor Signaling in Osteoblasts Accelerates Bone Fracture Healing.

    PubMed

    Wang, Liping; Hsiao, Edward C; Lieu, Shirley; Scott, Mark; O'Carroll, Dylan; Urrutia, Ashley; Conklin, Bruce R; Colnot, Celine; Nissenson, Robert A

    2015-10-01

    G-protein-coupled receptors (GPCRs) are key regulators of skeletal homeostasis and are likely important in fracture healing. Because GPCRs can activate multiple signaling pathways simultaneously, we used targeted disruption of G(i) -GPCR or activation of G(s) -GPCR pathways to test how each pathway functions in the skeleton. We previously demonstrated that blockade of G(i) signaling by pertussis toxin (PTX) transgene expression in maturing osteoblastic cells enhanced cortical and trabecular bone formation and prevented age-related bone loss in female mice. In addition, activation of G(s) signaling by expressing the G(s) -coupled engineered receptor Rs1 in maturing osteoblastic cells induced massive trabecular bone formation but cortical bone loss. Here, we test our hypothesis that the G(i) and G(s) pathways also have distinct functions in fracture repair. We applied closed, nonstabilized tibial fractures to mice in which endogenous G(i) signaling was inhibited by PTX, or to mice with activated G(s) signaling mediated by Rs1. Blockade of endogenous G(i) resulted in a smaller callus but increased bone formation in both young and old mice. PTX treatment decreased expression of Dkk1 and increased Lef1 mRNAs during fracture healing, suggesting a role for endogenous G(i) signaling in maintaining Dkk1 expression and suppressing Wnt signaling. In contrast, adult mice with activated Gs signaling showed a slight increase in the initial callus size with increased callus bone formation. These results show that G(i) blockade and G(s) activation of the same osteoblastic lineage cell can induce different biological responses during fracture healing. Our findings also show that manipulating the GPCR/cAMP signaling pathway by selective timing of G(s) and G(i) -GPCR activation may be important for optimizing fracture repair.

  16. Healing of Experimentally Simulated Fractures: Contact Neck Growth, and Strength Evolution of the Interface

    NASA Astrophysics Data System (ADS)

    Renard, F.; Dysthe, D.; Voisin, C.

    2008-12-01

    To investigate the physical processes operating in active fault zones, we conduct analogue laboratory experiments where we simulated a rough fracture that undergoes healing/shear cycles under dry condition or in the presence of a reactive fluid. This set-up is a surrogate for the healing/sealing of fractures and faults rocks, where fluid-rock interactions are operative at the millennium time scale. A rough slider of sodium chloride was left in contact with a flat glass plate under a constant normal load. The whole set-up was mounted on a microscope and left in a temperature-controlled box. The closure of the interface through several days was measured using high resolution displacement sensors and the contact surface was continuously imaged with a CCD camera. Under dry conditions, a small transient creep displacement perpendicularly to the fracture plane was measured. This deformation last for several minutes and finally stopped. Under fluid saturated conditions, a slow closure of the rough interface was measured over several days. This closure was concomitant with the growth of contact points, driven by surface tension forces. After 50 hours, up to 10% of the fracture surface was healed by this process. The force necessary to break the adhesion forces, allowing the sample to slide, was also measured after several periods of increasing holding times and showed a power law dependence with time. After each experiment, the fracture interface roughness was measured to nanometer resolution using white light interferometry. The morphology of the contacts was characterized by scaling relationships. Finally, we propose a macroscopic constitutive model of fracture closure and strength recovery, related to the dynamics of the contact asperities, which are seen to flatten and expand through time.

  17. Experimental Timescales of Fracture-Healing Rheological Behavior of Thermoreversible Gels

    NASA Astrophysics Data System (ADS)

    Thornell, Travis L.; Subramaniam, Krithika; Erk, Kendra A.

    Acrylic thermoreversible physical gels were used as a model soft material system to investigate fracture-healing behavior by shear rheometry. By using shear start-up experiments, gels at various concentrations and temperatures were measured to determine shear stress responses, and fracture was indicated by a decrease in shear stress (confirmed with rheophysical flow visualization experiments). Fractured gels were allowed to recover in the rheometer for set periods of time and were tested again using the same shear start-up procedure to evaluate the recovery kinetics of network strength. Relationships between the network recovery and the normalized ratio of the resting times and characteristic relaxation times of the gels were determined. It was found that resting times for fully healed networks needed to be 2 or 3 orders of magnitude greater than the relaxation times. The extent of fracture was also investigated. Gels that were deformed to smaller total strain magnitudes were suspected to have incomplete (or partial) fracture as results showed various responses for given resting times.

  18. 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.

  19. Molecular mechanisms controlling bone formation during fracture healing and distraction osteogenesis.

    PubMed

    Ai-Aql, Z S; Alagl, A S; Graves, D T; Gerstenfeld, L C; Einhorn, T A

    2008-02-01

    Fracture healing and distraction osteogenesis have important applications in orthopedic, maxillofacial, and periodontal treatment. In this review, the cellular and molecular mechanisms that regulate fracture repair are contrasted with bone regeneration that occurs during distraction osteogenesis. While both processes have many common features, unique differences are observed in the temporal appearance and expression of specific molecular factors that regulate each. The relative importance of inflammatory cytokines in normal and diabetic healing, the transforming growth factor beta superfamily of bone morphogenetic mediators, and the process of angiogenesis are discussed as they relate to bone repair. A complete summary of biological activities and functions of various bioactive factors may be found at COPE (Cytokines & Cells Online Pathfinder Encyclopedia), http://www.copewithcytokines.de/cope.cgi.

  20. Do estrogen and alendronate improve metaphyseal fracture healing when applied as osteoporosis prophylaxis?

    PubMed

    Kolios, Leila; Hoerster, Ann Kristin; Sehmisch, Stephan; Malcherek, Marie Christin; Rack, Thomas; Tezval, Mohammed; Seidlova-Wuttke, Dana; Wuttke, Wolfgang; Stuermer, Klaus Michael; Stuermer, Ewa Klara

    2010-01-01

    Osteoporosis is accompanied by predominantly metaphyseal fractures with a delayed and qualitatively reduced healing process. This study addressed the question of whether fracture healing in the context of osteoporosis prophylaxis is improved with estrogen (E) or alendronate (ALN). Thirty-six ovariectomized and 12 sham-operated 12-week-old rats received soy-free (osteoporotic C, sham), E-, or ALN- supplemented diets. After 10 weeks, a metaphyseal tibia osteotomy and standardized T-plate fixation were performed. After a 5-week healing process, the fracture callus was evaluated qualitatively by biomechanical bending test and quantitatively in microradiographic sections. The time course of callus formation was examined using fluorochrome-labeled histological sections. Administration of E improved the biomechanical properties of callus (stiffness [N/mm]: sham: 110.2 + or - 76.07, C: 41.28 + or - 33.70, E: 85.72 + or - 47.24, ALN: 72.07 + or - 34.68). The resistance to microfracturing seen in E-treated animals was significantly enhanced and even superior to sham (yield load [N] sham: 27.44 + or - 9.72, C: 21.04 + or - 12.47, E: 42.85 + or - 13.74(Delta), ALN: 25.28 + or - 6.4(.)) (* P < 0.05 vs. sham group, (Delta) P < 0.05 vs. C group, (*) P < 0.05 vs. E group). Trabecular bone in particular was improved, indicating the presence of physiological endosteal bridging (Tr.Dn [%] sham: 10.53 + or - 18.9, C: 1.01 + or - 0.14, E: 24.13 + or - 34.09(Delta), ALN: 3.99 + or - 8.3(.)). ALN did not help bone healing, as shown by mechanical tests. Compared to the C group, statistically, ALN did not show worse properties. The induction of callus formation under ALN treatment was slightly delayed (Tt.Cl [mm(2)] sham: 3.68 + or - 0.66, C: 3.44 + or - 0.42, E: 3.69 + or - 0.58, ALN: 3.06 + or - 0.56). Osteoporotic metaphyseal fracture healing was qualitatively and quantitatively improved by E prophylaxis. The process of fracture healing occurred nearly physiologically (shamlike

  1. 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.

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

    PubMed Central

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

    2016-01-01

    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. PMID:26840708

  3. Histological and biological changes in the epiphyseal plate during fracture healing.

    PubMed

    Papavasiliou, Athanasios V

    2002-01-01

    The alterations that the epiphyseal plate undergoes during fracture healing are well documented microscopically, yet there are no reports in the literature which discuss the cellular and molecular changes that accompany this process. We studied fracture healing in 49 Wistar rats (5 weeks old) in which we inflicted a fracture to the distal third of the femur of the right hind leg (experimental side). The rats were killed 2 weeks later, and we dissected both hind legs from the hip joint to the knee joint, detaching all the surrounding soft tissues. We manually detached the distal epiphyses and the epiphyseal plates from both femurs. A piece of the epiphyseal plate was removed from the epiphyseal side of the femurs. In 25 animals, and we analyzed the DNA content. In 8 animals, the specimen was studied under an electron microscope, and in the remaining 16 animals, the control and experimental sides were studied histologically. We found that healing was accompanied by an increase in DNA content, by a change in cellular activity, and by greatly accelerated apoptosis.

  4. Salidroside accelerates fracture healing through cell-autonomous and non-autonomous effects on osteoblasts.

    PubMed

    Guo, Xiao Qin; Qi, Lin; Yang, Jing; Wang, Yue; Wang, Chuan; Li, Zong Min; Li, Ling; Qu, Ye; Wang, Dan; Han, Ze Min

    2017-02-01

    Salidroside (SAL), a major active component of Rhodiola rosea L., exhibits diverse pharmacological effects. However, the direct roles of SAL in fracture healing remain largely unknown. Here, we demonstrate that SAL significantly promotes proliferation by altering the cell-cycle distribution of osteoblastic cells. SAL also greatly stimulates osteoblast differentiation and mineralization by inducing the expression of Runx2 and Osterix. In addition to its osteoblast-autonomous effects, SAL can activate the HIF-1α pathway coupling of angiogenesis and osteogenesis through cell-non-autonomous effects. Our in vitro results suggest that SAL significantly up-regulates HIF-1α expression at the mRNA and protein levels. Furthermore, the nuclear translocation and transcriptional activity of HIF-1α and the HIF-responsive gene VEGF increase following SAL treatment. Our mechanistic study revealed that the regulation of osteoblastic proliferation and HIF-1α expression partly involves MAPK/ERK and PI3K/Akt signaling. Our in vivo analysis also demonstrated that SAL can promote angiogenesis within the callus and accelerate fracture healing. Thus, SAL promotes skeletal regeneration in cell-autonomous and cell-non-autonomous ways and might be a potential therapy for accelerating fracture healing.

  5. Use of radiography to identify keel bone fractures in laying hens and assess healing in live birds.

    PubMed

    Richards, G J; Nasr, M A; Brown, S N; Szamocki, E M G; Murrell, J; Barr, F; Wilkins, L J

    2011-09-10

    The aim of this study was to use radiography to assess and characterise naturally occurring keel bone fractures in laying hens and monitor live birds over several weeks to examine the healing process. Twenty-four Lohmann brown commercial laying hens with varying degrees of keel bone fracture were used in the study. Birds were radiographed regularly over six weeks and the radiographic features and changing appearance of keel bone fractures were evaluated. The radiographic characteristics of old and new fractures were categorised and indicated that 80 per cent of birds entering the study with new fractures had healed after 35 days and five birds had incurred new fractures irrespective of their original fracture status.

  6. 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.

  7. Early stages of bone fracture healing: formation of a fibrin-collagen scaffold in the fracture hematoma.

    PubMed

    Echeverri, L F; Herrero, M A; Lopez, J M; Oleaga, G

    2015-01-01

    This work is concerned with the sequence of events taking place during the first stages of bone fracture healing, from bone breakup until the formation of early fibrous callus (EFC). The latter provides a scaffold over which subsequent remodeling processes will eventually result in successful bone repair. Specifically, some mathematical models are proposed to estimate the time required for (1) the formation immediately after fracture of a fibrin clot, described in terms of a phase transition in a polymerization process, and (2) the onset of EFC which is produced when fibroblasts arising from differentiation of chemotactically recruited mesenchymal stem cells remodel a previous fibrin clot by releasing a collagen matrix over it. An attempt has been made to keep models as simple as possible, so that a explicit dependence of the estimates obtained on relevant biochemical parameters involved is obtained.

  8. Locally applied simvastatin improves fracture healing at late period in osteoporotic rat

    NASA Astrophysics Data System (ADS)

    Tian, Faming; Zhang, Liu; Kang, Yuchuan; Zhang, Junshan; Ao, Jiao; Yang, Fang

    effect of simvastatin locally applied from a bioactive polymer coating of implants on osteoporotic fracture healing at late period. Methods:Femur fracture model was established on normal or osteotoporotic mature female SD rats, intramedullary stabilization was achieved with uncoated titanium Kirschnerwires in normal rats(group A),with polymer-only coated vs. polymer plus simvastatin coated titanium Kirschner wires in osteoporotic rats(group B and C, respectively).Femurs were harvested after 12 weeks, and underwent radiographic and histologic analysis, as well as immunohistochemical evaluation for BMP-2 expression. Results:Radiographic results demonstrated progressed callus in the simvastatin-treated groups compared to the uncoated group.The histologic analysis revealed a significantly processed callus with irregular-shaped newly formed bone trabeculae in simvastatin-treated group. Immunohistochemical evaluation showed markedly higher expression levels of B:MP-2 in simvastatin-treated group.Conclusions: The present study revealed a improved fracture healing under local application of simvastatin in osteoporotic rat,which might partially from upregulation of the B:MP-2 expression at fractured site.

  9. Review of techniques for monitoring the healing fracture of bones for implementation in an internally fixated pelvis.

    PubMed

    Wong, Lydia Chwang Yuh; Chiu, Wing Kong; Russ, Matthias; Liew, Susan

    2012-03-01

    Sacral fractures from high-impact trauma often cause instability in the pelvic ring structure. Treatment is by internal fixation which clamps the fractured edges together to promote healing. Healing could take up to 12 weeks whereby patients are bedridden to avoid hindrances to the fracture from movement or weight bearing activities. Immobility can lead to muscle degradation and longer periods of rehabilitation. The ability to determine the time at which the fracture is stable enough to allow partial weight-bearing is important to reduce hospitalisation time. This review looks into different techniques used for monitoring the fracture healing of bones which could lead to possible methods for in situ and non-invasive assessment of healing fracture in a fixated pelvis. Traditional techniques being used include radiology and CT scans but were found to be unreliable at times and very subjective in addition to being non in situ. Strain gauges have proven to be very effective for accurate assessment of fracture healing as well as stability for long bones with external fixators but may not be suitable for an internally fixated pelvis. Ultrasound provides in situ monitoring of stiffness recovery but only assesses local fracture sites close to the skin surface and has only been tested on long bones. Vibration analysis can detect non-uniform healing due to its assessment of the overall structure but may suffer from low signal-to-noise ratio due to damping. Impedance techniques have been used to assess properties of non-long bones but recent studies have only been conducted on non-biological materials and more research needs to be done before it can be applicable for monitoring healing in the fixated pelvis.

  10. Fracture and healing in magmas: a dual role on permeability evolution

    NASA Astrophysics Data System (ADS)

    Lamur, Anthony; Lavallée, Yan; Wall, Richard; Ashworth, James; Kendrick, Jackie; Wadsworth, Fabian

    2016-04-01

    The development of a permeable network in silicic volcanic conduits controls outgassing and plays a major role on the subsequent eruptive behaviour. Efficient outgassing, at higher permeabilities, is achieved through the coalescence of pores and fractures. Whilst the relationship between permeability and increasing connected porosity is now relatively well constrained, the effects of fractures have, on the other hand, rarely been investigated. Here, we present the results of an experimental study focusing on the impacts of tensile fracturing and healing on permeability. Permeability measurements have been performed on over 60 disk-shaped samples (26 mm diameter, 13 mm thickness) with connected porosities ranging from 2 to 45%. Our results for unfractured samples display the same porosity-permeability trend as previous studies and permeabilities span from 10-15 at low porosities to over 5x10-12 m2 at higher porosities. These samples were then broken via Brazilian tests and the resultant permeability of the rocks were then measured across the fracture zone. Whilst high porosity samples reached permeabilities of about 5x10-10 m2 (2 orders of magnitude higher than intact samples), low porosity samples, on the other hand, reached permeabilities around 5x10-12 m2 (more than 3 orders of magnitude above intact samples). Our results show that fracturing favours the development of a permeable network that adheres to a different permeability-porosity relationship than previously presented, and that this effect is emphasized in magmas with low connected porosities. The effect of fracture healing by diffusion on permeability has been investigated through a series of experiments on borosilicate standard glass (NIST 717a). These experiments were conducted at 560oC (viscosity of 1010.33 Pa.s) on pairs of columns pressed and held in contact at constant load for times varying between 0.5s and 15000 s before being pulled apart at a strain rate of 10-3s-1. Using Maxwell's theory of

  11. Formononetin promotes early fracture healing through stimulating angiogenesis by up-regulating VEGFR-2/Flk-1 in a rat fracture model.

    PubMed

    Huh, Jeong-Eun; Kwon, Na-Hyun; Baek, Young-Hyun; Lee, Jae-Dong; Choi, Do-Young; Jingushi, Seiya; Kim, Kang-il; Park, Dong-Suk

    2009-11-01

    Plant-derived phytoestrogens have bone protective effects, but the molecular mechanism behind these effects remains unclear. This study is aimed at fully characterizing the fracture healing process of formononetin, and investigating the mechanism underlying angiogenesis in calluses of a rat fracture model. Femoral fractures were produced in 2-month-old Sprague-Dawley rats. A 20 microg/kg or 200 microg/kg dose of formononetin was orally administrated once a day during the healing period of 21 days. The results showed that in the early stage of chondrogenesis (days 3), formononetin significantly increased the number of vessels, and expression of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR-2/flk-1) compared with control. However, the larger dose of formononetin had no significant difference on expression of VEGF and VEGFR-2/Flk-1 compared with that of the smaller dose of formononetin. After 7 days of administration, formononetin markedly induced differentiation of mesenchymal stem cells in the fracture site. After 14 days, gene expression of mesenchymal progenitors such as alkaline phosphatase (ALP), osteocalcin (OCN), osteopontin (OPN) and collagen type I (Col I), indicating osteogenic differentiation, was markedly stimulated by formononetin compared with control. These results suggest that formononetin promotes early fracture healing through angiogenesis activation in the early stage of fracture repair, and osteogenesis acceleration in the later stages, and thus may be beneficial for fracture healing.

  12. Investigation of rat bone fracture healing using pulsed 1.5 MHz, 30 mW/cm(2) burst ultrasound--axial distance dependency.

    PubMed

    Fung, Chak-Hei; Cheung, Wing-Hoi; Pounder, Neill M; de Ana, F Javier; Harrison, Andrew; Leung, Kwok-Sui

    2014-03-01

    This study investigated the effect of LIPUS on fracture healing when fractures were exposed to ultrasound at three axial distances: z=0 mm, 60 mm, and 130 mm. We applied LIPUS to rat fracture at these three axial distances mimicking the exposure condition of human fractures at different depths under the soft tissue. Measurement of LIPUS shows pressure variations in near field (nearby transducer); uniform profile was found beyond it (far field). We asked whether different positions of the fracture within the ultrasound field cause inconsistent biological effect during the healing process. Closed femoral fractured Sprague-Dawley rats were randomized into control, near-field (0mm), mid-near field (60 mm) or far-field (130 mm) groups. Daily LIPUS treatment (plane, but apodized source, see details in the text; 2.2 cm in diameter; 1.5 MHz sine waves repeating at 1 kHz PRF; spatial average temporal average intensity, ISATA=30 mW/cm(2)) was given to fracture site at the three axial distances. Weekly radiographs and endpoint microCT, histomorphometry, and mechanical tests were performed. The results showed that the 130 mm group had the highest tissue mineral density; and significantly higher mechanical properties than control at week 4. The 60 mm and 0 mm groups had significantly higher (i.e. p<0.05) woven bone percentage than control group in radiological, microCT and histomorphometry measurements. In general, LIPUS at far field augmented callus mineralization and mechanical properties; while near field and mid-near field enhanced woven bone formation. Our results indicated the therapeutic effect of LIPUS is dependent on the axial distance of the ultrasound beam. Therefore, the depth of fracture under the soft tissue affects the biological effect of LIPUS. Clinicians have to be aware of the fracture depth when LIPUS is applied transcutaneously.

  13. Secreted Frizzled Related Protein 1 is a Target to Improve Fracture Healing

    PubMed Central

    Gaur, Tripti; Wixted, John J.; Hussain, Sadiq; O’Connell, Shannon; Morgan, Elise F.; Ayers, David; Komm, Barry S.; Bodine, Peter V.; Stein, Gary S.; Lian, Jane B.

    2009-01-01

    Genetic studies have identified a high bone mass of phenotype in both human and mouse when canonical Wnt signaling is increased. Secreted frizzled related protein1 (sFRP1) is one of several Wnt antagonists and among the loss-of-function mouse models in which 32-week old mice exhibit a high bone mass phenotype. Here we show that impact fracture healing is enhanced in this mouse model of increased Wnt signaling at a physiologic level in young (8 week) sFRP1−/− mice which do not yet exhibit significant increase in BMD. The loss of sFRP1 function in vivo improves fracture repair by promoting early bone union without adverse effects on the quality of bone tissue reflected by increased mechanical strength. We observe a dramatic reduction of the cartilage callous, increased intramembranous bone formation with bone bridging by 14 days, and early bone remodeling during the 28 day fracture repair process in the sFRP1−/− mice. Our molecular analyses of gene markers indicate that the effect of sFRP1 loss-of-function during fracture repair is to accelerate bone healing after formation of the initial hematoma by directing mesenchymal stem cells into the osteoblast lineage via the canonical pathway. Further evidence to support this conclusion is the observation of maximal sFRP1 levels in the cartilaginous callus of a WT mouse, hence in sFRP1−/− mouse progenitor cells are shifted directly into osteoblast lineage. Thus, developing an antagonist to specifically inhibit sFRP1 represents a safe target for stimulating fracture repair and bone formation in metabolic bone disorders, osteoporosis and aging. PMID:19301255

  14. Analogous cellular contribution and healing mechanisms following digit amputation and phalangeal fracture in mice

    PubMed Central

    Dawson, Lindsay A.; Simkin, Jennifer; Sauque, Michelle; Pela, Maegan; Palkowski, Teresa

    2016-01-01

    Abstract Regeneration of amputated structures is severely limited in humans and mice, with complete regeneration restricted to the distal portion of the terminal phalanx (P3). Here, we investigate the dynamic tissue repair response of the second phalangeal element (P2) post amputation in the adult mouse, and show that the repair response of the amputated bone is similar to the proximal P2 bone fragment in fracture healing. The regeneration‐incompetent P2 amputation response is characterized by periosteal endochondral ossification resulting in the deposition of new trabecular bone, corresponding to a significant increase in bone volume; however, this response is not associated with bone lengthening. We show that cells of the periosteum respond to amputation and fracture by contributing both chondrocytes and osteoblasts to the endochondral ossification response. Based on our studies, we suggest that the amputation response represents an attempt at regeneration that ultimately fails due to the lack of a distal organizing influence that is present in fracture healing. PMID:27499878

  15. Healing of fracturing-bone disease occurring in patients on dialysis. A prospective study.

    PubMed

    Milne, F J; Hudson, G A; Meyers, A M; Baily, P; Barmeir, E; Dubowitz, B; Reis, P

    1982-06-19

    Ten patients developed fracturing-bone disease (osteomalacia) while on dialysis against water with high levels of aluminium. Eight patients remained on dialysis, using de-ionized or reverse-osmosis water, and 2 received a renal transplant. Clinical improvement as regards bone pain and proximal muscle weakness occurred in 6 months and radiographic evidence of healing of the pseudofractures was seen at approximately 12 months. Associated osteopenia and hyperparathyroidism were found in most patients, but no significant change in either was noted during the study period. The serum parathyroid hormone levels rose significantly in the patients who remained on dialysis. The chest and pelvic deformities typical of healed osteomalacia were seen. This dramatic improvement can only be attributed to the removal of some water-borne element, either by changing the water used in the dialysis or by successful renal transplantation. Aluminium-containing phosphate binders were used throughout the study in the patients on dialysis, and hypophosphataemia was never a feature.

  16. Enhancement of fracture healing by electrical stimulation in the comminuted intraarticular fracture of distal radius.

    PubMed

    Kohata, Kazuhiro; Itoh, Soichiro; Takeda, Shu; Kanai, Misa; Yoshioka, Taro; Suzuki, Hiroyuki; Yamashita, Kimihiro

    2013-01-01

    Effectiveness of an alternating electric current (AC) stimulation in prevention of bone deformity for comminuted intraarticular fracture of distal radius were verified by comparing postoperative results treated with a wrist-bridging external fixator combined with or without an AC stimulator (EF and NEF, respectively), and a palmar locking plate (LP). This study evaluated 92 cases (mean age 67.9 ± 11.4 years) of type C2 and 60 cases (mean age 69.7 ± 9.5 years) of type C3 distal radius fractures, as classified by the Association for Osteosynthesis. In total, 55 and 24 cases were treated with EF and NEF, respectively; and 73 cases were treated with LP. Callus appeared 27.5 ± 4.6 days postoperatively and the external skeletal fixation period was significantly shorter in the EF group than in the NEF group. The decrease in radial length was significantly lower in the EF group when compared to the LP group. There were no significant differences among the groups for the other radiographic and functional parameters. AC stimulation combined to the external fixation may be a promising method to prevent postoperative deformity in the severely comminuted intraarticular fractures by accelerating callus maturation and facilitating new bone bridging across the gap of fracture site.

  17. Irradiated human chondrocytes expressing bone morphogenetic protein 2 promote healing of osteoporotic bone fracture in rats.

    PubMed

    Yi, Youngsuk; Choi, Kyoung Baek; Lim, Chae-Lyul; Hyun, Jong-Pil; Lee, Hyeon-Youl; Lee, Kun Bok; Yun, Lillian; Ayverdi, Asli; Hwang, Sally; Yip, Vivian; Noh, Moon Jong; Lee, Kwan Hee

    2009-10-01

    Bone morphogenetic protein 2 (BMP2) was selected as a transgene to regenerate osteoporotic bone defects after several BMPs were tested using a bone formation study in nude mice. Human chondrocytes were transduced with a BMP2-containing retroviral vector, and single clones were selected. The cells were characterized over numerous passages for growth and BMP2 expression. The single clones were irradiated and tested for viability. BMP2 expression lasted for 3 weeks before dying off completely after approximately 1 month. Irradiated and non-irradiated transduced chondrocytes successfully healed fractures in osteoporotic rats induced by ovariectomy. The osteoinducing effect of irradiated cells was better than that of their non-irradiated counterparts or a chondrocytes-only control. This study showed that delivering BMP2 from the transduced and irradiated chondrocytes could be an effective and safe method of repairing osteoporotic bone fractures.

  18. Deletion of the homeobox gene PRX-2 affects fetal but not adult fibroblast wound healing responses.

    PubMed

    White, Philip; Thomas, David W; Fong, Steven; Stelnicki, Eric; Meijlink, Fritz; Largman, Corey; Stephens, Phil

    2003-01-01

    The phenotype of fibroblasts repopulating experimental wounds in vivo has been shown to influence both wound healing responses and clinical outcome. Recent studies have demonstrated that the human homeobox gene PRX-2 is strongly upregulated in fibroblasts within fetal, but not adult, mesenchymal tissues during healing. Differential homeobox gene expression by fibroblasts may therefore be important in mediating the scarless healing exhibited in early fetal wounds. RNase protection analysis demonstrated that murine Prx-2 expression was involved in fetal but not adult wound healing responses in vitro. Using fibroblasts established from homozygous mutant (Prx-2-/-) and wild-type (Prx-2+/+) murine skin tissues it was demonstrated that Prx-2 affected a number of fetal fibroblastic responses believed to be important in mediating scarless healing in vivo; namely cellular proliferation, extracellular matrix reorganization, and matrix metalloproteinase 2 and hyaluronic acid production. These data demonstrate how Prx-2 may contribute to the regulation of fetal, but not adult, fibroblasts and ultimately the wound healing phenotype. This study provides further evidence for the importance of homeobox transcription factors in the regulation of scarless wound healing. A further understanding of these processes will, it is hoped, enable the targeting of specific therapies in wound healing, both to effect scarless healing and to stimulate healing in chronic, nonhealing wounds such as venous leg ulcers.

  19. Healing of non-displaced fractures produced by fatigue loading of the mouse ulna.

    PubMed

    Martinez, Mario D; Schmid, Gregory J; McKenzie, Jennifer A; Ornitz, David M; Silva, Matthew J

    2010-06-01

    We developed a fatigue loading protocol in mice to produce a non-displaced ulnar fracture in vivo, and characterized the early healing response. Using adult (5 month) C57Bl/6 mice, we first determined that cyclic compression of the forelimb under load-control leads to increasing applied displacement and, eventually, complete fracture. We then subjected the right forelimbs of 80 mice to cyclic loading (2 Hz; peak force approximately 4N) and limited the displacement increase to 0.75 mm (60% of the average displacement increase at complete fracture). This fatigue protocol created a partial, non-displaced fracture through the medial cortex near the ulnar mid-shaft, and reduced ulnar strength and stiffness by >50%. Within 1 day, there was significant upregulation of genes related to hypoxia (Hif1a) and osteogenesis (Bmp2, Bsp) in loaded ulnae compared to non-loaded, contralateral controls. The gene expression response peaked in magnitude near day 7 (e.g., Osx upregulated 8-fold), and included upregulation of FGF-family genes (e.g., Fgfr3 up 6-fold). Histologically, a localized periosteal response was seen at the site of the fracture; by day 7 there was abundant periosteal woven bone surrounding a region of cartilage. From days 7 to 14, the woven bone became denser but did not increase in area. By day 14, the woven-bone response resulted in complete recovery of ulnar strength and stiffness, restoring mechanical properties to normal levels. In the future, the fatigue loading approach can be used create non-displaced bone fractures in transgenic and knockout mice to study the mechanisms by which the skeleton rapidly repairs damage.

  20. 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.

  1. Success of long bone fracture healing in ancient Egypt: a paleoepidemiological study of the Giza Necropolis skeletons.

    PubMed

    Erfan Zaki, Moushira

    2013-01-01

    Complications may provide information regarding the management of fractures in ancient populations. The aim of this study was to determine the rates of long-bone fractures and the proportion of misalignments as indicators of failed treatment or no treatment at all in skeletons from the Giza Necropolis dating to the Old Kingdom period (2700-2190 BC). We visually examined for fractures 2287 long bones of 204 adult skeletons (112 male and 92 female) and took x-rays of fractured bones in standard AP and ML views, so that we can analyse misalignments. Fractures were found in 45 of the 2287 examined long bones (1.97 %). Most of the fractures healed with good alignment, most likely as a result of successful treatment, and only three fractures showed misalignment.

  2. Healing

    PubMed Central

    Ventres, William B.

    2016-01-01

    My personal ethos of healing is an expression of the belief that I can and do act to heal patients while I attend to the traditional goals of medicine. The 7 supporting principles that inform my ethos are dignity, authenticity, integrity, transparency, solidarity, generosity, and resiliency. I invite others, including medical students, residents, and practicing physicians, to reflect and discover their own ethos of healing and the principles that guide their professional growth. A short digital documentary accompanies this essay for use as a reflective prompt to encourage personal and professional development. PMID:26755787

  3. The regeneration and augmentation of bone with injectable osteogenic cell sheet in a rat critical fracture healing model.

    PubMed

    Shimizu, Takamasa; Akahane, Manabu; Morita, Yusuke; Omokawa, Shohei; Nakano, Kenichi; Kira, Tsutomu; Onishi, Tadanobu; Inagaki, Yusuke; Okuda, Akinori; Kawate, Kenji; Tanaka, Yasuhito

    2015-08-01

    Limitations in the current treatment strategies make cases with compromised bone healing challenging clinical problems. Osteogenic cell sheets (OCSs), fabricated from rat bone marrow stromal cells (BMSCs), contain enriched osteoblasts and extracellular matrix. Here, we evaluated whether the minimally invasive percutaneous injection of OCSs without a scaffold could be used as a treatment to increase bone regeneration in a critical fracture healing model. Critical fracture healing model was created in the femora of 60 male Fischer 344 inbred rats using marrow ablation and periosteal removal. The rats were then randomly divided into two groups. Six hours after fracture, one group received an injection of OCSs (OCS group), while the second group was injected with phosphate-buffered saline (PBS) (control group). Fracture healing was evaluated using radiological, histological, micro-computed tomography (CT) and biomechanical analyses. The radiological and histological evaluations demonstrated enhanced bone regeneration in the OCS group compared with that in the control group. By 12 weeks, the hard callus had been remodelled via recorticalization in the OCS group. By contrast, no fracture union was found in the rats in the control group. Biomechanical testing revealed a significantly higher maximum bending load in the OCS group compared with that in the control group. The results of the present study demonstrate that the injection of entire OCSs can enhance bone regeneration and lead to bony union in a critical fracture healing model. Therefore, this procedure offers a minimally invasive technique to promote hard tissue reconstruction and, in particular, bone repair strategies for cases with compromised bone healing.

  4. Evaluation of high-resolution In Vivo MRI for longitudinal analysis of endochondral fracture healing in mice

    PubMed Central

    Müller-Graf, Fabian; Matthys, Romano; Hägele, Yvonne; Fischer, Verena; Jonas, René; Abaei, Alireza; Gebhard, Florian; Rasche, Volker; Ignatius, Anita

    2017-01-01

    Mice are extensively used for experimental bone-healing studies. However, there are few established nondestructive in vivo techniques for longitudinal fracture-healing analysis in mice, including in vivo micro-computed tomography (μCT) and radiography. Importantly, none of the established methods can discriminate between non-mineralized fibrous tissue and cartilage in the soft fracture callus. Therefore, the objective was to establish high-resolution in vivo magnetic resonance imaging (MRI) for the longitudinal assessment of soft callus formation during bone healing in mice. C57BL/6J mice received a femur osteotomy stabilized using an external fixator and were randomly assigned to five groups. Group 1 mice were scanned three times longitudinally during fracture healing using an optimized MRI scanning protocol to establish an algorithm to characterize the different fracture-callus tissues. Mice of groups 2–4 were scanned once on day 10, 14 or 21, respectively, euthanized after scanning and their femurs subjected to ex vivo μCT and histomorphometric analysis to compare the data assessed by MRI with μCT and histology. Control group 5 mice were not scanned. After 28 days, mice of groups 1 and 5 were euthanized and the fracture-healing outcome was evaluated by bending-test, μCT and histology to determine whether the repeated anesthesia, handling and the MRI measurements themselves influenced fracture healing. The callus-tissue values determined by MRI were mostly comparable to those obtained by μCT and histomorphometric analysis. However, at time points characterized by small relative bone or cartilage areas, MRI measurements were weakly comparable to histomorphometric data, possibly due to the inferior spatial resolution. Importantly, at the early and intermediate phases of healing, cartilage and fibrous-tissue values obtained by MRI were highly accurate. Furthermore, repeated anesthesia, handling and MRI scans did not impact bone healing. Therefore, we

  5. Effect of leptin combined with CoCl2 on healing in Sprague Dawley Rat fracture model

    PubMed Central

    Liu, Pengcheng; Liu, Junfeng; Xia, Kuo; Chen, Liyang; Wu, Xing

    2016-01-01

    To evaluate the effect of leptin combined with CoCl2 on rat femur fracture healing. 48 male Sprague Dawley rats were randomly divided into two main groups. Then standardized femur fractures were created to all rats. Control group rats were treated with 0.5 mL physiological saline, and experimental group rats were treated with 5 μg/Kg.d leptin and 15 mg/Kg.d CoCl2 along with 0.5 mL physiological saline for 42 days intraperitoneally. Each main group was divided into three subgroups for each evaluation at second, fourth and sixth weeks, each subgroup included eight rats. The radiological evaluation showed that the fracture healing progress of experimental group was superior to control group from second week. At fourth week, experimental group had better fracture healing progress than control group significantly. Results of biomechanics show the ultimate load (N) and deflection ultimate load (mm) of experimental group was significantly increased than that in control group from fourth week. The present result demonstrated that leptin combined with CoCl2 significantly increased the mRNA expression levels of HIF1A, Vegfa, Runx2, Bmp2, Bglap and Alpl. It suggested that leptin combined with CoCl2 have a positive effect on rat femur fracture healing by activating the HIF1A pathway. PMID:27468656

  6. Effect of Obesity on Bone Healing After Foot and Ankle Long Bone Fractures.

    PubMed

    Thorud, Jakob C; Mortensen, Spencer; Thorud, Jennifer L; Shibuya, Naohiro; Maldonado, Yolanda Munoz; Jupiter, Daniel C

    As obesity has become more common, fractures in the obese population have become more frequent. Concern exists regarding alterations in bone health and healing in obese patients. A matched case-control study was performed at 1 institution to evaluate whether an association exists between nonunion and a high body mass index in metatarsal and ankle fractures. A total of 48 patients with nonunion were identified, and control patients matched 2 to 1 (n = 96) were selected. The control patients were matched for age, sex, and fracture type. No association was identified between nonunion and the continuous body mass index (p = .23) or morbid obesity, with a body mass index of ≥40 kg/m(2) (p = .51). However, the results from both univariate and multivariate analysis suggested that patients with a current alcohol problem or a history of an alcohol problem might have a greater risk of nonunion. The odds ratio of a patient with a history of alcohol use experiencing nonunion was 2.7 (95% confidence interval 1.2 to 6.2). Further studies are warranted to confirm these findings.

  7. Systemic treatment with vanadium absorbed by Coprinus comatus promotes femoral fracture healing in streptozotocin-diabetic rats.

    PubMed

    Wang, Guangbin; Wang, Jiashi; Fu, Yonghui; Bai, Lunhao; He, Ming; Li, Bin; Fu, Qin

    2013-03-01

    The purpose of this study was to analyze the impact of vanadium absorbed by Coprinus comatus (VACC) on fracture healing in streptozotocin-diabetic rats. Forty-five male Wistar rats used were divided into three groups: normal rats (control), diabetic rats, and diabetic rats treated with VACC. A standardized fracture-healing model with a stable plate fixation was established for the rat femoral fracture. After a 4-week stable fixation, callus quality was assessed by microcomputerized tomography and histological and biomechanical examinations. In addition, bone samples were obtained to evaluate the content of mineral substances in bones. Compared with the diabetic group, vanadium treatment significantly increased bone mineral content and biomechanical strength and improved microstructural properties of the callus. The ultimate load was increased by 29.1 % (P<0.05), and the total bone volume of callus enhanced by 11.2 % (P<0.05) at 4 weeks post fracture. Vanadium also promoted callus bone formation, which caused a 35.5 % increase in the total area of callus. However, VACC did not accelerate the fracture repair process in histological analysis. In conclusion, the current study suggests that systemic treatment with vanadium could promote fracture healing in streptozotocin-diabetic rats.

  8. Effect of amino acids lysine and arginine on fracture healing in rabbits: A radiological and histomorphological analysis

    PubMed Central

    Sinha, Shivam; Goel, Satish Chandra

    2009-01-01

    Background: Amino acids like arginine and lysine have been suggested to hasten the process of fracture healing by improving the local blood supply, supplementing growth factors, and improving collagen synthesis. We studied the role of lysine and arginine in the fracture repair process with regard to the rate of healing, probable mechanisms involved in the process, and mutual synergism between these agents. Materials and Methods: In an experimental study, 40 rabbits were subjected to ulnar osteotomy. They were distributed in control (14) and test groups (26). Twenty-six animals in the test group were fed with a diet rich in lysine and arginine. Both the groups were followed radiologically and histologically till union. Results: There was better healing of osteotomy in terms of better vascularization, callus formation, and mineralization in the test group. The time of healing in the test group was reduced by a period of 2 weeks. Conclusion: We conclude that amino acids like arginine and lysine may hasten fracture healing. PMID:19838381

  9. A Biomechanical Comparison of Two Intramedullary Implants for Subtrochanteric Fracture in Two Healing Stages: A Finite Element Analysis

    PubMed Central

    Wu, Xinlei; Yang, Ming; Wu, Lijun; Niu, Wenxin

    2015-01-01

    Background. The biomechanical effect of two implants, namely, proximal femoral nail antirotation for Asia (PFNA-II) and Expert Asian Femoral Nail (A2FN), for treating subtrochanteric fracture during healing stages, is still unclear. Methods. A 3D finite element model of an intact femur was constructed and validated. The fractured and postoperative models were accordingly produced. The postoperative models were loaded with the peak joint forces during gait for the soft and hard callus stages. The effects of stress distribution on the implants, femoral head and callus, and the deformation of the proximal femur were examined. Results. Both implants showed similar biomechanical effect in two healing stages. As the healing duration increased, the von Mises stress of two implants and the tensile stress of the femoral head decreased, whereas the compressive stress of the femoral head increased. However, the PFNA-II operation resulted in higher stress on the implant, lower stress on the proximal femur, and lower compressive stress and higher tensile stress on the callus than A2FN operation. Conclusions. The A2FN implant may provide a biomechanically superior construct for subtrochanteric fracture healing. However, the upper screw of the A2FN implant may be more likely to be loose in the healing process. PMID:27019584

  10. Bioglass promotes wound healing by affecting gap junction connexin 43 mediated endothelial cell behavior.

    PubMed

    Li, Haiyan; He, Jin; Yu, Hongfei; Green, Colin R; Chang, Jiang

    2016-04-01

    It is well known that gap junctions play an important role in wound healing, and bioactive glass (BG) has been shown to help healing when applied as a wound dressing. However, the effects of BG on gap junctional communication between cells involved in wound healing is not well understood. We hypothesized that BG may be able to affect gap junction mediated cell behavior to enhance wound healing. Therefore, we set out to investigate the effects of BG on gap junction related behavior of endothelial cells in order to elucidate the mechanisms through which BG is operating. In in vitro studies, BG ion extracts prevented death of human umbilical vein endothelial cells (HUVEC) following hypoxia in a dose dependent manner, possibly through connexin hemichannel modulation. In addition, BG showed stimulatory effects on gap junction communication between HUVECs and upregulated connexin43 (Cx43) expression. Furthermore, BG prompted expression of vascular endothelial growth factor and basic fibroblast growth factor as well as their receptors, and vascular endothelial cadherin in HUVECs, all of which are beneficial for vascularization. In vivo wound healing results showed that the wound closure of full-thickness excisional wounds of rats was accelerated by BG with reduced inflammation during initial stages of healing and stimulated angiogenesis during the proliferation stage. Therefore, BG can stimulate wound healing through affecting gap junctions and gap junction related endothelial cell behaviors, including prevention of endothelial cell death following hypoxia, stimulation of gap junction communication and upregulation of critical vascular growth factors, which contributes to the enhancement of angiogenesis in the wound bed and finally to accelerate wound healing. Although many studies have reported that BG stimulates angiogenesis and wound healing, this work reveals the relationship between BG and gap junction connexin 43 mediated endothelial cell behavior and elucidates

  11. Effect of Pentoxifylline Administration on an Experimental Rat Model of Femur Fracture Healing With Intramedullary Fixation

    PubMed Central

    Vashghani Farahani, Mohammad Mahdi; Masteri Farahani, Reza; Mostafavinia, Ataroalsadat; Abbasian, Mohammad Reza; Pouriran, Ramin; Noruzian, Mohammad; Ghoreishi, Seyed Kamran; Aryan, Arefe; Bayat, Mohammad

    2015-01-01

    Background: Globally, musculoskeletal injuries comprise a major public health problem that contributes to a large burden of disability and suffering. Pentoxifylline (PTX) has been originally used as a hemorheologic drug to treat intermittent claudication. Previous test tube and in vivo studies reported the beneficial effects of PTX on bony tissue. Objectives: This study aims to evaluate the effects of different dosages of PTX on biomechanical properties that occur during the late phase of the fracture healing process following a complete femoral osteotomy in a rat model. We applied intramedullary pin fixation as the treatment of choice. Materials and Methods: This experimental study was conducted at the Shahid Beheshti University of Medical Sciences, Tehran, Iran. We used the simple random technique to divide 35 female rats into five groups. Group 1 received intraperitoneal (i.p.) PTX (50 mg/kg, once daily) injections, starting 15 days before surgery, and group 2, group 3, and group 4 received 50 mg/kg, 100 mg/kg, and 200 mg/kg i.p. PTX injections, respectively, once daily after surgery. All animals across groups received treatment for six weeks (until sacrificed). Complete surgical transverse osteotomy was performed in the right femur of all rats. At six weeks after surgery, the femurs were subjected to a three-point bending test. Results: Daily administration of 50 mg/kg PTX (groups 1 and 2) decreased the high stress load in repairing osteotomized femurs when compared with the control group. The highest dose of PTX (200 mg/kg) significantly increased the high stress load when compared with the control group (P = 0.030), group 1 (P = 0.023), group 2 (P = 0.008), and group 3 (P = 0.010), per the LSD findings. Conclusions: Treatment with 200 mg/kg PTX accelerated fracture healing when compared with the control group. PMID:26756019

  12. Micro-CT analysis with multiple thresholds allows detection of bone formation and resorption during ultrasound-treated fracture healing.

