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  1. How do bisphosphonates affect fracture healing?

    PubMed

    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. Excess dietary methionine does not affect fracture healing in mice

    PubMed Central

    Holstein, Joerg H.; Schmalenbach, Julia; Herrmann, Markus; Ölkü, Ilona; Garcia, Patric; Histing, Tina; Herrmann, Wolfgang; Menger, Michael D.; Pohlemann, Tim; Claes, Lutz

    2012-01-01

    Summary Background An elevated serum concentration of homocysteine (hyperhomocysteinemia) has been shown to disturb fracture healing. As the essential amino acid, methionine, is a precursor of homocysteine, we aimed to investigate whether excess methionine intake affects bone repair. Material/Methods We analyzed bone repair in 2 groups of mice. One group was fed a methionine-rich diet (n=13), and the second group received an equicaloric control diet without methionine supplementation (n=12). Using a closed femoral fracture model, bone repair was analyzed by histomorphometry and biomechanical testing at 4 weeks after fracture. Blood was sampled to measure serum concentrations of homocysteine, the bone formation marker osteocalcin, and the bone resorption marker collagen I C-terminal crosslaps Results Serum concentrations of homocysteine were significantly higher in the methionine group than in the control group, while serum markers of bone turnover did not differ significantly between the 2 groups. Histomorphometry revealed no significant differences in size and tissue composition of the callus between animals fed the methionine-enriched diet and those receiving the control diet. Accordingly, animals of the 2 groups showed a comparable bending stiffness of the healing bones. Conclusions We conclude that excess methionine intake causes hyperhomocysteinemia, but does not affect fracture healing in mice. PMID:23197225

  3. Local insulin therapy affects fracture healing in a rat model.

    PubMed

    Park, Andrew G; Paglia, David N; Al-Zube, Loay; Hreha, Jeremy; Vaidya, Swaroopa; Breitbart, Eric; Benevenia, Joseph; O'Connor, J Patrick; Lin, Sheldon S

    2013-05-01

    A significant number of lower extremity fractures result in mal-union necessitating effective treatments to restore ambulation. Prior research in diabetic animal fracture models demonstrated improved healing following local insulin application to the fracture site and indicated that local insulin therapy can aid bone regeneration, at least within an insulin-dependent diabetic animal model. This study tested whether local insulin therapy could accelerate femur fracture repair in normal, non-diabetic rats. High (20 units) and low (10 units) doses of insulin were delivered in a calcium sulfate carrier which provided sustained release of the exogenous insulin for 7 days after fracture. Histomorphometry, radiographic scoring, and torsional mechanical testing were used to measure fracture healing. The fracture calluses from rats treated with high-dose insulin had significantly more cartilage than untreated rats after 7 and 14 days of healing. After 4 weeks of healing, femurs from rats treated with low-dose insulin had significantly higher radiographic scores and mechanical strength (p < 0.05), compared to the no treatment control groups. The results of this study suggest that locally delivered insulin is a potential therapeutic agent for treating bone fractures. Further studies are necessary, such as large animal proof of concepts, prior to the clinical use of insulin for bone fracture treatment.

  4. 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

  5. Fracture healing and lipid mediators.

    PubMed

    O'Connor, J Patrick; Manigrasso, Michaele B; Kim, Brian D; Subramanian, Sangeeta

    2014-01-01

    Lipid mediators regulate bone regeneration during fracture healing. Prostaglandins and leukotrienes are well-known lipid mediators that regulate inflammation and are synthesized from the Ω-6 fatty acid, arachidonic acid. Cyclooxygenase (COX-1 or COX-2) and 5-lipoxygenase (5-LO) catalyze the initial enzymatic steps in the synthesis of prostaglandins and leukotrienes, respectively. Inhibition or genetic ablation of COX-2 activity impairs fracture healing in animal models. Genetic ablation of COX-1 does not affect the fracture callus strength in mice, suggesting that COX-2 activity is primarily responsible for regulating fracture healing. Inhibition of cyclooxygenase activity with nonsteroidal anti-inflammatory drugs (NSAIDs) is performed clinically to reduce heterotopic ossification, although clinical evidence that NSAID treatment impairs fracture healing remains controversial. In contrast, inhibition or genetic ablation of 5-LO activity accelerates fracture healing in animal models. Even though prostaglandins and leukotrienes regulate inflammation, loss of COX-2 or 5-LO activity appears to primarily affect chondrogenesis during fracture healing. Prostaglandin or prostaglandin analog treatment, prostaglandin-specific synthase inhibition and prostaglandin or leukotriene receptor antagonism also affect callus chondrogenesis. Unlike the Ω-6-derived lipid mediators, lipid mediators derived from Ω-3 fatty acids, such as resolvin E1 (RvE1), have anti-inflammatory activity. In vivo, RvE1 can inhibit osteoclastogenesis and limit bone resorption. Although Ω-6 and Ω-3 lipid mediators have clear-cut effects on inflammation, the role of these lipid mediators in bone regeneration is more complex, with apparent effects on callus chondrogenesis and bone remodeling. PMID:24795811

  6. Disruption of glucocorticoid signaling in chondrocytes delays metaphyseal fracture healing but does not affect normal cartilage and bone development

    PubMed Central

    Tu, Jinwen; Henneicke, Holger; Zhang, Yaqing; Stoner, Shihani; Cheng, Tegan L.; Schindeler, Aaron; Chen, Di; Tuckermann, Jan; Cooper, Mark S.; Seibel, Markus J.; Zhou, Hong

    2014-01-01

    States of glucocorticoid excess are associated with defects in chondrocyte function. Most prominently there is a reduction in linear growth but delayed healing of fractures that require endochondral ossification to also occur. In contrast, little is known about the role of endogenous glucocorticoids in chondrocyte function. As glucocorticoids exert their cellular actions through the glucocorticoid receptor (GR), we aimed to elucidate the role of endogenous glucocorticoids in chondrocyte function in vivo through characterization of tamoxifen-inducible chondrocyte-specific GR knockout (chGRKO) mice in which the GR was deleted at various post-natal ages. Knee joint architecture, cartilage structure, growth plates, intervertebral discs, long bone length and bone micro-architecture were similar in chGRKO and control mice at all ages. Analysis of fracture healing in chGRKO and control mice demonstrated that in metaphyseal fractures, chGRKO mice formed a larger cartilaginous callus at 1 and 2 week post-surgery, as well as a smaller amount of well-mineralized bony callus at the fracture site 4 week post-surgery, when compared to control mice. In contrast, chondrocyte-specific GR knockout did not affect diaphyseal fracture healing. We conclude that endogenous GC signaling in chondrocytes plays an important role during metaphyseal fracture healing but is not essential for normal long bone growth. PMID:25193158

  7. Older Age Does Not Affect Healing Time and Functional Outcomes After Fracture Nonunion Surgery

    PubMed Central

    Taormina, David P.; Shulman, Brandon S.; Karia, Raj; Spitzer, Allison B.; Konda, Sanjit R.

    2014-01-01

    Introduction: Elderly patients are at risk of fracture nonunion, given the potential setting of osteopenia, poorer fracture biology, and comorbid medical conditions. Risk factors predicting fracture nonunion may compromise the success of fracture nonunion surgery. The purpose of this study was to investigate the effect of patient age on clinical and functional outcome following long bone fracture nonunion surgery. Materials and Methods: A retrospective analysis of prospectively collected data identified 288 patients (aged 18-91) who were indicated for long bone nonunion surgery. Two-hundred and seventy-two patients satisfied study inclusion criteria and analyses were performed comparing elderly patients aged ≥65 years (n = 48) with patients <65 years (n = 224) for postoperative wound complications, Short Musculoskeletal Functional Assessment (SMFA) functional status, healing, and surgical revision. Regression analyses were performed to look for associations between age, smoking status, and history of previous nonunion surgery with healing and functional outcome. Twelve-month follow-up was obtained on 91.5% (249 of 272) of patients. Results: Despite demographic differences in the aged population, including a predominance of medical comorbidities (P < .01) and osteopenia (P = .02), there was no statistical differences in the healing rate of elderly patients (95.8% vs 95.1%, P = .6) or time to union (6.2 ± 4.1 months vs. 7.2 ± 6.6, P = .3). Rates of postoperative wound complications and surgical revision did not statistically differ. Elderly patients reported similar levels of function up to 12 months after surgery. Regression analyses failed to show any significant association between age and final union or time to union. There was a strong positive association between smoking and history of previous nonunion surgery with time to union. Age was associated (positively) with 12-month SMFA activity score. Conclusions: Smoking and failure of previous surgical

  8. Bioinformatics analysis of time-series genes profiling to explore key genes affected by age in fracture healing.

    PubMed

    Wang, Wei; Shen, Hao; Xie, Jingjing; Zhou, Qiang; Chen, Yu; Lu, Hua

    2014-06-01

    The present study was aimed to explore possible key genes and bioprocess affected by age during fracture healing. GSE589, GSE592 and GSE1371 were downloaded from gene expression omnibus database. The time-series genes of three age levels rats were firstly identified with hclust function in R. Then functional and pathway enrichment analysis for selected time-series genes were performed. Finally, the VennDiagram package of R language was used to screen overlapping n time-series genes. The expression changes of time-series genes in the rats of three age levels were classified into two types: one was higher expressed at 0 day, decreased at 3 day to 2 week, and increased from 4 to 6 week; the other was the opposite. Functional and pathways enrichment analysis showed that 12 time-series genes of adult and old rats were significantly involved in ECM-receptor interaction pathway. The expression changes of 11 genes were consistent with time axis, 10 genes were up-regulated at 3 days after fracture, and increased slowly in 6 week, while Itga2b was down-regulated. The functions of 106 overlapping genes were all associated with growth and development of bone after fracture. The key genes in ECM-receptor interaction pathway including Spp1, Ibsp, Tnn and Col3a1 have been reported to be related to fracture in literatures. The difference during fracture healing in three age levels rats is mainly related to age. The Spp1, Ibsp, Tnn and Col3a1 are possible potential age-related genes and ECM-receptor interaction pathway is the potential age-related process during fracture healing. PMID:24627361

  9. Current medical treatment strategies concerning fracture healing.

    PubMed

    Giannotti, Stefano; Bottai, Vanna; Dell'osso, Giacomo; Pini, Erica; De Paola, Gaia; Bugelli, Giulia; Guido, Giulio

    2013-05-01

    The morbidity and socioeconomic costs associated with bone healing are considerable. A number of fractures are complicated by impaired healing. This is prevalent in certain risk groups such as elderly, osteoporotics, post-menopausal women, and in people with malnutrition. The biologic process of fracture healing is complex and impacted by multiple factors. Some of them, such as the nutritional and health conditions, are patient-dependent, while others depend on the trauma experienced and stability of the fracture. Fracture healing disorders negatively affect the patient's quality of life and result in high health-care costs, as a second surgery is required to stabilize the fracture and stimulate bone biology. Future biotechnologies that accelerate fracture healing may be useful tools, which might also prevent the onset of these disorders. We list the characteristics of the drugs used for osteoporosis, but we point out in particular the use of strontium ranelate and teriparatide in our clinical practice in elderly patients, especially females, who reported fractures with risk of nonunion. This medical treatment could impaired fracture healing however, most of the evidence is obtained in animal studies and very few studies have been done in humans. Thus one could hypothesize the possibility of a medical treatment both as a preventive and as support to the synthesis. However, no clinical studies are available so far, and such studies are warranted before any conclusions can be drawn. A positive effect of osteoporosis treatments on bone healing is an interesting possibility and merits further clinical research. PMID:24133528

  10. Current medical treatment strategies concerning fracture healing.

    PubMed

    Giannotti, Stefano; Bottai, Vanna; Dell'osso, Giacomo; Pini, Erica; De Paola, Gaia; Bugelli, Giulia; Guido, Giulio

    2013-05-01

    The morbidity and socioeconomic costs associated with bone healing are considerable. A number of fractures are complicated by impaired healing. This is prevalent in certain risk groups such as elderly, osteoporotics, post-menopausal women, and in people with malnutrition. The biologic process of fracture healing is complex and impacted by multiple factors. Some of them, such as the nutritional and health conditions, are patient-dependent, while others depend on the trauma experienced and stability of the fracture. Fracture healing disorders negatively affect the patient's quality of life and result in high health-care costs, as a second surgery is required to stabilize the fracture and stimulate bone biology. Future biotechnologies that accelerate fracture healing may be useful tools, which might also prevent the onset of these disorders. We list the characteristics of the drugs used for osteoporosis, but we point out in particular the use of strontium ranelate and teriparatide in our clinical practice in elderly patients, especially females, who reported fractures with risk of nonunion. This medical treatment could impaired fracture healing however, most of the evidence is obtained in animal studies and very few studies have been done in humans. Thus one could hypothesize the possibility of a medical treatment both as a preventive and as support to the synthesis. However, no clinical studies are available so far, and such studies are warranted before any conclusions can be drawn. A positive effect of osteoporosis treatments on bone healing is an interesting possibility and merits further clinical research.

  11. [Stress shielding and fracture healing].

    PubMed

    Liu, J G; Xu, X X

    1994-08-01

    The influence of stress shielding after fracture fixation with plate on fracture healing was studied. The results of animal and biomechanical experiments as well as the clinical observations demonstrated that rigidity of the plate was not the only factor causing stress redistribution and stress shielding effects of bone. Either the internal fixation with different implants or external fixation with fixators all might lead to physical and chemical characteristic changes of bone tissue. In the early stage, the disturbance of blood supply and the bone structure remodeling may be the main reasons. Reaction to the implant was another cause in the middle stage. If the affected limb can take weight-bearing normally at late stage, the influences of plate on fracture healing mechanical properties of bone and the osteoporosis cause by stress shielding effects will become much less. The tissue of the affected limb was the most important factor which may cause osteoporosis and refracture. Osteoporosis, bone atrophy and immobilization syndrome of bone and joint can be prevented and treated by taking normal weight-bearing and overcoming infection and implant reaction. PMID:7994658

  12. Effect of osteoporosis medications on fracture healing.

    PubMed

    Hegde, V; Jo, J E; Andreopoulou, P; Lane, J M

    2016-03-01

    Antiosteoporotic medications are often used to concurrently treat a patient's fragility fractures and underlying osteoporosis. This review evaluates the existing literature from animal and clinical models to determine these drugs' effects on fracture healing. The data suggest that these medications may enhance bone healing, yet more thorough prospective studies are warranted. Pharmacologic agents that influence bone remodeling are an essential component of osteoporosis management. Because many patients are first diagnosed with osteoporosis when presenting with a fragility fracture, it is critical to understand how osteoporotic medications influence fracture healing. Vitamin D and its analogs are essential for the mineralization of the callus and may also play a role in callus formation and remodeling that enhances biomechanical strength. In animal models, antiresorptive medications, including bisphosphonates, denosumab, calcitonin, estrogen, and raloxifene, do not impede endochondral fracture healing but may delay repair due to impaired remodeling. Although bisphosphonates and denosumab delay callus remodeling, they increase callus volume and result in unaltered biomechanical properties. Calcitonin increases cartilage formation and callus maturation, resulting in improved biomechanical properties. Parathyroid hormone, an anabolic agent, has demonstrated promise in animal models, resulting in accelerated healing with increased callus volume and density, more rapid remodeling to mature bone, and improved biomechanical properties. Clinical data with parathyroid hormone have demonstrated enhanced healing in distal radius and pelvic fractures as well as postoperatively following spine surgery. Strontium ranelate, which may have both antiresorptive and anabolic properties, affects fracture healing differently in normal and osteoporotic bone. While there is no effect in normal bone, in osteoporotic bone, strontium ranelate increases callus bone formation, maturity, and

  13. Current medical treatment strategies concerning fracture healing

    PubMed Central

    Giannotti, Stefano; Bottai, Vanna; Dell’Osso, Giacomo; Pini, Erica; De Paola, Gaia; Bugelli, Giulia; Guido, Giulio

    2013-01-01

    Summary The morbidity and socioeconomic costs associated with bone healing are considerable. A number of fractures are complicated by impaired healing. This is prevalent in certain risk groups such as elderly, osteoporotics, post-menopausal women, and in people with malnutrition. The biologic process of fracture healing is complex and impacted by multiple factors. Some of them, such as the nutritional and health conditions, are patient-dependent, while others depend on the trauma experienced and stability of the fracture. Fracture healing disorders negatively affect the patient’s quality of life and result in high health-care costs, as a second surgery is required to stabilize the fracture and stimulate bone biology. Future biotechnologies that accelerate fracture healing may be useful tools, which might also prevent the onset of these disorders. We list the characteristics of the drugs used for osteoporosis, but we point out in particular the use of strontium ranelate and teriparatide in our clinical practice in elderly patients, especially females, who reported fractures with risk of nonunion. This medical treatment could impaired fracture healing however, most of the evidence is obtained in animal studies and very few studies have been done in humans. Thus one could hypothesize the possibility of a medical treatment both as a preventive and as support to the synthesis. However, no clinical studies are available so far, and such studies are warranted before any conclusions can be drawn. A positive effect of osteoporosis treatments on bone healing is an interesting possibility and merits further clinical research. PMID:24133528

  14. Fracture healing: mechanisms and interventions

    PubMed Central

    Einhorn, Thomas A.; Gerstenfeld, Louis C.

    2015-01-01

    Fractures are the most common large-organ, traumatic injuries to humans. The repair of bone fractures is a postnatal regenerative process that recapitulates many of the ontological events of embryonic skeletal development. Although fracture repair usually restores the damaged skeletal organ to its pre-injury cellular composition, structure and biomechanical function, about 10% of fractures will not heal normally. This article reviews the developmental progression of fracture healing at the tissue, cellular and molecular levels. Innate and adaptive immune processes are discussed as a component of the injury response, as are environmental factors, such as the extent of injury to the bone and surrounding tissue, fixation and the contribution of vascular tissues. We also present strategies for fracture treatment that have been tested in animal models and in clinical trials or case series. The biophysical and biological basis of the molecular actions of various therapeutic approaches, including recombinant human bone morphogenetic proteins and parathyroid hormone therapy, are also discussed. PMID:25266456

  15. Potent anti-inflammatory agent escin does not affect the healing of tibia fracture and abdominal wound in an animal model

    PubMed Central

    ZHANG, LEIMING; WANG, HONGSHENG; WANG, TIAN; JIANG, NA; YU, PENGFEI; LIU, FEIYAN; CHONG, YATING; FU, FENGHUA

    2012-01-01

    Escin, a potent anti-inflammatory and anti-edematous agent, has been widely used clinically in preventing inflammatory edema after trauma, such as fracture and surgery. The aim of this study was to investigate whether escin has an inhibitory effect on fracture healing, and whether escin has an inhibitory effect on wound healing after surgery. Male New Zealand white rabbits underwent tibial mid-diaphyseal osteotomy, and were administered escin once per day for 10 days. At weeks 2, 4 and 6, bone fracture healing and bone mineral density were measured. The histologic examination of callus, osteocalcin, alkaline phosphatase, calcium and phosphate in the serum were also assayed. In another experiment, the rats underwent midline laparotomy, and received escin once prior to or after the operation. Six days later, the abdominal incision wounds were excised for measuring hydroxyproline levels. The results showed that there were no significant differences in fracture healing between the model and rabbits administered escin, and escin did not affect the hydroxyproline levels in the abdominal incision wounds of the rats. These findings suggest that escin has no inhibitory effect on fracture and wound healing in animal models. PMID:22969961

  16. Effect of methotrexate on fracture healing.

    PubMed

    Satoh, Koichiro; Mark, Hans; Zachrisson, Peter; Rydevik, Björn; Byröd, Gunnar; Kikuchi, Shin-Ichi; Konno, Shin-Ichi; Sekiguchi, Miho

    2011-01-01

    Low doses of methotrexate (MTX) are safe and effective for treating adult and juvenile rheumatoid arthritis. However, because this powerful anti-inflammatory drug might negatively influence the healing of wounds and fractures, MTX administration is often stopped during surgical procedures. The present study assesses the effects of low- and high-dose MTX on early inflammatory processes and bone healing in an experimental model of fracture. Thirty male Sprague-Dawley rats were assigned to low- and high-dose MTX and control groups. A femur was cut using a reciprocating saw and a 2-mm fracture gap was made using a fixator. One or four weeks thereafter, macrophages were immunostained and new bone formation was histomorphometrically measured. Significantly less new bone was formed in the high-dose MTX, than in the control group (p< 0.01), whereas bone formation did not significantly differ between the low-dose MTX and control groups. These results suggested that a low dose of MTX does not affect the early process of endochondral bone formation during fracture healing, whereas a high dose might delay the progress of new periosteal bone formation. Although more macrophages were found in the groups treated with MTX, their impact on surrounding inflammatory processes remains unclear. PMID:21701078

  17. Impaired Fracture Healing after Hemorrhagic Shock

    PubMed Central

    Kobbe, Philipp; Pfeifer, Roman; Campbell, Graeme C.; Tohidnezhad, Mersedeh; Bergmann, Christian; Kadyrov, Mamed; Fischer, Horst; Glüer, Christian C.; 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. PMID:26106256

  18. 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. PMID:27055104

  19. 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.

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

    PubMed Central

    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. PMID:27055104

  1. Stimulation of angiogenesis by cilostazol accelerates fracture healing in mice.

    PubMed

    Herath, Steven C; Lion, Thorsten; Klein, Moritz; Stenger, David; Scheuer, Claudia; Holstein, Jörg H; Mörsdorf, Philipp; Rollmann, Mika F R; Pohlemann, Tim; Menger, Michael D; Histing, Tina

    2015-12-01

    Cilostazol, a selective phosphodiesterase-3 inhibitor, is known to control cyclic adenosine monophosphate (c-AMP) and to stimulate angiogenesis through upregulation of pro-angiogenic factors. There is no information, however, whether cilostazol affects fracture healing. We, therefore, studied the effect of cilostazol on callus formation and biomechanics during fracture repair. Bone healing was analyzed in a murine femur fracture stabilized with an intramedullary screw. Radiological, biomechanical, histomorphometric, histochemical, and protein biochemical analyses were performed at 2 and 5 weeks after fracture. Twenty-five mice received 30 mg/kg body weight cilostazol p.o. daily. Controls (n=24) received equivalent amounts of vehicle. In cilostazol-treated animals radiological analysis at 2 weeks showed an improved healing with an accelerated osseous bridging compared to controls. This was associated with a significantly higher amount of bony tissue and a smaller amount of cartilage tissue within the callus. Western blot analysis showed a higher expression of cysteine-rich protein 61 (CYR61), bone morphogenetic protein (BMP)-4, and receptor activator of NF-kappaB ligand (RANKL). At 5 weeks, improved fracture healing after cilostazol treatment was indicated by biomechanical analyses, demonstrating a significant higher bending stiffness compared to controls. Thus, cilostazol improves fracture healing by accelerating both bone formation and callus remodeling.

  2. Factors affecting rotator cuff healing.

    PubMed

    Mall, Nathan A; Tanaka, Miho J; Choi, Luke S; Paletta, George A

    2014-05-01

    Several studies have noted that increasing age is a significant factor for diminished rotator cuff healing, while biomechanical studies have suggested the reason for this may be an inferior healing environment in older patients. Larger tears and fatty infiltration or atrophy negatively affect rotator cuff healing. Arthroscopic rotator cuff repair, double-row repairs, performing a concomitant acromioplasty, and the use of platelet-rich plasma (PRP) do not demonstrate an improvement in structural healing over mini-open rotator cuff repairs, single-row repairs, not performing an acromioplasty, or not using PRP. There is conflicting evidence to support postoperative rehabilitation protocols using early motion over immobilization following rotator cuff repair. PMID:24806015

  3. Hyperbaric Hyperoxia Accelerates Fracture Healing in Mice

    PubMed Central

    Kawada, Shigeo; Wada, Eiji; Matsuda, Ryoichi; Ishii, Naokata

    2013-01-01

    Increased oxygen tension influences bone metabolism. This study comprised two main experiments: one aimed to determine the bone mineral apposition and bone formation rates in vivo under hyperbaric hyperoxia (HBO), and the other aimed to evaluate the effects of exposure to HBO on fracture healing. In experiment 1, male mice were exposed to HBO [90 min/day at 90% O2 at 2 atmospheres absolute (ATA) for 5 days]. In experiment 2, an open femur fracture model was created in mice, followed by exposure to HBO 5 times/week (90 min/day at 90% O2 at 2 ATA) for 6 weeks after surgery. In experiment 1, HBO treatment significantly increased the mineral apposition and bone formation rates in the lumbar vertebra and femur and type 1 collagen alpha 1 and alkaline phosphatase mRNA expression in the lumbar vertebra. In experiment 2, at 2 weeks after fracture, the fracture callus was significantly larger in the HBO group than in the non-HBO group. Furthermore, at 4 and 6 weeks after fracture, radiographic findings showed accelerated fracture healing in the HBO group. At 6 weeks after fracture, femur stiffness and maximum load were significantly higher in the HBO group than in the non-HBO group. Urinary 8-hydroxy-2′-deoxyguanosine and plasma calcium concentrations were not significantly different between groups. These results suggest that exposure to HBO enhances bone anabolism and accelerates fracture healing without causing oxidative DNA damage or disruption of plasma calcium homeostasis. PMID:23967323

  4. Local Erythropoietin Injection in Tibiofibular Fracture Healing

    PubMed Central

    Bakhshi, Hooman; Kazemian, Gholamhossein; Emami, Mohammad; Nemati, Ali; Karimi Yarandi, Hossein; Safdari, Farshad

    2013-01-01

    Background Erythropoietin (EPO), in addition to its function as an erythropoiesis regulator has a regenerative activity on some nonhematopoietic tissues. Animal studies have suggested a role for erythropoietin in bone healing. Objectives The present study aimed to evaluate the effects of local EPO injection in healing of tibiofibular fractures. Materials and Methods In a prospective double blind study, 60 patients with tibiofibular fracture were divided to equal EPO or placebo groups, randomly. Patients received local injection of either EPO or a placebo to the site of fracture two weeks after surgical fixation. Patients were followed by clinical and radiographic examination to determine the union rate. The period of fracture union and incidence of nonunion were compared between the two groups. Results The demographic data and types of fractures were similar in the both groups. The mean duration of the fracture union was 2.1 weeks shorter in those treated with EPO (P = 0.01). Nonunion was observed in 6 patients of the control group and 2 receiving EPO (P = 0.02). No patient experienced any adverse effect from local EPO injections. Conclusions EPO injection into the site of tibiofibular fractures may possibly accelerate healing. PMID:24350133

  5. Creep healing of fractures in rock salt

    SciTech Connect

    Costin, L. S.; Wawersik, W. R.

    1980-08-01

    Fracture and healing experiments were performed on specimens of bedded salt from the Salado formation, southeastern New Mexico. Short rod specimens (100 mm in diameter) were loaded to failure in tension. During each test, a crack was initiated along the axis of the specimen. The fracture toughness of the salt was determined from the resulting load-crack opening displacement record. After the test, each specimen was pieced back together, jacketed and placed in a pressure vessel under hydrostatic pressure for several days. The confining pressure (10 to 35 MPa), temperature (22 to 100/sup 0/C) and healing time (4 to 8 days) were varied to determine the effect of each on the healing process. Upon removal from the pressure vessel, each sample was retested and the toughness of the healed fracture was determined. Results show that the salt specimens regained 70 to 80% of their original strength under all conditions except at the lowest temperature and pressure where specimens regained only 20 to 30% of their original strength. It is suspected that the primary mechanism involved is creep of asperities along the fracture surface which forms an interlocking network. Thus, the healing pressure is probably the most significant variable.

  6. 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. PMID:24293603

  7. 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

  8. Fracture healing in the elderly: A review.

    PubMed

    Foulke, Bradley A; Kendal, Adrian R; Murray, David W; Pandit, Hemant

    2016-10-01

    Older patients are commonly at a higher risk of experiencing a bone fracture. Complications during fracture healing, including delayed union and non-union, can arise as a result of a multitude of patient and treatment factors. This review describes those factors which contribute to a greater risk of delayed union and non-union with particular reference to the elderly population and discusses therapies that may enhance the fracture healing process in the hope of reducing the incidence of delayed union and non-union. Increasing age does seem to increase the risk of delayed union or non-union. In addition, smoking and the treatment of post-fracture pain with non-steroidal anti-inflammatory drugs (NSAIDs) put the patient at the greatest risk, while ultrasound therapy appears to be a non-invasive, effective treatment option to reduce the risk of delayed union or non-union. The use of growth factors and of stem cells and the role of surgery are also discussed. PMID:27621238

  9. 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.

  10. Biglycan modulates angiogenesis and bone formation during fracture healing.

    PubMed

    Berendsen, Agnes D; Pinnow, Emily L; Maeda, Azusa; Brown, Aaron C; McCartney-Francis, Nancy; Kram, Vardit; Owens, Rick T; Robey, Pamela G; Holmbeck, Kenn; de Castro, Luis F; Kilts, Tina M; Young, Marian F

    2014-04-01

    Matrix proteoglycans such as biglycan (Bgn) dominate skeletal tissue and yet its exact role in regulating bone function is still unclear. In this paper we describe the potential role of (Bgn) in the fracture healing process. We hypothesized that Bgn could regulate fracture healing because of previous work showing that it can affect normal bone formation. To test this hypothesis, we created fractures in femurs of 6-week-old male wild type (WT or Bgn+/0) and Bgn-deficient (Bgn-KO or Bgn-/0) mice using a custom-made standardized fracture device, and analyzed the process of healing over time. The formation of a callus around the fracture site was observed at both 7 and 14 days post-fracture in WT and Bgn-deficient mice and immunohistochemistry revealed that Bgn was highly expressed in the fracture callus of WT mice, localizing within woven bone and cartilage. Micro-computed tomography (μCT) analysis of the region surrounding the fracture line showed that the Bgn-deficient mice had a smaller callus than WT mice. Histology of the same region also showed the presence of less cartilage and woven bone in the Bgn-deficient mice compared to WT mice. Picrosirius red staining of the callus visualized under polarized light showed that there was less fibrillar collagen in the Bgn-deficient mice, a finding confirmed by immunohistochemistry using antibodies to type I collagen. Interestingly, real time RT-PCR of the callus at 7 days post-fracture showed a significant decrease in relative vascular endothelial growth factor A (VEGF) gene expression by Bgn-deficient mice as compared to WT. Moreover, VEGF was shown to bind directly to Bgn through a solid-phase binding assay. The inability of Bgn to directly enhance VEGF-induced signaling suggests that Bgn has a unique role in regulating vessel formation, potentially related to VEGF storage or stabilization in the matrix. Taken together, these results suggest that Bgn has a regulatory role in the process of bone formation during

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

    PubMed

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

    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

  12. 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.

  13. The effect of aging on fracture healing in the rat.

    PubMed

    Bak, B; Andreassen, T T

    1989-11-01

    The effect of age on the biomechanical properties of healing tibial fractures was studied by comparing the fracture healing in 2-year-old male Wistar rats with the fracture healing in 3-month-old male Wistar rats after 40 and 80 days of healing. There were no significant differences in the mechanical parameters after 40 days of healing, but after 80 days, a considerable delay in the fracture healing process was noted in the old rats compared with the young adult rats when evaluated by maximum load, maximum stress, stiffness, and energy absorption in a three-point bending procedure. In the contralateral, nonfractured bones, the tibiae from the old animals sustained higher loads and had higher stiffness than the bones from the young adult animals, but stress values, elastic modulus, and capacity for energy absorption was much lower in the old animals.

  14. Ultrasound attenuation as a quantitative measure of fracture healing

    NASA Astrophysics Data System (ADS)

    Gheduzzi, Sabina; Humphrey, Victor F.; Dodd, Simon P.; Cunningham, James L.; Miles, Anthony W.

    2004-10-01

    The monitoring of fracture healing still relies upon the judgment of callus formation and on the manual assessment of the stiffness of the fracture. A diagnostic tool capable of quantitatively measuring healing progression of a fracture would allow the fine-tuning of the treatment regime. Ultrasound attenuation measurements were adopted as a possible method of assessing the healing process in human long bones. The method involves exciting ultrasonic waves at 200 kHz in the bone and measuring the reradiation along the bone and across the fracture zone. Seven cadaveric femora were tested in vitro in intact form and after creating a transverse fracture by sawing through the cortex. The effects of five different fracture types were investigated. A partial fracture, corresponding to a 50% cut through the cortex, a closed fracture, and fractures of widths varying between 1, 2, and 4 mm were investigated. The introduction of a fracture was found to produce a dramatic effect on the amplitude of the signal. Ultrasound attenuation was found to be sensitive to the presence of a fracture, even when the fracture was well reduced. It would therefore appear feasible to adopt attenuation across a fracture as a quantitative measurement of fracture healing.

  15. 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.

  16. Intact fibula improves fracture healing in a rat tibia osteotomy model.

    PubMed

    Shefelbine, Sandra J; Augat, Peter; Claes, Lutz; Beck, Alexander

    2005-03-01

    Rat tibia fractures are often used in fracture healing studies. Usually the fracture is stabilized with an intramedullary pin, which provides bending stiffness, but little torsional stiffness. The objective of this research was to determine the in vitro torsional rigidity of an osteotomized tibia with and without the fibula, and to determine if this difference influences the healing process in vivo. In vitro eleven rat tibias received an osteotomy, were stabilized with an intramedullary pin, and were tested in internal rotation to determine the torsional rigidity. The fibula was then manually broken and the torsional rigidity measured again. In vivo 18 rats received a tibial osteotomy, eight of which had an additional fractured fibula. After three weeks, the rats were sacrificed and the tibias were analyzed. Bone density in the fracture callus was measured with qCT. Bending rigidity and maximum breaking moment were determined in three-point bending. In vitro testing demonstrated that the torsional rigidity with an intact fibula was nearly two times higher than when the fibula was fractured. Though the torsional rigidity was still small in comparison with an intact bone, it resulted in a significantly different healing process in vivo. Rats with intact fibulas had significantly higher bone mineral density, bending rigidity, and maximum breaking moment compared to rats with a fractured fibula. These results indicate that torsional stability considerably affects the healing process. In a fracture model, it is critical to characterize the mechanical environment of the fracture.

  17. 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.

  18. Comparison of fracture healing among different inbred mouse strains.

    PubMed

    Manigrasso, Michaele B; O'Connor, J Patrick

    2008-06-01

    Quantitative trait locus analysis can be used to identify genes critically involved in biological processes. No such analysis has been applied to identifying genes that control bone fracture healing. To determine the feasibility of such an approach, healing of femur fractures was measured between C57BL/6, DBA/2, and C3H inbred strains of mice. Healing was assessed by radiography and histology and measured by histomorphometry and biomechanical testing. In all strains, radiographic bridging of the fracture was apparent after 3 weeks of healing. Histology showed that healing occurred through endochondral ossification in all strains. Histomorphometric measurements found more bone in the C57BL/6 fracture calluses 7 and 10 days after fracture. In contrast, more cartilage was present after 7 days in the C3H callus, which rapidly declined to levels less than those of C57BL/6 or DBA/2 mice by 14 days after fracture. An endochondral ossification index was calculated by multiplying the callus percent cartilage and bone areas as a measure of endochondral ossification. At 7 and 10 days after fracture, this value was higher in C57BL/6 mice. Using torsional mechanical testing, normalized structural and material properties of the C57BL/6 healing femurs were higher than values from the DBA/2 or C3H mice 4 weeks after fracture. The data indicate that fracture healing proceeds more rapidly in C57BL/6 mice and demonstrate that genetic variability significantly contributes to the process of bone regeneration. Large enough differences exist between C57BL/6 and DBA/2 or C3H mice to permit a quantitative trait locus analysis to identify genes controlling bone regeneration.

  19. Pentoxifylline and electromagnetic field improved bone fracture healing in rats

    PubMed Central

    Atalay, Yusuf; Gunes, Nedim; Guner, Mehmet Dervis; Akpolat, Veysi; Celik, Mustafa Salih; Guner, Rezzan

    2015-01-01

    Background The aim of this study was to evaluate the effects of a phosphodiesterase inhibitor pentoxifylline (PTX), electromagnetic fields (EMFs), and a mixture of both materials on bone fracture healing in a rat model. Materials and methods Eighty male Wistar rats were randomly divided into four groups: Group A, femur fracture model with no treatment; Group B, femur fracture model treated with PTX 50 mg/kg/day intraperitoneal injection; Group C, femur fracture model treated with EMF 1.5±0.2 Mt/50 Hz/6 hours/day; and Group D, femur fracture model treated with PTX 50 mg/kg/day intraperitoneal injection and EMF 1.5±0.2 Mt/50 Hz/6 hours/day. Results Bone fracture healing was significantly better in Group B and Group C compared to Group A (P<0.05), but Group D did not show better bone fracture healing than Group A (P>0.05). Conclusion It can be concluded that both a specific EMF and PTX had a positive effect on bone fracture healing but when used in combination, may not be beneficial. PMID:26388687

  20. Biofilms: do they affect wound healing?

    PubMed

    Thomson, Collette H

    2011-02-01

    Biofilms are known to exist in wounds, and it is suspected that their presence may delay wound healing, especially in chronic wounds; however, the evidence to support or refute this is not yet conclusive. This literature review has found that there is some evidence, both in vitro and in vivo, that the extracellular polysaccharide (EPS) matrix protects the biofilm from some inflammatory processes key to wound healing. The mechanisms of these effects and how this translates into clinical practice are still unknown. Strategies to manage biofilms within wounds are being investigated and may include use of silver, surgical debridedment, antibiotics and quorum-sensing inhibitors but no firm conclusions can yet be drawn from these studies. In conclusion, while there is a growing body of evidence to suggest that biofilms do indeed influence aspects of wound healing, there is still a large gap in our understanding of how this affects the wounds of clinical patients or how to improve rates of healing.

  1. 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.

  2. In vivo measurement of bending stiffness in fracture healing

    PubMed Central

    Hente, Reiner; Cordey, Jacques; Perren, Stephan M

    2003-01-01

    Background Measurement of the bending stiffness a healing fracture represents a valid variable in the assessment of fracture healing. However, currently available methods typically have high measurement errors, even for mild pin loosening. Furthermore, these methods cannot provide actual values of bending stiffness, which precludes comparisons among individual fractures. Thus, even today, little information is available with regards to the fracture healing pattern with respect to actual values of bending stiffness. Our goals were, therefore: to develop a measurement device that would allow accurate and sensitive measurement of bending stiffness, even in the presence of mild pin loosening; to describe the course of healing in individual fractures; and help to evaluate whether the individual pattern of bending stiffness can be predicted at an early stage of healing. Methods A new measurement device has been developed to precisely measure the bending stiffness of the healing fracture by simulating four-point-bending. The system was calibrated on aluminum models and intact tibiae. The influence of pin loosening on measurement error was evaluated. The system was tested at weekly intervals in an animal experiment to determine the actual bending stiffness of the fracture. Transverse fractures were created in the right tibia of twelve sheep, and then stabilized with an external fixator. At ten weeks, bending stiffness of the tibiae were determined in a four-point-bending test device to validate the in-vivo-measurement data. Results In-vivo bending stiffness can be measured accurately and sensitive, even in the early phase of callus healing. Up to a bending stiffness of 10 Nm/degree, measurement error was below 3.4% for one pin loose, and below 29.3% for four pins loose, respectively. Measurement of stiffness data over time revealed a significant logarithmic increase between the third and seventh weeks, whereby the logarithmic rate of change among sheep was similar, but

  3. Are OPG and RANKL involved in human fracture healing?

    PubMed

    Köttstorfer, Julia; Thomas, Anita; Gregori, Markus; Kecht, Mathias; Kaiser, Georg; Eipeldauer, Stefan; Sarahrudi, Kambiz

    2014-12-01

    Human fracture healing is a complex interaction of several cytokines that regulate osteoblast and osteoclast activity. By monitoring OPG (osteoprotegerin) and sRANKL we aimed to possibly predict normal or impaired fracture healing. In 64 patients with a fracture of a long bone serum level of sRANKL and OPG were evaluated with respect to bony union (n=57) or pseudarthrosis (n=7). Measurements were carried out at admission and at 1, 2, 4, 6, 8, 12, 24, and 48 weeks after the injury. Patients' serum levels were compared to 33 healthy controls. Fracture hematoma contained significantly higher sRANKL and OPG concentrations compared to patients serum (p=0.005, p=0.028). OPG level in fracture hematoma was higher compared to the unions serum level (p=0.028). sRANKL was decreased in unions during the observation period. In non-unions sRANKL and OPG levels showed a variable course, with no statistical significance. This is the first study to document the course of OPG and sRANKL in normal and delayed human fracture healing emphasizing its local and systemic involvement. We provide evidence of strongly enhanced OPG levels in patients with a long bone fracture compared to healthy controls. Further, levels of free sRANKL were decreased during regular fracture repair.

  4. Systemic treatment with telmisartan improves femur fracture healing in mice.

    PubMed

    Zhao, Xiong; Wang, Jia-xing; Feng, Ya-fei; Wu, Zi-xiang; Zhang, Yang; Shi, Lei; Tan, Quan-chang; Yan, Ya-bo; Lei, Wei

    2014-01-01

    Recent clinical studies indicated that angiotensin receptor blockers (ARBs) would decrease the risk of bone fractures in the elderly populations. There is little known about the role of the ARBs in the process of fracture healing. The purpose of the present study was to verify the hypothesis that systemic treatment with telmisartan has the ability to promote fracture healing. In this study, femur fractures were produced in 96 mature male BALB/c mice. Animals were treated with the ARBs telmisartan or vehicle. Fracture healing was analysed after 2, 5 and 10 weeks postoperatively using X-ray, biomechanical testing, histomorphometry, immunohistochemistry and micro-computed tomography (micro-CT). Radiological analysis showed the diameter of the callus in the telmisartan treated animals was significantly increased when compared with that of vehicle treated controls after two weeks of fracture healing. The radiologically observed promotion of callus formation was confirmed by histomorphometric analyses, which revealed a significantly increased amount of bone formation when compared with vehicle-treated controls. Biomechanical testing further showed a significantly greater peak torque at failure, and a higher torsional stiffness in telmisartan-treated animals compared with controls. There was an increased fraction of PCNA-positive cells and VEGF-positive cells in telmisartan-treated group compared with vehicle-treated controls. From the three-dimensional reconstruction of the bony callus, telmisartan-treated group significantly increased the values of BV/TV by 21.7% and CsAr by 26.0% compared to the vehicle-treated controls at 5 weeks post-fracture. In summary, we demonstrate in the current study that telmisartan could promote fracture healing in a mice model via increasing mechanical strength and improving microstructure. The most mechanism is probably by an increase of cell proliferation and neovascularization associated with a decreased VEGF expression in hypertrophic

  5. Systemic Treatment with Telmisartan Improves Femur Fracture Healing in Mice

    PubMed Central

    Wu, Zi-xiang; Zhang, Yang; Shi, Lei; Tan, Quan-chang; Yan, Ya-bo; Lei, Wei

    2014-01-01

    Recent clinical studies indicated that angiotensin receptor blockers (ARBs) would decrease the risk of bone fractures in the elderly populations. There is little known about the role of the ARBs in the process of fracture healing. The purpose of the present study was to verify the hypothesis that systemic treatment with telmisartan has the ability to promote fracture healing. In this study, femur fractures were produced in 96 mature male BALB/c mice. Animals were treated with the ARBs telmisartan or vehicle. Fracture healing was analysed after 2, 5 and 10 weeks postoperatively using X-ray, biomechanical testing, histomorphometry, immunohistochemistry and micro-computed tomography (micro-CT). Radiological analysis showed the diameter of the callus in the telmisartan treated animals was significantly increased when compared with that of vehicle treated controls after two weeks of fracture healing. The radiologically observed promotion of callus formation was confirmed by histomorphometric analyses, which revealed a significantly increased amount of bone formation when compared with vehicle-treated controls. Biomechanical testing further showed a significantly greater peak torque at failure, and a higher torsional stiffness in telmisartan-treated animals compared with controls. There was an increased fraction of PCNA-positive cells and VEGF-positive cells in telmisartan-treated group compared with vehicle-treated controls. From the three-dimensional reconstruction of the bony callus, telmisartan-treated group significantly increased the values of BV/TV by 21.7% and CsAr by 26.0% compared to the vehicle-treated controls at 5 weeks post-fracture. In summary, we demonstrate in the current study that telmisartan could promote fracture healing in a mice model via increasing mechanical strength and improving microstructure. The most mechanism is probably by an increase of cell proliferation and neovascularization associated with a decreased VEGF expression in hypertrophic

  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. Fracture healing in protease-activated receptor-2 deficient mice.

    PubMed

    O'Neill, Kevin R; Stutz, Christopher M; Mignemi, Nicholas A; Cole, Heather; Murry, Matthew R; Nyman, Jeffry S; Hamm, Heidi; Schoenecker, Jonathan G

    2012-08-01

    Protease-activated receptor-2 (PAR-2) provides an important link between extracellular proteases and the cellular initiation of inflammatory responses. The effect of PAR-2 on fracture healing is unknown. This study investigates the in vivo effect of PAR-2 deletion on fracture healing by assessing differences between wild-type (PAR-2(+/+)) and knock-out (PAR-2(-/-)) mice. Unilateral mid-shaft femur fractures were created in 34 PAR-2(+/+) and 28 PAR-2(-/-) mice after intramedullary fixation. Histologic assessments were made at 1, 2, and 4 weeks post-fracture (wpf), and radiographic (plain radiographs, micro-computed tomography (µCT)) and biomechanical (torsion testing) assessments were made at 7 and 10 wpf. Both the fractured and un-fractured contralateral femur specimens were evaluated. Polar moment of inertia (pMOI), tissue mineral density (TMD), bone volume fraction (BV/TV) were determined from µCT images, and callus diameter was determined from plain radiographs. Statistically significant differences in callus morphology as assessed by µCT were found between PAR-2(-/-) and PAR-2(+/+) mice at both 7 and 10 wpf. However, no significant histologic, plain radiographic, or biomechanical differences were found between the genotypes. The loss of PAR-2 was found to alter callus morphology as assessed by µCT but was not found to otherwise effect fracture healing in young mice.

  8. Role of mathematical modeling in bone fracture healing

    PubMed Central

    Pivonka, Peter; Dunstan, Colin R

    2012-01-01

    Bone fracture healing is a complex physiological process commonly described by a four-phase model consisting of an inflammatory phase, two repair phases with soft callus formation followed by hard callus formation, and a remodeling phase, or more recently by an anabolic/catabolic model. Data from humans and animal models have demonstrated crucial environmental conditions for optimal fracture healing, including the mechanical environment, blood supply and availability of mesenchymal stem cells. Fracture healing spans multiple length and time scales, making it difficult to know precisely which factors and/or phases to manipulate in order to obtain optimal fracture-repair outcomes. Deformations resulting from physiological loading or fracture fixation at the organ scale are sensed at the cellular scale by cells inside the fracture callus. These deformations together with autocrine and paracrine signals determine cellular differentiation, proliferation and migration. The local repair activities lead to new bone formation and stabilization of the fracture. Although experimental data are available at different spatial and temporal scales, it is not clear how these data can be linked to provide a holistic view of fracture healing. Mathematical modeling is a powerful tool to quantify conceptual models and to establish the missing links between experimental data obtained at different scales. The objective of this review is to introduce mathematical modeling to readers who are not familiar with this methodology and to demonstrate that once validated, such models can be used for hypothesis testing and to assist in clinical treatment as will be shown for the example of atrophic nonunions. PMID:24228159

  9. 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

  10. The initial phase of fracture healing is specifically sensitive to mechanical conditions.

    PubMed

    Klein, Petra; Schell, Hanna; Streitparth, Florian; Heller, Markus; Kassi, Jean-Pierre; Kandziora, Frank; Bragulla, Hermann; Haas, Norbert P; Duda, Georg N

    2003-07-01

    Interfragmentary movements affect the quality and quantity of callus formation. The mounting plane of monolateral external fixators may give direction to those movements. Therefore, the aim of this study was to determine the influence of the fixator mounting plane on the process of fracture healing. Identically configured fixators were mounted either medially or anteromedially on the tibiae of sheep. Interfragmentary movements and ground reaction forces were evaluated in vivo during a nine week period. Histomorphological and biomechanical parameters described the bone healing processes. Changing only the mounting plane led to a modification of interfragmentary movements in the initial healing phase. The difference in interfragmentary movements between the groups was only significant during the first post-operative period. However, these initial differences in mechanical conditions influenced callus tissue formation significantly. The group with the anteromedially mounted fixator, initially showing significantly more interfragmentary movements, ended up with a significantly smaller callus diameter and a significantly higher callus stiffness as a result of advanced fracture healing. This demonstrates that the initial phase of healing is sensitive to mechanical conditions and influences the course of healing. Therefore, initial mechanical stability of an osteosynthesis should be considered an important factor in clinical fracture treatment.

  11. 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.

  12. 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

  13. The effects of local platelet rich plasma delivery on diabetic fracture healing.

    PubMed

    Gandhi, Ankur; Doumas, Christopher; Dumas, Christopher; O'Connor, J Patrick; Parsons, J Russell; Lin, Sheldon S

    2006-04-01

    Several studies have documented that diabetes impairs bone healing clinically and experimentally. The percutaneous delivery of platelet rich plasma (PRP) was used in the diabetic BB Wistar femur fracture model to investigate the use of PRP as a concentrated source of critical early growth factors on bone healing. PRP delivery at the fracture site normalized the early (cellular proliferation and chondrogenesis) parameters while improving the late (mechanical strength) parameters of diabetic fracture healing. These results suggest a role for PRP in mediating diabetic fracture healing and potentially other high risk fractures.

  14. 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

  15. Traumatic subchondral fracture of the femoral head in a healed trochanteric fracture

    PubMed Central

    Lee, Sang Yang; Niikura, Takahiro; Iwakura, Takashi; Kurosaka, Masahiro

    2014-01-01

    An 82-year-old woman sustained a trochanteric fracture of the left femur after a fall. Fracture fixation was performed using proximal femoral nail antirotation (PFNA) II, and she was able to walk with a T-cane after 3 months. Eleven months following the operation, the patient presented with left hip pain after a fall. Radiographs showed a subchondral collapse of the femoral head located above the blade tip. The authors removed the PFNA-II and subsequently performed cemented bipolar hemiarthroplasty. Histological evaluation of the femoral head showed osteoporosis with no evidence of osteonecrosis. Repair tissue, granulation tissue and callus formation were seen at the collapsed subchondral area. Based on these findings, a traumatic subchondral fracture of the femoral head in a healed trochanteric fracture was diagnosed. A traumatic subchondral fracture of the femoral head may need to be considered as a possible diagnosis after internal fixation of the trochanteric fracture. PMID:25015169

  16. 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. PMID:25846213

  17. 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.

  18. Selective and non-selective cyclooxygenase inhibitors delay stress fracture healing in the rat ulna.

    PubMed

    Kidd, Lisa J; Cowling, Nick R; Wu, Andy C; Kelly, Wendy L; Forwood, Mark R

    2013-02-01

    Anti-inflammatory drugs are widely used to manage pain associated with stress fractures (SFxs), but little is known about their effects on healing of those injuries. We hypothesized that selective and non-selective anti-inflammatory treatments would retard the healing of SFx in the rat ulna. SFxs were created by cyclic loading of the ulna in Wistar rats. Ulnae were harvested 2, 4 or 6 weeks following loading. Rats were treated with non-selective NSAID, ibuprofen (30 mg/kg/day); selective COX-2 inhibition, [5,5-dimethyl-3-3 (3 fluorophenyl)-4-(4 methylsulfonal) phenyl-2 (5H)-furanone] (DFU) (2.0 mg/kg/day); or the novel c5a anatagonist PMX53 (10 mg/kg/day, 4 and 6 weeks only); with appropriate vehicle as control. Quantitative histomorphometric measurements of SFx healing were undertaken. Treatment with the selective COX-2 inhibitor, DFU, reduced the area of resorption along the fracture line at 2 weeks, without affecting bone formation at later stages. Treatment with the non-selective, NSAID, ibuprofen decreased both bone resorption and bone formation so that there was significantly reduced length and area of remodeling and lamellar bone formation within the remodeling unit at 6 weeks after fracture. The C5a receptor antagonist PMX53 had no effect on SFx healing at 4 or 6 weeks after loading, suggesting that PMX53 would not delay SFx healing. Both selective COX-2 inhibitors and non-selective NSAIDs have the potential to compromise SFx healing, and should be used with caution when SFx is diagnosed or suspected. PMID:22847634

  19. 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.

  20. 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

  1. "Inert" vehicles do affect wound healing.

    PubMed

    Eaglstein, W H; Mertz, P M

    1980-02-01

    The effect of a single daily application of U.S.P. petrolatum, an oil-in-water vanishing cream or a lotion on the rate of epidermal wound healing was determined in domestic white pigs. The superficial wounds were made with a dermatome and were not infected. In these studies, applications of U.S.P. white petrolatum retarded the rate of epidermal healing by 17% compared to untreated control wounds. Applications of an oil-in-water vanishing cream increased the rate of epidermal healing by 24% and a lotion increased the rate 15% compared to untreated control wounds.

  2. Osteoblast and osteocyte-specific loss of Connexin43 results in delayed bone formation and healing during murine fracture healing.

    PubMed

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

    2013-01-01

    Connexin43 (Cx43) plays an important role in osteoblastic differentiation in vitro, and bone formation in vivo. Mice with osteoblast/osteocyte-specific loss of Cx43 display decreased gap junctional intercellular communication (GJIC), bone density, and cortical thickness. To determine the role of Cx43 in fracture healing, a closed femur fracture was induced in Osteocalcin-Cre+; Cx43(flox/flox) (Cx43cKO) and Cre-; Cx43(flox/flox) (WT) mice. We tested the hypothesis that loss of Cx43 results in decreased bone formation and impaired healing following fracture. Here, we show that osteoblast and osteocyte-specific deletion of Cx43 results in decreased bone formation, bone remodeling, and mechanical properties during fracture healing. Cx43cKO mice display decreased bone volume, total volume, and fewer TRAP+ osteoclasts. Furthermore, loss of Cx43 in mature osteoblasts and osteocytes results in a significant decrease in torsional rigidity between 21 and 35 days post-fracture, compared to WT mice. These studies identify a novel role for the gap junction protein Cx43 during fracture healing, suggesting that loss of Cx43 can result in both decreased bone formation and bone resorption. Therefore, enhancing Cx43 expression or GJIC may provide a novel means to enhance bone formation during fracture healing.

  3. Biodistribution of Fracture-Targeted GSK3β Inhibitor-Loaded Micelles for Improved Fracture Healing.

    PubMed

    Low, Stewart A; Galliford, Chris V; Yang, Jiyuan; Low, Philip S; Kopeček, Jindřich

    2015-10-12

    Bone fractures constitute a major cause of morbidity and mortality especially in the elderly. Complications associated with osteoporosis drugs and the age of the patient slow bone turnover and render such fractures difficult to heal. Increasing the speed of fracture repair by administration of a fracture-targeted bone anabolic agent could find considerable application. Aspartic acid oligopeptides are negatively charged molecules at physiological pH that adsorb to hydroxyapatite, the mineral portion of bone. This general adsorption is the strongest where bone turnover is highest or where hydroxyapatite is freshly exposed. Importantly, both of these conditions are prominent at fracture sites. GSK3β inhibitors are potent anabolic agents that can promote tissue repair when concentrated in a damaged tissue. Unfortunately, they can also cause significant toxicity when administered systemically and are furthermore difficult to deliver due to their strong hydrophobicity. In this paper, we solve both problems by conjugating the hydrophobic GSK3β inhibitor to a hydrophilic aspartic acid octapeptide using a hydrolyzable bond, thereby generating a bone fracture-targeted water-soluble form of the drug. The resulting amphiphile is shown to assemble into micelles, extending its circulation time while maintaining its fracture-targeting abilities. For measurement of pharmacokinetics, an 125I was introduced at the location of the bromine in the GSK3β inhibitor to minimize any structural differences. Biodistribution studies demonstrate a greater than 4-fold increase in fracture accumulation over healthy bone. PMID:26331790

  4. Biodistribution of fracture-targeted GSK3β inhibitor-loaded micelles for improved fracture healing

    PubMed Central

    Low, Stewart A.; Galliford, Chris V.; Yang, Jiyuan; Low, Philip S.; Kopeček, Jindřich

    2016-01-01

    Bone fractures constitute a major cause of morbidity and mortality especially in the elderly. Complications associated with osteoporosis drugs and the age of the patient slow bone turnover and render such fractures difficult to heal. Increasing the speed of fracture repair by administration of a fracture-targeted bone anabolic agent could find considerable application. Aspartic acid oligopeptides are negatively charged molecules at physiological pH that adsorb to hydroxyapatite, the mineral portion of bone. This general adsorption is the strongest where bone turnover is highest or where hydroxyapatite is freshly exposed. Importantly, both of these conditions are prominent at fracture sites. GSK3β inhibitors are potent anabolic agents that can promote tissue repair when concentrated in a damaged tissue. Unfortunately, they can also cause significant toxicity when administered systemically and are furthermore difficult to deliver due to their strong hydrophobicity. In this paper, we solve both problems by conjugating the hydrophobic GSK3β inhibitor to a hydrophilic aspartic acid octapeptide using a hydrolyzable bond, thereby generating a bone fracture-targeted water-soluble form of the drug. The resulting amphiphile is shown to assemble into micelles, extending its circulation time while maintaining its fracture-targeting abilities. For measurement of pharmacokinetics, an 125I was introduced at the location of the bromine in the GSK3β inhibitor to minimize any structural differences. Biodistribution studies demonstrate a greater than 4-fold increase in fracture accumulation over healthy bone. PMID:26331790

  5. Constructing the toolbox: Patient-specific genetic factors of altered fracture healing

    PubMed Central

    Drissi, Hicham; Paglia, David N.; Alaee, Farhang; Yoshida, Ryu

    2014-01-01

    The multifaceted sequence of events that follow fracture repair can be further complicated when considering risk factors for impaired union, present in a large and growing percentage of the population. Risk factors such as diabetes, substance abuse, and poor nutrition affect both the young and old alike, and have been shown to dramatically impair the body’s natural healing processes. To this end, biotherapeudic interventions such as ultrasound, electrical simulation, growth factor treatment (BMP-2, BMP-7, PDGF-BB, FGF-2) have been evaluated in preclinical models and in some cases are used widely for patients with established non-union or risk/indication or impaired healing (ie. ultrasound, BMP-2, etc.). Despite the promise of these interventions, they have been shown to be reliant on patient compliance and can produce adverse side-effects such as heterotopic ossification. Gene and cell therapy approaches have attempted to apply controlled regimens of these factors and have produced promising results. However, there are safety and efficacy concerns that may limit the translation of these approaches. In addition, none of the above mentioned approaches consider genetic variation between individual patients. Several clinical and preclinical studies have demonstrated a genetic component to fracture repair and that SNPs and genetic background variation play major roles in the determination of healing outcomes. Despite this, there is a need for preclinical data to dissect the mechanism underlying the influence of specific gene loci on the processes of fracture healing, which will be paramount in the future of patient-centered interventions for fracture repair. PMID:25558470

  6. Mice Lacking Pten in Osteoblasts Have Improved Intramembranous and Late Endochondral Fracture Healing

    PubMed Central

    Burgers, Travis A.; Hoffmann, Martin F.; Collins, Caitlyn J.; Zahatnansky, Juraj; Alvarado, Martin A.; Morris, Michael R.; Sietsema, Debra L.; Mason, James J.; Jones, Clifford B.; Ploeg, Heidi L.; Williams, Bart O.

    2013-01-01

    The failure of an osseous fracture to heal (development of a non-union) is a common and debilitating clinical problem. Mice lacking the tumor suppressor Pten in osteoblasts have dramatic and progressive increases in bone volume and density throughout life. Since fracture healing is a recapitulation of bone development, we investigated the process of fracture healing in mice lacking Pten in osteoblasts (Ocn-cretg/+;Ptenflox/flox). Mid-diaphyseal femoral fractures induced in wild-type and Ocn-cretg/+;Ptenflox/flox mice were studied via micro-computed tomography (µCT) scans, biomechanical testing, histological and histomorphometric analysis, and protein expression analysis. Ocn-cretg/+;Ptenflox/flox mice had significantly stiffer and stronger intact bones relative to controls in all cohorts. They also had significantly stiffer healing bones at day 28 post-fracture (PF) and significantly stronger healing bones at days 14, 21, and 28 PF. At day 7 PF, the proximal and distal ends of the Pten mutant calluses were more ossified. By day 28 PF, Pten mutants had larger and more mineralized calluses. Pten mutants had improved intramembranous bone formation during healing originating from the periosteum. They also had improved endochondral bone formation later in the healing process, after mature osteoblasts are present in the callus. Our results indicate that the inhibition of Pten can improve fracture healing and that the local or short-term use of commercially available Pten-inhibiting agents may have clinical application for enhancing fracture healing. PMID:23675511

  7. Multiple roles of tumor necrosis factor-alpha in fracture healing.

    PubMed

    Karnes, Jonathan M; Daffner, Scott D; Watkins, Colleen M

    2015-09-01

    This review presents a summary of basic science evidence examining the influence of tumor necrosis factor-alpha (TNF-α) on secondary fracture healing. Multiple studies suggest that TNF-α, in combination with the host reservoir of peri-fracture mesenchymal stem cells, is a main determinant in the success of bone healing. Disease states associated with poor bone healing commonly have inappropriate TNF-α responses, which likely contributes to the higher incidence of delayed and nonunions in these patient populations. Appreciation of TNF-α in fracture healing may lead to new therapies to augment recovery and reduce the incidence of complications.

  8. 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

  9. 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.

  10. Healing of fractures with freeze-dried cortical bone plates. Comparison with compression plating.

    PubMed

    Malinin, T; Latta, L L; Wagner, J L; Brown, M D

    1984-11-01

    The healing of fractures of the radius with internal fixation by stainless-steel compression plates was compared with fractures fixed with freeze-dried bone-plate allografts. Fractures fixed with metallic plates gained slightly less than half the biomechanical strength of the contralateral control bone and healed without noticeable external callus formation. Bone-plated fractures regained three-fourths of the biomechanical strength of controls and healed by forming an external callus. Bone-plate allografts were eventually incorporated in the host bone. Allograft plates were vascularized and remodeled into cancellous bone in the process of incorporation in the host bones.

  11. 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.

  12. Implantable microelectromechanical sensors for diagnostic monitoring and post-surgical prediction of bone fracture healing.

    PubMed

    McGilvray, Kirk C; Unal, Emre; Troyer, Kevin L; Santoni, Brandon G; Palmer, Ross H; Easley, Jeremiah T; Demir, Hilmi Volkan; Puttlitz, Christian M

    2015-10-01

    The relationship between modern clinical diagnostic data, such as from radiographs or computed tomography, and the temporal biomechanical integrity of bone fracture healing has not been well-established. A diagnostic tool that could quantitatively describe the biomechanical stability of the fracture site in order to predict the course of healing would represent a paradigm shift in the way fracture healing is evaluated. This paper describes the development and evaluation of a wireless, biocompatible, implantable, microelectromechanical system (bioMEMS) sensor, and its implementation in a large animal (ovine) model, that utilized both normal and delayed healing variants. The in vivo data indicated that the bioMEMS sensor was capable of detecting statistically significant differences (p-value <0.04) between the two fracture healing groups as early as 21 days post-fracture. In addition, post-sacrifice micro-computed tomography, and histology data demonstrated that the two model variants represented significantly different fracture healing outcomes, providing explicit supporting evidence that the sensor has the ability to predict differential healing cascades. These data verify that the bioMEMS sensor can be used as a diagnostic tool for detecting the in vivo course of fracture healing in the acute post-treatment period.

  13. Implantable microelectromechanical sensors for diagnostic monitoring and post-surgical prediction of bone fracture healing.

    PubMed

    McGilvray, Kirk C; Unal, Emre; Troyer, Kevin L; Santoni, Brandon G; Palmer, Ross H; Easley, Jeremiah T; Demir, Hilmi Volkan; Puttlitz, Christian M

    2015-10-01

    The relationship between modern clinical diagnostic data, such as from radiographs or computed tomography, and the temporal biomechanical integrity of bone fracture healing has not been well-established. A diagnostic tool that could quantitatively describe the biomechanical stability of the fracture site in order to predict the course of healing would represent a paradigm shift in the way fracture healing is evaluated. This paper describes the development and evaluation of a wireless, biocompatible, implantable, microelectromechanical system (bioMEMS) sensor, and its implementation in a large animal (ovine) model, that utilized both normal and delayed healing variants. The in vivo data indicated that the bioMEMS sensor was capable of detecting statistically significant differences (p-value <0.04) between the two fracture healing groups as early as 21 days post-fracture. In addition, post-sacrifice micro-computed tomography, and histology data demonstrated that the two model variants represented significantly different fracture healing outcomes, providing explicit supporting evidence that the sensor has the ability to predict differential healing cascades. These data verify that the bioMEMS sensor can be used as a diagnostic tool for detecting the in vivo course of fracture healing in the acute post-treatment period. PMID:26174472

  14. 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

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

    PubMed Central

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

    2016-01-01

    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. PMID:26926165

  16. 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

  17. 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.

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

    PubMed

    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

  19. Analgesic effects of p38 kinase inhibitor treatment on bone fracture healing.

    PubMed

    Cottrell, Jessica A; Meyenhofer, Markus; Medicherla, Satyanarayana; Higgins, Linda; O'Connor, J Patrick

    2009-03-01

    Traditional and COX-2 selective non-steroidal anti-inflammatory drug (NSAID) treatment inhibits fracture healing in animal models. This indicates that either the inflammatory phase following a bone fracture is necessary for efficient or sufficient bone regeneration to heal the fracture or COX-2 may have a specific function during bone regeneration unrelated to inflammation. These observations also indicate that NSAID use during fracture healing may be contra-indicated. Thus, identification of different analgesics for fracture pain or other orthopaedic surgical procedures would be of significant clinical benefit. Inhibitors of p38 kinase also have significant analgesic properties. However, p38 kinase is a critical regulator of inflammation. To assess the potential use of p38 kinase inhibition as a therapeutic strategy to manage fracture pain, the analgesic properties of SCIO-469, a p38alpha kinase inhibitor, were assessed in a rat fracture model and compared to other common analgesics. In addition, the effects of SCIO-469 treatment on ultimate fracture healing outcomes were measured by radiography and torsional mechanical testing. The data indicate that SCIO-469 was an effective analgesic. No adverse events related to fracture healing were observed in rats treated with SCIO-469. Immunohistochemistry showed that p38 kinase is activated primarily in the first days following a fracture. These observations suggest that p38alpha kinase inhibition may be an effective therapeutic strategy to manage orthopaedic-related pain. These observations also indicate that COX-2 has a specific function during bone regeneration other than promoting inflammation.

  20. Simulated microgravity alters the expression of key genes involved in fracture healing

    NASA Astrophysics Data System (ADS)

    McCabe, N. Patrick; Androjna, Caroline; Hill, Esther; Globus, Ruth K.; Midura, Ronald J.

    2013-11-01

    Fracture healing in animal models has been shown to be altered in both ground based analogs of spaceflight and in those exposed to actual spaceflight. The molecular mechanisms behind altered fracture healing as a result of chronic exposure to microgravity remain to be elucidated. This study investigates temporal gene expression of multiple factors involved in secondary fracture healing, specifically those integral to the development of a soft tissue callus and the transition to that of hard tissue. Skeletally mature female rats were subjected to a 4 week period of simulated microgravity and then underwent a closed femoral fracture procedure. Thereafter, they were reintroduced to the microgravity and allowed to heal for a 1 or 2 week period. A synchronous group of weight bearing rats was used as a normal fracture healing control. Utilizing Real-Time quantitative PCR on mRNA from fracture callus tissue, we found significant reductions in the levels of transcripts associated with angiogenesis, chondrogenesis, and osteogenesis. These data suggest an altered fracture healing process in a simulated microgravity environment, and these alterations begin early in the healing process. These findings may provide mechanistic insight towards developing countermeasure protocols to mitigate these adaptations.

  1. Fracture healing with alendronate treatment in the Brtl/+ mouse model of osteogenesis imperfecta.

    PubMed

    Meganck, J A; Begun, D L; McElderry, J D; Swick, A; Kozloff, K M; Goldstein, S A; Morris, M D; Marini, J C; Caird, M S

    2013-09-01

    Osteogenesis imperfecta (OI) is a heritable bone dysplasia characterized by increased skeletal fragility. Patients are often treated with bisphosphonates to attempt to reduce fracture risk. However, bisphosphonates reside in the skeleton for many years and long-term administration may impact bone material quality. Acutely, there is concern about risk of non-union of fractures that occur near the time of bisphosphonate administration. This study investigated the effect of alendronate, a potent aminobisphosphonate, on fracture healing. Using the Brtl/+ murine model of type IV OI, tibial fractures were generated in 8-week-old mice that were untreated, treated with alendronate before fracture, or treated before and after fracture. After 2, 3, or 5 weeks of healing, tibiae were assessed using microcomputed tomography (μCT), torsion testing, quantitative histomorphometry, and Raman microspectroscopy. There were no morphologic, biomechanical or histomorphometric differences in callus between untreated mice and mice that received alendronate before fracture. Alendronate treatment before fracture did not cause a significant increase in cartilage retention in fracture callus. Both Brtl/+ and WT mice that received alendronate before and after fracture had increases in the callus volume, bone volume fraction and torque at failure after 5 weeks of healing. Raman microspectroscopy results did not show any effects of alendronate in wild-type mice, but calluses from Brtl/+ mice treated with alendronate during healing had a decreased mineral-to-matrix ratio, decreased crystallinity and an increased carbonate-to-phosphate ratio. Treatment with alendronate altered the dynamics of healing by preventing callus volume decreases later in the healing process. Fracture healing in Brtl/+ untreated animals was not significantly different from animals in which alendronate was halted at the time of fracture.

  2. 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.

  3. Stimulation of fracture healing with Electromagnetic Fields of Extremely Low Frequency (EMF of ELF)

    SciTech Connect

    Wahlstroem, O.

    1984-06-01

    This randomized, controlled study was performed to evaluate how electromagnetic fields affect the accumulation of /sup 99m/Technetium - methylendiphosphonate (Tc-MDP) in fresh fractures. Thirty women with Colles' fractures, aged 50-70 years, participated in this study--some in a control group and some in a treated group. After reduction, all patients were immobilized for four weeks. After randomization, 15 patients were treated by electromagnetic fields of extremely low frequency (EMF of ELF), which were generated by a coil and a battery-powered portable current generator during the time of immobilization. The frequency of the alternating magnetic field was 1-1000 Hz; the magnitude was 4 gauss (RMS (root-mean-square) value). The scintigrams were performed one, two, four, and eight weeks after the injury. The activity ratio in the fracture area was significantly higher at the examination of one and two weeks in the treated group than it was in the control group. The clinical relevance of the results is not known, but one interpretation of the data is that the stimulation with EMF of ELF improves (accelerates) the early phase of fracture healing. The data warrant further investigation of fresh fracture treatment with this method.

  4. 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.

  5. 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

  6. 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.

  7. BDNF and its TrkB receptor in human fracture healing.

    PubMed

    Kilian, Olaf; Hartmann, Sonja; Dongowski, Nicole; Karnati, Srikanth; Baumgart-Vogt, Eveline; Härtel, Frauke V; Noll, Thomas; Schnettler, Reinhard; Lips, Katrin Susanne

    2014-09-01

    Fracture healing is a physiological process of repair which proceeds in stages, each characterized by a different predominant tissue in the fracture gap. Matrix reorganization is regulated by cytokines and growth factors. Neurotrophins and their receptors might be of importance to osteoblasts and endothelial cells during fracture healing. The aim of this study was to examine the presence of brain-derived neurotrophic factor (BDNF) and its tropomyosin-related kinase B receptor (TrkB) during human fracture healing. BDNF and TrkB were investigated in samples from human fracture gaps and cultured cells using RT-PCR, Western blot, and immunohistochemistry. Endothelial cells and osteoblastic cell lines demonstrated a cytoplasmic staining pattern of BDNF and TrkB in vitro. At the mRNA level, BDNF and TrkB were expressed in the initial and osteoid formation phase of human fracture healing. In the granulation tissue of fracture gap, both proteins--BDNF and TrkB--are concentrated in endothelial and osteoblastic cells at the margins of woven bone suggesting their involvement in the formation of new vessels. There was no evidence of BDNF or TrkB during fracture healing in chondrocytes of human enchondral tissue. Furthermore, BDNF is absent in mature bone. Taken together, BDNF and TrkB are involved in vessel formation and osteogenic processes during human fracture healing. The detection of BDNF and its TrkB receptor during various stages of the bone formation process in human fracture gap tissue were shown for the first time. The current study reveals that both proteins are up-regulated in human osteoblasts and endothelial cells in fracture healing. PMID:24984919

  8. Strains caused by daily loading might be responsible for delayed healing of an incomplete atypical femoral fracture.

    PubMed

    Gustafsson, Anna; Schilcher, Jörg; Grassi, Lorenzo; Aspenberg, Per; Isaksson, Hanna

    2016-07-01

    Atypical femoral fractures are insufficiency fractures in the lateral femoral diaphysis or subtrochanteric region that mainly affect older patients on bisphosphonate therapy. Delayed healing is often seen in patients with incomplete fractures (cracks), and histology of bone biopsies shows mainly necrotic material inside the crack. We hypothesized that the magnitude of the strains produced in the soft tissue inside the crack during normal walk exceeds the limit for new bone formation, and thereby inhibit healing. A patient specific finite element model was developed, based on clinical CT images and high resolution μCT images of a biopsy from the crack site. Strain distributions in the femur and inside the crack were calculated for load cases representing normal walk. The models predicted large strains inside the crack, with strain levels above 10% in more than three quarters of the crack volume. According to two different tissue differentiation theories, bone would only form in less than 1-5% of the crack volume. This can explain the impaired healing generally seen in incomplete atypical fractures. Furthermore, the microgeometry of the crack highly influenced the strain distributions. Hence, a realistic microgeometry needs to be considered when modeling the crack. Histology of the biopsy showed signs of remodeling in the bone tissue adjacent to the fracture line, while the crack itself contained mainly necrotic material and signs of healing only in portions that seemed to have been widened by resorption. In conclusion, the poor healing capacity of incomplete atypical femoral fractures can be explained by biomechanical factors, and daily low impact activities are enough to cause strain magnitudes that prohibit bone formation. PMID:27113528

  9. Role of platelet-rich plasma in acceleration of bone fracture healing.

    PubMed

    Simman, Richard; Hoffmann, Andrea; Bohinc, R Jordan; Peterson, Wylan C; Russ, Andrew J

    2008-09-01

    Platelet-rich plasma (PRP) is a common therapy for acceleration of maxillofacial and spinal fusion bone-graft healing. This study analyzes the therapeutic role of PRP during long-bone fracture healing evaluated Lewis rats. Following creation of unilateral open femur fractures, either 500 microL thrombin-activated PRP (PRP treated group) or 500 microL saline (control group) were applied once to the fracture site. Fracture healing was analyzed after 1 and 4 weeks. Following 4 weeks of fracture healing, radiographic analysis demonstrated higher callus to cortex width ratio (P < 0.05) in the PRP group (PRP: 1.65 +/- 0.06; control: 1.48 +/- 0.05). Three-point load bearing showed increased bone strength following PRP treatment (PRP: 60.85 +/- 6.06 Newton, control: 47.66 +/- 5.49 Newton). Fracture histology showed enhanced bone formation in the PRP group. Immunohistochemistry and Western-blotting demonstrated healing-associated changes in transforming growth factor (TGF)-beta1 and bone morphogenetic protein (BMP)-2. Our results suggest that PRP accelerates bone fracture healing of rat femurs via modulation of TGF-beta1 and BMP-2 growth factor expression.

  10. Sensitivities of biomechanical assessment methods for fracture healing of long bones.

    PubMed

    Chen, G; Wu, F Y; Zhang, J Q; Zhong, G Q; Liu, F

    2015-07-01

    There is a controversy as to whether the biomechanical methods are feasible to assess fracture healing of long bones. This paper investigated the sensitivities of two biomechanical methods, torsion and bending, for assessing fracture healing of long bones; both a simplified beam model and finite element model of an artificial femur were employed. The results demonstrated that, in the initial healing stage, the whole-bone stiffness of the fractured bone is extremely sensitive to the variation of the callus stiffness at the fracture site; when the shear (or Young's) modulus of the callus reaches 15% that of the intact bone, the whole-bone stiffness rises up to 90% that of the intact bone. After that, the whole-bone torsional (or bending) stiffness increases slowly; it becomes less sensitive to the variation of the callus stiffness. These results imply that the whole-bone stiffness is of limited reliability to assess the healing quality particular at late stages of the healing process. The simplified model in this paper provided a theoretical framework to explain why the whole-bone stiffness is insensitive to the healing process of fractured long bones in the late stage of healing. The conclusions obtained from the simplified model were verified with the finite element simulations of the artificial femur. PMID:25983068

  11. Sensitivities of biomechanical assessment methods for fracture healing of long bones.

    PubMed

    Chen, G; Wu, F Y; Zhang, J Q; Zhong, G Q; Liu, F

    2015-07-01

    There is a controversy as to whether the biomechanical methods are feasible to assess fracture healing of long bones. This paper investigated the sensitivities of two biomechanical methods, torsion and bending, for assessing fracture healing of long bones; both a simplified beam model and finite element model of an artificial femur were employed. The results demonstrated that, in the initial healing stage, the whole-bone stiffness of the fractured bone is extremely sensitive to the variation of the callus stiffness at the fracture site; when the shear (or Young's) modulus of the callus reaches 15% that of the intact bone, the whole-bone stiffness rises up to 90% that of the intact bone. After that, the whole-bone torsional (or bending) stiffness increases slowly; it becomes less sensitive to the variation of the callus stiffness. These results imply that the whole-bone stiffness is of limited reliability to assess the healing quality particular at late stages of the healing process. The simplified model in this paper provided a theoretical framework to explain why the whole-bone stiffness is insensitive to the healing process of fractured long bones in the late stage of healing. The conclusions obtained from the simplified model were verified with the finite element simulations of the artificial femur.

  12. The Changed Route of Anterior Tibial Artery due to Healed Fracture

    PubMed Central

    Gökkuş, Kemal; Sagtas, Ergin; Comert, Nuri; Unal, Mehmet Bekir; Baloglu, Murat

    2016-01-01

    We would like to highlight unusual sequelae of healed distal third diaphyseal tibia fracture that was treated conservatively 36 years ago, in which we incidentally detected peripheral CT angiography. The anterior tibial artery was enveloped three-quarterly by the healing callus of the bone (distal tibia). PMID:27019760

  13. 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.

  14. 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

  15. 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. PMID:22973405

  16. 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

  17. Effects of prefracture irradiation on the biomechanical parameters of fracture healing.

    PubMed

    Widmann, R F; Pelker, R R; Friedlaender, G E; Panjabi, M M; Peschel, R E

    1993-05-01

    This study examined the effects on the biomechanical parameters of fracture healing of a single dose of 900 rad (the approximate single-dose equivalent of 2,500 rad in 10 divided doses), given 1 day prior to closed fracture of the femur. The femurs were recovered at 2, 3, 4, 8, and 16 weeks after fracture and were mounted and tested to failure in torsion; the results were compared with those in nonirradiated controls from a previously published study. Prefracture irradiation delayed the progressive increase in biomechanical parameters of fracture healing. The delay was statistically significant up to 8 weeks after fracture. At 4 weeks, the normalized torque was 44% that of intact bone in the treated group compared with 75% for the control group. Sixteen weeks after fracture, the biomechanical and histological parameters of fracture healing of the irradiated femurs were no different from those of the nonirradiated controls. Within the treated group, the irradiated fractures remained significantly weaker than their contralateral intact bone at all time intervals, with a torque of only 79% that of intact bone at 16 weeks. Thus, femoral fractures in rats healed (or regained substantial strength) following palliative doses of radiation delivered 1 day prior to injury, but the repair process was delayed compared with that of nonirradiated controls.

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

    PubMed

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

    2013-09-01

    Fracture repair occurs by two broad mechanisms: direct healing, and indirect healing with callus formation. The effects of bisphosphonates on fracture repair have been assessed only in models of indirect fracture healing. A rodent model of rigid compression plate fixation of a standardised tibial osteotomy was used. Ten skeletally mature Sprague-Dawley rats received daily subcutaneous injections of 1 µg/kg ibandronate (IBAN) and ten control rats received saline (control). Three weeks later a tibial osteotomy was rigidly fixed with compression plating. Six weeks later the animals were killed. Fracture repair was assessed with mechanical testing, radiographs and histology. The mean stress at failure in a four-point bending test was significantly lower in the IBAN group compared with controls (8.69 Nmm(-2) (sd 7.63) vs 24.65 Nmm(-2) (sd 6.15); p = 0.017). On contact radiographs of the extricated tibiae the mean bone density assessment at the osteotomy site was lower in the IBAN group than in controls (3.7 mmAl (sd 0.75) vs 4.6 mmAl (sd 0.57); p = 0.01). In addition, histological analysis revealed progression to fracture union in the controls but impaired fracture healing in the IBAN group, with predominantly cartilage-like and undifferentiated mesenchymal tissue (p = 0.007). Bisphosphonate treatment in a therapeutic dose, as used for risk reduction in fragility fractures, had an inhibitory effect on direct fracture healing. We propose that bisphosphonate therapy not be commenced until after the fracture has united if the fracture has been rigidly fixed and is undergoing direct osteonal healing. PMID:23997143

  19. 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

  20. Effect of Teriparatide on Healing of Atypical Femoral Fractures: A Systemic Review

    PubMed Central

    Lee, Seong-Hyun

    2015-01-01

    Background Bisphosphonates (BPs) are the most commonly used anti-osteoporotic drugs, which have been proven to reduce the risk of osteoporotic fractures. However, use of BPs, particularly for long periods of time, is associated with an increased risk of atypical femoral fracture (AFF). Healing of BP-associated AFF is usually delayed because of suppressed bone turnover. Teriparatide (TPTD), a recombinant form of parathyroid hormone (PTH), enhances bone healing in patients with delayed healing or non-union. Methods In this study, we summarized and performed a systemic review of the published literature on treatment of AFF using TPTD. Results Although there is a lack of level 1 studies on the evidence of TPTD in promoting bone union in AFFs, this systemic review of the available literature revealed that TPTD works positively in AFFs, and we put together the evidence that TPTD is a viable treatment option for enhancing fracture healing in AFFs. Conclusions While anecdotal evidence of beneficial effects of TPTD on fracture healing offer limited guidance for clinical decision making, a better understanding of the role of TPTD in fracture healing may be elucidated with future prospective trials. PMID:26713309

  1. 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. PMID:26447406

  2. Increased callus mass and enhanced strength during fracture healing in mice lacking the sclerostin gene.

    PubMed

    Li, Chaoyang; Ominsky, Michael S; Tan, Hong-Lin; Barrero, Mauricio; Niu, Qing-Tian; Asuncion, Franklin J; Lee, Edward; Liu, Min; Simonet, William S; Paszty, Chris; Ke, Hua Zhu

    2011-12-01

    Humans with inherited sclerostin deficiency have high bone mass. Targeted deletion of the sclerostin gene in mice (SOST-KO) causes increases in bone formation, bone mass and bone strength. Inhibition of sclerostin by a monoclonal antibody increases bone formation and enhances fracture healing in rodent and primate models. In this study, we describe the temporal progression of femoral fracture healing in SOST-KO mice compared with wild type (WT) control mice to further characterize the role of sclerostin in fracture healing. Sixty-seven male 9-10 week-old SOST-KO (N=37) and WT (N=30) mice underwent a closed femoral fracture. Weekly radiography was used to monitor the progress of healing. Histologic sections were used to characterize callus composition, evaluate callus bridging, and quantify lamellar bone formation on days 14 and 28. Densitometry and biomechanical testing were utilized to characterize bone mass and strength at the fractured and contralateral femurs on day 45. A significant improvement in time to radiographic healing (no discernible fracture line) was observed in SOST-KO mice, which corresponded to an increase in histologic bony bridging at 14 days (38% versus 0% in WT). Both genotypes appeared to be nearly fully bridged at 28 days post-fracture. The increased bridging at 14 days was associated with 97% greater bone area and 40% lower cartilage area in the callus of SOST-KO mice as compared to WT mice. Bone formation-related endpoints were higher in SOST-KO mice at both 14 and 28 days. At 45 days post-fracture, peak load and bone mass were significantly greater in the fractured femurs of SOST-KO mice as compared to WT mice. In conclusion, fractures in mice lacking sclerostin showed accelerated bridging, greater callus maturation, and increased bone formation and strength in the callus.

  3. 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.

  4. 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.

  5. Fourier Transform Infrared Spectroscopic Imaging of Fracture Healing in the Normal Mouse

    PubMed Central

    Gollwitzer, Hans; Yang, Xu; Spevak, Lyudmila; Lukashova, Lyudmila; Nocon, Allina; Fields, Kara; Pleshko, Nancy; Courtland, Hayden William; Bostrom, Mathias P.; Boskey, Adele L.

    2015-01-01

    Fourier transform infrared spectroscopic imaging (FTIRI) was used to study bone healing with spatial analysis of various callus tissues in wild type mice. Femoral fractures were produced in 28 male C57BL mice by osteotomy. Animals were sacrificed at 1, 2, 4, and 8 weeks to obtain callus tissue at well-defined healing stages. Following microcomputerized tomography, bone samples were cut in consecutive sections for FTIRI and histology, allowing for spatial correlation of both imaging methods in different callus areas (early calcified cartilage, woven bone, areas of intramembranous and endochondral bone formation). Based on FTIRI, mineral/matrix ratio increased significantly during the first 4 weeks of fracture healing in all callus areas and correlated with bone mineral density measured by micro-CT. Carbonate/phosphate ratio was elevated in newly formed calcified tissue and at week 2 attained values comparable to cortical bone. Collagen maturity and mineral crystallinity increased during weeks 1–8 in most tissues while acid phosphate substitution decreased. Temporal and callus area dependent changes were detected throughout the healing period. These data assert the usefulness of FTIRI for evaluation of fracture healing in the mouse and its potential to evaluate pathologic fracture healing and the effects of therapeutic interventions. PMID:26034749

  6. Correlations of radiographic analysis of healing fractures with strength: a statistical analysis of experimental osteotomies.

    PubMed

    Panjabi, M M; Walter, S D; Karuda, M; White, A A; Lawson, J P

    1985-01-01

    The assessment of fracture healing strength using routine roentgenograms is difficult and controversial. There are few experimental data that correlate radiographic appearance with the actual quantitative strength of healing fractures. However, this method is widely used in clinical practice. A study is presented in which transversely osteotomized rabbit tibiae were allowed to heal for 3 to 8 weeks. A pair of orthogonal roentgenograms was taken of each bone and the bones were tested for strength in a dynamic torsion testing machine. Statistical analyses were done to study the correlations between the roentgenographic and strength parameters. Cortical continuity was found to be the best single predictor of strength of a healing fracture (correlation coefficient r = 0.80). The least important predictor was the callus area (r = 0.17). Fracture displacement, callus thickness, and callus diameter had negative correlations. From these experimental findings in an animal model, we conclude that even under laboratory conditions the information gained from plain radiographs is not sufficient to accurately predict the strength of a healing fracture.

  7. Backstroke technique: an effective way to improve the healing of tibia fracture.

    PubMed

    Lee, Qi; Zeng, Bing-Fang; Luo, Cong-Feng; Wang, Jin-Wu; Lu, Nan-Ji

    2006-10-01

    To assess the method and results of applying a backstroke technique, we treated 43 patients with tibial shaft fracture using unreamed tibial nails (UTN). Of these patients, 27 suffered a closed fracture and 16 an open fracture. After the operation, the effect of treatment was evaluated: 42 of 43 cases were followed up from four to 18 months, averaging 13.6 months. The four-month and 12-month healing rates of open fracture were 54.6 and 80.9%, respectively, the former of which is significantly higher than the average rate of the AO/ASIF multicentre study. Our results indicate that applying a backstroke technique in treating tibial shaft fracture with UTN can improve the healing rate and reduce complications. PMID:16628441

  8. Influence of age on mechanical properties of healing fractures and intact bones in rats.

    PubMed

    Ekeland, A; Engesoeter, L B; Langeland, N

    1982-08-01

    Mechanical properties of fractured and intact femora have been studied in young and adult, male rats. A standardized, closed, mid-diaphyseal fracture was produced in the left femur, the right femur serving as control. The fracture was left to heal without immobilization. At various intervals, both fractured and intact femora were loaded in torsion until failure. The fractured femora regained the mechanical properties of the contralateral, intact bones after about 4 weeks in young and after about 12 weeks in adult rats. For intact bones, both the ultimate torsional moment (strength) and the torsional stiffness increased with age of the animals, whereas the ultimate torsional angle remained unchanged. For bone as a material, however, the ultimate torsional stress (strength) and the modulus of rigidity (stiffness) increased with age only in young rats, being almost constant in the adult animals. The various biomechanical parameters of the healing fractures did not reach those of the contralateral, intact bones simultaneously. The torsional moment required to twist a healing femoral fracture 20 degrees (0.35 radians), a deformation close to what an intact femur can resist, proved to be a functional and simple measure of the degree of fracture repair in rats.

  9. 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

  10. 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.