    PubMed

    Freeman, Theresa A; Patel, Payal; Parvizi, Javad; Antoci, Valentin; Shapiro, Irving M

    2009-05-01

    Multiple threshold algorithms applied to microcomputed tomography analysis were used to probe the effects of low-intensity pulsed ultrasound on fracture healing. Rat femurs were fractured in accordance with IACUC guidelines. Ultrasound treatment was administered daily to one femur; the contralateral bone was treated with a sham transducer. Each week for 3 weeks healing fractures were harvested and scanned by micro-CT. Remodeling activity was confirmed by evaluation of TRAP activity. Using thresholds of 331-700 and 225-330, area of cortical bone, and new bone formation, respectively, were identified, and by inference, regions of bone resorption. The increased sensitivity of this multithresholding procedure revealed that ultrasound treatment significantly increased the rate of fracture healing in vivo by activating both new bone formation and by increasing the removal of cortical bone in a time- and site-specific manner. At week 1, compared to the proximal side, there was a significant increase in new bone formation distal to the fracture site. Removal of the existing cortical bone followed the same pattern at week 2. Results of the study indicate that at sites of bone turnover, this multithresholding analytical technique can be used to provide quantitative information on bone formation, as well as resorption.

  13. Osteoblast-Specific Krm2 Overexpression and Lrp5 Deficiency Have Different Effects on Fracture Healing in Mice

    PubMed Central

    Liedert, Astrid; Röntgen, Viktoria; Schinke, Thorsten; Benisch, Peggy; Ebert, Regina; Jakob, Franz; Klein-Hitpass, Ludger; Lennerz, Jochen K.; Amling, Michael; Ignatius, Anita

    2014-01-01

    The canonical Wnt/β-catenin pathway plays a key role in the regulation of bone remodeling in mice and humans. Two transmembrane proteins that are involved in decreasing the activity of this pathway by binding to extracellular antagonists, such as Dickkopf 1 (Dkk1), are the low-density lipoprotein receptor related protein 5 (Lrp5) and Kremen 2 (Krm2). Lrp 5 deficiency (Lrp5−/−) as well as osteoblast-specific overexpression of Krm2 in mice (Col1a1-Krm2) result in severe osteoporosis occurring at young age. In this study, we analyzed the influence of Lrp5 deficiency and osteoblast-specific overexpression of Krm2 on fracture healing in mice using flexible and semi-rigid fracture fixation. We demonstrated that fracture healing was highly impaired in both mouse genotypes, but that impairment was more severe in Col1a1-Krm2 than in Lrp5−/− mice and particularly evident in mice in which the more flexible fixation was used. Bone formation was more reduced in Col1a1-Krm2 than in Lrp5−/− mice, whereas osteoclast number was similarly increased in both genotypes in comparison with wild-type mice. Using microarray analysis we identified reduced expression of genes mainly involved in osteogenesis that seemed to be responsible for the observed stronger impairment of healing in Col1a1-Krm2 mice. In line with these findings, we detected decreased expression of sphingomyelin phosphodiesterase 3 (Smpd3) and less active β-catenin in the calli of Col1a1-Krm2 mice. Since Krm2 seems to play a significant role in regulating bone formation during fracture healing, antagonizing KRM2 might be a therapeutic option to improve fracture healing under compromised conditions, such as osteoporosis. PMID:25061805

  14. 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

  15. Functional outcomes, morbidity, mortality, and fracture healing in 58 consecutive patients with geriatric odontoid fracture treated with cervical collar or posterior fusion.

    PubMed

    Molinari, William J; Molinari, Robert W; Khera, Oner A; Gruhn, William L

    2013-03-01

    Controversy exists as to the most effective management option for elderly patients with type II odontoid fractures. The purpose of this study is to evaluate outcomes associated with rigid cervical collar and posterior fusion surgery. Patients with ≥ 50% odontoid displacement were treated with posterior fusion surgery including C1-2 (PSF group, n = 25, average age = 80 years). Patients with < 50% odontoid displacement were treated with a rigid cervical collar for 12 weeks (collar group, n = 33, average age = 83 years). These inhomogeneous groups were followed for an average of 14 months. Fracture healing rates were higher in the operative group (28% versus 6%). Neck Disability Index scores were slightly lower in the nonoperative group (13 versus 18.3, p = 0.23). Analogue pain scores were also slightly lower in the nonoperative group (1.3 versus 1.9, p = 0.26). The mortality rate was 12.5% in the collar group and 20% in the operative group. Complications were higher in the operative group (24% versus 6%). Rates of type II odontoid facture healing and stability appear to be higher in geriatric patients treated with posterior fusion surgery. Fracture healing and stability did not correlate with improved outcomes with respect to levels of pain, function, and satisfaction. Mortality and complication rates are lower in those patients with lesser-displaced fractures who are treated with a cervical collar and early mobilization.

  16. The effects of pentoxifylline adminstration on fracture healing in a postmenopausal osteoporotic rat model

    PubMed Central

    Vashghani Farahani, Mohammad Mahdi; Ahadi, Reza; Abdollahifar, Mohammadamin

    2017-01-01

    Previous studies report positive effects of pentoxifylline (PTX) alone or in combination with other drugs on some pathologic bone diseases as well as an ability to accelerate osteogensis and fracture healing in both animal models and human patients. The aim of this present study was to evaluate the effects of PTX administration on Hounsfield unit and bone strength at catabolic response (bone resorbing) of a fracture in an experimental rat model of ovariectomy induced osteoporosis (OVX-D). Thirty adult female rats were divided into groups as follows: 1 (OVX, control, no treatment); 2 (OVX, sham: daily distilled water); 3 (OVX, daily alendronate: 3 mg/kg); 4 (OVX, twice daily 100 mg/kg PTX) and 5 (OVX, PTX+alenderonate). OVX was induced by bilateral ovariectomy in all rats. A complete standardized osteotomy of the right femur was made after 3.5 months. PTX and alendronate treatments were performed for eight weeks. Then, rats were euthanized and had its right femur subjected to computerized tomography scanning for measuring Hounsfield unit; eventually, the samples were sent for a three point bending test for evaluation of the bone strength. Administration of PTX with 200 mg/kg and alendronate alone and in combination showed no significant alteration in Hounsfield unit and biomechanical properties of repairing callus of the complete osteotomy compared with the control group. Results showed increased bending stiffness and stress high load mean values of repairing complete osteotomy in PTX-treated rats compared to the control OVX-D.

  17. Is obesity protective against wound healing complications in pilon surgery? Soft tissue envelope and pilon fractures in the obese.

    PubMed

    Graves, Matthew L; Porter, Scott E; Fagan, Bryan C; Brien, Glenn A; Lewis, Matthew W; Biggers, Marcus D; Woodall, James R; Russell, George V

    2010-08-11

    Open treatment of pilon fractures is associated with wound healing complications. A traumatized, limited soft tissue envelope contributes to wound healing complications. Obese patients have larger soft tissue envelopes around the ankle, theoretically providing a greater area for energy distribution and more accommodation to implants. This led us to test 2 hypotheses: (1) ankle dimensions in obese patients are larger than in lean patients, and (2) the increased soft tissue envelope volume translates into fewer wound complications. A consecutive series of 176 pilon fractures treated from March 2002 to December 2007 were retrospectively reviewed. Inclusion criteria were adults who received a preoperative computed tomography (CT) scan and were treated with a staged protocol including plating. Patients with body mass index (BMI) >30 were compared to those with BMI <30 for CT-derived ankle dimensions and wound complications. Comorbidities were evaluated for their role as potential confounders. Thirty-one fractures in obese patients were compared to 83 in lean patients. The average ratio of bone area to soft tissue area at the tibial plafond was 0.35 for the obese group and 0.38 for the lean group (P=.012). There were 8 major wound-healing complications. Four occurred in the obese group (incidence 13%), and 4 in the lean group (incidence 5%) (P=.252). Ankle dimensions in clinically obese patients are larger than in lean patients. Obesity does not appear to be protective of wound-healing complications, but rather there is a trend toward the opposite.

  18. Yeast-incorporated gallium promotes fracture healing by increasing callus bony area and improving trabecular microstructure on ovariectomized osteopenic rats.

    PubMed

    Pei, Yi; Fu, Qin

    2011-06-01

    The purpose of this study was to analyze the impact of yeast-incorporated gallium on fracture healing in ovariectomized osteopenic rats. Forty Wistar female rats used were divided into three groups: sham-operated rats (SHAM), ovariectomized (OVX) rats, and ovx rats treated with yeast-bound gallium (YG). A standardized fracture-healing model with stable plate fixation was established for rat femoral. After 4-week stable fixation, animals were killed to prepare bones for Micro-CT, biomechanical testing, and histomorphometry. In addition, bone samples were obtained to evaluate the content of mineral substances in bones. Quantitative analysis of the bones from animals in the organic gallium group revealed significantly increased mineral contents compared to bones from OVX and SHAM groups. Micro-CT showed that treatment with yeast-incorporated gallium increased BV/TV and trabecular thickness and decreased trabecular separation in ovx animals. Histomorphometric evaluation demonstrated that YG increased callus area and callus bone formation. Yeast-bound gallium also improved the biomechanical properties of bone healing. In conclusion, this study suggests that yeast-incorporated gallium could promote fracture healing in ovariectomized rats.

  19. 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.

  20. Impaired Angiogenesis during Fracture Healing in GPCR Kinase 2 Interacting Protein-1 (GIT1) Knock Out Mice

    PubMed Central

    Menon, Prashanthi; Pang, Jinjiang; Ho, Hsin-Chiu; Shi, Shanshan; Xie, Chao; Smolock, Elaine; Yan, Chen; Zuscik, Michael J.; Berk, Bradford C.

    2014-01-01

    G protein coupled receptor kinase 2 (GRK2) interacting protein-1 (GIT1), is a scaffold protein that plays an important role in angiogenesis and osteoclast activity. We have previously demonstrated that GIT1 knockout (GIT1 KO) mice have impaired angiogenesis and dysregulated osteoclast podosome formation leading to a reduction in the bone resorbing ability of these cells. Since both angiogenesis and osteoclast-mediated bone remodeling are involved in the fracture healing process, we hypothesized that GIT1 participates in the normal progression of repair following bone injury. In the present study, comparison of fracture healing in wild type (WT) and GIT1 KO mice revealed altered healing in mice with loss of GIT1 function. Alcian blue staining of fracture callus indicated a persistence of cartilagenous matrix in day 21 callus samples from GIT1 KO mice which was temporally correlated with increased type 2 collagen immunostaining. GIT1 KO mice also showed a decrease in chondrocyte proliferation and apoptosis at days 7 and 14, as determined by PCNA and TUNEL staining. Vascular microcomputed tomography analysis of callus samples at days 7, 14 and 21 revealed decreased blood vessel volume, number, and connection density in GIT1 KO mice compared to WT controls. Correlating with this, VEGF-A, phospho-VEGFR2 and PECAM1 (CD31) were decreased in GIT1 KO mice, indicating reduced angiogenesis with loss of GIT1. Finally, calluses from GIT1 KO mice displayed a reduced number of tartrate resistant acid phosphatase-positive osteoclasts at days 14 and 21. Collectively, these results indicate that GIT1 is an important signaling participant in fracture healing, with gene ablation leading to reduced callus vascularity and reduced osteoclast number in the healing callus. PMID:24586541

  1. The Selective Serotonin Reuptake Inhibitor Fluoxetine Directly Inhibits Osteoblast Differentiation and Mineralization During Fracture Healing in Mice.

    PubMed

    Bradaschia-Correa, Vivian; Josephson, Anne M; Mehta, Devan; Mizrahi, Matthew; Neibart, Shane S; Liu, Chao; Kennedy, Oran D; Castillo, Alesha B; Egol, Kenneth A; Leucht, Philipp

    2016-11-21

    Chronic use of selective serotonin reuptake inhibitors (SSRIs) for the treatment of depression has been linked to osteoporosis. In this study, we investigated the effect of chronic SSRI use on fracture healing in two murine models of bone regeneration. First, we performed a comprehensive analysis of endochondral bone healing in a femur fracture model. C57/BL6 mice treated with fluoxetine, the most commonly prescribed SSRI, developed a normal cartilaginous soft-callus at 14 days after fracture and demonstrated a significantly smaller and biomechanically weaker bony hard-callus at 28 days. In order to further dissect the mechanism that resulted in a smaller bony regenerate, we used an intramembranous model of bone healing and revealed that fluoxetine treatment resulted in a significantly smaller bony callus at 7 and 14 days postinjury. In order to test whether the smaller bony regenerate following fluoxetine treatment was caused by an inhibition of osteogenic differentiation and/or mineralization, we employed in vitro experiments, which established that fluoxetine treatment decreases osteogenic differentiation and mineralization and that this effect is serotonin-independent. Finally, in a translational approach, we tested whether cessation of the medication would result in restoration of the regenerative potential. However, histologic and μCT analysis revealed non-union formation in these animals with fibrous tissue interposition within the callus. In conclusion, fluoxetine exerts a direct, inhibitory effect on osteoblast differentiation and mineralization, shown in two disparate murine models of bone repair. Discontinuation of the drug did not result in restoration of the healing potential, but rather led to complete arrest of the repair process. Besides the well-established effect of SSRIs on bone homeostasis, our study provides strong evidence that fluoxetine use negatively impacts fracture healing. © 2016 American Society for Bone and Mineral Research.

  2. Should orthopedic surgeons consider the effects of gabapentin administration on bone healing while treating a long bone fracture: experimental study in a rat model

    PubMed Central

    Sofu, Hakan; Kockara, Nizamettin; Aydin, Bahattin Kerem; Suleyman, Bahadir; Tayfur, Mahir; Malkoc, Ismail

    2016-01-01

    Objective: The main purpose of the present study was to assess the radiographic, histological, and mechanical effects of gabapentin on fracture healing in a rat model of femur fracture. Materials and methods: A standard transverse fracture of the mid-diaphysis was created. A total of 60 female Wistar-Albino rats with the mean age of 13.5 ± 1.2 weeks were used for this experimental trial. The rats were randomized into four groups with 15 animals included in each group. Group A and B were the control groups whereas C and D were the treatment groups. Drugs were delivered by oral gavage twice a day with the daily dosage calculated according to body surface area conversion to the human equivalent dosing regimen of 1200 mg/day. Radiographic, histological, and biomechanical evaluation was performed. Results: We could not detect any statistically significant difference between the control and gabapentin treatment groups according to the comparative assessment of radiographic scores on the 15th and 30th days. Although no significant differences were found between the groups on the 15th day, histological scores were better in the control group on the 30th day. According to the results of biomechanical testing, the fractured femurs resected from the control group exhibited significantly more strength on the 30th day. Conclusions: According to the data we acquired during the present study, administration of gabapentin negatively affects the fracture healing process especially in the aspects of histological progression as well as the biomechanical strength of the callus in a rat model. PMID:27801642

  3. Serum leptin, bone mineral density and the healing of long bone fractures in men with spinal cord injury.

    PubMed

    Wang, Lei; Liu, Linjuan; Pan, Zhanpeng; Zeng, Yanjun

    2015-11-16

    Previously reported fracture rates in patients with spinal cord injury range from 1% to 20%. However, the exact role of spinal cord injury in bone metabolism has not yet been clarified. In order to investigate the effects of serum leptin and bone mineral density on the healing of long bone fractures in men with spinal cord injury, 15 male SCI patients and 15 matched controls were involved in our study. The outcome indicated that at 4 and 8 weeks after bone fracture, callus production in patients with spinal cord injury was lower than that in controls. Besides, bone mineral density was significantly reduced at 2, 4 and 8 weeks. In addition, it was found that at each time point, patients with spinal cord injury had significantly higher serum leptin levels than controls and no association was found between serum leptin level and bone mineral density of lumbar vertebrae. Moreover, bone mineral density was positively correlated with bone formation in both of the groups. These findings suggest that in early phases i.e. week 4 and 8, fracture healing was impaired in patients with spinal cord injury and that various factors participated in the complicated healing process, such as hormonal and mechanical factors.

  4. Does Anticoagulant Medication Alter Fracture-Healing? A Morphological and Biomechanical Evaluation of the Possible Effects of Rivaroxaban and Enoxaparin Using a Rat Closed Fracture Model

    PubMed Central

    Prodinger, Peter Michael; Burgkart, Rainer; Kreutzer, Kilian; Liska, Franz; Pilge, Hakan; Schmitt, Andreas; Knödler, Martina; Holzapfel, Boris Michael; Hapfelmeier, Alexander; Tischer, Thomas; Bissinger, Oliver

    2016-01-01

    Low molecular weight heparin (LMWH) is routinely used to prevent thromboembolism in orthopaedic surgery, especially in the treatment of fractures or after joint-replacement. Impairment of fracture-healing due to increased bone-desorption, delayed remodelling and lower calcification caused by direct osteoclast stimulation is a well-known side effect of unfractioned heparin. However, the effect of LMWH is unclear and controversial. Recent studies strongly suggest impairment of bone-healing in-vitro and in animal models, characterized by a significant decrease in volume and quality of new-formed callus. Since October 2008, Rivaroxaban (Xarelto) is available for prophylactic use in elective knee- and hip-arthroplasty. Recently, some evidence has been found indicating an in vitro dose independent reduction of osteoblast function after Rivaroxaban treatment. In this study, the possible influence of Rivaroxaban and Enoxaparin on bone-healing in vivo was studied using a standardized, closed rodent fracture-model. 70 male Wistar-rats were randomized to Rivaroxaban, Enoxaparin or control groups. After pinning the right femur, a closed, transverse fracture was produced. 21 days later, the animals were sacrificed and both femora harvested. Analysis was done by biomechanical testing (three-point bending) and micro CT. Both investigated substances showed histomorphometric alterations of the newly formed callus assessed by micro CT analysis. In detail the bone (callus) volume was enhanced (sign. for Rivaroxaban) and the density reduced. The bone mineral content was enhanced accordingly (sign. for Rivaroxaban). Trabecular thickness was reduced (sign. for Rivaroxaban). Furthermore, both drugs showed significant enlarged bone (callus) surface and degree of anisotropy. In contrast, the biomechanical properties of the treated bones were equal to controls. To summarize, the morphological alterations of the fracture-callus did not result in functionally relevant deficits. PMID:27455072

  5. Numerical simulation research to both the external fixation surgery scheme of intertrochanteric fracture and the healing process, and its clinical application.

    PubMed

    Wang, Xian-Kang; Ye, Jin-Duo; Gu, Fu-Shun; Wang, Ai-guo; Zhang, Chun-Qiu; Tian, Qian-Qian; Li, Xue; Dong, Li-Min

    2014-01-01

    In this paper, the single arm external fixation of intertrochanteric fracture healing process after surgery was simulated to obtain a postoperative fracture healing and stress distribution in the external fixator. Firstly CT images of intertrochanteric fracture are reconstructed into the femur solid model. Then based, the external fixator is installed on the model, which lastly formed a finite element model of unilateral external fixation for intertrochanteric fracture. The calculated results show: during the beginning of the fracture healing, there is much higher stress in both screws and femur in the model with solid screws than that in the model with hollow screw. The stress of the femur in the model with hollow screw is more evenly. During the middle time of Fracture healing, stress in the femoral head significantly decreases. And the stress at fracture site gradually increased with the healing occurrence. According to the results, the authors designed hollow screws to use external fixation surgery. Surgery confirmed that the use of hollow screws in fractures treatment can satisfy the strength requirements, and can effectively reduce operative time, less patient suffering. The research for external fixation can provide a reference, and promote the use of external fixation hollow screws.

  6. Stress-Shielding Effect of Nitinol Swan-Like Memory Compressive Connector on Fracture Healing of Upper Limb

    NASA Astrophysics Data System (ADS)

    Fu, Q. G.; Liu, X. W.; Xu, S. G.; Li, M.; Zhang, C. C.

    2009-08-01

    In this article, the stress-shielding effect of a Nitinol swan-like memory compressive connector (SMC) is evaluated. Patients with fracture healing of an upper limb after SMC internal fixation or stainless steel plate fixation were randomly selected and observed comparatively. With the informed consent of the SMC group, minimal cortical bone under the swan-body and swan-neck was harvested; and in the steel plate fixation group, minimal cortical bone under the steel plate and opposite side to the steel plate was also harvested for observation. Main outcome measurements were taken such as osteocyte morphology, Harversian canal histological observation under light microscope; radiographic observation of fracture healing, and computed tomography quantitative scanning of cortical bone. As a conclusion, SMC has a lesser stress-shielding effect to fixed bone than steel plate. Finally, the mechanism of the lesser stress-shielding effect of SMC is discussed.

  7. Osteoblast-Specific Loss of IGF1R Signaling Results in Impaired Endochondral Bone Formation During Fracture Healing.

    PubMed

    Wang, Tao; Wang, Yongmei; Menendez, Alicia; Fong, Chak; Babey, Muriel; Tahimic, Candice G T; Cheng, Zhiqiang; Li, Alfred; Chang, Wenhan; Bikle, Daniel D

    2015-09-01

    Insulin-like growth factors (IGFs) are important local regulators during fracture healing. Although IGF1 deficiency is known to increase the risk of delayed union or non-union fractures in the elderly population, the underlying mechanisms that contribute to this defect remains unclear. In this study, IGF1 signaling during fracture healing was investigated in an osteoblast-specific IGF1 receptor (IGF1R) conditional knockout (KO) mouse model. A closed tibial fracture was induced in IGF1R(flox/flox) /2.3-kb α1(1)-collagen-Cre (KO) and IGF1R(flox/flox) (control) mice aged 12 weeks. Fracture callus samples and nonfractured tibial diaphysis were collected and analyzed by μCT, histology, immunohistochemistry, histomorphometry, and gene expression analysis at 10, 15, 21, and 28 days after fracture. A smaller size callus, lower bone volume accompanied by a defect in mineralization, bone microarchitectural abnormalities, and a higher cartilage volume were observed in the callus of these KO mice. The levels of osteoblast differentiation markers (osteocalcin, alkaline phosphatase, collagen 1α1) were significantly reduced, but the early osteoblast transcription factor runx2, as well as chondrocyte differentiation markers (collagen 2α1 and collagen 10α1) were significantly increased in the KO callus. Moreover, increased numbers of osteoclasts and impaired angiogenesis were observed during the first 15 days of fracture repair, but decreased numbers of osteoclasts were found in the later stages of fracture repair in the KO mice. Although baseline nonfractured tibias of KO mice had decreased trabecular and cortical bone compared to control mice, subsequent studies with mice expressing the 2.3-kb α1(1)-collagen-Cre ERT2 construct and given tamoxifen at the time of fracture and so starting with comparable bone levels showed similar impairment in fracture repair at least initially. Our data indicate that not only is the IGF1R in osteoblasts involved in osteoblast differentiation

  8. Healing of 400 intra-alveolar root fractures. 1. Effect of pre-injury and injury factors such as sex, age, stage of root development, fracture type, location of fracture and severity of dislocation.

    PubMed

    Andreasen, J O; Andreasen, F M; Mejàre, I; Cvek, M

    2004-08-01

    This retrospective study consisted of 400 root-fractured, splinted or non-splinted incisors in young individuals aged 7-17 years (mean = 11.5 +/- 2.7 SD) who were treated in the period 1959-1995 at the Department of Pediatric Dentistry, Eastman Dental Institute, Stockholm. Four hundred of these root fractures were diagnosed at the time of injury; and 344 teeth were splinted with either cap-splints, orthodontic appliances, bonded metal wires, proximal bonding with composite resin or bonding with a Kevlar or glass fiber splint. In 56 teeth, no splinting was carried out for various reasons. In the present study, only pre-injury and injury factors were analyzed. In a second study, treatment variables will be analyzed. The average observation period was 3.1 years +/- 2.6 SD. The clinical and radiographic findings showed that 120 teeth out of 400 teeth (30%) had healed by hard tissue fusion of the fragments. Interposition of periodontal ligament (PDL) and bone between fragments was found in 22 teeth (5%), whereas interposition of PDL alone was found in 170 teeth (43%). Finally, non-healing, with pulp necrosis and inflammatory changes between fragments, was seen in 88 teeth (22%). In a univariate and multivariate stratified analysis, a series of clinical factors were analyzed for their relation to the healing outcome with respect to pulp healing vs. pulp necrosis and type of healing (hard tissue vs. interposition of bone and/or PDL or pulp necrosis). Young age, immature root formation and positive pulp sensibility at the time of injury were found to be significantly and positively related to both pulpal healing and hard tissue repair of the fracture. The same applied to concussion or subluxation (i.e. no displacement) of the coronal fragment compared to extrusion or lateral luxation (i.e. displacement). Furthermore, no mobility vs. mobility of the coronal fragment. Healing was progressively worsened with increased millimeter diastasis between fragments. Sex was a

  9. Functional Outcomes, Morbidity, Mortality, and Fracture Healing in 58 Consecutive Patients with Geriatric Odontoid Fracture Treated with Cervical Collar or Posterior Fusion

    PubMed Central

    Molinari, William J.; Molinari, Robert W.; Khera, Oner A.; Gruhn, William L.

    2013-01-01

    Controversy exists as to the most effective management option for elderly patients with type II odontoid fractures. The purpose of this study is to evaluate outcomes associated with rigid cervical collar and posterior fusion surgery. Patients with ≥ 50% odontoid displacement were treated with posterior fusion surgery including C1–2 (PSF group, n = 25, average age = 80 years). Patients with < 50% odontoid displacement were treated with a rigid cervical collar for 12 weeks (collar group, n = 33, average age = 83 years). These inhomogeneous groups were followed for an average of 14 months. Fracture healing rates were higher in the operative group (28% versus 6%). Neck Disability Index scores were slightly lower in the nonoperative group (13 versus 18.3, p = 0.23). Analogue pain scores were also slightly lower in the nonoperative group (1.3 versus 1.9, p = 0.26). The mortality rate was 12.5% in the collar group and 20% in the operative group. Complications were higher in the operative group (24% versus 6%). Rates of type II odontoid facture healing and stability appear to be higher in geriatric patients treated with posterior fusion surgery. Fracture healing and stability did not correlate with improved outcomes with respect to levels of pain, function, and satisfaction. Mortality and complication rates are lower in those patients with lesser-displaced fractures who are treated with a cervical collar and early mobilization. PMID:24436848

  10. Systemic and Local Administration of Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells Promotes Fracture Healing in Rats.

    PubMed

    Huang, Shuo; Xu, Liangliang; Zhang, Yifeng; Sun, Yuxin; Li, Gang

    2015-01-01

    Mesenchymal stem cells (MSCs) are immune privileged and a cell source for tissue repair. Previous studies showed that there is systemic mobilization of osteoblastic precursors to the fracture site. We hypothesized that both systemic and local administration of allogeneic MSCs may promote fracture healing. Bone marrow-derived MSCs and skin fibroblasts were isolated from GFP Sprague-Dawley rats, cultured, and characterized. Closed transverse femoral fracture with internal fixation was established in 48 adult male Sprague-Dawley rats, which were randomly assigned into four groups receiving PBS injection, MSC systemic injection, fibroblast systemic injection, and MSC fracture site injection; 2 × 10(6) cells were injected at 4 days after fracture. All animals were sacrificed at 5 weeks after fracture; examinations included weekly radiograph, micro-CT, mechanical testing, histology, immunohistochemistry, and double immunofluorescence. The callus size of MSC injection groups was significantly larger among all the groups. Radiographs and 3D reconstruction images showed that the fracture gaps united in the MSC injected groups, while gaps were still seen in the fibroblast and PBS injection groups. The mechanical properties were significantly higher in the MSC injection groups than those in the fibroblast and PBS groups, but no difference was found between the MSC local and systemic injection groups. Immunohistochemistry and double immunofluorescence demonstrated that GFP-positive MSCs were present in the callus in the MSC injection groups at 5 weeks after fracture, and some differentiated into osteoblasts. Quantitative analysis revealed the number of GFP-positive cells in the callus in the MSC systemic injection group was significantly lower than that of the MSC local injection group. The proportion of GFP osteoblasts in GFP-positive cells in the MSC systemic injection group was significantly lower than that of the MSC local injection group. These findings provide critical

  11. [Sonographic follow-up of secondary fracture healing. Initial experiences with morphologic and semiquantitative assessment of periosteal callus formation].

    PubMed

    Hannesschläger, G; Reschauer, R

    1990-08-01

    We report on the contribution of real-time sonography in comparison to plain radiographs to the assessment of fracture healing of 121 patients suffering fractures of the long bones of the lower limbs. Sonographic morphology of periosteal callus metamorphosis shows basically a persistent increase of echogenicity representing the temporal range from fracture haematoma to the "woven bone". Further criteria are the homogeneity of structure and the development of a marginal interface. Nonunion radiologically classified into hypertrophic and atrophic types may also be differentiated by sonographic criteria and may influence proper orthopaedic management. Regarding sonographic methods using an A-mode amplitude signal, the morphologic assessment of callus metamorphosis is more likely to be translated into clinical practice. Although it yields a variety of information, sonography will be unable to replace radiography due to methodical limitations.

  12. Inhibition of GSK-3β rescues the impairments in bone formation and mechanical properties associated with fracture healing in osteoblast selective connexin 43 deficient mice.

    PubMed

    Loiselle, Alayna E; Lloyd, Shane A J; Paul, Emmanuel M; Lewis, Gregory S; Donahue, Henry J

    2013-01-01

    Connexin 43 (Cx43) is the most abundant gap junction protein in bone and is required for osteoblastic differentiation and bone homeostasis. During fracture healing, Cx43 is abundantly expressed in osteoblasts and osteocytes, while Cx43 deficiency impairs bone formation and healing. In the present study we selectively deleted Cx43 in the osteoblastic lineage from immature osteoblasts through osteocytes and tested the hypothesis that Cx43 deficiency results in delayed osteoblastic differentiation and impaired restoration of biomechanical properties due to attenuated β-catenin expression relative to wild type littermates. Here we show that Cx43 deficiency results in alterations in the mineralization and remodeling phases of healing. In Cx43 deficient fractures the mineralization phase is marked by delayed expression of osteogenic genes. Additionally, the decrease in the RankL/Opg ratio, osteoclast number and osteoclast size suggest decreased osteoclast bone resorption and remodeling. These changes in healing result in functional deficits as shown by a decrease in ultimate torque at failure. Consistent with these impairments in healing, β-catenin expression is attenuated in Cx43 deficient fractures at 14 and 21 days, while Sclerostin (Sost) expression, a negative regulator of bone formation is increased in Cx43cKO fractures at 21 days, as is GSK-3β, a key component of the β-catenin proteasomal degradation complex. Furthermore, we show that alterations in healing in Cx43 deficient fractures can be rescued by inhibiting GSK-3β activity using Lithium Chloride (LiCl). Treatment of Cx43 deficient mice with LiCl restores both normal bone formation and mechanical properties relative to LiCl treated WT fractures. This study suggests that Cx43 is a potential therapeutic target to enhance fracture healing and identifies a previously unknown role for Cx43 in regulating β-catenin expression and thus bone formation during fracture repair.

  13. SDF-1/CXCR4 axis in Tie2-lineage cells including endothelial progenitor cells contributes to bone fracture healing.

    PubMed

    Kawakami, Yohei; Ii, Masaaki; Matsumoto, Tomoyuki; Kuroda, Ryosuke; Kuroda, Tomoya; Kwon, Sang-Mo; Kawamoto, Atsuhiko; Akimaru, Hiroshi; Mifune, Yutaka; Shoji, Taro; Fukui, Tomoaki; Kurosaka, Masahiro; Asahara, Takayuki

    2015-01-01

    CXC chemokine receptor 4 (CXCR4) is a specific receptor for stromal-derived-factor 1 (SDF-1). SDF-1/CXCR4 interaction is reported to play an important role in vascular development. On the other hand, the therapeutic potential of endothelial progenitor cells (EPCs) in fracture healing has been demonstrated with mechanistic insight of vasculogenesis/angiogenesis and osteogenesis enhancement at sites of fracture. The purpose of this study was to investigate the influence of the SDF-1/CXCR4 pathway in Tie2-lineage cells (including EPCs) in bone formation. We created CXCR4 gene conditional knockout mice using the Cre/loxP system and set two groups of mice: Tie2-Cre(ER) CXCR4 knockout mice (CXCR4(-/-) ) and wild-type mice (WT). We report here that in vitro, EPCs derived from of CXCR4(-/-) mouse bone marrow demonstrated severe reduction of migration activity and EPC colony-forming activity when compared with those derived from WT mouse bone marrow. In vivo, radiological and morphological examinations showed fracture healing delayed in the CXCR4(-/-) group and the relative callus area at weeks 2 and 3 was significantly smaller in CXCR4(-/-) group mice. Quantitative analysis of capillary density at perifracture sites also showed a significant decrease in the CXCR4(-/-) group. Especially, CXCR4(-/-) group mice demonstrated significant early reduction of blood flow recovery at fracture sites compared with the WT group in laser Doppler perfusion imaging analysis. Real-time RT-PCR analysis showed that the gene expressions of angiogenic markers (CD31, VE-cadherin, vascular endothelial growth factor [VEGF]) and osteogenic markers (osteocalcin, collagen 1A1, bone morphogenetic protein 2 [BMP2]) were lower in the CXCR4(-/-) group. In the gain-of-function study, the fracture in the SDF-1 intraperitoneally injected WT group healed significantly faster with enough callus formation compared with the SDF-1 injected CXCR4(-/-) group. We demonstrated that an EPC SDF-1/CXCR4 axis plays an

  14. The transcriptome of fracture healing defines mechanisms of coordination of skeletal and vascular development during endochondral bone formation.

    PubMed

    Grimes, Rachel; Jepsen, Karl J; Fitch, Jennifer L; Einhorn, Thomas A; Gerstenfeld, Louis C

    2011-11-01

    Fractures initiate one round of endochondral bone formation in which callus cells differentiate in a synchronous manner that temporally phenocopies the spatial variation of endochondral development of a growth plate. During fracture healing C57BL/6J (B6) mice initiate chondrogenesis earlier and develop more cartilage than bone, whereas C3H/HeJ (C3H) mice initiate osteogenesis earlier and develop more bone than cartilage. Comparison of the transcriptomes of fracture healing in these strains of mice identified the genes that showed differences in timing and quantitative expression and encode for the variations in endochondral bone development of the two mouse strains. The complement of strain-dependent differences in gene expression was specifically associated with ontologies related to both skeletal and vascular formation. Moreover, the differences in gene expression associated with vascular tissue formation during fracture healing were correlated with the underlying differences in development and function of the cardiovascular systems of these two strains of mice. Significant differences in gene expression associated with bone morphogenetic protein/transforming growth factor β (BMP/TGF-β) signal-transduction pathways were identified between the two strains, and a network of differentially expressed genes specific to the MAP kinase cascade was further defined as a subset of the genes of the BMP/TGF-β pathways. Other signal-transduction pathways that showed significant strain-specific differences in gene expression included the RXR/PPAR and G protein-related pathways. These data identify how bone and vascular regeneration are coordinated through expression of common sets of transcription and morphogenetic factors and suggest that there is heritable linkage between vascular and skeletal tissue development during postnatal regeneration.

  15. Chondrocytes transdifferentiate into osteoblasts in endochondral bone during development, postnatal growth and fracture healing in mice.

    PubMed

    Zhou, Xin; von der Mark, Klaus; Henry, Stephen; Norton, William; Adams, Henry; de Crombrugghe, Benoit

    2014-12-01

    One of the crucial steps in endochondral bone formation is the replacement of a cartilage matrix produced by chondrocytes with bone trabeculae made by osteoblasts. However, the precise sources of osteoblasts responsible for trabecular bone formation have not been fully defined. To investigate whether cells derived from hypertrophic chondrocytes contribute to the osteoblast pool in trabecular bones, we genetically labeled either hypertrophic chondrocytes by Col10a1-Cre or chondrocytes by tamoxifen-induced Agc1-CreERT2 using EGFP, LacZ or Tomato expression. Both Cre drivers were specifically active in chondrocytic cells and not in perichondrium, in periosteum or in any of the osteoblast lineage cells. These in vivo experiments allowed us to follow the fate of cells labeled in Col10a1-Cre or Agc1-CreERT2 -expressing chondrocytes. After the labeling of chondrocytes, both during prenatal development and after birth, abundant labeled non-chondrocytic cells were present in the primary spongiosa. These cells were distributed throughout trabeculae surfaces and later were present in the endosteum, and embedded within the bone matrix. Co-expression studies using osteoblast markers indicated that a proportion of the non-chondrocytic cells derived from chondrocytes labeled by Col10a1-Cre or by Agc1-CreERT2 were functional osteoblasts. Hence, our results show that both chondrocytes prior to initial ossification and growth plate chondrocytes before or after birth have the capacity to undergo transdifferentiation to become osteoblasts. The osteoblasts derived from Col10a1-expressing hypertrophic chondrocytes represent about sixty percent of all mature osteoblasts in endochondral bones of one month old mice. A similar process of chondrocyte to osteoblast transdifferentiation was involved during bone fracture healing in adult mice. Thus, in addition to cells in the periosteum chondrocytes represent a major source of osteoblasts contributing to endochondral bone formation in vivo.

  16. Superior Potential of CD34-Positive Cells Compared to Total Mononuclear Cells for Healing of Nonunion Following Bone Fracture.

    PubMed

    Fukui, Tomoaki; Mifune, Yutaka; Matsumoto, Tomoyuki; Shoji, Taro; Kawakami, Yohei; Kawamoto, Atsuhiko; Ii, Masaaki; Akimaru, Hiroshi; Kuroda, Tomoya; Horii, Miki; Yokoyama, Ayumi; Alev, Cantas; Kuroda, Ryosuke; Kurosaka, Masahiro; Asahara, Takayuki

    2015-01-01

    We recently demonstrated that the local transplantation of human peripheral blood (PB) CD34(+) cells, an endothelial/hematopoietic progenitor cell-rich population, contributes to fracture repair via vasculogenesis/angiogenesis and osteogenesis. Human PB mononuclear cells (MNCs) are also considered a potential cell fraction for neovascularization. We have previously shown the feasibility of human PB MNCs to enhance fracture healing. However, there is no report directly comparing the efficacy for fracture repair between CD34(+) cells and MNCs. In addition, an unhealing fracture model, which does not accurately resemble a clinical setting, was used in our previous studies. To overcome these issues, we compared the capacity of human granulocyte colony-stimulating factor-mobilized PB (GM-PB) CD34(+) cells and human GM-PB MNCs in a nonunion model, which more closely resembles a clinical setting. First, the effect of local transplantation of 1 × 10(5) GM-PB CD34(+) cells (CD34(+) group), 1 × 10(7) GM-PB MNCs (containing approximately 1 × 10(5) GM-PB CD34(+) cells) (MNC group), and phosphate-buffered saline (PBS) (PBS group) on nonunion healing was compared. Similar augmentation of blood flow recovery at perinonunion sites was observed in the CD34(+) and MNC groups. Meanwhile, a superior effect on nonunion repair was revealed by radiological, histological, and functional assessment in the CD34(+) group compared with the other groups. Moreover, through in vivo and in vitro experiments, excessive inflammation induced by GM-PB MNCs was confirmed and believed to be one of the mechanisms underlying this potency difference. These results strongly suggest that local transplantation of GM-PB CD34(+) cells is a practical and effective strategy for treatment of nonunion after fracture.

  17. 5. Accelerated Fracture Healing Targeting Periosteal Cells: Possibility of Combined Therapy of Low-Intensity Pulsed Ultrasound (LIPUS), Bone Graft, and Growth Factor (bFGF).

    PubMed

    Uchida, Kentaro; Urabe, Ken; Naruse, Koji; Mikuni-Takagaki, Yuko; Inoue, Gen; Takaso, Masashi

    2016-08-01

    We have studied the mechanism of fracture healing, and the effect of LIPUS, bone graft and growth factor on accelerating fracture healing. We present here the results of our research. To examine callus formation cells in fracture healing, we made marrow GFP chimera mice and a fracture model of marrow mesenchymal stem cell GFP chimera mice. It was demonstrated that periosteal cells were essential for callus formation. We focused on periosteal cells and examined the effect of LIPUS. In an in vitro experiment using a cultured part of the femur, LIPUS promoted ossification of the periosteal tissue. Further, LIPUS accelerated VEGF expression in the experiment using the femoral fracture model of mice. From these results, it was suggested that activation of periosteal cells might play a role in the fracture healing mechanism of LIPUS. Next, we discussed the possibility of combined therapy of LIPUS, bone graft and growth factor. Therapy involving the topical administration of bFGF using a controlled release system and bone graft could promote callus formation. In addition, LIPUS was able to promote membranaceous ossification after the bone graft. It was suggested that combined therapy of LIPUS, bone graft and bFGF could be a new option for treating fractures.

  18. The Effects of Targeted Deliveries of Lovastatin and Tocotrienol on Ossification-Related Gene Expressions in Fracture Healing in an Osteoporosis Rat Model

    PubMed Central

    Ibrahim, Nurul ‘Izzah; Mohamed, Norazlina; Soelaiman, Ima Nirwana; Shuid, Ahmad Nazrun

    2015-01-01

    Osteoporotic drugs are used to prevent fragility fractures, but their role in fracture healing still remains unknown. Thus, alternative agents with suitable mode of delivery are needed to promote fracture healing. This study was performed to investigate the effects of direct deliveries of lovastatin and tocotrienol to fracture sites on ossification-related gene expression in fracture healing in a postmenopausal osteoporosis model. Forty-eight Sprague Dawley female rats were divided into six groups. Group I comprised the sham-operated rats, while Groups II–VI were ovariectomized rats. After 8 weeks, the right tibiae of all rats were fractured and stabilized. Group I and Group II were given two single injections of lovastatin and tocotrienol carriers. Group III was given an estrogen preparation at 64.5 µg/kg daily via oral gavages. Group IV was injected with lovastatin particles (750 µg/kg), while Group V was injected with tocotrienol particles (60 mg/kg). Group VI received two single injections of 750 µg/kg lovastatin particles and 60 mg/kg tocotrienol particles. After 4 weeks, the gene expressions were measured. Group VI showed significantly higher gene expressions of osteocalcin, BMP-2, VEGF-α, and RUNX-2 compared to Group II. In conclusion, combined treatment of lovastatin and tocotrienol upregulated the expression of genes related to fracture healing. PMID:26501302

  19. Fractures Due to Gunshot Wounds: Do Retained Bullet Fragments Affect Union?

    PubMed Central

    Riehl, John T.; Connolly, Keith; Haidukewych, George; Koval, Ken

    2015-01-01

    Background Many types of projectiles, including modern hollow point bullets, fragment into smaller pieces upon impact, particularly when striking bone. This study was performed to examine the effect on time to union with retained bullet material near a fracture site in cases of gunshot injury. Methods All gunshot injuries operatively treated with internal fixation at a Level 1 Trauma Center between March 2008 and August 2011 were retrospectively reviewed. Retained bullet load near the fracture site was calculated based on percentage of material retained compared to the cortical diameter of the involved bone. Analyses were performed to assess the effect of the lead-cortical ratio and amount of comminution on time to fracture union. Results Thirty-two patients (34 fractures) met the inclusion criteria, with an equal number of comminuted (17) and non-comminuted fractures (17). Seventeen of 34 fractures (50%) united within 4 months, 16/34 (47%) developed a delayed union, and 1/34 (3%) developed a nonunion requiring revision surgery. Sixteen of 17 fractures (94%) that united by 4 months had a cumulative amount of bullet fragmentation retained near the fracture site of less than 20% of the cortical diameter. Nine out of 10 fractures (90%) with retained fragments near the fracture site was equal to or exceeding 20% of the cortical diameter had delayed or nonunion. Fracture comminution had no effect on time to union. Conclusions The quantity of retained bullet material near the fracture site was more predictive of the rate of fracture union than was comminution. Fractures with bullet fragmentation equal to or exceeding 20% of the cortical width demonstrated a significantly higher rate of delayed union/nonunion compared to those fractures with less retained bullet material, which may indicate a local cytotoxic effect from lead on bone healing. These findings may influence decisions on timing of secondary surgeries. Level of Evidence Level III PMID:26361445

  20. 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

  1. Interaction of age and mechanical stability on bone defect healing: an early transcriptional analysis of fracture hematoma in rat.