  11. Novel Perfused Compression Bioreactor System as an in vitro Model to Investigate Fracture Healing

    PubMed Central

    Hoffmann, Waldemar; Feliciano, Sandra; Martin, Ivan; de Wild, Michael; Wendt, David

    2015-01-01

    Secondary bone fracture healing is a physiological process that leads to functional tissue regeneration via endochondral bone formation. In vivo studies have demonstrated that early mobilization and the application of mechanical loads enhances the process of fracture healing. However, the influence of specific mechanical stimuli and particular effects during specific phases of fracture healing remain to be elucidated. In this work, we have developed and provided proof-of-concept of an in vitro human organotypic model of physiological loading of a cartilage callus, based on a novel perfused compression bioreactor (PCB) system. We then used the fracture callus model to investigate the regulatory role of dynamic mechanical loading. Our findings provide a proof-of-principle that dynamic mechanical loading applied by the PCB can enhance the maturation process of mesenchymal stromal cells toward late hypertrophic chondrocytes and the mineralization of the deposited extracellular matrix. The PCB provides a promising tool to study fracture healing and for the in vitro assessment of alternative fracture treatments based on engineered tissue grafts or pharmaceutical compounds, allowing for the reduction of animal experiments. PMID:25699254

  12. HIF-1α change in serum and callus during fracture healing in ovariectomized mice

    PubMed Central

    Li, Wenliang; Wang, Kejie; Liu, Zhiwei; Ding, Wenge

    2015-01-01

    The purpose was to detect the effects of ovariectomy (OVX) on femoral fracture healing through different angiogenesis and HIF-1α expression in mice. Thirty-six young female C57 mice were randomized into two groups: OVX and age-matched intact control (CON). The femoral fracture was generated at 3 weeks after OVX or CON. At 2 or 4 weeks after fracture, the femoral fracture area was evaluated healing status by bone mineral density (BMD), callus formation and mineralization and neovascularization in callus, biomechanical analysis, and HIF-1α tests. OVX mice showed lower BMD as compared with CON mice. Callus geometric microstructural parameters of the femora in OVX mice were significantly lower than CON mice. OVX induced significant changes of biomechanical parameters in the femoral fracture healing area. The callus forming, callus neovascularization and HIF-1α tests in OVX mice were significantly lower than in CON mice. HIF-1α results have the positive proportion with osteoporotic fracture healing. PMID:25755698

  13. 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.

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

    PubMed

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

    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. Periosteal PTHrP Regulates Cortical Bone Remodeling During Fracture Healing.

    PubMed

    Wang, Meina; Nasiri, Ali R; Broadus, Arthur E; Tommasini, Steven M

    2015-12-01

    Parathyroid hormone-related protein (PTHrP) is widely expressed in the fibrous outer layer of the periosteum (PO), and the PTH/PTHrP type I receptor (PTHR1) is expressed in the inner PO cambial layer. The cambial layer gives rise to the PO osteoblasts (OBs) and osteoclasts (OCs) that model/remodel the cortical bone surface during development as well as during fracture healing. PTHrP has been implicated in the regulation of PO modeling during development, but nothing is known as regards a role of PTHrP in this location during fracture healing. We propose that PTHrP in the fibrous layer of the PO may be a key regulatory factor in remodeling bone formation during fracture repair. We first assessed whether PTHrP expression in the fibrous PO is associated with PO osteoblast induction in the subjacent cambial PO using a tibial fracture model in PTHrP-lacZ mice. Our results revealed that both PTHrP expression and osteoblast induction in PO were induced 3 days post-fracture. We then investigated a potential functional role of PO PTHrP during fracture repair by performing tibial fracture surgery in 10-week-old CD1 control and PTHrP conditional knockout (PTHrP cKO) mice that lack PO PTHrP. We found that callus size and formation as well as woven bone mineralization in PTHrP cKO mice were impaired compared to that in CD1 mice. Concordant with these findings, functional enzyme staining revealed impaired OB formation and OC activity in the cKO mice. We conclude that deleting PO PTHrP impairs cartilaginous callus formation, maturation and ossification as well as remodeling during fracture healing. These data are the initial genetic evidence suggesting that PO PTHrP may induce osteoblastic activity and regulate fracture healing on the cortical bone surface. PMID:26164475

  16. 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.

  17. Amifostine Preserves Osteocyte Number and Osteoid Formation in Fracture Healing Following Radiotherapy

    PubMed Central

    Donneys, Alexis; Tchanque-Fossuo, Catherine N.; Blough, Jordan T.; Nelson, Noah S.; Deshpande, Sagar S.; Buchman, Steven R.

    2013-01-01

    Purpose Radiation is known to diminish osteocyte count and function leading to bone weakening. A treatment strategy to mitigate these consequences could have immense therapeutic ramifications. We have previously demonstrated significantly diminished osteocyte count and mineralization capacity in a rat model of fracture healing after radiotherapy. We hypothesize that amifostine (AMF) will preserve osteocyte number and function in this model. Materials and Methods Thirty-six rats were divided into three groups: fracture, radiated fracture, and radiated fracture with AMF. Radiated groups underwent human equivalent radiotherapy to the mandible prior to fixator placement and mandibular osteotomy. The AMF group received a subcutaneous injection prior to each dose of radiotherapy. After 40 days, mandibles were harvested for histologic processing. Quantification of osteocyte count (Oc), empty lacunae (EL) and osteoid ratio (OV/TV) was performed and the results were compared using ANOVA (p<0.05). Results Radiated fractures demonstrated significantly diminished Oc, increased EL and diminished capacity to produce new osteoid at the fracture site as measured with OV/TV when compared to non-radiated fractures. In mandibles treated with amifostine, these metrics were not statistically different than control, indicating a preservation of osteocyte number and function. Conclusions Our results support the hypothesis that amifostine preserves osteocyte number and function, thereby preventing the pernicious effects of radiotherapy on the cellular environment of fracture healing. Based on these findings, we encourage future investigation of this promising therapy for use in the prevention of pathologic fractures and osteoradionecrosis. PMID:24342580

  18. Inhibition of angiotensin-converting enzyme stimulates fracture healing and periosteal callus formation – role of a local renin-angiotensin system

    PubMed Central

    Garcia, P; Schwenzer, S; Slotta, JE; Scheuer, C; Tami, AE; Holstein, JH; Histing, T; Burkhardt, M; Pohlemann, T; Menger, MD

    2010-01-01

    Background and purpose: The renin-angiotensin system (RAS) regulates blood pressure and electrolyte homeostasis. In addition, ‘local’ tissue-specific RAS have been identified, regulating regeneration, cell growth, apoptosis, inflammation and angiogenesis. Although components of the RAS are expressed in osteoblasts and osteoclasts, a local RAS in bone has not yet been described and there is no information on whether the RAS is involved in fracture healing. Therefore, we studied the expression and function of the key RAS component, angiotensin-converting enzyme (ACE), during fracture healing. Experimental approach: In a murine femur fracture model, animals were treated with the ACE inhibitor perindopril or vehicle only. Fracture healing was analysed after 2, 5 and 10 weeks using X-ray, micro-CT, histomorphometry, immunohistochemistry, Western blotting and biomechanical testing. Key results: ACE was expressed in osteoblasts and hypertrophic chondrocytes in the periosteal callus during fracture healing, accompanied by expression of the angiotensin type-1 and type-2 receptors. Perindopril treatment reduced blood pressure and bone mineral density in unfractured femora. However, it improved periosteal callus formation, bone bridging of the fracture gap and torsional stiffness. ACE inhibition did not affect cell proliferation, but reduced apoptotic cell death. After 10 week treatment, a smaller callus diameter and bone volume after perindopril treatment indicated an advanced stage of bone remodelling. Conclusions: Our study provides evidence for a local RAS in bone that influenced the process of fracture healing. We show for the first time that inhibition of ACE is capable of accelerating bone healing and remodelling. PMID:20233225

  19. Parameters for Lithium Treatment Are Critical in Its Enhancement of Fracture-Healing in Rodents

    PubMed Central

    Bernick, Joshua; Wang, Yufa; Sigal, Ian A.; Alman, Benjamin A.; Whyne, Cari M.; Nam, Diane

    2014-01-01

    Background: Lithium, a treatment for bipolar disorder, is not clinically indicated for use in fracture management but has been reported to positively influence bone biology. It is hypothesized that lithium dosing for beneficial effects on bone health may be much lower than the dosing required for psychotropic benefits in patients with bipolar disorder. A preclinical study with a rodent fracture model was utilized to best define the lowest effective dose, best timing of treatment onset, and optimal treatment duration for the use of lithium as a new treatment in fracture care. Methods: A design-of-experiments approach was used to assess the parameters of dose, timing of treatment onset, and treatment duration. Closed femoral shaft fractures were generated and analyzed with use of destructive torsional mechanical testing and microcomputed tomography-based image analysis. Eleven different outcome measures were quantified, with maximum yield torque as the primary study outcome, to assess the quality of long-bone fracture-healing. Results: Fracture-healing was maximized with a lithium treatment combination of a low dose (twenty milligrams per kilogram of body weight per day), later onset of lithium treatment (seven days after fracture), and longer treatment duration (two weeks), with maximum yield torque displaying a 46% increase compared with nontreated and sham-treated controls (481.1 ± 104.0 N-mm compared with 329.9 ± 135.8 N-mm; p = 0.04). Design-of-experiments analysis determined the timing of treatment onset to be the most influential parameter for improving fracture-healing, with femora treated at a later onset (seven days after fracture) showing a significant (21%) increase in maximum yield torque compared with those treated at an earlier onset (three days after fracture) (p = 0.01). Conclusions: A later onset of lithium administration significantly improved femoral fracture-healing. Trends indicated that a lower dose and longer treatment duration also had a

  20. 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

  1. 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.

  2. [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.

  3. 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.

  4. Impaired Fracture Healing Caused by Deficiency of the Immunoreceptor Adaptor Protein DAP12.

    PubMed

    Kamimura, Masayuki; Mori, Yu; Sugahara-Tobinai, Akiko; Takai, Toshiyuki; Itoi, Eiji

    2015-01-01

    Osteoclasts play an important role in bone metabolism, but their exact role in fracture healing remains unclear. DAP12 is an immunoadaptor protein with associated immunoreceptors on myeloid lineage cells, including osteoclasts. Its deficiency causes osteopetrosis due to suppression of osteoclast development and activation. In this report, we assessed the impact of DAP12 on the fracture healing process using C57BL/6 (B6) and DAP12-/- mice. Healing was evaluated using radiography, micro-CT, histology, immunohistochemistry and real-time RT-PCR. Radiography showed lower callus volume and lower callus radiolucency in DAP12-/- mice during later stages. Micro-CT images and quantitative structural analysis indicated that DAP12-/- mice developed calluses of dense trabecular structures and experienced deteriorated cortical shell formation on the surface. Histologically, DAP12-/- mice showed less cartilaginous resorption and woven bone formation. In addition, prominent cortical shell formation was much less in DAP12-/- mice. Immunohistochemistry revealed lower invasion of F4/80 positive monocytes and macrophages into the fracture hematoma in DAP12-/- mice. The expression levels of Col1a1, Col2a1 and Col10a1 in DAP12-/- mice increased and subsequently became higher than those in B6 mice. There was a decrease in the gene expression of Tnf during the early stages in DAP12-/- mice. Our results indicate that DAP12 deficiency impairs fracture healing, suggesting a significant role of DAP12 in the initial inflammatory response, bone remodeling and regeneration. PMID:26030755

  5. 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.

  6. Micro-computed tomography assessment of the progression of fracture healing in mice.

    PubMed

    O'Neill, Kevin R; Stutz, Christopher M; Mignemi, Nicholas A; Burns, Michael C; Murry, Matthew R; Nyman, Jeffry S; Schoenecker, Jonathan G

    2012-06-01

    The mouse fracture model is ideal for research into the pathways of healing because of the availability of genetic and transgenic mice and the ability to create cell-specific genetic mutations. While biomechanical tests and histology are available to assess callus integrity and tissue differentiation, respectively, micro-computed tomography (μCT) analysis has increasingly been utilized in fracture studies because it is non-destructive and provides descriptions of the structural and compositional properties of the callus. However, the dynamic changes of μCT properties that occur during healing are not well defined. Thus, the purpose of this study was to determine which μCT properties change with the progression of fracture repair and converge to values similar to unfractured bone in the mouse femur fracture model. A unilateral femur fracture was performed in C57BL/6 mice and intramedullary fixation performed. Fractured and un-fractured contralateral specimens were harvested from groups of mice between 2 and 12 weeks post-fracture. Parameters describing callus based on μCT were obtained, including polar moment of inertia (J), bending moment of inertia (I), total volume (TV), tissue mineral density (TMD), total bone volume fraction (BV/TV), and volumetric bone mineral density (vBMD). For comparison, plain radiographs were used to measure the callus diameter (D) and area (A); and biomechanical properties were evaluated using either three-point bending or torsion. The μCT parameters J, I, TV, and TMD converged toward their respective values of the un-fractured femurs over time, although significant differences existed between the two sides at every time point evaluated (p<0.05). Radiograph measurement D changed with repair progression in similar manner to TV. In contrast, BV/TV and BMD increased and decreased over time with statistical differences between callus and un-fractured bone occurring sporadically. Similarly, none of the biomechanical properties were found

  7. Oxygen as a critical determinant of bone fracture healing-a multiscale model.

    PubMed

    Carlier, Aurélie; Geris, Liesbet; van Gastel, Nick; Carmeliet, Geert; Van Oosterwyck, Hans

    2015-01-21

    A timely restoration of the ruptured blood vessel network in order to deliver oxygen and nutrients to the fracture zone is crucial for successful bone healing. Indeed, oxygen plays a key role in the aerobic metabolism of cells, in the activity of a myriad of enzymes as well as in the regulation of several (angiogenic) genes. In this paper, a previously developed model of bone fracture healing is further improved with a detailed description of the influence of oxygen on various cellular processes that occur during bone fracture healing. Oxygen ranges of the cell-specific oxygen-dependent processes were established based on the state-of-the art experimental knowledge through a rigorous literature study. The newly developed oxygen model is compared with previously published experimental and in silico results. An extensive sensitivity analysis was also performed on the newly introduced oxygen thresholds, indicating the robustness of the oxygen model. Finally, the oxygen model was applied to the challenging clinical case of a critical sized defect (3mm) where it predicted the formation of a fracture non-union. Further model analyses showed that the harsh hypoxic conditions in the central region of the callus resulted in cell death and disrupted bone healing thereby indicating the importance of a timely vascularization for the successful healing of a large bone defect. In conclusion, this work demonstrates that the oxygen model is a powerful tool to further unravel the complex spatiotemporal interplay of oxygen delivery, diffusion and consumption with the several healing steps, each occurring at distinct, optimal oxygen tensions during the bone repair process. PMID:25452136

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

    PubMed Central

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

    2012-01-01

    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. PMID:23107765

  9. 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. PMID:25044211

  10. Milk thistle: a future potential anti-osteoporotic and fracture healing agent.

    PubMed

    Mohd Fozi, Nur Farhana; Mazlan, Mazliadiyana; Shuid, Ahmad Nazrun; Isa Naina, Mohamed

    2013-12-01

    Osteoporosis is a progressive disease of the skeleton characterised by bone fragility due to a reduction in bone mass and possibly to alteration in bone architecture that lead to a propensity to fracture with minimum trauma. Most osteoporotic fractures occur at locations rich in trabecular or cancellous bone and usually related to post menopausal women. Recently, silymarin received attention due to its alternative beneficial effect on bone formation. It is a mixture of flavonoids with powerful antioxidant properties. This review focuses on the use of milk thistle or silymarin for the treatment of osteoporosis that may be related to fracture bone. Silymarin shows potent antioxidant herb that may modulate multiple genes in favour of helping to build bone and prevent bone loss. In the mouse fracture healing model, silymarin supplementation improved tibial healing with elevated BMD and serum levels of ALP and osteocalcin. Silymarin also demonstrated clear estrogenic antiosteoporotic effects in bone structure. Silymarin appears to play a crucial role to prevent bone loss and might regulate osteogenesis and may be beneficial for fracture healing. If silymarin is considered for the use of post menopausal women, it may be used for the treatment of osteoporosis. It would be of great benefit to postmenopausal women to develop an oestrogen antagonist that is as potent and efficacious as oestrogen in preventing bone loss without the major side effect associated with HRT.

  11. 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

  12. Bone turnover markers for early detection of fracture healing disturbances: A review of the scientific literature.

    PubMed

    Sousa, Cristina P; Dias, Isabel R; Lopez-Peña, Mónica; Camassa, José A; Lourenço, Paulo J; Judas, Fernando M; Gomes, Manuela E; Reis, Rui L

    2015-01-01

    Imaging techniques are the standard method for assessment of fracture healing processes. However, these methods are perhaps not entirely reliable for early detection of complications, the most frequent of these being delayed union and non-union. A prompt diagnosis of such disorders could prevent prolonged patient distress and disability. Efforts should be directed towards the development of new technologies for improving accuracy in diagnosing complications following bone fractures. The variation in the levels of bone turnover markers (BTMs) have been assessed with regard to there ability to predict impaired fracture healing at an early stage, nevertheless the conclusions of some studies are not consensual. In this article the authors have revised the potential of BTMs as early predictors of prognosis in adult patients presenting traumatic bone fractures but who did not suffer from osteopenia or postmenopausal osteoporosis. The available information from the different studies performed in this field was systematized in order to highlight the most promising BTMs for the assessment of fracture healing outcome. PMID:25993365

  13. Increased Fracture Collapse after Intertrochanteric Fractures Treated by the Dynamic Hip Screw Adversely Affects Walking Ability but Not Survival

    PubMed Central

    Fang, Christian; Gudushauri, Paata; Wong, Tak-Man; Lau, Tak-Wing; Pun, Terence; Leung, Frankie

    2016-01-01

    In osteoporotic hip fractures, fracture collapse is deliberately allowed by commonly used implants to improve dynamic contact and healing. The muscle lever arm is, however, compromised by shortening. We evaluated a cohort of 361 patients with AO/OTA 31.A1 or 31.A2 intertrochanteric fracture treated by the dynamic hip screw (DHS) who had a minimal follow-up of 3 months and an average follow-up of 14.6 months and long term survival data. The amount of fracture collapse and shortening due to sliding of the DHS was determined at the latest follow-up and graded as minimal (<1 cm), moderate (1-2 cm), or severe (>2 cm). With increased severity of collapse, more patients were unable to maintain their premorbid walking function (minimal collapse = 34.2%, moderate = 33.3%, severe = 62.8%, and p = 0.028). Based on ordinal regression of risk factors, increased fracture collapse was significantly and independently related to increasing age (p = 0.037), female sex (p = 0.024), A2 fracture class (p = 0.010), increased operative duration (p = 0.011), poor reduction quality (p = 0.000), and suboptimal tip-apex distance of >25 mm (p = 0.050). Patients who had better outcome in terms of walking function were independently predicted by younger age (p = 0.036), higher MMSE marks (p = 0.000), higher MBI marks (p = 0.010), better premorbid walking status (p = 0.000), less fracture collapse (p = 0.011), and optimal lag screw position in centre-centre or centre-inferior position (p = 0.020). According to Kaplan-Meier analysis, fracture collapse had no association with mortality from 2.4 to 7.6 years after surgery. In conclusion, increased fracture collapse after fixation of geriatric intertrochanteric fractures adversely affected walking but not survival. PMID:26955637

  14. Comparison of effects of the bisphosphonate alendronate versus the RANKL inhibitor denosumab on murine fracture healing.

    PubMed

    Gerstenfeld, Louis C; Sacks, Daniel J; Pelis, Megan; Mason, Zachary D; Graves, Dana T; Barrero, Mauricio; Ominsky, Michael S; Kostenuik, Paul J; Morgan, Elise F; Einhorn, Thomas A

    2009-02-01

    The role of osteoclast-mediated resorption during fracture healing was assessed. The impact of two osteoclast inhibitors with different mechanisms of action, alendronate (ALN) and denosumab (DMAB), were examined during fracture healing. Male human RANKL knock-in mice that express a chimeric (human/murine) form of RANKL received unilateral transverse femur fractures. Mice were treated biweekly with ALN 0.1 mg/kg, DMAB 10 mg/kg, or PBS (control) 0.1 ml until death at 21 and 42 days after fracture. Treatment efficacy assessed by serum levels of TRACP 5b showed almost a complete elimination of TRACP 5b levels in the DMAB-treated animals but only approximately 25% reduction of serum levels in the ALN-treated mice. Mechanical testing showed that fractured femurs from both ALN and DMAB groups had significantly increased mechanical properties at day 42 compared with controls. muCT analysis showed that callus tissues from DMAB-treated mice had significantly greater percent bone volume and BMD than did both control and ALN-treated tissues at both 21 and 42 days, whereas ALN-treated bones only had greater percent bone volume and BMC than control at 42 days. Qualitative histological analysis showed that the 21-and 42-day ALN and DMAB groups had greater amounts of unresorbed cartilage or mineralized cartilage matrix compared with the controls, whereas unresorbed cartilage could still be seen in the DMAB groups at 42 days after fracture. Although ALN and DMAB delayed the removal of cartilage and the remodeling of the fracture callus, this did not diminish the mechanical integrity of the healing fractures in mice receiving these treatments. In contrast, strength and stiffness were enhanced in these treatment groups compared with control bones.

  15. Micro-computed tomography assessment of fracture healing: relationships among callus structure, composition, and mechanical function.

    PubMed

    Morgan, Elise F; Mason, Zachary D; Chien, Karen B; Pfeiffer, Anthony J; Barnes, George L; Einhorn, Thomas A; Gerstenfeld, Louis C

    2009-02-01

    Non-invasive characterization of fracture callus structure and composition may facilitate development of surrogate measures of the regain of mechanical function. As such, quantitative computed tomography- (CT-) based analyses of fracture calluses could enable more reliable clinical assessments of bone healing. Although previous studies have used CT to quantify and predict fracture healing, it is unclear which of the many CT-derived metrics of callus structure and composition are the most predictive of callus mechanical properties. The goal of this study was to identify the changes in fracture callus structure and composition that occur over time and that are most closely related to the regain of mechanical function. Micro-computed tomography (microCT) imaging and torsion testing were performed on murine fracture calluses (n=188) at multiple post-fracture timepoints and under different experimental conditions that alter fracture healing. Total callus volume (TV), mineralized callus volume (BV), callus mineralized volume fraction (BV/TV), bone mineral content (BMC), tissue mineral density (TMD), standard deviation of mineral density (sigma(TMD)), effective polar moment of inertia (J(eff)), torsional strength, and torsional rigidity were quantified. Multivariate statistical analyses, including multivariate analysis of variance, principal components analysis, and stepwise regression were used to identify differences in callus structure and composition among experimental groups and to determine which of the microCT outcome measures were the strongest predictors of mechanical properties. Although calluses varied greatly in the absolute and relative amounts of mineralized tissue (BV, BMC, and BV/TV), differences among timepoints were most strongly associated with changes in tissue mineral density. Torsional strength and rigidity were dependent on mineral density as well as the amount of mineralized tissue: TMD, BV, and sigma(TMD) explained 62% of the variation in

  16. Differential inhibition of fracture healing by non-selective and cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs.

    PubMed

    Gerstenfeld, Louis C; Thiede, Mark; Seibert, Karen; Mielke, Cindy; Phippard, Deborah; Svagr, Bohus; Cullinane, Dennis; Einhorn, Thomas A

    2003-07-01

    . Histological analysis at 21 days showed that the calluses in the ketorolac-treated group contained substantial amounts of residual cartilage while neither the control nor the parecoxib-treated animals showed comparable amounts of cartilage at this stage. These results demonstrate that ketorolac and parecoxib delay fracture healing in this model, but in this study daily administration of ketorolac, a non-selective COX inhibitor had a greater affect on this process. They further demonstrate that a COX-2 selective NSAID, such as parecoxib (valdecoxib), has only a small effect on delaying fracture healing even at doses that are known to fully inhibit prostaglandin production.

  17. Corroboration of mechanoregulatory algorithms for tissue differentiation during fracture healing: Comparison with in vivo results.

    PubMed

    Isaksson, Hanna; van Donkelaar, Corrinus C; Huiskes, Rik; Ito, Keita

    2006-05-01

    Several mechanoregulation algorithms proposed to control tissue differentiation during bone healing have been shown to accurately predict temporal and spatial tissue distributions during normal fracture healing. As these algorithms are different in nature and biophysical parameters, it raises the question of which reflects the actual mechanobiological processes the best. The aim of this study was to resolve this issue by corroborating the mechanoregulatory algorithms with more extensive in vivo bone healing data from animal experiments. A poroelastic three-dimensional finite element model of an ovine tibia with a 2.4 mm gap and external callus was used to simulate the course of tissue differentiation during fracture healing in an adaptive model. The mechanical conditions applied were similar to those used experimentally, with axial compression or torsional rotation as two distinct cases. Histological data at 4 and 8 weeks, and weekly radiographs, were used for comparison. By applying new mechanical conditions, torsional rotation, the predictions of the algorithms were distinguished successfully. In torsion, the algorithms regulated by strain and hydrostatic pressure failed to predict healing and bone formation as seen in experimental data. The algorithm regulated by deviatoric strain and fluid velocity predicted bridging and healing in torsion, as observed in vivo. The predictions of the algorithm regulated by deviatoric strain alone did not agree with in vivo data. None of the algorithms predicted patterns of healing entirely similar to those observed experimentally for both loading modes. However, patterns predicted by the algorithm based on deviatoric strain and fluid velocity was closest to experimental results. It was the only algorithm able to predict healing with torsional loading as seen in vivo.

  18. 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.

  19. Exogenous Parathyroid Hormone-Related Peptide Promotes Fracture Healing in Lepr(-/-) Mice.

    PubMed

    Liu, Anlong; Li, Yishan; Wang, Yinhe; Liu, Li; Shi, Hongfei; Qiu, Yong

    2015-12-01

    Diabetic osteoporosis continues to surge worldwide, increasing the risk of fracture. We have previously demonstrated that haploinsufficiency of endogenous parathyroid hormone-related peptide (PTHrP) impairs fracture healing. However, whether an exogenous supply of PTHrP can repair bone damage and accelerate fracture healing remains unclear. This study aimed to assess the efficacy and safety of PTHrP in healing fractures. Standardized mid-diaphyseal femur fractures were generated in 12-week-old wild-type and leptin receptor null Lepr(-/-) mice. After administration of PTHrP for 2 weeks, callus tissue properties were analyzed by radiography, micro-computed tomography, histology, histochemistry, immunohistochemistry, and molecular biology techniques. At 2 weeks post-fracture, cartilaginous callus areas were reduced, while total callus and bony callus areas were increased in PTHrP-treated Lepr(-/-) animals and control wild-type mice, compared with vehicle-treated Lepr(-/-) mice. The following parameters were enhanced both in Lepr(-/-) mice after treatment with PTHrP and vehicle-treated wild-type animals, compared with vehicle-treated Lepr(-/-) mice: osteoblast numbers; tissue alkaline phosphatase (ALP) and Type I collagen immunopositive areas; mRNA levels of ALP, Type I collagen, osteoprotegerin, and receptor activator for nuclear factor-κ B ligand; protein levels of Runt-related transcription factor 2 and insulin-like growth factor-1; and the number and surface of osteoclasts. In conclusion, exogenous PTHrP by subcutaneous injection promotes fracture repair in Lepr(-/-) mice by increasing callus formation and accelerating cell transformation: upregulated osteoblastic gene and protein expression, increased endochondral bone formation, osteoblastic bone formation, and osteoclastic bone resorption. However, complete repair was not obtained in PTHrP-treated Lepr(-/-) mice as in control wild-type animals. PMID:26314884

  20. Bioinformatics and Microarray Analysis of miRNAs in Aged Female Mice Model Implied New Molecular Mechanisms for Impaired Fracture Healing

    PubMed Central

    He, Bing; Zhang, Zong-Kang; Liu, Jin; He, Yi-Xin; Tang, Tao; Li, Jie; Guo, Bao-Sheng; Lu, Ai-Ping; Zhang, Bao-Ting; Zhang, Ge

    2016-01-01

    Impaired fracture healing in aged females is still a challenge in clinics. MicroRNAs (miRNAs) play important roles in fracture healing. This study aims to identify the miRNAs that potentially contribute to the impaired fracture healing in aged females. Transverse femoral shaft fractures were created in adult and aged female mice. At post-fracture 0-, 2- and 4-week, the fracture sites were scanned by micro computed tomography to confirm that the fracture healing was impaired in aged female mice and the fracture calluses were collected for miRNA microarray analysis. A total of 53 significantly differentially expressed miRNAs and 5438 miRNA-target gene interactions involved in bone fracture healing were identified. A novel scoring system was designed to analyze the miRNA contribution to impaired fracture healing (RCIFH). Using this method, 11 novel miRNAs were identified to impair fracture healing at 2- or 4-week post-fracture. Thereafter, function analysis of target genes was performed for miRNAs with high RCIFH values. The results showed that high RCIFH miRNAs in aged female mice might impair fracture healing not only by down-regulating angiogenesis-, chondrogenesis-, and osteogenesis-related pathways, but also by up-regulating osteoclastogenesis-related pathway, which implied the essential roles of these high RCIFH miRNAs in impaired fracture healing in aged females, and might promote the discovery of novel therapeutic strategies. PMID:27527150

  1. 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.

  2. 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

  3. Shock wave therapy as a treatment of nonunions, avascular necrosis, and delayed healing of stress fractures.

    PubMed

    Furia, John P; Rompe, Jan D; Cacchio, Angelo; Maffulli, Nicola

    2010-12-01

    Shock wave therapy (SWT) stimulates angiogenesis and osteogenesis. SWT is commonly used to treat soft tissue musculoskeletal conditions such as fasciopathies and tendinopathies. Recent basic science and clinical data suggest that SWT can also be used to treat disorders of bone. Nonunions, avascular necrosis, and delayed healing of stress fractures have all been successfully treated with SWT. Success rates with SWT are equal to those with standard surgical treatment, but SWT has the advantage of decreased morbidity. The procedure is safe, well tolerated, yields few complications, and, typically, can be performed on an outpatient basis. SWT is a viable noninvasive alternative to stimulate healing of bone.

  4. Amifostine Protects Vascularity and Improves Unions in a Model of Irradiated Mandibular Fracture Healing

    PubMed Central

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

    2013-01-01

    Background Pathologic fractures after irradiation (XRT) can be a devastating problem for cancer patients as XRT has a pernicious effect on bone healing in a large part due to impairment of vascularity. Our aim is to ascertain whether Amifostine (AMF), a radio-protective drug, will preserve the vascularity of the irradiated mandible, thereby improving bony healing and unions after exposure to a human equivalent dose of radiation (HEDR) in our murine model of mandibular fracture repair. Methods Rats were randomized into: Fx (n=9), XRT/Fx (n=5) and AMF/XRT/Fx (n=7). XRT/Fx and AMF/XRT/Fx underwent HEDR directed at the left hemimandible. AMF/XRT/Fx received AMF concomitantly with HEDR. All animals underwent unilateral left-mandibular osteotomy with external fixation set to a 2.1mm fracture gap. Fracture healing was allowed for 40 days prior to perfusion with Microfil. Vascular radiomorphometrics were quantified with micro-computed tomography. Results We observed a 100% rate of bony union in the non-irradiated Fx compared to 25% in XRT/Fx. Union rate in AMF/XRT/Fx more than doubled to 57%. We also saw substantial increase in Vessel Number (123%,p<0.05) and a corresponding decrease in Vessel Separation (55.5%,p<0.05) in AMF/XRT/Fx versus XRT/Fx and no differences between Fx and AMF/XRT/Fx. Conclusions We report that AMF prophylaxis maintains vascularity at levels seen in non-irradiated Fx specimens, correlating with a significant increase in bony unions after HEDR. Our results set the stage for exploration of this targeted therapy alone, and in combination with other treatments, to mitigate the harmful effects of XRT on fracture repair and bone healing in the clinical setting. PMID:24281582

  5. 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.

  6. Assessment of the healing process in distal radius fractures by high resolution peripheral quantitative computed tomography.

    PubMed

    de Jong, Joost J A; Willems, Paul C; Arts, Jacobus J; Bours, Sandrine G P; Brink, Peter R G; van Geel, Tineke A C M; Poeze, Martijn; Geusens, Piet P; van Rietbergen, Bert; van den Bergh, Joop P W

    2014-07-01

    In clinical practice, fracture healing is evaluated by clinical judgment in combination with conventional radiography. Due to limited resolution, radiographs don't provide detailed information regarding the bone micro-architecture and bone strength. Recently, assessment of in vivo bone density, architectural and mechanical properties at the microscale became possible using high resolution peripheral quantitative computed tomography (HR-pQCT) in combination with micro finite element analysis (μFEA). So far, such techniques have been used mainly to study intact bone. The aim of this study was to explore whether these techniques can also be used to assess changes in bone density, micro-architecture and bone stiffness during fracture healing. Therefore, the fracture region in eighteen women, aged 50 years or older with a stable distal radius fracture, was scanned using HR-pQCT at 1-2 (baseline), 3-4, 6-8 and 12weeks post-fracture. At 1-2 and 12 weeks post-fracture the distal radius at the contra-lateral side was also scanned as control. Standard bone density, micro-architectural and geometric parameters were calculated and bone stiffness in compression, torsion and bending was assessed using μFEA. A linear mixed effect model with time post-fracture as fixed effect was used to detect significant (p-value ≤0.05) changes from baseline. Wrist pain and function were scored using the patient-rated wrist evaluation (PRWE) questionnaire. Correlations between the bone parameters and the PRWE score were calculated by Spearman's correlation coefficient. At the fracture site, total and trabecular bone density increased by 11% and 20%, respectively, at 6-8 weeks, whereas cortical density was decreased by 4%. Trabecular thickness increased by 23-31% at 6-8 and 12 weeks and the intertrabecular area became blurred, indicating intertrabecular bone formation. Compared to baseline, calculated bone stiffness in compression, torsion and bending was increased by 31% after 12 weeks. A

  7. 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. PMID:26840708

  8. 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

  9. 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.

  10. Impaired Fracture Healing Caused by Deficiency of the Immunoreceptor Adaptor Protein DAP12

    PubMed Central

    Kamimura, Masayuki; Mori, Yu; Sugahara-Tobinai, Akiko; Takai, Toshiyuki; Itoi, Eiji

    2015-01-01

    Osteoclasts play an important role in bone metabolism, but their exact role in fracture healing remains unclear. DAP12 is an immunoadaptor protein with associated immunoreceptors on myeloid lineage cells, including osteoclasts. Its deficiency causes osteopetrosis due to suppression of osteoclast development and activation. In this report, we assessed the impact of DAP12 on the fracture healing process using C57BL/6 (B6) and DAP12–/– mice. Healing was evaluated using radiography, micro-CT, histology, immunohistochemistry and real-time RT-PCR. Radiography showed lower callus volume and lower callus radiolucency in DAP12–/– mice during later stages. Micro-CT images and quantitative structural analysis indicated that DAP12–/– mice developed calluses of dense trabecular structures and experienced deteriorated cortical shell formation on the surface. Histologically, DAP12–/– mice showed less cartilaginous resorption and woven bone formation. In addition, prominent cortical shell formation was much less in DAP12–/– mice. Immunohistochemistry revealed lower invasion of F4/80 positive monocytes and macrophages into the fracture hematoma in DAP12–/– mice. The expression levels of Col1a1, Col2a1 and Col10a1 in DAP12–/– mice increased and subsequently became higher than those in B6 mice. There was a decrease in the gene expression of Tnf during the early stages in DAP12–/– mice. Our results indicate that DAP12 deficiency impairs fracture healing, suggesting a significant role of DAP12 in the initial inflammatory response, bone remodeling and regeneration. PMID:26030755

  11. 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.

  12. Fracture Healing Is Delayed in Immunodeficient NOD/scid‑IL2Rγcnull Mice

    PubMed Central

    Recknagel, Stefan; Erbacher, Annika; Müller, Ingo; Schrezenmeier, Hubert; Ehrnthaller, Christian; Gebhard, Florian; Ignatius, Anita

    2016-01-01

    Following bone fracture, the repair process starts with an inflammatory reaction at the fracture site. Fracture healing is disturbed when the initial inflammation is increased or prolonged, whereby, a balanced inflammatory response is anticipated to be crucial for fracture healing, because it may induce down-stream responses leading to tissue repair. However, the impact of the immune response on fracture healing remains poorly understood. Here, we investigated bone healing in NOD/scid-IL2Rγcnull mice, which exhibit severe defects in innate and adaptive immunity, by biomechanical testing, histomorphometry and micro-computed tomography. We demonstrated that NOD/scid-IL2Rγcnull mice exhibited normal skeletal anatomy and a mild bone phenotype with a slightly reduced bone mass in the trabecular compartment in comparison to immunocompetent Balb/c mice. Fracture healing was impaired in immunodeficient NOD/scid-IL2Rγcnull mice. Callus bone content was unaffected during the early healing stage, whereas it was significantly reduced during the later healing period. Concomitantly, the amount of cartilage was significantly increased, indicating delayed endochondral ossification, most likely due to the decreased osteoclast activity observed in cells isolated from NOD/scid-IL2Rγcnull mice. Our results suggest that—under aseptic, uncomplicated conditions—the immediate immune response after fracture is non-essential for the initiation of bone formation. However, an intact immune system in general is important for successful bone healing, because endochondral ossification is delayed in immunodeficient NOD/scid-IL2Rγcnull mice. PMID:26849055

  13. 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.

  14. 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

  15. Fracture healing after reamed and unreamed intramedullary nailing in sheep tibia.

    PubMed

    Högel, F; Schlegel, U; Südkamp, N; Müller, C

    2011-07-01

    Intramedullary nailing is a well-established method for stabilisation of long-bone shaft fractures. It is still a controversy as to whether the procedure should be done by an unreamed or reamed technique. In the present animal study, 24 sheep were treated with intramedullary nailing. Midshaft fractures (Arbeitsgemeinschaft für Osteosynthese (AO) type 42-A2/3) were created. Eight sheep were treated with an unreamed nailing technique (UN), a further eight sheep underwent tibia nailing by the reamed technique using the conventional AO reaming system (RC) and in a further eight sheep, reamed nailing was performed using an experimental reaming system (RE). Intra-operatively, the intramedullary pressure was measured and, during a healing time of 10 weeks, the growth of callus formation was labelled with fluorescence markers after 4 and 6 weeks. After 10 weeks, the animals were euthanised and the quality of fracture healing was determined by recording stiffness in torsion, antero-posterior and mediolateral bending and the load at yield. In addition, the callus formation at the fracture zone was evaluated by fluorescence microscopy and macroradiographs. The results showed a decrease of intramedullary pressure when reamed nailing was performed with the RE (72.5 mmHg) system compared with the conventional AO reaming system (227 mmHg). Mechanical testing did not reveal any significant differences either for torsional or bending stiffness or for load at yield for any of the three procedures. Histological evaluation showed a similar callus formation for the UN group and the RE group. Callus formation in the UN (65 mm(2)) and RE (63 mm(2)) groups showed a higher increase during the first 6 weeks than those treated with the conventional AO reaming system (27 mm(2)). This means that, especially during the first weeks of fracture healing, damage to the bone by the reaming process can be reduced by reaming with a reaming device with lowered cutting flutes and smaller drive

  16. Mechanics and mechano-biology of fracture healing in normal and osteoporotic bone.

    PubMed

    Augat, Peter; Simon, Ulrich; Liedert, Astrid; Claes, Lutz

    2005-03-01

    Fracture repair, which aims at regaining the functional competence of a bone, is a complex and multifactorial process. For the success of fracture repair biology and mechanics are of immense importance. The biological and mechanical environments must be compatible with the processes of cell and tissue proliferation and differentiation. The biological environment is characterized by the vascular supply and by many biochemical components, the biochemical milieu. A good vascular supply is a prerequisite for the initiation of the fracture repair process. The biochemical milieu involves complex interactions among local and systemic regulatory factors such as growth factors or cytokines. The mechanical environment is determined by the local stress and strain within the fracture. However, the local stress and strain is not accessible, and the mechanical environment, therefore, is described by global mechanical factors, e.g., gap size or interfragmentary movement. The relationship between local stress and strain and the global mechanical factors can be obtained by numerical models (Finite Element Model). Moreover, there is considerable interaction between biological factors and mechanical factors, creating a biomechanical environment for the fracture healing process. The biomechanical environment is characterized by osteoblasts and osteocytes that sense the mechanical signal and express biological markers, which effect the repair process. This review will focus on the effects of biomechanical factors on fracture repair as well as the effects of age and osteoporosis.

  17. Validation of a standardised gait score to predict the healing of tibial fractures.

    PubMed

    Macri, F; Marques, L F; Backer, R C; Santos, M J; Belangero, W D

    2012-04-01

    There is no absolute method of evaluating healing of a fracture of the tibial shaft. In this study we sought to validate a new clinical method based on the systematic observation of gait, first by assessing the degree of agreement between three independent observers regarding the gait score for a given patient, and secondly by determining how such a score might predict healing of a fracture. We used a method of evaluating gait to assess 33 patients (29 men and four women, with a mean age of 29 years (15 to 62)) who had sustained an isolated fracture of the tibial shaft and had been treated with a locked intramedullary nail. There were 15 closed and 18 open fractures (three Gustilo and Anderson grade I, seven grade II, seven grade IIIA and one grade IIIB). Assessment was carried out three and six months post-operatively using videos taken with a digital camera. Gait was graded on a scale ranging from 1 (extreme difficulty) to 4 (normal gait). Bivariate analysis included analysis of variance to determine whether the gait score statistically correlated with previously validated and standardised scores of clinical status and radiological evidence of union. An association was found between the pattern of gait and all the other variables. Improvement in gait was associated with the absence of pain on weight-bearing, reduced tenderness over the fracture, a higher Radiographic Union Scale in Tibial Fractures score, and improved functional status, measured using the Brazilian version of the Short Musculoskeletal Function Assessment questionnaire (all p < 0.001). Although further study is needed, the analysis of gait in this way may prove to be a useful clinical tool. PMID:22434473

  18. The contributions of dietary protein and mineral to the healing of experimental fractures. A biomechanical study.

    PubMed

    Einhorn, T A; Bonnarens, F; Burstein, A H

    1986-12-01

    We examined the contributions of dietary protein and mineral to fracture-healing by assessing the mechanical properties of fracture callus in rats that were fed a diet that was deficient in or enriched by these nutrients. In order to isolate the effects of diet on fracture-healing, we developed a method for producing a standard closed femoral fracture with minimum-soft-tissue injury. Three groups of animals were studied. Group I was a control group, in which the rats did not undergo an operation. The rats in Group II underwent intramedullary pinning of the right femur, but no fracture was created. The rats in Group III underwent pinning identical to that used for Group II, after which a closed, transverse femoral fracture was produced. Immediately after surgery, the animals in each group were subdivided into five diet-treatment subgroups. Subgroup A received a regular diet; Subgroup B received a protein-free diet; and Subgroup C received a mineral-free diet that was lacking in calcium, phosphorus, and vitamin D. Subgroup D received a protein-supplemented diet that was composed of three times the calculated requirement of protein, and Subgroup E received a mineral-supplemented diet that was composed of three times the calculated requirements of calcium and phosphorus as well as a therapeutic dose of vitamin D, equivalent to that used in the treatment of osteomalacia. At the end of five weeks, the animals were killed and the right femur of each one was subjected to torsion-testing to failure.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Experimental study of effect of stress-relaxation bone plate on fracture healing.

    PubMed

    Zhang, Xianlong; Zhang, Wei; Dai, Kerong

    2000-11-15

    OBJECTIVE: To study the change of the stress shi elding rate of stress-relaxation plate in vivo and its influence on fracture he aling. METHODS: The diaphyses of bilateral tibias in 70 New Zealand ra bbits were osteotomized and fixed with stress-relaxation plates (SRP, the SRP g roup) and rigid plates (RP, the RP group), respectively. The fracture healing pr ocess in these 2 groups was investigated by radiography, light and polarized l ight microscopy and biomechanical test at 2 to 48 weeks postoperatively. RESULTS: Early after fixation the stress shielding rate was abo ut 70% in both groups. While in the SRP group the stress shielding rate decrease d gradually as time passed, which was significantly lower than that of the RP gr oup (P<0.05) by the end of the 8th postoperative week, and stabilized at the level of about 27% at 36-48 weeks after fixation. Abund ant external callus associated with the formation of cartilaginous callus could be observed in the SRP group at 2-4 weeks postoperatively. The transformation o f the callus into the lamellar bone began at 8-12 weeks, the collagen gradually arranged in order, and the mechanical nature of the united bone was gradually s trengthened, too. In the RP group, the external callus was scarce at the early s tage of fracture healing, and the callus remodeling at the late stage of fractur e healing was dominated by bone absorption. The ultimate bending strength (UBS) was only 57.95% of that of the normal by 48 weeks. CONCLUSIONS: The decrease of the stress shielding rate of SRP i n vivo was well interrelated with the time of fixation. The application of SRP c ould promote the callus formation and bone reconstruction thus to favor the reco very of the mechanical strength of the united bone. PMID:11874675

  20. Extracorporeal shockwave therapy (ESWT) ameliorates healing of tibial fracture non-union unresponsive to conventional therapy.