    PubMed

    Ode, Andrea; Duda, Georg N; Geissler, Sven; Pauly, Stephan; Ode, Jan-Erik; Perka, Carsten; Strube, Patrick

    2014-01-01

    Among other stressors, age and mechanical constraints significantly influence regeneration cascades in bone healing. Here, our aim was to identify genes and, through their functional annotation, related biological processes that are influenced by an interaction between the effects of mechanical fixation stability and age. Therefore, at day three post-osteotomy, chip-based whole-genome gene expression analyses of fracture hematoma tissue were performed for four groups of Sprague-Dawley rats with a 1.5-mm osteotomy gap in the femora with varying age (12 vs. 52 weeks - biologically challenging) and external fixator stiffness (mechanically challenging). From 31099 analysed genes, 1103 genes were differentially expressed between the six possible combinations of the four groups and from those 144 genes were identified as statistically significantly influenced by the interaction between age and fixation stability. Functional annotation of these differentially expressed genes revealed an association with extracellular space, cell migration or vasculature development. The chip-based whole-genome gene expression data was validated by q-RT-PCR at days three and seven post-osteotomy for MMP-9 and MMP-13, members of the mechanosensitive matrix metalloproteinase family and key players in cell migration and angiogenesis. Furthermore, we observed an interaction of age and mechanical stimuli in vitro on cell migration of mesenchymal stromal cells. These cells are a subpopulation of the fracture hematoma and are known to be key players in bone regeneration. In summary, these data correspond to and might explain our previously described biomechanical healing outcome after six weeks in response to fixation stiffness variation. In conclusion, our data highlight the importance of analysing the influence of risk factors of fracture healing (e.g. advanced age, suboptimal fixator stability) in combination rather than alone.

  2. Instantaneous healing of micro-fractures during coseismic slip: Evidence from microstructure and Ti in quartz geochemistry within an exhumed pseudotachylyte-bearing fault in tonalite

    NASA Astrophysics Data System (ADS)

    Bestmann, Michel; Pennacchioni, Giorgio; Mostefaoui, Smail; Göken, Mathias; de Wall, Helga

    2016-06-01

    Exhumed faults within the tonalitic Adamello pluton (Southern Alps) were seismic at depth as indicated by the presence of pseudotachylytes (solidified friction-induced melts). During cooling of tonalite, early-formed joints were first exploited by localized ductile shear zones associated with deposition of quartz veins (at ~ 500 °C), and later by pseudotachylyte-bearing cataclastic faults (at ~ 250-300 °C ambient temperature). Adjacent to pseudotachylytes, quartz of the host tonalite shows pervasive thin (1-10 μm wide) healed micro-fractures and ultra-fine (1-2 μm grain size) recrystallized aggregates along micro-shear zones. Under cathodoluminescence (CL) the healed micro-fractures have a darker gray shade than the host "magmatic" quartz that reflects a change in Ti concentrations ([Ti]) as indicated by NanoSIMS measurements. [Ti] vary from 35-55 ppm in the CL-lighter host quartz to 10-13 ppm along the CL-darker healed micro-fractures. These [Ti] were inherited by the ultra-fine recrystallized aggregates that overprinted both the magmatic quartz and the healed micro-fractures during the high temperature transient related to frictional seismic slip. Based on Ti-in-quartz thermometry, we infer that micro-fracture healing occurred at higher temperatures than the ambient temperatures of faulting (250-300 °C at 0.2 GPa), for which [Ti] < 1 ppm would be expected. Micro-fracture healing can be ascribed to the stage of seismic slip of faults on the basis of the observation that: (i) they are absent in the host rock surrounding high-T quartz veins un-exploited by faults; and (ii) they locally occur at the tip of pseudotachylyte injection veins filling new fractures developed during the propagation of the earthquake rupture. The relatively high [Ti] of micro-fractures are therefore interpreted to reflect quartz healing by a fluid overheated during the initial stages of frictional seismic slip and escaping from fault surface through the damage zone. This suggests that

  3. Influence of internal fixator flexibility on murine fracture healing as characterized by mechanical testing and microCT imaging.

    PubMed

    Steck, Roland; Ueno, Masaki; Gregory, Laura; Rijken, Noortje; Wullschleger, Martin E; Itoman, Moritoshi; Schuetz, Michael A

    2011-08-01

    Mechanically well-defined stabilization systems have only recently become available, providing standardized conditions for studying the role of the mechanical environment on mouse bone fracture healing. The aim of this study was to characterize the time course of strength recovery and callus development of mouse femoral osteotomies stabilized with either low or high flexibility (in bending and torsion) internal fixation plates. Animals were euthanized and femora excised at 14, 21, and 28 days post-osteotomy for microCT analysis and torsional strength testing. While a larger mineralized callus was observed in osteotomies under more flexible conditions at all time points, the earlier bridging of the mineralized callus under less flexible conditions by 1 week resulted in an earlier recovery of torsional strength in mice stabilized with low flexibility fixation. Ultimate torque values for these bones were significantly higher at 14 and 21 days post-osteotomy compared to bones with the more flexible stabilization. Our study confirms the high reproducibility of the results that are achieved with this new implant system, therefore making it ideal for studying the influence of the mechanical environment on murine fracture healing under highly standardized conditions.

  4. Demineralized Bone Matrix Add-On for Acceleration of Bone Healing in Atypical Subtrochanteric Femoral Fracture: A Consecutive Case-Control Study

    PubMed Central

    Kulachote, Noratep; Sirisreetreerux, Norachart; Chanplakorn, Pongsthorn; Fuangfa, Praman; Suphachatwong, Chanyut; Wajanavisit, Wiwat

    2016-01-01

    Background. Delayed union and nonunion are common complications in atypical femoral fractures (AFFs) despite having good fracture fixation. Demineralized bone matrix (DBM) is a successfully proven method for enhancing fracture healing of the long bone fracture and nonunion and should be used in AFFs. This study aimed to compare the outcome after subtrochanteric AFFs (ST-AFFs) fixation with and without DBM. Materials and Methods. A prospective study was conducted on 9 ST-AFFs patients using DBM (DBM group) during 2013-2014 and compared with a retrospective consecutive case series of ST-AFFs patients treated without DBM (2010–2012) (NDBM group, 9 patients). All patients were treated with the same standard guideline and followed up until fractures completely united. Postoperative outcomes were then compared. Results. DBM group showed a significant shorter healing time than NDBM group (28.1 ± 14.4 versus 57.9 ± 36.8 weeks, p = 0.04). Delayed union was found in 4 patients (44%) in DBM group compared with 7 patients (78%) in NDBM group (p > 0.05). No statistical difference of nonunion was demonstrated between both groups (DBM = 1 and NDBM = 2, p > 0.05). Neither postoperative infection nor severe local tissue reaction was found. Conclusions. DBM is safe and effective for accelerating the fracture healing in ST-AFFx and possibly reduces nonunion after fracture fixation. Trial registration number is TCTR20151021001. PMID:27022610

  5. Instantaneous healing of micro-fractures during coseismic slip: evidence from microstructure and Ti in quartz geochemistry within an exhumed pseudotachylyte-bearing fault in tonalite

    NASA Astrophysics Data System (ADS)

    Bestmann, Michel; Pennacchioni, Giorgio; Moustefaoui, Smail; Göken, Mathias; de Wall, Helga

    2016-04-01

    This study presents detailed microstructural and trace element (Ti) analysis of quartz deformation microstructures associated with seismic slip in order to constrain the complex deformation history during an earthquake event. Exhumed faults within the tonalitic Adamello pluton (Southern Alps) were seismic at depth as indicated by the presence of pseudotachylytes (solidified friction-induced melts). During cooling of tonalite, early-formed joints were first exploited by localized ductile shear zones associated with deposition of quartz veins (at ~500 °C), and later by pseudotachylyte-bearing cataclastic faults (at ~250-300 °C ambient temperature). Adjacent to pseudotachylytes, quartz of the host tonalite shows pervasive thin (1-10 μm wide) healed micro-fractures and ultra-fine (1-2 μm grain size) recrystallized aggregates along micro-shear zones. Under cathodoluminescence (CL) the healed micro-fractures have darker gray shade than the host "magmatic" quartz that reflects a change in Ti concentrations [Ti] as indicated by NanoSIMS measurements. [Ti] vary from 35-55 ppm of the CL-lighter host quartz to 11-15 ppm along the CL-darker healed micro-fractures. These [Ti] were inherited by overprinting recrystallization aggregates developed during the high temperature transient related to frictional seismic slip. Based on Ti-in-quartz thermometry, micro-fracture healing occurred at higher temperatures than the ambient temperatures of faulting (250-300 °C at 0.2 GPa). Micro-fracture healing can be ascribed to the stage of seismic slip of faulting on the basis of the observation that: (i) they are absent in the host rock surrounding earlier high-T quartz veins un-exploited by faults; (ii) they locally occur at the tip of pseudotachylyte injection veins filling new fractures developed during the propagation of the earthquake rupture tip. The relatively high [Ti] of micro-fractures are interpreted to reflect quartz healing by a fluid overheated during the initial stages of

  6. Rescue of Impaired Fracture Healing in COX-2−/− Mice via Activation of Prostaglandin E2 Receptor Subtype 4

    PubMed Central

    Xie, Chao; Liang, Bojian; Xue, Ming; Lin, Angela S.P.; Loiselle, Alayna; Schwarz, Edward M.; Guldberg, Robert E.; O'Keefe, Regis J.; Zhang, Xinping

    2009-01-01

    Although the essential role of cyclooxygenase (COX)-2 in fracture healing is known, the targeted genes and molecular pathways remain unclear. Using prostaglandin E2 receptor (EP)2 and EP4 agonists, we examined the effects of EP receptor activation in compensation for the lack of COX-2 during fracture healing. In a fracture-healing model, COX-2−/− mice showed delayed initiation and impaired endochondral bone repair, accompanied by a severe angiogenesis deficiency. The EP4 agonist markedly improved the impaired healing in COX-2−/− mice, as evidenced by restoration of bony callus formation on day 14, a near complete reversal of bone formation, and an approximately 70% improvement of angiogenesis in the COX-2−/− callus. In comparison, the EP2 agonist only marginally enhanced bone formation in COX-2−/− mice. To determine the differential roles of EP2 and EP4 receptors on COX-2-mediated fracture repair, the effects of selective EP agonists on chondrogenesis were examined in E11.5 long-term limb bud micromass cultures. Only the EP4 agonist significantly increased cartilage nodule formation similar to that observed during prostaglandin E2 treatment. The prostaglandin E2/EP4 agonist also stimulated MMP-9 expression in bone marrow stromal cell cultures. The EP4 agonist further restored the reduction of MMP-9 expression in the COX-2−/− fracture callus. Taken together, our studies demonstrate that EP2 and EP4 have differential functions during endochondral bone repair. Activation of EP4, but not EP2 rescued impaired bone fracture healing in COX-2−/− mice. PMID:19628768

  7. Investigation of the Microstructural Mechanism of Relaxation and Fracture Healing in Asphalt

    DTIC Science & Technology

    1993-04-12

    FOR THE AIR FORCE OFFICE OF SCIENTIFIC RESEARCH FINAL REPORT GRANT NO. AFOSR-89-0520 DTIC * APRIL 12, 1993 uN 2 a 1993 TEXAS TRANSPORTATION INSTITUTE...throuqh Vibration Analysis . 114 APPROACH TO FUTURE RESEARCH ....... ..... .................. 117 MICROSTRUCTURAL FATIGUE RELATIONSHIPS...microdamage healing. This report contains one appendix entitled "Characterization of Damage Growth in Asphalt Concrete ." This appendix supports the

  8. Severe complications in wound healing and fracture treatment in two brothers with congenital insensitivity to pain with anhidrosis.

    PubMed

    Rapp, Marion; Spiegler, Juliane; Härtel, Christoph; Gillessen-Kaesbach, Gabrielle; Kaiser, Martin M

    2013-01-01

    Congenital insensitivity to pain with anhidrosis is an autosomal recessive disorder caused by mutations in the neurotrophic tyrosine receptor kinase 1 (NTRK1) gene, which encodes the receptor for nerve growth factor. We report the clinical and radiological pitfalls in the diagnosis and treatment of two brothers, aged 5 and 8 years, with congenital insensitivity to pain with anhidrosis, the older brother having a proven NTRK1 mutation. In the neonatal period, both presented with recurrent episodes of fever of unknown origin, but their clinical problems changed later. In addition to severe mental retardation and self-harming behaviour, the older brother developed recurrent nonbacterial destructive infections of both the calcaneus and later the talus. No immunodeficiency was found. The younger brother had three complex fractures with a long history of healing problems: overwhelming production of callus, osteomyelitis and movement restrictions. He has less mental retardation than his older brother and shows no self-mutilation.

  9. Parathyroid hormone and bone healing.

    PubMed

    Ellegaard, M; Jørgensen, N R; Schwarz, P

    2010-07-01

    Fracture healing is a complex process, and a significant number of fractures are complicated by impaired healing and non-union. Impaired healing is prevalent in certain risk groups, such as the elderly, osteoporotics, people with malnutrition, and women after menopause. Currently, no pharmacological treatments are available. There is therefore an unmet need for medications that can stimulate bone healing. Parathyroid hormone (PTH) is the first bone anabolic drug approved for the treatment of osteoporosis, and intriguingly a number of animal studies suggest that PTH could be beneficial in the treatment of fractures and could thus be a potentially new treatment option for induction of fracture healing in humans. Furthermore, fractures in animals with experimental conditions of impaired healing such as aging, estrogen withdrawal, and malnutrition can heal in an expedited manner after PTH treatment. Interestingly, fractures occurring at both cancellous and cortical sites can be treated successfully, indicating that both osteoporotic and nonosteoporotic fractures can be the target of PTH-induced healing. Finally, the data suggest that PTH partly prevents the delay in fracture healing caused by aging. Recently, the first randomized, controlled clinical trial investigating the effect of PTH on fracture healing was published, indicating a possible clinical benefit of PTH treatment in inducing fracture healing. The aim of this article is therefore to review the evidence for the potential of PTH in bone healing, including the underlying mechanisms for this, and to provide recommendations for the clinical testing and use of PTH in the treatment of impaired fracture healing in humans.

  10. Single-incision approach improves wound healing and bone union for treating mid-to-lower segment of tibiofibular fracture.

    PubMed

    Zhang, Yongguang; Zhuang, Yuehong; Wang, Benhai; Xu, Hao; Chen, Jinshui; Lin, Songqing

    2015-01-01

    The mid-to-lower segment of tibiofibular fractures (MLTFs) is commonly encountered in clinical practice, which is conventionally treated by the double-incision surgical approach. However, the double-incision approach frequently makes the closure of the wound extremely difficult and sometimes results in necrosis of skin around fractured sites. In the present study, our experience of using a single-incision surgical approach for treating MLTF was exhibited. From February 2005 to December 2013, the clinical outcomes of 212 patients with MLTFs who underwent either double-incision approach or single-incision approach were retrospectively evaluated and compared. Both groups were similar with respect to injury mechanism and all patients were followed up with the efficacies of treatment evaluated by Johner-Wruth criteria. The results demonstrated that the effective rate and the rate of excellent and good efficacy in the single-incision group were significantly higher than those in the double-incision group (P<0.05). In addition, the rates of skin wound healing and bone union after surgery in the single-incision group were significantly higher than those in the double-incision group (P<0.05). These findings indicate that the single-incision surgical approach, which holds the advantages of being milder in trauma, fewer in complications and better in function restoration, might be used as an alternative method for treating MLTFs.

  11. Benzo[a]pyrene impedes self-renewal and differentiation of mesenchymal stem cells and influences fracture healing.

    PubMed

    Zhou, Yiqing; Jiang, Rong; An, Liqin; Wang, Hong; Cheng, Sicheng; Qiong, Shi; Weng, Yaguang

    2017-06-01

    Mesenchymal stem cells (MSCs) are implicated in the bone-forming process during fracture repair. Benzo[a]pyrene (BaP)-a cigarette smoke component and powerful motivator of the aryl hydrocarbon receptor (Ahr)-unfavorably influences bone condition and osteoblast differentiation. The first thing we noticed decreases self-renewal and differentiation of human bone marrow mesenchymal stem (hBM-MSCs) from smokers and activates Ahr signaling in MSCs by up-regulating the Ahr target gene cytochrome P450 (CYP) 1B1 expression. In vitro studies, we employed C3H10T1/2 and bone marrow mesenchymal stem cells (BM-MSCs) with BaP and discovered that BaP impaired innate properties of MSCs. Further investigation into MSCs showed that exposure to BaP activated Ahr signaling and inhibited TGF-β1/SMAD4 and TGF-β1/ERK/AKT signaling pathways. Corresponding with the outcomes, tibial fracture calluses produced by BaP-administered rats appeared to delay healing. This effect of BaP was abrogated by resveratrol, a natural Ahr antagonist, in vitro and in vivo. These data demonstrated that Ahr may play a key role in BaP-impaired innate properties by inhibiting SMAD-dependent signaling pathways TGF-β1/SMAD4 and SMAD-independent TGF-β1/ERK/AKT signaling pathways. Furthermore, resveratrol inhibited MSCs from adverse effects caused by BaP.

  12. 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

  13. Prediction of fracture healing under axial loading, shear loading and bending is possible using distortional and dilatational strains as determining mechanical stimuli

    PubMed Central

    Steiner, Malte; Claes, Lutz; Ignatius, Anita; Niemeyer, Frank; Simon, Ulrich; Wehner, Tim

    2013-01-01

    Numerical models of secondary fracture healing are based on mechanoregulatory algorithms that use distortional strain alone or in combination with either dilatational strain or fluid velocity as determining stimuli for tissue differentiation and development. Comparison of these algorithms has previously suggested that healing processes under torsional rotational loading can only be properly simulated by considering fluid velocity and deviatoric strain as the regulatory stimuli. We hypothesize that sufficient calibration on uncertain input parameters will enhance our existing model, which uses distortional and dilatational strains as determining stimuli, to properly simulate fracture healing under various loading conditions including also torsional rotation. Therefore, we minimized the difference between numerically simulated and experimentally measured courses of interfragmentary movements of two axial compressive cases and two shear load cases (torsional and translational) by varying several input parameter values within their predefined bounds. The calibrated model was then qualitatively evaluated on the ability to predict physiological changes of spatial and temporal tissue distributions, based on respective in vivo data. Finally, we corroborated the model on five additional axial compressive and one asymmetrical bending load case. We conclude that our model, using distortional and dilatational strains as determining stimuli, is able to simulate fracture-healing processes not only under axial compression and torsional rotation but also under translational shear and asymmetrical bending loading conditions. PMID:23825112

  14. Nanoparticles migration in fractured rocks and affects on contaminant migration

    NASA Astrophysics Data System (ADS)

    Missana, Tiziana; Garcia-Gutierrez, Miguel; Alonso, Ursula

    2014-05-01

    In previous studies, the transport behavior of artificial (gold and latex) and natural (smectite clay) colloids, within a planar fracture in crystalline rock, was analyzed. In order to better understand the effects of colloid size, shape and surface charge on nanoparticle migration and especially on filtration processes on natural rock surfaces, different clay colloids and oxide nanoparticles were selected and their transport studied as a function of the residence time. In all the cases, (a fraction of) the nanoparticles travelled in the fracture as fast as or faster than water (with a retardation factor, Rf ≤ 1) and the observed Rf, was related to the Taylor dispersion coefficient, accounting for colloid size, water velocity and fracture width. However, under most of the cases, in contrast to the behavior of a conservative tracer, colloids recovery was much lower than 100 %. Differences in recovery between different nanoparticles, under similar residence times, were analyzed. In order to evaluate the possible consequences, on contaminant migration, of the presence of nanoparticles in the system, transport tests were carried out with both colloids and sorbing radionuclides. The overall capacity for colloids of enhancing radionuclide migration in crystalline rock fractures is discussed. Acknowledgments: The research leading to these results received funding from EU FP7/2007-2011 grant agreement Nº 295487 (BELBAR, Bentonite Erosion: effects on the Long term performance of the engineered Barrier and Radionuclide Transport) and by the Spanish Government under the project NANOBAG (CTM2011-2797).

  15. Fracture Behavior of Ultra-Low-Carbon Steel Plate and Heat-Affected-Zone.

    DTIC Science & Technology

    1990-12-01

    ganese-molybdenum steel caused an increase in the DBTT . However. it cannot be assumed that the presence of these TiN cubes always causes detrimental...Department Research & Development Report 0 N Fracture Behavior of Ultra-Low-Carbon Steel Plate and Heat-Affected-Zone by M. G. Vassilaros CO a- Co -e DTIC...Materials Engineering Department Research & Development Report Fracture Behavior of Ultra-Low-Carbon Steel Plate and Heat-Affected-Zone by M. G

  16. Melt fracturing and healing: A mechanism for degassing and origin of silicic obsidian

    USGS Publications Warehouse

    Cabrera, A.; Weinberg, R.F.; Wright, H.M.N.; Zlotnik, S.; Cas, Ray A.F.

    2011-01-01

    We present water content transects across a healed fault in pyroclastic obsidian from Lami pumice cone, Lipari, Italy, using synchrotron Fourier transform infrared spectroscopy. Results indicate that rhyolite melt degassed through the fault surface. Transects define a trough of low water content coincident with the fault trace, surrounded on either side by high-water-content plateaus. Plateaus indicate that obsidian on either side of the fault equilibrated at different pressure-temperature (P-T) conditions before being juxtaposed. The curves into the troughs indicate disequilibrium and water loss through diffusion. If we assume constant T, melt equilibrated at pressures differing by 0.74 MPa before juxtaposition, and the fault acted as a low-P permeable path for H2O that diffused from the glass within time scales of 10 and 30 min. Assuming constant P instead, melt on either side could have equilibrated at temperatures differing by as much as 100 ??C, before being brought together. Water content on the fault trace is particularly sensitive to post-healing diffusion. Its preserved value indicates either higher temperature or lower pressure than the surroundings, indicative of shear heating and dynamic decompression. Our results reveal that water contents of obsidian on either side of the faults equilibrated under different P-T conditions and were out of equilibrium with each other when they were juxtaposed due to faulting immediately before the system was quenched. Degassing due to faulting could be linked to cyclical seismic activity and general degassing during silicic volcanic activity, and could be an efficient mechanism of producing low-water-content obsidian. ?? 2011 Geological Society of America.

  17. A novel coupled system of non-local integro-differential equations modelling Young's modulus evolution, nutrients' supply and consumption during bone fracture healing

    NASA Astrophysics Data System (ADS)

    Lu, Yanfei; Lekszycki, Tomasz

    2016-10-01

    During fracture healing, a series of complex coupled biological and mechanical phenomena occurs. They include: (i) growth and remodelling of bone, whose Young's modulus varies in space and time; (ii) nutrients' diffusion and consumption by living cells. In this paper, we newly propose to model these evolution phenomena. The considered features include: (i) a new constitutive equation for growth simulation involving the number of sensor cells; (ii) an improved equation for nutrient concentration accounting for the switch between Michaelis-Menten kinetics and linear consumption regime; (iii) a new constitutive equation for Young's modulus evolution accounting for its dependence on nutrient concentration and variable number of active cells. The effectiveness of the model and its predictive capability are qualitatively verified by numerical simulations (using COMSOL) describing the healing of bone in the presence of damaged tissue between fractured parts.

  18. Effects of Platelet Rich Plasma on Healing Rate of Long Bone Non-union Fractures: A Randomized Double-Blind Placebo Controlled Clinical Trial

    PubMed Central

    Ghaffarpasand, Fariborz; Shahrezaei, Mostafa; Dehghankhalili, Maryam

    2016-01-01

    Objective: To determine the effects of platelet rich plasma PRP on healing rates of long bone non-union fracture. Method: This was a randomized double-blind placebo controlled clinical trial being performed in a 12-month period. We included 75 adult (>18 years) patients suffering from long bone (Femur, Tibia, Humerus and Ulna) non-union fracture who were randomly assigned to receive 5mL PRP (n=37) or 5mL normal saline as placebo (n=38) in the site of fracture after intramedullary nailing or open reduction and internal fixation (ORIF) along with autologous bone graft. Patients were followed each 45 days till 9 months and were evaluated both clinically and radiologically in each visit. The healing rate, failure rate, incidence of infection, mal-union and limb shortening were recorded and compared between groups after 9 months of follow-up. Results: The healing rate was significantly higher in PRP group compared to placebo (81.1% vs. 55.3%; p=0.025). The limb shortening was significantly higher in those who received placebo (2.61±1.5 vs. 1.88±1.2mm; p=0.030). Injection of PRP was also associated with lower pain scores ( p=0.003) and shorter healing duration ( p=0.046). The surgical site infection ( p=0.262) and mal-union rate ( p=0.736) were comparable between groups. Conclusion: Application of PRP along with autologous bone graft in the site of non-union of long bone after intramedullary nailing or ORIF results in higher cure rate, shorter healing duration, lower limb shortening and less postoperative pain. Higher infection rate might be a complication of PRP application. Clinical Trial Registry: This trial is registered with the Iranian Clinical Trials Registry (IRCT201208262445N1; www.irct.ir). PMID:27540547

  19. Fracture Toughness of Carbon Fiber Composites Containing Various Fiber Sizings and a Puncture Self-Healing Thermoplastic Matrix

    NASA Technical Reports Server (NTRS)

    Cano, Roberto J.; Grimsley, Brian W.; Ratcliffe, James G.; Gordon, Keith L.; Smith, Joseph G.; Siochi, Emilie J.

    2015-01-01

    Ongoing efforts at NASA Langley Research Center (LaRC) have resulted in the identification of several commercially available thermoplastic resin systems which self-heal after ballistic impact and through penetration. One of these resins, polybutylene graft copolymer (PBg), was selected as a matrix for processing with unsized carbon fibers to fabricate reinforced composites for further evaluation. During process development, data from thermo-physical analyses was utilized to determine a processing cycle to fabricate laminate panels, which were analyzed by photo microscopy and acid digestion. The process cycle was further optimized based on these results to fabricate panels for mechanical property characterization. The results of the processing development effort of this composite material, as well as the results of the mechanical property characterization, indicated that bonding between the fiber and PBg was not adequate. Therefore, three sizings were investigated in this work to assess their potential to improve fiber/matrix bonding compared to previously tested unsized IM7 fiber. Unidirectional prepreg was made at NASA LaRC from three sized carbon fibers and utilized to fabricate test coupons that were tested in double cantilever beam configurations to determine GIc fracture toughness.

  20. The Pulse of the Crust: Slow fracture and rapid healing during the seismic cycle (Louis Néel Medal Lecture)

    NASA Astrophysics Data System (ADS)

    Meredith, Philip

    2016-04-01

    Earthquake ruptures and volcanic eruptions are the most dramatic manifestations of the dynamic failure of a critically stressed crust. However, these are actually very rare events in both space and time; and most of the crust spends most of its time in a highly stressed but subcritical state. Under upper crustal conditions most rocks accommodate applied stresses in a brittle manner through cracking, fracturing and faulting. Cracks can grow at all scales from the grain scale to the crustal scale, and under different stress regimes. Under tensile stresses, single, long cracks tend to grow at the expense of shorter ones; while under all-round compressive, multiple microcracks tend to coalesce to form macroscopic fractures or faults. Deformation in the crust also occurs over a wide range of strain rates, from the very slow rates associated with tectonic loading up to the very fast rates occurring during earthquake rupture. It is now well-established that reactions between chemically-active pore fluids and the rock matrix can lead to time-dependent, subcritical crack propagation and failure in rocks. In turn, this can allow them to deform and fail over extended periods of time at stresses well below their short-term strength, and even at constant stress; a process known as brittle creep. Such cracking at constant stress eventually leads to accelerated deformation and critical, dynamic failure. However, in the period between sequential dynamic failure events, fractures can become subject to chemically-enhanced time-dependent strength recovery processes such as healing or the growth of mineral veins. We show that such strengthening can be much faster than previously suggested and can occur over geologically very short time-spans. These observations of ultra-slow cracking and ultra-fast healing have profound implications for the evolution and dynamics of the Earth's crust. To obtain a complete understanding of crustal dynamics we require a detailed knowledge of all these

  1. [Alternative surgical method in malalignment of healed distal radius fracture: Kapandji-Sauvé procedure].

    PubMed

    Pechlaner, S

    1998-11-01

    Malunion after distal radius fracture with subluxation of the distal radioulnar joint can considerably limit the function of the hand. If the malunion cannot be eliminated by the corrective osteotomy of the radius, care must be taken not to additionally impair the stability of the wrist joint and the carpus, in the event of any necessary salvage procedure. In the Kapandji-Sauvé procedure, an arthrodesis is carried out after repositioning of the distal radioulnar joint. By segment resection of the ulnar shaft, a new joint is made to permit forearm rotation. Between 1984 and 1995, a total of 96 patients were treated with this procedure in our hospital. It was possible to re-examine 87 of those patients after an average period of 4 1/2 (1 to 11) years. The average age of the patients was 59 (14 to 72) years. In 25 cases the results were very good and in 52 cases good. In nine cases the results were poor. In one case the result was unsatisfactory.

  2. Surface-enhanced Raman scattering study of the healing of radial fractures treated with or without Huo-Xue-Hua-Yu decoction therapy

    NASA Astrophysics Data System (ADS)

    Chen, Weiwei; Huang, Hao; Chen, Rong; Feng, Shangyuan; Yu, Yun; Lin, Duo; Lin, Jia

    2014-11-01

    This study aimed to assess, through surface-enhanced Raman scattering (SERS) spectroscopy, the incorporation of calcium hydroxyapatite (CHA ~960 cm-1) and other biochemical substances in the repair of complete radial fractures in rabbits treated with or without Huo-Xue-Hua-Yu decoction (HXHYD) therapy. A total of 18 rabbits with complete radial fractures were randomly divided into two groups; one group was treated with HXHYD therapy and the other without therapy acted as a control. The animals were sacrificed at 15, 30 and 45 d after surgery. Specimens were routinely prepared for SERS measurement and high quality SERS spectra from a mixture of bone tissues and silver nanoparticles were obtained. The mineral-to-matrix ratios from the control and treated groups were calculated. Results showed that both deposition content of CHA measured by SERS spectroscopy and the mineral-to-matrix ratio in the treated group were always greater than those of the control group during the experiment, demonstrating that HXHYD therapy is effective in improving fracture healing and that SERS spectroscopy might be a novel tool to assess fracture healing.

  3. Embryonic stem cell therapy improves bone quality in a model of impaired fracture healing in the mouse; tracked temporally using in vivo micro-CT.

    PubMed

    Taiani, J T; Buie, H R; Campbell, G M; Manske, S L; Krawetz, R J; Rancourt, D E; Boyd, S K; Matyas, J R

    2014-07-01

    In the current study, we used an estrogen-deficient mouse model of osteoporosis to test the efficacy of a cell-generated bone tissue construct for bone augmentation of an impaired healing fracture. A reduction in new bone formation at the defect site was observed in ovariectomized fractures compared to the control group using repeated measures in vivo micro-computed tomography (μCT) imaging over 4 weeks. A significant increase in the bone mineral density (BMD), trabecular bone volume ratio, and trabecular number, thickness and connectivity were associated with fracture repair in the control group, whereas the fractured bones of the ovariectomized mice exhibited a loss in all of these parameters (p<0.001). In a separate group, ovariectomized fractures were treated with murine embryonic stem (ES) cell-derived osteoblasts loaded in a three-dimensional collagen I gel and recovery of the bone at the defect site was observed. A significant increase in the trabecular bone volume ratio (p<0.001) and trabecular number (p<0.01) was observed by 4 weeks in the fractures treated with cell-loaded collagen matrix compared to those treated with collagen I alone. The stem cell-derived osteoblasts were identified at the fracture site at 4 weeks post-implantation through in situ hybridization histochemistry. Although this cell tracking method was effective, the formation of an ectopic cellular nodule adjacent to the knee joints of two mice suggested that alternative in vivo cell tracking methods should be employed in order to definitively assess migration of the implanted cells. To our knowledge, this study is the first of its kind to examine the efficacy of stem cell therapy for fracture repair in an osteoporosis-related fracture model in vivo. The findings presented provide novel insight into the use of stem cell therapies for bone injuries.

  4. Risk of infection and secondary displacement in pediatric supracondylar or lateral condyle fractures treated with unburied Kirchener-wires removed before complete bone healing.

    PubMed

    Aubret, Sylvain; Lecointe, Thibaut; Mansour, Mounira; Rousset, Marie; Andreacchio, Antonio; Pereira, Bruno; Charles, Yann Philippe; Canavese, Federico

    2016-11-29

    This study evaluated the risk of infection and of secondary displacement among children with displaced lateral condyle or supracondylar fractures treated by surgery. The study included a consecutive sample of 84 supracondylar fractures and 21 lateral condyle fractures treated with closed reduction and percutaneous pinning. The mean time to Kirchener wire removal was 29 days (range: 25-37 days) postsurgery. Two out of 105 (1.9%) patients developed infectious complications and two of 105 (1.9%) patients had a secondary displacement. Removal of unburied Kirchener wires before complete bone healing in the physician's office does not increase risk of infection or the risk of secondary displacement. The protocol does, however, enable significant savings and eliminates the need for additional anaesthetic.

  5. Evidence for efficacy of drugs affecting bone metabolism in preventing hip fracture.

    PubMed Central

    Kanis, J. A.; Johnell, O.; Gullberg, B.; Allander, E.; Dilşen, G.; Gennari, C.; Lopes Vaz, A. A.; Lyritis, G. P.; Mazzuoli, G.; Miravet, L.

    1992-01-01

    OBJECTIVE--To examine the effects of taking drugs affecting bone metabolism on the risk of hip fracture in women aged over 50 years. DESIGN--Retrospective, population based, case-control study by questionnaire. SETTING--14 centres in six countries in southern Europe. SUBJECTS--2086 women with hip fracture and 3532 control women matched for age. MAIN OUTCOME MEASURES--Number of drugs affecting bone metabolism taken and length taken for. RESULTS--Women taking drugs affecting bone metabolism had a significantly decreased risk of hip fracture. After adjustment for differences in other risk factors, the relative risk of hip fractures was 0.55 (95% confidence interval 0.31 to 0.85) in women taking oestrogens, 0.75 (0.60 to 0.94) in those taking calcium, and 0.69 (0.51 to 0.92) in those taking calcitonin. The fall in risk was not significant for anabolic steroids (0.6 (0.29 to 1.22)). Neither vitamin D nor fluorides were associated with a significant decrease in the risk of hip fracture. The effect on hip fracture risk increased significantly with increasing duration of exposure (risk ratio 0.8 (0.61 to 1.05) for less than median exposure v 0.66 (0.5 to 0.88) for greater than median exposure). Drugs were equally effective in older and younger women, with the exception of oestrogen. CONCLUSIONS--Oestrogen, calcium, and calcitonins significantly decrease the risk of hip fracture. Short term intervention late in the natural course of osteoporosis may have significant effects on the incidence of hip fracture. PMID:1463947

  6. Suitability of DCPs with screw locking elements to allow sufficient interfragmentary motion to promote secondary bone healing of osteoporotic fractures.

    PubMed

    Cuadrado, A; Yánez, A; Carta, J A; Garcés, G

    2013-06-01

    This paper analyses the suitability of a system comprising a Dynamic Compression Plate (DCP) and Screw Locking Elements (SLEs) to allow sufficient interfragmentary motion to promote secondary bone healing in osteoporotic fractures. Four fixation systems were mounted on bone-simulating reinforced epoxy bars filled with solid rigid polyurethane foam. Group 1, used for comparison purposes, represents a system comprised of a Locking Compression Plate (LCP) and eight locking screws. Groups 2 and 3 represent a system comprised of a DCP plate with eight cortical screws and two SLEs placed on the screws furthest from (group 2) and nearest to (group 3) the fracture. Group 4 represents the system comprised of a DCP plate with SLEs placed on all eight cortical screws. Cyclic compression tests of up to 10,000 load cycles were performed in order to determine the parameters of interest, namely the stiffnesses and the interfragmentary motion of the various configurations under consideration. Tukey's multiple comparison test was used to analyse the existence or otherwise of significant differences between the means of the groups. At 10,000 cycles, interfragmentary motion at the far cortex for group 2 was 0.60±0.04 mm and for group 3 0.59±0.03 mm (there being no significant differences: p=0.995). The mean interfragmentary motion at the far cortex of the LCP construct was 70% less than that of the two groups with 2SLEs (there being significant differences: p=1.1×10(-8)). In the case of group 4 this figure was 45% less than in groups 2 and 3 (there being significant differences: p=5.6×10(-6)). At 10,000 cycles, interfragmentary motion at the near cortex for group 2 was 0.24±0.06 mm and for group 3 0.24±0.03 mm (there being no significant differences: p=1.000). The mean interfragmentary motion at the near cortex of the LCP construct was 70.8% less than that of the two groups with 2SLEs (there being significant differences: p=0.011). In the case of group 4 this figure was 66

  7. Transforming growth factor Beta family: insight into the role of growth factors in regulation of fracture healing biology and potential clinical applications.

    PubMed

    Poniatowski, Łukasz A; Wojdasiewicz, Piotr; Gasik, Robert; Szukiewicz, Dariusz

    2015-01-01

    The transforming growth factor beta (TGF-β) family forms a group of three isoforms, TGF-β1, TGF-β2, and TGF-β3, with their structure formed by interrelated dimeric polypeptide chains. Pleiotropic and redundant functions of the TGF-β family concern control of numerous aspects and effects of cell functions, including proliferation, differentiation, and migration, in all tissues of the human body. Amongst many cytokines and growth factors, the TGF-β family is considered a group playing one of numerous key roles in control of physiological phenomena concerning maintenance of metabolic homeostasis in the bone tissue. By breaking the continuity of bone tissue, a spread-over-time and complex bone healing process is initiated, considered a recapitulation of embryonic intracartilaginous ossification. This process is a cascade of local and systemic phenomena spread over time, involving whole cell lineages and various cytokines and growth factors. Numerous in vivo and in vitro studies in various models analysing cytokines and growth factors' involvement have shown that TGF-β has a leading role in the fracture healing process. This paper sums up current knowledge on the basis of available literature concerning the role of the TGF-β family in the fracture healing process.

  8. Transforming Growth Factor Beta Family: Insight into the Role of Growth Factors in Regulation of Fracture Healing Biology and Potential Clinical Applications

    PubMed Central

    Poniatowski, Łukasz A.; Gasik, Robert

    2015-01-01

    The transforming growth factor beta (TGF-β) family forms a group of three isoforms, TGF-β1, TGF-β2, and TGF-β3, with their structure formed by interrelated dimeric polypeptide chains. Pleiotropic and redundant functions of the TGF-β family concern control of numerous aspects and effects of cell functions, including proliferation, differentiation, and migration, in all tissues of the human body. Amongst many cytokines and growth factors, the TGF-β family is considered a group playing one of numerous key roles in control of physiological phenomena concerning maintenance of metabolic homeostasis in the bone tissue. By breaking the continuity of bone tissue, a spread-over-time and complex bone healing process is initiated, considered a recapitulation of embryonic intracartilaginous ossification. This process is a cascade of local and systemic phenomena spread over time, involving whole cell lineages and various cytokines and growth factors. Numerous in vivo and in vitro studies in various models analysing cytokines and growth factors' involvement have shown that TGF-β has a leading role in the fracture healing process. This paper sums up current knowledge on the basis of available literature concerning the role of the TGF-β family in the fracture healing process. PMID:25709154

  9. 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

  10. Comparison of the microfracture localization in granite between fracturation and slip of a preexisting macroscopic healed joint by acoustic emission measurements

    NASA Astrophysics Data System (ADS)

    Jouinaux, Laurence; Masuda, Koji; Lei, Xinglin; Nishizawa, Osamu; Kusunose, Kinichiro; Liu, Liqiang; Ma, Wentao

    2001-05-01

    Experiments of fracturation and slip of a preexisting macroscopic healed joint have been performed under triaxial deformation on granite from Mayet de Montagne (France). This granite shows high grain-scale inhomogeneity. Acoustic emissions have been recorded and hypocenters have been determined during the entire experiments. For both rupture experiment and slip experiment, precursory localization of microfractures in the final rupture plane has been observed in the early stage of deformation, well before the dilatancy. It is likely that not only initial closure of favorably oriented cracks but also breaking of partially cemented grains or slipping between grains may occur in the pseudoelastic phase and are already localized on the final rupture plane where the shear stress seems to be concentrate. This behavior is observed in both cases where stress heterogeneity and rupture nucleation are controlled by (1) medium-scale heterogeneity at the grain scale (HS sample) or (2) macroscopic heterogeneity in the form of a preexisting healed joint (JS sample). The sample with the healed joint exhibited ˜1.6 times more acoustic emission events than the intact sample. The presence of the healed joint significantly weakened the sample.

  11. Healin' groovy: movement affects the appearance of the healing grid illusion.

    PubMed

    Fukuda, Haruaki; Seno, Takeharu

    2012-01-01

    Vection alters the perception of a visual illusion. It enhances the illusory completion of the healing grid (Kanai, 2005, Best Illusion of the Year Contest, Vision Sciences Society). When we perceive our self-motion, the mode of vision is different from that of when we are stationary.

  12. Acceleration of bone formation during fracture healing by injectable collagen powder and human basic fibroblast growth factor containing a collagen-binding domain from Clostridium histolyticum collagenase.

    PubMed

    Saito, Wataru; Uchida, Kentaro; Ueno, Masaki; Matsushita, Osamu; Inoue, Gen; Nishi, Nozomu; Ogura, Takayuki; Hattori, Shunji; Fujimaki, Hisako; Tanaka, Keisuke; Takaso, Masashi

    2014-09-01

    Growth factor delivered with implantable biomaterials has been used to both accelerate and ensure healing of open fractures in human patients. However, a major limitation of implantable biomaterials is the requirement for open surgical placement. Here, we developed an injectable collagen material-based bone formation system consisting of injectable collagen powder with fibril morphology and collagen triple helix conformation, and basic fibroblast growth factor (bFGF) fused to the collagen-binding domain (CBD) of Clostridium histolyticum collagenase. The affinity of the CBD towards collagen was confirmed by the results of collagen-binding assays. Moreover, the combination of the collagen binding-bFGF fusion protein (CB-bFGF) with injectable collagen powder induced bone formation at protein concentrations lower than those required for bFGF alone in mice fracture models. Taken together, these properties suggest that the CB-bFGF/collagen powder composite is a promising injectable material for bone repair in the clinical setting.