    PubMed

    Haffner, Nicolas; Antonic, Vlado; Smolen, Daniel; Slezak, Paul; Schaden, Wolfgang; Mittermayr, Rainer; Stojadinovic, Alexander

    2016-07-01

    Tibial non-unions are common cause of demanding revision surgeries and are associated with a significant impact on patients' quality of life and health care costs. Extracorporeal shockwave therapy (ESWT) has been shown to improve osseous healing in vitro and in vivo. The main objective of present study was to evaluate the efficacy of ESWT in healing of tibial non-unions unresponsive to previous surgical and non-surgical measures. A retrospective multivariant analysis of a prospective open, single-centre, clinical trial of tibia non-union was conducted. 56 patients with 58 eligible fractures who met the FDA criteria were included. All patients received 3000-4000 impulses of electrohydraulic shockwaves at an energy flux density of 0.4mJ/mm(2) (-6dB). On average patients underwent 1.9 times (±1.3SD) surgical interventions prior to ESWT displaying the rather negatively selected cohort and its limited therapy responsiveness. In 88.5% of patients receiving ESWT complete bone healing was observed after six months irrespective of underlying pathology. The multivariant analysis showed that time of application is important for therapy success. Patients achieving healing received ESWT earlier: mean number of days between last surgical intervention and ESWT (healed - 355.1 days±167.4SD vs. not healed - 836.7 days±383.0SD; p<0.0001). ESWT proved to be a safe, effective and non-invasive treatment modality in tibial non-unions recalcitrant to standard therapies. The procedure is well tolerated, time-saving, lacking side effects, with potential to significantly decrease health care costs. Thus, in our view, ESWT should be considered the treatment of first choice in established tibial non-unions.

  1. Extracorporeal shockwave therapy (ESWT) ameliorates healing of tibial fracture non-union unresponsive to conventional therapy.

    PubMed

    Haffner, Nicolas; Antonic, Vlado; Smolen, Daniel; Slezak, Paul; Schaden, Wolfgang; Mittermayr, Rainer; Stojadinovic, Alexander

    2016-07-01

    Tibial non-unions are common cause of demanding revision surgeries and are associated with a significant impact on patients' quality of life and health care costs. Extracorporeal shockwave therapy (ESWT) has been shown to improve osseous healing in vitro and in vivo. The main objective of present study was to evaluate the efficacy of ESWT in healing of tibial non-unions unresponsive to previous surgical and non-surgical measures. A retrospective multivariant analysis of a prospective open, single-centre, clinical trial of tibia non-union was conducted. 56 patients with 58 eligible fractures who met the FDA criteria were included. All patients received 3000-4000 impulses of electrohydraulic shockwaves at an energy flux density of 0.4mJ/mm(2) (-6dB). On average patients underwent 1.9 times (±1.3SD) surgical interventions prior to ESWT displaying the rather negatively selected cohort and its limited therapy responsiveness. In 88.5% of patients receiving ESWT complete bone healing was observed after six months irrespective of underlying pathology. The multivariant analysis showed that time of application is important for therapy success. Patients achieving healing received ESWT earlier: mean number of days between last surgical intervention and ESWT (healed - 355.1 days±167.4SD vs. not healed - 836.7 days±383.0SD; p<0.0001). ESWT proved to be a safe, effective and non-invasive treatment modality in tibial non-unions recalcitrant to standard therapies. The procedure is well tolerated, time-saving, lacking side effects, with potential to significantly decrease health care costs. Thus, in our view, ESWT should be considered the treatment of first choice in established tibial non-unions. PMID:27158008

  2. 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.

  3. 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. PMID:24239510

  4. 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

  5. A biomechanical comparison of the effects of constant and cyclic compression on fracture healing in rabbit long bones.

    PubMed

    Panjabi, M M; White, A A; Wolf, J W

    1979-12-01

    In a biomechanical study, the strength of healing experimental fractures in rabbit tibias was compared for two different healing environments. During the healing period large constant compression was applied to one leg, while the other leg was subjected to cyclic compression forces. Rabbits were sacrificed at 3, 4, 5, 6, and 8 weeks after the operation. The healing bones were tested in a dynamic torsion testing machine. Results indicate that on an average basis the cyclic compression treated bones exhibited higher torque and energy absorption to failure, but lower stiffness as compared with the constant compression treated bones, during the 30 to 50 days' healing period. These differences were statistically significant. Additionally, it was estimated that a 27 per cent saving in healing time may be realized for a bone treated with cyclic as compared with constant compression.

  6. An external fixation method and device to study fracture healing in rats.

    PubMed

    Mark, Hans; Bergholm, Jan; Nilsson, Anders; Rydevik, Björn; Strömberg, Lennart

    2003-08-01

    We wished to establish a reproducible model for fracture fixation to be used in fracture healing research and therefore developed an external fixation construct and surgical procedure adapted to Sprague-Dawley rats. We evaluated the mechanical properties of the construct in brass rods and rat bone, in an Instron test machine with axial and transverse loading, and the in vivo performance. We found that the mechanical properties of the construct in brass rods were predictable and could be repeated in rat femora. In all tests, the axial load was about 10 times the transverse for the same degree of deformation. The stiffness among fixators was uniform. 1 mm pins caused about 50% less stiffness than 1.2 mm pins in axial loading of rat bone (p < 0.001) and brass rods (p < 0.001) as well as in transverse loading of brass rods (p < 0.001). Loosening of 1 or 2 screws that lock the pins to the fixator reduced stiffness by about 50% in axial loading of rat bone (p = 0.009) and brass rods (p = 0.05). A change in the distance between the bone surface and the fixator was linearly related to the stiffness in axial loading of rat bone (p < 0.001) and brass rods (p < 0.001) and in transverse loading of brass rods (p < 0.001). If the bone ends touched each other, the axial stiffness of the construct increased almost 10 times (265 N/mm), as compared to a fracture gap size of 2 mm (31 N/mm). In vivo experiments had a complication rate of less than 10% when we used 1.2 mm pins, 6 mm offset and rats weighing 350-450 g. Our method and device for experimental external fixation of rat femora are reliable and the findings are reproducible. These can be used in bone repair and fracture healing research. PMID:14521302

  7. Diabetes reduces mesenchymal stem cells in fracture healing through a TNFα-mediated mechanism

    PubMed Central

    Tian, Chen; Alblowi, Jazia; Kayal, Rayyan A.; Einhorn, Thomas A.; Gerstenfeld, Louis C.; Pignolo, Robert J.; Graves, Dana T.

    2015-01-01

    Aims/hypothesis Diabetes interferes with bone formation and impairs fracture healing, an important complication in humans and animal models. The aim of this study was to examine the impact of diabetes on mesenchymal stem cells (MSCs) during fracture repair. Methods Fracture of the long bones was induced in a streptozotocin-induced type 1 diabetic mouse model with or without insulin or a specific TNFα inhibitor, pegsunercept. MSCs were detected with cluster designation-271 (also known as p75 neurotrophin receptor) or stem cell antigen-1 (Sca-1) antibodies in areas of new endochondral bone formation in the calluses. MSC apoptosis was measured by TUNEL assay and proliferation was measured by Ki67 antibody. In vitro apoptosis and proliferation were examined in C3H10T1/2 and human-bone-marrow-derived MSCs following transfection with FOXO1 small interfering (si)RNA. Results Diabetes significantly increased TNFα levels and reduced MSC numbers in new bone area. MSC numbers were restored to normal levels with insulin or pegsunercept treatment. Inhibition of TNFα significantly reduced MSC loss by increasing MSC proliferation and decreasing MSC apoptosis in diabetic animals, but had no effect on MSCs in normoglycaemic animals. In vitro experiments established that TNFα alone was sufficient to induce apoptosis and inhibit proliferation of MSCs. Furthermore, silencing forkhead box protein O1 (FOXO1) prevented TNFα-induced MSC apoptosis and reduced proliferation by regulating apoptotic and cell cycle genes. Conclusions/interpretation Diabetes-enhanced TNFα significantly reduced MSC numbers in new bone areas during fracture healing. Mechanistically, diabetes-enhanced TNFα reduced MSC proliferation and increased MSC apoptosis. Reducing the activity of TNFα in vivo may help to preserve endogenous MSCs and maximise regenerative potential in diabetic patients. PMID:25563724

  8. Healing.

    PubMed

    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

  9. [Fracture healing after intramedullary nailing of simple tibial shaft fractures. A clinical comparison of reamed and unreamed procedures].

    PubMed

    Ruchholtz, S; Nast-Kolb, D; Betz, A; Schweiberer, L

    1995-07-01

    From January 1990 to June 1993, 56 patients with simple tibial shaft fractures were treated in the Surgical Department of the University/Municipal Hospital in Munich by primary intramedullary nailing, and 44 of these patients were followed up. The results in 17 who underwent unreamed intramedullary nailing (UTN) were compared with those in 27 in whom reamed procedures (RTN) were applied. There was no difference between the two groups in age, fracture type and localization. Soft tissue trauma prevailed, with 35% I degrees open fractures in the UTN group (RTN group, 3%). UTN patients were operated on an average of 45 h after trauma, and RTN patients, 5 days after trauma. Both groups showed about the same proportion of good and very good results (criteria of Johner and Wruhs), with 83% in the UTN group and 84% in the RTN group. The rate of complications was the same in both groups (11%), and we did not find any kind of infection. Two complications requiring revisions (nonunion, perforation of the nail) after UTN stress the importance of two-dimensional barring in the main fragments (especially when close to the metaphysis) and of reduced weight-bearing for 6 weeks after the operation. The slightly greater intramedullar instability after UTN did not cause a higher rate of nonunions or of fracture healing in a wrong position than RTN. The X-ray findings showed beginning osseous reunion after 13 weeks in the UTN group. This corresponds to earlier painless full weight-bearing after an average of 9.7 weeks, as against 12 weeks in the RTN group.

  10. 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.

  11. EXOGEN ultrasound bone healing system for long bone fractures with non-union or delayed healing: a NICE medical technology guidance.

    PubMed

    Higgins, Ailish; Glover, Matthew; Yang, Yaling; Bayliss, Susan; Meads, Catherine; Lord, Joanne

    2014-10-01

    A routine part of the process for developing National Institute for Health and Care Excellence (NICE) medical technologies guidance is a submission of clinical and economic evidence by the technology manufacturer. The Birmingham and Brunel Consortium External Assessment Centre (EAC; a consortium of the University of Birmingham and Brunel University) independently appraised the submission on the EXOGEN bone healing system for long bone fractures with non-union or delayed healing. This article is an overview of the original evidence submitted, the EAC's findings, and the final NICE guidance issued.

  12. Expression of Sulf1 and Sulf2 in cartilage, bone and endochondral fracture healing.

    PubMed

    Zaman, G; Staines, K A; Farquharson, C; Newton, P T; Dudhia, J; Chenu, C; Pitsillides, A A; Dhoot, G K

    2016-01-01

    SULF1/SULF2 enzymes regulate cell signalling that impacts the growth and differentiation of many tissues. To determine their possible role in cartilage and bone growth or repair, their expression was examined during development and bone fracture healing using RT-PCR and immunochemical analyses. Examination of epiphyseal growth plates revealed differential, inverse patterns of SULF1 and SULF2 expressions, with the former enriched in quiescent and the latter in hypertrophic chondrocyte zones. Markedly higher levels of both SULFs, however, were expressed in osteoblasts actively forming bone when compared with proliferating pre-osteoblasts in the periosteum or the entombed osteocytes which express the lowest levels. The increased expression of Sulf1 and Sulf2 in differentiating osteoblasts was further confirmed by RT-PCR analysis of mRNA levels in rat calvarial osteoblast cultures. SULF1 and SULF2 were expressed in most foetal articular chondrocytes but down-regulated in a larger subset of cells in the post-natal articular cartilage. Unlike adult articular chondrocytes, SULF1/SULF2 expression varied markedly in post-natal hypertrophic chondrocytes in the growth plate, with very high SULF2 expression compared with SULF1 apparent during neonatal growth in both primary and secondary centres of ossification. Similarly, hypertrophic chondrocytes expressed greatly higher levels of SULF2 but not SULF1 during bone fracture healing. SULF2 expression unlike SULF1 also spread to the calcifying matrix around the hypertrophic chondrocytes indicating its possible ligand inhibiting role through HSPG desulphation. Higher levels of SULF2 in both developing and healing bone closely correlated with parallel increases in hedgehog signalling analysed by ptc1 receptor expression. PMID:26464246

  13. The axolotl limb: a model for bone development, regeneration and fracture healing.

    PubMed

    Hutchison, Cara; Pilote, Mireille; Roy, Stéphane

    2007-01-01

    Among vertebrates, urodele amphibians (e.g., axolotls) have the unique ability to perfectly regenerate complex body parts after amputation. The limb has been the most widely studied due to the presence of three defined axes and its ease of manipulation. Hence, the limb has been chosen as a model to study the process of skeletogenesis during axolotl development, regeneration and to analyze this animal's ability to heal bone fractures. Extensive studies have allowed researchers to gain some knowledge of the mechanisms controlling growth and pattern formation in regenerating and developing limbs, offering an insight into how vertebrates are able to regenerate tissues. In this study, we report the cloning and characterization of two axolotl genes; Cbfa-1, a transcription factor that controls the remodeling of cartilage into bone and PTHrP, known for its involvement in the differentiation and maturation of chondrocytes. Whole-mount in situ hybridization and immunohistochemistry results show that Cbfa-1, PTHrP and type II collagen are expressed during limb development and regeneration. These genes are expressed during specific stages of limb development and regeneration which are consistent with the appearance of skeletal elements. The expression pattern for Cbfa-1 in late limb development was similar to the expression pattern found in the late stages of limb regeneration (i.e. re-development phase) and it did not overlap with the expression of type II collagen. It has been reported that the molecular mechanisms involved in the re-development phase of limb regeneration are a recapitulation of those used in developing limbs; therefore the detection of Cbfa-1 expression during regeneration supports this assertion. Conversely, PTHrP expression pattern was different during limb development and regeneration, by its intensity and by the localization of the signal. Finally, despite its unsurpassed abilities to regenerate, we tested whether the axolotl was able to regenerate non

  14. Fracture-induced mechanophore activation and solvent healing in poly(methyl methacrylate)

    NASA Astrophysics Data System (ADS)

    Celestine, Asha-Dee N.

    of the crack tip. Control specimens in which the mechanophore is absent or tethered in positions in which no mechanochemical activation is expected are also tested and exhibit no change in color or fluorescence intensity with crack propagation. The relationship between fracture-induced mechanophore activation in rubber toughened SP-PMMA and the strain and stress ahead of the propagating crack is also studied. SP activation is again detected and quantified by in situ fluorescence imaging. Digital Image Correlation (DIC) is used to measure the strain ahead of the crack tip. The corresponding stress is generated through the use of the Hutchinson-Rice-Rosengren (HRR) singularity field equations. Mechanophore activation ahead of the crack tip is shown to follow a power law distribution that is closely aligned with strain. The potential of SP as a damage sensor is explored further by incorporating the spiropyran into the core of rubber nanoparticles. SP-linked rubber nanoparticles are synthesized using a seeded emulsion polymerization process and incorporated into cross-linked PMMA at a concentration of 5 wt%. Cylindrical specimens are torsion tested and the activation of the SP within the nanoparticles is monitored via full field fluorescence imaging. SP activation within the core is shown to increase with shear strain. Autonomous damage repair in PMMA is also investigated. The first demonstration of fully autonomous self-healing in PMMA is achieved through the use of solvent microcapsules. Solvent microcapsules with a PMMA-anisole liquid core are prepared and embedded within a linear PMMA matrix. Specimens of the microcapsule-loaded material are then fabricated for Double Cleavage Drilled Compression (DCDC) fracture testing. The DCDC specimens, containing increasing concentrations of solvent microcapsules, are tested and then allowed to heal for a fixed period of time before a second DCDC test. The healing efficiency of each material system is evaluated based on the

  15. 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

  16. Low-intensity pulsed ultrasound accelerates rat femoral fracture healing by acting on the various cellular reactions in the fracture callus.

    PubMed

    Azuma, Y; Ito, M; Harada, Y; Takagi, H; Ohta, T; Jingushi, S

    2001-04-01

    Low-intensity pulsed ultrasound (LIPUS) has been shown to accelerate fracture healing in both animal models and clinical trials, but the mechanism of action remains unclear. In fracture healing, various consecutive cellular reactions occurred until repair. We investigated whether the advanced effects of LIPUS depended on the duration and timing of LIPUS treatment in a rat closed femoral fracture model to determine the target of LIPUS in the healing process. Sixty-nine Long-Evans male rats that have bilateral closed femoral fractures were used. The right femur was exposed to LIPUS (30 mW/cm2 spatial and temporal average [SATA], for 20 minutes/day), and the left femur was used as a control. Rats were divided into four groups according to timing and duration of treatment (Ph-1, days 1-8; Ph-2, days 9-16; Ph-3, days 17-24; throughout [T], days 1-24 after the fracture). Animals were killed on day 25. After radiographs and microfocus X-ray computed tomography (muCT) tomograms were taken, the hard callus area (HCA), bone mineral content (BMC) at the fracture site, and mechanical torsion properties were measured, and histological analysis was conducted. Interestingly, the maximum torque of the LIPUS-treated femur was significantly greater than that of the controls in all groups without any changes in HCA and BMC. The multiviewing of three-dimensional (3D) muCT reconstructions and histology supported our findings that the partial LIPUS treatment time was able to accelerate healing, but longer treatment was more effective. These results suggest that LIPUS acts on some cellular reactions involved in each phase of the healing process such as inflammatory reaction, angiogenesis, chondrogenesis, intramembranous ossification, endochondral ossification, and bone remodeling.

  17. Neuromuscular electrical stimulation enhances fracture healing: results of an animal model.

    PubMed

    Park, Sang-Hyun; Silva, Mauricio

    2004-03-01

    Neuromuscular electrical stimulation (NMES) could simulate physiological muscle functions known to be associated with the normal bone healing process. The object of the present study was to evaluate the effect of NMES on fracture healing, using an animal model. Thirty rabbits received unilateral, transverse, mid-tibial, 3-mm gapped osteotomies that were stabilized with double-bar external fixators. The femoral vein was ligated to induce venous stasis. From the fourth post-operative day, the study group was treated with 1 h daily of NMES for four weeks, while the control group was treated without NMES. For NMES, two surface electrodes were used: one above the patellar tendon and another around the lateral thigh. Callus area and mineral content at the osteotomy gap were measured, biweekly, using computerized tomographic examinations. Biomechanical properties of healing were evaluated with a torsion test, eight weeks after the index operation. Osteotomies treated with NMES exhibited 31% (p=0.01) higher mineral content and 27% (p=0.009) larger callus area than control osteotomies at eight weeks. The maximum torque, torsional stiffness, angular displacement at maximum torque, and energy required to failure of specimens in the study group were 62% (p=0.006), 29% (p=0.03), 34.6% (p=0.008), and 124% (p<0.0001) higher, respectively, than those in the control group at eight weeks. The results of the present study demonstrated that the use of NMES can enhance callus development and mineralization, with the consequent improvement in biomechanical properties of the healing bone.

  18. Role of Simvastatin on fracture healing and osteoporosis: a systematic review on in vivo investigations.

    PubMed

    Moshiri, Ali; Sharifi, Ali Mohammad; Oryan, Ahmad

    2016-07-01

    Simvastatin is a lipid lowering drug whose beneficial role on bone metabolism was discovered in 1999. Several in vivo studies evaluated its role on osteoporosis and fracture healing, however, controversial results are seen in the literature. For this reason, Simvastatin has not been the focus of any clinical trials as yet. This systematic review clears the mechanisms of action of Simvastatin on bone metabolism and focuses on in vivo investigations that have evaluated its role on osteoporosis and fracture repair to find out (i) whether Simvastatin is effective on treatment of osteoporosis and fracture repair, and (ii) which of the many available protocols may have the ability to be translated in the clinical setting. Simvastatin induces osteoinduction by increasing osteoblast activity and differentiation and inhibiting their apoptosis. It also reduces osteoclastogenesis by decreasing both the number and activity of osteoclasts and their differentiation. Controversial results between the in vivo studies are mostly due to the differences in the route of administration, dose, dosage and carrier type. Local delivery of Simvastatin through controlled drug delivery systems with much lower doses and dosages than the systemic route seems to be the most valuable option in fracture healing. However, systemic delivery of Simvastatin with much higher doses and dosages than the clinical ones seems to be effective in managing osteoporosis. Simvastatin, in a particular range of doses and dosages, may be beneficial in managing osteoporosis and fracture injuries. This review showed that Simvastatin is effective in the treatment of osteoporosis and fracture healing.

  19. 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.

  20. Delayed Fracture Healing and Increased Callus Adiposity in a C57BL/6J Murine Model of Obesity-Associated Type 2 Diabetes Mellitus

    PubMed Central

    Brown, Matthew L.; Yukata, Kiminori; Farnsworth, Christopher W.; Chen, Ding-Geng; Awad, Hani; Hilton, Matthew J.; O'Keefe, Regis J.; Xing, Lianping; Mooney, Robert A.; Zuscik, Michael J.

    2014-01-01

    Introduction Impaired healing and non-union of skeletal fractures is a major public health problem, with morbidity exacerbated in patients with diabetes mellitus (DM). DM is prevalent worldwide and affects approximately 25.8 million US adults, with >90% having obesity-related type 2 DM (T2DM). While fracture healing in type 1 DM (T1DM) has been studied using animal models, an investigation into delayed healing in an animal model of T2DM has not yet been performed. Methods Male C57BL/6J mice at 5 weeks of age were placed on either a control lean diet or an experimental high-fat diet (HFD) for 12 weeks. A mid-diaphyseal open tibia fracture was induced at 17 weeks of age and a spinal needle was used for intra-medullary fixation. Mice were sacrificed at days 7, 10, 14, 21, 28, and 35 for micro-computed tomography (μCT), histology-based histomorphometry and molecular analyses, and biomechanical testing. Results HFD-fed mice displayed increased body weight and impaired glucose tolerance, both characteristic of T2DM. Compared to control mice, HFD-fed mice with tibia fractures showed significantly (p<0.001) decreased woven bone at day 28 by histomorphometry and significantly (p<0.01) decreased callus bone volume at day 21 by μCT. Interestingly, fracture calluses contained markedly increased adiposity in HFD-fed mice at days 21, 28, and 35. HFD-fed mice also showed increased PPARγ immunohistochemical staining at day 14. Finally, calluses from HFD-fed mice at day 35 showed significantly (p<0.01) reduced torsional rigidity compared to controls. Discussion Our murine model of T2DM demonstrated delayed fracture healing and weakened biomechanical properties, and was distinctly characterized by increased callus adiposity. This suggests altered mesenchymal stem cell fate determination with a shift to the adipocyte lineage at the expense of the osteoblast lineage. The up-regulation of PPARγ in fracture calluses of HFD-fed mice is likely involved in the proposed fate switching

  1. Nitric oxide-mediated vasodilation increases blood flow during the early stages of stress fracture healing.

    PubMed

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

    2014-02-15

    Despite the strong connection between angiogenesis and osteogenesis in skeletal repair conditions such as fracture and distraction osteogenesis, little is known about the vascular requirements for bone formation after repetitive mechanical loading. Here, established protocols of damaging (stress fracture) and nondamaging (physiological) forelimb loading in the adult rat were used to stimulate either woven or lamellar bone formation, respectively. Positron emission tomography was used to evaluate blood flow and fluoride kinetics at the site of bone formation. In the group that received damaging mechanical loading leading to woven bone formation (WBF), (15)O water (blood) flow rate was significantly increased on day 0 and remained elevated 14 days after loading, whereas (18)F fluoride uptake peaked 7 days after loading. In the group that received nondamaging mechanical loading leading to lamellar bone formation (LBF), (15)O water and (18)F fluoride flow rates in loaded limbs were not significantly different from nonloaded limbs at any time point. The early increase in blood flow rate after WBF loading was associated with local vasodilation. In addition, Nos2 expression in mast cells was increased in WBF-, but not LBF-, loaded limbs. The nitric oxide (NO) synthase inhibitor N(ω)-nitro-l-arginine methyl ester was used to suppress NO generation, resulting in significant decreases in early blood flow rate and bone formation after WBF loading. These results demonstrate that NO-mediated vasodilation is a key feature of the normal response to stress fracture and precedes woven bone formation. Therefore, patients with impaired vascular function may heal stress fractures more slowly than expected. PMID:24356518

  2. Healing following implantation of periodontitis affected roots into bone tissue.

    PubMed

    Karring, T; Nyman, S; Lindhe, J

    1980-04-01

    The aim of the present experiment was to study whether new connective tissue attachment can occur to root surfaces which have been exposed to the oral environment and subsequently implanted into bone tissue. Twelve teeth in three beagle dogs were subjected to progressive periodontal breakdown to half the root length by placing cotton floss ligatures around the neck of the teeth. Following crown resection and root hemisection, the teeth were root filled and the roots thoroughly scaled and planed. Each root was extracted and implanted into bone cavities prepared in edentolous areas of the jaws in such a way that epithelial migration into the wound and bacterial infection were prevented during healing. Root implantation and sacrifice of the animals were scheduled to allow for observation periods of 1, 2 and 3 months. The results demonstrated that new connective tissue attachment did not occur to root surfaces which had been exposed to the oral environment, but healing was characterized by repair phenomena, i.e. mainly root resorption and ankylosis. In those areas of the roots where periodontal ligament tissue was preserved following tooth extraction, a functionally oriented attachment apparatus was reformed. The results indicate that in addition to apical migration of junctional epithelium and regrowth of subgingival plaque, the type of cells which repopulate the wound area may jeopardize new connective tissue attachment.

  3. 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

  4. Fractures

    PubMed Central

    Hall, Michael C.

    1963-01-01

    Recent studies on the epidemiology and repair of fractures are reviewed. The type and severity of the fracture bears a relation to the age, sex and occupation of the patient. Bone tissue after fracture shows a process of inflammation and repair common to all members of the connective tissue family, but it repairs with specific tissue. Cartilage forms when the oxygen supply is outgrown. After a fracture, the vascular bed enlarges. The major blood supply to healing tissue is from medullary vessels and destruction of them will cause necrosis of the inner two-thirds of the cortex. Callus rapidly mineralizes, but full mineralization is achieved slowly; increased mineral metabolism lasts several years after fracture. PMID:13952119

  5. Mesenchymal Stem Cells with Increased Stromal Cell-Derived Factor 1 Expression Enhanced Fracture Healing

    PubMed Central

    Ho, Chih-Yuan; Hua, Jia; Coathup, Melanie; Kalia, Priya; Blunn, Gordon

    2015-01-01

    Treatment of critical size bone defects pose a challenge in orthopedics. Stem cell therapy together with cytokines has the potential to improve bone repair as they cause the migration and homing of stem cells to the defect site. However, the engraftment, participation, and recruitment of other cells within the regenerating tissue are important. To enhance stem cell involvement, this study investigated overexpression of stem cells with stromal cell-derived factor 1 (SDF-1) using an adenovirus. We hypothesized that these engineered cells would effectively increase the migration of native cells to the site of fracture, enhancing bone repair. Before implantation, we showed that SDF-1 secreted by transfected cells increased the migration of nontransfected cells. In a rat defect bone model, bone marrow mesenchymal stem cells overexpressing SDF-1 showed significantly (p=0.003) more new bone formation within the gap and less bone mineral loss at the area adjacent to the defect site during the early bone healing stage. In conclusion, SDF-1 was shown to play an important role in accelerating fracture repair and contributing to bone repair in rat models, by recruiting more host stem cells to the defect site and encouraging osteogenic differentiation and production of bone. PMID:25251779

  6. Teriparatide for the rapid resolution of delayed healing of atypical fractures associated with long-term bisphosphonate use

    PubMed Central

    Mastaglia, Silvina R.; Aguilar, Gabriel; Oliveri, Beatriz

    2016-01-01

    Bisphosphonates (BPs) are the most widely used drugs to treat osteoporosis. However, recent reports associated to long-term BPs use with atypical low-impact fractures and prodromal pain. It is estimated that 26% of the cases of atypical fractures associated with the long-term use of BPs show delayed healing or nonunion. Teriparatide [PTH1-34] (TPTD) is an anabolic drug shown to be effective in stimulating bone formation. The aim was to describe the course of a right diaphyseal femoral fracture sustained by a patient on long-term BPs treatment. A 57-year-old postmenopausal Caucasian female presented with delayed healing of a right femoral diaphyseal fracture 10 months after the fracture, despite having received orthopedic treatment. The fracture was preceded by progressive, severe, and bilateral thigh pain. Her medical history included osteopenia that was treated with alendronate over 7 years. On presentation at our clinic, the patient ambulated with the aid of a walking cane. The diagnosis was an atypical right femoral fracture associated with long-term alendronate use. The levels of the following parameters were measured: mineral metabolism laboratory: intact parathormone, 40 ng/mL (reference values (rv): 10–65 ng/mL); 25-hydroxyvitamin D, 40 ng/mL (rv: >30 ng/mL); serum Crosslaps, 318 ng/mL (rv: 80–590 ng/mL); and bone-specific alkaline phosphatase, 76UI/L (rv: 31–95UI/L)]. Magnetic resonance imaging of the left femur was performed, which revealed a diaphyseal stress fracture. She was prescribed 20 μg/day of subcutaneous (s.c.) TPTD (PTH1-34, Forteo; Eli Lilly Co., Indianapolis, IN, United States). A computed tomography scan performed 3 months later showed that the fracture had healed; the patient was able to resume her usual activities. Twenty micrograms per day of s.c. TPD accelerated the healing of the atypical fracture associated with long-term alendronate therapy, allowing a fast recovery of ambulation and quality of life. PMID:27708978

  7. 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.

  8. 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.

  9. 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.

  10. Finite element analysis of a bone healing model: 1-year follow-up after internal fixation surgery for femoral fracture

    PubMed Central

    Jiang-jun, Zhou; Min, Zhao; Ya-bo, Yan; Wei, Lei; Ren-fa, Lv; Zhi-yu, Zhu; Rong-jian, Chen; Wei-tao, Yu; Cheng-fei, Du

    2014-01-01

    Objective: Finite element analysis was used to compare preoperative and postoperative stress distribution of a bone healing model of femur fracture, to identify whether broken ends of fractured bone would break or not after fixation dislodgement one year after intramedullary nailing. Method s: Using fast, personalized imaging, bone healing models of femur fracture were constructed based on data from multi-slice spiral computed tomography using Mimics, Geomagic Studio, and Abaqus software packages. The intramedullary pin was removed by Boolean operations before fixation was dislodged. Loads were applied on each model to simulate a person standing on one leg. The von Mises stress distribution, maximum stress, and its location was observed. Results : According to 10 kinds of display groups based on material assignment, the nodes of maximum and minimum von Mises stress were the same before and after dislodgement, and all nodes of maximum von Mises stress were outside the fracture line. The maximum von Mises stress node was situated at the bottom quarter of the femur. The von Mises stress distribution was identical before and after surgery. Conclusion : Fast, personalized model establishment can simulate fixation dislodgement before operation, and personalized finite element analysis was performed to successfully predict whether nail dislodgement would disrupt femur fracture or not. PMID:24772140

  11. 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

  12. 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

    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

  13. 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.

  14. Cement/caprock fracture healing experiments to assess the integrity of CO2 injection wells

    NASA Astrophysics Data System (ADS)

    Du Frane, W. L.; Mason, H. E.; Walsh, S. D.; Ruddle, D. G.; Carroll, S.

    2012-12-01

    It has been speculated that fractures along wellbore cement/caprock interfaces may provide a path for release of carbon from both long-term sequestration-sites and CO2-based enhanced oil recovery operations. The goal of this study is to evaluate the potential for fracture growth and healing in the wellbore environment, and its impact on wellbore permeability. A series of flow-through experiments was conducted, in which sample cores containing a planar fracture between impermeable caprock (compacted quartz, from 13,927' depth in Kern County) and cement (Portland G cured by ATSM standards) were reacted with brine containing variable amounts of carbonic acid (pCO2 between 0 and 3 MPa). The initial fracture geometry was controlled by grinding the caprock and cement pieces flat, and then bead blasting topography into the cement surfaces. Runs lasted 4-8 days with cores and brine maintained at constant temperature (60 °C). Constant confining pressure (24.8 MPa) was applied to cores, while brine was flowed with constant rates (0.05-0.10 mL/min) and pore pressure (12.4 MPa). Geomechanical and geochemical responses of the fractures were monitored by in situ measurements of differential pressure, and by periodically sampling output brine to analyze compositional changes. In every experiment the total permeability of samples cores decreased substantially. For runs using brine with pCO2 = 3 MPa, sample permeability continually decreased by over a factor of 200. Sample permeability also decreased by a factor of 50 having stabilized after ~3 days in a run using brine without CO2 (pCO2 = 0 MPa). These reductions in permeability appear to be the result of chemically-induced changes to the mechanical properties of the cement surface. Prior to reaction, the cement-caprock samples had high strength and elastic response to changes in stress during loading. After the experiments, the samples were weaker, and showed inelastic response to changes in stress during unloading. All cement

  15. The Effect of Teriparatide on Fracture Healing of Osteoporotic Patients: A Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Lou, Shenghan; Lv, Houchen; Wang, Guoqi; Zhang, Licheng; Li, Ming; Li, Zhirui; Zhang, Lihai

    2016-01-01

    Purpose. This meta-analysis is to assess the effectiveness of teriparatide in fracture healing and clinical function improvement of the osteoporotic patients. Methods. We searched PubMed, Embase, Web of Science, and the Cochrane databases for randomized and quasi-randomized controlled trials comparing teriparatide to placebo, no treatment, or comparator interventions in the osteoporotic patients. Results. Five studies with 251 patients were included. Patients treated with teriparatide therapy had a significant shorter radiological fracture healing time compared with those in the control group (mean difference [MD] −4.54 days, 95% confidence interval [CI] −8.80 to −0.28). Stratified analysis showed that lower limb group had significant shorter healing time (MD −6.24 days, 95% CI −7.20 to −5.29), but upper limb group did not (MD −1 days, 95% CI −2.02 to 0.2). Patients treated with teriparatide therapy showed better functional outcome than those in the control group (standardized mean difference [SMD] −1.02, 95% CI −1.81 to −0.22). Patients with therapy duration over 4 weeks would have better functional outcome (SMD −1.68, 95% CI −2.07 to −1.29). Conclusions. Teriparatide is effective in accelerating fracture healing and improving functional outcome of osteoporotic women. However, more clinical studies are warranted in order to determine whether the results are applicable to males and the clinical indications for teriparatide after osteoporotic fractures. PMID:27429980

  16. Prediction of the time course of callus stiffness as a function of mechanical parameters in experimental rat fracture healing studies--a numerical study.

    PubMed

    Wehner, Tim; Steiner, Malte; Ignatius, Anita; Claes, Lutz

    2014-01-01

    Numerous experimental fracture healing studies are performed on rats, in which different experimental, mechanical parameters are applied, thereby prohibiting direct comparison between each other. Numerical fracture healing simulation models are able to predict courses of fracture healing and offer support for pre-planning animal experiments and for post-hoc comparison between outcomes of different in vivo studies. The aims of this study are to adapt a pre-existing fracture healing simulation algorithm for sheep and humans to the rat, to corroborate it using the data of numerous different rat experiments, and to provide healing predictions for future rat experiments. First, material properties of different tissue types involved were adjusted by comparing experimentally measured callus stiffness to respective simulated values obtained in three finite element (FE) models. This yielded values for Young's moduli of cortical bone, woven bone, cartilage, and connective tissue of 15,750 MPa, 1,000 MPa, 5 MPa, and 1 MPa, respectively. Next, thresholds in the underlying mechanoregulatory tissue differentiation rules were calibrated by modifying model parameters so that predicted fracture callus stiffness matched experimental data from a study that used rigid and flexible fixators. This resulted in strain thresholds at higher magnitudes than in models for sheep and humans. The resulting numerical model was then used to simulate numerous fracture healing scenarios from literature, showing a considerable mismatch in only 6 of 21 cases. Based on this corroborated model, a fit curve function was derived which predicts the increase of callus stiffness dependent on bodyweight, fixation stiffness, and fracture gap size. By mathematically predicting the time course of the healing process prior to the animal studies, the data presented in this work provides support for planning new fracture healing experiments in rats. Furthermore, it allows one to transfer and compare new in vivo

  17. Long-term effects of saw osteotomy versus random fracturing on bone healing and remodeling in a sheep tibia model.

    PubMed

    Dumont, Clemens; Kauer, Fritz; Bohr, Stefan; Schmidtmann, Ulrich; Knopp, Werner; Engelhardt, Thomas; Stürmer, Ewa Klara; Stürmer, Klaus Michael

    2009-05-01

    This article is about the evaluation of possible differences in biomechanical or histomorphological properties of bone healing between saw osteotomy and random fracturing after 6 months. A standardized, 30 degrees oblique monocortical saw osteotomy of sheep tibia was carried out, followed by manual fracture completion of the opposed cortical bone. Fixation was performed by bridge plating (4.5 mm, LCDCP, broad). X-rays were taken immediately after surgery and at the end of the study. Polychrome fluorescent staining was performed according to a standardized protocol in the 2nd, 4th 6th, 10th, 14th, 18th, 22th and 26th week. Ten sheep were comprehensively evaluated. Data for stiffness and histomorphology are reported. The average bending stiffness of the operated bone was higher (1.7 (SD 0.3) with plate (MP) vs. 1.5 without plate) than for the intact bone (1.4 (SD 0.2), though no significant differences in bending stiffness were observed (P>0.05). Fluorescence staining revealed small numbers of blood vessels and less fragment resorption and remodeling in the osteotomy gap. Bone healing after saw osteotomy shows a very close resemblance to 'normal' fracture healing. However, vascular density, fragment resorption, fragment remodeling, and callus remodeling are reduced at the osteotomy.

  18. [Fracture healing of the ethmoid bone--a contribution to rhinologic management of naso-ethmoid injuries].

    PubMed

    Hosemann, W; Gottsauner, A; Leuwer, A; Farmand, M; Wenning, W; Göde, U; Stenglein, C; von Glass, W

    1993-08-01

    Severe maxillofacial trauma accompanied by a dislocated ethmoidal bone fracture was confirmed by CT imaging in 15 adult patients. Routine surgical management included reduction of fractures, miniplate fixation and/or intermaxillary fixation with interosseous wiring. The fractured ethmoidal cell system was left to heal spontaneously. A follow-up examination including endoscopy of the nasal cavity as well as active anterior rhinomanometry and computed tomography was carried out approximately 24 months after surgery. The fractured ethmoidal cell system showed a clear tendency to spontaneously reventilate and drain. However, in 8 of 30 sides a traumatic obstruction of the anterior ethmoid led to secondary frontal sinus mucositis. 12 out of 30 maxillary sinuses ranged from marked mucosal swelling to the development of a traumatic mucocele. Altogether, 9 of the 15 patients suffered from paranasal sinusitis. Routine debridement of every fractured ethmoidal cell system does not appear to be necessary. In case of fractures of the anterior ethmoid with probable obstruction of the nasofrontal duct and/or maxillary sinus ostium, endonasal endoscopic surgery is recommended for minimally invasive reconstruction of the ventilation and drainage of the frontal and maxillary sinus during primary surgical management. Furthermore, patients with severe naso-orbito-ethmoidal fractures should undergo rhinological follow-up examination including CT-imaging approximately 3 months after surgery.

  19. Dynamic locking plates provide symmetric axial dynamization to stimulate fracture healing.

    PubMed

    Tsai, Stanley; Fitzpatrick, Daniel C; Madey, Steven M; Bottlang, Michael

    2015-08-01

    Axial dynamization of an osteosynthesis construct can promote fracture healing. This biomechanical study evaluated a novel dynamic locking plate that derives symmetric axial dynamization by elastic suspension of locking holes within the plate. Standard locked and dynamic plating constructs were tested in a diaphyseal bridge-plating model of the femoral diaphysis to determine the amount and symmetry of interfragmentary motion under axial loading, and to assess construct stiffness under axial loading, torsion, and bending. Subsequently, constructs were loaded until failure to determine construct strength and failure modes. Finally, strength tests were repeated in osteoporotic bone surrogates. One body-weight axial loading of standard locked constructs produced asymmetric interfragmentary motion that was over three times smaller at the near cortex (0.1 ± 0.01 mm) than at the far cortex (0.32 ± 0.02 mm). Compared to standard locked constructs, dynamic plating constructs enhanced motion by 0.32 mm at the near cortex and by 0.33 mm at the far cortex and yielded a 77% lower axial stiffness (p < 0.001). Dynamic plating constructs were at least as strong as standard locked constructs under all test conditions. In conclusion, dynamic locking plates symmetrically enhance interfragmentary motion, deliver controlled axial dynamization, and are at least comparable in strength to standard locked constructs. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1218-1225, 2015.

  20. Aryl Hydrocarbon Receptor-Mediated Impairment of Chondrogenesis and Fracture Healing by Cigarette Smoke and Benzo(α)pyrene

    PubMed Central

    Kung, Ming H.; Yukata, Kiminori; O’Keefe, Regis J.; Zuscik, Michael J.

    2012-01-01

    The clinical literature strongly suggests that bone healing in cigarette smokers is impaired. Since cigarette smoke (CS) contains numerous polycyclic aromatic hydrocarbons (PAHs), and since dioxins impair bone formation in vivo via the Aryl Hydrocarbon Receptor (AHR), we investigated the impact of PAH/AHR signaling on chondrogenesis and on healing in a mouse tibial fracture model. We established that CS activates AHR signaling in fractures by up-regulating the AHR target gene cytochrome p4501A1 (Cyp1A1). For in vitro studies, we employed the mouse limb bud micromass chondrogenesis model. After confirming that chondrocytes express AHR during differentiation, we treated cells with a prototypical PAH found in CS, benzo(α)pyrene (BaP), or cigarette smoke extract (CSE). Both BaP and CSE both strongly inhibited chondrogenesis in mesenchymal cells generated from E11 limb buds, with BaP also accelerating chondrocyte hypertrophy in cultures generated from E12 limb buds. Detection of DNA adducts in the BaP-treated cultures suggests that the distinct phenotypic effects of BaP may be due to the formation of reactive metabolites. Blockade of AHR signaling with the AHR antagonist MNF reverses the effects of BaP, but not CSE, suggesting that CSE inhibition of chondrogenesis is AHR-independent. Correlating with these results, tibial fracture calluses from BaP-treated mice were smaller and contained less mineralized tissue than vehicle controls. Overall, BaP is identified as a potent inhibitor of chondrogenesis in vitro with correlated effects on fracture healing similar to those of CS itself, suggesting a basis for PAHs as key compounds in the influence of CS on fracture repair. PMID:21567390

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

    PubMed

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

    2010-09-01

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

  2. Failure of a helium-neon laser to affect components of wound healing in vitro.

    PubMed

    Colver, G B; Priestley, G C

    1989-08-01

    The red light of a helium-neon (He-Ne) laser has been reported to stimulate wound healing and cell growth. To investigate the nature of its influence on wound healing we have studied seven components of the healing process in vitro: human skin fibroblast, epithelial and endothelial cell proliferation, cellular migration from skin explants, collagen lattice contraction, collagen synthesis and glycosaminoglycans (GAG) secretion. We used a 5 mW He-Ne laser emitting a I mm diameter beam of wavelength 633 nm. Cellular proliferation was not affected by irradiation three times a day for 3 days. There was no effect on cellular migration or on the rate of collagen lattice contraction. The rate of collagen synthesis, measured as the incorporation of 3H-proline into collagenase-sensitive protein, was no greater than that of controls and GAG secretion did not increase in the irradiated group. We have not found any significant effects of He-Ne irradiation.

  3. 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.

  4. 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

  5. Dynamic locking plates provide symmetric axial dynamization to stimulate fracture healing.

    PubMed

    Tsai, Stanley; Fitzpatrick, Daniel C; Madey, Steven M; Bottlang, Michael

    2015-08-01

    Axial dynamization of an osteosynthesis construct can promote fracture healing. This biomechanical study evaluated a novel dynamic locking plate that derives symmetric axial dynamization by elastic suspension of locking holes within the plate. Standard locked and dynamic plating constructs were tested in a diaphyseal bridge-plating model of the femoral diaphysis to determine the amount and symmetry of interfragmentary motion under axial loading, and to assess construct stiffness under axial loading, torsion, and bending. Subsequently, constructs were loaded until failure to determine construct strength and failure modes. Finally, strength tests were repeated in osteoporotic bone surrogates. One body-weight axial loading of standard locked constructs produced asymmetric interfragmentary motion that was over three times smaller at the near cortex (0.1 ± 0.01 mm) than at the far cortex (0.32 ± 0.02 mm). Compared to standard locked constructs, dynamic plating constructs enhanced motion by 0.32 mm at the near cortex and by 0.33 mm at the far cortex and yielded a 77% lower axial stiffness (p < 0.001). Dynamic plating constructs were at least as strong as standard locked constructs under all test conditions. In conclusion, dynamic locking plates symmetrically enhance interfragmentary motion, deliver controlled axial dynamization, and are at least comparable in strength to standard locked constructs. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1218-1225, 2015. PMID:25721801

  6. Chondrocytes Transdifferentiate into Osteoblasts in Endochondral Bone during Development, Postnatal Growth and Fracture Healing in Mice

    PubMed Central

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

    2014-01-01

    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

  7. 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

  8. Quantitative histological evaluation of early fracture healing of cortical bones immobilized by stainless steel and composite plates.

    PubMed

    Akeson, W H; Woo, S L; Coutts, R D; Matthews, J V; Gonsalves, M; Amiel, D

    1975-11-24

    Internal fixation devices of less bending stiffness than conventional plates made of stainless steel or vitallium were compared with conventional plates in a study of fracture healing. The material for this investigation was a fine graphite fiber reinforced methyl methacrylate resin composite with a modulus of elasticity approximately ten times less than that of stainless steel. Osteotomies were performed on canine radii. Internal fixation was accomplished by means of a composite plate on the left side, and a stainless steel plate on the right. Clinical assessment, as well as biomechanical and quantitative histological techniques, were used to compare osteotomy healing of the two sides. At four months, all osteotomies had healed and the bioengineering tests showed radii from the two sides had equivalent strength. However, significantly less cortical porosity was found in the side with the composite plate (6.8 per cent), as compared to that of the stainless steel plated side (14 per cent). These results suggest that a less stiff fixation plate may have some advantage in the treatment of long bone fracture if there is no implant failure, and if union rates are equivalent.

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

    PubMed

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

    2015-10-01

    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

  10. 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. PMID:27441766

  11. 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

  12. 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

  13. Accelerated fracture healing in the geriatric, osteoporotic rat with recombinant human platelet-derived growth factor-BB and an injectable beta-tricalcium phosphate/collagen matrix.

    PubMed

    Hollinger, Jeffrey O; Onikepe, Andrew O; MacKrell, Jim; Einhorn, Thomas; Bradica, Gino; Lynch, Samuel; Hart, Charles E

    2008-01-01

    Aging and osteoporosis contribute to decreased bone mass and bone mineral density as well as compromised fracture healing rates and bone repair quality. Consequently, the purpose of this study was to determine if recombinant human platelet-derived growth factor-BB (rhPDGF-BB) delivered in an injectable beta-tricalcium phosphate/collagen matrix would enhance tibial fracture healing in geriatric (>2 years of age), osteoporotic rats. A total of 80 rats were divided equally among four groups: Fracture alone; Fracture plus matrix; Fracture plus matrix and either 0.3 mg/mL or 1.0 mg/mL rhPDGF-BB. At 3 and 5 weeks, rats were euthanized and treatment outcome was assessed histologically, radiographically, biomechanically, and by micro-CT. Results indicated rhPDGF-BB-treated fractures in osteoporotic, geriatric rats caused a statistically significant time-dependent increase in torsional strength 5 weeks after treatment. The healed fractures were equivalent in torsional strength to the contralateral, unoperated tibiae. Data from the study are the first, to our knowledge, to underscore rhPDGF-BB efficacy in an injectable beta-tricalcium phosphate/collagen matrix accelerated fracture repair in a geriatric, osteoporotic rat model.

  14. In-vivo imaging of the fracture healing in medaka revealed two types of osteoclasts before and after the callus formation by osteoblasts.

    PubMed

    Takeyama, Kazuhiro; Chatani, Masahiro; Takano, Yoshiro; Kudo, Akira

    2014-10-15

    The fracture healing research, which has been performed in mammalian models not only for clinical application but also for bone metabolism, revealed that generally osteoblasts are induced to enter the fracture site before the induction of osteoclasts for bone remodeling. However, it remains unknown how and where osteoclasts and osteoblasts are induced, because it is difficult to observe osteoclasts and osteoblasts in a living animal. To answer these questions, we developed a new fracture healing model by using medaka. We fractured one side of lepidotrichia in a caudal fin ray without injuring the other soft tissues including blood vessels. Using the transgenic medaka in which osteoclasts and osteoblasts were visualized by GFP and DsRed, respectively, we found that two different types of functional osteoclasts were induced before and after osteoblast callus formation. The early-induced osteoclasts resorbed the bone fragments and the late-induced osteoclasts remodeled the callus. Both types of osteoclasts were induced near the surface on the blood vessels, while osteoblasts migrated from adjacent fin ray. Transmission electron microscopy revealed that no significant ruffled border and clear zone were observed in early-induced osteoclasts, whereas the late-induced osteoclasts had clear zones but did not have the typical ruffled border. In the remodeling of the callus, the expression of cox2 mRNA was up-regulated at the fracture site around vessels, and the inhibition of Cox2 impaired the induction of the late-induced osteoclasts, resulting in abnormal fracture healing. Finally, our developed medaka fracture healing model brings a new insight into the molecular mechanism for controlling cellular behaviors during the fracture healing. PMID:25131195

  15. A retrospective study using the pressure ulcer scale for healing (PUSH) tool to examine factors affecting stage II pressure ulcer healing in a Korean acute care hospital.

    PubMed

    Park, Kyung Hee

    2014-09-01

    Stage II pressure ulcers (PUs) should be managed promptly and appropriately in order to prevent complications. To identify the factors affecting Stage II PU healing and optimize care, the electronic medical records of patients with a Stage II PU in an acute care hospital were examined. Patient and ulcer characteristics as well as nutritional assessment variables were retrieved, and ulcer variables were used to calculate Pressure Ulcer Scale for Healing (PUSH) scores. The effect of all variables on healing status (healed versus nonhealed) and change in PUSH score for healing rate were compared. Records of 309 Stage II PUs from 155 patients (mean age 61.2 ± 15.2 [range 5-89] years, 182 [58.9%] male) were retrieved and analyzed. Of those, 221 healed and 88 were documented as not healed at the end of the study. The variables that were significantly different between patients with PUs that did and did not heal were: major diagnosis (P = 0.001), peripheral arterial disease (P = 0.007), smoking (P = 0.048), serum albumin ( <2.5 g/dL) (P = 0.002), antidepressant use (P = 0.035), vitamin use (P = 0.006), history of surgery (P <0.001), PU size (P = 0.003), Malnutrition Universal Screening Tool (MUST) score (P = 0.020), Braden scale score (P = 0.003), and mean arterial pressure (MAP, mm Hg) (P = 0.026). The Cox proportional hazard model showed a significant positive difference in PUSH score change -indicative of healing - when pressure-redistribution surfaces were used (P <0.001, HR = 2.317), PU size was small (≤3.0 cm2, P = 0.006, HR = 1.670), MAP (within a range of 52-112 mm Hg) was higher P = 0.010, HR = 1.016), and patients were provided multivitamins (P = 0.037, HR=1.431). The results of this study suggest strategies for healing Stage II PUs in the acute care setting should include early recognition of lower-stage PUs, the provision of static pressure-redistribution surfaces and multivitamins, and maintaining higher MAP may facilitate healing and prevent deterioration

  16. 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

  17. The role of the lateral pterygoid muscle in the sagittal fracture of mandibular condyle (SFMC) healing process.

    PubMed

    Liu, Chng-Kui; Liu, Ping; Meng, Fan-Wen; Deng, Bang-Lian; Xue, Yang; Mao, Tian-Qiu; Hu, Kai-Jin

    2012-06-01

    The aim of this study was to examine the role of the lateral peterygoid muscle in the reconstruction of the shape of the condyle during healing of a sagittal fracture of the mandibular condyle. Twenty adult sheep were divided into 2 groups: all had a unilateral operation on the right side when the anterior and posterior attachments of the discs were cut, and an oblique vertical osteotomy was made from the lateral pole of the condyle to the medial side of the condylar neck. Ten sheep had the lateral pterygoid muscle cut, and the other 10 sheep did not. Sheep were killed at 4 weeks (n=2 from each group), 12 weeks (n=4), and 24 weeks (n=4) postoperatively. Computed tomograms (CT) were taken before and after operations. We dissected the joints, and recorded with the naked eye the shape, degree of erosion, and amount of calcification of the temporomandibular joint (TMJ). In the group in which the lateral peterygoid muscle had not been cut the joints showed overgrowth of new bone and more advanced ankylosis. Our results show that the lateral pterygoid muscle plays an important part in reconstructing the shape of the condyle during the healing of a sagittal fracture of the mandibular condyle, and combined with the dislocated and damaged disc is an important factor in the aetiology of traumatic ankylosis of the TMJ.

  18. Capturing the wide variety of impaired fracture healing phenotypes in Neurofibromatosis Type 1 with eight key factors: a computational study.

    PubMed

    Carlier, A; Brems, H; Ashbourn, J M A; Nica, I; Legius, E; Geris, L

    2016-01-01

    Congenital pseudarthrosis of the tibia (CPT) is a rare disease which normally presents itself during early childhood by anterolateral bowing of the tibia and spontaneous tibial fractures. Although the exact etiology of CPT is highly debated, 40-80% of CPT patients are carriers of a mutation in the Neurofibromatosis Type 1 (NF1) gene, which can potentially result in an altered phenotype of the skeletal cells and impaired bone healing. In this study we use a computational model of bone regeneration to examine the effect of the Nf1 mutation on bone fracture healing by altering the parameter values of eight key factors which describe the aberrant cellular behaviour of Nf1 haploinsufficient and Nf1 bi-allelically inactivated cells. We show that the computational model is able to predict the formation of a hamartoma as well as a wide variety of CPT phenotypes through different combinations of altered parameter values. A sensitivity analysis by "Design of Experiments" identified the impaired endochondral ossification process and increased infiltration of fibroblastic cells as key contributors to the degree of severity of CPT. Hence, the computational model results have added credibility to the experimental hypothesis of a genetic cause (i.e. Nf1 mutation) for CPT. PMID:26822862

  19. Capturing the wide variety of impaired fracture healing phenotypes in Neurofibromatosis Type 1 with eight key factors: a computational study

    PubMed Central

    Carlier, A.; Brems, H.; Ashbourn, J. M. A.; Nica, I.; Legius, E.; Geris, L.

    2016-01-01

    Congenital pseudarthrosis of the tibia (CPT) is a rare disease which normally presents itself during early childhood by anterolateral bowing of the tibia and spontaneous tibial fractures. Although the exact etiology of CPT is highly debated, 40–80% of CPT patients are carriers of a mutation in the Neurofibromatosis Type 1 (NF1) gene, which can potentially result in an altered phenotype of the skeletal cells and impaired bone healing. In this study we use a computational model of bone regeneration to examine the effect of the Nf1 mutation on bone fracture healing by altering the parameter values of eight key factors which describe the aberrant cellular behaviour of Nf1 haploinsufficient and Nf1 bi-allelically inactivated cells. We show that the computational model is able to predict the formation of a hamartoma as well as a wide variety of CPT phenotypes through different combinations of altered parameter values. A sensitivity analysis by “Design of Experiments” identified the impaired endochondral ossification process and increased infiltration of fibroblastic cells as key contributors to the degree of severity of CPT. Hence, the computational model results have added credibility to the experimental hypothesis of a genetic cause (i.e. Nf1 mutation) for CPT. PMID:26822862

  20. 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.

  1. 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

  2. CYR61 (CCN1) protein expression during fracture healing in an ovine tibial model and its relation to the mechanical fixation stability.

    PubMed

    Lienau, Jasmin; Schell, Hanna; Epari, Devakara R; Schütze, Norbert; Jakob, Franz; Duda, Georg N; Bail, Hermann J

    2006-02-01

    The formation of new blood vessels is a prerequisite for bone healing. CYR61 (CCN1), an extracellular matrix-associated signaling protein, is a potent stimulator of angiogenesis and mesenchymal stem cell expansion and differentiation. A recent study showed that CYR61 is expressed during fracture healing and suggested that CYR61 plays a significant role in cartilage and bone formation. The hypothesis of the present study was that decreased fixation stability, which leads to a delay in healing, would lead to reduced CYR61 protein expression in fracture callus. The aim of the study was to quantitatively analyze CYR61 protein expression, vascularization, and tissue differentiation in the osteotomy gap and relate to the mechanical fixation stability during the course of healing. A mid-shaft osteotomy of the tibia was performed in two groups of sheep and stabilized with either a rigid or semirigid external fixator, each allowing different amounts of interfragmentary movement. The sheep were sacrificed at 2, 3, 6, and 9 weeks postoperatively. The tibiae were tested biomechanically and histological sections from the callus were analyzed immunohistochemically with regard to CYR61 protein expression and vascularization. Expression of CYR61 protein was upregulated at the early phase of fracture healing (2 weeks), decreasing over the healing time. Decreased fixation stability was associated with a reduced upregulation of the CYR61 protein expression and a reduced vascularization at 2 weeks leading to a slower healing. The maximum cartilage callus fraction in both groups was reached at 3 weeks. However, the semirigid fixator group showed a significantly lower CYR61 immunoreactivity in cartilage than the rigid fixator group at this time point. The fraction of cartilage in the semirigid fixator group was not replaced by bone as quickly as in the rigid fixator group leading to an inferior histological and mechanical callus quality at 6 weeks and therefore to a slower healing. The

  3. Suture materials affect peri-implant bone healing and implant osseointegration.

    PubMed

    Villa, Oscar; Lyngstadaas, Staale P; Monjo, Marta; Satué, Maria; Rønold, Hans J; Petzold, Christiane; Wohlfahrt, Johan C

    2015-09-01

    The aim of this study was to evaluate the effects of the remnants of two suture materials on osseointegration of titanium implants in a rabbit tibial model. Calibrated defects were prepared in the tibia of five Chinchilla rabbits. Filaments of nonresorbable (NR) nylon or resorbable (R) chitosan were placed at the bone to implant interface, whereas control sites had no suture material. After a healing period of 4 weeks, a pull-out test procedure was performed followed by enzymatic analyses of the wound fluid and relative quantification of mRNA levels for bone-related and cytokine markers from the peri-implant bone. A trend toward a reduced pull-out force was observed in the NR group (NR: 23.0 ± 12.8 N; R: 33.9 ± 11.3 N; control: 33.6 ± 24.0 N). Similarly, the bone resorption marker vacuolar type H+-ATPase was increased in the NR group compared with that in the control group (P = 0.041). The R group showed trends for lower alkaline phosphatase activity and osteocalcin expression and higher total protein content and RNA compared with the control group. In this submerged healing model, peri-implant bone healing was marginally affected by the two suture materials tested. However, there was a tendency toward better osseointegration and lower expression of bone resorption markers in the R group compared with the control group.

  4. Suture materials affect peri-implant bone healing and implant osseointegration.

    PubMed

    Villa, Oscar; Lyngstadaas, Staale P; Monjo, Marta; Satué, Maria; Rønold, Hans J; Petzold, Christiane; Wohlfahrt, Johan C

    2015-09-01

    The aim of this study was to evaluate the effects of the remnants of two suture materials on osseointegration of titanium implants in a rabbit tibial model. Calibrated defects were prepared in the tibia of five Chinchilla rabbits. Filaments of nonresorbable (NR) nylon or resorbable (R) chitosan were placed at the bone to implant interface, whereas control sites had no suture material. After a healing period of 4 weeks, a pull-out test procedure was performed followed by enzymatic analyses of the wound fluid and relative quantification of mRNA levels for bone-related and cytokine markers from the peri-implant bone. A trend toward a reduced pull-out force was observed in the NR group (NR: 23.0 ± 12.8 N; R: 33.9 ± 11.3 N; control: 33.6 ± 24.0 N). Similarly, the bone resorption marker vacuolar type H+-ATPase was increased in the NR group compared with that in the control group (P = 0.041). The R group showed trends for lower alkaline phosphatase activity and osteocalcin expression and higher total protein content and RNA compared with the control group. In this submerged healing model, peri-implant bone healing was marginally affected by the two suture materials tested. However, there was a tendency toward better osseointegration and lower expression of bone resorption markers in the R group compared with the control group. PMID:26369486

  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. Ginsenoside Rg1 promotes osteogenic differentiation of rBMSCs and healing of rat tibial fractures through regulation of GR-dependent BMP-2/SMAD signaling

    PubMed Central

    Gu, Yanqing; Zhou, Jinchun; Wang, Qin; Fan, Weimin; Yin, Guoyong

    2016-01-01

    Fracture healing is closely related to the number and activity of bone marrow mesenchymal stem cells (BMSCs) near the fracture site. The present study was to investigate the effect of Rg1 on osteogenic differentiation of cultured BMSCs and related mechanisms and on the fracture healing in a fracture model. In vitro experiments showed that Rg1 promoted the proliferation and osteogenic differentiation of BMSCs. Western blot analyses demonstrated that Rg1 promoted osteogenic differentiation of BMSCs through the glucocorticoid receptor (GR)-dependent BMP-2/Smad signaling pathway. In vivo, X-ray examination showed that callus growth in rats treated with Rg1 was substantially faster than that in control rats after fracture. The results of H&E and Safranin-O/Fast Green staining revealed that, compared with controls, rats in the Rg1 treatment group had a significantly higher proportion of trabecular bone but a much lower proportion of fibers and cartilage components inside the callus. Micro-CT suggested that bone mineral density (BMD), percent bone volume (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th) were significantly increased in the treatment group, whereas trabecular separation (Tb.Sp) was significantly reduced. Thus, Rg1 promotes osteogenic differentiation by activating the GR/BMP-2 signaling pathway, enhances bone calcification, and ultimately accelerates the fracture healing in rats. PMID:27141994

  7. Cementless Titanium Mesh Fixation of Osteoporotic Burst Fractures of the Lumbar Spine Leads to Bony Healing: Results of an Experimental Sheep Model

    PubMed Central

    Roepenack, Paula; Roesner, Jan; Herlyn, Philipp Karl Ewald; Martin, Heiner; Reichel, Martin; Rotter, Robert; Vollmar, Brigitte; Mittlmeier, Thomas; Gradl, Georg

    2016-01-01

    Introduction. Current treatment strategies for osteoporotic vertebral compression fractures (VCFs) focus on cement-associated solutions. Complications associated with cement application are leakage, embolism, adjacent fractures, and compromise in bony healing. This study comprises a validated VCF model in osteoporotic sheep in order to (1) evaluate a new cementless fracture fixation technique using titanium mesh implants (TMIs) and (2) demonstrate the healing capabilities in osteoporotic VCFs. Methods. Twelve 5-year-old Merino sheep received ovariectomy, corticosteroid injections, and a calcium/phosphorus/vitamin D-deficient diet for osteoporosis induction. Standardized VCFs (type AO A3.1) were created, reduced, and fixed using intravertebral TMIs. Randomly additional autologous spongiosa grafting (G1) or no augmentation was performed (G2, n = 6 each). Two months postoperatively, macroscopic, micro-CT and biomechanical evaluation assessed bony consolidation. Results. Fracture reduction succeeded in all cases without intraoperative complications. Bony consolidation was proven for all cases with increased amounts of callus development for G2 (58.3%). Micro-CT revealed cage integration. Neither group showed improved results with biomechanical testing. Conclusions. Fracture reduction/fixation using TMIs without cement in osteoporotic sheep lumbar VCF resulted in bony fracture healing. Intravertebral application of autologous spongiosa showed no beneficial effects. The technique is now available for clinical use; thus, it offers an opportunity to abandon cement-associated complications. PMID:27019848

  8. Low-magnitude high-frequency vibration enhanced mesenchymal stem cell recruitment in osteoporotic fracture healing through the SDF-1/CXCR4 pathway.

    PubMed

    Wei, F Y; Chow, S K; Leung, K S; Qin, J; Guo, A; Yu, O L; Li, G; Cheung, W H

    2016-01-01

    Low-magnitude high-frequency vibration (LMHFV) has been proven to promote osteoporotic fracture healing. Mechanical stimulation was reported to enhance SDF-1/CXCR4 signalling in mesenchymal stem cells (MSCs). We hypothesised that LMHFV promoted osteoporotic fracture healing by enhancing MSC migration through the SDF-1/CXCR4 pathway. 152 ovariectomised SD-rats received closed femoral fracture in groups of vibration+MSC (VMG) (20 min/d, 5 d/week), vibration+MSC+AMD3100 (VMAG; AMD, a CXCR4 inhibitor) (1 mg/kg/d, intraperitoneal), MSC (MG) (1 × 106 MSC, intracardiac) or control (CG) for a treatment duration of 2, 4 or 8 weeks. MSC migration was evaluated by ex-vivo green fluorescent protein signal in the callus; and fracture healing was examined by weekly radiographs, endpoint computed-tomography and mechanical test. At week-2 and week-4, ex-vivo callus GFP intensity of VMG was significantly higher than other groups (p < 0.05). From week-2 to week-3, both callus width and callus area in VMG were significantly larger; and from week-7 to week-8, smaller than other groups (p < 0.05). At week-8, high-density bone volume fraction, bone volume fraction, bone mineral density and stiffness in VMG were significantly higher than other 3 groups (p < 0.05). This study demonstrated that LMHFV promoted MSC migration and fracture healing in osteoporotic rats. This effect was attenuated by CXCR4 inhibitor, providing strong evidence that SDF-1-mediated MSC migration was one of the important mechanisms through which LMHFV enhanced fracture healing. PMID:27215741

  9. 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

  10. 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.

  11. Gait and function as tools for the assessment of fracture repair - the role of movement analysis for the assessment of fracture healing.

    PubMed

    Rosenbaum, Dieter; Macri, Felipe; Lupselo, Fernando Silva; Preis, Osvaldo Cristiano

    2014-06-01

    Assessment of gait and function might be as sensitive tool to monitor the progress of fracture healing. Currently available assessment tools for function use instrumented three dimensional gait analysis or pedobarography. The analysis is focused on gait or movement parameters and seeks to identify abnormalities or asymmetries between legs or arms. The additional inclusion of muscle function by electromyography can further elucidate functional performance and its temporal development. Alternative approaches abstain from directly assessing function in the laboratory but rather determine the amount of activities of daily living or the mere ability to perform defined tasks such as walking, stair climbing or running. Some of these methods have been applied to determine recovery after orthopaedic interventions including fracture repair. The combination of lab-based functional measurements and assessment of physical activities in daily live may offer a valuable level of information about the gait quality and quantity of individual patients which sheds light on functional limitations or rehabilitation of gait and mobility after a disease or injury and the respective conservative, medical or surgical treatment.

  12. Sostdc1 deficiency accelerates fracture healing by promoting the expansion of periosteal mesenchymal stem cells.

    PubMed

    Collette, Nicole M; Yee, Cristal S; Hum, Nicholas R; Murugesh, Deepa K; Christiansen, Blaine A; Xie, LiQin; Economides, Aris N; Manilay, Jennifer O; Robling, Alexander G; Loots, Gabriela G

    2016-07-01

    Loss of Sostdc1, a growth factor paralogous to Sost, causes the formation of ectopic incisors, fused molars, abnormal hair follicles, and resistance to kidney disease. Sostdc1 is expressed in the periosteum, a source of osteoblasts, fibroblasts and mesenchymal progenitor cells, which are critically important for fracture repair. Here, we investigated the role of Sostdc1 in bone metabolism and fracture repair. Mice lacking Sostdc1 (Sostdc1(-/-)) had a low bone mass phenotype associated with loss of trabecular bone in both lumbar vertebrae and in the appendicular skeleton. In contrast, Sostdc1(-/-) cortical bone measurements revealed larger bones with higher BMD, suggesting that Sostdc1 exerts differential effects on cortical and trabecular bone. Mid-diaphyseal femoral fractures induced in Sostdc1(-/-) mice showed that the periosteal population normally positive for Sostdc1 rapidly expands during periosteal thickening and these cells migrate into the fracture callus at 3days post fracture. Quantitative analysis of mesenchymal stem cell (MSC) and osteoblast populations determined that MSCs express Sostdc1, and that Sostdc1(-/-) 5day calluses harbor >2-fold more MSCs than fractured wildtype controls. Histologically a fraction of Sostdc1-positive cells also expressed nestin and α-smooth muscle actin, suggesting that Sostdc1 marks a population of osteochondral progenitor cells that actively participate in callus formation and bone repair. Elevated numbers of MSCs in D5 calluses resulted in a larger, more vascularized cartilage callus at day 7, and a more rapid turnover of cartilage with significantly more remodeled bone and a thicker cortical shell at 21days post fracture. These data support accelerated or enhanced bone formation/remodeling of the callus in Sostdc1(-/-) mice, suggesting that Sostdc1 may promote and maintain mesenchymal stem cell quiescence in the periosteum.

  13. Connecting biology and mechanics in fracture healing: an integrated mathematical modeling framework for the study of nonunions.

    PubMed

    Geris, L; Sloten, J Vander; Van Oosterwyck, H

    2010-12-01

    Both mechanical and biological factors play an important role in normal as well as impaired fracture healing. This study aims to provide a mathematical framework in which both regulatory mechanisms are included. Mechanics and biology are coupled by making certain parameters of a previously established bioregulatory model dependent on local mechanical stimuli. To illustrate the potential added value of such a framework, this coupled model was applied to investigate whether local mechanical stimuli influencing only the angiogenic process can explain normal healing as well as overload-induced nonunion development. Simulation results showed that mechanics acting directly on angiogenesis alone was not able to predict the formation of overload-induced nonunions. However, the direct action of mechanics on both angiogenesis and osteogenesis was able to predict overload-induced nonunion formation, confirming the hypotheses of several experimental studies investigating the interconnection between angiogenesis and osteogenesis. This study shows that mathematical models can assist in testing hypothesis on the nature of the interaction between biology and mechanics.

  14. Secreted biofilm factors adversely affect cellular wound healing responses in vitro.

    PubMed

    Jeffery Marano, Robert; Jane Wallace, Hilary; Wijeratne, Dulharie; William Fear, Mark; San Wong, Hui; O'Handley, Ryan

    2015-08-17

    Although most chronic wounds possess an underlying pathology, infectious agents also contribute. In many instances, pathogens exist as biofilms forming clusters surrounded by a secreted extracellular substance. We hypothesized that compounds secreted by biofilm bacteria may inhibit normal wound healing events including cell proliferation and migration. Conditioned media from two common bacterial species associated with chronic skin wounds and chronic tympanic membrane perforations, Staphylococcus aureus and Pseudomonas aeruginosa, were evaluated for their capacity to affect keratinocyte proliferation and migration. Additionally, proteomic analysis was performed to identify proteins within the biofilm conditioned media that may contribute to these observed effects. Biofilm conditioned media from both species inhibited proliferation in human tympanic membrane derived keratinocytes, whereas only biofilm conditioned media from S. aureus inhibited migration. Human epidermal keratinocytes were found to be more sensitive to the effects of the conditioned media resulting in high levels of cell death. Heat treatment and microfiltration suggested that S. aureus activity was due to a protein, while P. aeruginosa activity was more likely due to a small molecule. Proteomic analysis identified several proteins with putative links to delayed wound healing. These include alpha hemolysin, alcohol dehydrogenase, fructose-bisphosphate aldolase, lactate dehydrogenase and epidermal cell differentiation inhibitor.

  15. Secreted biofilm factors adversely affect cellular wound healing responses in vitro.

    PubMed

    Jeffery Marano, Robert; Jane Wallace, Hilary; Wijeratne, Dulharie; William Fear, Mark; San Wong, Hui; O'Handley, Ryan

    2015-01-01

    Although most chronic wounds possess an underlying pathology, infectious agents also contribute. In many instances, pathogens exist as biofilms forming clusters surrounded by a secreted extracellular substance. We hypothesized that compounds secreted by biofilm bacteria may inhibit normal wound healing events including cell proliferation and migration. Conditioned media from two common bacterial species associated with chronic skin wounds and chronic tympanic membrane perforations, Staphylococcus aureus and Pseudomonas aeruginosa, were evaluated for their capacity to affect keratinocyte proliferation and migration. Additionally, proteomic analysis was performed to identify proteins within the biofilm conditioned media that may contribute to these observed effects. Biofilm conditioned media from both species inhibited proliferation in human tympanic membrane derived keratinocytes, whereas only biofilm conditioned media from S. aureus inhibited migration. Human epidermal keratinocytes were found to be more sensitive to the effects of the conditioned media resulting in high levels of cell death. Heat treatment and microfiltration suggested that S. aureus activity was due to a protein, while P. aeruginosa activity was more likely due to a small molecule. Proteomic analysis identified several proteins with putative links to delayed wound healing. These include alpha hemolysin, alcohol dehydrogenase, fructose-bisphosphate aldolase, lactate dehydrogenase and epidermal cell differentiation inhibitor. PMID:26278131

  16. Delayed healing of a navicular stress fracture, following limited weight-bearing activity

    PubMed Central

    Robinson, Matthew; Fulcher, Mark

    2014-01-01

    This report describes a 21-year-old man, a semiprofessional football (soccer) player, with a navicular stress fracture. It highlights the difficulty in diagnosing the condition and the complications arising from inadequate management. The case discusses the optimal management of these stress fractures and the detrimental role of weight-bearing recovery. The diagnosis of navicular stress fractures is challenging, and a high index of suspicion is required. The available literature indicates that limited weightbearing is not an appropriate treatment for navicular stress injuries. Non-weight-bearing (NWB) cast immobilisation for 6–8 weeks appears to be the gold standard treatment; however, open reduction with internal fixation (ORIF) has similar success rates and an equal return-to-play time but should also be followed by a period of NWB. NWB cast immobilisation for 6 weeks remains a good second option at any time following failed limited weight-bearing activity. PMID:24618870

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

    PubMed

    Bigham-Sadegh, Amin; Oryan, Ahmad

    2015-06-01

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

  18. 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

  19. Collective review: bioactive implants coated with poly(D,L-lactide) and growth factors IGF-I, TGF-beta1, or BMP-2 for stimulation of fracture healing.

    PubMed

    Schmidmaier, Gerhard; Lucke, Martin; Schwabe, Philipp; Raschke, Michael; Haas, Norbert P; Wildemann, Britt

    2006-01-01

    Demographic data reveal that due to the increasing aging of the population, complications with the musculoskeletal system will increase in the next years. One major problem in orthopedic and trauma surgery are the delayed healing or non-unions of long bone fractures. The exogenous application of growth factors can stimulate the bone healing to reduce these complications. Beside the choice of the optimal growth factor the application system is important. Therefore, we developed a new bioactive coating method for implants, which is based on a biodegradable poly(D,L-lactide) (coating thickness: 10 mum). This coating allows the incorporation of growth factors and the controlled release of these factors during the healing process without the need for further devices. The effect of different growth factors (IGF-I, TGF-beta1, and BMP-2) locally released from coated intramedullary implants on fracture healing was investigated with biomechanical and histological analysis in rats. All investigated growth factors stimulated the fracture healing as assessed with biomechanical tests and histological analysis. The local application of combined IGF-I and TGF-beta1 had the most stimulating effect on fracture healing, followed by the effect of BMP-2, IGF-I, and TGF-beta1 alone. Bioactive coating of biomechanical well-established implants can on the one hand stabilize the fracture and on the other hand stimulate healing processes to increase healing and to reduce the rate of complications.

  20. 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.

  1. Does the Time of Postoperative Bisphosphonate Administration Affect the Bone Union in Osteoporotic Intertrochanteric Fracture of Femur?

    PubMed Central

    Cho, Yoon Je; Chun, Young Soo; Kang, Joon Soon; Jung, Gwang Young; Lee, Jun Hee

    2015-01-01

    Purpose This study was designed to investigate the effect of bisphosphonate administration starting time on bone healing and to identify the best administration time following surgical treatment of osteoporotic intertrochanteric fractures. Materials and Methods Two hundreds and eighty four patients (284 hips; 52 males, 232 females) who underwent surgery following osteoporotic intertrochanteric fracture from December 2002 to December 2012 were retrospectively analyzed. The average follow-up period was 68.4 months. The patients were divided into three groups according to the time of bisphosphonate administration after operation: 1 week (group A; n=102), 1 month (group B; n=89), and 3 months (group C; n=93). Koval scores and change of Koval scores 1 year after operation were used for clinical evaluation. For radiologic evaluation, the time of callus appearance across the fracture line on sagittal and coronal radiographs and the time to absence of pain during hip motion was judged as the time of bone union. Results Koval scores one year after surgery for groups A, B, and C were 2.44, 2.36, and 2.43 (P=0.895), respectively. The mean time of union was 12.4, 11.9, and 12.3 weeks after operation in the three groups (P=0.883), respectively. There were zero cases of nonunion. There were 3, 5, and 7 cases of fixative displacement in the three groups, respectively, but the distribution showed no significant difference (P>0.472). Conclusion The initiating time of bisphosphonate administration following surgery does not affect the clinical outcomes in patients with osteoporotic intertrochanteric fracture. PMID:27536634

  2. The administration of intermittent parathyroid hormone affects functional recovery from trochanteric fractured neck of femur

    PubMed Central

    Chesser, T. J. S.; Fox, R.; Harding, K.; Halliday, R.; Barnfield, S.; Willett, K.; Lamb, S.; Yau, C.; Javaid, M. K.; Gray, A. C.; Young, J.; Taylor, H.; Shah, K.; Greenwood, R.

    2016-01-01

    Aims We wished to assess the feasibility of a future randomised controlled trial of parathyroid hormone (PTH) supplements to aid healing of trochanteric fractures of the hip, by an open label prospective feasibility and pilot study with a nested qualitative sub study. This aimed to inform the design of a future powered study comparing the functional recovery after trochanteric hip fracture in patients undergoing standard care, versus those who undergo administration of subcutaneous injection of PTH for six weeks. Patients and Methods We undertook a pilot study comparing the functional recovery after trochanteric hip fracture in patients 60 years or older, admitted with a trochanteric hip fracture, and potentially eligible to be randomised to either standard care or the administration of subcutaneous PTH for six weeks. Our desired outcomes were functional testing and measures to assess the feasibility and acceptability of the study. Results A total of 724 patients were screened, of whom 143 (20%) were eligible for recruitment. Of these, 123 were approached and 29 (4%) elected to take part. However, seven patients did not complete the study. Compliance with the injections was 11 out of 15 (73%) showing the intervention to be acceptable and feasible in this patient population. Take home message: Only 4% of patients who met the inclusion criteria were both eligible and willing to consent to a study involving injections of PTH, so delivering this study on a large scale would carry challenges in recruitment and retention. Methodological and sample size planning would have to take this into account. PTH administration to patients to enhance fracture healing should still be considered experimental. Cite this article: Bone Joint J 2016;98-B:840–5. PMID:27235530

  3. Effects of Low-Dose Microwave on Healing of Fractures with Titanium Alloy Internal Fixation: An Experimental Study in a Rabbit Model

    PubMed Central

    Zhang, Han; Fu, Tengfei; Jiang, Lan; Bai, Yuehong

    2013-01-01

    Background Microwave is a method for improving fracture repair. However, one of the contraindications for microwave treatment listed in the literature is surgically implanted metal plates in the treatment field. The reason is that the reflection of electromagnetic waves and the eddy current stimulated by microwave would increase the temperature of magnetic implants and cause heat damage in tissues. Comparing with traditional medical stainless steel, titanium alloy is a kind of medical implants with low magnetic permeability and electric conductivity. But the effects of microwave treatment on fracture with titanium alloy internal fixation in vivo were not reported. The aim of this article was to evaluate the security and effects of microwave on healing of a fracture with titanium alloy internal fixation. Methods Titanium alloy internal fixation systems were implanted in New Zealand rabbits with a 3.0 mm bone defect in the middle of femur. We applied a 30-day microwave treatment (2,450MHz, 25W, 10 min per day) to the fracture 3 days after operation. Temperature changes of muscle tissues around implants were measured during the irradiation. Normalized radiographic density of the fracture gap was measured on the 10th day and 30th day of the microwave treatment. All of the animals were killed after 10 and 30 days microwave treatment with histologic and histomorphometric examinations performed on the harvested tissues. Findings The temperatures did not increase significantly in animals with titanium alloy implants. The security of microwave treatment was also supported by histology of muscles, nerve and bone around the implants. Radiographic assessment, histologic and histomorphometric examinations revealed significant improvement in the healing bone. Conclusion Our results suggest that, in the healing of fracture with titanium alloy internal fixation, a low dose of microwave treatment may be a promising method. PMID:24086626

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. Polymer cable/grip-plate system with locking screws for stable fixation to promote healing of trochanteric osteotomies or fractures in revision total hip arthroplasty.

    PubMed

    Berend, Keith R; Willen, Jacob L; Morris, Michael J; Adams, Joanne B; Lombardi, Adolph V

    2014-11-01

    Multiple methods have been proposed to establish stable fixation to promote healing of trochanteric osteotomies or fractures in revision total hip arthroplasty (revTHA), from wiring techniques through cable-plate systems with or without supplemental locking screws. The purpose of this study is to report the clinical results of a single cable-plate system with locked screw fixation in revTHA. Between 2009 and 2012, 27 grip-plates (Supercable® System, Kinamed Inc., Camarillo, CA) were used in 26 patients in 27 revTHA procedures. Utilization was 12 1-hole (50 mm) grip-plates, 10 2-hole (135 mm) grip-plates, four 4-hole (190 mm) grip-plates, and one 6-hole (245 mm) grip-plate. There were 14 women and 12 men. Age averaged 63.2 years and BMI averaged 29.4 kg/m2. At average 2.5 year follow-up, grip-plate fixation was considered successful in 22 hips (81%) with five failures. Three failures consisted of 50 mm/short grip-plates used in one trochanteric slide, and two intraoperative trochanteric fractures during revTHA. The two additional failures were related to pre-revision trochanteric avulsion from bony necrosis of the proximal femur. An additional three grip-plates were removed electively for soft-tissue irritation and pain but with successful fixation and bony healing. Thus 70% of hips were free of reoperation related to the grip-plate. All other hips had successful fixation and the grip-plate was not symptomatic. In this study, the cable-grip system and isoelastic Supercables provided reliable fixation for adequate healing of difficult ETO and trochanteric fractures with an 81% rate of mechanical success with radiographic and clinical healing observed.

  9. Pregnancy affects cellular activity, but not tissue mechanical properties, in the healing rabbit medial collateral ligament.

    PubMed

    Hart, D A; Reno, C; Frank, C B; Shrive, N G

    2000-05-01

    Recently, evidence has been accumulating that ligament and joint laxity is altered in women and rabbits during pregnancy. Furthermore, many female adolescents injure ligaments through participation in athletics and other activities. Therefore, to determine whether pregnancy has different effects on the injured and uninjured medial collateral ligament of the rabbit knee, we investigated cellular changes (mRNA levels) and alterations in tissue properties (biomechanics) accompanying pregnancy in animals with the medial collateral ligament injured during adolescence and bred for their primigravid pregnancy as young adults. Assessment of mRNA levels for matrix molecules, matrix metalloproteinases and tissue inhibitor of metalloproteinase-1, growth factors and sex hormone receptors, inflammatory cytokines, inducible nitric oxide synthase, and cyclooxygenase-2 by semiquantitative reverse transcription-polymerase chain reaction revealed that pregnancy had different impacts on scar and uninjured tissue for six of 15 genes assessed. A pregnancy-associated increase in laxity of the medial collateral ligament was observed for rabbits in the uninjured primigravida group; however, no increase was observed for injured rabbits during pregnancy. The injured ligament was already significantly more lax than the normal counterpart, and pregnancy did not lead to additional laxity or prevent the normal decline in laxity as the scar matured in nonpregnant animals. These results indicate that the impact of pregnancy on laxity and cell activity of the medial collateral ligament is dependent on whether the ligament is uninjured or injured. Pregnancy had no significant effect on structural (stiffness and failure load), material (stress at failure and Young's modulus), or viscoelastic (cyclic and static relaxation) properties of tissue from uninjured or injured medial collateral ligament. Therefore, the properties of the healing ligament were not adversely affected during pregnancy in this

  10. Experimental study in order to assess the effects of limited periosteum stripping on the fracture healing and to compare osteosynthesis using plates and screws with intramedullary Kirschner wire fixation.

    PubMed

    Neagu, Tiberiu Paul; Enache, Valentin; Cocoloş, Ion; Ţigliş, Mirela; Cobilinschi, Cristian; Ţincu, Radu

    2016-01-01

    There are many studies that investigate indirect and direct fracture healing but few mention the effect of periosteum stripping on consolidation of fractures. Most of these studies use only one method of osteosynthesis for each group. Therefore, we reported a new developed murine model in order to assess if limited periosteum stripping influence significantly the quality of the fracture healing process by comparing two different osteosynthesis methods to reduce simultaneously bilateral femur fractures. We applied the experimental protocol for a number of 12 rats. We used plates and screws to reduce femoral osteotomy for the right hind limb and intramedullary Kirschner wire for the left hind limb. Clinical, radiological and histological assessments were made for a period of eight weeks. The absence of a healthy hind limb led to a slower healing process based on the histological findings and to implant failure based on radiological findings. In summary, complete fracture healing was not achieved during this experimental study. Therefore, we consider that future studies are needed for a better understanding of the effects of periosteum removal on the fracture healing process. PMID:27516016

  11. 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

  12. 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.

  13. Fracture healing in mice lacking Pten in osteoblasts: a micro-computed tomography image-based analysis of the mechanical properties of the femur.

    PubMed

    Collins, Caitlyn J; Vivanco, Juan F; Sokn, Scott A; Williams, Bart O; Burgers, Travis A; Ploeg, Heidi-Lynn

    2015-01-21

    In the United States, approximately eight million osseous fractures are reported annually, of which 5-10% fail to create a bony union. Osteoblast-specific deletion of the gene Pten in mice has been found to stimulate bone growth and accelerate fracture healing. Healing rates at four weeks increased in femurs from Pten osteoblast conditional knock-out mice (Pten-CKO) compared to wild-type mice (WT) of the same genetic strain as measured by an increase in mechanical stiffness and failure load in four-point bending tests. Preceding mechanical testing, each femur was imaged using a Skyscan 1172 micro-computed tomography (μCT) scanner (Skyscan, Kontich, Belgium). The present study used µCT image-based analysis to test the hypothesis that the increased femoral fracture force and stiffness in Pten-CKO were due to greater section properties with the same effective material properties as that of the WT. The second moment of area and section modulus were computed in ImageJ 1.46 (National Institutes of Health) and used to predict the effective flexural modulus and the stress at failure for fourteen pairs of intact and callus WT and twelve pairs of intact and callus Pten-CKO femurs. For callus and intact femurs, the failure stress and tissue mineral density of the Pten-CKO and WT were not different; however, the section properties of the Pten-CKO were more than twice as large 28 days post-fracture. It was therefore concluded, when the gene Pten was conditionally knocked-out in osteoblasts, the resulting increased bending stiffness and force to fracture were due to increased section properties.

  14. Fracture Healing in Mice Lacking Pten in Osteoblasts: A Micro-Computed Tomography Image-Based Analysis of the Mechanical Properties of the Femur

    PubMed Central

    Collins, Caitlyn J.; Vivanco, Juan; Sokn, Scott; Williams, Bart O.; Burgers, Travis A.; Ploeg, Heidi-Lynn

    2014-01-01

    In the United States, approximately 8 million osseous fractures are reported annually, of which 5-10% fail to create a bony union. Osteoblast-specific deletion of the gene Pten in mice has been found to stimulate bone growth and accelerate fracture healing. Healing rates at four weeks increased in femurs from Pten osteoblast conditional knock-out mice (Pten-CKO) compared to wild-type mice (WT) of the same genetic strain as measured by an increase in mechanical stiffness and failure load in four-point bending tests. Preceding mechanical testing, each femur was imaged using a Skyscan 1172 micro-computed tomography (μCT) scanner (Skyscan, Kontich, Belgium). The present study used μCT image-based analysis to test the hypothesis that the increased femoral fracture force and stiffness in Pten-CKO were due to greater section properties with the same effective material properties as that of the WT. The second moment of area and section modulus were computed in ImageJ 1.46 (National Institutes of Health) and used to predict the effective flexural modulus and the stress at failure for fourteen pairs of intact and callus WT and twelve pairs of intact and callus Pten-CKO femurs. For callus and intact femurs, the failure stress and tissue mineral density of the Pten-CKO and WT were not different; however, the section properties of the Pten-CKO were more than twice as large 28 days post-fracture. It was therefore concluded, when the gene Pten was conditionally knocked-out in osteoblasts, the resulting increased bending stiffness and force to fracture were due to increased section properties. PMID:25498366

  15. 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.

  16. 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

  17. A new growth factor controlled drug release system to promote healing of bone fractures: nanospheres of recombinant human bone morphogenetic-2 and polylactic acid.

    PubMed

    Chen, Lin; Liu, Lei; Li, Cai; Tan, Yinghui; Zhang, Gang

    2011-04-01

    To prepare a new drug control release system, which can markedly promote the healing of bone fractures. Optimized water-in-oil-in-water multiple emulsion evaporation method, prepared nanospheres of recombinant human bone morphogenetic-2 and polylactic acid (rhBMP-2-PLA-Ns). Its physical character was determined by the enzyme linked immunosorbent assay method. Its bioactivity was measured with the microculture tetrazolium test immunohistochemical analyses, alizarin red staining and western blot analysis. rhBMP-2-PLA-Ns exhibited an even and uniform spherical appearance without adhesion, with a particle size distribution between 35 and 65 nm, and a mean size of 45 nm. The drug loading volume and encapsulation efficiency reached ([124.73 +/- 0.41] x 10(-3))% and (90.54 +/- 1.32)%, respectively. The drug release in vitro persisted for 14 days, with a mean concentration of 73.44 +/- 5.38 ng/ml, and corresponded to the Higuichi equation (r = 0.9962). The microculture tetrazolium test showed that 4 days later, the optical density value ranking was rhBMP-2-PLA-N group > rhBMP-2 group > blank control group. Fluorescence immunocytochemical analysis showed that 10 days later the fluorescent density of the rhBMP-2-PLA-N group was significantly higher than the other two groups. Western blot analysis confirmed that the amount of vascular endothelial growth factor in the rhBMP-2-PLA-N group was the greatest. This study showed that rhBMP-2-PLA-Ns have excellent biological activity, can promote proliferation, differentiation and mineralization of osteoblasts. The drug release time is suitable for fracture healing and is an ideal delivery system for fracture healing. PMID:21776677

  18. Smoking affects the self-healing capacity of periodontal tissues. A histological study in the rat.

    PubMed

    Benatti, Bruno Braga; César-Neto, João Batista; Gonçalves, Patrícia Furtado; Sallum, Enílson Antônio; Nociti, Francisco Humberto

    2005-10-01

    This study aimed to evaluate in rats the impact of cigarette smoke inhalation (CSI) and nicotine administration (NA) on a periodontal healing model in the absence of a plaque biofilm. Wistar rats (n = 42) were assigned to three groups: Group 1, control (n = 14); Group 2, NA (3 mg kg(-1)) (n = 14); and Group 3, CSI (n = 14). Thirty days after CSI and NA exposure, fenestration defects were created buccally to the distal root of the first mandibular molar. The animals were killed 21 d later and their mandibles were processed for histological examination. The percentage of bone fill and the density of newly formed bone were assessed histometrically. Intergroup analysis demonstrated that compared to the control and NA groups, CSI was associated with a reduced rate of bone repair. No new cementum had been formed along the root surface in any of the three groups. It is concluded that cigarette smoke reduces the self-healing capacity of periodontal tissues.