  13. Experiences in the management of anastomotic leakages and analysis of the factors affecting leakage healing in patients with esophagogastric junction cancer

    PubMed Central

    Ding, Ningning; He, Jie; Gao, Shugeng; Zhao, Yue; Yang, Ding; Sun, Kelin; Cheng, Guiyu; Mu, Juwei; Xue, Qi; Wang, Dali; Zhao, Jun; Gao, Yushun; Liu, Xiangyang; Fang, Dekang; Li, Jian; Wang, Yonggang; Huang, Jinfeng; Wang, Bing; Zhang, Liangze

    2017-01-01

    Background It was reported in the literatures that the incidence of anastomotic leakage in patients with esophagogastric junction cancer decreased due to application of staplers and closure devices as well as gastric conduit technique in recent years, however, it increased slightly at our center since widely using the above devices and gastric conduit techniques from 2009. The objective of this study was to summarize our experiences in the management of anastomotic leakages and analyze the factors affecting leakage healing in the patients with esophagogastric junction cancer after surgical resection in recent 6 years. Methods All patients who received surgical resections for esophagogastric junction cancer and diagnosed anastomotic leak at our center between January 2009 and December 2014 were retrospectively analyzed, we also enrolled the patients who had a longer hospital stay (>30 days) as they may develop anastomotic leak. The binary logistic regression in SPSS 16.0 was applied to analyze the factors that may affect leakage healing. Results Of the 1,815 surgically treated esophagogastric junction cancer patients, 91 cases were diagnosed anastomotic leakage postoperatively. The patients were divided into two groups based on the median leakage healing time (40 days) in this series: fast healing group (37 cases) and slowly healing group (54 cases). All factors that may affect the leakage healing were put into analysis by using binary logistic regression. The results of the analysis showed that leakage size (OR =1.073, P=0.004), thoracic drainage (OR =12.937, P=0.037) and smoking index ≤400 (OR =1.001, P=0.04) significantly affected the healing time, while drinking history (P=0.177), duration of fever after anastomotic leak developed (P=0.084), and hypoproteinemia after leak (P=0.169) also apparently but not significantly affect the healing time. Conclusions Though many factors may affect leakage healing in the esophagogastric junction carcinoma patients, leakage

  14. Activation of the δ-opioid receptor promotes cutaneous wound healing by affecting keratinocyte intercellular adhesion and migration

    PubMed Central

    Bigliardi, P L; Neumann, C; Teo, Y L; Pant, A; Bigliardi-Qi, M

    2015-01-01

    BACKGROUND AND PURPOSE In addition to its analgesic functions, the peripheral opioid receptor system affects skin homeostasis by influencing cell differentiation, migration and adhesion; also, wound healing is altered in δ-opioid receptor knockout mice (DOPr–/–). Hence, we investigated δ-opioid receptor effects on the expression of several proteins of the desmosomal junction complex and on the migratory behaviour of keratinocytes. EXPERIMENTAL APPROACH Expression levels of desmosomal cadherins in wild-type and DOPr–/– mice, and the morphology of intercellular adhesion in human keratinocytes were analysed by immunofluorescence. To investigate the δ-opioid receptor activation pathway, protein expression was studied using Western blot and its effect on cellular migration determined by in vitro live cell migration recordings from human keratinocytes. KEY RESULTS Expression of the desmosomal cadherins, desmogleins 1 and 4, was up-regulated in skin from DOPr–/– mice, and down-regulated in δ-opioid receptor-overexpressing human keratinocytes. The localization of desmoplakin expression was rearranged from linear arrays emanating from cell borders to puncta in cell periphery, resulting in less stable intercellular adhesion. Migration and wound recovery were enhanced in human keratinocyte monolayers overexpressing δ-opioid receptors in vitro. These δ-opioid receptor effects were antagonized by specific PKCα/β inhibition indicating they were mediated through the PKC signalling pathway. Finally, cells overexpressing δ-opioid receptors developed characteristically long but undirected protrusions containing filamentous actin and δ-opioid receptors, indicating an enhanced migratory phenotype. CONCLUSION AND IMPLICATIONS Opioid receptors affect intercellular adhesion and wound healing mechanisms, underlining the importance of a cutaneous neuroendocrine system in wound healing and skin homeostasis. LINKED ARTICLES This article is part of a themed section on

  15. A biomechanical sorting of clinical risk factors affecting osteoporotic hip fracture.

    PubMed

    Luo, Y

    2016-02-01

    Osteoporotic fracture has been found associated with many clinical risk factors, and the associations have been explored dominantly by evidence-based and case-control approaches. The major challenges emerging from the studies are the large number of the risk factors, the difficulty in quantification, the incomplete list, and the interdependence of the risk factors. A biomechanical sorting of the risk factors may shed lights on resolving the above issues. Based on the definition of load-strength ratio (LSR), we first identified the four biomechanical variables determining fracture risk, i.e., the risk of fall, impact force, bone quality, and bone geometry. Then, we explored the links between the FRAX clinical risk factors and the biomechanical variables by looking for evidences in the literature. To accurately assess fracture risk, none of the four biomechanical variables can be ignored and their values must be subject-specific. A clinical risk factor contributes to osteoporotic fracture by affecting one or more of the biomechanical variables. A biomechanical variable represents the integral effect from all the clinical risk factors linked to the variable. The clinical risk factors in FRAX mostly stand for bone quality. The other three biomechanical variables are not adequately represented by the clinical risk factors. From the biomechanical viewpoint, most clinical risk factors are interdependent to each other as they affect the same biomechanical variable(s). As biomechanical variables must be expressed in numbers before their use in calculating LSR, the numerical value of a biomechanical variable can be used as a gauge of the linked clinical risk factors to measure their integral effect on fracture risk, which may be more efficient than to study each individual risk factor.

  16. Tocotrienol Supplementation Improves Late-Phase Fracture Healing Compared to Alpha-Tocopherol in a Rat Model of Postmenopausal Osteoporosis: A Biomechanical Evaluation

    PubMed Central

    Mohamad, Sharlina; Shuid, Ahmad Nazrun; Mokhtar, Sabarul Afian; Abdullah, Shahrum; Soelaiman, Ima Nirwana

    2012-01-01

    This study investigated the effects of α-tocopherol and palm oil tocotrienol supplementations on bone fracture healing in postmenopausal osteoporosis rats. 32 female Sprague-Dawley rats were divided into four groups. The first group was sham operated (SO), while the others were ovariectomised. After 2 months, the right femora were fractured under anesthesia and fixed with K-wire. The SO and ovariectomised-control rats (OVXC) were given olive oil (vehicle), while both the alpha-tocopherol (ATF) and tocotrienol-enriched fraction (TEF) groups were given alpha-tocopherol and tocotrienol-enriched fraction, respectively, at the dose of 60 mg/kg via oral gavages 6 days per week for 8 weeks. The rats were then euthanized and the femora dissected out for bone biomechanical testing to assess their strength. The callous of the TEF group had significantly higher stress parameter than the SO and OVXC groups. Only the SO group showed significantly higher strain parameter compared to the other treatment groups. The load parameter of the OVXC and ATF groups was significantly lower than the SO group. There was no significant difference in the Young's modulus between the groups. In conclusion, tocotrienol is better than α-tocopherol in improving the biomechanical properties of the fracture callous in postmenopausal osteoporosis rat model. PMID:22829855

  17. Electricity and colloidal stability: how charge distribution in the tissue can affects wound healing.

    PubMed

    Farber, Paulo Luiz; Hochman, Bernardo; Furtado, Fabianne; Ferreira, Lydia Masako

    2014-02-01

    The role of endogenous electric fields in wound healing is still not fully understood. Electric fields are of fundamental importance in various biological processes, ranging from embryonic development to disease progression, as described by many investigators in the last century. This hypothesis brings together some relevant literature on the importance of electric fields in physiology and pathology, the theory of biologically closed electric circuits, skin battery (a phenomenon that occurs after skin injury and seems to be involved in tissue repair), the relationship between electric charge and interstitial exclusion, and how skin tissues can be regarded as colloidal systems. The importance of electric charges, as established in the early works on the subject and the relevance of zeta potential and colloid stability are also analyzed, and together bring a new light for the physics involved in the wound repair of all the body tissues.

  18. Fracture pain-Traveling unknown pathways.

    PubMed

    Alves, Cecília J; Neto, Estrela; Sousa, Daniela M; Leitão, Luís; Vasconcelos, Daniel M; Ribeiro-Silva, Manuel; Alencastre, Inês S; Lamghari, Meriem

    2016-04-01

    An increase of fracture incidence is expected for the next decades, mostly due to the undeniable increase of osteoporotic fractures, associated with the rapid population ageing. The rise in sports-related fractures affecting the young and active population also contributes to this increased fracture incidence, and further amplifies the economical burden of fractures. Fracture often results in severe pain, which is a primary symptom to be treated, not only to guarantee individual's wellbeing, but also because an efficient management of fracture pain is mandatory to ensure proper bone healing. Here, we review the available data on bone innervation and its response to fracture, and discuss putative mechanisms of fracture pain signaling. In addition, the common therapeutic approaches to treat fracture pain are discussed. Although there is still much to learn, research in fracture pain has allowed an initial insight into the mechanisms involved. During the inflammatory response to fracture, several mediators are released and will putatively activate and sensitize primary sensory neurons, in parallel, intense nerve sprouting that occurs in the fracture callus area is also suggested to be involved in pain signaling. The establishment of hyperalgesia and allodynia after fracture indicates the development of peripheral and central sensitization, still, the underlying mechanisms are largely unknown. A major concern during the treatment of fracture pain needs to be the preservation of proper bone healing. However, the most common therapeutic agents, NSAIDS and opiates, can cause significant side effects that include fracture repair impairment. The understanding of the mechanisms of fracture pain signaling will allow the development of mechanisms-based therapies to effectively and safely manage fracture pain.

  19. Fractures

    MedlinePlus

    A fracture is a break, usually in a bone. If the broken bone punctures the skin, it is called an open ... falls, or sports injuries. Other causes are low bone density and osteoporosis, which cause weakening of the ...

  20. Optimal Treatment of Malignant Long Bone Fracture: Influence of Method of Repair and External Beam Irradiation on the Pathway and Efficacy of Fracture Healing

    DTIC Science & Technology

    2015-10-01

    imaged and have been sacrificed according to protocol schedule. Both 6 month (Group III) and 3 month (Group IV) specimens underwent biomechanical...noticed with ten 6- month specimens and seven 3- month specimens. Figure 6 demonstrates the sample counts for the different healing patterns. Several...mm plate) at final 6 month testing. Tissue histomorphometry at 2 weeks demonstrated a statistically significant increase in overall callus size

  1. Generation of a specific immunological response to FGF-2 does not affect wound healing or reproduction.

    PubMed

    Plum, Stacy M; Vu, Hong A; Mercer, Bobby; Fogler, William E; Fortier, Anne H

    2004-02-01

    Angiogenesis, the process of new capillary formation from pre-existing vessels, has been established as an important mechanism involved in pathologic processes, such as cancer, as well as in normal physiology (Ribatti, D.; Vacca, A.; Roncali, L.; Dammacco, F. Angiogenesis under normal and pathological conditions. Haematologica 1991, 76 (4), 311-320). Basic fibroblast growth factor (FGF-2) is a critical mediator of angiogenesis that is important for normal reproduction and wound healing. FGF-2 mediates its pro-angiogenic effects by binding to heparin sulfate proteoglycan in addition to a tyrosine kinase receptor (Baird, A.; Schubert, D.; Ling, N.; Guillemin, R. Receptor and heparin-binding domain of basic fibroblast growth factor. Proc. Natl. Acad. Sci. U. S. A. 1998, 5 (7), 2324-2328; Richard, C.; Roghani, M.; Moscatelli, D. Fibroblast growth factor (FGF)-2 mediates cell attachment through interactions with two FGF receptor-1 isoforms and extracellular matrix or cell-associated heparin sulfate proteoglycans. Biochem. Biophys. Res. Commun. 2000, 276 (2), 399-405; Casu, B.; Guerrini, M.; Naggi, A.; Perez, M.; Torri, G.; Ribatti, D.; Carminati, P.; Giannini, G.; Penco, S.; Pisano, C.; Belleri, M.; Rusnati, M.; Presta, M. Short heparin sequences spaced by glycol-split urinate residues are antagonists of fibroblast growth factor 2 and angiogenesis inhibitors. Biochemistry 2002, 41 (33), 10519-10528; Murphy, P.V.; Pitt, N.; O'Brien, A.; Enright, P.M.; Dunne, A.; Wilson, S.J.; Duane, R.M.; O'Boyle, K.M. Identification of novel inhibitors of fibroblast growth factor (FGF-2) binding to heparin and endothelial cell survival from a structurally diverse carbohybrid library. Bioorg. Med. Chem. Lett. 2002, 12 (22), 3287-3290). We developed a liposomal-based peptide vaccine, L(HBD) that targets the heparin binding domain of the FGF-2 molecule. This vaccine, when inoculated into mice, inhibits angiogenesis in response to FGF-2 in a hepatic sponge model as well as tumor progression

  2. Development of an Injectable Salmon Fibrinogen-Thrombin Matrix to Enhance Healing of Compound Fractures of Extremities

    DTIC Science & Technology

    2012-09-01

    TM, Bateman SW, Cole LK, Smeak DD. 2006. Evaluation of a local anesthetic delivery 614 system for the postoperative analgesic management of canine...examined. Blood samples have been collected and basic blood parameters measured and evaluated for the production of adverse immune reaction. In...also evaluated since this may have an impact on the healing process. Numerical scores are assigned to each parameter to permit comparison between

  3. Oblique shear fractures of the lunate.

    PubMed

    Freeland, Alan E; Ahmad, Nawaiz

    2003-08-01

    Traumatic fractures of the lunate are rare. This article presents two patients who had displaced oblique lunate fractures and distal radius fractures. Both fractures achieved union; however, transient avascular necrosis occurred in the proximal healing of one patient.

  4. Stress fracture healing: fatigue loading of the rat ulna induces upregulation in expression of osteogenic and angiogenic genes that mimic the intramembranous portion of fracture repair.

    PubMed

    Wohl, Gregory R; Towler, Dwight A; Silva, Matthew J

    2009-02-01

    Woven bone is formed in response to fatigue-induced stress fractures and is associated with increased local angiogenesis. The molecular mechanisms that regulate this woven bone formation are unknown. Our objective was to measure the temporal and spatial expression of osteo- and angiogenic genes in woven bone formation in response to increasing levels of fatigue-induced damage. We used the rat forelimb compression model to produce four discrete levels of fatigue damage in the right ulna of 115 male Fischer rats. Rats were killed at 0 (1 h), 1, 3 and 7 days after loading. Using qRT-PCR, we quantified gene expression associated with osteogenesis (BMP2, Msx2, Runx2, Osx, BSP, Osc), cell proliferation (Hist4), and angiogenesis (VEGF, PECAM-1) from the central half of the ulna. The spatial distribution of BMP2, BSP and PCNA was assessed by immunohistochemistry or in situ hybridization in transverse histological sections 1, 4, and 7 mm distal to the ulnar mid-diaphysis. One hour after loading, BMP2 was significantly upregulated in neurovascular structures in the medial ulnar periosteum. Expression of angiogenic markers (VEGF, PECAM-1) increased significantly between Day 0 and 1 and, as with BMP2 expression, remained upregulated through Day 7. While Osx and BSP were upregulated on Day 1, the other osteogenic genes (Msx2, Runx2, Osx, BSP and Osc) were induced on Day 3 in association with the initiation of periosteal woven bone formation and continued through Day 7. The magnitude of osteogenic gene expression, particularly matrix genes (BSP, Osc) was significantly proportional the level of fatigue damage. The woven bone response to fatigue injury is remarkably similar to the "intramembranous" portion of fracture repair - rapid formation of periosteal woven bone characterized by early BMP2 expression, cell proliferation, and upregulation of osteogenic genes. We speculate that woven bone repair of fatigue damage may be an abbreviated fracture response without the requirement

  5. Bone healing in 2016

    PubMed Central

    Buza, John A.; Einhorn, Thomas

    2016-01-01

    Summary Delayed fracture healing and nonunion occurs in up to 5–10% of all fractures, and can present a challenging clinical scenario for the treating physician. Methods for the enhancement of skeletal repair may benefit patients that are at risk of, or have experienced, delayed healing or nonunion. These methods can be categorized into either physical stimulation therapies or biological therapies. Physical stimulation therapies include electrical stimulation, low-intensity pulsed ultrasonography, or extracorporeal shock wave therapy. Biological therapies can be further classified into local or systemic therapy based on the method of delivery. Local methods include autologous bone marrow, autologous bone graft, fibroblast growth factor-2, platelet-rich plasma, platelet-derived growth factor, and bone morphogenetic proteins. Systemic therapies include parathyroid hormone and bisphosphonates. This article reviews the current applications and supporting evidence for the use of these therapies in the enhancement of fracture healing. PMID:27920804

  6. The history of the walls of the Acropolis of Athens and the natural history of secondary fracture healing process.

    PubMed

    Lyritis, G P

    2000-09-01

    During its long and adventurous history, the Acropolis of Athens has been a site of many dramatic events. It suffered its most disastrous destruction during the Persian wars. Under the command of King Xerxes, the Persians invaded Athens and ruined the Temple of the Parthenon and the walls of the Acropolis. After their victorious sea battle at Salamis, the Athenians, led by Themistocles, returned home and tried to repair the damage. Their priority still was to defend their city by restoring the walls of the Acropolis. Materials of all kinds were salvaged from the ruins of the Acropolis and used for an immediate reconstruction of the walls. Later, when the Athenians became the leaders of the Greek world, it was decided that the walls should be rebuilt in a proper artistic way. Themistocles suggested that a small section of the walls, which had formerly been a part of the urgent restoration, should remain in place so as to remind the citizens of this historical event. This is a characteristic example of the biological and mechanical adaptation of fracture callus to musculoskeletal function. After a period of urgency with the fixation of a fracture by means of a primitive secondary callus formation, the broken limb gradually returns to its usual function. Increased mechanical loading enhances the remodelling of the callus and the replacement of woven bone with lamellar bone.

  7. The Prevalence of Fragility Fractures in a Population of a Region of Southern Italy Affected by Thyroid Disorders

    PubMed Central

    Notarnicola, Angela; Pesce, Vito; Mudoni, Simona; Tafuri, Silvio; Moretti, Biagio

    2016-01-01

    In the literature there is no clear evidence of a relationship between thyropathies and fragility fractures. The aim of our study is to define the prevalence of thyroid disease in a study sample made up of subjects with fragility fractures and from the same geographical area. We retrospectively studied the “hospital discharge records” (HDR) in the Apulian Database for the period 2008–2013 in order to identify all those patients with fragility fractures that required hospitalization. After detecting the prevalent population, we identified the patients affected by thyroid disease. We observed that, between 2008 and 2013 in Apulia, 16,636 patients were affected by hyperthyroidism. In the same period there were 92,341 subjects with hypothyroidism. The incidence of fragility fractures was 4.5% in the population with hyperthyroidism. As regards the population with hypothyroidism, the incidence of fragility fractures was 3.7%. Furthermore, we assessed the statistical connection between thyroid disease and fragility fractures revealing a higher incidence in patients with hyperthyroidism and clinical hypothyroidism. PMID:27807539

  8. Development of novel self-healing and antibacterial dental composite containing calcium phosphate nanoparticles

    PubMed Central

    Wu, Junling; Weir, Michael D.; Melo, Mary Anne S.; Xu, Hockin H. K.

    2015-01-01

    Objectives Fracture and secondary caries are the primary reasons for dental restoration failure. The objective of this study was to develop a self-healing composite to heal cracks, while containing dimethylaminohexadecyl methacrylate (DMAHDM) for antibacterial function and nanoparticles of amorphous calcium phosphate (NACP) for remineralization. Methods Microcapsules were synthesized with poly(urea-formaldehyde) (PUF) shells containing triethylene glycol dimethacrylate (TEGDMA) and N,N-dihydroxyethyl-p-toluidine (DHEPT) as healing liquid. Composite contained 20 mass% of NACP and 35% glass fillers. In addition, composite contained 0%, 2.5%, 5%, 7.5%, or 10% of microcapsules. A single edge V-notched beam method measured fracture toughness (KIC) and self-healing efficiency. A dental plaque microcosm biofilm model was used to test the antibacterial properties. Results Incorporation of microcapsules up to 7.5% into the composite did not adversely affect the mechanical properties (p > 0.1). Successful self-healing was achieved, with KIC recovery of 65–81% (mean ± sd; n = 6) to regain the load-bearing capability after composite fracture. The self-healing DMAHDM-NACP composite displayed a strong antibacterial potency, inhibiting biofilm viability and lactic acid production, and reducing colony-forming units by 3–4 orders of magnitude, compared to control composite without DMAHDM. Conclusions A dental composite was developed with triple benefits of self-healing after fracture, antibacterial activity, and remineralization capability for the first time. Clinical significance The self-healing, antibacterial and remineralizing composite may be promising for tooth cavity restorations to combat bulk fracture and secondary caries. The method of using triple agents (self-healing microcapsules, DMAHDM, and NACP) may have wide applicability to other dental composites, adhesives, sealants and cements. PMID:25625674

  9. [Triple fracture of the shoulder suspensory complex].

    PubMed

    Tamimi Mariño, I; Martin Rodríguez, I; Mora Villadeamigo, J

    2013-01-01

    The superior suspensory complex of the shoulder (SSCS) is a ring shaped structure composed of bones and soft tissues that play a fundamental role in the stability of the shoulder joint. Isolated injuries of the SSCS are relatively common, but injuries that affect 3 components are extremely unusual. We present a triple injury of the SSCS in a 26 year old patient with a Neer type ii clavicular fracture, a Kuhn type iii acromion fracture and an Ogawa type i coracoid fracture. An open reduction and stabilization of the clavicle was performed with 2 Kirschner nails. The acromial fracture was synthesized with 2 cannulated screws, and the coracoid fracture was treated conservatively. After 24 months of follow up the patient had an excellent functional outcome according to the Constat-Murley shoulder score and QuickDASH scoring system, and all the fractures healed correctly.

  10. How reactive fluids alter fracture walls and affect shale-matrix accessibility

    NASA Astrophysics Data System (ADS)

    Fitts, J. P.; Deng, H.; Peters, C. A.

    2014-12-01

    Predictions of mass transfer across fracture boundaries and fluid flow in fracture networks provide fundamental inputs into risk and life cycle assessments of geologic energy technologies including oil and gas extraction, geothermal energy systems and geologic CO2 storage. However, major knowledge gaps exist due to the lack of experimental observations of how reactive fluids alter the pore structures and accessible surface area within fracture boundaries that control the mass transfer of organics, metals and salts, and influence fluid flow within the fracture. To investigate the fracture and rock matrix properties governing fracture boundary alteration, we developed a new flow-through cell that enables time-dependent 2D x-ray imaging of mineral dissolution and/or precipitation at a fracture surface. The parallel plate design provides an idealized fracture geometry to investigate the relationship between flow rate, reaction rate, and mineral spatial heterogeneity and variation. In the flow-cell, a carbonate-rich sample of Eagle Ford shale was reacted with acidified brine. The extent and rate of mineral dissolution were correlated with calcite abundance relative to less soluble silicate minerals. Three-dimensional x-ray tomography of the reacted fracture wall shows how calcite dissolution left behind a porous network of silicate minerals. And while this silicate network essentially preserved the location of the initial fracture wall, the pore network structures within the fracture boundary were dramatically altered, such that the accessible surface area of matrix components increased significantly. In a second set of experiments with a limestone specimen, however, the extent of dissolution and retreat of the fracture wall was not strictly correlated with the occurrence of calcite. Instead, the pattern and extent of dissolution suggested secondary causes such as calcite morphology, the presence of argillaceous minerals and other diagenetic features. Our experiments

  11. Microstructures relevant to brittle fracture initiation at the heat-affected zone of weldment of a low carbon steel

    SciTech Connect

    Ohya, K.; Kim, J.; Yokoyama, K.; Nagumo, M.

    1996-09-01

    Charpy toughness of the heat-affected zone (HAZ) of weldment of a low carbon steel has been investigated by means of an instrumented Charpy test and fractographic analysis. Microstructures were varied with thermal cycles simulating double-pass welding. The ductile-brittle transition temperature is the most deteriorated at an intermediate second-cycle heating temperature. The origin of the difference in the transition temperatures has been analyzed to exist in the brittle fracture initiation stage. Fractographic examination correlating with microstructural features has revealed that the brittle fracture initiation site is associated with the intersection of bainitic ferrite areas with different orientations rather than the martensite-austenite constituents. The role of the constraint of plastic deformation on the brittle fracture initiation is discussed.

  12. Factors affecting transfusion requirement after hip fracture: Can we reduce the need for blood?

    PubMed Central

    Desai, Sagar J.; Wood, Kristi S.; Marsh, Jackie; Bryant, Dianne; Abdo, Hussein; Lawendy, Abdel-Rahman; Sanders, David W.

    2014-01-01

    Background Hip fractures are common injuries that result in blood loss and frequently require the transfusion of blood products. We sought to identify risk factors leading to increased blood transfusion in patients presenting with hip fractures, especially those factors that are modifiable. Methods We retrospectively reviewed the cases of all patients who had fixation of their hip fractures between October 2005 and February 2010. The need for transfusion was correlated with potential risk factors, including age, sex, preoperative hemoglobin, fracture type, fixation method and more. Results A total of 835 patients had fixation of their hip fractures during the study period; 631 met the inclusion criteria and 249 of them (39.5%) were transfused. We found an association between need for blood transfusion and female sex (p = 0.018), lower preoperative hemoglobin (p < 0.001), fracture type (p < 0.001) and fixation method (p < 0.001). Compared with femoral neck fractures, there was a 2.37 times greater risk of blood transfusion in patients with intertrochanteric fractures (p < 0.001) and a 4.03 times greater risk in those with subtrochanteric fractures (p < 0.001). Dynamic hip screw (DHS) fixation decreased the risk of transfusion by about half compared with intramedullary nail or hemiarthroplasty. We found no association with age, delay to operation (p = 0.17) or duration of surgery (p = 0.30). Conclusion The only modifiable risk factor identified was fixation method. When considering blood transfusion requirements in isolation, we suggest a potential benefit in using a DHS for intertrochanteric and femoral neck fractures amenable to DHS fixation. PMID:25265109

  13. Molecular Mechanisms of Soft Tissue Regeneration and Bone Formation in Mice: Implication in Fracture Repair and Wound Healing in Humans

    DTIC Science & Technology

    2008-04-01

    affect cell cycle progression through G1 phase by directly or indirectly controlling the genes for cyclins D2 and D3 . Therefore, we postulated that...Runx1t1 may regulate the osteoblast proliferation by directly inhibiting cell cycle regulatory genes including cyclins D1, D2 and D3 . We...investigated expression levels of cyclins D1, D2 , and D3 12- and 24-hours after the suppression of Runx1t1. MC3T3 cell were transfected with Runx1t1 or

  14. Correlation of the microstructure and fracture toughness of the heat-affected zones of an SA 508 steel

    SciTech Connect

    Kim, S.; Kang, S.Y.; Oh, S.J.; Kwon, S.J.; Lee, S.; Kim, J.H.; Hong, J.H.

    2000-04-01

    In this study, microstructures of a heat-affected zone (HAZ) of an SA 508 steel were identified by Moessbauer spectroscopy in conjunction with microscopic observations, and were correlated with fracture toughness. Specimens with the peak temperature raised to 1350 C showed mostly martensite. With the peak temperature raised to 900 C, the martensite fraction was reduced, while bainite or martensite islands were formed because of the slow cooling from the lower austenite region and the increase in the prior austenite grain size. As the martensite fraction present inside the HAZ increased, hardness and strength tended to increase, whereas fracture toughness decreased. The microstructures were not changed much from the base metal because of the minor tempering effect when it was raised to 650 C or 700 C. However, fracture toughness of the subcritical HAZ with the peak temperature raised to 650 C to 700 C was seriously reduced after postweld heat treatment (PWHT) because carbide particles were of primary importance in initiating voids. Thus, the most important microstructural factors affecting fracture toughness were the martensite fraction before PWHT and the carbide fraction after PWHT.

  15. Fracture After Total Hip Replacement

    MedlinePlus

    ... er Total Hip Replacement cont. • Dislocation • Limb length inequality • Poor fracture healing • Repeat fracture • Lack of in- ... Surgeons (AAOS). To learn more about your orthopaedic health, please visit orthoinfo.org. Page ( 5 ) AAOS does ...

  16. Healing or Not Healing.

    PubMed

    Padilla, Sabino; Sanchez, Mikel; Padilla, Ione; Orive, Gorka; Anitua, Eduardo

    2016-01-01

    Healing process might be considered as a byproduct of the mechanisms underlying the biological defense system consisting of hemostasis and clotting, the innate immune system, and fibrogenesis. But there is no biological process that does not potentially entail high costs through trade-offs with other life-history parameters and that might be seen as collateral damage. Depending on the balance among the robust and flexible modular defense system, which will be deployed in many different arrays, the structural outcome of the healing process will not resolve with a unitary outcome. Drawing on the regenerative potential of platelets, plasma biomolecules and fibrin matrix, several systems of producing autologous platelets-and plasma derived products (APPDPs) have been developed and aimed at enhancing the natural in vivo tissue regenerative capacity of damaged tissues. Despite the care with which the medical staff elaborate and apply autologous platelets-and plasma derived products, some pitfalls arise regarding the composition of autologous plasma-and platelet derived products, the modalities of their application, and the in vitro versus in vivo evaluations, all of which can deeply influence tissue healing - a process which is already unpredictable, without a unitary mechanism that might be deployed in many different structural and functional arrays which culminate in the tissue repair. A biological approach to the application of autologous platelets-and plasma derived products is crucial to obtaining optimum functional healing outcomes in addition to avoiding poor clinical results and reaching misleading conclusions.

  17. Evaluation of Crack Arrest Fracture Toughness of Parent Plate, Weld Metal and Heat Affected Zone of BIS 812 EMA Ship Plate Steel

    DTIC Science & Technology

    1993-10-01

    34- EVALUATION OF CRACK ARREST FRACTURE TOUGHNESS OF PARENT PLATE, WELD METAL 0 AND HEAT AFFECTED ZONE OF BIS 812 EMA SHIP PLATE STEEL IA BURCH MRL-TR...had a deleterious effect on the crack arrest properties of this particular steel . Tests on each of these regions revealed that, far the combination of...fracture toughness assessment is not a requirement for qualification for this steel , crack arrest fracture toughness, Kj, can be used to • 0 characterise the

  18. Complications of hip fractures: A review

    PubMed Central

    Carpintero, Pedro; Caeiro, Jose Ramón; Carpintero, Rocío; Morales, Angela; Silva, Samuel; Mesa, Manuel

    2014-01-01

    Nowadays, fracture surgery represents a big part of the orthopedic surgeon workload, and usually has associated major clinical and social cost implications. These fractures have several complications. Some of these are medical, and other related to the surgical treatment itself. Medical complications may affect around 20% of patients with hip fracture. Cognitive and neurological alterations, cardiopulmonary affections (alone or combined), venous thromboembolism, gastrointestinal tract bleeding, urinary tract complications, perioperative anemia, electrolytic and metabolic disorders, and pressure scars are the most important medical complications after hip surgery in terms of frequency, increase of length of stay and perioperative mortality. Complications arising from hip fracture surgery are fairly common, and vary depending on whether the fracture is intracapsular or extracapsular. The main problems in intracapsular fractures are biological: vascularization of the femoral head, and lack of periosteum -a major contributor to fracture healing- in the femoral neck. In extracapsular fractures, by contrast, the problem is mechanical, and relates to load-bearing. Early surgical fixation, the role of anti-thromboembolic and anti-infective prophylaxis, good pain control at the perioperative, detection and management of delirium, correct urinary tract management, avoidance of malnutrition, vitamin D supplementation, osteoporosis treatment and advancement of early mobilization to improve functional recovery and falls prevention are basic recommendations for an optimal maintenance of hip fractured patients. PMID:25232517

  19. Assessment of bone healing on tibial fractures treated with wire osteosynthesis associated or not with infrared laser light and biphasic ceramic bone graft (HATCP) and guided bone regeneration (GBR): Raman spectroscopy study

    NASA Astrophysics Data System (ADS)

    Bastos de Carvalho, Fabíola; Aciole, Gilberth Tadeu S.; Aciole, Jouber Mateus S.; Silveira, Landulfo, Jr.; Nunes dos Santos, Jean; Pinheiro, Antônio L. B.

    2011-03-01

    The aim of this study was to evaluate, through Raman spectroscopy, the repair of complete tibial fracture in rabbits fixed with wire osteosynthesis - WO, treated or not with infrared laser light (λ 780nm, 50mW, CW) associated or not to the use of HATCP and GBR. Surgical fractures were created under general anesthesia (Ketamine 0.4ml/Kg IP and Xilazine 0.2ml/Kg IP), on the tibia of 15 rabbits that were divided into 5 groups and maintained on individual cages, at day/night cycle, fed with solid laboratory pelted diet and had water ad libidum. On groups II, III, IV and V the fracture was fixed with WO. Animals of groups III and V were grafted with hydroxyapatite + GBR technique. Animals of groups IV and V were irradiated at every other day during two weeks (16J/cm2, 4 x 4J/cm2). Observation time was that of 30 days. After animal death the specimens were kept in liquid nitrogen for further analysis by Raman spectroscopy. Raman spectroscopy showed significant differences between groups (p<0.001). It is concluded that IR laser light was able to accelerate fracture healing and the association with HATCP and GBR resulted on increased deposition of calcium hydroxyapatite.

  20. Distal Radial Fractures in the Superelderly: Does Malunion Affect Functional Outcome?

    PubMed Central

    Clement, N. D.; Duckworth, A. D.; Court-Brown, C. M.; McQueen, M. M.

    2014-01-01

    Purpose. The management of unstable distal radial fractures in the superelderly (≥80 years old) remains controversial. The aim of this study was to compare the functional outcome of super-elderly patients with and without malunion after a distal radial fracture. Methods. We identified 51 superelderly patients living independently with displaced fractures from a prospective database of 4024 patients with distal radial fractures. Activities of daily living, presence of wrist pain, whether the wrist had returned to its normal level function, grip strength and ROM were recorded. The dorsal angulation was measured radiographically. Results. There were 17 (33.3%) patients defined to have a malunion. The outcomes of the independent patients with and without malunion were compared at a mean follow-up of 15 months. No difference was observed in activities of daily living (P = 0.28), wrist pain (P = 0.14), whether the wrist had returned to its normal level function (P = 0.25), grip strength (P = 0.31), or ROM (P = 0.41). An increasing degree of dorsal angulation correlated with diminished ROM (P = 0.038), but did not correlate with activities of daily living (P = 0.10). Conclusions. Malunion of the distal radius does not influence the functional outcome of independent superelderly patients. PMID:24967123

  1. Chronic Electromagnetic Exposure at Occupational Safety Level Does Not Affect the Metabolic Profile nor Cornea Healing after LASIK Surgery.

    PubMed

    Crouzier, David; Dabouis, Vincent; Gentilhomme, Edgar; Vignal, Rodolphe; Bourbon, Fréderic; Fauvelle, Florence; Debouzy, Jean-Claude

    2014-01-01

    LASIK eye surgery has become a very common practice for myopic people, especially those in the military. Sometimes undertaken by people who need to keep a specific medical aptitude, this surgery could be performed in secret from the hierarchy and from the institute medical staff. However, even though the eyes have been previously described as one of the most sensitive organs to electromagnetic fields in the human body, no data exist on the potential deleterious effects of electromagnetic fields on the healing eye. The consequences of chronic long-lasting radar exposures at power density, in accordance with the occupational safety standards (9.71 GHz, 50 W/m(2)), were investigated on cornea healing. The metabolic and clinical statuses after experimental LASIK keratotomy were assessed on the different eye segments in a New Zealand rabbit model. The analysis methods were performed after 5 months of exposure (1 hour/day, 3 times/week). Neither clinical or histological examinations, nor experimental data, such as light scattering, (1)H-NMR HRMAS metabolomics, (13)C-NMR spectra of lipidic extracts, and antioxidant status, evidenced significant modifications. It was concluded that withdrawing the medical aptitude of people working in electromagnetic field environments (i.e., radar operators in the navy) after eye surgery was not justified.

  2. Chronic Electromagnetic Exposure at Occupational Safety Level Does Not Affect the Metabolic Profile nor Cornea Healing after LASIK Surgery

    PubMed Central

    Dabouis, Vincent; Gentilhomme, Edgar; Vignal, Rodolphe; Bourbon, Fréderic; Fauvelle, Florence; Debouzy, Jean-Claude

    2014-01-01

    LASIK eye surgery has become a very common practice for myopic people, especially those in the military. Sometimes undertaken by people who need to keep a specific medical aptitude, this surgery could be performed in secret from the hierarchy and from the institute medical staff. However, even though the eyes have been previously described as one of the most sensitive organs to electromagnetic fields in the human body, no data exist on the potential deleterious effects of electromagnetic fields on the healing eye. The consequences of chronic long-lasting radar exposures at power density, in accordance with the occupational safety standards (9.71 GHz, 50 W/m2), were investigated on cornea healing. The metabolic and clinical statuses after experimental LASIK keratotomy were assessed on the different eye segments in a New Zealand rabbit model. The analysis methods were performed after 5 months of exposure (1 hour/day, 3 times/week). Neither clinical or histological examinations, nor experimental data, such as light scattering, 1H-NMR HRMAS metabolomics, 13C-NMR spectra of lipidic extracts, and antioxidant status, evidenced significant modifications. It was concluded that withdrawing the medical aptitude of people working in electromagnetic field environments (i.e., radar operators in the navy) after eye surgery was not justified. PMID:24757560

  3. Healing of a mechano-responsive material

    NASA Astrophysics Data System (ADS)

    Vetter, A.; Sander, O.; Duda, G. N.; Weinkamer, R.

    2013-12-01

    While contribution of physics to model fracture of materials is significant, the “reversed” process of healing is hardly investigated. Inspired by fracture healing that occurs as a self-repair process in nature, e.g. in bone, we computationally study the conditions under which a material can repair itself. In our model the material around a fracture is assumed mechano-responsive: it processes the information of i) local stiffness and ii) local strain and responds by local stiffening. Depending on how information i) and ii) is processed, healing evolves via fundamentally different paths.

  4. The perception of time heals all wounds: temporal distance affects willingness to forgive following an interpersonal transgression.

    PubMed

    Wohl, Michael J A; McGrath, April L

    2007-07-01

    Prior research has assessed the temporal unfolding of forgiveness and found that forgiveness becomes more likely as time distances the victim from the transgression. These findings lend credence to the axiom "time heals all wounds." This research examines the effect of time perception on forgiveness of others by experimentally manipulating temporal distance. In Experiment 1, respondents reported greater willingness to forgive the transgressor when more time had elapsed since the transgression. Experiments 2 and 3 determined the influence of subjective temporal distance on willingness to forgive. Participants who perceived a hypothetical (Experiment 2) or real (Experimental 3) transgression to be farther away in time were more willing to forgive the target than were participants who perceived the event to be temporally closer. Results suggest that temporal appraisals of an event are central to the forgiveness process.

  5. Case 24: Stress Fracture of the Tibia

    DTIC Science & Technology

    2008-03-01

    strengthening was started. At six-week follow up, periosteal involvement was subsiding and a healing sclerotic band was seen across the tibial shaft on...stress fracture. Fig. 2: Axial CT showing the periosteal reaction. Female athletes have the greater tendency of acquiring tibial stress...extremity to include the vertebral body, femoral neck, tibial diaphysis, metatarsal shaft and calcaneous are most commonly affected. If the offending

  6. Mechanisms affecting the transport and retention of bacteria, bacteriophage and microspheres in laboratory-scale saturated fractures

    NASA Astrophysics Data System (ADS)

    Seggewiss, G.; Dickson, S. E.

    2013-12-01

    Groundwater is becoming an increasingly important water source due to the ever-increasing demands from agricultural, residential and industrial consumers. In search of more secure sources, wells are routinely finished over large vertical depths in bedrock aquifers, creating new hydraulic pathways and thus increasing the risk of cross contamination. Moreover, hydraulic pathways are also being altered and created by increasing water withdrawal rates from these wells. Currently, it is not well understood how biological contaminants are transported through, and retained in, fractured media thereby making risk assessment and land use decisions difficult. Colloid transport within fractured rock is a complex process with several mechanisms affecting transport and retention, including: advection, hydrodynamic dispersion, diffusion, size exclusion, adsorption, and decay. Several researchers have investigated the transport of bacteria, bacteriophage, and microspheres (both carboxylated and plain) to evaluate the effects of surface properties and size on transport and retention. These studies have suggested that transport is highly dependent on the physico-chemical properties of the particle, the fracture, and the carrying fluid. However, these studies contain little detail regarding the specific mechanisms responsible for transport beyond speculating about their existence. Further, little work has been done to compare the transport of these particulate materials through the same fracture, allowing for direct observations based on particulate size and surface properties. This research examines the similarities and differences in transport and retention between four different particles through two different laboratory-scale, saturated fractures. This work is designed to explore the effects of particle size, surface properties, ionic strength of the carrying solution, and aperture field characteristics on transport and retention in single, saturated fractures. The particulates

  7. [Atlas fracture due to aneurysmal bone cyst after minor trauma].

    PubMed

    Topp, T; Krüger, A; Zettl, R; Figiel, J; Ruchholtz, S; Frangen, T M

    2014-05-01

    Aneurysmal bone cysts predominantly occur in young adults and the long bones, the lumbar spine and the pelvis are mainly affected. This article presents the case of a 22-year-old woman with the very rare localization of an aneurysmal bone cyst of the atlas and an atlas fracture after a minor trauma. The initial radiological diagnosis was a suspicted aneurysmal bone cyst which was confirmed histologically. Due to the unstable fracture it was decided to carry out surgical treatment with occipitocervical stabilization in combination with a transoral bone graft. After a period of 11 months the fracture had completely healed and the implants were removed without any complications.

  8. The Effect of Healing on the Brittle Compressive Strength of Ice that Contains Faults

    NASA Astrophysics Data System (ADS)

    Nodder, Stephen Thomas

    We report the parameters that affect the healing of Columbic (C) faulted (or analogue) S2 columnar ice and the effect that healing has on the resistance to frictional sliding. Healing is defined as the restoration of mechanical strength to an interface in ice during periods of dormancy when the driving forces for sliding along the interface falls below the level required for continuous sliding. Damaged laboratory grown polycrystalline specimens of ice, freshwater and saline, were tested under a variety of conditions (biaxial confining stresses (60kPa to 750 kPa), biaxial confinement times (3s to 18 hours), temperatures (-3°C to -30°C), three surface roughnesses) to explore the effect of these parameters on healing. The damage was imparted as a C-fault created under low confinement or as a fault made using a bandsaw cut (termed saw-cut fault) or as a smoothed bandsaw cut (termed smooth fault). Healing was quantified through the uniaxial fracture strength, as defined by the maximum force before failure divided by the area over which that force was applied. The uniaxial fracture strengths show that the degree of healing is dependent upon time, temperature, confinement, and salinity but not dependent on roughness. The greater the degree of healing, the more the ice behaves like virgin material in that the failure strength approaches that for undamaged ice and the failure plane becomes less dependent on the pre-existing fault. Biaxial confinement experiments allowed for healing to be quantified by the resistance to sliding, i.e. as a friction coefficient. These experiments illustrate that the friction coefficient is dependent on both the magnitude of the healing force and the length of time the specimen is held under biaxial confinement. We show that the underlying mechanism involved in healing is pressure sintering caused by the creep of connecting asperities.

  9. Partial gravity unloading inhibits bone healing responses in a large animal model.

    PubMed

    Gadomski, Benjamin C; McGilvray, Kirk C; Easley, Jeremiah T; Palmer, Ross H; Santoni, Brandon G; Puttlitz, Christian M

    2014-09-22

    The reduction in mechanical loading associated with space travel results in dramatic decreases in the bone mineral density (BMD) and mechanical strength of skeletal tissue resulting in increased fracture risk during spaceflight missions. Previous rodent studies have highlighted distinct bone healing differences in animals in gravitational environments versus those during spaceflight. While these data have demonstrated that microgravity has deleterious effects on fracture healing, the direct translation of these results to human skeletal repair remains problematic due to substantial differences between rodent and human bone. Thus, the objective of this study was to investigate the effects of partial gravitational unloading on long-bone fracture healing in a previously-developed large animal Haversian bone model. In vivo measurements demonstrated significantly higher orthopedic plate strains (i.e. load burden) in the Partial Unloading (PU) Group as compared to the Full Loading (FL) Group following the 28-day healing period due to inhibited healing in the reduced loading environment. DEXA BMD in the metatarsus of the PU Group decreased 17.6% (p<0.01) at the time of the ostectomy surgery. Four-point bending stiffness of the PU Group was 4.4 times lower than that of the FL Group (p<0.01), while µCT and histomorphometry demonstrated reduced periosteal callus area (p<0.05), mineralizing surface (p<0.05), mineral apposition rate (p<0.001), bone formation rate (p<0.001), and periosteal/endosteal osteoblast numbers (p<0.001/p<0.01, respectively) as well as increased periosteal osteoclast number (p<0.05). These data provide strong evidence that the mechanical environment dramatically affects the fracture healing cascade, and likely has a negative impact on Haversian system healing during spaceflight.