  19. Mechanical Bowel Preparation Does Not Affect Anastomosis Healing in an Experimental Rat Model

    PubMed Central

    Piroglu, Isılay; Tulgar, Serkan; Thomas, David Terence; Cakiroglu, Basri; Piroglu, Mustafa Devrim; Bozkurt, Yasin; Gergerli, Ruken; Ates, Nagihan Gozde

    2016-01-01

    Background Mechanical bowel preparation before colorectal surgery is commonly performed, but its benefits are controversial. The aim of this study was to compare the effects of mechanical bowel preparation on healing of colonic anastomosis and tissue strength. Material/Methods After institutional review board approval, 20 adult Wistar albino rats were randomly divided into 2 groups of 10 animals each. Mechanical bowel preparation including sodium phosphate was performed on the experimental group via a feeding tube, whereas no bowel preparation procedures were performed on the control group. Transverse colon resection and anastomosis were performed on all rats under general anaesthesia. On postoperative day 5, re-laparotomy was performed and the anastomotic areas were resected. Animals were killed, after which bursting pressure and tissue hydroxyproline concentrations were measured, histopathological examination was performed, and we evaluated and compared the results. Results There were no differences between control and experimental groups in bursting pressure, tissue hydroxyproline concentrations, or histopathological examination results (P>0.05). Conclusions Our study demonstrated no significant difference between bursting pressures, tissue hydroxyproline levels, or modified wound healing score at postoperative day 5 between rats undergoing and not undergoing mechanical bowel preparation. Mechanical bowel preparation is not essential for healing or strength of colonic anastomosis in rats. PMID:26725402

  20. Proximal fifth metatarsal fractures.

    PubMed

    Ramponi, Denise R

    2013-01-01

    The most common fracture of the foot is a fracture of the proximal fifth metatarsal. In general, there are 3 types of fractures involving the proximal fifth metatarsal area, including a proximal diaphyseal stress fracture, a Jones fracture, and an avulsion fracture of the tuberosity. Some fractures of the fifth metatarsal heal without difficulty, whereas some have the potential for nonunion or delayed healing. Each fracture has some variation in the anatomical location on the fifth metatarsal, the mechanism of injury, the radiographic findings, and the treatment plan. Avulsion fractures of the tuberosity often heal without difficulty, yet fractures distal to the area of insertion of the peroneus brevis tendon are prone to nonunion and delayed healing (). Differential diagnosis of a fifth metatarsal midfoot injury includes ankle sprains, midfoot sprains, plantar facial ruptures, peroneus tendon ruptures, and other foot fractures.

  1. A multi-centre retrospective study of mandibular fractures: do occlusal support and the mandibular third molar affect mandibular angle and condylar fractures?

    PubMed

    Hasegawa, T; Sadakane, H; Kobayashi, M; Tachibana, A; Oko, T; Ishida, Y; Fujita, T; Takenono, I; Komatsubara, H; Takeuchi, J; Ichiki, K; Miyai, D; Komori, T

    2016-09-01

    This retrospective study was performed to investigate the influence of occlusal support and the presence, state, and position of mandibular third molars on the incidence of mandibular angle and condylar fractures. The following variables were investigated: age, sex, cause of fracture, presence and state (impaction, angulation, and the number of roots) of the mandibular third molars, site of the mandibular fracture, presence of occlusal support, duration of intermaxillary fixation, and postoperative complications. Various risk factors for mandibular angle and condylar fractures were investigated by univariate analysis. The risk of mandibular angle fracture was significantly higher in patients with occlusal support and mandibular third molars. The risk of condylar fracture was significantly higher in patients without occlusal support or mandibular third molars. The position and angulation of the mandibular third molars were not significant risk factors in mandibular angle and condylar fractures. This study demonstrated the influence of occlusal support and the presence of mandibular third molars on the incidence of mandibular angle and condylar fractures. The presence of occlusal support may be a more important factor affecting mandibular angle or condylar fractures than the position of the mandibular third molars.

  2. Oxidized (non)-regenerated cellulose affects fundamental cellular processes of wound healing

    PubMed Central

    Wagenhäuser, M. U.; Mulorz, J.; Ibing, W.; Simon, F.; Spin, J. M.; Schelzig, H.; Oberhuber, A.

    2016-01-01

    In this study we investigated how hemostats such as oxidized regenerated cellulose (ORC, TABOTAMP) and oxidized non-regenerated cellulose (ONRC, RESORBA CELL) influence local cellular behavior and contraction of the extracellular matrix (ECM). Human stromal fibroblasts were inoculated in vitro with ORC and ONRC. Cell proliferation was assayed over time, and migration was evaluated by Live Cell imaging microscopy. Fibroblasts grown in collagen-gels were treated with ORC or ONRC, and ECM contraction was measured utilizing a contraction assay. An absolute pH decline was observed with both ORC and ONRC after 1 hour. Mean daily cell proliferation, migration and matrix contraction were more strongly inhibited by ONRC when compared with ORC (p < 0.05). When control media was pH-lowered to match the lower pH values typically seen with ORC and ONRC, significant differences in cell proliferation and migration were still observed between ONRC and ORC (p < 0.05). However, in these pH conditions, inhibition of matrix contraction was only significant for ONRC (p < 0.05). We find that ORC and ONRC inhibit fibroblast proliferation, migration and matrix contraction, and stronger inhibition of these essential cellular processes of wound healing were observed for ONRC when compared with ORC. These results will require further validation in future in vivo experiments to clarify the clinical implications for hemostat use in post-surgical wound healing. PMID:27557881

  3. Oxidized (non)-regenerated cellulose affects fundamental cellular processes of wound healing.

    PubMed

    Wagenhäuser, M U; Mulorz, J; Ibing, W; Simon, F; Spin, J M; Schelzig, H; Oberhuber, A

    2016-01-01

    In this study we investigated how hemostats such as oxidized regenerated cellulose (ORC, TABOTAMP) and oxidized non-regenerated cellulose (ONRC, RESORBA CELL) influence local cellular behavior and contraction of the extracellular matrix (ECM). Human stromal fibroblasts were inoculated in vitro with ORC and ONRC. Cell proliferation was assayed over time, and migration was evaluated by Live Cell imaging microscopy. Fibroblasts grown in collagen-gels were treated with ORC or ONRC, and ECM contraction was measured utilizing a contraction assay. An absolute pH decline was observed with both ORC and ONRC after 1 hour. Mean daily cell proliferation, migration and matrix contraction were more strongly inhibited by ONRC when compared with ORC (p < 0.05). When control media was pH-lowered to match the lower pH values typically seen with ORC and ONRC, significant differences in cell proliferation and migration were still observed between ONRC and ORC (p < 0.05). However, in these pH conditions, inhibition of matrix contraction was only significant for ONRC (p < 0.05). We find that ORC and ONRC inhibit fibroblast proliferation, migration and matrix contraction, and stronger inhibition of these essential cellular processes of wound healing were observed for ONRC when compared with ORC. These results will require further validation in future in vivo experiments to clarify the clinical implications for hemostat use in post-surgical wound healing. PMID:27557881

  4. Do nonsteroidal anti-inflammatory drugs affect bone healing? A critical analysis.

    PubMed

    Pountos, Ippokratis; Georgouli, Theodora; Calori, Giorgio M; Giannoudis, Peter V

    2012-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) play an essential part in our approach to control pain in the posttraumatic setting. Over the last decades, several studies suggested that NSAIDs interfere with bone healing while others contradict these findings. Although their analgesic potency is well proven, clinicians remain puzzled over the potential safety issues. We have systematically reviewed the available literature, analyzing and presenting the available in vitro animal and clinical studies on this field. Our comprehensive review reveals the great diversity of the presented data in all groups of studies. Animal and in vitro studies present so conflicting data that even studies with identical parameters have opposing results. Basic science research defining the exact mechanism with which NSAIDs could interfere with bone cells and also the conduction of well-randomized prospective clinical trials are warranted. In the absence of robust clinical or scientific evidence, clinicians should treat NSAIDs as a risk factor for bone healing impairment, and their administration should be avoided in high-risk patients. PMID:22272177

  5. Effect of a bioabsorbable, super-high molecular weight poly-D,L-lactic acid plate containing recombinant human bone morphogenetic protein-2 for fracture healing

    PubMed Central

    ZHOU, NING-FENG; HUANG, YU-FENG; WANG, JIN-WU

    2015-01-01

    The aim of this study was to investigate the effect of a bioabsorbable, super-high molecular weight poly-D,L-lactic acid (PDLLA) plate exhibiting the sustained release of recombinant human bone morphogenetic protein-2 (rhBMP-2) (PDLLA-rhBMP-2) on the treatment of fracture with internal fixation. A total of 32 New Zealand rabbits were randomly allocated to one of four groups (2, 4, 8 and 12 weeks), and a 2.5-mm middle ulnar osteotomy was performed bilaterally. The right side (experimental side) was fixed internally with PDLLA-rhBMP-2, and the left side (control side) was fixed with a normal PDLLA plate. At 2, 4, 8 and 12 weeks after surgery, the gross pathology of the ulnas was examined and radiographic, histological and computer image analyses were performed. The results demonstrated that the ulna fractures were fixed stably with the two bioactive plates at 2, 4, 8 and 12 weeks after surgery. At the 8-week time-point, 7 rabbits exhibited good healing at the osteotomy site on the experimental side. At 12 weeks after surgery, 8 rabbits exhibited good healing at the osteotomy site on both sides, but the experimental side showed enhanced compatibility between the plates and surrounding tissue, faster bone formation, a greater bone regeneration mass and better medullary canal structure compared with the control side. In conclusion, PPLLA-rhBMP-2 may be effectively used to treat fracture or nonunion at a non-weight-bearing site. PMID:26640559

  6. 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.

  7. 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

  8. 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.

  9. 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. PMID:26851411

  10. Fractures

    MedlinePlus

    ... commonly happen because of car accidents, falls, or sports injuries. Other causes are low bone density and osteoporosis, which cause weakening of the bones. Overuse can cause stress fractures, which are very small cracks in the ...

  11. Expression of sclerostin scFv and the effect of sclerostin scFv on healing of osteoporotic femur fracture in rats.

    PubMed

    Yao, Qi; Ni, Jie; Hou, Yu; Ding, Lixiang; Zhang, Licheng; Jiang, Hua

    2014-06-01

    Osteoporosis is a systemic metabolic disease characterized by low bone mass with deterioration of the bony microstructure which leads to both bone brittleness and increased risk of fracture. Sclerostin is a protein encoded by the SOST gene which is specifically expressed in osteocyte. Monoclonal antibodies of sclerostin can promote bone formation by antagonizing its inhibitory action. However, the effectiveness of monoclonal antibodies to exert such effects are limited by the large molecular mass and high immunogenicity. Here, we report that we purified a high immune affinity, single-chain antibody of SOST: SOST-single-chain Fv (scFv). Real-time polymerase chain reaction amplification of the variable regions of the heavy- and light-chain gene from a secretory anti-SOST antibody was performed. Animal experiments showed that SOST-scFv promoted bone healing in a rat model of osteoporosis.

  12. Ankle fracture - aftercare

    MedlinePlus

    ... that surgery can allow faster and more reliable healing. In children, the fracture involves the part of ... will use a special walking boot as the healing progresses. You will need to learn: How to ...

  13. Bone Morphogenetic Protein for the Healing of Tibial Fracture: A Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Jiang, Chaoyin; Wang, Chunyang; Chen, Hua; Chai, Yimin

    2015-01-01

    Purpose To review the evidence from RCTs on clinical outcomes and benefit of acute tibial fracture and nonunion treated with and without BMPs. Material We searched multiple databases (MEDLINE, EMABSE, BIOSIS and Cochrane central) as well as reference lists of articles and contacted authors. Evaluated outcomes included union rate, revision rate, hardware failure and infection. The weighted and standard mean difference (WMD and SMD) or the relative risk (RR) was calculated for continuous or dichotomous data respectively. The quality of the trial was assessed, and meta-analyses were performed with the Cochrane Collaboration’s REVMAN 5.0 software. Results Eight RCTs involving 1113 patients were included. For acute tibial fracture, BMP group was associated with a higher rate of union (RR, 1.16; 95% CI, 1.04 to 1.30) and a lower rate of revision (RR, 0.68; 95% CI, 0.54 to 0.85) compared with control group. No significant differences were found in rate of hardware failure and infection. The pooled RR for achieving union for tibial fracture nonunion was 0.98 (95% CI, 0.86 to 1.13). There was no significant difference between the two groups in the rate of revision (RR, 0.48; 95% CI, 0.13 to 1.85) and infection (RR, 0.61; 95% CI, 0.37 to 1.02). Conclusion Study on acute tibial fractures suggests that BMP is more effective that controls, for bone union and for decreasing the rate of surgical revision to achieve union. For the treatment of tibial fracture nonunion, BMP leads to similar results to as autogenous bone grafting. Finally, well-designed RCTs of BMP for tibial fracture treatment are also needed. PMID:26509264

  14. Can words heal? Using affect labeling to reduce the effects of unpleasant cues on symptom reporting

    PubMed Central

    Constantinou, Elena; Van Den Houte, Maaike; Bogaerts, Katleen; Van Diest, Ilse; Van den Bergh, Omer

    2014-01-01

    Processing unpleasant affective cues induces elevated momentary symptom reports, especially in persons with high levels of symptom reporting in daily life. The present study aimed to examine whether applying an emotion regulation strategy, i.e. affect labeling, can inhibit these emotion influences on symptom reporting. Student participants (N = 61) with varying levels of habitual symptom reporting completed six picture viewing trials of homogeneous valence (three pleasant, three unpleasant) under three conditions: merely viewing, emotional labeling, or content (non-emotional) labeling. Affect ratings and symptom reports were collected after each trial. Participants completed a motor inhibition task and self-control questionnaires as indices of their inhibitory capacities. Heart rate variability was also measured. Labeling, either emotional or non-emotional, significantly reduced experienced affect, as well as the elevated symptoms reports observed after unpleasant picture viewing. These labeling effects became more pronounced with increasing levels of habitual symptom reporting, suggesting a moderating role of the latter variable, but did not correlate with any index of general inhibitory capacity. Our findings suggest that using an emotion regulation strategy, such as labeling emotional stimuli, can reverse the effects of unpleasant stimuli on symptom reporting and that such strategies can be especially beneficial for individuals suffering from medically unexplained physical symptoms. PMID:25101048

  15. Effect of Pulsed Wave Low-Level Laser Therapy on Tibial Complete Osteotomy Model of Fracture Healing With an Intramedullary Fixation

    PubMed Central

    Mostafavinia, Atarodalsadat; Masteri Farahani, Reza; Abbasian, Mohammadreza; Vasheghani Farahani, Mohammadmehdi; Fridoni, Mohammadjavad; Zandpazandi, Sara; Ghoreishi, Seyed Kamran; Abdollahifar, Mohammad Amin; Pouriran, Ramin; Bayat, Mohammad

    2015-01-01

    Background: Fractures pose a major worldwide challenge to public health, causing tremendous disability for the society and families. According to recent studies, many in vivo and in vitro experiments have shown the positive effects of PW LLLT on osseous tissue. Objectives: The aim of this study was to evaluate the outcome of infrared pulsed wave low-level laser therapy (PW LLLT) on the fracture healing process in a complete tibial osteotomy in a rat model, which was stabilized by an intramedullary pin. Materials and Methods: This experimental study was conducted at Shahid Beheshti University of Medical Sciences in Tehran, Iran. We performed complete tibial osteotomies in the right tibias for the population of 15 female rats. The rats were divided randomly into three different groups: I) Control rats with untreated bone defects; II) Rats irradiated by a 0.972 J/cm2 PW LLLT; and III) Rats irradiated by a 1.5 J/cm2 PW LLLT. The right tibias were collected six weeks following the surgery and a three-point bending test was performed to gather results. Immediately after biomechanical examination, the fractured bones were prepared for histological examinations. Slides were examined using stereological method. Results: PW LLLT significantly caused an increase in maximum force (N) of biomechanical repair properties for osteotomized tibias in the first and second laser groups (30.0 ± 15.9 and 32.4 ± 13.8 respectively) compared to the control group (8.6 ± 4.5) LSD test, P = 0.019, P = 0.011 respectively). There was a significant increase in the osteoblast count of the first and second laser groups (0.53 ± 0.06, 0.41 ± 0.06 respectively) compared to control group (0.31 ± 0.04) (LSD test, P = 0001, P = 0.007 respectively). Conclusions: This study confirmed the efficacy of PW LLLT on biomechanical strength, trabecular bone volume, callus volume, and osteoblast number of repairing callus in a complete tibial osteotomy animal model at a relatively late stage of the bone

  16. Local transplantation of ex vivo expanded bone marrow-derived CD34-positive cells accelerates fracture healing.

    PubMed

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

    2012-01-01

    Transplantation of bone marrow (BM) CD34(+) cells, an endothelial/hematopoietic progenitor-enriched cell population, has shown therapeutic efficiency in the treatment of ischemic diseases enhancing neovascularization. However, the number of CD34(+) cells obtained from bone marrow is not sufficient for routine clinical application. To overcome this issue, we developed a more efficient and clinically applicable CD34(+) cell expansion method. Seven-day ex vivo expansion culture of BM CD34(+) cells with a cocktail of five growth factors containing VEGF, SCF, IL-6, Flt-3 ligand, and TPO resulted in reproducible more than 20-fold increase in cell number. The favorable effect of the local transplantation of culture expanded (cEx)-BM CD34(+) cells on rat unhealing fractures was equivalent or higher than that of nonexpanded (fresh) BM CD34(+) cells exhibiting sufficient therapeutic outcome with frequent vasculogenic/osteogenic differentiation of transplanted cEx-BM CD34(+) cells and fresh BM CD34(+) cells as well as intrinsic enhancement of angiogenesis/osteogenesis at the treated fracture sites. Specifically, cEx-BM CD34(+) cell treatment demonstrated the best blood flow recovery at fracture sites compared with the nonexpanded BM CD34(+) cells. In vitro, cEx-BM CD34(+) cells showed higher colony/tube-forming capacity than nonexpanded BM CD34(+) cells. Both cells demonstrated differentiation potential into osteoblasts. Since fresh BM CD34(+) cells can be easily collected from fracture sites at the time of primary operation and stored for future use, autologous cEx-BM CD34(+) cell transplantation would be not only a simple but also a promising therapeutic strategy for unhealing fractures in the field of orthopedic trauma surgery.

  17. 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. PMID:15758516

  18. 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

  19. Comparison between different methods for biomechanical assessment of ex vivo fracture callus stiffness in small animal bone healing studies.

    PubMed

    Steiner, Malte; Volkheimer, David; Meyers, Nicholaus; Wehner, Tim; Wilke, Hans-Joachim; Claes, Lutz; Ignatius, Anita

    2015-01-01

    For ex vivo measurements of fracture callus stiffness in small animals, different test methods, such as torsion or bending tests, are established. Each method provides advantages and disadvantages, and it is still debated which of those is most sensitive to experimental conditions (i.e. specimen alignment, directional dependency, asymmetric behavior). The aim of this study was to experimentally compare six different testing methods regarding their robustness against experimental errors. Therefore, standardized specimens were created by selective laser sintering (SLS), mimicking size, directional behavior, and embedding variations of respective rat long bone specimens. For the latter, five different geometries were created which show shifted or tilted specimen alignments. The mechanical tests included three-point bending, four-point bending, cantilever bending, axial compression, constrained torsion, and unconstrained torsion. All three different bending tests showed the same principal behavior. They were highly dependent on the rotational direction of the maximum fracture callus expansion relative to the loading direction (creating experimental errors of more than 60%), however small angular deviations (<15°) were negligible. Differences in the experimental results between the bending tests originate in their respective location of maximal bending moment induction. Compared to four-point bending, three-point bending is easier to apply on small rat and mouse bones under realistic testing conditions and yields robust measurements, provided low variation of the callus shape among the tested specimens. Axial compressive testing was highly sensitive to embedding variations, and therefore cannot be recommended. Although it is experimentally difficult to realize, unconstrained torsion testing was found to be the most robust method, since it was independent of both rotational alignment and embedding uncertainties. Constrained torsional testing showed small errors (up to

  20. 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

  1. [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.

  2. Unusual stress fracture in an adolescent baseball pitcher affecting the trochlear groove of the olecranon.

    PubMed

    Blake, Joseph J; Block, John J; Hannah, Gene A; Kan, J Herman

    2008-07-01

    Stress fractures of the proximal ulna are known to occur in throwing athletes. Most cases extend to involve the olecranon, and cases limited to the trochlear groove are rare. In this report we present a 17-year-old elite baseball pitcher with a stress fracture of the trochlear groove of the proximal ulna. Diagnosis was made by demonstration of characteristic signal changes on MRI of the elbow. The fracture occurred at the cortical notch, also known as the pseudodefect of the trochlear groove. This case suggests that the cortical notch serves as an area of weakness predisposing pitchers to development of a stress fracture.

  3. 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

  4. Does Sitagliptin Affect the Rate of Osteoporotic Fractures in Type 2 Diabetes? Population-Based Cohort Study

    PubMed Central

    Josse, Robert G.; Lin, Mu; Eurich, Dean T.

    2016-01-01

    Context: Type 2 diabetes and osteoporosis are both common, chronic, and increase with age, whereas type 2 diabetes is also a risk factor for major osteoporotic fractures (MOFs). However, different treatments for type 2 diabetes can affect fracture risk differently, with metaanalyses showing some agents increase risk (eg, thiazolidinediones) and some reduce risk (eg, sitagliptin). Objective: To determine the independent association between new use of sitagliptin and MOF in a large population-based cohort study. Design, Setting, and Subjects: A sitagliptin new user study design employing a nationally representative Unites States claims database of 72 738 insured patients with type 2 diabetes. We used 90-day time-varying sitagliptin exposure windows and controlled confounding by using multivariable analyses that adjusted for clinical data, comorbidities, and time-updated propensity scores. Main Outcomes: We compared the incidence of MOF (hip, clinical spine, proximal humerus, distal radius) in new users of sitagliptin vs nonusers over a median 2.2 years follow-up. Results: At baseline, the median age was 52 years, 54% were men, and median A1c was 7.5%. There were 8894 new users of sitagliptin and 63 834 nonusers with a total 181 139 person-years of follow-up. There were 741 MOF (79 hip fractures), with 53 fractures (4.8 per 1000 person-years) among new users of sitagliptin vs 688 fractures (4.0 per 1000 person-years) among nonusers (P = .3 for difference). In multivariable analyses, sitagliptin was not associated with fracture (adjusted hazard ratio 1.1, 95% confidence interval 0.8–1.4; P = .7), although insulin (P < .001), sulfonylureas (P < .008), and thiazolidinedione (P = .019) were each independently associated with increased fracture risk. Conclusions: Even in a young population with type 2 diabetes, osteoporotic fractures were not uncommon. New use of sitagliptin was not associated with fracture, but other commonly used second-line agents for type 2 diabetes

  5. 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 ...

  6. Anatomical factors affecting the selection of an operative approach for fibular fractures involving the posterior malleolus

    PubMed Central

    WANG, XU; MA, XIN; ZHANG, CHAO; HUANG, JIAZHANG; JIANG, JIANYUAN

    2013-01-01

    Several operative approaches are available at present for the exposure and fixation of distal fibular fractures combined with posterior malleolus fractures. The present study was designed to study the anatomical characteristics of the distal fibula and to thereby evaluate the advantages and limitations of various operative approaches, as well as their indications for specific conditions. Ten leg specimens from below the knee joint were dissected using posterior, lateral and posterolateral approaches to the fibula. The adjacent vulnerable structures, including nerves, blood vessels, tendons and ligaments, were carefully examined and their distances from the posterior malleolus were recorded. The distance was 7.2±4.1 mm between the sural nerve and the posterior section of the fibula, 79.2±23.5 mm between the lateral malleolus tip and the point where the shape changes in the lower fibula and 66.4±17.4 mm between the lateral malleolus and the jointed tendon of the peroneal and flexor hallux longus muscles. The widest anteroposterior diameter of the distal fibula was 27.3±3.5 mm. Various approaches have certain advantages and limitations when these anatomical factors are taken into account. The choice should be based on the height of the fibular fracture line, the type of posterior malleolus fracture, the effect of the fracture on the stability of the ankle joint and the materials used for internal fixation. PMID:23403714

  7. TGF-β1 expression in wound healing is acutely affected by experimental malnutrition and early enteral feeding.

    PubMed

    Alves, Claudia Cristina; Torrinhas, Raquel Susana; Giorgi, Ricardo; Brentani, Maria Mitzi; Logullo, Angela Flavia; Waitzberg, Dan Linetzky

    2014-10-01

    Malnutrition is associated with the delay or failure of healing. We assessed the effect of experimental malnutrition and early enteral feeding with standard diet or diet supplemented with arginine and antioxidants on the levels of mRNA encoding growth factors in acute, open wound healing. Standardised cutaneous dorsal wounds and gastrostomies for enteral feeding were created in malnourished (M, n = 27) and eutrophic control (E, n = 30) Lewis male adult rats. Both M and E rats received isocaloric and isonitrogenous regimens with oral chow and saline (C), standard (S) or supplemented (A) enteral diets. On post-trauma day 7, mRNA levels of growth factor genes were analysed in wound granulation tissue by reverse transcription polymerase chain reaction (RT-PCR). M(C) rats had significantly lower transforming growth factor β(TGF-β1 ) mRNA levels than E(C) rats (2·58 ± 0·83 versus 3·53 ± 0·57, P < 0·01) and in comparison with M(S) and M(A) rats (4·66 ± 2·49 and 4·61 ± 2·11, respectively; P < 0·05). VEGF and KGF-7 mRNA levels were lower in M(A) rats than in E(A) rats (0·74 ± 0·16 versus 1·25 ± 0·66; and 1·07 ± 0·45 versus 1·79 ± 0·89, respectively; P≤ 0·04), but did not differ from levels in E(C) and M(C) animals. In experimental open acute wound healing, previous malnutrition decreased local mRNA levels of TGF-β1 genes, which was minimised by early enteral feeding with standard or supplemented diets.

  8. Displaced patella fractures.

    PubMed

    Della Rocca, Gregory J

    2013-10-01

    Displaced patella fractures often result in disruption of the extensor mechanism of the knee. An intact extensor mechanism is a requirement for unassisted gait. Therefore, operative treatment of the displaced patella fracture is generally recommended. The evaluation of the patella fracture patient includes examination of extensor mechanism integrity. Operative management of patella fractures normally includes open reduction with internal fixation, although partial patellectomy is occasionally performed, with advancement of quadriceps tendon or patellar ligament to the fracture bed. Open reduction with internal fixation has historically been performed utilizing anterior tension band wiring, although comminution of the fracture occasionally makes this fixation construct inadequate. Supplementation or replacement of the tension band wire construct with interfragmentary screws, cerclage wire or suture, and/or plate-and-screw constructs may add to the stability of the fixation construct. Arthrosis of the patellofemoral joint is very common after healing of patella fractures, and substantial functional deficits may persist long after fracture healing has occurred.

  9. 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.

  10. 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. PMID:24757560

  11. Factors affecting the functional results of open reduction and internal fixation for fracture-dislocations of the proximal interphalangeal joint.

    PubMed

    Watanabe, Kentaro; Kino, Yoshitake; Yajima, Hiroki

    2015-01-01

    To clarify the factors affecting functional results of fracture-dislocations of the proximal interphalangeal (PIP) joint treated by open reduction and internal fixation (ORIF), 60 patients, including 38 patients with a dorsal fracture-dislocation and 22 with a pilon fracture, were analysed. The mean ratio of articular surface involvement was 48.5% and a depressed central fragment existed in 75.3% of the cases. ORIF was performed in 47 patients through a lateral approach using Kirschner wires and in 13 through a palmar approach using a plate or screws. The mean flexion, extension and range of motion (ROM) of the PIP joint was 89.5°, 11.5° and 78.0°, respectively. Stepwise regression analysis revealed that a delayed start of active motion exercise after surgery, elderly age and ulnar ray digit were factors affecting functional outcomes. Although ORIF allows accurate restoration of the articular surfaces, an early start of motion exercise is essential for good results.

  12. The time-of-day of myocardial infarction onset affects healing through oscillations in cardiac neutrophil recruitment.

    PubMed

    Schloss, Maximilian J; Horckmans, Michael; Nitz, Katrin; Duchene, Johan; Drechsler, Maik; Bidzhekov, Kiril; Scheiermann, Christoph; Weber, Christian; Soehnlein, Oliver; Steffens, Sabine

    2016-01-01

    Myocardial infarction (MI) is the leading cause of death in Western countries. Epidemiological studies show acute MI to be more prevalent in the morning and to be associated with a poorer outcome in terms of mortality and recovery. The mechanisms behind this association are not fully understood. Here, we report that circadian oscillations of neutrophil recruitment to the heart determine infarct size, healing, and cardiac function after MI Preferential cardiac neutrophil recruitment during the active phase (Zeitgeber time, ZT13) was paralleled by enhanced myeloid progenitor production, increased circulating numbers of CXCR2(hi) neutrophils as well as upregulated cardiac adhesion molecule and chemokine expression. MI at ZT13 resulted in significantly higher cardiac neutrophil infiltration compared to ZT5, which was inhibited by CXCR2 antagonism or neutrophil-specific CXCR2 knockout. Limiting exaggerated neutrophilic inflammation at this time point significantly reduced the infarct size and improved cardiac function. PMID:27226028

  13. Estimated lean mass and fat mass differentially affect femoral bone density and strength index but are not FRAX independent risk factors for fracture.

    PubMed

    Leslie, William D; Orwoll, Eric S; Nielson, Carrie M; Morin, Suzanne N; Majumdar, Sumit R; Johansson, Helena; Odén, Anders; McCloskey, Eugene V; Kanis, John A

    2014-11-01

    Although increasing body weight has been regarded as protective against osteoporosis and fractures, there is accumulating evidence that fat mass adversely affects skeletal health compared with lean mass. We examined skeletal health as a function of estimated total body lean and fat mass in 40,050 women and 3600 men age ≥50 years at the time of baseline dual-energy X-ray absorptiometry (DXA) testing from a clinical registry from Manitoba, Canada. Femoral neck bone mineral density (BMD), strength index (SI), cross-sectional area (CSA), and cross-sectional moment of inertia (CSMI) were derived from DXA. Multivariable models showed that increasing lean mass was associated with near-linear increases in femoral BMD, CSA, and CSMI in both women and men, whereas increasing fat mass showed a small initial increase in these measurements followed by a plateau. In contrast, femoral SI was relatively unaffected by increasing lean mass but was associated with a continuous linear decline with increasing fat mass, which should predict higher fracture risk. During mean 5-year follow-up, incident major osteoporosis fractures and hip fractures were observed in 2505 women and 180 men (626 and 45 hip fractures, respectively). After adjustment for fracture risk assessment tool (FRAX) scores (with or without BMD), we found no evidence that lean mass, fat mass, or femoral SI affected prediction of major osteoporosis fractures or hip fractures. Findings were similar in men and women, without significant interactions with sex or obesity. In conclusion, skeletal adaptation to increasing lean mass was positively associated with BMD but had no effect on femoral SI, whereas increasing fat mass had no effect on BMD but adversely affected femoral SI. Greater fat mass was not independently associated with a greater risk of fractures over 5-year follow-up. FRAX robustly predicts fractures and was not affected by variations in body composition. PMID:24825359

  14. Audiologic Patterns of Otic Capsule Preserving Temporal Bone Fracture: Effects of the Affected Subsites

    PubMed Central

    Kim, So Young; Kim, Yoon Joong; Kim, Young Ho; Park, Min-Hyun

    2016-01-01

    Objectives. This study was aimed to assess the relationship between the type of temporal bone area involved and conductive hearing loss. Methods. We enrolled 97 patients who visited the otolaryngology clinics of Seoul National University Hospital or Boramae Medical Center, Seoul Metropolitan Government-Seoul National University with temporal bone fracture between January 2004 and January 2014. Audiometric parameters, including initial and improved air-bone (AB) conduction gap values, were reviewed in accordance with the temporal bone computed tomography (external auditory canal [EAC], middle ear [ME], mastoid [M], and ossicle [O]). Results. Patients with ossicular chain involvement exhibited a larger AB gap compared to those with no ossicular chain involvement at 250, 1,000, 2,000, and 4,000 Hz. Among the groups without ossicular chain involvement, the initial AB gap was largest in patients with EAC+ME+M involvement, followed by the ME+M and M-only involvement groups. The greatest improvement in the AB gap was observed in the EAC+ME+M group followed by the ME+M and M-only groups, irrespective of ossicular chain involvement. Improvements in AB gap values were smallest at 2,000 Hz. Conclusion. Conductive hearing loss pattern differed according to the temporal bone area involved. Therefore, areas such as the hematoma and hemotympanum, as well as the fracture line of the temporal bone area, must be evaluated to predict audiologic patterns with otic capsule preserving temporal bone fracture. PMID:27337953

  15. 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

  16. 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.

  17. Clavicle fractures: individualizing treatment for fracture type.

    PubMed

    Housner, Jeffrey A; Kuhn, John E

    2003-12-01

    Clavicle fractures are common injuries in both children and adults. In most cases, the diagnosis can be made readily from the patient's history and physical examination. X-rays are helpful to confirm the diagnosis, to assess the severity of the fracture, and to follow interval healing. Most fractures are treated nonoperatively, and surgical intervention is typically reserved for unstable distal clavicle fractures. Nonoperative options involve either a sling-and-swathe or figure-of-eight splint. Return-to-play decisions should be individualized based on the age of the patient, location and severity of the fracture, degree of clinical and radiographic healing, and the sport in which the athlete will be participating.

  18. Impaired bone healing in multitrauma patients is associated with altered leukocyte kinetics after major trauma

    PubMed Central

    Bastian, Okan W; Kuijer, Anne; Koenderman, Leo; Stellato, Rebecca K; van Solinge, Wouter W; Leenen, Luke PH; Blokhuis, Taco J

    2016-01-01

    Animal studies have shown that the systemic inflammatory response to major injury impairs bone regeneration. It remains unclear whether the systemic immune response contributes to impairment of fracture healing in multitrauma patients. It is well known that systemic inflammatory changes after major trauma affect leukocyte kinetics. We therefore retrospectively compared the cellular composition of peripheral blood during the first 2 weeks after injury between multitrauma patients with normal (n=48) and impaired (n=32) fracture healing of the tibia. The peripheral blood-count curves of leukocytes, neutrophils, monocytes, and thrombocytes differed significantly between patients with normal and impaired fracture healing during the first 2 weeks after trauma (P-values were 0.0122, 0.0083, 0.0204, and <0.0001, respectively). Mean myeloid cell counts were above reference values during the second week after injury. Our data indicate that leukocyte kinetics differ significantly between patients with normal and impaired fracture healing during the first 2 weeks after major injury. This finding suggests that the systemic immune response to major trauma can disturb tissue regeneration. PMID:27274302

  19. Osteosynthesis of fragility fractures.

    PubMed

    Tarantino, Umberto; Iundusi, Riccardo; Lecce, Domenico; Tempesta, Valerio; Perrone, Fabio Luigi; Rao, Cecilia; Cerocchi, Irene; Gasbarra, Elena

    2011-04-01

    The deepening knowledge about bone pathophysiology, together with the development of less invasive bone implants, fitted for the treatment of fragility fractures, the continuous advances in the creation of osteoconductive and osteoinductive biomaterials, the availability of bone active agents, capable of modulating fracture healing, actually represent the orthopaedic "weapons" to improve the surgical outcome and quality of life in patients with osteoporosis.

  20. Evaluation of a topical herbal agent for the promotion of bone healing.

    PubMed

    Siu, Wing-Sum; Ko, Chun-Hay; Lam, Ka-Wing; Wat, Elaine; 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

  1. Magnet Healing?

    NASA Astrophysics Data System (ADS)

    Finegold, Leonard

    2000-03-01

    Many people are convinced that static magnets—applied to their skin—will heal ills, and many businesses sell such magnets. The biophysics of such healing was reviewed [1] together with the general biophysics of static fields. Birds and insects do use the earth’s magnetic field for navigation. While insect and frog egg development can clearly be influenced by high fields (7 T and 17 T respectively), there is no experimental evidence that small magnetic fields (of less than 0.5 T) might heal, and much evidence that they cannot heal. A puzzle to the physics community is: How to show laypersons that simple magnets (very probably) do not heal, however attractive that idea might be. [1] L. Finegold, The Physics of "Alternative Medicine": Magnet Therapy, The Scientific Review of Alternative Medicine 3:26-33 (1999).

  2. Archetypal healing.

    PubMed

    Jones, D; Churchill, J E

    1994-01-01

    With emphasis on healing versus curing, the authors draw from a wide assortment of treatment methods for psychospiritual relief of pain in the terminally ill. These archetypal methods include: life-review therapy; ministry of presence; clinical hypnosis; myths, symbols, rituals, and community; creative therapies. In life-review therapy, the ill person shares his/her life story with the provider much like the healing rituals of the ancient storyteller did in his community. In the ministry of presence, the caregiver focuses on sharing his vulnerability, not his professional skills. Clinical hypnosis emphasizes the naturalness and simplicity of accessing the unconscious along with problem areas of the hypnoclinician. Myths, symbols, rituals, and community serve as nurturing agents in the intervention of pain, while creative therapies such as music, drama, crafts, and art continue to be powerful healing instruments. Archetypal healing produces relief of pain in the caregiver, as well as the ill, with emphasis on healing versus curing. PMID:8117487

  3. Metatarsal shaft fractures and fractures of the proximal fifth metatarsal.

    PubMed

    Fetzer, Gary B; Wright, Rick W

    2006-01-01

    Metatarsal fractures represent a relatively common injury, especially in athletes. The pertinent anatomy, evaluation, diagnosis, classification, and treatment of acute and chronic (stress) metatarsal shaft fractures are discussed. Fractures of the proximal fifth metatarsal, which are unique and important injuries, are also discussed. Treatment remains relatively straightforward for the traumatic metatarsal injury, whereas traditional stress fractures typically heal with decreased activity. The problematic proximal fifth metatarsal fracture (Jones fracture) frequently requires surgical intervention in patients who want to avoid non-weight-bearing cast immobilization. The authors' current treatment for this fracture includes the option of intramedullary fixation versus cast immobilization.

  4. Pathological fractures in children

    PubMed Central

    De Mattos, C. B. R.; Binitie, O.; Dormans, J. P.

    2012-01-01

    Pathological fractures in children can occur as a result of a variety of conditions, ranging from metabolic diseases and infection to tumours. Fractures through benign and malignant bone tumours should be recognised and managed appropriately by the treating orthopaedic surgeon. The most common benign bone tumours that cause pathological fractures in children are unicameral bone cysts, aneurysmal bone cysts, non-ossifying fibromas and fibrous dysplasia. Although pathological fractures through a primary bone malignancy are rare, these should be recognised quickly in order to achieve better outcomes. A thorough history, physical examination and review of plain radiographs are crucial to determine the cause and guide treatment. In most benign cases the fracture will heal and the lesion can be addressed at the time of the fracture, or after the fracture is healed. A step-wise and multidisciplinary approach is necessary in caring for paediatric patients with malignancies. Pathological fractures do not have to be treated by amputation; these fractures can heal and limb salvage can be performed when indicated. PMID:23610658

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

    PubMed

    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

  6. 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

  7. Wound Healing and Care

    MedlinePlus

    ... heal through natural scar formation. continue The Healing Process Before healing begins, the body gears up to ... dry at all times to help the healing process. As the body does its healing work on ...

  8. How wounds heal

    MedlinePlus

    ... How scrapes heal; How puncture wounds heal; How burns heal; How pressure sores heal; How lacerations heal ... from germs. Not all wounds bleed. For example, burns, some puncture wounds, and pressure sores do not ...

  9. 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.

  10. Factors affecting neurological deficits and intractable back pain in patients with insufficient bone union following osteoporotic vertebral fracture

    PubMed Central

    Hoshino, Masatoshi; Terai, Hidetomi; Tsujio, Tadao; Nabeta, Masaharu; Namikawa, Takashi; Matsumura, Akira; Suzuki, Akinobu; Takayama, Kazushi; Takaoka, Kunio

    2009-01-01

    The purpose of this study was to examine factors affecting the severity of neurological deficits and intractable back pain in patients with insufficient bone union following osteoporotic vertebral fracture (OVF). Reports of insufficient union following OVF have recently increased. Patients with this lesion have various degrees of neurological deficits and back pain. However, the factors contributing to the severity of these are still unknown. A total of 45 patients with insufficient union following OVF were included in this study. Insufficient union was diagnosed based on the findings of vertebral cleft on plain radiography or CT, as well as fluid collection indicating high-intensity change on T2-weighted MRI. Multivariate logistic regression analysis was performed to determine the factors contributing to the severity of neurological deficits and back pain in the patients. Age, sex, level of fracture, duration after onset of symptoms, degree of local kyphosis, degree of angular instability, ratio of occupation by bony fragments, presence or absence of protrusion of flavum, and presence or absence of ossification of the anterior longitudinal ligament (OALL) in the adjacent level were used as explanatory variables, while severity of neurological deficits and back pain were response variables. On multivariate analysis, factors significantly affecting the severity of neurological deficits were angular instability of more than 15° [adjusted odds ratio (OR), 9.24 (95% confidence interval, CI 1.49–57.2); P < 0.05] and ratio of occupation by bony fragments in the spinal canal of more than 42% [adjusted OR 9.23 (95%CI 1.15–74.1); P < 0.05]. The factor significantly affecting the severity of back pain was angular instability of more than 15° [adjusted OR 14.9 (95%CI 2.11–105); P < 0.01]. On the other hand, presence of OALL in the adjacent level reduced degree of back pain [adjusted OR 0.14 (95%CI 0.03–0.76); P < 0.05]. In this study, pronounced angular

  11. Effects of Oxides on Tensile and Charpy Impact Properties and Fracture Toughness in Heat Affected Zones of Oxide-Containing API X80 Linepipe Steels

    NASA Astrophysics Data System (ADS)

    Sung, Hyo Kyung; Sohn, Seok Su; Shin, Sang Yong; Oh, Kyung Shik; Lee, Sunghak

    2014-06-01

    This study is concerned with effects of complex oxides on acicular ferrite (AF) formation, tensile and Charpy impact properties, and fracture toughness in heat affected zones (HAZs) of oxide-containing API X80 linepipe steels. Three steels were fabricated by adding Mg and O2 to form oxides, and various HAZ microstructures were obtained by conducting HAZ simulation tests under different heat inputs. The no. of oxides increased with increasing amount of Mg and O2, while the volume fraction of AF present in the steel HAZs increased with increasing the no. of oxides. The strengths of the HAZ specimens were generally higher than those of the base metals because of the formation of hard microstructures of bainitic ferrite and granular bainite. When the total Charpy absorbed energy was divided into the fracture initiation and propagation energies, the fracture initiation energy was maintained constant at about 75 J at room temperature, irrespective of volume fraction of AF. The fracture propagation energy rapidly increased from 75 to 150 J and saturated when the volume fraction of AF exceeded 30 pct. At 253 K (-20 °C), the total absorbed energy increased with increasing volume fraction of AF, as the cleavage fracture was changed to the ductile fracture when the volume fraction of AF exceeded 45 pct. Thus, 45 vol pct of AF at least was needed to improve the Charpy impact energy, which could be achieved by forming a no. of oxides. The fracture toughness increased with increasing the no. of oxides because of the increased volume fraction of AF formed around oxides. The fracture toughness did not show a visible correlation with the Charpy absorbed energy at room temperature, because toughness properties obtained from these two toughness testing methods had different significations in view of fracture mechanics.

  12. 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.

  13. 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

  14. 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 abuse, war,…

  15. Healing fractured families: parents' and elders' perspectives on the impact of colonization and youth suicide prevention in a pacific northwest American Indian tribe.