  10. Local administration of AAV-DJ pseudoserotype expressing COX2 provided early onset of transgene expression and promoted bone fracture healing in mice.

    PubMed

    Lakhan, R; Baylink, D J; Lau, K-H W; Tang, X; Sheng, M H-C; Rundle, C H; Qin, X

    2015-09-01

    We have previously obtained compelling proof-of-principle evidence for COX2 gene therapy for fracture repair using integrating retroviral vectors. For this therapy to be suitable for patient uses, a suitable vector with high safety profile must be used. Accordingly, this study sought to evaluate the feasibility of AAV as the vector for this COX2 gene therapy, because AAV raises less safety issues than the retroviral vectors used previously. However, an appropriate AAV serotype is required to provide early increase in and adequate level of COX2 expression that is needed for fracture repair. Herein, we reported that AAV-DJ, an artificial AAV pseudoserotype, is highly effective in delivering COX2 gene to fracture sites in a mouse femoral fracture model. Compared with AAV-2, the use of AAV-DJ led to ~5-fold increase in infectivity in mesenchymal stem cells (MSCs) and provided an earlier and significantly higher level of transgene expression at the fracture site. Injection of this vector at a dose of 7.5 × 10(11) genomic copies led to high COX2 level at the fracture site on day 3 after injections and significantly promoted fracture union at 21 days, as analyzed by radiography and μ-CT. The therapeutic effect appears to involve enhanced osteoblastic differentiation of MSCs and remodeling of callus tissues to laminar bone. This interpretation is supported by the enhanced expression of several key genes participating in the fracture repair process. In conclusion, AAV-DJ is a promising serotype for the AAV-based COX2 gene therapy of fracture repair in humans.

  11. Stress and wound healing.

    PubMed

    Cohen, I

    1979-01-01

    An experiment was performed to compare the effects of stressors--cold, heat and noise--on primary wound activity (i.e., wound closure in the first 24 h after wound infliction) and on rate of healing in mice. A significant correlation was found between reduced primary wound activity and a faster rate of healing. Conversely, a correlation was found between relatively greater primary wound activity and a slower rate of healing. A possible explanation of this correlation is a compensatory mechanism inherent to the skin healing process. This mechanism is visualized as (1) stress exposure affecting the skin by (a) causing it to become thinner and tauter and (b) causing it to have less elastic recoil; therefore, (2) when a square wound is produced in stressed skin, (a) the wound does not recoil readily or gapes soon after cutting and (b) a longer wound perimeter results. Because there is evidence that rate of healing is governed by cells on the wound perimeter, the greater the perimeter, the greater the number of cells that will undergo rapid mitosis and the faster will be the rate of healing. Therefore, stressed skin will heal at a faster rate, compensating for the loss of elasticity and cellular depletion caused by stress. This study is of interest to anthropology because it deals with dynamic adaptation, trying to grasp the meaning of the elusive endocrine interface between environmental stimulation and a measurable physical entity like healing. This work may have revealed a functional complex that is common to the healing of all mammalian skin, whereby retarding effects of stress on the healing process are obviated.

  12. Chronic Omega-3 Polyunsaturated Fatty Acid Treatment Variably Affects Cellular Repolarization in a Healed Post-MI Arrhythmia Model

    PubMed Central

    Bonilla, Ingrid M.; Nishijima, Yoshinori; Vargas-Pinto, Pedro; Baine, Stephen H.; Sridhar, Arun; Li, Chun; Billman, George E.; Carnes, Cynthia A.

    2016-01-01

    Introduction: Over the last 40 years omega-3 polyunsaturated fatty acids (PUFAs) have been shown to be anti-arrhythmic or pro-arrhythmic depending on the method and duration of administration and model studied. We previously reported that omega-3 PUFAs do not confer anti-arrhythmic properties and are pro-arrhythmic in canine model of sudden cardiac death (SCD). Here, we evaluated the effects of chronic omega-3 PUFA treatment in post-MI animals susceptible (VF+) or resistant (VF−) to ventricular tachyarrhythmias. Methods: Perforated patch clamp techniques were used to measure cardiomyocyte action potential durations (APD) at 50 and 90% repolarization and short term variability of repolarization. The early repolarizing transient outward potassium current Ito was also studied. Results: Omega-3 PUFAs prolonged the action potential in VF− myocytes at both 50 and 90% repolarization. Short term variability of repolarization was increased in both untreated and treated VF− myocytes vs. controls. Ito was unaffected by omega-3 PUFA treatment. Omega-3 PUFA treatment attenuated the action potential prolongation in VF+ myocytes, but did not return repolarization to control values. Conclusions: Omega-3 PUFAs do not confer anti-arrhythmic properties in the setting of healed myocardial infarction in a canine model of SCD. In canines previously resistant to ventricular fibrillation (VF−), omega-3 PUFA treatment prolonged the action potential in VF− myocytes, and may contribute to pro-arrhythmic responses. PMID:27378936

  13. A 6-year exercise program improves skeletal traits without affecting fracture risk: a prospective controlled study in 2621 children.

    PubMed

    Detter, Fredrik; Rosengren, Björn E; Dencker, Magnus; Lorentzon, Mattias; Nilsson, Jan-Åke; Karlsson, Magnus K

    2014-06-01

    Most pediatric exercise intervention studies that evaluate the effect on skeletal traits include volunteers and follow bone mass for less than 3 years. We present a population-based 6-year controlled exercise intervention study in children with bone structure and incident fractures as endpoints. Fractures were registered in 417 girls and 500 boys in the intervention group (3969 person-years) and 835 girls and 869 boys in the control group (8245 person-years), all aged 6 to 9 years at study start, during the 6-year study period. Children in the intervention group had 40 minutes daily school physical education (PE) and the control group 60 minutes per week. In a subcohort with 78 girls and 111 boys in the intervention group and 52 girls and 54 boys in the control group, bone mineral density (BMD; g/cm(2) ) and bone area (mm(2) ) were measured repeatedly by dual-energy X-ray absorptiometry (DXA). Peripheral quantitative computed tomography (pQCT) measured bone mass and bone structure at follow-up. There were 21.7 low and moderate energy-related fractures per 1000 person-years in the intervention group and 19.3 fractures in the control group, leading to a rate ratio (RR) of 1.12 (0.85, 1.46). Girls in the intervention group, compared with girls in the control group, had 0.009 g/cm(2) (0.003, 0.015) larger gain annually in spine BMD, 0.07 g (0.014, 0.123) larger gain in femoral neck bone mineral content (BMC), and 4.1 mm(2) (0.5, 7.8) larger gain in femoral neck area, and at follow-up 24.1 g (7.6, 40.6) higher tibial cortical BMC (g) and 23.9 mm(2) (5.27, 42.6) larger tibial cross-sectional area. Boys with daily PE had 0.006 g/cm(2) (0.002, 0.010) larger gain annually in spine BMD than control boys but at follow-up no higher pQCT values than boys in the control group. Daily PE for 6 years in at study start 6- to 9-year-olds improves bone mass and bone size in girls and bone mass in boys, without affecting the fracture risk.

  14. A 5-year exercise program in pre- and peripubertal children improves bone mass and bone size without affecting fracture risk.

    PubMed

    Detter, Fredrik T L; Rosengren, Björn E; Dencker, Magnus; Nilsson, J-Å; Karlsson, Magnus K

    2013-04-01

    We studied the effect in children of an exercise intervention program on fracture rates and skeletal traits. Fractures were registered for 5 years in a population-based prospective controlled exercise intervention study that included children aged 6-9 years at study start, 446 boys and 362 girls in the intervention group and 807 boys and 780 girls in the control group. Intervention subjects received 40 min/school day of physical education and controls, 60 min/week. In 73 boys and 48 girls in the intervention group and 52 boys and 48 girls in the control group, bone mineral density (BMD, g/cm(2)) and bone area (mm(2)) were followed annually by dual-energy X-ray absorptiometry, after which annual changes were calculated. At follow-up we also assessed trabecular and cortical volumetric BMD (g/cm(3)) and bone structure by peripheral computed tomography in the tibia and radius. There were 20.0 fractures/1,000 person-years in the intervention group and 18.5 fractures/1,000 person-years in the control group, resulting in a rate ratio of 1.08 (0.79-1.47) (mean and 95 % CI). The gain in spine BMD was higher in both girls (difference 0.01 g/cm(2), 0.005-0.019) and boys (difference 0.01 g/cm(2), 0.001-0.008) in the intervention group. Intervention girls also had higher gain in femoral neck area (difference 0.04 mm(2), 0.005-0.083) and at follow-up larger tibial bone mineral content (difference 0.18 g, 0.015-0.35), larger tibial cortical area (difference 17 mm(2), 2.4-31.3), and larger radial cross-sectional area (difference 11.0 mm(2), 0.63-21.40). As increased exercise improves bone mass and in girls bone size without affecting fracture risk, society ought to encourage exercise during growth.

  15. Genetic analysis identifies DDR2 as a novel gene affecting bone mineral density and osteoporotic fractures in Chinese population.

    PubMed

    Guo, Yan; Yang, Tie-Lin; Dong, Shan-Shan; Yan, Han; Hao, Ruo-Han; Chen, Xiao-Feng; Chen, Jia-Bin; Tian, Qing; Li, Jian; Shen, Hui; Deng, Hong-Wen

    2015-01-01

    DDR2 gene, playing an essential role in regulating osteoblast differentiation and chondrocyte maturation, may influence bone mineral density (BMD) and osteoporosis, but the genetic variations actually leading to the association remain to be elucidated. Therefore, the aim of this study was to investigate whether the genetic variants in DDR2 are associated with BMD and fracture risk. This study was performed in three samples from two ethnicities, including 1,300 Chinese Han subjects, 700 Chinese Han subjects (350 with osteoporotic hip fractures and 350 healthy controls) and 2,286 US white subjects. Twenty-eight SNPs in DDR2 were genotyped and tested for associations with hip BMD and fractures. We identified 3 SNPs in DDR2 significantly associated with hip BMD in the Chinese population after multiple testing adjustments, which were rs7521233 (P = 1.06×10-4, β: -0.018 for allele C), rs7553831 (P = 1.30×10-4, β: -0.018 for allele T), and rs6697469 (P = 1.59×10-3, β: -0.015 for allele C), separately. These three SNPs were in high linkage disequilibrium. Haplotype analyses detected two significantly associated haplotypes, including one haplotype in block 2 (P = 9.54×10-4, β: -0.016) where these three SNPs located. SNP rs6697469 was also associated with hip fractures (P = 0.043, OR: 1.42) in the Chinese population. The effect on fracture risk was consistent with its association with lower BMD. However, in the white population, we didn't observe significant associations with hip BMD. eQTL analyses revealed that SNPs associated with BMD also affected DDR2 mRNA expression levels in Chinese. Our findings, together with the prior biological evidence, suggest that DDR2 could be a new candidate for osteoporosis in Chinese population. Our results also reveal an ethnic difference, which highlights the need for further genetic studies in each ethnic group.

  16. Effect of cell-based VEGF gene therapy on healing of a segmental bone defect.

    PubMed

    Li, Ru; Stewart, Duncan J; von Schroeder, Herbert P; Mackinnon, Erin S; Schemitsch, Emil H

    2009-01-01

    Fracture healing requires coordinated coupling between osteogenesis and angiogenesis in which vascular endothelial growth factor (VEGF) plays a key role. We hypothesized that targeted over-expression of angiogenic and osteogenic factors within the fracture would promote bone healing by inducing development of new blood vessels and stimulating/affecting proliferation, survival, and activity of skeletal cells. Using a cell-based method of gene transfer, without viral vector, 5.0 x 10(6) fibroblasts transfected with VEGF were delivered to a 10-mm bone defect in rabbit tibiae (Group 1) (n = 9); control groups were treated with fibroblasts (Group 2) (n = 7), or saline (Group 3) (n = 7) only. After 12 weeks, eight tibial fractures healed in Group 1, compared to four each in Groups 2 and 3. In Group 1, ossification was seen across the entire defect; in Groups 2 and 3, the defects were fibrous and sparsely ossified. Group 1 had more positively stained (CD31) vessels than Groups 2 and 3. MicroCT 3-D showed complete bridging of the new bone for Group 1, but incomplete healing for Groups 2 and 3. MicroCT bone structural parameters showed significant differences between VEGF treatment and control groups (p < 0.05). These results indicate that the cell-based VEGF gene therapy has significant angiogenic and osteogenic effects to enhance healing of a segmental defect in the long bone of rabbits.

  17. Evaluation of a Topical Herbal Agent for the Promotion of Bone Healing

    PubMed Central

    Siu, Wing-Sum; Ko, Chun-Hay; Lam, Ka-Wing; Shum, Wai-Ting; Lau, Clara Bik-San; Ko, Kam-Ming; Hung, Leung-Kim; Lau, David Tai-Wai; Leung, Ping-Chung

    2015-01-01

    A topically used Chinese herbal paste, namely, CDNR, was designed to facilitate fracture healing which is usually not addressed in general hospital care. From our in vitro studies, CDNR significantly inhibited the release of nitric oxide from RAW264.7 cells by 51 to 77%. This indicated its anti-inflammatory effect. CDNR also promoted the growth of bone cells by stimulating the proliferation of UMR106 cells up to 18%. It also increased the biomechanical strength of the healing bone in a drill-hole defect rat model by 16.5% significantly. This result revealed its in vivo efficacy on facilitation of bone healing. Furthermore, the detection of the chemical markers of CDNR in the skin and muscle of the treatment area demonstrated its transdermal properties. However, CDNR did not affect the bone turnover markers in serum of the rats. With its anti-inflammatory and bone formation properties, CDNR is found effective in promoting bone healing. PMID:25810746

  18. Bone Healing by Using Ilizarov External Fixation Combined with Flexible Intramedullary Nailing versus Ilizarov External Fixation Alone in the Repair of Tibial Shaft Fractures: Experimental Study

    PubMed Central

    Popkov, A. V.; Kononovich, N. A.; Gorbach, E. N.; Tverdokhlebov, S. I.; Irianov, Y. M.; Popkov, D. A.

    2014-01-01

    Purpose. Our research was aimed at studying the radiographic and histological outcomes of using flexible intramedullary nailing (FIN) combined with Ilizarov external fixation (IEF) versus Ilizarov external fixation alone on a canine model of an open tibial shaft fracture. Materials and Methods. Transverse diaphyseal tibial fractures were modelled in twenty dogs. Fractures in the dogs of group 1 (n = 10) were stabilized with the Ilizarov apparatus while it was combined with FIN in group 2 (n = 10). Results. On day 14, a bone tissue envelope started developing round the FIN wires. Histologically, we revealed only endosteal bone union in group 1 while in group 2 the radiographs revealed complete bone union on day 28. At the same time-point, the areas of cancellous and mature lamellar bone tissues were observed in the intermediary area in group 2. The periosteal layers were formed of the trabeculae net of lamellar structure and united the bone fragments. The frame was removed at 30 days after the fracture in group 2 and after 45 days in group 1 according to bone regeneration. Conclusion. The combination of the Ilizarov apparatus and FIN accelerates bone repair and augments stabilization of tibial shaft fractures as compared with the use of the Ilizarov fixation alone. PMID:25379523

  19. Integrating Epigenomic Elements and GWASs Identifies BDNF Gene Affecting Bone Mineral Density and Osteoporotic Fracture Risk

    PubMed Central

    Guo, Yan; Dong, Shan-Shan; Chen, Xiao-Feng; Jing, Ying-Aisha; Yang, Man; Yan, Han; Shen, Hui; Chen, Xiang-Ding; Tan, Li-Jun; Tian, Qing; Deng, Hong-Wen; Yang, Tie-Lin

    2016-01-01

    To identify susceptibility genes for osteoporosis, we conducted an integrative analysis that combined epigenomic elements and previous genome-wide association studies (GWASs) data, followed by validation at population and functional levels, which could identify common regulatory elements and predict new susceptibility genes that are biologically meaningful to osteoporosis. By this approach, we found a set of distinct epigenomic elements significantly enriched or depleted in the promoters of osteoporosis-associated genes, including 4 transcription factor binding sites, 27 histone marks, and 21 chromatin states segmentation types. Using these epigenomic marks, we performed reverse prediction analysis to prioritize the discovery of new candidate genes. Functional enrichment analysis of all the prioritized genes revealed several key osteoporosis related pathways, including Wnt signaling. Genes with high priority were further subjected to validation using available GWASs datasets. Three genes were significantly associated with spine bone mineral density, including BDNF, PDE4D, and SATB2, which all closely related to bone metabolism. The most significant gene BDNF was also associated with osteoporotic fractures. RNA interference revealed that BDNF knockdown can suppress osteoblast differentiation. Our results demonstrated that epigenomic data could be used to indicate common epigenomic marks to discover additional loci with biological functions for osteoporosis. PMID:27465306

  20. Acceleration of bone formation during fracture healing by poly(pro-hyp-gly)10 and basic fibroblast growth factor containing polycystic kidney disease and collagen-binding domains from Clostridium histolyticum collagenase.

    PubMed

    Sekiguchi, Hiroyuki; Uchida, Kentaro; Inoue, Gen; Matsushita, Osamu; Saito, Wataru; Aikawa, Jun; Tanaka, Keisuke; Fujimaki, Hisako; Miyagi, Masayuki; Takaso, Masashi

    2016-06-01

    Growth factor delivered in combination with animal-derived collagen materials has been used to accelerate bone fracture healing in human patients. However, the introduction of bovine proteins into humans carries the risk of zoonotic and immunologic complications. Here, we developed a collagen-like polypeptide-based bone formation system consisting of poly(Pro-Hyp-Gly)10 , which mimics the triple helical conformation of collagen, and basic fibroblast growth factor (bFGF) fused to the polycystic kidney disease (PKD) domain and collagen-binding domain (CBD) of Clostridium histolyticum collagenase. Circular dichroism spectral analysis showed that when pepsin-soluble bovine type I collagen was treated at 50°C, a positive signal corresponding to the collagen triple helix at 220 nm was not detected. In contrast, poly(Pro-Hyp-Gly)10 retained the 220-nm positive peak, even when treated at 80°C. The combination of the collagen binding-bFGF fusion protein (bFGF-PKD-CBD) with poly(Pro-Hyp-Gly)10 induced greater bone formation compared to bFGF alone in mice bone fracture models. Taken together, these properties suggest that the bFGF-PKD-CBD/poly(Pro-Hyp-Gly)10 composite is a promising material for bone repair in the clinical setting. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1372-1378, 2016.

  1. Surgical approach to bone healing in osteoporosis

    PubMed Central

    Pesce, Vito; Speciale, Domenico; Sammarco, Giulio; Patella, Silvio; Spinarelli, Antonio; Patella, Vittorio

    2009-01-01

    Osteoporotic fractures represent one of the most common cause of disability and one of the major voice in the health economic budget in many countries of the world. Fragility fractures are especially meta-epiphyseal fractures, in skeletal sites with particular biomechanic characteristic (hip, vertebrae), complex and with more fragments, with slow healing process (mineralization and remodeling) and co-morbidity. The healing of a fracture in osteoporotic bone passes through the normal stages and concludes with union of the fracture although the healing process is prolonged. Fractures in the elderly osteoporotic patients represent a challenge to the orthopaedic surgeons. Osteoporosis does not only increase the risk of fracture but also represents a problem in osteofixation of fractures in fracture treatment. The major technical problem that surgeons face, is the difficulty to obtain a stable fixation of an implant due to osteoporotic bone. The load transmitted at the bone-implant interface can often exceed the reduced strain tolerance of osteoporotic bone. In the treatment of osteoporotic fractures it is important to consider different aspects: general conditions of elderly patient and comorbidity, the reduced muscular and bone mass and the increased bone fragility, structural modifications as medullary expansion. The aim of surgical treatment is to obtain a stable fixation that reduces pain and permits an early mobilization. PMID:22461162

  2. Self-healing polymers

    NASA Technical Reports Server (NTRS)

    Klein, Daniel J. (Inventor)

    2011-01-01

    A three dimensional structure fabricated from a self-healing polymeric material, comprising poly(ester amides) obtained from ethylene glycol, azelaic acid and 1,1-aminoundecanoic acid, wherein polymeric material has a melt index above 2.5 g/10 min. as determined by ASTM D1238 at 190.degree. C. and 2.16kg, impact resistance and ductility sufficient to resist cracking and brittle fracture upon impact by a 9 mm bullet fired at a temperature of about 29.degree. C. at subsonic speed in a range from about 800 feet/sec to about 1000 feet/sec. It has been determined that the important factors necessary for self-healing behavior of polymers include sufficient impact strength, control of the degree of crystallinity, low melting point and the ability to instantly melt at impacted area.

  3. Crack Healing in Polymers.

    DTIC Science & Technology

    1983-10-17

    have shown experimentally and theoretically that Y - t°m° (24) YM ,. No (25) such that Y remains constant during healing and fracture. The number of...chains per unit volume, Nv., is Nv W (26) where p is the density and Na is Avogadros number. The strain energy density per chain, Uc, is therefore...force f = ol dl/dt, from the integral of fdl, as dlUp= I PoI(’i)dl (30) 4. where io is the monomer friction coefficient and dl/dt is a constant pull-out

  4. Measurement of ulnar variance and radial inclination on X-rays of healed distal radius fractures. With the axis of the distal radius or ulna?

    PubMed

    Thuysbaert, Gilles; Ringburg, Akkie; Petronilia, Steven; Vanden Berghe, Alex; Hollevoet, Nadine

    2015-06-01

    Ulnar variance and radial inclination are radiological parameters frequently used to evaluate displacement of distal radius fractures. In most studies measurements are based on the long central axis of the distal radius, although the axis of the distal ulna can also be used. The purpose of this study was to determine which axis is more reliable. Four observers performed measurements on standard anteroposterior digital wrist X-rays of 20 patients taken 1 and 2 months after sustaining an extra-articular distal radius fracture. Intraobserver reliability was similar with both methods. No difference was found in interobserver reliability between both methods for ulnar variance, but for radial inclination it was better with the axis through the radius. Measurements on two X-rays of the same wrist taken at a different moment were similar with both methods. It can be concluded that the central axis of the distal radius can remain the basis to determine ulnar variance and radial inclination.

  5. Quality of Bone Healing: Perspectives and Assessment Techniques

    DTIC Science & Technology

    2014-01-01

    uniquely restricted to appositional growth; therefore, all activities occur on bone surfaces, either the outer periosteal or marrow- oriented...Standardized scoring systems such as the radio- graphic union score for tibial fractures39 allow for a reduction in the variability of assessing fracture...O’Connor B, Kenwright J. Measuring stiffness can define healing of tibial fractures. J Bone Joint Surg 1994; 76-B: 389–94. Guda et al. Bone healing

  6. Decreased BMP2 signal in GIT1 knockout mice slows bone healing

    PubMed Central

    Fan, Jin; Zhou, Hao; Zuscik, Michael J.; Xie, Chao; Yin, Guoyong; Berk, Bradford C.

    2015-01-01

    Endochondral ossification, an important stage of fracture healing, is regulated by a variety of signaling pathways. Transforming growth factor b (TGFb) superfamily plays important roles and comprises TGFbs, bone morphogenetic proteins (BMPs), and growth differentiation factors. TGFbs primarily regulate cartilage formation and endochondral ossification. BMP2 shows diverse efficacy, from the formation of skeleton and extraskeletal organs to the osteogenesis and remodeling of bone. G-protein-coupled receptor kinase 2-interacting protein-1 (GIT1), a shuttle protein in osteoblasts, facilitates fracture healing by promoting bone formation and increasing the secretion of vascular endothelial growth factor. Our study examined whether GIT1 regulates fracture healing through the BMP2 signaling pathway and/or through the TGFb signaling pathway. GIT1 knockout (KO) mice exhibited delayed fracture healing, chondrocyte accumulation in the fracture area, and reduced staining intensity of phosphorylated Smad1/5/8 (pSmad1/5/8) and Runx2. Endochondral mineralization diminished while the staining intensity of phosphorylated Smad2/3 (pSmad2/3) showed no significant change. Bone marrow mesenchymal stem cells extracted from GIT1 KO mice showed a decline of pSmad1/5/8 levels and of pSmad1/5/8 translocated into the cell nucleus after BMP2 stimulus. We detected no significant change in the pSmad2/3 level after TGFb1 stimulus. Data obtained from reporter gene analysis of C3H10T1/2 cells cultured in vitro confirmed these findings. GIT1-siRNA inhibited transcription in the cell nucleus via pSmad1/5/8 after BMP2 stimulus but had no significant effect on transcription via pSmad2/3 after TGFb1 stimulus. Our results indicate that GIT1 regulates Smad1/5/8 phosphorylation and mediates BMP2 regulation of Runx2 expression, thus affecting endochondral ossification at the fracture site. PMID:25138700

  7. Bilateral mandibular fracture related to osteoradionecrosis

    PubMed Central

    Goyal, Shikha; Mohanti, Bidhu Kalyan

    2015-01-01

    Mandible is the most frequently affected bone during head and neck irradiation. Late changes in the mandible may manifest in the form of reduced bone density, dental caries, loss of spongiosa trabeculations, delayed healing following dental extraction, pathologic fractures, osteoradionecrosis, trismus, growth defects in children or second malignancies. Pathologic fractures of mandibular bone are rare and may be spontaneous or traumatic (following dental extraction). We report the case of a 55-year lady, who had undergone surgery and adjuvant radiotherapy for carcinoma oral tongue T2N0M0 on a cobalt-60 unit and was disease-free. After a follow-up of 8 years post-irradiation, she presented with sudden onset oral pain and inability to open mouth. Pantomogram showed fracture at the junction of body and ramus of the mandible bilaterally. PMID:26097342

  8. Healing Invisible Wounds

    ERIC Educational Resources Information Center

    Adams, Erica J.

    2010-01-01

    As many as 9 in 10 justice-involved youth are affected by traumatic childhood experiences. According to "Healing Invisible Wounds: Why Investing in Trauma-Informed Care for Children Makes Sense," between 75 and 93 percent of youth currently incarcerated in the justice system have had at least one traumatic experience, including sexual…

  9. Occurrence and pattern of long bone fractures in growing dogs with normal and osteopenic bones.

    PubMed

    Kumar, K; Mogha, I V; Aithal, H P; Kinjavdekar, P; Singh, G R; Pawde, A M; Kushwaha, R B

    2007-11-01

    A retrospective study was undertaken to record the occurrence and pattern of long bone fractures, and the efficacy of Intramedullary (IM) Steinmann pin fixing in growing dogs. All the records of growing dogs during a 10-year-period were screened to record the cause of trauma, the age and sex of the animal, the bone involved, the type and location of the fracture, the status of fixation, alignment, maintenance of fixation and fracture healing. The results were analysed and comparisons were made between growing dogs with normal and osteopenic bones. Among the 310 cases of fractures recorded, the bones were osteopenic in 91 cases (29%). Minor trauma was the principal cause of fracture in dogs with osteopenia (25%), and indigenous breeds were most commonly affected (38%). Fractures in dogs with osteopenic bones were most commonly recorded in the age group of 2-4 months (53%), whereas fractures in normal dogs were almost equally distributed between 2 and 8 months of age. Male dogs were affected significantly more often in both groups. In osteopenic bones, most fractures were recorded in the femur (56%), and they were distributed equally along the length of the bone. Whereas in normal bones, fractures were almost equally distributed in radius/ulna, femur and tibia, and were more often recorded at the middle and distal third of long bones. Oblique fractures were most common in both groups; however, comminuted fractures were more frequent in normal bones, whereas incomplete fractures were more common in osteopenic bones. Ninety-nine fracture cases treated with IM pinning (66 normal, 33 osteopenic) were evaluated for the status of fracture reduction and healing. In a majority of the cases (61%) with osteopenic bones, the diameter of the pin was relatively smaller than the diameter of the medullary cavity (<70-75%), whereas in 68% of the cases in normal bones the pin diameter was optimum. The status of fracture fixing was satisfactory to good in significantly more

  10. Scaphoid Proximal Pole Fracture Following Headless Screw Fixation

    PubMed Central

    Rancy, Schneider K.; Zelken, Jonathan A.; Lipman, Joseph D.; Wolfe, Scott W.

    2015-01-01

    Background Headless screw fixation of scaphoid fractures and nonunions yields predictably excellent outcomes with a relatively low complication profile. However, intramedullary implants affect the load to failure and stress distribution within bone and may be implicated in subsequent fracture. Case Description We describe a posttraumatic fracture pattern of the scaphoid proximal pole originating at the previous headless screw insertion site in three young male patients with healed scaphoid nonunions. Each fracture was remarkably similar in shape and size, comprised the volar proximal pole, and was contiguous with the screw entry point. Treatment was challenging but successful in all cases. Literature Review Previous reports have posited that stress-raisers secondary to screw orientation may be implicated in subsequent peri-implant fracture of the femoral neck. Repeat scaphoid fracture after screw fixation has also been reported. However, the shape and locality of secondary fracture have not been described, nor has the potential role of screw fixation in the production of distinct fracture patterns. Clinical Relevance Hand surgeons must be aware of this difficult complication that may follow antegrade headless screw fixation of scaphoid fracture nonunion, and of available treatment strategies. PMID:26855840

  11. Labral Healing

    PubMed Central

    Catan, Agustín; Vilaseca, Tomas; Arroquy, Damián; Carboni, Martín; Guiñazú, Jorge Eduardo; Orlowsky, Belén; Irigoitia, Nicolas; Chahla, Jorge

    2017-01-01

    Objectives: The purpouse of this study was to evaluate MRI images of labral repair after one year, trying to stablish MRI images as a reliable tool for the diagnosis of labral healing. Methods: One hundred and sixty-two patients presenting with femoroacetabular impingement that underwent an arthroscopic surgery were treated between 2012 and 2015. Of these, 124 met the selection criteria and were included in this study. Only patients with 12 months of follow up and labral repair were included. Patients with previous hip surgery were excluded. Coronal, sagittal and axial MRI cuts were evaluated by three independent observers, an arthroscopic hip surgery, a fellow in hip arthroscopic surgery and a musculoeskeletal radiologist. Results: on regard of our statistics 68% of the patients had labral healing images, 16% had no healing signals and 16% unsatisfactory images. Just in the 47% the observers had a 100% of agreement. Interobserver variation was: intraobserver agreement was 94% ( arthroscopic surgeon), 72 % (radiologist), 67 % (fellow). Conclusion: The main finding of this study was that a high inter and intraobserver variability was found when analysing the healing status of hip repaired labrums. Assessment of labrum healing after an arthroscopic repair should not only rely on imaging methods and therefore should be concurrently performed with a comprehensive physical examination.

  12. Effects of parathyroid hormone 1-34 on osteogenic and chondrogenic differentiation of human fracture haematoma-derived cells in vitro.

    PubMed

    Dogaki, Yoshihiro; Lee, Sang Yang; Niikura, Takahiro; Koga, Takaaki; Okumachi, Etsuko; Nishida, Kotaro; Kuroda, Ryosuke; Kurosaka, Masahiro

    2016-10-01

    Parathyroid hormone (PTH) 1-34 has been shown to accelerate fracture healing. Previously, we reported that progenitor cells with osteogenic and chondrogenic potential exist in human fracture haematoma, suggesting that the fracture haematoma-derived progenitor cells (HCs) contribute to fracture healing. However, there has been no study investigating the effect of PTH on HCs. We investigated the effect of pulsatile and continuous PTH treatment on human fracture HCs in vitro. HCs were isolated from seven patients. The HCs were divided into four groups: growth medium; control [osteogenic medium (OM) without PTH]; PTH-C (OM with continuous PTH); and PTH-P (OM with pulsatile PTH) groups. Osteogenic differentiation potential and proliferation of HCs were compared among the four groups. For chondrogenesis, the HCs were divided into two groups: control [chondrogenic medium (CM) without PTH]; and PTH-C (CM with continuous PTH) groups, and chondrogenic differentiation potential was analysed. PTH treatment did not affect cell proliferation, regardless of the mode of administration. Osteogenic activity was also not significantly affected by continuous PTH treatment but significantly inhibited by pulsatile PTH treatment. Conversely, chondrogenic differentiation was significantly inhibited by continuous PTH treatment. Our results revealed that PTH treatment on HCs, either continuous or pulsatile, does not exhibit any positive effect, and indicates that exogenous PTH administration after fracture has no effect on HCs. PTH may not have a positive effect at the fracture site during the early stage of fracture healing in which haematoma formation occurs. Copyright © 2013 John Wiley & Sons, Ltd.

  13. The effect of crutches, an orthosis TheraTogs, and no walking aids on the recovery of gait in a patient with delayed healing post hip fracture: A case report.

    PubMed

    Maguire, Clare; Sieben, Judith M; Scheidhauer, Heike; Romkes, Jacqueline; Suica, Zorica; de Bie, Robert A

    2016-01-01

    Accelerated rehabilitation following hip fracture and joint replacement, including early unrestricted weight-bearing and muscle strengthening, has gained importance in hastening functional recovery and hospital discharge. The influence of walking aids on these parameters is sparsely investigated. In this case report, we document the effect of walking with crutches; an orthotic garment and strapping system, TheraTogs; and no walking aids over 3-4-week periods on walking speed, trunk sway, and muscle activity measured with electromyography (EMG). The patient was a 49-year-old female showing delayed healing following a conservatively treated avulsion fracture of the greater trochanter 12 weeks previously with a 14-year history of total hip arthroplasty. EMG analysis showed muscle activity increased with TheraTogs and decreased with crutches compared with walking with no aids. Walking speed improved at a faster rate in the TheraTogs phase than in the crutches phase and reduced in no-walking-aids phase. Mean speed (SD) for each phase was: crutches 1.11 (0.08) m/s, TheraTogs 1.35 (0.11) m/s, and no-aids 1.19 (0.14) m/s. Trunk sway increased in the crutch and no-aids phases, and became more stable in the TheraTogs phase. In this patient, function and recovery rate of all measured parameters increased more in the TheraTogs phase than the crutches or no-aids phase. This may be because muscle activity was facilitated enabling active support of recovering structures.

  14. Nose fracture

    MedlinePlus

    Fracture of the nose; Broken nose; Nasal fracture; Nasal bone fracture; Nasal septal fracture ... A fractured nose is the most common fracture of the face. It ... with other fractures of the face. Sometimes a blunt injury can ...

  15. Pressurized vascular systems for self-healing materials

    PubMed Central

    Hamilton, A. R.; Sottos, N. R.; White, S. R.

    2012-01-01

    An emerging strategy for creating self-healing materials relies on embedded vascular networks of microchannels to transport reactive fluids to regions of damage. Here we investigate the use of active pumping for the pressurized delivery of a two-part healing system, allowing a small vascular system to deliver large volumes of healing agent. Different pumping strategies are explored to improve the mixing and subsequent polymerization of healing agents in the damage zone. Significant improvements in the number of healing cycles and in the overall healing efficiency are achieved compared with prior passive schemes that use only capillary forces for the delivery of healing agents. At the same time, the volume of the vascular system required to achieve this superior healing performance is significantly reduced. In the best case, nearly full recovery of fracture toughness is attained throughout 15 cycles of damage and healing, with a vascular network constituting just 0.1 vol% of the specimen. PMID:21957119

  16. Healing and Shear Stress Reduction on Single Fracture of Rock Salt and Limestone under Slide-Hold-Slide Direct Shear Condition

    NASA Astrophysics Data System (ADS)

    Kishida, K.; Yano, T.; Yasuhara, H.

    2012-12-01

    In order to clarify the influence of the holding state on the shear strength in the shear process of a single rock fracture, slide-hold-slide (SHS) direct shear-flow coupling tests were carried out on single rock fractures at several confining stresses and under saturated/unsaturated conditions (Kishida, et al., 2011). Consequently, the mortar specimen could be confirmed as the significant shear strength recovery on the SHS process. In this research, the SHS direct shear tests are carried out on the halite (rock salt) and the limestone. In the case of rock salt, a single tensile fracture is artificially created by cutting away. On the other hand, the limestone has a natural rock joint. The experiments are carried out under various normal confining stress conditions and are employed various holding period at the residual state. Figure 1 shows the shear stress - shear displacement of the SHS direct shear experiments on the rock salt. From all cases, the shear stress increases at the initial phase of the experiments, and then, the shear stress reaches at the peak shear strength. After that, the shear stress slightly decreases such as strain softening. Finally, the shear stress reaches to the residual stress state. In every SHS processes, the shear stress is reducing in various hold period. And then, the shear stress is increasing in the process of re-sliding. The shear stress in the process of re-sliding takes over the value at the start time of the holding process. The shear stress reaches at the peak, and then, it reaches the residual stress state. In all cases, as the holding period becomes longer, it is confirmed that the decrement of the shear stress in the holding process is increasing and the increment of the shear stress at the re-sliding process is increasing. Therefore, it is confirmed that the time dependence of shear strength recovery can be observed. In addition, Dieterich's A constant value for the regression lines (Dieterich, 1972, 1994) is plotted

  17. The use of platelets to affect functional healing of an anterior cruciate ligament (ACL) autograft in a caprine ACL reconstruction model.

    PubMed

    Spindler, Kurt P; Murray, Martha M; Carey, James L; Zurakowski, David; Fleming, Braden C

    2009-05-01

    Many anterior cruciate ligament (ACL) reconstructions have increased laxity postoperatively. We hypothesized that enhancing an ACL graft with a collagen-platelet composite (CPC) would improve knee laxity and graft structural properties. We also hypothesized the platelet concentration in the CPC would affect these parameters. Twelve goats underwent ACL reconstruction with autologous patellar tendon graft. In six goats, a collagen-platelet composite was placed around the graft (CPC group). In the remaining six goats, the collagen scaffold only was used (COLL group). Three goats were excluded due to complications. After 6 weeks in vivo, anterior-posterior (AP) laxity and tensile properties of the ACL reconstructed knees were measured and normalized against the contralateral intact knee. At a knee flexion angle of 30 degrees, the average increase in AP laxity was 40% less in the CPC group than the COLL group (p = 0.045). At 60 degrees, the AP laxity was 30% less in the CPC group, a difference that was close to statistical significance (p = 0.080). No differences were found between treatment groups with respect to the structural properties (p > 0.30). However, there were significant correlations between serum platelet concentration and AP laxity (R2 = 0.643; p = 0.009), maximum load (R2 = 0.691; p = 0.006), and graft stiffness (R2 = 0.840; p < 0.001). In conclusion, use of a CPC to enhance healing of an allograft ACL reconstruction inversely correlated with early sagittal plane laxity and the systemic platelet count was highly predictive of ACL reconstruction graft strength and stiffness at 6 weeks. These findings emphasize the importance of further research on delineating the effect of platelets in treating of ACL injuries.

  18. Micromechanical processes of frictional aging and the affect of shear stress on fault healing: insights from material characterization and ultrasonic velocity measurements

    NASA Astrophysics Data System (ADS)

    Ryan, K. L.; Marone, C.

    2015-12-01

    During the seismic cycle, faults repeatedly fail and regain strength. The gradual strength recovery is often referred to as frictional healing, and existing works suggest that healing can play an important role in determining the mode of fault slip ranging from dynamic rupture to slow earthquakes. Laboratory studies can play an important role in identifying the processes of frictional healing and their evolution with shear strain during the seismic cycle. These studies also provide data for laboratory-derived friction constitutive laws, which can improve dynamic earthquake models. Previous work shows that frictional healing varies with shear stress on a fault during the interseismic period. Unfortunately, the micromechanical processes that cause shear stress dependent frictional healing are not well understood and cannot be incorporated into current earthquake models. In fault gouge, frictional healing involves compaction and particle rearrangement within sheared granular layers. Therefore, to address these issues, we investigate the role grain size reduction plays in frictional re-strengthening processes at different levels of shear stress. Sample material was preserved from biaxial deformation experiments on granular Westerly granite. The normal stress was held constant at 25 MPa and we performed several 100 second slide-hold-slide tests in each experiment. We conducted a series of 5 experiments each with a different value of normalized shear stress (ranging from 0 to 1), defined as the ratio of the pre-hold shear stress to the shear stress during the hold. The particle size distribution for each sample was analyzed. In addition, acoustic measurements were recorded throughout our experiments to investigate variations in ultrasonic velocity and signal amplitude that reflect changes in the elastic moduli of the layer. Acoustic monitoring provides information about healing mechanisms and can provide a link between laboratory studies and tectonic fault zones.

  19. How wounds heal

    MedlinePlus

    ... care to prevent infection. Continue Reading Stages of Wound Healing Wounds heal in stages. The smaller the wound, ... How lacerations heal References Leong M, Phillips LG. Wound healing. In: Townsend CM, Beauchamp RD, Evers BM, Mattox ...

  20. How does a physical activity programme in elementary school affect fracture risk? A prospective controlled intervention study in Malmo, Sweden

    PubMed Central

    Cöster, Marcus E; Fritz, Jesper; Nilsson, Jan-Åke; Karlsson, Caroline; Rosengren, Björn E; Dencker, Magnus; Karlsson, Magnus K

    2017-01-01

    Objectives Recent evidence from the 7-year follow-up of the Pediatric Osteoporosis Prevention (POP) study indicates an inverse correlation between years of participation in a physical activity (PA) intervention and fracture risk in children. However, we could not see a statistically significant reduction in fracture risk, which urged for an extension of the intervention. Setting The study was conducted in 4 neighbouring elementary schools, where 1 school functioned as intervention school. Participants We included all children who began first grade in these 4 schools between 1998 and 2012. This resulted in 1339 children in the intervention group and 2195 children in the control group, all aged 6–8 years at the state of the study. Intervention We launched an 8-year intervention programme with 40 min of moderate PA per school day, while the controls continued with the Swedish national standard of 60 min of PA per week. Primary outcome measure We used the regional radiographic archive to register objectively verified fractures and we estimated annual fracture incidences and incidence rate ratios (IRRs). Results During the first year after initiation of the intervention, the fracture IRR was 1.65 (1.05 to 2.08) (mean 95% CI). For each year of the study, the fracture incidence rate in the control group compared with the intervention group increased by 15.7% (5.6% to 26.8%) (mean 95% CI). After 8 years, the IRR of fractures was 52% lower in the intervention group than in the control group (IRR 0.48 (0.25 to 0.91) (mean 95% CI))]. Conclusions Introduction of the school-based intervention programme is associated with a higher fracture risk in the intervention group during the first year followed by a gradual reduction, so that during the eighth year, the fracture risk was lower in the intervention group. Trial registration number NCT00633828. PMID:28235964

  1. Self-Healing Software

    NASA Astrophysics Data System (ADS)

    Frei, Regina; Serugendo, Giovanna Di Marzo

    The following sections are included: * Introduction * Self-Awareness as an Aspect of Self-Healing * A Working Taxonomy for Software Self-Healing * Failures, errors and faults * Approaches to Software Self-Healing * Self-healing at code level * Self-healing through self-organisation * Self-healing based on policies * Architectures for self-healing * Model-based solutions for self-healing * Discussion and Conclusion

  2. The osteogenic activity of human mandibular fracture haematoma-derived progenitor cells is affected by bisphosphonate in vitro.

    PubMed

    Imai, Y; Hasegawa, T; Takeda, D; Akashi, M; Komori, T

    2015-03-01

    It is known that bisphosphonates (BPs) suppress the activity of osteoclasts; however, it has not been reported whether BPs affect the potential of human mandibular fracture haematoma-derived cells (MHCs) for bone differentiation. In this study, we examined whether the degree of bone differentiation changes following the administration of BP in vitro. The effects of alendronate and risedronate (10(-8) to 10(-7)M (mol/l)) on cell proliferation were evaluated at 4 and 8 days, after which BP treatment was applied for 4, 8, 14, and 20 days prior to assessing the alkaline phosphatase (ALP) activity and performing the mineralization assay. Alendronate 10(-8) and 10(-7)M and risedronate 10(-7)M decreased the degree of cell proliferation on day 8 (P<0.05). Using an ELISA, the ALP activity of the control, alendronate 10(-8)M, risedronate 10(-8)M, and risedronate 10(-7)M groups were 112.1±10.2%, 156.1±24.3%, 138.8±16.5%, and 133.3±10.3%, respectively, at 14 days after treatment (day 0 in each group was considered to be 100%). ALP activity was significantly higher in the alendronate 10(-8)M and risedronate 10(-8) and 10(-7)M groups than in the control group (P=0.010, 0.014, and 0.009, respectively). It is possible that BPs increase the potential of MHCs for osteogenic differentiation depending on the concentration of the drug.