    PubMed

    Strickland, C June; Walsh, Elaine; Cooper, Michelle

    2006-01-01

    Suicide rates among American Indian youth in the United States are two to three times the national average. Risk factors for American Indian youth include depression, alcohol use, hopelessness and stress, and family conflict, abuse, poverty, and instability. In this descriptive study, the authors aimed to obtain parents' and elders' perspectives on community needs and to identify strengths on which the community might build to reduce youth suicide risk. Data were collected from focus groups with 40 American Indian parents and from individual interviews with 9 American Indian elders. The major task participants addressed was holding the family together and healing intergenerational pains. Topics parents discussed were holding onto cultural values, holding the family together, getting through school, and getting a job. These findings substantiate previous research and provide useful information for the design of culturally appropriate family or community-based interventions to prevent American Indian youth suicide.

  16. 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

  17. 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

  18. The Impact of Strontium Ranelate on Metaphyseal Bone Healing in Ovariectomized Rats.

    PubMed

    Komrakova, Marina; Weidemann, Anna; Dullin, Christian; Ebert, Joachim; Tezval, Mohammad; Stuermer, Klaus Michael; Sehmisch, Stephan

    2015-10-01

    The following questions were addressed: whether therapy with strontium ranelate (SR) should be continued or interrupted if the fractures occur during SR treatment and whether SR could be applied directly after fracture to improve bone healing. Sprague-Dawley rats (3 month old) were ovariectomized (Ovx, n = 48) or left intact (n = 12). After 8 weeks, a bilateral transverse osteotomy of the tibia metaphysis was created in all rats. Ovx rats were divided into four groups: Ovx; SR applied directly after Ovx until osteotomy (prophylaxis, SR pr, 8 weeks); SR applied after osteotomy (therapy, SR th, 5 weeks); SR applied during the whole experiment (pr + th, 13 weeks). SR dosage was 625 mg/kg body weight/day, administered in the feed. Five weeks later, tibiae were analyzed by biomechanical, histological, micro-CT, and gene expression analyses. The SR pr + th treatment increased total bone mineral density (BMD), bone volume fraction, cortical BMD and volume, callus area and density, serum alkaline phosphatase, tartrate-resistant acid phosphatase mRNA, accelerated osteotomy bridging, and callus formation at weeks 2 and 3 of healing and decreased the osteoprotegerin/receptor activator of nuclear factor kB ligand mRNA ratio. SR th enlarged callus area and improved callus formation during the 5th week of healing. SR pr improved cortical BMD preserving bone after SR discontinuation (5-week rest); the bone healing was not affected. SR content in the tibia metaphysis was the highest in SR pr + th group and was not different between SR pr and SR th. SR has a positive effect on osteoporotic bone healing in rat and SR treatment can be continued after the fracture occurs or applied directly after the fracture. PMID:26084691

  19. Biomechanical Concepts for Fracture Fixation.

    PubMed

    Bottlang, Michael; Schemitsch, Christine E; Nauth, Aaron; Routt, Milton; Egol, Kenneth A; Cook, Gillian E; Schemitsch, Emil H

    2015-12-01

    Application of the correct fixation construct is critical for fracture healing and long-term stability; however, it is a complex issue with numerous significant factors. This review describes a number of common fracture types and evaluates their currently available fracture fixation constructs. In the setting of complex elbow instability, stable fixation or radial head replacement with an appropriately sized implant in conjunction with ligamentous repair is required to restore stability. For unstable sacral fractures with vertical or multiplanar instabilities, "standard" iliosacral screw fixation is not sufficient. Periprosthetic femur fractures, in particular Vancouver B1 fractures, have increased stability when using 90/90 fixation versus a single locking plate. Far cortical locking combines the concept of dynamization with locked plating to achieve superior healing of a distal femur fracture. Finally, there is no ideal construct for syndesmotic fracture stabilization; however, these fractures should be fixed using a device that allows for sufficient motion in the syndesmosis. In general, orthopaedic surgeons should select a fracture fixation construct that restores stability and promotes healing at the fracture site, while reducing the potential for fixation failure.

  20. 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.

  1. Fatigue Fractures

    PubMed Central

    Morris, James M.

    1968-01-01

    Fatigue (or stress) fracture of bone in military recruits has been recognized for many years. Most often it is a metatarsal bone that is involved but the tarsal bones, calcaneus, tibia, fibula, femur, and pelvis are occasionally affected. Reports of such fractures in the ribs, ulna and vertebral bodies may be found in the literature. In recent years, there has been increasing awareness of the occurrence of fatigue fractures in the civilian population. Weekend sportsmen, athletes in an early phase of training, and persons engaged in unaccustomed, repetitive, vigorous activity are potential victims of such a fracture. The signs and symptoms, roentgenographic findings, treatment and etiology of fatigue fractures are dealt with in this presentation. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5.Figure 6. PMID:5652745

  2. 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 ...

  3. Factors affecting the discharge destination of hip fracture patients who live alone and have been admitted to an inpatient rehabilitation unit

    PubMed Central

    Hayashi, Hiroyuki; Iwai, Midori; Matsuoka, Hiroka; Nakashima, Daiki; Nakamura, Shugo; Kubo, Ayumi; Tomiyama, Naoki

    2016-01-01

    [Purpose] (1) The aim of this study was to examine relations between clinical and functional assessment and discharge destination and (2) to identify the optimal cutoff point for estimating discharge to home after inpatient rehabilitation. [Subjects] The subjects were 54 hip fracture patients (15 males, 39 females; mean age 81.3 ± 7.4 years) living alone. [Methods] The patients were classified into two groups: those discharged to home and those admitted to an institution. Age, gender, side of fracture, fracture type, number of comorbidities, Functional Independence Measure motor score, and Functional Independence Measure cognitive score were compared between groups. Multiple logistic regression analysis was conducted with discharge to home as the dependent variable and age, gender, side of fracture, fracture type, number of comorbidities, Functional Independence Measure motor score, and Functional Independence Measure cognitive score as independent variables. A receiver operating characteristic curve analysis was used to identify a cutoff point for classification of the patients into the two groups. [Results] Multiple logistic regression analysis showed that the Functional Independence Measure cognitive score was a significant variable affecting the discharge destination. The receiver operating characteristic curve analysis revealed that discharge to home was predicted accurately by a Functional Independence Measure cognitive score of 23.5. [Conclusion] Information from this study is expected to be useful for determining discharge plans and for the setting of treatment goals. PMID:27190457

  4. Interactions between MSCs and Immune Cells: Implications for Bone Healing

    PubMed Central

    Kovach, Tracy K.; Dighe, Abhijit S.; Lobo, Peter I.; Cui, Quanjun

    2015-01-01

    It is estimated that, of the 7.9 million fractures sustained in the United States each year, 5% to 20% result in delayed or impaired healing requiring therapeutic intervention. Following fracture injury, there is an initial inflammatory response that plays a crucial role in bone healing; however, prolonged inflammation is inhibitory for fracture repair. The precise spatial and temporal impact of immune cells and their cytokines on fracture healing remains obscure. Some cytokines are reported to be proosteogenic while others inhibit bone healing. Cell-based therapy utilizing mesenchymal stromal cells (MSCs) is an attractive option for augmenting the fracture repair process. Osteoprogenitor MSCs not only differentiate into bone, but they also exert modulatory effects on immune cells via a variety of mechanisms. In this paper, we review the current literature on both in vitro and in vivo studies on the role of the immune system in fracture repair, the use of MSCs in the enhancement of fracture healing, and interactions between MSCs and immune cells. Insight into this paradigm can provide valuable clues in identifying cellular and noncellular targets that can potentially be modulated to enhance both natural bone healing and bone repair augmented by the exogenous addition of MSCs. PMID:26000315

  5. Gingival Wound Healing

    PubMed Central

    Cáceres, M.; Martínez, C.; Oyarzún, A.; Martínez, J.

    2015-01-01

    Gingival wound healing comprises a series of sequential responses that allow the closure of breaches in the masticatory mucosa. This process is of critical importance to prevent the invasion of microbes or other agents into tissues, avoiding the establishment of a chronic infection. Wound healing may also play an important role during cell and tissue reaction to long-term injury, as it may occur during inflammatory responses and cancer. Recent experimental data have shown that gingival wound healing is severely affected by the aging process. These defects may alter distinct phases of the wound-healing process, including epithelial migration, granulation tissue formation, and tissue remodeling. The cellular and molecular defects that may explain these deficiencies include several biological responses such as an increased inflammatory response, altered integrin signaling, reduced growth factor activity, decreased cell proliferation, diminished angiogenesis, reduced collagen synthesis, augmented collagen remodeling, and deterioration of the proliferative and differentiation potential of stem cells. In this review, we explore the cellular and molecular basis of these defects and their possible clinical implications. PMID:25527254

  6. Closed reduction of the mandibular fracture.

    PubMed

    Blitz, Meredith; Notarnicola, Kurt

    2009-03-01

    The search for the ideal method of treatment for mandibular fractures has continued for thousands of years. These injuries have unique and problematic features for adequate reliable wound healing. Oral and maxillofacial surgeons must learn and master several techniques for mandibular fracture treatment. The age-old successful management of these injuries using closed reduction techniques always should be considered when mandibular trauma presents. The closed reduction remains a mainstay of mandibular fracture treatment. An adequate knowledge of anatomy, multiple closed reduction techniques, and the physiology of fracture healing must be adequately understood and technically mastered by the oral and maxillofacial surgical team for the present and future of mandibular fracture management.

  7. Self-healing of hierarchical materials.

    PubMed

    Bosia, Federico; Abdalrahman, Tamer; Pugno, Nicola M

    2014-02-01

    We present a theoretical and numerical analysis of the mechanical behavior of self-healing materials using an analytical model and numerical calculations both based on a Hierarchical Fiber Bundle Model, and applying them to graphene- or carbon-nanotube-based materials. The self-healing process can be described essentially through a single parameter, that is, the healing rate, but numerical simulations also highlight the influence of the location of the healing process on the overall strengthening and toughening of the material. The role of hierarchy is discussed, showing that full-scale hierarchical structures can in fact acquire more favorable properties than smaller, nonhierarchical ones through interaction with the self-healing process, thus inverting the common notion in fracture mechanics that specimen strength increases with decreasing size. Further, the study demonstrates that the developed analytical and numerical tools can be useful to develop strategies for the optimization of strength and toughness of synthetic bioinspired materials. PMID:24364755

  8. Tibial Stress Fractures in Athletes.

    PubMed

    Feldman, John J; Bowman, Eric N; Phillips, Barry B; Weinlein, John C

    2016-10-01

    Tibial stress fractures are common in the athlete. There are various causes of these fractures, the most common being a sudden increase in training intensity. Most of these injuries are treated conservatively; however, some may require operative intervention. Intervention is mostly dictated by location of the fracture and failure of conservative treatment. There are several surgical options available to the treating surgeon, each with advantages and disadvantages. The physician must understand the nature of the fracture and the likelihood for it to heal in a timely manner in order to best treat these fractures in this patient subset. PMID:27637660

  9. Femur fracture repair - discharge

    MedlinePlus

    ... surgery, your surgeon will make a cut to open your fracture. Your surgeon will then use special metal devices to hold your bones in place while they heal. These devices are called ... is open reduction and internal fixation (ORIF). In the most ...

  10. Dorsal radiocarpal fracture dislocation.

    PubMed

    Tanzer, T L; Horne, J G

    1980-11-01

    A case of a rare radiocarpal fracture dislocation in a 17-year-old girl, with persisting loss of radiocarpal joint space following reduction under hematoma block, is described. The wrist joint was exposed, and two osteochondral fragments were rotated 90 degrees and secured with 2.7-mm AO screws. Satisfactory healing followed 3 months postinjury.

  11. [Risk of infection in centro-medullary locking nailing of open fractures of the femur and tibia].

    PubMed

    Jenny, J Y; Jenny, G; Gaudias, J; Kempf, I

    1995-01-01

    Intramedullary reamed locking nail of open fractures remains controversial because of the risk of infection. 1,474 closed reamed locked nailings were performed between 1974 and 1989 for femoral (744 cases) or tibial (730 cases) fractures. 349 fractures were open: 100 femoral fractures (51 Gustilo and Anderson Grade I and 49 Grade II) and 249 tibial fractures (140 Grade I, 99 Grade II et 10 Grade III). 24 femoral (3.2%) and 46 tibial (6.3%) nails were followed by infection. This difference is significant (p < 0.01). Reoperations for infection occur more frequently for femoral than tibial fractures (p < 0.05). There is no difference between the results of infection treatment between femoral or tibial fractures. Traumatic opening of the femoral fracture site does not affect the occurrence of an infection, its severity or the results of its treatment. Traumatic opening of the tibial fracture site significantly increases the infection rate (p < 0.001), and the incidence of infection increases with the severity of the soft tissue lesions; but the severity of the infection and the results of its treatment are not modified. Acute closed reamed intramedullary locking nail is the best treatment for open femoral or tibial fractures with respect to the bone healing and infection rate for Grade I and II fractures. For Grade III fractures, nailing must be followed by a coverage flap. PMID:8623602

  12. 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.

  13. Inter-trabecular bone formation: a specific mechanism for healing of cancellous bone

    PubMed Central

    Sandberg, Olof H; Aspenberg, Per

    2016-01-01

    Background and purpose Studies of fracture healing have mainly dealt with shaft fractures, both experimentally and clinically. In contrast, most patients have metaphyseal fractures. There is an increasing awareness that metaphyseal fractures heal partly through mechanisms specific to cancellous bone. Several new models for the study of cancellous bone healing have recently been presented. This review summarizes our current knowledge of cancellous fracture healing. Methods We performed a review of the literature after doing a systematic literature search. Results Cancellous bone appears to heal mainly via direct, membranous bone formation that occurs freely in the marrow, probably mostly arising from local stem cells. This mechanism appears to be specific for cancellous bone, and could be named inter-trabecular bone formation. This kind of bone formation is spatially restricted and does not extend more than a few mm outside the injured region. Usually no cartilage is seen, although external callus and cartilage formation can be induced in meta­physeal fractures by mechanical instability. Inter-trabecular bone formation seems to be less sensitive to anti-inflammatory treatment than shaft fractures. Interpretation The unique characteristics of inter-trabecular bone formation in metaphyseal fractures can lead to differences from shaft healing regarding the effects of age, loading, or drug treatment. This casts doubt on generalizations about fracture healing based solely on shaft fracture models. PMID:27357416

  14. Local Application of Ibandronate/Gelatin Sponge Improves Osteotomy Healing in Rabbits

    PubMed Central

    Xia, Zhidao; Liu, Yueju; Peggrem, Shaun; Geng, Tao; Yang, Zhaoxu; Li, Han; Xu, Bin; Zhang, Chi; Triffitt, James T.; Zhang, Yingze

    2015-01-01

    Delayed healing or non-union of skeletal fractures are common clinical complications. Ibandronate is a highly potent anti-catabolic reagent used for treatment of osteopenia and fracture prevention. We hypothesized that local application of ibandronate after fracture fixation may improve and sustain callus formation and therefore prevent delayed healing or non-union. This study tested the effect of local application of an ibandronate/gelatin sponge composite on osteotomy healing. A right-side distal-femoral osteotomy was created surgically, with fixation using a k-wire, in forty adult male rabbits. The animals were divided into four groups of ten animals and treated by: (i) intravenous injection of normal saline (Control); (ii) local implantation of absorbable gelatin sponge (GS); (iii) local implantation of absorbable GS containing ibandronate (IB+GS), and (iv) intravenous injection of ibandronate (IB i.v.). At two and four weeks the affected femora were harvested for X-ray photography, computed tomography (CT), biomechanical testing and histopathology. At both time-points the results showed that the calluses in both the ibandronate-treated groups, but especially in the IB+GS group, were significantly larger than in the control and GS groups. At four weeks the cross sectional area (CSA) and mechanical test results of ultimate load and energy in the IB+GS group were significantly higher than in other groups. Histological procedures showed a significant reduction in osteoclast numbers in the IB+GS and IB i.v. groups at day 14. The results indicate that local application of an ibandronate/gelatin sponge biomaterial improved early osteotomy healing after surgical fixation and suggest that such treatment may be a valuable local therapy to enhance fracture repair and potentially prevent delayed or non-union. PMID:25951178

  15. A unified theory of bone healing and nonunion: BHN theory.

    PubMed

    Elliott, D S; Newman, K J H; Forward, D P; Hahn, D M; Ollivere, B; Kojima, K; Handley, R; Rossiter, N D; Wixted, J J; Smith, R M; Moran, C G

    2016-07-01

    This article presents a unified clinical theory that links established facts about the physiology of bone and homeostasis, with those involved in the healing of fractures and the development of nonunion. The key to this theory is the concept that the tissue that forms in and around a fracture should be considered a specific functional entity. This 'bone-healing unit' produces a physiological response to its biological and mechanical environment, which leads to the normal healing of bone. This tissue responds to mechanical forces and functions according to Wolff's law, Perren's strain theory and Frost's concept of the "mechanostat". In response to the local mechanical environment, the bone-healing unit normally changes with time, producing different tissues that can tolerate various levels of strain. The normal result is the formation of bone that bridges the fracture - healing by callus. Nonunion occurs when the bone-healing unit fails either due to mechanical or biological problems or a combination of both. In clinical practice, the majority of nonunions are due to mechanical problems with instability, resulting in too much strain at the fracture site. In most nonunions, there is an intact bone-healing unit. We suggest that this maintains its biological potential to heal, but fails to function due to the mechanical conditions. The theory predicts the healing pattern of multifragmentary fractures and the observed morphological characteristics of different nonunions. It suggests that the majority of nonunions will heal if the correct mechanical environment is produced by surgery, without the need for biological adjuncts such as autologous bone graft. Cite this article: Bone Joint J 2016;98-B:884-91. PMID:27365465

  16. Seasonal Temperature and Pin Site Care Regimen Affect the Incidence of Pin Site Infection in Pediatric Supracondylar Humeral Fractures

    PubMed Central

    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. PMID:26064957

  17. Subtrochanteric femur fracture after removal of screws for femoral neck fracture in a child.

    PubMed

    Song, Kwang Soon; Lee, Si Wook

    2015-01-01

    Displaced femoral neck fractures are rare in children and are associated with a high rate of complications. Subtrochanteric fractures after cannulated screw fixation of femoral neck fractures in adults are well recognized, and there are several reports on the topic. However, there are no reports on complications related to hardware or subtrochanteric fractures after removal of the screws in the treatment of femoral neck fractures in children. Here we report the case of a 10-year-old boy who sustained a subtrochanteric fracture after the screw removal and healing that followed a femoral neck fracture. PMID:25566556

  18. Elastic stable intramedullary nailing for severely displaced distal tibial fractures in children.

    PubMed

    Shen, Kaiying; Cai, Haiqing; Wang, Zhigang; Xu, Yunlan

    2016-09-01

    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:27684849

  19. Hybrid External Fixation for Arbeitsgemeinschaft für Osteosynthesefragen (AO) 43-C Tibial Plafond Fractures.

    PubMed

    Abd-Almageed, Emad; Marwan, Yousef; Esmaeel, Ali; Mallur, Amarnath; El-Alfy, Barakat

    2015-01-01

    Arbeitsgemeinschaft für Osteosynthesefragen (AO) type 43-C tibial plafond/pilon fractures represent a challenge for the treating orthopedic surgeon. We assessed the outcomes of using hybrid external fixation for this fracture type. The present prospective cohort study was started in August 2009 and ended by July 2012. Thirty consecutive patients (mean age 37.4 ± 10.7 years) with a type C tibial plafond fracture who had presented to our tertiary care orthopedic hospital were included. Motor vehicle accidents and fall from height were the cause of the fracture in 14 (46.7%) and 13 (43.3%) patients, respectively. A type C3 fracture was present in 25 patients (83.3%), and type C1 and C2 fractures were present in 2 (6.7%) and 3 (10.0%) patients, respectively. Nine fractures (30.0%) were open. Hybrid external fixation was used for all fractures. All fractures were united; clinical healing was achieved by a mean of 18.1 ± 2.2 weeks postoperatively and radiologic healing at a mean of 18.9 ± 1.9 weeks. The fixator was removed at a mean of 20.4 ± 2.0 weeks postoperatively. At a mean follow-up point of 13.4 ± 2.6 months, the mean modified Mazur ankle score was 84.6 ± 10.4. It was not associated with wound classification (p = .256). The most commonly seen complication was ankle osteoarthritis (17 patients; 56.7%); however, it was mild in >50.0% of the affected patients. In conclusion, using hybrid external fixation for type C tibial plafond fractures resulted in good outcomes. However, this should be investigated further in studies with a higher level of evidence.

  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. Clinical and surgical approach of severe bone fragility fracture: clinical case of 4 fragility fracture in patient with heavy osteoporosis.

    PubMed

    Giannotti, Stefano; Bottai, Vanna; Pini, Erica; Dell'osso, Giacomo; De Paola, Gaia; Guido, Giulio

    2013-01-01

    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

  2. Genome-wide association study using extreme truncate selection identifies novel genes affecting bone mineral density and fracture risk.

    PubMed

    Duncan, Emma L; Danoy, Patrick; Kemp, John P; Leo, Paul J; McCloskey, Eugene; Nicholson, Geoffrey C; Eastell, Richard; Prince, Richard L; Eisman, John A; Jones, Graeme; Sambrook, Philip N; Reid, Ian R; Dennison, Elaine M; Wark, John; Richards, J Brent; Uitterlinden, Andre G; Spector, Tim D; Esapa, Chris; Cox, Roger D; Brown, Steve D M; Thakker, Rajesh V; Addison, Kathryn A; Bradbury, Linda A; Center, Jacqueline R; Cooper, Cyrus; Cremin, Catherine; Estrada, Karol; Felsenberg, Dieter; Glüer, Claus-C; Hadler, Johanna; Henry, Margaret J; Hofman, Albert; Kotowicz, Mark A; Makovey, Joanna; Nguyen, Sing C; Nguyen, Tuan V; Pasco, Julie A; Pryce, Karena; Reid, David M; Rivadeneira, Fernando; Roux, Christian; Stefansson, Kari; Styrkarsdottir, Unnur; Thorleifsson, Gudmar; Tichawangana, Rumbidzai; Evans, David M; Brown, Matthew A

    2011-04-01

    Osteoporotic fracture is a major cause of morbidity and mortality worldwide. Low bone mineral density (BMD) is a major predisposing factor to fracture and is known to be highly heritable. Site-, gender-, and age-specific genetic effects on BMD are thought to be significant, but have largely not been considered in the design of genome-wide association studies (GWAS) of BMD to date. We report here a GWAS using a novel study design focusing on women of a specific age (postmenopausal women, age 55-85 years), with either extreme high or low hip BMD (age- and gender-adjusted BMD z-scores of +1.5 to +4.0, n = 1055, or -4.0 to -1.5, n = 900), with replication in cohorts of women drawn from the general population (n = 20,898). The study replicates 21 of 26 known BMD-associated genes. Additionally, we report suggestive association of a further six new genetic associations in or around the genes CLCN7, GALNT3, IBSP, LTBP3, RSPO3, and SOX4, with replication in two independent datasets. A novel mouse model with a loss-of-function mutation in GALNT3 is also reported, which has high bone mass, supporting the involvement of this gene in BMD determination. In addition to identifying further genes associated with BMD, this study confirms the efficiency of extreme-truncate selection designs for quantitative trait association studies.

  3. Genome-Wide Association Study Using Extreme Truncate Selection Identifies Novel Genes Affecting Bone Mineral Density and Fracture Risk

    PubMed Central

    Duncan, Emma L.; Danoy, Patrick; Kemp, John P.; Leo, Paul J.; McCloskey, Eugene; Nicholson, Geoffrey C.; Eastell, Richard; Prince, Richard L.; Eisman, John A.; Jones, Graeme; Sambrook, Philip N.; Reid, Ian R.; Dennison, Elaine M.; Wark, John; Richards, J. Brent; Uitterlinden, Andre G.; Spector, Tim D.; Esapa, Chris; Cox, Roger D.; Brown, Steve D. M.; Thakker, Rajesh V.; Addison, Kathryn A.; Bradbury, Linda A.; Center, Jacqueline R.; Cooper, Cyrus; Cremin, Catherine; Estrada, Karol; Felsenberg, Dieter; Glüer, Claus-C.; Hadler, Johanna; Henry, Margaret J.; Hofman, Albert; Kotowicz, Mark A.; Makovey, Joanna; Nguyen, Sing C.; Nguyen, Tuan V.; Pasco, Julie A.; Pryce, Karena; Reid, David M.; Rivadeneira, Fernando; Roux, Christian; Stefansson, Kari; Styrkarsdottir, Unnur; Thorleifsson, Gudmar; Tichawangana, Rumbidzai; Evans, David M.; Brown, Matthew A.

    2011-01-01

    Osteoporotic fracture is a major cause of morbidity and mortality worldwide. Low bone mineral density (BMD) is a major predisposing factor to fracture and is known to be highly heritable. Site-, gender-, and age-specific genetic effects on BMD are thought to be significant, but have largely not been considered in the design of genome-wide association studies (GWAS) of BMD to date. We report here a GWAS using a novel study design focusing on women of a specific age (postmenopausal women, age 55–85 years), with either extreme high or low hip BMD (age- and gender-adjusted BMD z-scores of +1.5 to +4.0, n = 1055, or −4.0 to −1.5, n = 900), with replication in cohorts of women drawn from the general population (n = 20,898). The study replicates 21 of 26 known BMD–associated genes. Additionally, we report suggestive association of a further six new genetic associations in or around the genes CLCN7, GALNT3, IBSP, LTBP3, RSPO3, and SOX4, with replication in two independent datasets. A novel mouse model with a loss-of-function mutation in GALNT3 is also reported, which has high bone mass, supporting the involvement of this gene in BMD determination. In addition to identifying further genes associated with BMD, this study confirms the efficiency of extreme-truncate selection designs for quantitative trait association studies. PMID:21533022

  4. 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.

  5. 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...

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Factors That Impair Wound Healing.

    PubMed

    Anderson, Kristin; Hamm, Rose L

    2012-12-01

    The body's response to tissue injury in a healthy individual is an intricate, sequential physiologic process that results in timely healing with full re-epithelialization, resolution of drainage, and return of function to the affected tissue. Chronic wounds, however, do not follow this sequence of events and can challenge the most experienced clinician if the underlying factors that are impairing wound healing are not identified. The purpose of this article is to present recent information about factors that impair wound healing with the underlying pathophysiological mechanism that interferes with the response to tissue injury. These factors include co-morbidities (diabetes, obesity, protein energy malnutrition), medications (steroids, non-steroidal anti-inflammatory drugs or NSAIDs, anti-rejection medications), oncology interventions (radiation, chemotherapy), and life style habits (smoking, alcohol abuse). Successful treatment of any chronic wound depends upon identification and management of the factors for each individual.

  12. Olecranon stress fracture in a weight lifter: a case report.

    PubMed

    Rao, P S; Rao, S K; Navadgi, B C

    2001-02-01

    Stress fractures have been reported in the upper limb of sportspeople involved in upper limb dominated events. Olecranon stress fractures have been cited in baseball pitchers, javelin throwers, and gymnasts. The unusual case of a stress fracture of the olecranon in a young weight lifter is reported here. The minimally displaced stress fracture was treated with tension band and two Kirschner wires. The fracture healed in four months and the patient returned to light sports activity after six months.

  13. A theory of crack healing in polymers

    NASA Astrophysics Data System (ADS)

    Wool, R. P.; O'Connor, K. M.

    1981-10-01

    A theory of crack healing in polymers is presented in terms of the stages of crack healing, namely, (a) surface rearrangement, (b) surface approach, (c) wetting, (d) diffusion, and (e) randomization. The recovery ratio R of mechanical properties with time was determined as a convolution product, R = Rh (t)*φ(t), where Rh (t) is an intrinsic healing function, and φ(t) is a wetting distribution function for the crack interface or plane in the material. The reptation model of a chain in a tube was used to describe self-diffusion of interpenetrating random coil chains which formed a basis for Rh (t). Applications of the theory are described, including crack healing in amorphous polymers and melt processing of polymer resins by injection or compression molding. Relations are developed for fracture stress σ, strain ɛ, and energy E as a function of time t, temperature T, pressure P, and molecular weight M. Results include (i) during healing or processing at thealed state at t = t∞, σ,ɛ˜M1/2, E˜M; (iv) the time to achieve complete healing, t∞ ˜M3, ˜exp P, ˜exp 1/T. Chain fracture, creep, and stress relaxation are also discussed. New concepts for strength predictions are introduced.

  14. Advanced Reservoir Characterization and Evaluation of CO2 Gravity Drainage in the Naturally Fractured Spraberry Reservoir

    SciTech Connect

    David S. Schechter

    1997-12-17

    Natural fractures exert a strong influence over oil production in Spraberry Trend Area reservoirs in the Permian Basin of west Texas. The importance of the fracture network has been known since the 1950s, but until recently, there has been very little detailed study of the fractures themselves. In 1996, a horizontal Spraberry well was cored as part of a DOE Class III Field Demonstration Project. Fractures from the horizontal core as well as other fractures encountered in vertical Spraberry cores were analyzed in detail for information on both large scale features including orientation and spacing and small-scale features such as the relationships between fracture mineralization and matrix rock composition. At least three sets of fractures are found within the upper and middle Spraberry cores. These sets have distinct orientations, spacing, mineralization, distribution with respect to lithology, and surface characteristics (Lorenz, 1997). Fractures found in the 1U zone of the upper Spraberry have a NE strike, and tend to be partly mineralized with barite, quartz, and dolomite. Distribution of these mineral phases can greatly affect conductivity between the fractures and the rock matrix. The 5U zone of the upper Spraberry contains fractures with NNE and ENE orientations. The NNE set of fractures has stepped fracture surfaces indicating a shear origin, and minor amounts of quartz and dolomite mineralization. The ENE fracture set has smooth planar surfaces of tension origin with some calcite mineralization present. Natural fractures in black shales overlying both the 1U and the 5U have an ENE orientation similar to unmineralized fractures in the 5U. No fractures were encountered in similar shales underlying reservoir zones. A set of hairline fractures, most completely healed with calcite cement was also found in some Middle Spraberry cores. The unique nature of each of these fracture sets implies that fracturing probably occurred as several separate events and

  15. 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

  16. 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

  17. Words that heal.

    PubMed

    Spurio, Maria Grazia

    2015-09-01

    The value of words in the healing process runs constant to the path of therapeutic treatment, the net of exchanges and relationships between brain chemistry and the right words in order to heal is subtle and intricate. Psychotherapy, a treatment with words, is shown to be a treatment that directly affects the brain and that is able to change it stably, even in its anatomical structure and function. According to Kandel (1999), a leading living scientist and Nobel Prize winner for medicine and physiology, American neurologist and psychiatrist, psychotherapy is a real cure, a biological treatment, as it produces behavioral changes through new words and new experiences. The article offers a brief overview of the use of the fantasy of argument, since the time of the classical rethoric of the sophists up to the new rethoric, to illustrate how the structure of the speech, and the dialectic ability of opposing different thoughts, closely resembles the way of thinking. Consequently the choice of words can be considered an instrument of great impact that is inserted in the stream of thoughts that determines the attitude of a person, and therefore, his/her actions. This happens whenever you communicate voluntarily, and not simply when interacting. The right choice of words remains a turning point in all of our relationships, not only in therapeutic situations, but in every other social relationship in life, family or friends.

  18. Words that heal.

    PubMed

    Spurio, Maria Grazia

    2015-09-01

    The value of words in the healing process runs constant to the path of therapeutic treatment, the net of exchanges and relationships between brain chemistry and the right words in order to heal is subtle and intricate. Psychotherapy, a treatment with words, is shown to be a treatment that directly affects the brain and that is able to change it stably, even in its anatomical structure and function. According to Kandel (1999), a leading living scientist and Nobel Prize winner for medicine and physiology, American neurologist and psychiatrist, psychotherapy is a real cure, a biological treatment, as it produces behavioral changes through new words and new experiences. The article offers a brief overview of the use of the fantasy of argument, since the time of the classical rethoric of the sophists up to the new rethoric, to illustrate how the structure of the speech, and the dialectic ability of opposing different thoughts, closely resembles the way of thinking. Consequently the choice of words can be considered an instrument of great impact that is inserted in the stream of thoughts that determines the attitude of a person, and therefore, his/her actions. This happens whenever you communicate voluntarily, and not simply when interacting. The right choice of words remains a turning point in all of our relationships, not only in therapeutic situations, but in every other social relationship in life, family or friends. PMID:26417732

  19. The course of bone healing is influenced by the initial shear fixation stability.

    PubMed

    Schell, H; Epari, D R; Kassi, J P; Bragulla, H; Bail, H J; Duda, G N

    2005-09-01

    Fracture healing is influenced by fixation stability and experimental evidence suggests that the initial mechanical conditions may determine the healing outcome. We hypothesised that mechanical conditions influence not only the healing outcome, but also the early phase of fracture healing. Additionally, it was hypothesised that decreased fixation stability characterised by an increased shear interfragmentary movement results in a delay in healing. Sixty-four sheep underwent a mid-shaft tibial osteotomy which was treated with either a rigid or a semi-rigid external fixator. Animals were sacrificed at 2, 3, 6 and 9 weeks postoperatively and the fracture callus was analysed using radiological, biomechanical and histological techniques. The tibia treated with semi-rigid fixation showed inferior callus stiffness and quality after 6 weeks. At 9 weeks, the calluses were no longer distinguishable in their mechanical competence. The calluses at 9 weeks produced under rigid fixation were smaller and consisted of a reduced fibrous tissue component. These results demonstrate that the callus formation over the course of healing differed both morphologically and in the rate of development. In this study, we provide evidence that the course of healing is influenced by the initial fixation stability. The semi-rigid fixator did not result in delayed healing, but a less optimal healing path was taken. An upper limit of stability required for successful healing remains unknown, however a limit by which healing is less optimal has been determined.

  20. What is esoteric healing?

    PubMed

    Settersten, Lori

    2011-06-01

    Esoteric Healing is a type of energy healing that originated from the teachings of Djwhal Khul and Alice Bailey first published in the early 1950s. Esoteric Healing instructors and practitioners are located in more than 19 countries throughout the world. Nurses and nurse practitioners as well as other health professionals (e.g., psychologists and physicians) have integrated Esoteric Healing into their current practice and/or have a separate practice in Esoteric Healing. According to Dochterman and Bulechek, the nursing diagnosis "energy field, disturbed" is defined as a "disruption in the flow of energy surrounding a person's being." Esoteric Healing is proposed to assist a person in balancing her or his flow of energy. In this article, Esoteric Healing is defined, and the components of the energy field according to the teachings of Esoteric Healing are differentiated. The basic Esoteric Healing treatment procedure, treatment protocols, and indications for when Esoteric Healing may be an appropriate healing modality option are described. Finally, research on Esoteric Healing is addressed.

  1. Posterior malleolus fracture.

    PubMed

    Irwin, Todd A; Lien, John; Kadakia, Anish R

    2013-01-01

    Posterior malleolus fractures are a common component of ankle fractures. The morphology is variable; these fractures range from small posterolateral avulsion injuries to large displaced fracture fragments. The integrity of the posterior malleolus and its ligamentous attachment is important for tibiotalar load transfer, posterior talar stability, and rotatory ankle stability. Fixation of posterior malleolus fractures in the setting of rotational ankle injuries has certain benefits, such as restoring articular congruity and rotatory ankle stability, as well as preventing posterior talar translation, but current indications are unclear. Fragment size as a percentage of the anteroposterior dimension of the articular surface is often cited as an indication for fixation, although several factors may contribute to the decision, such as articular impaction, comminution, and syndesmotic stability. Outcome studies show that, in patients with ankle fractures, the presence of a posterior malleolus fracture negatively affects prognosis. Notable variability is evident in surgeon practice. PMID:23281469

  2. Recurrent fracture of the humerus in a softball player.

    PubMed

    Kuschner, S H; Lane, C S

    1999-11-01

    Fracture of a normal humerus can occur during the act of throwing an object. We present the case of a young woman who sustained a spiral fracture of the distal humeral shaft with concomitant radial nerve palsy while throwing a softball and who, after clinical and radiographic evidence of bony healing, suffered a repeat humerus fracture, also while throwing a softball.

  3. Recurrent Proximal Femur Fractures in a Teenager With Osteogenesis Imperfecta on Continuous Bisphosphonate Therapy: Are We Overtreating?

    PubMed

    Vasanwala, Rashida F; Sanghrajka, Anish; Bishop, Nicholas J; Högler, Wolfgang

    2016-07-01

    Long-term bisphosphonate (BP) therapy in adults with osteoporosis is associated with atypical femoral fractures, caused by increased material bone density and prolonged suppression of bone remodeling which may reduce fracture toughness. In children with osteogenesis imperfecta (OI), long-term intravenous BP therapy improves bone structure and mass without further increasing the already hypermineralized bone matrix, and is generally regarded as safe. Here we report a teenage girl with OI type IV, who was started on cyclical intravenous pamidronate therapy at age 6 years because of recurrent fractures. Transiliac bone biopsy revealed classical structural features of OI but unusually low bone resorption surfaces. She made substantial improvements in functional ability, bone mass, and fracture rate. However, after 5 years of pamidronate therapy she started to develop recurrent, bilateral, nontraumatic, and proximal femur fractures, which satisfied the case definition for atypical femur fractures. Some fractures were preceded by periosteal reactions and prodromal pain. Pamidronate was discontinued after 7 years of therapy, following which she sustained two further nontraumatic femur fractures, and continued to show delayed tibial osteotomy healing. Despite rodding surgery, and very much in contrast to her affected, untreated, and normally mobile mother, she remains wheelchair-dependent. The case of this girl raises questions about the long-term safety of BP therapy in some children, in particular about the risk of oversuppressed bone remodeling with the potential for microcrack accumulation, delayed healing, and increased stiffness. The principal concern is whether there is point at which benefit from BP therapy could turn into harm, where fracture risk increases again. This case should stimulate debate whether current adult atypical femoral fracture guidance should apply to children, and whether low-frequency, low-dose cyclical, intermittent, or oral treatment

  4. Surgical management of multiple metatarsal fractures in a chinchilla (Chinchilla lanigera).

    PubMed

    Desprez, Isabelle; Pignon, Charly; Decambron, Adeline; Donnelly, Thomas M

    2016-10-01

    CASE DESCRIPTION A 3-month-old sexually intact female chinchilla (Chinchilla lanigera) was examined for sudden onset of non-weight-bearing lameness of the right hind limb. CLINICAL FINDINGS On physical examination, the right pes was swollen. An open wound on the medial aspect of the metatarsal region exposed the second metatarsal bone, and the pes was displaced laterally. Radiographs of the right pes revealed oblique displaced fractures of the 4 metatarsal bones. TREATMENT AND OUTCOME Surgical treatment was elected, and enrofloxacin was administered prior to surgery. The protruding fragment of the second metatarsal bone was excised, and the third and fourth metatarsal bones were repaired with intramedullary pins and external skeletal fixation. The chinchilla was bearing weight on the affected limb 9 days after surgery with only mild lameness. The implants were removed 35 days after surgery when radiographs showed bony union of the third and fourth metatarsal bones and continued reduction of the fractures of the second and fifth metatarsal bones. Fifty-six days after surgery, the chinchilla was bearing full weight on the limb, and radiographs showed bony union of the third, fourth, and fifth metatarsal bones. CLINICAL RELEVANCE Findings suggested that intramedullary pinning combined with an epoxy resin external fixator may be an effective technique for metatarsal fracture repair in chinchillas. This method allowed physiologic positioning of the limb and functional hind limb use during fracture healing. Prospective studies of fracture healing in exotic small mammals are indicated. PMID:27654167

  5. Surgical management of multiple metatarsal fractures in a chinchilla (Chinchilla lanigera).

    PubMed

    Desprez, Isabelle; Pignon, Charly; Decambron, Adeline; Donnelly, Thomas M

    2016-10-01

    CASE DESCRIPTION A 3-month-old sexually intact female chinchilla (Chinchilla lanigera) was examined for sudden onset of non-weight-bearing lameness of the right hind limb. CLINICAL FINDINGS On physical examination, the right pes was swollen. An open wound on the medial aspect of the metatarsal region exposed the second metatarsal bone, and the pes was displaced laterally. Radiographs of the right pes revealed oblique displaced fractures of the 4 metatarsal bones. TREATMENT AND OUTCOME Surgical treatment was elected, and enrofloxacin was administered prior to surgery. The protruding fragment of the second metatarsal bone was excised, and the third and fourth metatarsal bones were repaired with intramedullary pins and external skeletal fixation. The chinchilla was bearing weight on the affected limb 9 days after surgery with only mild lameness. The implants were removed 35 days after surgery when radiographs showed bony union of the third and fourth metatarsal bones and continued reduction of the fractures of the second and fifth metatarsal bones. Fifty-six days after surgery, the chinchilla was bearing full weight on the limb, and radiographs showed bony union of the third, fourth, and fifth metatarsal bones. CLINICAL RELEVANCE Findings suggested that intramedullary pinning combined with an epoxy resin external fixator may be an effective technique for metatarsal fracture repair in chinchillas. This method allowed physiologic positioning of the limb and functional hind limb use during fracture healing. Prospective studies of fracture healing in exotic small mammals are indicated.

  6. [Body temperature regulation as a prognostic criterion for the postoperative period in patients with femoral fractures].

    PubMed

    Samokhin, A V

    2002-01-01

    Frequency is studied of adequate, redundant, inert, and reduced types of thermoreactivity in healthy subjects and patients with fractures. Definition of type of thermoreactivity to cooling in patients with fractures of the thighbone permits prognosticating the course of the bone fracture healing process. The symptom of distal hyperthermia/hypothermia is unspecific but is regarded as a supplementary index of the type of thermoreactivity and character of the course of the fracture healing process. PMID:12073260

  7. Healing invisible wounds and rebuilding livelihoods: Emerging lessons for combining livelihood and psychosocial support in fragile and conflict-affected settings.

    PubMed

    Kumar, Samhita; Willman, Alys

    2016-09-01

    Populations living in fragile and conflict-affected settings (FCS) endure serious hardship, often including witnessing or having direct exposure to violence. These experiences adversely affect the mind, body, and spirit, and diminish the capacity of individuals and communities to take full advantage of economic empowerment opportunities. A small but growing number of programs have begun to combine psychosocial support with livelihood support in FCS, with some promising indication that this combination can enhance project outcomes. This paper assesses evidence to generate a 'hypothesis of change' that combining psychosocial with livelihood support can improve development outcomes in FCS. We reviewed evaluations of three categories of programs: (i) those that provide psychosocial support and assess impact on economic empowerment, (ii) those that provide livelihood support and assess impact on psychosocial well-being, and (iii) those that combine both types of support and assess impact on one or both outcomes. PMID:27638241

  8. 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.

  9. Thyroid-Stimulating Hormone Within Normal Range Does Not Affect Bone Turnover in Euthyroid Postmenopausal Women with Osteoporotic Fracture - A Preliminary Report

    PubMed Central

    Nowacki, Wieslaw; Sypniewska, Grazyna

    2011-01-01

    Background Pathogenic role of TSH suppression in the damaged bone tissue, in contrast to increased concentrations of thyroid hormones is still unknown. The aim of study was to evaluate the relationship between serum TSH and biochemical bone turnover markers in postmenopausal women with normal thyroid function and to answer whether the differences in TSH concentration within reference range may affect bone metabolism. Material and Methods 34 women (60-93 years old) admitted to the hospital after osteoporotic fracture participated in the study. Serum propeptide of type 1 procollagen (P1NP) as a bone formation marker and crosslinked C-terminal telopeptides (CTX-I), as a bone resorption marker and TSH were assayed. Results Median P1NP (p=0,05) was significantly higher in the 1st tertile of TSH values (0,35-1,88 mlU/mL). In the 3rd tertile of TSH concentrations (3,42-4,94 mlU/mL), the highest CTX-I value was found that exceed the reference range for age. No differences were found in bone markers between a group of euthyroid and a group of subjects with TSH<0,35 mlU/mL. No relationship was observed between TSH and bone formation and resorption markers in the whole group of euthyroid postmenopausal women, however bone formation was found to be in the lower reference range for age in the euthyroid subjects as well as in these with decreased TSH. Weight and BMI correlated negatively with CTX (r=-0,68 p<0,03) in fractured women in the 1st tertile of TSH. Conclusion We found no consistent evidence that TSH concentrations within reference range was associated with changes in bone turnover markers.

  10. Treating Tibia Fractures With Far Cortical Locking Implants.

    PubMed

    Rice, Christopher; Christensen, Thomas; Bottlang, Michael; Fitzpatrick, Dan; Kubiak, Erik

    2016-01-01

    Compared with conventional plating, the relatively new technology of far cortical locking (FCL) allows for more flexible fixation. Increased flexibility of FCL constructs is thought to better stimulate secondary osteosynthesis and lead to improved healing for certain fracture patterns. We conducted a study to compare healing rates and complications of tibial fractures treated with FCL or standard plating techniques. Twenty-two patients with fractures of the tibia (Orthopaedic Trauma Association 41ABC, 42C, 43C) were included in the study. Twelve tibia fractures were treated with FCL and 10 with standard plating (locking or nonlocking). Mean follow-up was 47 weeks in the FCL group and 41 weeks in the control group. The fracture healing rate was 92% in the FCL group and 100% in the control group (difference not statistically significant). Of note, there were 2 open fractures in the FCL group and 0 in the control group. The groups had similar complication rates. Our study data suggest FCL implants are not inferior to conventional plating techniques. Given that FCL-treated fractures tended to be more complex, the groups' similar fracture healing rates may indicate improved fracture healing with FCL technology, but this possibility requires further investigation. PMID:26991582

  11. 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.

  12. 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.

  13. 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.

  14. 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. PMID:15486623

  15. 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.

  16. Diagnosis and management of metatarsal fractures.

    PubMed

    Hatch, Robert L; Alsobrook, John A; Clugston, James R

    2007-09-15

    Patients with metatarsal fractures often present to primary care settings. Initial evaluation should focus on identifying any conditions that require emergent referral, such as neurovascular compromise and open fractures. The fracture should then be characterized and treatment initiated. Referral is generally indicated for intra-articular or displaced metatarsal fractures, as well as most fractures that involve the first metatarsal or multiple metatarsals. If the midfoot is injured, care should be taken to evaluate the Lisfranc ligament. Injuries to this ligament require referral or specific treatment based on severity. Nondisplaced fractures of the metatarsal shaft usually require only a soft dressing followed by a firm, supportive shoe and progressive weight bearing. Stress fractures of the first to fourth metatarsal shafts typically heal well with rest alone and usually do not require immobilization. Avulsion fractures of the proximal fifth metatarsal tuberosity can usually be managed with a soft dressing. Proximal fifth metatarsal fractures that are distal to the tuberosity have a poorer prognosis. Radiographs should be carefully examined to distinguish these fractures from tuberosity fractures. Treatment of fractures distal to the tuberosity should be individualized based on the characteristics of the fracture and patient preference. Nondisplaced fractures of the proximal portion of metatarsals 1 through 4 can be managed acutely with a posterior splint followed by a molded, non-weight-bearing, short leg cast. If radiography reveals a normal position seven to 10 days after injury, progressive weight bearing may be started, and the cast may be removed three to four weeks later.

  17. Stress and Wound Healing

    PubMed Central

    Christian, Lisa M.; Graham, Jennifer E.; Padgett, David A.; Glaser, Ronald; Kiecolt-Glaser, Janice K.

    2009-01-01

    Over the past decade it has become clear that stress can significantly slow wound healing: stressors ranging in magnitude and duration impair healing in humans and animals. For example, in humans, the chronic stress of caregiving as well as the relatively brief stress of academic examinations impedes healing. Similarly, restraint stress slows healing in mice. The interactive effects of glucocorticoids (e.g. cortisol and corticosterone) and proinflammatory cytokines [e.g. interleukin-1β (IL-1β), IL-lα, IL-6, IL-8, and tumor necrosis factor-α] are primary physiological mechanisms underlying the stress and healing connection. The effects of stress on healing have important implications in the context of surgery and naturally occurring wounds, particularly among at-risk and chronically ill populations. In research with clinical populations, greater attention to measurement of health behaviors is needed to better separate behavioral versus direct physiological effects of stress on healing. Recent evidence suggests that interventions designed to reduce stress and its concomitants (e.g., exercise, social support) can prevent stress-induced impairments in healing. Moreover, specific physiological mechanisms are associated with certain types of interventions. In future research, an increased focus on mechanisms will help to more clearly elucidate pathways linking stress and healing processes. PMID:17709956

  18. [Sarmiento's method of conservative treatment of leg fractures].

    PubMed

    Dewijze, M; Pe, M; Tondeur, G

    1985-01-01

    The authors present a prospective series of 32 fractures of the tibia, treated by Sarmiento's technique. Consolidation of the fracture has been obtained in 3 to 4 months. Five open tibia fractures healed in 4 months. Functional recovery is complete in 90% of the cases. Two failures needed late surgical treatment (one centro-medullary nailing and one plate-fixation). These fractures are studied in detail. PMID:3984632

  19. 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.

  20. 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. PMID:26611923

  1. 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

  2. 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

  3. Use of teriparatide in osteoporotic fracture patients.

    PubMed

    Collinge, Cory; Favela, Juan

    2016-01-01

    Teriparatide [PTH (1-34)] is a genetically engineered analog of human parathyroid hormone that acts as an anabolic drug by increasing activity in both osteoblasts and osteoclasts. Intermittent (once-daily) doses of teriparatide seem to stimulate osteoblast activity and therefore result in a net increase of bone formation. It is recommended for use in post-menopausal women (PMW), men with hypogonadal osteoporosis, as well as men and women with glucocorticoid-induced osteoporosis. In vivo studies have generated important findings regarding teriparatide's role in the enhancement of fracture healing. The intention of this article is to review the clinical findings of teriparatide to stimulate fracture healing. The drug was shown in a prospective randomized, double blind study to achieve earlier radiographic cortical bridging of three of four cortices (7.4 weeks) compared to patients who were assigned to the placebo group (9.1 weeks). Another study compared mean time for healing and functional outcome in two groups of elderly women who had suffered osteoporotic pelvic fractures: one group received daily 100 μg parathyroid hormone (1-84) injections, while the other group received no treatment. Patients who received the PTH (1-84) injections accelerated radiographic and clinical fracture healing (7.8 weeks) when compared to patients who received no treatment (12.6 weeks, p<0.001). Numerous case series state the safety and potential benefits of teriparatide use in patients recovering from fractures. In the following scenarios, teriparatide might be considered in patients with osteoporosis and a fracture: (1) patients with severe osteoporosis with use of bisphosphonates for a number of years with a fracture not expected to predictably unite, e.g. atypical femur fracture or open tibia fracture, (2) in cases where an osteoporotic patient has failed fracture healing and is considering surgical treatment e.g. non-union surgery. It seems prudent to reevaluate these patients

  4. Self-healing biomaterials.

    PubMed

    Brochu, Alice B W; Craig, Stephen L; Reichert, William M

    2011-02-01

    The goal of this review is to introduce the biomaterials community to the emerging field of self-healing materials, and also to suggest how one could utilize and modify self-healing approaches to develop new classes of biomaterials. A brief discussion of the in vivo mechanical loading and resultant failures experienced by biomedical implants is followed by presentation of the self-healing methods for combating mechanical failure. If conventional composite materials that retard failure may be considered zeroth generation self-healing materials, then taxonomically speaking, first generation self-healing materials describe approaches that "halt" and "fill" damage, whereas second generation self-healing materials strive to "fully restore" the prefailed material structure. In spite of limited commercial use to date, primarily because the technical details have not been suitably optimized, it is likely from a practical standpoint that first generation approaches will be the first to be employed commercially, whereas second generation approaches may take longer to implement. For self-healing biomaterials the optimization of technical considerations is further compounded by the additional constraints of toxicity and biocompatibility, necessitating inclusion of separate discussions of design criteria for self-healing biomaterials.

  5. Metacarpal and metatarsal fractures in dogs.

    PubMed

    Muir, P; Norris, J L

    1997-08-01

    Metacarpal fractures were more common than metatarsal fractures in this retrospective study of 37 dogs. Fractures of one metacarpal or metatarsal bone occurred in 24 per cent of the dogs, two metacarpal bones in 16 per cent, three metacarpal or metatarsal bones in 19 per cent, and four metacarpal or metatarsal bones in 41 per cent. Eighty-seven per cent of the dogs with fractures of four bones had fracture displacement or malalignment of at least one digit. Progressive fracture healing usually occurred irrespective of stabilisation method. For malaligned fractures, however, external coaptation did not consistently improve alignment. Fracture alignment was consistently improved by open reduction and internal fixation of acute fractures with bone plates. Fractures of four bones occurred most often in the distal metacarpus as opposed to the proximal metatarsus. Therefore, open reduction and internal fixation may be more commonly indicated for severe metacarpal fractures, because fracture displacement or axial malalignment was significantly associated with fractures of the mid or distal regions of the metacarpus or metatarsus (P = 0.052).

  6. [Femoral neck fracture].

    PubMed

    Gierer, P; Mittlmeier, T

    2015-03-01

    The incidence of femoral neck fractures increases exponentially with rising age. Young patients are rarely affected but when they are it is mostly due to high energy accidents, whereas older patients suffer from femoral neck fractures by low energy trauma due to osteoporotic changes of the bone mineral density. Treatment options have not essentially changed over the last few years. Non-operative treatment may be a choice in non-dislocated and impacted fractures. Due to the high risk of secondary fracture displacement prophylactic screw osteosynthesis is recommended even in Garden type I fractures. Osteosynthetic fracture stabilization with cannulated screws or angle stable sliding screws, is usually applied in non-displaced fractures and fractures in younger patients. Older patients need rapid mobilization after surgery; therefore, total hip arthroplasty and hemiarthroplasty are commonly used with a low incidence of secondary complications. In addition to sufficient operative treatment a guideline conform osteoprosis therapy should be initiated for the prophylaxis of further fractures and patients should undertake a suitable rehabilitation.

  7. Hoffa's fracture - lateral meniscus obstructing the fracture reduction - a case report.

    PubMed

    Jain, Sumit Kumar; Jadaan, Mutaz; Rahall, Elias

    2015-02-01

    Hoffa's fracture is a coronal fracture of the posterior femoral condyle and is an unusual injury. It can be easily missed on plain radiographs. There is no dearth of literature on Hoffa's fracture, its various presentations, management and rehabilitation principles. The intra-articular nature of the fracture, vulnerable blood supply of the posterior femoral condyle, involvement of the weight bearing articular surface of the knee and the unstable fracture pattern necessitate the surgical management. We encountered an unusual case of Hoffa's fracture where the lateral meniscus was blocking the reduction of fractured fragments. The patient required mini arthrotomy to remove the meniscus from in between the bone fragments. The fracture was fixed with two anteroposterior screws and knee was immobilised in extension. A gentle knee range of movements was commenced after the wound had healed but weight bearing was delayed for 12 weeks. PMID:25554423

  8. 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.

  9. 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.

  10. Delayed union of the distal ulna in a child after both bone forearm fracture.

    PubMed

    Fike, E A; Bartal, E

    1998-01-01

    Fractures of the distal third of the forearm are common in children. These fractures are known to heal readily and rapidly. We describe a 10-year-old boy who had a closed, low-energy fracture of the distal radius and ulna. The radius healed promptly, but the ipsilateral ulna had radiographic evidence of delayed union. We have not found a report of a nonunion of this kind in the literature. With the increasing use of internal fixation and the lack of guidance in the literature, we questioned the standard use of closed treatment. We treated this patient nonoperatively, despite the delay in union, and the fracture healed in 4 months.

  11. 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

  12. [Recent progress in orthopaedic managements of osteoporosis-related fractures].

    PubMed

    Yamamoto, Seizo

    2011-07-01

    Recent progress in orthopaedic treatment of osteoporosis-related fractures was reviewed. In the treatment of femoral neck fractures, impacted or nondisplaced type is treated by three cannulated cancellous pins. Displaced type of femoral neck fracture is treated by bipolar prosthesis. Results of femoral neck fractures are influenced by the complications of each patients. Osteoporotic spine fractures are commonly healed within 2 or 3 months. Spinal compression with paraparesis or paraplegia is unusual complication in burst type of spine fractures. Surgical decompression, bone grafting and stabilization with instrumentation can result in some correction of deformity and neurogenic recovery. Distal radius fractures are common fractures in the eldery. Recently advances includes external fixation and plate fixation for the comminuted fractures in the distal radius. Treatments of osteoporosis-related fractures are still difficult problems to be resolved. PMID:21774371

  13. 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

  14. 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.

  15. 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.

  16. Fractures of the growing mandible.

    PubMed

    Kushner, George M; Tiwana, Paul S

    2009-03-01

    Oral and maxillofacial surgeons must constantly weigh the risks of surgical intervention for pediatric mandible fractures against the wonderful healing capacity of children. The majority of pediatric mandibular fractures can be managed with closed techniques using short periods of maxillomandibular fixation or training elastics alone. Generally, the use of plate- and screw-type internal fixation is reserved for difficult fractures. This article details general and special considerations for this surgery including: craniofacial growth & development, surgical anatomy, epidemiology evaluation, various fractures, the role rigid internal fixation and the Risdon cable in pediatric maxillofacial trauma. It concludes with suggestions concerning long-term follow-up care in light of the mobility, insurance obstacles, and family dynamics facing the patient population.

  17. Traumatic Fracture in a patient of Osteopoikilosis with Review of Literature

    PubMed Central

    Bansal, Rohan; Pathak, Aditya C; Sheth, Binoti; Patil, Atul K

    2013-01-01

    Introduction: Osteopoikilosis or osteopathia condensans disseminata is a rare hereditary autosomal dominant sclerosing bone dysplasia. Patients are usually asymptomatic and the diagnosis is usually made incidentally on radiographs which show presence of symmetric, multiple, well defined, small ovoid areas of increased radiodensity clustered in peri-articular osseous regions with propensity for epiphyseal and metaphyseal involvement. There are no increased risks of pathological fracture in a case of osteopoikilosis and traumatic fracture healing in a case of osteopoikilosis is similar to fracture occurring in other normal patients. Case Report: A 34 years male, electrician came with history of accidental fall from height while working in office leading to development of pain and swelling over left lower leg and ankle diagnosed with Ruedi-Allgower classification type I pilon fracture(without fibula fracture) no distal neuro-vascular deficit. Patient was offered surgical treatment in form of open reduction and internal fixation of tibial fracture by plate osteosynthesis using antero-medial approach, showed complete union and was followed up for eight months. Conclusion: Osteopoikilosis has a benign course and it should always be kept as a possible differential diagnosis for osteoblastic metastasis to avoid diagnositic dilemma. Diagnosis can be settled by routine x-rays (for type, extent and site of lesions, bones affected), clinical features of patient, histopathology and other systemic or pre-existing conditions. PMID:27298900

  18. THE ROLE OF MECHANOBIOLOGY IN TENDON HEALING

    PubMed Central

    Killian, Megan L.; Cavinatto, Leonardo; Galatz, Leesa M.; Thomopoulos, Stavros

    2011-01-01

    Mechanical cues affect tendon healing, homeostasis, and development in a variety of settings. Alterations in the mechanical environment are known to result in changes in the expression of extracellular matrix proteins, growth factors, transcription factors, and cytokines that can alter tendon structure and cell viability. Loss of muscle force in utero or in the immediate postnatal period delays tendon and enthesis development. The response of healing tendons to mechanical load varies depending on anatomic location. Flexor tendons require motion to prevent adhesion formation, yet excessive force results in gap formation and subsequent weakening of the repair. Excessive motion in the setting of anterior cruciate ligament reconstruction causes accumulation of macrophages, which are detrimental to tendon graft healing. Complete removal of load is detrimental to rotator cuff healing, yet large forces are also harmful. Controlled loading can enhance healing in most settings; however, a fine balance must be reached between loads that are too low (leading to a catabolic state) and too high (leading to micro-damage). This review will summarize existing knowledge of the mechanobiology of tendon development, homeostasis, and healing. PMID:22244066

  19. Systems-based approaches toward wound healing

    PubMed Central

    Buganza-Tepole, Adrian; Kuhl, Ellen

    2013-01-01

    Wound healing in the pediatric patient is of utmost clinical and social importance, since hypertrophic scarring can have aesthetic and psychological sequelae, from early childhood to late adolescence. Wound healing is a well-orchestrated reparative response affecting the damaged tissue at the cellular, tissue, organ, and system scales. While tremendous progress has been made towards understanding wound healing at the individual temporal and spatial scales, its effects across the scales remain severely understudied and poorly understood. Here we discuss the critical need for systems-based computational modeling of wound healing across the scales, from short-term to long-term and from small to large. We illustrate the state of the art in systems modeling by means of three key signaling mechanisms: oxygen tension regulating angiogenesis and revascularization; TGF-β kinetics controlling collagen deposition; and mechanical stretch stimulating cellular mitosis and extracellular matrix remodeling. The complex network of biochemical and biomechanical signaling mechanisms and the multi-scale character of the healing process make systems modeling an integral tool in exploring personalized strategies for wound repair. A better mechanistic understanding of wound healing in the pediatric patient could open new avenues in treating children with skin disorders such as birth defects, skin cancer, wounds, and burn injuries. PMID:23314298

  20. 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.

  1. 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. PMID:21629425

  2. Adenosine receptor agonists for promotion of dermal wound healing

    PubMed Central

    Valls, María D.; Cronstein, Bruce N.; Montesinos, M. Carmen

    2009-01-01

    Wound healing is a dynamic and complex process that involves a well coordinated, highly regulated series of events including inflammation, tissue formation, revascularization and tissue remodeling. However, this orderly sequence is impaired in certain pathophysiological conditions such as diabetes mellitus, venous insufficiency, chronic glucocorticoid use, aging and malnutrition. Together with proper wound care, promotion of the healing process is the primary objective in the management of chronic poorly healing wounds. Recent studies have demonstrated that A2A adenosine receptor agonists promote wound healing in normal and diabetic animals and one such agonist, Sonedenoson, is currently being evaluated as a prospective new therapy of diabetic foot ulcers. We will review the mechanisms by which adenosine receptor activation affects the function of the cells and tissues that participate in wound healing, emphasizing the potential beneficial impact of adenosine receptor agonists in diabetic impaired healing. PMID:19041853

  3. 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.

  4. Organic semiconductors: Healing contact

    NASA Astrophysics Data System (ADS)

    Risko, Chad; Brédas, Jean-Luc

    2013-12-01

    Traps in organic semiconducting crystals are healed when a perfluoropolyether oil is deposited on the surface of these materials, thus making possible the detection of intrinsic features of charge-carrier transport in rubrene and tetracene.

  5. Can serial scintigraphic studies detect delayed fracture union in man

    SciTech Connect

    O'Reilly, R.J.; Cook, D.J.; Gaffney, R.D.; Angel, K.R.; Paterson, D.C.

    1981-01-01

    The uptake of the bone-seeking tracer technetium-99m-methylenediphosphonate increases following bone fracture as bone healing occurs. To investigate the pattern of change in normal healing and compare it with delayed union and nonunion, an analysis of automated computer profiles was carried out on serial scan data for 22 patients. The type of fracture (simple, comminuted, etc.) influenced the appearance of the activity profile; however, no significant differences in the patterns of change were noted between normal healing and delayed or non-union.

  6. 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.

  7. Elbow Fractures

    MedlinePlus

    ... and held together with pins and wires or plates and screws. Fractures of the distal humerus (see ... doctor. These fractures usually require surgical repair with plates and/or screw, unless they are stable. SIGNS ...

  8. Saliva and wound healing.

    PubMed

    Brand, Henk S; Veerman, Enno C I

    2013-01-01

    Wounds in the oral cavity heal faster and with less scarring than wounds in other parts of the body. One of the factors implicated in this phenomenon is the presence of saliva, which promotes the healing of oral wounds in several ways. Saliva creates a humid environment, which improves the survival and functioning of inflammatory cells that are crucial for wound healing. Furthermore, saliva contains a variety of proteins that play a role in the various stages of the intraoral wound healing. Tissue factor, present in salivary exosomes, accelerates the clotting of blood dramatically. The subsequent proliferation of epithelial cells is promoted by growth factors in saliva, especially epidermal growth factor. The importance of secretory leucocyte protease inhibitor is demonstrated by the observation that in the absence of this salivary protein, oral wound healing is considerably delayed. Members of the salivary histatin family promote wound closure in vitro by enhancing cell spreading and cell migration. Cell proliferation is not enhanced by histatin. Cyclization of histatin increased its biological activity approximately 1,000-fold compared to linear histatin. These studies suggest that histatins could potentially be used for the development of new wound healing medications.

  9. Treatment of fractures of the tibial and/or fibular malleoli in 30 cats.

    PubMed

    Roch, S P; Störk, C K; Gemmill, T J; Downes, C; Pink, J; McKee, W M

    2009-08-01

    Five cats were treated for a fracture of the medial malleolus, 10 for a fracture of the lateral malleolus and 15 for fractures of both malleoli. Open reduction and internal fixation with Kirschner wires (K-wires) with or without a tension band wire was applied to 26 of the fractures. Unilateral-uniplanar or bilateral-uniplanar transarticular external skeletal fixators were applied to provide coaptation in 19 cases and appeared to be well tolerated. In 24 cases fracture healing was assessed radiographically between four and eight weeks after treatment. In seven cases fracture healing was good, in 12 cases it was reasonable, in four cases it was poor and in one case with two fractures healing was poor in one and reasonable in the other. The 12 fractures treated by open reduction and internal fixation with K-wires and a tension band wire all showed evidence of good or reasonable healing. The nine fractures treated by open reduction and internal fixation with K-wires without a tension band wire showed evidence of good or reasonable healing in six cases and poor healing in three cases. Complications occurred in nine of the cats and included persistent talocrural instability, soft tissue necrosis, implant migration and external fixator pin breakage. Twenty-one of the cats were followed up by telephone questionnaire for between 5.5 and 84 months; the owner satisfaction was excellent in 17 cases, good in two cases, moderate in one case and poor in one case. PMID:19666914

  10. Stress fractures of the upper limb.

    PubMed

    Brukner, P

    1998-12-01

    Stress fractures are commonly found in the lower limb, but also occur in the upper limb, and are particularly associated with upper limb-dominated sports such as tennis and swimming and those involving throwing activities. Stress fractures of the clavicle and scapula are rare but have been reported, whereas those of the humerus are more frequent and have been described mainly in adolescent baseball pitchers. Olecranon stress fractures occur in throwers and gymnasts. Stress fractures of the ulna and radius have also been reported in a number of different upper limb-dominated sports. In all cases, these fractures heal with conservative management. The physician should consider stress fracture as a possible diagnosis in cases of upper limb pain of bony origin where the pain is associated with overuse.

  11. Suture Bridge Fixation Technique for Posterior Cruciate Ligament Avulsion Fracture.

    PubMed

    Lee, Kwang Won; Yang, Dae Suk; Lee, Gyu Sang; Choy, Won Sik

    2015-12-01

    We presented a surgical technique including a suture bridge technique with relatively small incision for the reduction and fixation of posterior ligament avulsion fractures. A suture anchor was used to hold the avulsed fragment and a knotless anchor was used to continuously compress the bony fragment into the fracture site, thereby maintaining reduction during healing.

  12. 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

  13. Combined surgical therapy and orthotic management of stress and tuberosity avulsion fracture of the fifth metatarsal bone: a case report.

    PubMed

    Darabos, Nikica; Obrovac, Karlo; Knez, Nikica; Darabos, Anela; Hudetz, Damir; Elabjer, Esmat

    2009-01-01

    The incidence of fifth metatarsal fracture is somewhat common in sports and can be complicated in nature. Fractures of the fifth metatarsal can occur at a number of locations. Although some of these fractures respond well to conservative treatment, others have been notoriously hard to heal, with high rates of nonunions and other complications. Foot orthotic devices are commonly used as aids in the treatment of foot problems. In our case, we considered the combined effect of the surgical treatment and application of the custom-made foot orthoses. Special attention was taken with adjustments to the orthotic devices along and beneath the affected regions of the foot for adequate pain management and quick recovery to return to normal sports activities. Requirements for computer aided design/computer aided manufacturing orthotic design and manufacturing in this case were specific and considerably different from the usual procedure.

  14. 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

  15. Special Review: Accelerating fracture repair in humans: a reading of old experiments and recent clinical trials

    PubMed Central

    Aspenberg, Per

    2013-01-01

    Based on their mode of action and preclinical data, one would expect bisphosphonates to improve the healing of fractures in cancellous bone, and bone morphogenetic proteins (BMPs) to reduce the risk of non-union in severe shaft fractures. Parathyreoid hormone (PTH) can be expected to accelerate fracture healing in general. The clinical data in support of this is meager. Stimulation of cancellous bone healing and strength by bisphosphonates has been inadvertently shown in the context of implant fixation, but not convincingly in fractures per se. The clinical BMP literature is confusing, and the chance of ever demonstrating reduced numbers of non-union are small, due to power issues. Still, acceleration of ‘normal' healing may be possible, but largely remains to show. For PTH, the two available clinical trials both show accelerated healing, but none of them is flawless, and there is a need for better studies. PMID:24404375

  16. 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.

  17. 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.

  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. Metatarsal fractures.

    PubMed

    Rammelt, Stefan; Heineck, Jan; Zwipp, Hans

    2004-09-01

    Metatarsal fractures are relatively common and if malunited, a frequent source of pain and disability. Nondisplaced fractures and fractures of the second to fourth metatarsal with displacement in the horizontal plane can be treated conservatively with protected weight bearing in a cast shoe for 4-6 weeks. In most displaced fractures, closed reduction can be achieved but maintenance of the reduction needs internal fixation. Percutaneous pinning is suitable for most fractures of the lesser metatarsals. Fractures with joint involvement and multiple fragments frequently require open reduction and plate fixation. Transverse fractures at the metaphyseal-diaphyseal junction of the fifth metatarsal ("Jones fractures") require an individualized approach tailored to the level of activity and time to union. Avulsion fractures of the fifth metatarsal bone are treated by open reduction and tension-band wiring or screw fixation if displaced more than 2 mm or with more that 30% of the joint involved. The metatarsals are the most common site of stress fractures, most of which are treated nonoperatively. Symptomatic posttraumatic deformities need adequate correction, in most cases by osteotomy across the former fracture site.

  20. Pathological pelvic fracture following long-term bisphosphonate use in a 63-year-old woman

    PubMed Central

    Watson, H I; Hopper, G P; Gupta, S; Roberts, J L

    2014-01-01

    A 63-year-old woman presented with a low energy pelvic fracture, which showed no signs of healing. Initial fractures were to the right hemipelvis, later followed by a right fractured neck of femur. We present a complicated patient journey, management dilemmas and highlight the growing concern with long-term bisphosphonate treatment. PMID:25312895

  1. 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.

  2. 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

  3. Pubic and sacral insufficiency fractures: clinical course and radiologic findings

    SciTech Connect

    De Smet, A.A.; Neff, J.R.

    1985-09-01

    Distinctive vertical insufficiency fractures of the pelvis were found in nine osteopenic patients. Each patient had subacute pelvic pain without antecedent trauma. The sacral fractures healed fairly quickly, but the pubic fractures often had a protracted course. All nine patients had skeletal demineralization due to metabolic bone disease, radiation therapy, or multiple myeloma. Recognition of the association between public and sacral insufficiently fractures should aid in recognizing the diffuse nature of the skeletal disease so that unnecessary biopsy of the fracture sites can be avoided. Plain films, tomographic scans, and radionuclide bone scans are reviewed.

  4. Stress fracture of the ipsilateral first rib in a pitcher.

    PubMed

    Gurtler, R; Pavlov, H; Torg, J S

    1985-01-01

    This stress fracture of the left first rib in a 17-year-old, left-handed high school baseball pitcher represents the first of its type reported in the literature. Two similar cases have been reported in pitchers, but the fracture was on the nondominant side in both cases. In contrast to most cases of this rare lesion, the stress fracture we report occurred acutely and was documented roentgenographically from onset to complete healing 9 months later.

  5. 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.

  6. Role of matrix metalloproteinases in non-healing venous ulcers.

    PubMed

    Amato, Bruno; Coretti, Guido; Compagna, Rita; Amato, Maurizio; Buffone, Gianluca; Gigliotti, Diego; Grande, Raffaele; Serra, Raffaele; de Franciscis, Stefano

    2015-12-01

    Chronic venous ulceration (CVU) of the lower limbs is a common condition affecting 1% of the adult population in Western countries, which is burdened with a high complication rate and a marked reduction in the quality of life often due to prolonged healing time. Several metalloproteinases (MMPs) such as MMP-9 together with neutrophil gelatinase-associated lipocalin (NGAL) appear to be involved in the onset and healing phases of venous ulcer, but it is still unclear how many biochemical components are responsible for prolonged healing time in those ulcers. In this study, we evaluate the role of MMP-1 and MMP-8 in long lasting and refractory venous ulcers. In a 2-year period we enroled 45 patients (28 female and 17 male, median age 65) with CVU. The enroled population was divided into two groups: group I were patients with non-healing ulcers (ulcers that had failed to heal for more than 2 months despite appropriate treatments) and group II were patients with healing ulcers (ulcers in healing phases). MMP-1 and MMP-8 were measured in fluids and tissues of healing and non-healing ulcers by means of enzyme-linked immunosorbent assay (ELISA) and Western blot analysis, respectively. In particular the patterns of the collagenases MMP-1 and MMP-8 in healing wounds were distinct, with MMP-8 appearing in significantly greater amounts especially in the non-healing group. Our findings suggest that MMP-1, and MMP-8 are overexpressed in long lasting CVU. Therefore, this dysregulation may represent the main cause of the pathogenesis of non-healing CVU.

  7. [Advances in the effects of pH value of micro-environment on wound healing].

    PubMed

    Tian, Ruirui; Li, Na; Wei, Li

    2016-04-01

    Wound healing is a complex regeneration process, which is affected by lots of endogenous and exogenous factors. Researches have confirmed that acid environment could prevent wound infection and accelerate wound healing by inhibiting bacteria proliferation, promoting oxygen release, affecting keratinocyte proliferation and migration, etc. In this article, we review the literature to identify the potential relationship between the pH value of wound micro-environment and the progress of wound healing, and summarize the clinical application of variation of pH value of micro-environment in wound healing, thereby to provide new treatment strategy for wound healing.

  8. 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

  9. Augmentation of tendon-to-bone healing.

    PubMed

    Atesok, Kivanc; Fu, Freddie H; Wolf, Megan R; Ochi, Mitsuo; Jazrawi, Laith M; Doral, M Nedim; Lubowitz, James H; Rodeo, Scott A

    2014-03-19

    Tendon-to-bone healing is vital to the ultimate success of the various surgical procedures performed to repair injured tendons. Achieving tendon-to-bone healing that is functionally and biologically similar to native anatomy can be challenging because of the limited regeneration capacity of the tendon-bone interface. Orthopaedic basic-science research strategies aiming to augment tendon-to-bone healing include the use of osteoinductive growth factors, platelet-rich plasma, gene therapy, enveloping the grafts with periosteum, osteoconductive materials, cell-based therapies, biodegradable scaffolds, and biomimetic patches. Low-intensity pulsed ultrasound and extracorporeal shockwave treatment may affect tendon-to-bone healing by means of mechanical forces that stimulate biological cascades at the insertion site. Application of various loading methods and immobilization times influence the stress forces acting on the recently repaired tendon-to-bone attachment, which eventually may change the biological dynamics of the interface. Other approaches, such as the use of coated sutures and interference screws, aim to deliver biological factors while achieving mechanical stability by means of various fixators. Controlled Level-I human trials are required to confirm the promising results from in vitro or animal research studies elucidating the mechanisms underlying tendon-to-bone healing and to translate these results into clinical practice.

  10. 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.

  11. 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.

  12. [Saliva and wound healing].

    PubMed

    Veerman, E C I; Oudhoff, M J; Brand, H S

    2011-05-01

    The oral mucosa is frequently exposed to mechanical forces, which may result in tissue damage. Saliva contributes to the repair of the oral mucosa in several ways. In the first place, it creates a humid environment to improve the function of inflammatory cells. During the last few years, it has been shown that saliva also contains a large number of proteins with a role in wound healing. Saliva contains growth factors, especially Epidermal Growth FACTOR, which promotes the proliferation of epithelial cells. Trefoil factor 3 and histatin promote the process of wound closure. The importance of Secretory Leucocyte Protease Inhibitor is demonstrated by the fact that in the absence of this salivary protein, oral wound healing is considerably delayed. Understanding these salivary proteins opens the way for the development of new wound healing medications.

  13. Wnt Signaling During Fracture Repair

    PubMed Central

    Secreto, Frank J.; Hoeppner, Luke H.; Westendorf, Jennifer J.

    2010-01-01

    Bone is one of the few tissues in the body with the capacity to regenerate and repair itself. In most cases, fractures are completely repaired in a relatively short period of time; however, in a small percentage of cases, healing never occurs and non-union is the result. Fracture repair and bone regeneration require the localized re-activation of signaling cascades that are crucial for skeletal development. The Wnt/β-catenin signaling pathway is one such developmental pathway whose role in bone formation and regeneration has been recently appreciated. During the last decade, much has learned about how Wnt pathways regulate bone mass. Small molecules and biologics aimed at this pathway are now being tested as potential new anabolic agents. Here we review recent data demonstrating that Wnt pathways are active during fracture repair and that increasing the activities of Wnt pathway components accelerates bone regeneration. PMID:19631031

  14. Metacarpal fractures in the athlete.

    PubMed

    Rettig, A C; Ryan, R; Shelbourne, K D; McCarroll, J R; Johnson, F; Ahlfeld, S K

    1989-01-01

    Fifty-six fractures of the metacarpal occurring in 53 athletes were studied from September 1985 to December 1986, regarding mechanism of injury, type of fracture, type of treatment, and time lost from sport. Age range of the patients was 8 to 28 years with greater than 77% being in the 14 to 18 year age range, the high school athlete. Twenty-nine of the fractures occurred in football, 14 in basketball, and the remainder were divided between various other sports. The most common mechanism of injury involved falls or hitting an object such as a helmet or another player. Fractures were evenly divided regarding which digit was involved in football, whereas most basketball injuries occurred in the fourth and fifth metacarpal. Fractures were analyzed as to type of radiographic appearance and this was correlated with time lost from competition or participation. No significant difference among fracture type regarding time lost was noted. Forty-six of the fractures (82%) were minimally displaced or undisplaced and were treated by means of simple casting and/or splinting whereas 10 were displaced. Two of the 10 underwent closed reduction and casting; 3 underwent closed reduction and percutaneous pin fixation; and 5 (9%) underwent open reduction internal fixation using AO type plates and screws. All fractures healed primarily clinically and radiographically. The average time lost from practice or competition in this group overall was 13.7 days, (range, 0 to 56 days). Average time lost from basketball was 19.8 days and from football 10.63 days overall. Average time lost from sport in stable fractures treated with casting or splinting was 12.3 days.(ABSTRACT TRUNCATED AT 250 WORDS)

  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. Primed Mesenchymal Stem Cells Alter Healing and Improve Rat Medial Collateral Ligament Healing

    PubMed Central

    Saether, Erin E.; Chamberlain, Connie S.; Aktas, Erdem; Leiferman, Ellen M.; Brickson, Stacey L.; Vanderby, Ray

    2016-01-01

    Cell therapy with mesenchymal stem cells (MSCs) can improve tissue healing. It is possible, however, that priming MSCs prior to implantation can further enhance their therapeutic benefit. This study was then performed to test whether priming MSCs to be more anti-inflammatory would enhance healing in a rat ligament model, i.e. a medial collateral ligament (MCL). MSCs were primed for 48 hours using polyinosinic acid and polycytidylic acid (Poly (I:C)) at a concentration of 1µg/ml. Rat MCLs were surgically transected and administered 1×106 cells in a carrier solution at the time of injury. A series of healing metrics were analyzed at days 4 and 14 post-injury in the ligaments that received primed MSCs, unprimed MSCs, or no cells (controls). Applying primed MSCs beneficially altered healing by affecting endothelialization, type 2 macrophage presence, apoptosis, procollagen 1α, and IL-1Ra levels. When analyzing MSC localization, both primed and unprimed MSCs co-localized with endothelial cells and pericytes suggesting a supportive role in angiogenesis. Priming MSCs prior to implantation altered key ligament healing events, resulted in a more anti-inflammatory environment, and improved healing. PMID:26530282

  18. 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

  19. Surgical treatment and a unique management of rostral mandibular fracture with cerclage wire in a horse.

    PubMed

    Naddaf, Hadi; Sabiza, Soroush; Kavosi, Narges

    2015-01-01

    A 3-year-old Arabian colt was presented for a major gingiva wound at the right rostral part of mandible. After clinical assessments, rostral mandibular fracture was determined. Stabilization of fractured region was achieved via cerclage wire application under general anesthesia. Fixation wires were left in place for 6 weeks. A 3 -month follow up revealed complete fracture healing. The purpose of this case report was to give clinical information about rostral mandibular fractures and treatment of these fractures and nutrition protocol in a horse, as this fracture is of the most common type of jaw fracture sustained by young horses.

  20. Surgical treatment and a unique management of rostral mandibular fracture with cerclage wire in a horse.

    PubMed

    Naddaf, Hadi; Sabiza, Soroush; Kavosi, Narges

    2015-01-01

    A 3-year-old Arabian colt was presented for a major gingiva wound at the right rostral part of mandible. After clinical assessments, rostral mandibular fracture was determined. Stabilization of fractured region was achieved via cerclage wire application under general anesthesia. Fixation wires were left in place for 6 weeks. A 3 -month follow up revealed complete fracture healing. The purpose of this case report was to give clinical information about rostral mandibular fractures and treatment of these fractures and nutrition protocol in a horse, as this fracture is of the most common type of jaw fracture sustained by young horses. PMID:26261717

  1. Surgical treatment and a unique management of rostral mandibular fracture with cerclage wire in a horse

    PubMed Central

    Naddaf, Hadi; Sabiza, Soroush; Kavosi, Narges

    2015-01-01

    A 3-year-old Arabian colt was presented for a major gingiva wound at the right rostral part of mandible. After clinical assessments, rostral mandibular fracture was determined. Stabilization of fractured region was achieved via cerclage wire application under general anesthesia. Fixation wires were left in place for 6 weeks. A 3 -month follow up revealed complete fracture healing. The purpose of this case report was to give clinical information about rostral mandibular fractures and treatment of these fractures and nutrition protocol in a horse, as this fracture is of the most common type of jaw fracture sustained by young horses. PMID:26261717

  2. 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

  3. 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

  4. Healing Racism: Education's Role.

    ERIC Educational Resources Information Center

    Rutstein, Nathan, Ed.; Morgan, Michael, Ed.

    The 16 essays in this collection address how to lessen the effects of racism through classroom education by emphasizing the oneness of humanity and the relatedness of all human beings. These selections offer advice about healing racism from the early grades through secondary education. The essays are: (1) "Racism as a Disease" (John Woodall); (2)…

  5. Phytochemicals in Wound Healing

    PubMed Central

    Thangapazham, Rajesh L.; Sharad, Shashwat; Maheshwari, Radha K.

    2016-01-01

    Significance: Traditional therapies, including the use of dietary components for wound healing and skin regeneration, are very common in Asian countries such as China and India. The increasing evidence of health-protective benefits of phytochemicals, components derived from plants is generating a lot of interest, warranting further scientific evaluation and mechanistic studies. Recent Advances: Phytochemicals are non-nutritive substances present in plants, and some of them have the potential to provide better tissue remodeling when applied on wounds and to also act as proangiogenic agents during wound healing. Critical Issues: In this review, we briefly discuss the current understanding, important molecular targets, and mechanism of action(s) of some of the phytochemicals such as curcumin, picroliv, and arnebin-1. We also broadly review the multiple pathways that these phytochemicals regulate to enhance wound repair and skin regeneration. Future Directions: Recent experimental data on the effects of phytochemicals on wound healing and skin regeneration establish the potential clinical utility of plant-based compounds. Additional research in order to better understand the exact mechanism and potential targets of phytochemicals in skin regeneration is needed. Human studies a2nd clinical trials are pivotal to fully understand the benefits of phytochemicals in wound healing and skin regeneration. PMID:27134766

  6. 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…

  7. Healing Magazine, 2002.

    ERIC Educational Resources Information Center

    DiBiase, Miriam H., Ed.

    2002-01-01

    This newly designed volume of "Healing Magazine" features practical, clinical information aimed at sharing current work in children's mental health. The first issue shares information on guiding children through times of trauma, particularly after the events of September 11th. Two articles provide information on debriefing after trauma and talking…

  8. 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 new…

  9. 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…

  10. Epithelial mechanobiology, skin wound healing, and the stem cell niche.

    PubMed

    Evans, Nicholas D; Oreffo, Richard O C; Healy, Eugene; Thurner, Philipp J; Man, Yu Hin

    2013-12-01

    Skin wound healing is a vital process that is important for re-establishing the epithelial barrier following disease or injury. Aberrant or delayed skin wound healing increases the risk of infection, causes patient morbidity, and may lead to the formation of scar tissue. One of the most important events in wound healing is coverage of the wound with a new epithelial layer. This occurs when keratinocytes at the wound periphery divide and migrate to re-populate the wound bed. Many approaches are under investigation to promote and expedite this process, including the topical application of growth factors and the addition of autologous and allogeneic tissue or cell grafts. The mechanical environment of the wound site is also of fundamental importance for the rate and quality of wound healing. It is known that mechanical stress can influence wound healing by affecting the behaviour of cells within the dermis, but it remains unclear how mechanical forces affect the healing epidermis. Tensile forces are known to affect the behaviour of cells within epithelia, however, and the material properties of extracellular matrices, such as substrate stiffness, have been shown to affect the morphology, proliferation, differentiation and migration of many different cell types. In this review we will introduce the structure of the skin and the process of wound healing. We will then discuss the evidence for the effect of tissue mechanics in re-epithelialisation and, in particular, on stem cell behaviour in the wound microenvironment and in intact skin. We will discuss how the elasticity, mechanical heterogeneity and topography of the wound extracellular matrix impact the rate and quality of wound healing, and how we may exploit this knowledge to expedite wound healing and mitigate scarring. PMID:23746929

  11. Epithelial mechanobiology, skin wound healing, and the stem cell niche.

    PubMed

    Evans, Nicholas D; Oreffo, Richard O C; Healy, Eugene; Thurner, Philipp J; Man, Yu Hin

    2013-12-01

    Skin wound healing is a vital process that is important for re-establishing the epithelial barrier following disease or injury. Aberrant or delayed skin wound healing increases the risk of infection, causes patient morbidity, and may lead to the formation of scar tissue. One of the most important events in wound healing is coverage of the wound with a new epithelial layer. This occurs when keratinocytes at the wound periphery divide and migrate to re-populate the wound bed. Many approaches are under investigation to promote and expedite this process, including the topical application of growth factors and the addition of autologous and allogeneic tissue or cell grafts. The mechanical environment of the wound site is also of fundamental importance for the rate and quality of wound healing. It is known that mechanical stress can influence wound healing by affecting the behaviour of cells within the dermis, but it remains unclear how mechanical forces affect the healing epidermis. Tensile forces are known to affect the behaviour of cells within epithelia, however, and the material properties of extracellular matrices, such as substrate stiffness, have been shown to affect the morphology, proliferation, differentiation and migration of many different cell types. In this review we will introduce the structure of the skin and the process of wound healing. We will then discuss the evidence for the effect of tissue mechanics in re-epithelialisation and, in particular, on stem cell behaviour in the wound microenvironment and in intact skin. We will discuss how the elasticity, mechanical heterogeneity and topography of the wound extracellular matrix impact the rate and quality of wound healing, and how we may exploit this knowledge to expedite wound healing and mitigate scarring.

  12. [Distal humerus fractures in children].

    PubMed

    Schneidmueller, D; Boettger, M; Laurer, H; Gutsfeld, P; Bühren, V

    2013-11-01

    Fractures of the distal humerus belong to the most common injuries of the upper arm in childhood. Most frequently occurring is the supracondylar fracture of the distal humerus. In these cases and in the second most common epicondylar fractures, the metaphysis is affected and these fractures are therefore extra-articular. They have to be distinguished from articular fractures regarding therapy and prognosis. The growth potential of the distal epiphysis is very limited as is the possibility of spontaneous correction so that major dislocations should not be left uncorrected. Unstable and especially dislocated articular fractures must be anatomically reconstructed employing various osteosynthetic techniques, mostly combined with immobilization. Insufficient reconstruction, growth disturbance and non-union can result in axial deformities, such as cubitus valgus and varus, restriction of motion, pain and nerve palsy.

  13. Effects of genistein on early-stage cutaneous wound healing

    SciTech Connect

    Park, Eunkyo; Lee, Seung Min; Jung, In-Kyung; Lim, Yunsook; Kim, Jung-Hyun

    2011-07-08

    Highlights: {yields} We examine the effect of genistein on cutaneous wound healing. {yields} Genistein enhanced wound closure during the early stage of wound healing. {yields} These genistein effects on wound closure were induced by reduction of oxidative stress through increasing antioxidant capacity and modulation of pro-inflammatory cytokine expression. -- Abstract: Wound healing occurs in three sequential phases: hemostasis and inflammation, proliferation, and remodeling. Inflammation, the earliest phase, is considered a critical period for wound healing because immune cells remove damaged tissues, foreign debris, and remaining dead tissue. Wound healing would be delayed without inflammation, and this phase is affected by antioxidation capacity. Therefore, we hypothesized that genistein, which has an antioxidant effect, might modulate the wound healing process by altering the inflammatory response. After three days of acclimation, mice were divided into three groups: control, 0.025% genistein, and 0.1% genistein. After two weeks of an experimental diet, skin wounds were induced. Wounded skin areas were imaged, and the healing rate calculated. To measure lipid peroxidation, antioxidant enzyme expression and activity, and pro-inflammatory cytokine expression, skin and liver tissues were harvested at 12, 24, 48, and 72 h. Genistein did not affect body weight. The rate of wound closure in mice fed genistein was significantly faster than in the control group during the early stage of wound healing, especially in first three days. Cu, Zn-SOD and Mn-SOD expression in wound skin tissue in the 0.1% genistein group was lower than in the control group. However, CAT expression did not differ among groups. We also found that genist