  3. The haematoma and its role in bone healing.

    PubMed

    Schell, H; Duda, G N; Peters, A; Tsitsilonis, S; Johnson, K A; Schmidt-Bleek, K

    2017-12-01

    Fracture treatment is an old endeavour intended to promote bone healing and to also enable early loading and regain of function in the injured limb. However, in today's clinical routine the healing potential of the initial fracture haematoma is still not fully recognized. The Arbeitsgemeinschaft für Osteosynthesefragen (AO) formed in Switzerland in 1956 formulated four AO principles of fracture treatment which are still valid today. Fracture treatment strategies have continued to evolve further, as for example the relatively new concept of minimally invasive plate osteosynthesis (MIPO). This MIPO treatment strategy harbours the benefit of an undisturbed original fracture haematoma that supports the healing process. The extent of the supportive effect of this haematoma for the bone healing process has not been considered in clinical practice so far. The rising importance of osteoimmunological aspects in bone healing supports the essential role of the initial haematoma as a source for inflammatory cells that release the cytokine pattern that directs cell recruitment towards the injured tissue. In reviewing the potential benefits of the fracture haematoma, the early development of angiogenic and osteogenic potentials within the haematoma are striking. Removing the haematoma during surgery could negatively influence the fracture healing process. In an ovine open tibial fracture model the haematoma was removed 4 or 7 days after injury and the bone that formed during the first two weeks of healing was significantly reduced in comparison with an undisturbed control. These findings indicate that whenever possible the original haematoma formed upon injury should be conserved during clinical fracture treatment to benefit from the inherent healing potential.

  4. Multifunctional composites: Healing, heating and electromagnetic integration

    NASA Astrophysics Data System (ADS)

    Plaisted, Thomas Anthony John

    2007-12-01

    Multifunctional materials, in the context of this research, integrate other functions into materials that foremost have outstanding structural integrity. Details of the integration of electromagnetic, heating, and healing functionalities into fiber-reinforced polymer composites are presented. As a result of fiber/wire integration through textile braiding and weaving, the dielectric constant of a composite may be tuned from negative to positive values. These wires are further leveraged to uniformly heat the composite through resistive heating. A healing functionality is introduced by utilizing a polymer matrix with the ability to heal internal cracking through thermally-reversible covalent bonds based on Diels-Alder cycloaddition. The Double Cleavage Drilled Compression (DCDC) specimen is applied to study the fracture and healing characteristics of the neat polymer. This method allows for quantitative evaluation of incremental crack growth, and ensures that the cracked sample remains in one piece after the test, improving the ability to re-align the fracture surfaces prior to healing. Initially, the fracture strength of PMMA is studied with various DCDC geometries to develop a model of the propagation of a crack within this type of specimen. Applied to the healable polymer (2MEP4F), repeated fracture-healing cycles demonstrate that treatment at temperatures between 85 to 95°C results in full fracture toughness recovery and no dimensional changes due to creep. The fracture toughness after each fracturing and healing cycle has been calculated, using the model, to yield a fracture toughness of about 0.71 MPa·m1/2 for this material at room temperature. Glass and carbon fiber-reinforced composites have been fabricated with the 2MEP4F polymer, and the ability of this polymer to heal microcracks in fiber-reinforced composites is demonstrated. Microcracks have been introduced into the composites by cryogenic cycling in liquid nitrogen, causing a reduction in the storage

  5. Triplane fractures in the hand.

    PubMed

    Garcia Mata, S; Hidalgo Ovejero, A; Martinez Grande, M

    1999-02-01

    Two new cases of triplane fracture of the distal tibia are reported in the proximal phalanx of the thumb and the distal radius, respectively, of a 12-year-old girl and a 13-year-old boy. Neither fracture showed any displacement, achieving healing at 4 weeks of external immobilization. Triplane fractures can occur across growth plates other than the distal tibia. Because of the rapid physiologic physeal arrest, the potential for growth deformity is null. In cases without displacement, these fractures should be treated conservatively by external immobilization, as one would treat a one-plane fracture.

  6. The Biology of Bone and Ligament Healing.

    PubMed

    Cottrell, Jessica A; Turner, Jessica Cardenas; Arinzeh, Treena Livingston; O'Connor, J Patrick

    2016-12-01

    This review describes the normal healing process for bone, ligaments, and tendons, including primary and secondary healing as well as bone-to-bone fusion. It depicts the important mediators and cell types involved in the inflammatory, reparative, and remodeling stages of each healing process. It also describes the main challenges for clinicians when trying to repair bone, ligaments, and tendons with a specific emphasis on Charcot neuropathy, fifth metatarsal fractures, arthrodesis, and tendon sheath and adhesions. Current treatment options and research areas are also reviewed.

  7. Wound Healing Problems in the Mouth

    PubMed Central

    Politis, Constantinus; Schoenaers, Joseph; Jacobs, Reinhilde; Agbaje, Jimoh O.

    2016-01-01

    Wound healing is a primary survival mechanism that is largely taken for granted. The literature includes relatively little information about disturbed wound healing, and there is no acceptable classification describing wound healing process in the oral region. Wound healing comprises a sequence of complex biological processes. All tissues follow an essentially identical pattern to complete the healing process with minimal scar formation. The oral cavity is a remarkable environment in which wound healing occurs in warm oral fluid containing millions of microorganisms. The present review provides a basic overview of the wound healing process and with a discussion of the local and general factors that play roles in achieving efficient would healing. Results of oral cavity wound healing can vary from a clinically healed wound without scar formation and with histologically normal connective tissue under epithelial cells to extreme forms of trismus caused by fibrosis. Many local and general factors affect oral wound healing, and an improved understanding of these factors will help to address issues that lead to poor oral wound healing. PMID:27853435

  8. Decrepitation and crack healing of fluid inclusions in San Carlos olivine

    SciTech Connect

    Wanamaker, B.J. ); Wong, Tengfong ); Evans, B. )

    1990-09-10

    Fluid inclusions break, or decrepitate, when the fluid pressure exceeds the least principal lithostatic stress by a critical amount. After decrepitation, excess fluid pressure is relaxed, resulting in crack arrest; subsequently, crack healing may occur. The authors developed a linear elastic fracture mechanics model to analyze new data on decrepitation and crack arrest in San Carlos Olivine, compared the model with previous fluid inclusion investigations, and used it to interpret some natural decrepitation microstructures. The common experimental observation that smaller inclusions may sustain higher internal fluid pressures without decrepitating may be rationalized by assuming that flaws associated with the inclusion scale with the inclusion size. According to the model, the length of the crack formed by decrepitation depends on the lithostatic pressure at the initiation of cracking, the initial sizes of the flaw and the inclusion, and the critical stress intensity factor. Further experiments show that microcracks in San Carlos olivine heal within several days at 1,280 to 1,400{degree}C; healing rates depend on the crack geometry, temperature, and chemistry of the buffering gas. The regression distance of the crack tip during healing can be related to time through a power law with exponent n = 0.6. Chemical changes which become apparent after extremely long heat-treatments significantly affect the healing rates. Many of the inclusions in the San Carlos xenoliths stretched, decrepitated, and finally healed during uplift. The crack arrest model indicates that completely healed cracks had an initial fluid pressure of the order of 1 GPa. Using the crack arrest model and the healing kinetics, they estimate the ascent rate of these xenoliths to be between 0.001 and 0.1 m/s.

  9. The administration of intermittent parathyroid hormone affects functional recovery from pertrochanteric fractured neck of femur: a protocol for a prospective mixed method pilot study with randomisation of treatment allocation and blinded assessment (FRACTT)

    PubMed Central

    Chesser, Tim; Fox, Rebecca; Harding, Karen; Greenwood, Rosemary; Javaid, Kassim; Barnfield, Steven; Halliday, Ruth; Willett, Keith; Lamb, Sallie

    2014-01-01

    Introduction Pertrochanteric hip fractures occur in an elderly population and cause considerable morbidity and loss of functional ability as the fracture heals. Recently, parathyroid hormone (PTH), which is licensed for the treatment of osteoporosis, has been shown to potentially accelerate bone healing in animal and human studies. If its administration could allow a faster functional recovery after pertrochanteric hip fracture, then a patient's hospital stay may be reduced and rehabilitation could be potentially accelerated. PTH can currently only be administered by subcutaneous injection. The acceptability of this intervention is unknown in this elderly population. The aim of this pilot study is to inform the design of a future powered study comparing the functional recovery after pertrochanteric hip fracture in patients undergoing standard care versus those who undergo administration of subcutaneous injection of PTH. Methods and analysis The study is an open label, prospective, randomised, comparative pilot study with blinded outcomes assessment to establish feasibility of the trial design. Patients will be randomised to receive a 6-week course of PTH or usual treatment. Functional outcomes will be assessed at 6 weeks and 12 weeks. Blinded assessment will be used to minimise the effect of bias of an open label study design. A nested qualitative study will investigate the patient experience of, and expectations following, hip fracture and the patient important aspects of recovery compared with the outcome measures proposed. Results Results will be analysed to establish the potential recruitment, compliance and retention rates using 95% CIs, and trial outcomes quoted with SDs and 95% CIs for the effect size. Ethics and dissemination The study has been approved by the South West 2 Research Ethics committee (reference 10/H0206/34). The findings of this study will be disseminated to the medical community via presentations to orthopaedic, orthogeriatric and

  10. Pediatric Hand Fractures

    PubMed Central

    Nellans, Kate W.; Chung, Kevin C.

    2014-01-01

    Summary Pediatric hand fractures are common childhood injuries. Identification of the fractures in the emergency room setting can be challenging owing to the physes and incomplete ossification of the carpus that are not revealed in the xrays. Most simple fractures can be treated with appropriate immobilization through buddy taping, finger splints, or casting. If correctly diagnosed, reduced and immobilized, these fractures usually result in excellent clinical outcomes. However, fractures may require operative stabilization if they have substantial angulation or rotation, extend into the joint, or cannot be held in a reduced position with splinting alone. Most fractures can be treated operatively with closed reduction and percutaneous pinning if addressed within the first week following the injury. In children, the thick, vascular-rich periosteum and bony remodeling potential make anatomic reductions and internal fixation rarely necessary. Most fractures complete bony healing in 3-4 weeks, with the scaphoid being a notable exception. Following immobilization, children rarely develop hand stiffness and formal occupational therapy is usually not necessary. Despite the high potential for excellent outcomes in pediatric hand fractures, some fractures remain difficult to diagnose and treat. PMID:24209954

  11. Seasonal Temperature and Pin Site Care Regimen Affect the Incidence of Pin Site Infection in Pediatric Supracondylar Humeral Fractures.

    PubMed

    Kao, Hsuan-Kai; Chen, Mei-Chuan; Lee, Wei-Chun; Yang, Wen-E; Chang, Chia-Hsieh

    2015-01-01

    Pin site infection is a common complication after fracture fixation and bone lengthening, and daily pin site care is recommended. Weather is a strong environmental factor of infection, but few articles studied the issue of weather and pin site infection. We performed a prospective comparative study of 61 children with supracondylar humeral fractures treated by closed reduction and percutaneous pinning. The patients were divided into high-temperature season or low-temperature season by the months they received surgery. The patients within each season were further allocated to 2 groups by the different postoperative pin site care methods of daily care or noncare. The infection rate per patient was significantly higher in the high-temperature season compared to low-temperature season (45% versus 19%, P = 0.045). In the high-temperature season, the infection rate per patient was significantly higher in the daily care group versus the noncare group (70% versus 20%, P = 0.001). In the low-temperature season, the infection rate per patient was not significantly different in the daily care group versus the noncare group (10% versus 27.3%, P = 0.33). We recommend that careful monitoring of infection signs, rather than pin site cleaning, would be appropriate in the treatment of pediatric supracondylar humeral fractures, especially during the summer months.

  12. Horizontally root fractured teeth with pulpal vitality - two case reports

    PubMed Central

    Silva, Luciano; Álvares, Pâmella; Arruda, José Alcides; Silva, Leni Verônica; Rodrigues, Cleomar; Sobral, Ana Paula Veras; Silveira, Marcia

    2016-01-01

    This case study reports the successful outcome of horizontal root fractures of two different patients, which took place in permanent incisors. Report 1 describes a case of a 29-year-old patient who suffered a mandibular trauma affecting mainly the lower central incisors, caused by a car accident. A panoramic radiograph was taken right after the accident and showed a horizontal root fracture in the middle third of tooth 42, which went untreated. Report 2 illustrates a case of a 17-year-old male patient who searched for orthodontic therapy and the periapical radiograph showed horizontal root fracture in tooth 11 caused by a previous trauma, which went untreated as well. There was healing through the reestablishment of pulp activity and dental coloration without professional intervention. PMID:28070245

  13. Laboratory Evidence of Strength Recovery of Healed Faults

    NASA Astrophysics Data System (ADS)

    Masuda, K.

    2015-12-01

    Fault zones consist of a fault core and a surrounding damage zone. Fault zones are typically characterized by the presence of many healed surfaces, the strength of which is unknown. If a healed fault recovers its strength such that its cohesion is equal to or greater than that of the host rock, repeated cycles of fracture and healing may be one mechanism producing wide fault zones. I present laboratory evidence supporting the strength recovery of healed fault surface, obtained by AE monitoring, strain measurements and X-ray CT techniques. The loading experiment was performed with a specimen collected from an exhumed fault zone. Healed surfaces of the rock sample were interpreted to be parallel to slip surfaces. The specimen was a cylinder with 50 mm diameter and 100 mm long. The long axis of the specimen was inclined with respect to the orientation of the healed surfaces. The compression test used a constant loading rate under 50 MPa of confining pressure. Macroscopic failure occurred when the applied differential stress reached 439 MPa. The macro-fracture surface created during the experiment was very close to the preexisting plane. The AE hypocenters closely match the locations of the preexisting healed surface and the new fault plane. The experiment also revealed details of the initial stage of fault development. The new fault zone developed near, but not precisely on the preexisting healed fault plane. An area of heterogeneous structure where stress appears to have concentrated, was where the AEs began, and it was also where the fracture started. This means that the healed surface was not a weak surface and that healing strengthened the fault such that its cohesion was equal to or greater than that of the intact host rock. These results suggest that repeated cycles of fracture and healing may be the main mechanism creating wide fault zones with multiple fault cores and damage zones.

  14. Autonomic healing of polymer composites.

    PubMed

    White, S R; Sottos, N R; Geubelle, P H; Moore, J S; Kessler, M R; Sriram, S R; Brown, E N; Viswanathan, S

    2001-02-15

    Structural polymers are susceptible to damage in the form of cracks, which form deep within the structure where detection is difficult and repair is almost impossible. Cracking leads to mechanical degradation of fibre-reinforced polymer composites; in microelectronic polymeric components it can also lead to electrical failure. Microcracking induced by thermal and mechanical fatigue is also a long-standing problem in polymer adhesives. Regardless of the application, once cracks have formed within polymeric materials, the integrity of the structure is significantly compromised. Experiments exploring the concept of self-repair have been previously reported, but the only successful crack-healing methods that have been reported so far require some form of manual intervention. Here we report a structural polymeric material with the ability to autonomically heal cracks. The material incorporates a microencapsulated healing agent that is released upon crack intrusion. Polymerization of the healing agent is then triggered by contact with an embedded catalyst, bonding the crack faces. Our fracture experiments yield as much as 75% recovery in toughness, and we expect that our approach will be applicable to other brittle materials systems (including ceramics and glasses).

  15. Elastic stable intramedullary nailing for severely displaced distal tibial fractures in children

    PubMed Central

    Shen, Kaiying; Cai, Haiqing; Wang, Zhigang; Xu, Yunlan

    2016-01-01

    Abstract Elastic stable intramedullary nailing (ESIN) has became a well-accepted method of osteosynthesis of diaphyseal fractures in the skeletally immature patient for many advantages, the purpose of this study is to evaluate the preliminary results of this minimally invasive treatment for severely displaced distal tibial diaphyseal metaphyseal junction (DTDMJ) fractures. This study was carried out over a 6-year period. Twenty-one severely displaced DTDMJ fractures treated using ESIN were evaluated clinically and radiographically. Complications were assessed: the patients were evaluated with regard to nonunion, malunion, infection, growth arrest, leg length discrepancy, implant irritation, and joint function. Mean age at the time of surgery was 7.8 years (range between 5.3 and 14.8 years), mean body weight 34.1 kg, all fractures were transverse or mild oblique type, including 3 open fractures, 5 multifragmented fractures, and 4 fractures associated with polytrauma; 6 cases were treated with antegrade ESIN of tibia while 15 cases need combined retrograde fibula and antegrade tibia fixation treatments. Follow-ups were ranging from 11 to 36 months, 19 fractures showed both clinical and radiographic evidence of healing within 5 months; all cases had full range motion of knee and ankle with symmetrical foot progress angle. Nail removal was at a mean 7.1 months, at final follow-up, no growth arrest or disturbances occurred. Five patients had complications; leg length discrepancy had decreased yet affected 2 patients, 2 cases showed delayed union, and 1 case developed restricted dorsal extension at the metatarsophalangeal joint of the hallux. ESIN is the treatment of choice for pediatric severely displaced DTDMJ fractures that cannot be reduced by closed reduction or ones that cannot be casted. The advantages include faster fracture healing, excellent functional and cosmetic results, safe and reliable surgical technique, and lower severe complication rate. PMID

  16. Biomimetic Self-Healing

    DTIC Science & Technology

    2015-07-21

    ELEMENT NUMBER 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 6. AUTHOR(S) 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8...PERFORMING ORGANIZATION REPORT NUMBER 10. SPONSOR/MONITOR’S ACRONYM(S) 11. SPONSOR/MONITOR’S REPORT NUMBER(S) 9. SPONSORING/MONITORING AGENCY...soundness; to cure (of a disease or wound).”[1] Self-healing provides an important evolutionary advantage,[2] since living organisms are affected both

  17. Photodynamic Therapy Treatment to Enhance Fracture Healing

    DTIC Science & Technology

    2013-06-01

    Military  Health  System Research Symposium (MHSRS);    13.‐ 16. August 2012 in Fort Lauderdale, FL, USA       The  Effect  of Photodynamic Therapy (PDT...ORGANIZATION: Sunnybrook Health Sciences Centre Toronto, ON, Canada M4N 3M5 REPORT DATE...Sunnybrook Health Sciences Centre 8. PERFORMING ORGANIZATION REPORT NUMBER Toronto, ON, Canada M4N 3M5

  18. Avulsion fractures in athletes.

    PubMed Central

    Orava, S.; Ala-Ketola, L.

    1977-01-01

    34 cases of avulsion fractures are described. Each fracture took place during athletic training or competition. Excepting six sportsmen participating in a general fitness programme, every patient was an active competitive athlete. There were six women and 28 men; their average age was 20.1 years, raised by a few middle-aged "fitness sportsmen". Most avulsion fractures took place in sprinters and hurdlers; next were middle and long distance renner, footballers, fitness joggers, skiers and ice-hockey players. The most usual location of a fracture was the anterior pelvic spines; avulsion fractures were also detected in various parts of lower limbs. There were fewer avulsion fractures in the area of the trunk and upper extremities. Roetgenologically, the diagnosis of an avulsion fracture is generally easy to make. However, the diagnosis is facilitated by knowing the mechanism of the injury, the technique of the athletic event, and some of the training methods. Generally, a fracture heals well, even if it requires both sufficient immobilisation and some delay in resuming physical exertion. PMID:884433

  19. Evaluation of crack arrest fracture toughness of parent plate, weld metal and heat affected zone of BIS 812 EMA ship plate steel

    NASA Astrophysics Data System (ADS)

    Burch, I. A.

    1993-10-01

    The steel chosen for the pressure hull of the Collins class submarine has undergone evaluation to compare the crack arrest fracture toughness, K(Ia), of the parent plate with that of weld metal and heat affected zone. The tests were conducted over a range of subzero temperatures on specimens slightly outside the ASTM standard test method specimen configuration. Shallow face grooved specimens were used to vary the propagating crack velocity from that of non face grooved specimens and determine if K(Ia), is sensitive to changes in crack velocity. The weld metal, heat affected zone (HAZ), and parent plate were assessed to determine if the welding process had a deleterious effect on the crack arrest properties of this particular steel. Tests on each of these regions revealed that, for the combination of parent plate, welding procedure and consumables, no adverse effect on crack arrest properties was encountered. Crack arrest fracture toughness of the weld metal and HAZ was superior to that of the parent plate at comparable temperatures.

  20. Clinical and surgical approach of severe bone fragility fracture: clinical case of 4 fragility fracture in patient with heavy osteoporosis

    PubMed Central

    Giannotti, Stefano; Bottai, Vanna; Pini, Erica; Dell’Osso, Giacomo; De Paola, Gaia; Guido, Giulio

    2013-01-01

    Summary An accurate diagnosis of osteoporosis and a proper treatment are today recognized to be the most important facts for prevention and for a correct arrangement and treatment of fragility fractures. In the text the Authors describe a case of severe osteoporosis aggravated by 2 femur fractures and 2 periprosthetic fractures occurred in 2 months. In such cases the orthopaedic surgeon needs to formulate first a clinical osteoporotic pattern, than its treatment together with a surgery suitable choice, that has to take into consideration of the bone structural characteristics. In the case described one can note that fractures healing occurred thanks to both an improvement in surgical techniques and antiosteoporotic pharmacological support; in the specific case the Authors used strontium ranelate for its osteoinductive capacity. In our opinion is crucial that the treatment used by orthopaedic surgeons is not related only to the “by-hand” treatment but take into consideration both the underlying disease and the possibility of positively affect bone healing with specific drug therapy. PMID:23858312

  1. The Multifaceted Role of the Vasculature in Endochondral Fracture Repair

    PubMed Central

    Bahney, Chelsea S.; Hu, Diane P.; Miclau, Theodore; Marcucio, Ralph S.

    2015-01-01

    Fracture healing is critically dependent upon an adequate vascular supply. The normal rate for fracture delayed or non-union is estimated to be between 10 and 15%, and annual fracture numbers are approximately 15 million cases per year. However, when there is decreased vascular perfusion to the fracture, incidence of impaired healing rises dramatically to 46%. Reduction in the blood supply to the fracture can be the result of traumatic injuries that physically disrupt the vasculature and damage supportive soft tissue, the result of anatomical location (i.e., distal tibia), or attributed to physiological conditions such as age, diabetes, or smoking. The role of the vasculature during repair is multifaceted and changes during the course of healing. In this article, we review recent insights into the role of the vasculature during fracture repair. Taken together these data highlight the need for an updated model for endochondral repair to facilitate improved therapeutic approaches to promote bone healing. PMID:25699016

  2. Bone tissue engineering and regenerative medicine: targeting pathological fractures.

    PubMed

    Nguyen, Duong T; Burg, Karen J L

    2015-01-01

    Patients with bone diseases have the highest risk of sustaining fractures and of suffering from nonunion bone healing due to tissue degeneration. Current fracture management strategies are limited in design and functionality and do not effectively promote bone healing within a diseased bone environment. Fracture management approaches include pharmaceutical therapy, surgical intervention, and tissue regeneration for fracture prevention, fracture stabilization, and fracture site regeneration, respectively. However, these strategies fail to accommodate the pathological nature of fragility fractures, leading to unwanted side effects, implant failures, and nonunions. To target fragility fractures, fracture management strategies should include bioactive bone substitutes designed for the pathological environment. However, the clinical outcome of these materials must be predictable within various disease environments. Initial development of a targeted treatment strategy should focus on simulating the physiological in vitro bone environment to predict clinical effectiveness of the engineered bone. An in vitro test system can facilitate reduction of implant failures and non-unions in fragility fractures.

  3. Revascularization in Maxillofacial Bone Healing.

    DTIC Science & Technology

    1985-11-21

    administration of cortisone or acetylsalicylic acid did not affect giant cell or capsule formation around the particles. Therefore, this reparative granuloma was...other aspects of healing have special requirements. Thus sulfur-containing amino acids are important for granulation tissue formation (Edwards and...Dunphy, 1957). Capillary endothelium and collagen fibril formation, essential to revascularization, are decreased by ascorbic acid deficiency; the latter

  4. Salter-Harris II forearm fracture reduction and fixation using a buttress plate

    PubMed Central

    Barnes, Jonathan; Webb, Mark; Fearon, Paul v

    2014-01-01

    Distal radius fractures are common injuries in children. Those that affect the growth plate (physis) need to be managed carefully as inadequate management may lead to long-term deformity and a reduction in function. However, different management strategies all have drawbacks and controversy exists over how best to manage these cases. This is the case of a 13-year-old girl who presented with a Salter Harris II fracture, which was managed using a novel approach of utilising a T plate in a buttress mode to stabilise the fracture after anatomical reduction. This provided effective fracture fixation and should allow good bone healing without causing any iatrogenic growth plate damage and without fixing a plate across the physis, which may need removal in the future. PMID:24488665

  5. Intramedullary bone cementing for the treatment of Colles fracture in elderly patients.

    PubMed

    Ikeda, Kazuo; Osamura, Naoki; Hagiwara, Norio; Yamauchi, Daisuke; Tomita, Katsuro

    2004-01-01

    Eighteen patients with Colles fractures, mean age 70 years (range 55-91), were treated by intramedullary bone cementing. The best indication for this technique was an unstable extra-articular Colles fracture with osteoporosis. Bone cement was packed into the canal that was made by curettage of intramedullary cancellous bone from the dorsal fracture site. Intramedullary cementing caused little bleeding from the medullary canal and no irritation of the extensor tendons. Because of rigid fixation, patients could use the affected hand for light activities without any external orthosis the day after surgery. Cortical healing was seen in all cases within three months and there was no cement loosening or other complications during the mean 28 month (range 6-43) follow up period. Intramedullary bone cementing is one of the optimal treatments for Colles fractures in elderly patients.

  6. Complications of mandibular fractures.

    PubMed

    Zweig, Barry E

    2009-03-01

    Before any definitive treatment of mandibular fractures, the patient needs to be evaluated for more potentially life-threatening injuries. Complications can and do occur with treatment of mandibular fractures and can occur during any of the phases of treatment. The development of an accurate diagnosis and appropriate treatment plan is vital in achieving optimal success and decreasing complications. Knowledge of the anatomy and the principles of bone healing is also an important factor in preventing complications. To limit long-term untoward effects, complications should be recognized early and the appropriate treatment should be started before a minor complication becomes a complex one that is more difficult to manage.

  7. Cold temperature delays wound healing in postharvest sugarbeet roots

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Storage temperature affects the rate and extent of wound-healing in a number of root and tuber crops. The effect of storage temperature on wound-healing in sugarbeet (Beta vulgaris L.) roots, however, is largely unknown. Wound-healing of sugarbeet roots was investigated using surface-abraded roots s...

  8. Lap shear strength and healing capability of self-healing adhesive containing epoxy/mercaptan microcapsules

    NASA Astrophysics Data System (ADS)

    Ghazali, Habibah; Ye, Lin; Zhang, Ming-Qiu

    2016-03-01

    The aim of this work is to develop a self-healing polymeric adhesive formulation with epoxy/mercaptan microcapsules. Epoxy/mercaptan microcapsules were dispersed into a commercialize two-part epoxy adhesive for developing self-healing epoxy adhesive. The influence of different content of microcapsules on the shear strength and healing capability of epoxy adhesive were investigated using single-lap-joints with average thickness of adhesive layer of about 180 µm. This self-healing adhesive was used in bonding of 5000 series aluminum alloys adherents after mechanical and alkaline cleaning surface treatment. The adhesion strength was measured and presented as function of microcapsules loading. The results indicated that the virgin lap shear strength was increased by about 26% with addition of 3 wt% of self-healing microcapsules. 12% to 28% recovery of the shear strength is achieved after self-healing depending on the microcapsules content. Scanning electron microscopy was used to study fracture surface of the joints. The self-healing adhesives exhibit recovery of both cohesion and adhesion properties with room temperature healing.

  9. Decreased BMP2 signal in GIT1 knockout mice slows bone healing.

    PubMed

    Sheu, T J; Zhou, Wei; Fan, Jin; Zhou, Hao; Zuscik, Michael J; Xie, Chao; Yin, Guoyong; Berk, Bradford C

    2014-12-01

    Endochondral ossification, an important stage of fracture healing, is regulated by a variety of signaling pathways. Transforming growth factor β (TGFβ) superfamily plays important roles and comprises TGFβs, bone morphogenetic proteins (BMPs), and growth differentiation factors. TGFβs primarily regulate cartilage formation and endochondral ossification. BMP2 shows diverse efficacy, from the formation of skeleton and extraskeletal organs to the osteogenesis and remodeling of bone. G-protein-coupled receptor kinase 2-interacting protein-1 (GIT1), a shuttle protein in osteoblasts, facilitates fracture healing by promoting bone formation and increasing the secretion of vascular endothelial growth factor. Our study examined whether GIT1 regulates fracture healing through the BMP2 signaling pathway and/or through the TGFβ signaling pathway. GIT1 knockout (KO) mice exhibited delayed fracture healing, chondrocyte accumulation in the fracture area, and reduced staining intensity of phosphorylated Smad1/5/8 (pSmad1/5/8) and Runx2. Endochondral mineralization diminished while the staining intensity of phosphorylated Smad2/3 (pSmad2/3) showed no significant change. Bone marrow mesenchymal stem cells extracted from GIT1 KO mice showed a decline of pSmad1/5/8 levels and of pSmad1/5/8 translocated into the cell nucleus after BMP2 stimulus. We detected no significant change in the pSmad2/3 level after TGFβ1 stimulus. Data obtained from reporter gene analysis of C3H10T1/2 cells cultured in vitro confirmed these findings. GIT1-siRNA inhibited transcription in the cell nucleus via pSmad1/5/8 after BMP2 stimulus but had no significant effect on transcription via pSmad2/3 after TGFβ1 stimulus. Our results indicate that GIT1 regulates Smad1/5/8 phosphorylation and mediates BMP2 regulation of Runx2 expression, thus affecting endochondral ossification at the fracture site.

  10. Possible benefits of strontium ranelate in complicated long bone fractures.

    PubMed

    Alegre, Duarte Nuno; Ribeiro, Costa; Sousa, Carlos; Correia, João; Silva, Luís; de Almeida, Luís

    2012-02-01

    Osteoporosis drugs are prescribed to prevent fragility fractures, which is the principal aim of the management of osteoporosis. However, if fracture does occur, then it is also important to promote a fast and uneventful healing process. Despite this, little is known about the effect of osteoporosis drugs on bone healing in humans. Strontium ranelate is an osteoporosis agent that increases bone formation and reduces bone resorption and may therefore be beneficial in fracture healing. We report four cases of fracture non-union for up to 20 months. Treatment with strontium ranelate (2 g/day) for between 6 weeks and 6 months appeared to contribute to bone consolidation in the four cases. Animal studies support beneficial effects of strontium ranelate on bone healing via improvement of bone material properties and microarchitecture in the vicinity of the fracture. The clinical cases described herein provide new information on these effects, in the absence of randomized controlled studies on the clinical efficacy of pharmacological treatments in osteoporosis in fracture repair. Further studies are necessary. Fracture healing is an important topic in orthopedic research and is also a concern for patients with postmenopausal osteoporosis. Evidence from case reports and animal studies suggests that strontium ranelate improves bone microarchitecture and accelerates fracture healing. A positive effect of osteoporosis treatments on bone healing is an interesting possibility and merits further clinical research.

  11. Solid state self-healing system: Effects of using PDGEBA, PVC and PVA as linear healing agents

    NASA Astrophysics Data System (ADS)

    Muhamad, Noor Nabilah; Jamil, Mohd. Suzeren Md.; Abdullah, Shahrum

    2014-09-01

    The solid state self-healing system was obtained by employing a thermosetting epoxy resin, into which a thermoplastic is dissolved. In this study, the effect of healing efficiency was investigated by using different thermoplastic polymers which are poly(bisphenol-A-co-epichlorohydrin), polyvinyl chloride and polyvinyl alcohol as healing agents. Healing was achieved by heating the fractured resins to a specific temperature i.e. above their glass transition temperature (Tg) which obtained from dynamic mechanical analysis (DMA) to mobilize the polymeric chains of the healing agent. The curing reaction in the epoxy resins were characterized by means of Fourier transform infrared spectroscopy (FTIR). Izod impact test was been performed to demonstrate self-healing of the different specimens. Under test, it was found that healable resin with PDGEBA has highest healing efficiency followed by PVC and PVA, with 63%, 35% and 18% of average percentage healing efficiencies respectively. These results are due to the different solubility parameters of the thermoset/network and thermoplastic polymer which led to the phase separation. Morphological studies prove the fracture-healing process and morphological properties of the resins.

  12. Rehabilitative strategies following hand fractures.

    PubMed

    Hays, Peyton L; Rozental, Tamara D

    2013-11-01

    The importance of rehabilitation in the management of hand fractures cannot be overstated. The breadth of rehabilitative strategies ranges from heat and range-of-motion exercises to more complex splinting and tendon gliding modalities. The goals, however, are clear: control pain; limit soft tissue swelling; provide support for fracture healing; restore motion, strength, and function; and enable the return to work and daily activities.

  13. Non-Union in Upper Limb Fractures - Clinical Evaluation and Treatment Options.

    PubMed

    Neumann, M V; Zwingmann, J; Jaeger, M; Hammer, T O; Südkamp, N P

    2016-01-01

    Although non-unions in the upper limb are rare different treatment options of this challenging situation are still affected with up to 20% of failure rate due to current literature. Risk factors for delayed and non-union of fractures are mainly the size of the fracture gap and bone loss of open fractures or in primary surgery followed by other relevant internal and external factors. In the upper limb non-unions of long bones are described with up to 30% after operative intervention. Especially in the upper limb range of motion is limited in non-union cases and disables adjacent joints like the shoulder, elbow and wrist hence reducing the total activity level of affected patients. Beside careful investigation of the causes leading to the non-union a comprehensive treatment plan should be defined to achieve successful results. Treatment can be non-operative in several, selected cases, but in the majority of cases revision surgery is necessary to achieve osseous healing. Our own experience showed that non-union in the upper limb are rare and account for only 1.7% of all surgical managed upper limb fractures. Non-union of upper limb fractures occur most frequently in clavicle fractures followed by humeral fractures. Atrophic non-union is the most frequent reason for osseous non-union (57%) and osseous healing after revision surgery in non-unions is completed after a mean of 6.45 months. This article will give a brief overview of the genesis, clinical evaluation, treatment options and recommendations in upper limb non-unions according to the current literature. Key words: fracture, upper-limb, non-union, osteosynthesis, cancellous bone-graft.

  14. Fractures in anisotropic media

    NASA Astrophysics Data System (ADS)

    Shao, Siyi

    Rocks may be composed of layers and contain fracture sets that cause the hydraulic, mechanical and seismic properties of a rock to be anisotropic. Coexisting fractures and layers in rock give rise to competing mechanisms of anisotropy. For example: (1) at low fracture stiffness, apparent shear-wave anisotropy induced by matrix layering can be masked or enhanced by the presence of a fracture, depending on the fracture orientation with respect to layering, and (2) compressional-wave guided modes generated by parallel fractures can also mask the presence of matrix layerings for particular fracture orientations and fracture specific stiffness. This report focuses on two anisotropic sources that are widely encountered in rock engineering: fractures (mechanical discontinuity) and matrix layering (impedance discontinuity), by investigating: (1) matrix property characterization, i.e., to determine elastic constants in anisotropic solids, (2) interface wave behavior in single-fractured anisotropic media, (3) compressional wave guided modes in parallel-fractured anisotropic media (single fracture orientation) and (4) the elastic response of orthogonal fracture networks. Elastic constants of a medium are required to understand and quantify wave propagation in anisotropic media but are affected by fractures and matrix properties. Experimental observations and analytical analysis demonstrate that behaviors of both fracture interface waves and compressional-wave guided modes for fractures in anisotropic media, are affected by fracture specific stiffness (controlled by external stresses), signal frequency and relative orientation between layerings in the matrix and fractures. A fractured layered medium exhibits: (1) fracture-dominated anisotropy when the fractures are weakly coupled; (2) isotropic behavior when fractures delay waves that are usually fast in a layered medium; and (3) matrix-dominated anisotropy when the fractures are closed and no longer delay the signal. The

  15. Effects of water-aging on self-healing dental composite containing microcapsules

    PubMed Central

    Wu, Junling; Weir, Michael D.; Melo, Mary Anne S.; Strassler, Howard E.; Xu, Hockin H. K.

    2016-01-01

    Objectives The objectives of this study were to develop a self-healing dental composite containing poly(urea-formaldehyde) (PUF) shells with triethylene glycol dimethacrylate (TEGDMA) and N,N-dihydroxyethyl-p-toluidine (DHEPT) as healing liquid, and to investigate the mechanical properties of the composite and its self-healing efficacy after water-aging for 6 months. Methods PUF microspheres were synthesized encapsulating a TEGDMA-DHEPT healing liquid. Composite containing 30% of a resin matrix and 70% of glass fillers by mass was incorporated with 0%, 2.5%, 5%, 7.5% and 10% of microcapsules. A flexural test was used to measure flexural strength and elastic modulus. A single edge V-notched beam method was used to measure fracture toughness (KIC) and self-healing efficacy. Specimens were water-aged at 37 °C for 1 d to 6 months and then tested for self-healing. Fractured specimens were healed while being immersed in water to examine self-healing efficacy, in comparison with that in air. Results Incorporation of up to 7.5% of microcapsules into the resin composite achieved effective self-healing, without adverse effects on the virgin mechanical properties of the composite (p > 0.1). An excellent self-healing efficacy of 64%–77% recovery was obtained (mean ± sd; n = 6). Six months of water-aging did not decrease the self-healing efficacy compared to 1 d (p > 0.1). Exposure to water did not decrease the healing efficacy, compared to that healed in air (p > 0.1). Conclusions A composite was developed with excellent self-healing efficacy even while being immersed in water. The self-healing efficacy did not decrease with increasing water-aging time for 6 months. Clinical significance The novel self-healing composite may be promising for dental applications to heal cracks, resist fracture, and increase the durability and longevity. PMID:26808158

  16. Effect of the combination of basic fibroblast growth factor and cysteine on corneal epithelial healing after photorefractive keratectomy in patients affected by myopia

    PubMed Central

    Meduri, Alessandro; Scorolli, Lucia; Scalinci, Sergio Zaccaria; Grenga, Pier Luigi; Lupo, Stefano; Rechichi, Miguel; Meduri, Enrico

    2014-01-01

    Background: This study sought to evaluate the effect of basic fibroblast growth factor eye drops and cysteine oral supplements on corneal healing in patients treated with photorefractive keratectomy (PRK). Materials and Methods: One hundred and twenty patients treated bilaterally with PRK for myopia were enrolled at one of two eye centers (Clinica Santa Lucia, Bologna, Italy and Department of Ophthalmology, University of Magna Graecia, Catanzaro, Italy) and were treated at the former center. Sixty patients included in the study group (Group 1) were treated postoperatively with topical basic fibroblast growth factor plus oral L-cysteine supplements, whereas 60 subjects included in the control group (Group 2) received basic fibroblast growth factor eye drops. We recorded the rate of corneal re-epithelialization and patients were followed-up every 30 days for 6 months. Statistical analyses were performed on the collected data. Results: The eyes in Group 1 demonstrated complete re-epithelialization at Day 5, whereas the eyes in Group 2 achieved this status on Day 6. No side-effects were reported. Conclusions: Patients treated with basic fibroblast growth factor eye drops and L-cysteine oral supplements benefit from more rapid corneal re-epithelialization. In human eyes, this combination treatment appeared to be safe and effective in accelerating corneal surfacing after surgery. Financial Disclosure: No author has any financial or proprietary interest in any material or method used in this study. Trial Registration: Current Controlled Trials ISRCTN73824458. PMID:24145571

  17. Comparison of the effect on bone healing process of different implants used in minimally invasive plate osteosynthesis: limited contact dynamic compression plate versus locking compression plate

    PubMed Central

    Xue, Zichao; Xu, Haitao; Ding, Haoliang; Qin, Hui; An, Zhiquan

    2016-01-01

    Minimally invasive plate osteosynthesis (MIPO) has been widely accepted because of its satisfactory clinical outcomes. However, the implant construct that works best for MIPO remains controversial. Different plate designs result in different influence mechanisms to blood flow. In this study, we created ulnar fractures in 42 beagle dogs and fixed the fractures using MIPO. The dogs were randomly divided into two groups and were fixed with a limited contact dynamic compression plate (LC-DCP) or a locking compression plate (LCP). Our study showed that with MIPO, there was no significant difference between the LCP and the LC-DCP in terms of fracture fixation, bone formation, or mineralization. Combined with the previous literature, we inferred that the healing process is affected by the quality of fracture reduction more than plate selection. PMID:27885262

  18. Mechanics of Hydraulic Fractures

    NASA Astrophysics Data System (ADS)

    Detournay, Emmanuel

    2016-01-01

    Hydraulic fractures represent a particular class of tensile fractures that propagate in solid media under pre-existing compressive stresses as a result of internal pressurization by an injected viscous fluid. The main application of engineered hydraulic fractures is the stimulation of oil and gas wells to increase production. Several physical processes affect the propagation of these fractures, including the flow of viscous fluid, creation of solid surfaces, and leak-off of fracturing fluid. The interplay and the competition between these processes lead to multiple length scales and timescales in the system, which reveal the shifting influence of the far-field stress, viscous dissipation, fracture energy, and leak-off as the fracture propagates.

  19. Do Bisphosphonate-related Atypical Femoral Fractures and Osteonecrosis of the Jaw Affect the Same Group of Patients? A Pilot Study

    PubMed Central

    Afif, Haitham; Mukka, Sebastian; Sjödén, Göran; Sayed-Noor, Arkan S.

    2014-01-01

    Bisphosphonates (BPs) are commonly used drugs in clinical practice. In this pilot study, we investigated whether bisphosphonate-related atypical femoral fractures (AFF) and osteonecrosis of the jaw (ONJ) occurred simultaneously in the same group of patients. Six ONJ patients were examined by an orthopedic surgeon and 5 AFF patients were examined by a dentist to look for manifestations of simultaneous occurrence of AFF in ONJ patients and vice versa. The required radiological investigations and previous medical and dental records were available. No simultaneous occurrence of AFF and ONJ was found in the examined patients. In this pilot study with limited sample size, no manifestations of simultaneous occurrence of AFF and ONJ were found. This could be an indication that these complications have different pathophysiologies and affect different subgroups of patients on long-term BP treatment. PMID:24744836

  20. Gene therapy for bone healing.

    PubMed

    Evans, Christopher H

    2010-06-23

    Clinical problems in bone healing include large segmental defects, spinal fusions, and the nonunion and delayed union of fractures. Gene-transfer technologies have the potential to aid healing by permitting the local delivery and sustained expression of osteogenic gene products within osseous lesions. Key questions for such an approach include the choice of transgene, vector and gene-transfer strategy. Most experimental data have been obtained using cDNAs encoding osteogenic growth factors such as bone morphogenetic protein-2 (BMP-2), BMP-4 and BMP-7, in conjunction with both nonviral and viral vectors using in vivo and ex vivo delivery strategies. Proof of principle has been convincingly demonstrated in small-animal models. Relatively few studies have used large animals, but the results so far are encouraging. Once a reliable method has been developed, it will be necessary to perform detailed pharmacological and toxicological studies, as well as satisfy other demands of the regulatory bodies, before human clinical trials can be initiated. Such studies are very expensive and often protracted. Thus, progress in developing a clinically useful gene therapy for bone healing is determined not only by scientific considerations, but also by financial constraints and the ambient regulatory environment.

  1. Gene therapy for bone healing

    PubMed Central

    Evans, Christopher H.

    2015-01-01

    Clinical problems in bone healing include large segmental defects, nonunion and delayed union of fractures, and spinal fusions. Gene-transfer technologies have the potential to aid healing by permitting the local delivery and sustained expression of osteogenic gene products within osseous lesions. Key questions for such an approach include the choice of transgene, vector and gene-transfer strategy. Most experimental data have been obtained using cDNAs encoding osteogenic growth factors such as bone morphogenetic protein-2 (BMP-2), BMP-4 and BMP-7, in conjunction with both nonviral and viral vectors using in vivo and ex vivo delivery strategies. Proof of principle has been convincingly demonstrated in small-animal models. Relatively few studies have used large animals, but the results so far are encouraging. Once a reliable method has been developed, it will be necessary to perform detailed pharmacological and toxicological studies, as well as satisfy other demands of the regulatory bodies, before human clinical trials can be initiated. Such studies are very expensive and often protracted. Thus, progress in developing a clinically useful gene therapy for bone healing is determined not only by scientific considerations, but also by financial constraints and the ambient regulatory environment. PMID:20569532

  2. A new self-healing epoxy with tungsten (VI) chloride catalyst.

    PubMed

    Kamphaus, Jason M; Rule, Joseph D; Moore, Jeffrey S; Sottos, Nancy R; White, Scott R

    2008-01-06

    Using self-healing materials in commercial applications requires healing chemistry that is cost-effective, widely available and tolerant of moderate temperature excursions. We investigate the use of tungsten (VI) chloride as a catalyst precursor for the ring-opening metathesis polymerization of exo-dicyclopentadiene (exo-DCPD) in self-healing applications as a means to achieve these goals. The environmental stability of WCl6 using three different delivery methods was evaluated and the associated healing performance was assessed following fracture toughness recovery protocols. Both as-received and recrystallized forms of the WCl6 resulted in nearly complete fracture recovery in self-activated tests, where healing agent is manually injected into the crack plane, at 12wt% WCl6 loading. In situ healing using 15wt% microcapsules of the exo-DCPD produced healing efficiencies of approximately 20%.

  3. [Bone disease with Pain. Colles' fracture].

    PubMed

    Yajima, Hiroshi

    2008-11-01

    The distal radius is one of the most commonly fractured long bone. Colles' fracture results from a fall on the dorsiflexed and pronated hand. The dinner-fork deformity is the typical deformity of the Colles' fracture. For patients with no or a little displacement, conservative treatment is applied. The non-bridge type external fixator is applied for patients without an intra articular fracture. For patients with a comminuted fracture, the locking plate (volar approach) is recommended. During the healing period, shoulder, elbow and finger exercise should be insisted.

  4. Adapting traditional healing practices.

    PubMed

    Weiser, J

    1999-01-01

    The Aboriginal people in Canada have been noted to have low self-esteem, subsequently increasing their risk of HIV. To this effect, two traditional healing practices are being used to help these people avoid HIV infection, and to live more healthily and positively if they are infected. The first method is the Medicine Wheel, which is a traditional model used to represent the complex interrelationship among all living things and show how their immune system is physically affected by their emotions and worries. Many Aboriginal AIDS Organizations, counselors and others are now using this AIDS teaching Wheel model. Meanwhile, the second method is the Sharing Circles, which provide an environment where people feel safe to talk about HIV and give participants a sense of support and a means for expression without stigma or judgement. As a result, many people who attend HIV circles begin to take better care of themselves and of others. Overall, it is emphasized that these traditional healing practices can be effectively adapted for use in HIV counseling and education.

  5. Wound Healing and Care

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Wound Healing and Care KidsHealth > For Teens > Wound Healing and Care Print A A A What's in ... mouth, or sunken eyes. There's good news about wound healing when you're a teen: Age is on ...

  6. [Severely displaced radial neck fractures after minimally invasive joystick reduction and Prévot nailing: long-term course in childhood].

    PubMed

    Yarar, S; Sommerfeldt, D W; Gehrmann, S; Rueger, J M

    2007-05-01

    Significantly displaced radial neck fractures in children are at risk for functional problems due to malaligned healing or growth disturbances at the proximal growth plate. Anatomic reduction is needed, especially in older children (aged 10+ years). Elastic stable intramedullary nailing (ESIN) (1993 Metaizeau) is the preferred method. When closed reduction is not possible, we use a joystick technique to fully reduce the radial head. The aim of this study was to challenge the hypothesis that this manipulation leads to secondary complications by affecting blood flow. Also, we asked the question to which extent an additional injury to the growth plate leads to functional problems concerning range of motion in the elbow joint. We undertook a retrospective analysis of children with severely displaced radial head fractures that occurred as isolated incidents or in combination with complex elbow fractures who had been treated by us with this technique between 1998 and 2004. We collected data on the clinical and radiological healing process.

  7. Posterior arch bifocal fracture of the atlas vertebra: a variant of Jefferson fracture.

    PubMed

    Abuamara, S; Dacher, J N; Lechevallier, J

    2001-07-01

    Fracture of the atlas vertebra is rare in children. We report two paediatric cases of bifocal pedicular fracture of the posterior arch of C1. Evaluation was performed by nonenhanced computed tomography scan, which successively confirmed both diagnosis and healing. In both cases, nonoperative management was successful.

  8. Low dose erythropoietin stimulates bone healing in mice.

    PubMed

    Garcia, P; Speidel, V; Scheuer, C; Laschke, M W; Holstein, J H; Histing, T; Pohlemann, T; Menger, M D

    2011-02-01

    Beyond its classical role in regulation of erythropoiesis, erythropoietin (EPO) has been shown to exert protective and regenerative actions in a variety of non-hematopoietic tissues. However, little is known about potential actions in bone regeneration. To analyze fracture healing in mice, a femoral 0.25 mm osteotomy gap was stabilized with a pin-clip technique. Animals were treated with 500 U EPO/kg bw per day or with vehicle only. After 2 and 5 weeks, fracture healing was analyzed biomechanically, radiologically and histologically. Expression of PCNA and NFκB was examined by Western blot analysis. Vascularization was analyzed by immunohistochemical staining of PECAM-1. Circulating endothelial progenitor cells were measured by flow-cytometry. Herein, we demonstrate that EPO-treatment significantly accelerates bone healing in mice. This is indicated by a significantly greater biomechanical stiffness and a higher radiological density of the periosteal callus at 2 and 5 weeks after fracture and stabilization. Histological analysis demonstrated significantly more bone and less cartilage and fibrous tissue in the periosteal callus. Endosteal vascularization was significantly increased in EPO-treated animals when compared to controls. The number of circulating endothelial progenitor cells was significantly greater in EPO-treated animals. The herein shown acceleration of healing by EPO may represent a promising novel treatment strategy for fractures with delayed healing and non-union formation.

  9. Shoulder Fractures

    MedlinePlus

    ... Journal of Hand Surgery (JHS) Home Anatomy Shoulder Fractures Email to a friend * required fields From * To * ... create difficulty with its function. Types of Shoulder Fractures The type of fracture varies by age. Most ...

  10. Stress Fractures

    MedlinePlus

    Stress fractures Overview By Mayo Clinic Staff Stress fractures are tiny cracks in a bone. They're caused by ... up and down or running long distances. Stress fractures can also arise from normal use of a ...

  11. Greenstick Fractures

    MedlinePlus

    Greenstick fractures Overview By Mayo Clinic Staff A greenstick fracture occurs when a bone bends and cracks, instead of breaking completely into separate pieces. The fracture looks similar to what happens when you try ...

  12. Permeability of WIPP Salt During Damage Evolution and Healing

    SciTech Connect

    BODNER,SOL R.; CHAN,KWAI S.; MUNSON,DARRELL E.

    1999-12-03

    The presence of damage in the form of microcracks can increase the permeability of salt. In this paper, an analytical formulation of the permeability of damaged rock salt is presented for both initially intact and porous conditions. The analysis shows that permeability is related to the connected (i.e., gas accessible) volumetric strain and porosity according to two different power-laws, which may be summed to give the overall behavior of a porous salt with damage. This relationship was incorporated into a constitutive model, known as the Multimechanism Deformation Coupled Fracture (MDCF) model, which has been formulated to describe the inelastic flow behavior of rock salt due to coupled creep, damage, and healing. The extended model was used to calculate the permeability of rock salt from the Waste Isolation Pilot Plant (WIPP) site under conditions where damage evolved with stress over a time period. Permeability changes resulting from both damage development under deviatoric stresses and damage healing under hydrostatic pressures were considered. The calculated results were compared against experimental data from the literature, which indicated that permeability in damaged intact WIPP salt depends on the magnitude of the gas accessible volumetric strain and not on the total volumetric strain. Consequently, the permeability of WIPP salt is significantly affected by the kinetics of crack closure, but shows little dependence on the kinetics of crack removal by sintering.

  13. Constitutive representation of damage development and healing in WIPP salt

    SciTech Connect

    Chan, K.S.; Bodner, S.R.; Fossum, A.F

    1994-12-31

    There has been considerable interest in characterizing and modeling the constitutive behavior of rock salt with particular reference to long-term creep and creep failure. The interest is motivated by the projected use of excavated rooms in salt rock formations as repositories for nuclear waste. It is presumed that closure of those rooms by creep ultimately would encapsulate the waste material, resulting in its effective isolation. A continuum mechanics approach for treating damage healing is formulated as part of a constitutive model for describing coupled creep, fracture, and healing in rock salt. Formulation of the healing term is, described and the constitutive model is evaluated against experimental data of rock salt from the Waste Isolation Pilot Plant (WIPP) site. The results indicate that healing anistropy in WIPP salt can be modeled with an appropriate power-conjugate equivalent stress, kinetic equation, and evolution equation for damage healing.

  14. Autonomic Healing of Epoxy Using Micro-Encapsulated Dicyclopentadiene

    SciTech Connect

    THOMA, STEVEN G.; GIUNTA, RACHEL K.; STAVIG, MARK E.; EMERSON, JOHN A.; MORALES, ALFREDO M.

    2003-05-01

    The autonomic healing ability of an epoxy adhesive containing micro-encapsulated dicyclopentadiene (DCPD) was evaluated. The epoxy resin used was Epon 828 cured with either Versamid 140 or diethylenetriamine (DETA). Variables included total weight percent of microcapsules (MCs) and catalyst, as well as the catalyst to DCPD ratio. The degree of healing was determined by the fracture toughness before and after ''healing'' using double-cantilever beam analysis. It was found that the degree of self-healing was most directly related to the contact area (i.e. crack width) during healing. Temperature also played a significant role. Observed differences between the results of this study and those in literature are discussed.

  15. Targeted Self-Healing by Magnetically Guiding Microcapsules.

    PubMed

    Crall, Matthew D; Keller, Michael W

    2017-02-22

    Magnetically guided microcapsules are used to achieve self-healing with 1/10th of the healing components required using traditional self-healing approaches. Microcapsules are rendered responsive to magnetic fields by suspending magnetic nanoparticles in the core material. The nanoparticles are surface-modified to enable urea-formaldehyde encapsulation within a phenyl acetate core. Magnetic fields are used to guide the microcapsules to the expected fracture location in tapered double-cantilever beam (TDCB) epoxy specimens. This guiding method achieves an order of magnitude increase in local microcapsule concentration over controls, resulting in successful self-healing at microcapsule concentrations as low as 0.025 wt %. Additionally, the observed healing is both more consistent and significantly higher than that of control specimens, remaining relatively constant across all weight percentages tested.

  16. Mathematical modeling in wound healing, bone regeneration and tissue engineering.

    PubMed

    Geris, Liesbet; Gerisch, Alf; Schugart, Richard C

    2010-12-01

    The processes of wound healing and bone regeneration and problems in tissue engineering have been an active area for mathematical modeling in the last decade. Here we review a selection of recent models which aim at deriving strategies for improved healing. In wound healing, the models have particularly focused on the inflammatory response in order to improve the healing of chronic wound. For bone regeneration, the mathematical models have been applied to design optimal and new treatment strategies for normal and specific cases of impaired fracture healing. For the field of tissue engineering, we focus on mathematical models that analyze the interplay between cells and their biochemical cues within the scaffold to ensure optimal nutrient transport and maximal tissue production. Finally, we briefly comment on numerical issues arising from simulations of these mathematical models.

  17. Repeated self-healing of microvascular carbon fibre reinforced polymer composites

    NASA Astrophysics Data System (ADS)

    Coope, T. S.; Wass, D. F.; Trask, R. S.; Bond, I. P.

    2014-11-01

    A self-healing, high performance, carbon fibre reinforced polymer (CFRP) composite is demonstrated by embedding a Lewis-acid catalytic curing agent within a laminate, manufactured using out of autoclave (OOA) composite manufacturing methods. Two configurations of healing agent delivery, pre-mixed and autonomous mixing, are investigated via injection of a healing agent through bio-inspired microvascular channels exposed on Mode I fractured crack planes. Healing is effected when an epoxy resin-solvent healing agent mixture reaches the boundary of embedded solid-state scandium(III) triflate (Sc(OTf)3) catalyst, located on the crack plane, to initiate the ring-opening polymerisation (ROP) of epoxides. Tailored self-healing agents confer high healing efficiency values after multiple healing cycles (69-108%) to successfully mitigate against crack propagation within the composite microstructure.

  18. Femur Fractures in Professional Athletes: A Case Series

    PubMed Central

    Sikka, Robby; Fetzer, Gary; Hunkele, Thomas; Sugarman, Eric; Boyd, Joel

    2015-01-01

    Objective: To discuss return to play after femur fractures in several professional athletes. Background: Femur fractures are rare injuries and can be associated with significant morbidity and mortality. No reports exist, to our knowledge, on return to play after treatment of isolated femur fractures in professional athletes. Return to play is expected in patients with femur fractures, but recovery can take more than 1 year, with an expected decrease in performance. Treatment: Four professional athletes sustained isolated femur fractures during regular-season games. Two athletes played hockey, 1 played football, and 1 played baseball. Three players were treated with anterograde intramedullary nails, and 1 was treated with retrograde nailing. All players missed the remainder of the season. At an average of 9.5 months (range, 7–13 months) from the time of injury, all athletes were able to return to play. One player required the removal of painful hardware, which delayed his return to sport. Final radiographs revealed that all fractures were well healed. No athletes had subjective complaints or concerns that performance was affected by the injury at an average final follow-up of 25 months (range, 22–29 months). Uniqueness: As the size and speed of players increase, on-field trauma may result in significant injury. All players returned to previous levels of performance or exceeded previous statistical performance levels. Conclusions: In professional athletes, return to play from isolated femur fractures treated with either an anterograde or retrograde intramedullary nail is possible within 1 year. Return to the previous level of performance is possible, and it is important to develop management protocols, including rehabilitation guidelines, for such injuries. However, return to play may be delayed by subsequent procedures, including hardware removal. PMID:25680071

  19. The healing Buddha.

    PubMed

    Chen, Thomas S N; Chen, Peter S Y

    2004-11-01

    The iconography of the healing Buddha embraces two healing traditions, symbolized by the healing stone lapis lazuli from Central Asia and by the myrobalan fruit from the ayurvedic medicine of ancient India. The first mention of the healing Buddha is in Buddhist texts of the first century BC, and the earliest extant icons date from the fourth century AD. This suggests the cult of the healing Buddha was a relatively late development in the history of Buddhism. Worshippers sought his help in alleviating spiritual, mental and physical suffering, as well as for medical cures. In China followers believed he was also a cosmic Buddha, to whom one appealed for longevity and protection from disasters. This form of faith-based healing remains vibrant in China, Japan and Tibet to this day.

  20. Effects of alloying elements on mechanical and fracture properties of base metals and simulated heat-affected zones of SA 508 steels

    NASA Astrophysics Data System (ADS)

    Kim, Sangho; Lee, Sunghak; Im, Young-Roc; Lee, Hu-Chul; Oh, Yong Jun; Hong, Jun Hwa

    2001-04-01

    This study was aimed at developing low-alloy steels for nuclear reactor pressure vessels by investigating the effects of alloying elements on mechanical and fracture properties of base metals and heat-affected zones (HAZs). Four steels whose compositions were variations of the composition specification for SA 508 steel (class 3) were fabricated by vacuum-induction melting and heat treatment, and their tensile properties and Charpy impact toughness were evaluated. Microstructural analyses indicated that coarse M3C-type carbides and fine M2C-type carbides were precipitated along lath boundaries and inside laths, respectively. In the steels having decreased carbon content and increased molybdenum content, the amount of fine M2C carbides was greatly increased, while that of coarse M3C carbides was decreased, thereby leading to the improvement of tensile properties and impact toughness. Their simulated HAZs also had sufficient impact toughness after postweld heat treatment (PWHT). These findings suggested that the low-alloy steels with high strength and toughness could be processed by decreasing carbon and manganese contents and by increasing molybdenum content.

  1. Enhanced Healing of Segmental Bone Defects by Modulation of the Mechanical Environment

    DTIC Science & Technology

    2013-10-01

    AE, Kenwright J. The influence of induced micromovement upon the healing of experimental tibial fractures. J Bone Joint Surg Br 1985;67-4:650-5. 4...Kenwright J, Goodship AE. Controlled mechanical stimulation in the treatment of tibial fractures. Clin Orthop Relat Res 1989-241:36-47. 5. Perren...7. Larsson S, Kim W, Caja VL, Egger EL, Inoue N, Chao EY. Effect of early axial dynamization on tibial bone healing: a study in dogs. Clin Orthop

  2. Self-healing materials.

    PubMed

    Hager, Martin D; Greil, Peter; Leyens, Christoph; van der Zwaag, Sybrand; Schubert, Ulrich S

    2010-12-14

    Self-healing materials are able to partially or completely heal damage inflicted on them, e.g., crack formation; it is anticipated that the original functionality can be restored. This article covers the design and generic principles of self-healing materials through a wide range of different material classes including metals, ceramics, concrete, and polymers. Recent key developments and future challenges in the field of self-healing materials are summarised, and generic, fundamental material-independent principles and mechanism are discussed and evaluated.

  3. Transparotid approach for mandibular condylar neck and subcondylar fractures.

    PubMed

    Croce, A; Moretti, A; Vitullo, F; Castriotta, A; Rosa, De M; Citraro, L

    2010-12-01

    Mandibular condylar neck fractures and subcondylar fractures represent, respectively, 19-29% and 62-70% of all mandibular fractures; treatment involves some problems, common to both, concerning the choice of an adequate approach. Herewith, personal experience is reported related to the surgical treatment of some cases of mandibular condylar neck and subcondylar fractures by transparotid approaches with partial parotidectomy, removing the salivary tissue overlying the condylar neck and/or the subcondylar region. Over the last 5 years, we observed 22 fractures of the condylar neck and 10 fractures of the subcondylar region. In 13 patients (11 male, 2 female, age range 10-68 years, mean 33 years), 10 of whom had other mandibular and/or other maxillo-facial and skeleton fractures - 50% of these with dislocated condylar heads - and the other 3 for their free choice, regarding the different treatments, 18 transparotid approaches with partial parotidectomy (bilateral in 5 cases), were performed reducing and fixing 12 condylar neck fractures and 5 subcondylar region fractures with appropriate plates (2.0 mm) and screws. After surgery, no intermaxillary fixation was performed. Complications included 4 salivary fistulae (bilateral in 1 patient), which closed spontaneously after 4 or 5 weeks with a dressing, 1 case of Frey's syndrome, which healed after 2 treatments with botulin and 6 cases of transient facial palsy lasting 4-8 weeks (1 case bilateral) affecting zygomatic, buccal and marginal mandibular nerves. During follow-up, functional parameters considered were: restoration of original pre-injury occlusion; vertical, lateral and protrusion mandibular movements. All patients re-acquired the original pre-injury occlusion; the maximal post-operative intrinsical distance was at least 40 mm after a variable period of rehabilitation and lateral and protrusion movements also led to satisfactory final results. All patients were free of pain and had no deflection or clicking upon

  4. Principles of Wound Management and Wound Healing in Exotic Pets.

    PubMed

    Mickelson, Megan A; Mans, Christoph; Colopy, Sara A

    2016-01-01

    The care of wounds in exotic animal species can be a challenging endeavor. Special considerations must be made in regard to the animal's temperament and behavior, unique anatomy and small size, and tendency toward secondary stress-related health problems. It is important to assess the entire patient with adequate systemic evaluation and consideration of proper nutrition and husbandry, which could ultimately affect wound healing. This article summarizes the general phases of wound healing, factors that affect healing, and principles of wound management. Emphasis is placed on novel methods of treating wounds and species differences in wound management and healing.

  5. An electronically instrumented internal fixator for the assessment of bone healing

    PubMed Central

    Kowald, B.; Seide, K.; Aljudaibi, M.; Faschingbauer, M.; Juergens, C.; Gille, J.

    2016-01-01

    Objectives The monitoring of fracture healing is a complex process. Typically, successive radiographs are performed and an emerging calcification of the fracture area is evaluated. The aim of this study was to investigate whether different bone healing patterns can be distinguished using a telemetric instrumented femoral internal plate fixator. Materials and Methods An electronic telemetric system was developed to assess bone healing mechanically. The system consists of a telemetry module which is applied to an internal locking plate fixator, an external reader device, a sensor for measuring externally applied load and a laptop computer with processing software. By correlation between externally applied load and load measured in the implant, the elasticity of the osteosynthesis is calculated. The elasticity decreases with ongoing consolidation of a fracture or nonunion and is an appropriate parameter for the course of bone healing. At our centre, clinical application has been performed in 56 patients suffering nonunion or fracture of the femur. Results A total of 39 cases of clinical application were reviewed for this study. In total, four different types of healing curves were observed: fast healing; slow healing; plateau followed by healing; and non-healing. Conclusion The electronically instrumented internal fixator proved to be valuable for the assessment of bone healing in difficult healing situations. Cost-effective manufacturing is possible because the used electronic components are derived from large-scale production. The incorporation of microelectronics into orthopaedic implants will be an important innovation in future clinical care. Cite this article: B. Kienast, B. Kowald, K. Seide, M. Aljudaibi, M. Faschingbauer, C. Juergens, J. Gille. An electronically instrumented internal fixator for the assessment of bone healing. Bone Joint Res 2016;5:191–197. DOI: 10.1302/2046-3758.55.2000611. PMID:27226357

  6. Effects of alloying elements on fracture toughness in the transition temperature region of base metals and simulated heat-affected zones of Mn-Mo-Ni low-alloy steels

    NASA Astrophysics Data System (ADS)

    Kim, Sangho; Im, Young-Roc; Lee, Sunghak; Lee, Hu-Chul; Kim, Sung-Joon; Hong, Jun Hwa

    2004-07-01

    This study is concerned with the effects of alloying elements on fracture toughness in the transition temperature region of base metals and heat-affected zones (HAZs) of Mn-Mo-Ni low-alloy steels. Three kinds of steels whose compositions were varied from the composition specification of SA 508 steel (grade 3) were fabricated by vacuum-induction melting and heat treatment, and their fracture toughness was examined using an ASTM E1921 standard test method. In the steels that have decreased C and increased Mo and Ni content, the number of fine M2C carbides was greatly increased and the number of coarse M3C carbides was decreased, thereby leading to the simultaneous improvement of tensile properties and fracture toughness. Brittle martensite-austenite (M-A) constituents were also formed in these steels during cooling, but did not deteriorate fracture toughness because they were decomposed to ferrite and fine carbides after tempering. Their simulated HAZs also had sufficient impact toughness after postweld heat treatment. These findings indicated that the reduction in C content to inhibit the formation of coarse cementite and to improve toughness and the increase in Mo and Ni to prevent the reduction in hardenability and to precipitate fine M2C carbides were useful ways to improve simultaneously the tensile and fracture properties of the HAZs as well as the base metals.

  7. Rock fracture processes in chemically reactive environments

    NASA Astrophysics Data System (ADS)

    Eichhubl, P.

    2015-12-01

    Rock fracture is traditionally viewed as a brittle process involving damage nucleation and growth in a zone ahead of a larger fracture, resulting in fracture propagation once a threshold loading stress is exceeded. It is now increasingly recognized that coupled chemical-mechanical processes influence fracture growth in wide range of subsurface conditions that include igneous, metamorphic, and geothermal systems, and diagenetically reactive sedimentary systems with possible applications to hydrocarbon extraction and CO2 sequestration. Fracture processes aided or driven by chemical change can affect the onset of fracture, fracture shape and branching characteristics, and fracture network geometry, thus influencing mechanical strength and flow properties of rock systems. We are investigating two fundamental modes of chemical-mechanical interactions associated with fracture growth: 1. Fracture propagation may be aided by chemical dissolution or hydration reactions at the fracture tip allowing fracture propagation under subcritical stress loading conditions. We are evaluating effects of environmental conditions on critical (fracture toughness KIc) and subcritical (subcritical index) fracture properties using double torsion fracture mechanics tests on shale and sandstone. Depending on rock composition, the presence of reactive aqueous fluids can increase or decrease KIc and/or subcritical index. 2. Fracture may be concurrent with distributed dissolution-precipitation reactions in the hostrock beyond the immediate vicinity of the fracture tip. Reconstructing the fracture opening history recorded in crack-seal fracture cement of deeply buried sandstone we find that fracture length growth and fracture opening can be decoupled, with a phase of initial length growth followed by a phase of dominant fracture opening. This suggests that mechanical crack-tip failure processes, possibly aided by chemical crack-tip weakening, and distributed

  8. Microgravity and the implications for wound healing.

    PubMed

    Farahani, Ramin Mostofizadeh; DiPietro, Luisa A

    2008-10-01

    Wound healing is a sophisticated response ubiquitous to various traumatic stimuli leading to an anatomical/functional disruption. The aim of present article was to review the current evidence regarding the effects of microgravity on wound healing dynamics. Modulation of haemostatic phase because of alteration of platelet quantity and function seems probable. Furthermore, production of growth factors that are released from activated platelets and infiltration/function of inflammatory cells seem to be impaired by microgravity. Proliferation of damaged structures is dependent on orchestrated function of various growth factors, for example transforming growth factors, platelet-derived growth factor and epidermal growth factor, all of which are affected by microgravitational status. Moreover, gravity-induced alterations of gap junction, neural inputs, and cell populations have been reported. It may be concluded that different cellular and extracellular element involved in the healing response are modified through effect of microgravity which may lead to impairment in healing dynamics.

  9. Cutaneous wound healing in Ehlers-Danlos syndrome.

    PubMed

    Freeman, L J; Hegreberg, G A; Robinette, J D

    1989-01-01

    Wound healing in five dogs and five cats affected with a connective tissue dysplasia resembling Ehlers-Danlos syndrome of humans was compared with wound healing in 10 nonaffected animals. Six skin incisions on the lateral aspects of the thorax and abdomen of each animal were sutured and assessed daily for 75 days for evidence of healing. All wounds in nonaffected dogs, affected cats, and nonaffected cats healed by first intention. Three incisions in affected dogs had dehiscence of all or part of the incision line and healed by granulation, contraction, and epithelialization. Biopsies taken at 3, 6, 9, 12, 15, and 75 days were compared histologically to determine if there were any differences in rates of healing between affected and nonaffected animals. Epidermal thickening and scab formation were noted at days 3 and 6 in both affected and nonaffected animals. Infiltration with mononuclear cells and fibroplasia steadily increased from day 6 to day 15 in all groups. Collagen fibril formation was evident by day 9. At day 75, incision sites were recognized by fine, more compact collagen bundles and lack of adnexal structures, as compared with the adjacent dermis in both affected and nonaffected animals. Although delayed wound healing has been reported to be a complication of Ehlers-Danlos syndrome in humans, using clinical and histologic criteria, wound healing in dogs and cats with Ehlers-Danlos syndrome appears to be similar to nonaffected animals.

  10. Self Healing Percolation

    NASA Astrophysics Data System (ADS)

    Scala, Antonio

    2015-03-01

    We introduce the concept of self-healing in the field of complex networks modelling; in particular, self-healing capabilities are implemented through distributed communication protocols that exploit redundant links to recover the connectivity of the system. Self-healing is a crucial in implementing the next generation of smart grids allowing to ensure a high quality of service to the users. We then map our self-healing procedure in a percolation problem and analyse the interplay between redundancies and topology in improving the resilience of networked infrastructures to multiple failures. We find exact results both for planar lattices and for random lattices, hinting the role of duality in the design of resilient networks. Finally, we introduce a cavity method approach to study the recovery of connectivity after damage in self-healing networks. CNR-PNR National Project ``Crisis-Lab,'' EU HOME/2013/CIPS/AG/4000005013 project CI2C and EU FET project MULTIPLEX nr.317532.

  11. Current Options for Determining Fracture Union

    PubMed Central

    Morshed, Saam

    2014-01-01

    Determining whether a bone fracture is healed is one of the most important and fundamental clinical determinations made in orthopaedics. However, there are currently no standardized methods of assessing fracture union, which in turn has created significant disagreement among orthopaedic surgeons in both clinical and research settings. An extensive amount of research has been dedicated to finding novel and reliable ways of determining healing with some promising results. Recent advancements in imaging techniques and introduction of new radiographic scores have helped decrease the amount of disagreement on this topic among physicians. The knowledge gained from biomechanical studies of bone healing has helped us refine our tools and create more efficient and practical research instruments. Additionally, a deeper understanding of the molecular pathways involved in the bone healing process has led to emergence of serologic markers as possible candidates in assessment of fracture union. In addition to our current physician centered methods, patient-centered approaches assessing quality of life and function are gaining popularity in assessment of fracture union. Despite these advances, assessment of union remains an imperfect practice in the clinical setting. Therefore, clinicians need to draw on multiple modalities that directly and indirectly measure or correlate with bone healing when counseling patients. PMID:26556422

  12. Transport efficiency and dynamics of hydraulic fracture networks

    NASA Astrophysics Data System (ADS)

    Sachau, Till; Bons, Paul; Gomez-Rivas, Enrique

    2015-08-01

    Intermittent fluid pulses in the Earth's crust can explain a variety of geological phenomena, for instance the occurrence of hydraulic breccia. Fluid transport in the crust is usually modeled as continuous darcian flow, ignoring that sufficient fluid overpressure can cause hydraulic fractures as fluid pathways with very dynamic behavior. Resulting hydraulic fracture networks are largely self-organized: opening and healing of hydraulic fractures depends on local fluid pressure, which is, in turn, largely controlled by the fracture network. We develop a crustal-scale 2D computer model designed to simulate this process. To focus on the dynamics of the process we chose a setup as simple as possible. Control factors are constant overpressure at a basal fluid source and a constant 'viscous' parameter controlling fracture-healing. Our results indicate that at large healing rates hydraulic fractures are mobile, transporting fluid in intermittent pulses to the surface and displaying a 1/fα behavior. Low healing rates result in stable networks and constant flow. The efficiency of the fluid transport is independent from the closure dynamics of veins or fractures. More important than preexisting fracture networks is the distribution of fluid pressure. A key requirement for dynamic fracture networks is the presence of a fluid pressure gradient.

  13. Interlocking Intramedullary Nails in Fracture Treatment.

    PubMed

    Ouyang, Xiao; Wang, Jing Rong; Hong, Shi Dong; Xin, Feng; Wang, Lin; Yang, Xiao Wei; Wang, Jian

    2015-09-01

    The aim of this study is to evaluate interlocking intramedullary nails in the treatment of fractures. We retrospectively reviewed 68 adult patients (for a total of 95 fractures) with isolated long-bone fractures who were treated with interlocking intramedullary nails between January 2010 and January 2012. The patients were followed for 18 months to observe the healing of the fracture, time, and the occurrence of complications in the shoulder, knee, and hip joint functions. After about a follow-up period of 26.2 months (range 18-39 months), all cases obtained bony union. The mean time to fracture union was 5.2 months. Cases of knees and hip joint functions of the femoral or tibial fracture and shoulder functions of the humeral fractures were observed. The interlocking intramedullary nails may be considered as an alternative method for isolated diaphyseal fractures of the extremities. The advantages of this method include small operative scars, reliable fixations, better fracture healings, and fewer complications.

  14. Scaphoid fracture in the elite athlete.

    PubMed

    Belsky, Mark R; Leibman, Matthew I; Ruchelsman, David E

    2012-08-01

    Scaphoid fracture remains a common, potentially devastating, injury that can impair upper extremity function. Early recognition with proper imaging and treatment provides the best opportunity to heal and return to a normal activity level. Surgical treatment offers the patient a quicker return to the rehabilitation of the extremity and therefore an earlier return to elite play. There is evidence that healing occurs faster if the fractured scaphoid is fixed with internal fixation. Absolute compliance by the athlete and the training program that surrounds the athlete is critical to protect the wrist while maintaining the necessary conditioning of an elite athlete.

  15. Performance monitoring of large-scale autonomously healed concrete beams under four-point bending through multiple non-destructive testing methods

    NASA Astrophysics Data System (ADS)

    Karaiskos, G.; Tsangouri, E.; Aggelis, D. G.; Van Tittelboom, K.; De Belie, N.; Van Hemelrijck, D.

    2016-05-01

    Concrete is still the leading structural material due to its low production cost and great structural design flexibility. Although it is distinguished by such a high durability and compressive strength, it is vulnerable in a series of ambient and operational degradation factors which all too frequently result in crack formation that can adversely affect its mechanical performance. The autonomous healing system, using encapsulated polyurethane-based, expansive, healing agent embedded in concrete, is triggered by the crack formation and propagation and promises material repair and operational service life extension. As shown in our previous studies, the formed cracks on small-scale concrete beams are sealed and repaired by filling them with the healing agent. In the present study, the crack formation and propagation in autonomously healed, large-scale concrete beams are thoroughly monitored through a combination of non-destructive testing (NDT) methods. The ultrasonic pulse velocity (UPV), using embedded low-cost and aggregate-size piezoelectric transducers, the acoustic emission (AE) and the digital image correlation (DIC) are the NDT methods which are comprehensively used. The integrated ultrasonic, acoustic and optical monitoring system introduces an experimental configuration that detects and locates the four-point bending mode fracture on large-scale concrete beams, detects the healing activation process and evaluates the subsequent concrete repair.

  16. Use of an osteoconductive compound as an aid in the management of a maxillary fracture in a boa constrictor.

    PubMed

    Rahal, Sheila C; Teixeira, Carlos R; Vulcano, Luiz C; Aguiar, Antonio J A

    2011-03-01

    A boa constrictor was presented with a short oblique compound fracture of the rostral third of the right maxilla. The fracture was reduced and biomaterial was placed around the fracture. A computed tomography scan at 1.5 mo post-surgery showed that the fracture had healed with slight displacement of the bone fragments.

  17. [Atlas fractures].

    PubMed

    Schären, S; Jeanneret, B

    1999-05-01

    Fractures of the atlas account for 1-2% of all vertebral fractures. We divide atlas fractures into 5 groups: isolated fractures of the anterior arch of the atlas, isolated fractures of the posterior arch, combined fractures of the anterior and posterior arch (so-called Jefferson fractures), isolated fractures of the lateral mass and fractures of the transverse process. Isolated fractures of the anterior or posterior arch are benign and are treated conservatively with a soft collar until the neck pain has disappeared. Jefferson fractures are divided into stable and unstable fracture depending on the integrity of the transverse ligament. Stable Jefferson fractures are treated conservatively with good outcome while unstable Jefferson fractures are probably best treated operatively with a posterior atlanto-axial or occipito-axial stabilization and fusion. The authors preferred treatment modality is the immediate open reduction of the dislocated lateral masses combined with a stabilization in the reduced position using a transarticular screw fixation C1/C2 according to Magerl. This has the advantage of saving the atlanto-occipital joints and offering an immediate stability which makes immobilization in an halo or Minerva cast superfluous. In late instabilities C1/2 with incongruency of the lateral masses occurring after primary conservative treatment, an occipito-cervical fusion is indicated. Isolated fractures of the lateral masses are very rare and may, if the lateral mass is totally destroyed, be a reason for an occipito-cervical fusion. Fractures of the transverse processes may be the cause for a thrombosis of the vertebral artery. No treatment is necessary for the fracture itself.

  18. Effect of CoCl₂ on fracture repair in a rat model of bone fracture.

    PubMed

    Huang, Jiang; Liu, Liming; Feng, Mingli; An, Shuai; Zhou, Meng; Li, Zheng; Qi, Jiajian; Shen, Huiliang

    2015-10-01

    Low oxygen availability is known to activate the hypoxia-inducible factor-1α (HIF-1α) pathway, which is involved in the impairment of fracture healing. However, the role of low oxygen in fracture healing remains to be fully elucidated. In the present study, rats were divided into two groups and treated with CoCl2 or saline, respectively. Mice with tibial fractures were sacrificed at 14, 28 and 42 days subsequent to fracture. Autoradiography was performed to measure healing of the bone tissue. In addition, the effects of cobalt chloride (CoCl2) on the expression of two major angiogenic mediators, HIF‑1α and vascular endothelial growth factor (VEGF), as well as the osteoblast markers runt‑related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and osteocalcin (OC) were determined at mRNA and protein levels by reverse transcription‑quantitative polymerase chain reaction, western blot analysis and immunohistochemistry. Systemic administration of CoCl2 (15 mg/kg/day intraperitoneally) significantly promoted fracture healing and mechanical strength. The present study demonstrated that in rats treated with CoCl2, the expression of HIF‑1α, VEGF, Runx2, ALP and OC was significantly increased at mRNA and protein levels, and that CoCl2 treatment enhances fracture repair in vivo.

  19. Clinical analysis of the rap stress stimulator applied for crus fracture after skeletal external fixation

    PubMed Central

    Zhuang, Ping; Hong, Jiayuan; Chen, Wei; Wu, Jin

    2015-01-01

    Introduction Open crus fracture is still difficult in clinical treatment because of the delayed fracture union and high rate of nonunion after the operation. A consensus has been reached that mechanical stress can promote fracture healing. We independently developed a stress stimulator, which can provide longitudinal pressure for the fixed fracture end of the lower legs to promote fracture healing. The purpose of this study is to explore the advantages and clinical effect of the rap stress stimulator applied for open crus fracture after skeletal external fixation. Material and methods One hundred and sixty-five patients (183 limbs) who suffered from open tibia and fibula fracture received skeletal external fixation, of which 108 limbs were treated with the rap stress stimulator after external fixation and 75 limbs were treated with regular functional exercises of muscle contraction and joint activity only. Then the fracture healing time and rate of nonunion were compared between the two groups. Results The mean fracture healing time and rate of nonunion in the group treated with the rap stress stimulator were 138.27 ±4.45 days and 3.70% respectively, compared to 153.43 ±4.89 days and 10.67% in the group treated without the stimulator. Conclusions The rap stress stimulator significantly shortened the fracture healing time and reduced the rate of nonunion for treating open tibia and fibula fractures. PMID:26170856

  20. Fracture and Fatigue

    DTIC Science & Technology

    1988-04-01

    fracture. The main additional categories of crack growth are elastic-plastic crack growth, fatigue crack growth, and crack growth as affected by...FRACTURE AND FATIGUE R. 0. RITCHIE W. W. GERBERICH J. H. UNDERWOOD DTIC AM ELECTE JUL 1 11988 APRIL 1988 FH US ARMY ARMAMENT RESEARCH, DEVELOPMENT AND...other authorized documents. N The use of trade name(s) and/or manufacturer (s) does not constitute an official indorsement or approval. DESTRUCTION NOTICE

  1. Basics in nutrition and wound healing.

    PubMed

    Wild, Thomas; Rahbarnia, Arastoo; Kellner, Martina; Sobotka, Lubos; Eberlein, Thomas

    2010-09-01

    Wound healing is a process that can be divided into three different phases (inflammatory, proliferative, and maturation). Each is characterized by certain events that require specific components. However, wound healing is not always a linear process; it can progress forward and backward through the phases depending on various intrinsic and extrinsic factors. If the wound-healing process is affected negatively, this can result in chronic wounds. Chronic wounds demand many resources in the clinical daily routine. Therefore, local wound management and good documentation of the wound is essential for non-delayed wound healing and prevention of the development of chronic wounds. During the wound-healing process much energy is needed. The energy for the building of new cells is usually released from body energy stores and protein reserves. This can be very challenging for undernourished and malnourished patients. Malnutrition is very common in geriatric patients and patients in catabolic phases of stress such as after injury or surgery. For that reason a close survey of the nutritional status of patients is necessary to start supplementation quickly, if applicable. Wound healing is indeed a very complex process that deserves special notice. There are some approaches to develop guidelines but thus far no golden standard has evolved. Because wounds, especially chronic wounds, cause also an increasing economic burden, the development of guidelines should be advanced.

  2. Fracture opening/propagation behavior and their significance on pressure-time records during hydraulic fracturing

    SciTech Connect

    Takashi Kojima; Yasuhiko Nakagawa; Koji Matsuki; Toshiyuki Hashida

    1992-01-01

    Hydraulic fracturing with constant fluid injection rate was numerically modeled for a pair of rectangular longitudinal fractures intersecting a wellbore in an impermeable rock mass, and numerical calculations have been performed to investigate the relations among the form of pressure-time curves, fracture opening/propagation behavior and permeability of the mechanically closed fractures. The results have shown that both permeability of the fractures and fluid injection rate significantly influence the form of the pressure-time relations on the early stage of fracture opening. Furthermore it has been shown that wellbore pressure during fracture propagation is affected by the pre-existing fracture length.

  3. A Concert between Biology and Biomechanics: The Influence of the Mechanical Environment on Bone Healing

    PubMed Central

    Glatt, Vaida; Evans, Christopher H.; Tetsworth, Kevin

    2017-01-01

    In order to achieve consistent and predictable fracture healing, a broad spectrum of growth factors are required to interact with one another in a highly organized response. Critically important, the mechanical environment around the fracture site will significantly influence the way bone heals, or if it heals at all. The role of the various biological factors, the timing, and spatial relationship of their introduction, and how the mechanical environment orchestrates this activity, are all crucial aspects to consider. This review will synthesize decades of work and the acquired knowledge that has been used to develop new treatments and technologies for the regeneration and healing of bone. Moreover, it will discuss the current state of the art in experimental and clinical studies concerning the application of these mechano-biological principles to enhance bone healing, by controlling the mechanical environment under which bone regeneration takes place. This includes everything from the basic principles of fracture healing, to the influence of mechanical forces on bone regeneration, and how this knowledge has influenced current clinical practice. Finally, it will examine the efforts now being made for the integration of this research together with the findings of complementary studies in biology, tissue engineering, and regenerative medicine. By bringing together these diverse disciplines in a cohesive manner, the potential exists to enhance fracture healing and ultimately improve clinical outcomes. PMID:28174539

  4. Skull fracture

    MedlinePlus

    ... compress the underlying brain tissue (subdural or epidural hematoma). A simple fracture is a break in the bone without damage ... Causes of skull fracture can include: Head trauma Falls, automobile accidents, physical assault, and sports

  5. Rib Fractures

    MedlinePlus

    ... From Brain Injury Additional Content Medical News Rib Fractures By Thomas G. Weiser, MD, MPH, Department of ... Hemothorax Injury to the Aorta Pulmonary Contusion Rib Fractures Tension Pneumothorax Traumatic Pneumothorax (See also Introduction to ...

  6. Hand Fractures

    MedlinePlus

    ... Thumb Arthritis Thumb Sprains Trigger Finger Tumors Wrist Fracture Hand Safety Fireworks Safety Lawnmower Safety Snowblower safety ... Tunnel Ganglion Cysts Thumb Arthritis Trigger Finger Wrist Fracture Hand Safety Fireworks Safety Lawnmower Safety Snowblower safety ...

  7. Identifying Fracture Types and Relative Ages Using Fluid Inclusion Stratigraphy

    SciTech Connect

    Dilley, Lorie M.; Norman, David; Owens, Lara

    2008-06-30

    Enhanced Geothermal Systems (EGS) are designed to recover heat from the subsurface by mechanically creating fractures in subsurface rocks. Understanding the life cycle of a fracture in a geothermal system is fundamental to the development of techniques for creating fractures. Recognizing the stage of a fracture, whether it is currently open and transmitting fluids; if it recently has closed; or if it is an ancient fracture would assist in targeting areas for further fracture stimulation. Identifying dense fracture areas as well as large open fractures from small fracture systems will also assist in fracture stimulation selection. Geothermal systems are constantly generating fractures, and fluids and gases passing through rocks in these systems leave small fluid and gas samples trapped in healed microfractures. Fluid inclusions trapped in minerals as the fractures heal are characteristic of the fluids that formed them, and this signature can be seen in fluid inclusion gas analysis. Our hypothesis is that fractures over their life cycle have different chemical signatures that we can see in fluid inclusion gas analysis and by using the new method of fluid inclusion stratigraphy (FIS) the different stages of fractures, along with an estimate of fracture size can be identified during the well drilling process. We have shown with this study that it is possible to identify fracture locations using FIS and that different fractures have different chemical signatures however that signature is somewhat dependent upon rock type. Open, active fractures correlate with increase concentrations of CO2, N2, Ar, and to a lesser extent H2O. These fractures would be targets for further enhancement. The usefulness of this method is that it is low cost alternative to current well logging techniques and can be done as a well is being drilled.

  8. Irrigation solutions in open fractures of the lower extremities: evaluation of isotonic saline and distilled water

    PubMed Central

    Olufemi, Olukemi Temiloluwa; Adeyeye, Adeolu Ikechukwu

    2017-01-01

    Introduction: Open fractures are widely considered as orthopaedic emergencies requiring immediate intervention. The initial management of these injuries usually affects the ultimate outcome because open fractures may be associated with significant morbidity. Wound irrigation forms one of the pivotal principles in the treatment of open fractures. The choice of irrigation fluid has since been a source of debate. This study aimed to evaluate and compare the effects of isotonic saline and distilled water as irrigation solutions in the management of open fractures of the lower extremities. Wound infection and wound healing rates using both solutions were evaluated. Methods: This was a prospective hospital-based study of 109 patients who presented to the Accident and Emergency department with open lower limb fractures. Approval was sought and obtained from the Ethics Committee of the Hospital. Patients were randomized into either the isotonic saline (NS) or the distilled water (DW) group using a simple ballot technique. Twelve patients were lost to follow-up, while 97 patients were available until conclusion of the study. There were 50 patients in the isotonic saline group and 47 patients in the distilled water group. Results: Forty-one (42.3%) of the patients were in the young and economically productive strata of the population. There was a male preponderance with a 1.7:1 male-to-female ratio. The wound infection rate was 34% in the distilled water group and 44% in the isotonic saline group (p = 0.315). The mean time ± SD to wound healing was 2.7 ± 1.5 weeks in the distilled water group and 3.1 ± 1.8 weeks in the isotonic saline group (p = 0.389). Conclusions: It was concluded from this study that the use of distilled water compares favourably with isotonic saline as an irrigation solution in open fractures of the lower extremities. PMID:28134091

  9. Facial fractures.

    PubMed Central

    Carr, M. M.; Freiberg, A.; Martin, R. D.

    1994-01-01

    Emergency room physicians frequently see facial fractures that can have serious consequences for patients if mismanaged. This article reviews the signs, symptoms, imaging techniques, and general modes of treatment of common facial fractures. It focuses on fractures of the mandible, zygomaticomaxillary region, orbital floor, and nose. Images p520-a p522-a PMID:8199509

  10. Healing Childhood Trauma Worldwide

    ERIC Educational Resources Information Center

    Kuban, Caelan

    2012-01-01

    Millions of the world's children are exposed to traumatic events and relationships every day. Whatever the cause, this overwhelming stress produces a host of unsettling symptoms and reactions. The author highlights six practical principles that undergird healing interventions.

  11. Studies on Wound Healing

    DTIC Science & Technology

    1992-04-01

    therapy on wound repair have been amply demonstrated. Increased oxygen supply promotes wound healing whereas decreased oxygen supply retards repair...appmarn as early as 6 hms afte the a~ddton of DMF (Figl. 2). The increase was linea during the 24 hrs period of observaumoe in order toconfimn if the...Examine the effect of superoxide on collagen synthesis in vivo, * Examine the effect of increased superoxide levels on wound healing , and * Develop strategies to administer superoxide to wounds.

  12. Metalloproteinases and Wound Healing

    PubMed Central

    Caley, Matthew P.; Martins, Vera L.C.; O'Toole, Edel A.

    2015-01-01

    Significance: Matrix metalloproteinases (MMPs) are present in both acute and chronic wounds. They play a pivotal role, with their inhibitors, in regulating extracellular matrix degradation and deposition that is essential for wound reepithelialization. The excess protease activity can lead to a chronic nonhealing wound. The timed expression and activation of MMPs in response to wounding are vital for successful wound healing. MMPs are grouped into eight families and display extensive homology within these families. This homology leads in part to the initial failure of MMP inhibitors in clinical trials and the development of alternative methods for modulating the MMP activity. MMP-knockout mouse models display altered wound healing responses, but these are often subtle phenotypic changes indicating the overlapping MMP substrate specificity and inter-MMP compensation. Recent Advances: Recent research has identified several new MMP modulators, including photodynamic therapy, protease-absorbing dressing, microRNA regulation, signaling molecules, and peptides. Critical Issues: Wound healing requires the controlled activity of MMPs at all stages of the wound healing process. The loss of MMP regulation is a characteristic of chronic wounds and contributes to the failure to heal. Future Directions: Further research into how MMPs are regulated should allow the development of novel treatments for wound healing. PMID:25945285

  13. Treatment of Palatal Fractures by Osteosynthesis with 2.0-mm Locking Plates as External Fixator

    PubMed Central

    Cienfuegos, Ricardo; Sierra, Eduardo; Ortiz, Benjamin; Fernández, Gerardo

    2010-01-01

    Treatment options for palatal fractures range from orthodontic braces, acrylic bars, and arch bars for maxillomandibular fixation to internal fixation, with plates and screws placed under the palate mucosa and periosteum, together with pyriform aperture or alveolar plating plus buttress reconstruction. Forty-five patients, ages 4 to 56, were treated using medium- or high-profile locking plates placed over the palatal mucosa as an external fixator for palatal fractures, together with treatment for other associated facial fractures. In open fractures, plates were placed after approximating the edges of the mucosal wounds. Plates and screws for palate fixation were removed at 12 weeks, when computed tomography scans provided evidence of fracture healing. All palatal fractures healed by 12 weeks, with no cases of mucosal necrosis, bone exposure, fistulae, or infections. This approach achieves adequate stability, reduces the risk of bone and mucosal necrosis, and promotes healing of mucosal wounds in case of open fractures. PMID:22132261

  14. C2-fractures: part II. A morphometrical analysis of computerized atlantoaxial motion, anatomical alignment and related clinical outcomes.

    PubMed

    Koller, Heiko; Acosta, Frank; Forstner, Rosemarie; Zenner, Juliane; Resch, Herbert; Tauber, Mark; Lederer, Stefan; Auffarth, Alexander; Hitzl, Wolfgang

    2009-08-01

    investigation of C2-fracture morphology, posttreatment C2-alignment and atlantoaxial rotation allowed a unique outcome analysis that focused on the identification of risk factors for poor outcome and the interdependencies of outcome variables that should be addressed in studies on C2-fractures. We recognized that reduced rotation of C1-2 per se was not a concern for the patients. However, patients with worse clinical outcomes had reduced total neck rotation and rotation C1-2. In turn, C2-fractures, especially fractures affecting the lateral mass that healed with atlantoaxial deformity and malunion, had higher incidence of atlantoaxial degeneration and osteoarthritis. Patients with increased severity of C2-malunion and new onset atlantoaxial arthritis had worse clinical outcomes and significantly reduced rotation C1-2. The current study offers detailed insight into the radiographical, functional and clinical outcome of C2-fractures. It significantly adds to the understanding of C2-fractures.

  15. New insights into microRNAs in skin wound healing.

    PubMed

    Fahs, Fatima; Bi, Xinling; Yu, Fu-Shin; Zhou, Li; Mi, Qing-Sheng

    2015-12-01

    Chronic wounds are a major burden to overall healthcare cost and patient morbidity. Chronic wounds affect a large portion of the US, and billions of healthcare dollars are spent in their treatment and management. microRNAs (miRNAs) are small, noncoding double-stranded RNAs that post-transcriptionally downregulate the expression of protein-coding genes. Studies have identified miRNAs involved in all three phases of wound healing including inflammation, proliferation, and remodeling. Some miRNAs have been demonstrated in vitro with primary keratinocyte wound healing model and in vivo with mouse wound healing model through regulation of miRNA expression to affect the wound healing process. This review updates the current miRNAs involved in wound healing and discusses the future therapeutic implications and research directions.

  16. Electrosprayed Multi-Core Alginate Microcapsules as Novel Self-Healing Containers

    NASA Astrophysics Data System (ADS)

    Hia, Iee Lee; Pasbakhsh, Pooria; Chan, Eng-Seng; Chai, Siang-Piao

    2016-10-01

    Alginate microcapsules containing epoxy resin were developed through electrospraying method and embedded into epoxy matrix to produce a capsule-based self-healing composite system. These formaldehyde free alginate/epoxy microcapsules were characterized via light microscope, field emission scanning electron microscope, fourier transform infrared spectroscopy and thermogravimetric analysis. Results showed that epoxy resin was successfully encapsulated within alginate matrix to form porous (multi-core) microcapsules with pore size ranged from 5–100 μm. The microcapsules had an average size of 320 ± 20 μm with decomposition temperature at 220 °C. The loading capacity of these capsules was estimated to be 79%. Under in situ healing test, impact specimens showed healing efficiency as high as 86% and the ability to heal up to 3 times due to the multi-core capsule structure and the high impact energy test that triggered the released of epoxy especially in the second and third healings. TDCB specimens showed one-time healing only with the highest healing efficiency of 76%. The single healing event was attributed by the constant crack propagation rate of TDCB fracture test. For the first time, a cost effective, environmentally benign and sustainable capsule-based self-healing system with multiple healing capabilities and high healing performance was developed.

  17. Electrosprayed Multi-Core Alginate Microcapsules as Novel Self-Healing Containers.

    PubMed

    Hia, Iee Lee; Pasbakhsh, Pooria; Chan, Eng-Seng; Chai, Siang-Piao

    2016-10-03

    Alginate microcapsules containing epoxy resin were developed through electrospraying method and embedded into epoxy matrix to produce a capsule-based self-healing composite system. These formaldehyde free alginate/epoxy microcapsules were characterized via light microscope, field emission scanning electron microscope, fourier transform infrared spectroscopy and thermogravimetric analysis. Results showed that epoxy resin was successfully encapsulated within alginate matrix to form porous (multi-core) microcapsules with pore size ranged from 5-100 μm. The microcapsules had an average size of 320 ± 20 μm with decomposition temperature at 220 °C. The loading capacity of these capsules was estimated to be 79%. Under in situ healing test, impact specimens showed healing efficiency as high as 86% and the ability to heal up to 3 times due to the multi-core capsule structure and the high impact energy test that triggered the released of epoxy especially in the second and third healings. TDCB specimens showed one-time healing only with the highest healing efficiency of 76%. The single healing event was attributed by the constant crack propagation rate of TDCB fracture test. For the first time, a cost effective, environmentally benign and sustainable capsule-based self-healing system with multiple healing capabilities and high healing performance was developed.

  18. Electrosprayed Multi-Core Alginate Microcapsules as Novel Self-Healing Containers

    PubMed Central

    Hia, Iee Lee; Pasbakhsh, Pooria; Chan, Eng-Seng; Chai, Siang-Piao

    2016-01-01

    Alginate microcapsules containing epoxy resin were developed through electrospraying method and embedded into epoxy matrix to produce a capsule-based self-healing composite system. These formaldehyde free alginate/epoxy microcapsules were characterized via light microscope, field emission scanning electron microscope, fourier transform infrared spectroscopy and thermogravimetric analysis. Results showed that epoxy resin was successfully encapsulated within alginate matrix to form porous (multi-core) microcapsules with pore size ranged from 5–100 μm. The microcapsules had an average size of 320 ± 20 μm with decomposition temperature at 220 °C. The loading capacity of these capsules was estimated to be 79%. Under in situ healing test, impact specimens showed healing efficiency as high as 86% and the ability to heal up to 3 times due to the multi-core capsule structure and the high impact energy test that triggered the released of epoxy especially in the second and third healings. TDCB specimens showed one-time healing only with the highest healing efficiency of 76%. The single healing event was attributed by the constant crack propagation rate of TDCB fracture test. For the first time, a cost effective, environmentally benign and sustainable capsule-based self-healing system with multiple healing capabilities and high healing performance was developed. PMID:27694922

  19. Self-Healing of Unentangled Polymer Networks with Reversible Bonds

    PubMed Central

    Stukalin, Evgeny B.; Cai, Li-Heng; Kumar, N. Arun; Leibler, Ludwik; Rubinstein, Michael

    2013-01-01

    Self-healing polymeric materials are systems that after damage can revert to their original state with full or partial recovery of mechanical strength. Using scaling theory we study a simple model of autonomic self-healing of unentangled polymer networks. In this model one of the two end monomers of each polymer chain is fixed in space mimicking dangling chains attachment to a polymer network, while the sticky monomer at the other end of each chain can form pairwise reversible bond with the sticky end of another chain. We study the reaction kinetics of reversible bonds in this simple model and analyze the different stages in the self-repair process. The formation of bridges and the recovery of the material strength across the fractured interface during the healing period occur appreciably faster after shorter waiting time, during which the fractured surfaces are kept apart. We observe the slowest formation of bridges for self-adhesion after bringing into contact two bare surfaces with equilibrium (very low) density of open stickers in comparison with self-healing. The primary role of anomalous diffusion in material self-repair for short waiting times is established, while at long waiting times the recovery of bonds across fractured interface is due to hopping diffusion of stickers between different bonded partners. Acceleration in bridge formation for self-healing compared to self-adhesion is due to excess non-equilibrium concentration of open stickers. Full recovery of reversible bonds across fractured interface (formation of bridges) occurs after appreciably longer time than the equilibration time of the concentration of reversible bonds in the bulk. PMID:24347684

  20. Self-Healing of Polymer Networks with Reversible Bonds

    NASA Astrophysics Data System (ADS)

    Rubinstein, Michael

    2015-03-01

    Self-healing polymeric materials are systems that after damage can revert to their original state with full or partial recovery of mechanical strength. Using scaling theory we study a simple model of autonomic self-healing of polymer networks. In this model one of the two end monomers of each polymer chain is fixed in space mimicking dangling chains attachment to a polymer network, while the sticky monomer at the other end of each chain can form pairwise reversible bond with the sticky end of another chain. We study the reaction kinetics of reversible bonds in this simple model and analyze the different stages in the self-repair process. The formation of bridges and the recovery of the material strength across the fractured interface during the healing period occur appreciably faster after shorter waiting time, during which the fractured surfaces are kept apart. We observe the slowest formation of bridges for self-adhesion after bringing into contact two bare surfaces with equilibrium (very low) density of open stickers in comparison with self-healing. The primary role of anomalous diffusion in material self-repair for short waiting times is established, while at long waiting times the recovery of bonds across fractured interface is due to hopping diffusion of stickers between different bonded partners. Acceleration in bridge formation for self-healing compared to self-adhesion is due to excess nonequilibrium concentration of open stickers. Full recovery of reversible bonds across fractured interface (formation of bridges) occurs after appreciably longer time than the equilibration time of the concentration of reversible bonds in the bulk. The model is extended to describe enhanced toughness of dual networks with both permanent and reversible cross-links. This work was done in collaboration with Drs. Ludwik Leibler, Li-Heng Cai, Evgeny B. Stukalin, N. Arun Kumar and supported by the National Science Foundation.

  1. Biologically inspired autonomous structural materials with controlled toughening and healing

    NASA Astrophysics Data System (ADS)

    Garcia, Michael E.; Sodano, Henry A.

    2010-04-01

    The field of structural health monitoring (SHM) has made significant contributions in the field of prognosis and damage detection in the past decade. The advantageous use of this technology has not been integrated into operational structures to prevent damage from propagating or to heal injured regions under real time loading conditions. Rather, current systems relay this information to a central processor or human operator, who then determines a course of action such as altering the mission or scheduling repair maintenance. Biological systems exhibit advanced sensory and healing traits that can be applied to the design of material systems. For instance, bone is the major structural component in vertebrates; however, unlike modern structural materials, bone has many properties that make it effective for arresting the propagation of cracks and subsequent healing of the fractured area. The foremost goal for the development of future adaptive structures is to mimic biological systems, similar to bone, such that the material system can detect damage and deploy defensive traits to impede damage from propagating, thus preventing catastrophic failure while in operation. After sensing and stalling the propagation of damage, the structure must then be repaired autonomously using self healing mechanisms motivated by biological systems. Here a novel autonomous system is developed using shape memory polymers (SMPs), that employs an optical fiber network as both a damage detection sensor and a network to deliver stimulus to the damage site initiating adaptation and healing. In the presence of damage the fiber optic fractures allowing a high power laser diode to deposit a controlled level of thermal energy at the fractured sight locally reducing the modulus and blunting the crack tip, which significantly slows the crack growth rate. By applying a pre-induced strain field and utilizing the shape memory recovery effect, thermal energy can be deployed to close the crack and return

  2. 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

  3. [Perioperative hypothermia. Impact on wound healing].

    PubMed

    Pietsch, A P; Lindenblatt, N; Klar, E

    2007-09-01

    Mild perioperative hypothermia is a common complication of anesthesia and surgery associated with several adverse effects including impaired wound healing and more frequently leads to wound infections. Perioperative hypothermia affects the hemostasis and various immune functions and therefore interferes with the initial phases of the wound healing process. Furthermore, perioperative hypothermia contributes to wound complications by inhibition of deposition of collagen and prolongation of postoperative catabolism. Wound complications prolong hospitalization and substantially increase medical costs. Thus, maintaining normothermia perioperatively is essential to reduce the number of wound complications.

  4. Treatment of proximal fifth metatarsal bone fractures in athletes.

    PubMed

    Japjec, M; Starešinić, M; Starjački, M; Žgaljardić, I; Štivičić, J; Šebečić, B

    2015-11-01

    Proximal fifth metatarsal (V MT) bone fractures are common injuries that are a major diagnostic and therapeutic challenge. Lawrence and Botte considered different treatment options and the possibility of recovery and divided these fractures into three different regions: tuberosity avulsion fractures (zone I), acute fractures of the metaphysis at the level of the intermetatarsal junction (zone II) and proximal diaphysis stress fracture (zone III). A total of 42 athletes with fracture of the V MT bone in zone II and III were treated in our institution during a 6-year period. All patients were offered surgical treatment, but nine patients refused surgery. Thus, the patients were divided into two groups: group 1 comprised 33 patients who underwent an intramedullary screw fixation operation under regional anaesthesia immediately after the fracture was diagnosed; group 2 contained the remaining nine patients who had refused surgery and received conservative therapy with non-weight-bearing short-leg casts or orthosis. Follow-up ranged from 6 to 24 months. All fractures healed in group 1: healing occurred within 8 weeks in 26 patients and was prolonged to 16 to 18 weeks in four patients. In group 2, fractures healed in four patients but did not heal in five patients even after 6 months. Four of the five patients in whom the fracture did not heal required subsequent osteosynthesis because they had constant problems that caused absence from sport. After the operation, their fractures healed in an average of 10 weeks. One patient decided not to undergo the operation due to the absence of subjective symptoms. Three patients in group 1 who started intensive training sustained a refracture and underwent re-operation in which osteosynthesis was performed with a stronger screw. The fractures then healed again. Treatment results were evaluated radiologically and clinically using the Modified Foot Score. Results in group 1 were significantly better than those in group 2 and there

  5. Wound healing in urology.

    PubMed

    Ninan, Neethu; Thomas, Sabu; Grohens, Yves

    2015-03-01

    Wound healing is a dynamic and complex phenomenon of replacing devitalized tissues in the body. Urethral healing takes place in four phases namely inflammation, proliferation, maturation and remodelling, similar to dermal healing. However, the duration of each phase of wound healing in urology is extended for a longer period when compared to that of dermatology. An ideal wound dressing material removes exudate, creates a moist environment, offers protection from foreign substances and promotes tissue regeneration. A single wound dressing material shall not be sufficient to treat all kinds of wounds as each wound is distinct. This review includes the recent attempts to explore the hidden potential of growth factors, stem cells, siRNA, miRNA and drugs for promoting wound healing in urology. The review also discusses the different technologies used in hospitals to treat wounds in urology, which make use of innovative biomaterials synthesised in regenerative medicines like hydrogels, hydrocolloids, foams, films etc., incorporated with growth factors, drug molecules or nanoparticles. These include surgical zippers, laser tissue welding, negative pressure wound therapy, and hyperbaric oxygen treatment.

  6. Advances and Perspectives on Tissue Repair and Healing

    NASA Astrophysics Data System (ADS)

    Pinheiro, Antonio L. B.; Marques, Aparecida M. C.; de Sousa, Ana Paula C.; Aciole, Jouber M. S.; Soares, Luiz G. P.

    2011-08-01

    Wound healing involves local and systemic responses that reflect the etiology of the lesion, type of tissue, systemic condition and others. Despite being essentially the same for different wounds, the pattern of healing may change due to intrinsic and/or extrinsic factors. The type of tissue has also to be considered. Several therapeutic approaches have been used to improve healing including phototherapies such as Laser, LEDs and Lamps. Their effects on soft and mineralized tissues are well reported. The choice of appropriated parameters is essential for the results of the treatment and includes wavelength, power density, energy, duration and frequency of application and others. We studied the effects of different types of light on the healing of both soft and mineralized tissues using different models. We found that the use of Laser and polarized light are effective on improving the healing of diabetic and undernourished animals. We also found that Laser light is capable of improving the healing of drug-induced impairment and on increasing the survival rate of flaps on both diabetic and non-diabetic animals. We have also studied and shown the influence of the laser parameters on the healing of surgical and laser wounds. Lately we verified the positive effect of LEDs on healing. We used Laser/LED light for improving bone healing in conditions such as in dental implants, autologous grafts, biomaterials and fractures. From these reports and our own experience we have no doubt whatsoever that the use of phototherapies, carried out with appropriate parameters, promotes quicker tissue repair.

  7. Far cortical locking screws in distal femur fractures.

    PubMed

    Adams, John D; Tanner, Stephanie L; Jeray, Kyle J

    2015-03-01

    Distal femur fractures routinely heal by secondary bone healing, which relies on interfragmentary motion. Periarticular locking plates are commonly used for fixation in distal femur fractures but are associated with a high nonunion rate, likely due to the stiffness of the constructs. Far cortical locking (FCL) screws are designed to allow micromotion at the near cortex while maintaining purchase in only the far cortex. Although clinical data are limited, these screws have been shown in biomechanical studies to provide excellent interfragmentary motion, and animal models have shown increased callus formation compared with traditional locking screws. The purpose of this study was to examine the clinical effects that FCL screws have on healing in distal femur fractures treated with locked constructs. In this retrospective case series, 15 patients with a distal femur fracture treated with MotionLoc screws (Zimmer, Warsaw, Indiana) were analyzed. Serial radiographs were evaluated for callus presence and time to union. All fractures were either 33-A3 or 33-C2 according to the AO classification system, and 5 (33%) were open. Bone loss was recorded in 2 patients. There were no nonunions, and average time to union was 24 weeks. There were no implant failures, and all 5 open fractures, including the 2 with bone loss, healed without intervention. There was 1 reoperation due to painful hardware. Although this is a small case series, these results are promising. Far cortical locking screws may provide the answer to the high nonunion rate associated with distal femur fractures treated with traditional locked constructs.

  8. Bilateral iatrogenic [corrected] maxillary fractures after dental treatment in two aged horses.

    PubMed

    Widmer, A; Fürst, A; Bettschart, R; Makara, M; Geyer, H; Kummer, M

    2010-01-01

    This clinical report describes two horses with bilateral maxillary fractures following dental treatment. The fractures occurred during dental treatment by a veterinarian, and both had rostral, transverse, and complete bilateral maxillary fractures with instability and minimal displacement. The fractures were repaired using bilateral intraoral wiring with the patients under general anesthesia. The postoperative period was without complications and the fractures healed as expected. Maxillary fractures during or after routine dental treatment are rare, but can occur, especially in older horses. Appropriate sedation and, if necessary, regional nerve blocks might reduce the risk of iatrogenic fractures of the maxilla. General anesthesia must be considered for tooth extraction in horses that are difficult to restrain.

  9. Toughening and healing of continuous fibre reinforced composites with bis-maleimide based pre-pregs

    NASA Astrophysics Data System (ADS)

    Kostopoulos, V.; Kotrotsos, A.; Tsantzalis, S.; Tsokanas, P.; Christopoulos, A. C.; Loutas, T.

    2016-08-01

    Unidirectional (UD) pre-pregs containing self-healing materials based on Diels-Alder reaction bis-maleimide (BMI) polymers were successfully incorporated on the mid-plane of UD carbon fibre reinforced polymers. The fracture toughness of these composites and the introduced healing capability were measured under mode I loading. The interlaminar fracture toughness was enhanced considerably, since the maximum load (P max) of the modified composite increased approximately 1.5 times and the mode I fracture energy (G IC) displayed a significant increase of almost 3.5 times when compared to the reference composites. Furthermore the modified composites displayed a healing efficiency (HE) value of about 30% for P max and 20% for G IC after the first healing, appearing to be an almost stable behaviour after the third healing cycle. The HE displayed a decrease of 20% and 15% for P max and G IC values, respectively, after the fifth healing cycle. During the tests, the monitored acoustic emission (AE) activity of the samples showed that there is no significant difference due to the presence of BMI polymer in terms of AE hits. Moreover, optical microscopy not only showed that the epoxy matrix at the interface is partly infiltrated by the BMI polymer, but it also revealed the presence of pulled out fibres at the fractured surface, indicating ductile behaviour.

  10. Host Defense Peptides in Wound Healing

    PubMed Central

    Steinstraesser, Lars; Koehler, Till; Jacobsen, Frank; Daigeler, Adrien; Goertz, Ole; Langer, Stefan; Kesting, Marco; Steinau, Hans; Eriksson, Elof; Hirsch, Tobias

    2008-01-01

    Host defense peptides are effector molecules of the innate immune system. They show broad antimicrobial action against gram-positive and -negative bacteria, and they likely play a key role in activating and mediating the innate as well as adaptive immune response in infection and inflammation. These features make them of high interest for wound healing research. Non-healing and infected wounds are a major problem in patient care and health care spending. Increasing infection rates, growing bacterial resistance to common antibiotics, and the lack of effective therapeutic options for the treatment of problematic wounds emphasize the need for new approaches in therapy and pathophysiologic understanding. This review focuses on the current knowledge of host defense peptides affecting wound healing and infection. We discuss the current data and highlight the potential future developments in this field of research. PMID:18385817

  11. Is Casting for Non-Displaced Simple Scaphoid Waist Fracture Effective? A CT Based Assessment of Union

    PubMed Central

    Grewal, Ruby; Suh, Nina; MacDermid, Joy C.

    2016-01-01

    Objective: The purpose of this study is to report the union rate and time to union for acute non-displaced scaphoid waist fractures treated with a short arm thumb spica cast. Methods: A database was searched (2006-2013) to identify acute undisplaced scaphoid waist fractures. Cases that were not given a trial of casting were excluded (n=33). X-rays, CT scans and health records for each patient were reviewed to extract data. Results: 172 patients met inclusion criteria. There were 138 males, 34 females, the mean age was 30 ± 16 years. The union rate was 99.4% (1 nonunion/172 subjects). The mean time to union was approximately 7.5 weeks (53 ± 37 days). Energy of injury, age or gender did not affect union rates or time to union. Cysts did not affect the union rate (p=0.73) but patients with cystic resorption along the fracture line required approximately 10 weeks for union (69 ± 60 days) compared to 7 weeks (51 ± 34 days) for those without cysts (p=0.05). Diabetes did not affect the union rate (p=0.81) but was found to increase the risk of delayed union (p=0.05). There was a weak, but statistically significant correlation between the number of days before the fracture was casted and the length of time needed to achieve union (r=0.27, p=0.001). Conclusion: Non-displaced scaphoid waist fractures have a high healing rate with appropriate identification and immobilization. Follow-up CT scans to assess healing can identify union within a shorter time frame (~7 weeks) than previously reported in the literature. PMID:27708739

  12. Factors Affecting Specific-Capacity Tests and their Application--A Study of Six Low-Yielding Wells in Fractured-Bedrock Aquifers in Pennsylvania

    USGS Publications Warehouse

    Risser, Dennis W.

    2010-01-01

    This report by the U.S. Geological Survey, prepared in cooperation with the Pennsylvania Department of Environmental Protection, Bureau of Mining and Reclamation, evaluates factors affecting the application of specific-capacity tests in six low-yielding water wells in areas of coal mining or quarrying in Pennsylvania. Factors such as pumping rate, duration of pumping, aquifer properties, wellbore storage, and turbulent flow were assessed by theoretical analysis and by completing multiple well tests, selected to be representative of low-yielding household-supply wells in areas of active coal mining or quarrying. All six wells were completed in fractured-bedrock aquifers--five in coal-bearing shale, siltstone, sandstone, limestone, and coal of Pennsylvanian and Permian age and one in limestone of Cambrian age. The wells were pumped 24 times during 2007-09 at rates from 0.57 to 14 gallons per minute during tests lasting from 22 to 240 minutes. Geophysical logging and video surveys also were completed to determine the depth, casing length, and location of water-yielding zones in each of the test wells, and seasonal water-level changes were measured during 2007-09 by continuous monitoring at each well. The tests indicated that specific-capacity values were reproducible within about ? 20 percent if the tests were completed at the same pumping rate and duration. A change in pumping duration, pumping rate, or saturated aquifer thickness can have a substantial effect on the comparability of repeated tests. The largest effect was caused by a change in aquifer thickness in well YO 1222 causing specific capacity from repeated tests to vary by a factor of about 50. An increase in the duration of pumping from 60 to 180 minutes caused as much as a 62 percent decrease in specific capacity. The effect of differing pumping rates on specific capacity depends on whether or not the larger rate causes the water level in the well to fall below a major water-yielding zone; when this

  13. [Diagnosis of the scaphoid bone : Fractures, nonunion, circulation, perfusion].

    PubMed

    Kahl, T; Razny, F K; Benter, J P; Mutig, K; Hegenscheid, K; Mutze, S; Eisenschenk, A

    2016-11-01

    The clinical relevance of scaphoid bone fractures is reflected by their high incidence, accounting for approximately 60 % among carpal fractures and for 2-3 % of all fractures. With adequate therapy most scaphoid bone fractures heal completely without complications. Insufficient immobilization or undiagnosed fractures increase the risk of nonunion and the development of pseudarthrosis.X-ray examination enables initial diagnosis of scaphoid fracture in 70-80 % of cases. Positive clinical symptoms by negative x‑ray results require further diagnostics by multi-slice spiral CT (MSCT) or MRI to exclude or confirm a fracture. In addition to the diagnosis and description of fractures MSCT is helpful for determining the stage of nonunion. Contrast enhanced MRI is the best method to assess the vitality of scaphoid fragments.

  14. Conservative Approach to Unilateral Condylar Fracture in a Growing Patient: A 2.5-Year Follow Up

    PubMed Central

    Tuna, Elif Bahar; Dündar, Aysun; Çankaya, Abdülkadir Burak; Gençay, Koray

    2012-01-01

    Condylar fractures in children are especially important because of the risk of a mandibular growth-center being affected in the condylar head, which can lead to growth retardation and facial asymmetry. The purpose of this article is to follow up the two and half year clinical and radiological evaluation of the conservative treatment of a 10 year-old patient, who had a unilateral green-stick type fracture. The patient presented with painful facial swelling localized over the left condylar region, limited mouth-opening and mandibular deviation to the left. Panoramic radiography and computed tomography confirmed the diagnosis of incomplete fracture on the left condyle with one side of the bone fractured and the other bent. Closed reduction was chosen to allow for initial fibrous union of the fracture segments and remodeling with a normal functional stimulus. A non-rigid mandibular splint was applied in order to remove the direct pressure on the fracture side of the mandible. Clinical and radiologic examination after 30 months revealed uneventful healing with reduction of the condylar head and remodeling of the condylar process following conservative treatment. PMID:22276078

  15. Biomimetic Self-Healing.

    PubMed

    Diesendruck, Charles E; Sottos, Nancy R; Moore, Jeffrey S; White, Scott R

    2015-09-01

    Self-healing is a natural process common to all living organisms which provides increased longevity and the ability to adapt to changes in the environment. Inspired by this fitness-enhancing functionality, which was tuned by billions of years of evolution, scientists and engineers have been incorporating self-healing capabilities into synthetic materials. By mimicking mechanically triggered chemistry as well as the storage and delivery of liquid reagents, new materials have been developed with extended longevity that are capable of restoring mechanical integrity and additional functions after being damaged. This Review describes the fundamental steps in this new field of science, which combines chemistry, physics, materials science, and mechanical engineering.

  16. Spirituality, healing and medicine.

    PubMed Central

    Aldridge, D

    1991-01-01

    The natural science base of modern medicine influences the way in which medicine is delivered and may ignore the spiritual factors associated with illness. The history of spirituality in healing presented here reflects the growth of scientific knowledge, demands for religious renewal, and the shift in the understanding of the concept of health within a broader cultural context. General practitioners have been willing to entertain the idea of spiritual healing and include it in their daily practice, or referral network. Recognizing patients' beliefs in the face of suffering is an important factor in health care practice. PMID:1777299

  17. Retrospective review of 234 scaphoid fractures and nonunions treated with arthroscopy for union and complications.

    PubMed

    Slade, J F; Gillon, T

    2008-01-01

    The purpose of this paper is to retrospectively review 234 consecutive cases of scaphoid fractures and nonunions treated using arthroscopy with the dorsal percutaneous implantation of a headless compression screw for healing and complications. Solid union of fracture is determined by CT scan. We identified 126 acute injuries, including 65 proximal pole fractures; 67 grossly displaced fractures; 12 trans-scaphoid perilunate dislocations including four trans-scaphoid trans-capitate fractures; and ten combined scaphoid and distal radius fractures. 108 scaphoid nonunions were identified. 98 were correctly aligned and ten had a humpback deformity which was correctable using arthroscopic assisted reduction techniques at the time of surgery. 82 presented with a fracture gap 2mm or greater requiring percutaneous bone grafting. 12 cases of avascular necrosis (AVN) were identified by MRI. 20 nonunions had surgery performed at other institutions. The mean time to surgery for the nonunions was 20 months. 99% union rate of acute scaphoid fractures was obtained by 12 weeks, as determined by CT scan. Two complications were identified (3%). One case of delayed healing was identified. this delayed union was treated with percutaneous bone grafting and continued on to heal uneventfully. The other complication was a case of volar trans-scaphoid peri-lunate dislocation. While the fracture healed, the patient developed a traumatic dislocation requiring a capitate-lunate arthrodesis. Treatment of scaphoid nonunions resulted in ten cases of delayed healing, which were treated with repeat percutaneous bone grafting. This represented a 9% complication rate. of the ten cases of delayed unions that were re-bone grafted, four failed to heal by nine months. This resulted in a 96% union rate of our nonunion group by nine months. when acute fracture healing was compared to nonunions the average healing of acute fractures as determined by CT scanning measuring trabecular bridging was 12 weeks

  18. Interacting Cracks in an Environmentally Assisted Fracture

    NASA Astrophysics Data System (ADS)

    Levandovsky, Artem; Balazs, Anna

    2006-03-01

    We perform the study of environmentally assisted fracture within the framework of a lattice model. Formation of an ensemble of environmentally assisted microcracks, their coalescence and formation of crack ``avalanches'' lead to a very rich dynamical picture. Under specific condition crack healing can occur due to cohesive forces, which hold material together and tend to pull atoms together even if they are separated by a crack over several lattice units. We investigate the dynamical interplay between crack formation, arrest, healing and re-cracking. The goal here is to provide an understanding of the conditions leading to the phenomena of crack healing that happens along with the crack formation. We study the morphology of crack patterns with the intentions to establish a way to enhance the healing property of a material sample.

  19. Enhancement of wound healing by shikonin analogue 93/637 in normal and impaired healing.

    PubMed

    Mani, H; Sidhu, G S; Singh, A K; Gaddipati, J; Banaudha, K K; Raj, K; Maheshwari, R K

    2004-01-01

    Wound healing is a complicated biological process, which involves interactions of multiple cell types, various growth factors, their mediators and the extracellular matrix proteins. In this study, we evaluated the effects of shikonin analogue 93/637 (SA), derived from the plant Arnebia nobilis, on normal and hydrocortisone-induced impaired healing in full thickness cutaneous punch wounds in rats. SA (0.1%) was applied topically daily as an ointment in polyethylene glycol base on wounds. SA treatment significantly accelerated healing of wounds, as measured by wound contraction compared to controls in hydrocortisone-impaired animals. SA treatment promoted formation of granulation tissue including cell migration and neovascularization, collagenization and reepithelialization. The expression of basic fibroblast growth factor (bFGF) was higher as revealed by immunohistochemistry in treated wounds compared to controls. However, the expression of transforming growth factor-beta(1) was not affected by SA treatment. Since bFGF is known to accelerate wound healing, the increased expression of bFGF by SA may be partly responsible for the enhancement of wound healing. These studies suggest that SA could be further studied for clinical use to enhance wound healing.

  20. Self-healing phenomena of graphene: potential and applications

    NASA Astrophysics Data System (ADS)

    VijayaSekhar, K.; Acharyya, Swati Ghosh; Debroy, Sanghamitra; Miriyala, V. Pavan Kumar; Acharyya, Amit

    2016-01-01

    The present study investigates the self healing behavior of both pristine and defected single layer graphene using a molecular dynamic simulation. Single layer graphene containing various defects such as preexisting vacancies and differently oriented pre-existing cracks were subjected to uniaxial tensile loading till fracture occurred. Once the load was relaxed, the graphene was found to undergo self healing. It was observed that this self healing behaviour of cracks holds irrespective of the nature of pre-existing defects in the graphene sheet. Cracks of any length were found to heal provided the critical crack opening distance lies within 0.3-0.5 nm for a pristine sheet and also for a sheet with pre-existing defects. Detailed bond length analysis of the graphene sheet was done to understand the mechanism of self healing of graphene. The paper also discusses the immense potential of the self healing phenomena of graphene in the field of graphene based sub-nano sensors for crack sensing.

  1. Effects of shear load on frictional healing

    NASA Astrophysics Data System (ADS)

    Ryan, K. L.; Marone, C.

    2014-12-01

    During the seismic cycle of repeated earthquake failure, faults regain strength in a process known as frictional healing. Laboratory studies have played a central role in illuminating the processes of frictional healing and fault re-strengthening. These studies have also provided the foundation for laboratory-derived friction constitutive laws, which have been used extensively to model earthquake dynamics. We conducted laboratory experiments to assess the affect of shear load on frictional healing. Frictional healing is quantified during slide-hold-slide (SHS) tests, which serve as a simple laboratory analog for the seismic cycle in which earthquakes (slide) are followed by interseismic quiescence (hold). We studied bare surfaces of Westerly granite and layers of Westerly granite gouge (thickness of 3 mm) at normal stresses from 4-25 MPa, relative humidity of 40-60%, and loading and unloading velocities of 10-300 μm/s. During the hold period of SHS tests, shear stress on the sample was partially removed to investigate the effects of shear load on frictional healing and to isolate time- and slip-dependent effects on fault healing. Preliminary results are consistent with existing works and indicate that frictional healing increases with the logarithm of hold time and decreases with normalized shear stress τ/τf during the hold. During SHS tests with hold periods of 100 seconds, healing values ranged from (0.013-0.014) for τ/τf = 1 to (0.059-0.063) for τ/τf = 0, where τ is the shear stress during the hold period and τf is the shear stress during steady frictional sliding. Experiments on bare rock surfaces and with natural and synthetic fault gouge materials are in progress. Conventional SHS tests (i.e. τ/τf = 1) are adequately described by the rate and state friction laws. However, previous experiments in granular quartz suggest that zero-stress SHS tests are not well characterized by either the Dieterich or Ruina state evolution laws. We are investigating

  2. Indigenous Healing Legacies.

    ERIC Educational Resources Information Center

    Taliman, Valerie

    2001-01-01

    On a tour of Cuba, Native scholars from North and South America reconnected with the "extinct" Taino people and shared their knowledge of traditional healing herbs. Western science is just beginning to validate the tremendous knowledge base that indigenous healers have developed--most indigenous medicinal knowledge is useful for finding…

  3. Fetal skin wound healing.

    PubMed

    Buchanan, Edward P; Longaker, Michael T; Lorenz, H Peter

    2009-01-01

    The developing fetus has the ability to heal wounds by regenerating normal epidermis and dermis with restoration of the extracellular matrix (ECM) architecture, strength, and function. In contrast, adult wounds heal with fibrosis and scar. Scar tissue remains weaker than normal skin with an altered ECM composition. Despite extensive investigation, the mechanism of fetal wound healing remains largely unknown. We do know that early in gestation, fetal skin is developing at a rapid pace and the ECM is a loose network facilitating cellular migration. Wounding in this unique environment triggers a complex cascade of tightly controlled events culminating in a scarless wound phenotype of fine reticular collagen and abundant hyaluronic acid. Comparison between postnatal and fetal wound healing has revealed differences in inflammatory response, cellular mediators, cytokines, growth factors, and ECM modulators. Investigation into cell signaling pathways and transcription factors has demonstrated differences in secondary messenger phosphorylation patterns and homeobox gene expression. Further research may reveal novel genes essential to scarless repair that can be manipulated in the adult wound and thus ameliorate scar.

  4. Native American Healing Traditions

    ERIC Educational Resources Information Center

    Portman, Tarrell A. A.; Garrett, Michael T.

    2006-01-01

    Indigenous healing practices among Native Americans have been documented in the United States since colonisation. Cultural encapsulation has deterred the acknowledgement of Native American medicinal practices as a precursor to folk medicine and many herbal remedies, which have greatly influenced modern medicine. Understanding Native American…

  5. Wound Healing and Care

    MedlinePlus

    ... of collagen. So they're tougher and less flexible than the skin around them. Caring for Serious Wounds at Home Serious wounds don't heal overnight. It can take weeks for the body to build new tissue. So after you leave ...

  6. Bruise healing - slideshow

    MedlinePlus

    ... Indications URL of this page: //medlineplus.gov/ency/presentations/100207.htm Bruise healing - series—Indications To use the sharing features on this page, please enable JavaScript. Go to slide 1 out of 3 Go to slide 2 ...

  7. Educators Healing Racism.

    ERIC Educational Resources Information Center

    Quisenberry, Nancy L., Ed.; McIntyre, D. John, Ed.

    This book presents a collection of essays on racism and the role of teachers in healing racism. There are three sections with nine papers. After an "Introduction" (D. John McIntyre), Section 1, "Historical Perspectives," includes: (1) "Racism in Education" (Gwendolyn Duhon Boudreaux, Rose Duhon-Sells, Alice Duhon-Ross, and Halloway C. Sells); and…

  8. Fibronectin and wound healing.

    PubMed

    Grinnell, F

    1984-01-01

    I have tried to briefly review the evidence (summarized in Table II) indicating that fibronectin is important in cutaneous wound healing. Fibronectin appears to be an important factor throughout this process. It promotes the spreading of platelets at the site of injury, the adhesion and migration of neutrophils, monocytes, fibroblasts, and endothelial cells into the wound region, and the migration of epidermal cells through the granulation tissue. At the level of matrix synthesis, fibronectin appears to be involved both in the organization of the granulation tissue and basement membrane. In terms of tissue remodeling, fibronectin functions as a nonimmune opsonin for phagocytosis of debris by fibroblasts, keratinocytes, and under some circumstances, macrophages. Fibronectin also enhances the phagocytosis of immune-opsonized particles by monocytes, but whether this includes phagocytosis of bacteria remains to be determined. In general, phagocytosis of bacteria has not appeared to involve fibronectin. On the contrary, the presence of fibronectin in the wound bed may promote bacterial attachment and infection. Because of the ease of experimental manipulations, wound healing experiments have been carried out on skin more frequently than other tissues. As a result, the possible role of fibronectin has not been investigated thoroughly in the repair of internal organs and tissues. Nevertheless, it seems reasonable to speculate that fibronectin plays a central role in all wound healing situations. Finally, the wound healing