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Sample records for accelerated fracture healing

  1. Bone morphogenetic protein-7 accelerates fracture healing in osteoporotic rats

    PubMed Central

    Diwan, Ashish D; Leong, Anthony; Appleyard, Richard; Bhargav, Divya; Fang, Zhi Ming; Wei, Aiqun

    2013-01-01

    Background: Osteoporosis is characterized by low bone mass, bone fragility and increased susceptibility to fracture. Fracture healing in osteoporosis is delayed and rates of implant failure are high with few biological treatment options available. This study aimed to determine whether a single dose of bone morphogenetic protein-7 (BMP-7) in a collagen/carboxy-methyl cellulose (CMC) composite enhanced fracture healing in an osteoporotic rat model. Materials and Methods: An open femoral midshaft osteotomy was performed in female rats 3 months post-ovarectomy. Rats were randomized to receive either BMP-7 composite (n = 30) or composite alone (n = 30) at the fracture site during surgery. Thereafter calluses were collected on days 12, 20 and 31. Callus cross-sectional area, bone mineral density, biomechanical stiffness and maximum torque, radiographic bony union and histological callus maturity were evaluated at each time point. Results: There were statistically significant increases in bone mineral density and callus cross-section area at all time points in the BMP-7 group as compared to controls and biomechanical readings showed stronger bones at day 31 in the BMP-7 group. Histological and radiographic evaluation indicated significant acceleration of bony union in the BMP-7 group as compared to controls. Conclusion: This study demonstrated that BMP-7 accelerates fracture healing in an oestrogen-deficient environment in a rat femoral fracture healing model to scientific relevance level I. The use of BMP-7 composite could offer orthopedic surgeons an advantage over oestrogen therapy, enhancing osteoporotic fracture healing with a single, locally applied dose at the time of surgery, potentially overcoming delays in healing caused by the osteoporotic state. PMID:24379457

  2. Local ZnCl2 accelerates fracture healing.

    PubMed

    Wey, Aaron; Cunningham, Catherine; Hreha, Jeremy; Breitbart, Eric; Cottrell, Jessica; Ippolito, Joseph; Clark, Devin; Lin, Hsuan-Ni; Benevenia, Joseph; O'Connor, J Patrick; Lin, Sheldon S; Paglia, David N

    2014-06-01

    This study evaluated the effect of local zinc chloride (ZnCl2 ), an insulin mimetic agent, upon the early and late parameters of fracture healing in rats using a standard femur fracture model. Mechanical testing, radiographic scoring, histomorphometry, qualitative histological scoring, PCNA immunohistochemistry, and local growth factor analysis were performed. Fractures treated with local ZnCl2 possessed significantly increased mechanical properties compared to controls at 4 weeks post fracture. The radiographic scoring analysis showed increased cortical bridging at 4 weeks in the 1.0 (p=0.0015) and 3.0 (p<0.0001) mg/kg ZnCl2 treated groups. Histomorphometry of the fracture callus at day 7 showed 177% increase (p=0.036) in percent cartilage and 133% increase (p=0.002) in percent mineralized tissue with local ZnCl2 treatment compared to controls. Qualitative histological scoring showed a 2.1× higher value at day 7 in the ZnCl2 treated group compared to control (p = 0.004). Cell proliferation and growth factors, VEGF and IGF-I, within fracture calluses treated with local ZnCl2 were increased at day 7. The results suggest local administration of ZnCl2 increases cell proliferation, causing increased growth factor production which yields improved chondrogenesis and endochondral ossification. Ultimately, these events lead to accelerated fracture healing as early as 4 weeks post fracture. PMID:24574139

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

    PubMed

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

    2015-10-21

    Surface topography can affect cell adhesion, morphology, polarity, cytoskeleton organization, and osteogenesis. However, little is known about the effect of topography on the fracture healing in repairing nonunion and large bone defects. Microgrooved topography on the surface of bone implants may promote cell migration into the fracture gap to accelerate fracture healing. To prove this hypothesis, we used an in vitro fracture (wound) healing assay on the microgrooved polycaprolactone substrates to study the effect of microgroove widths and depths on the osteoblast-like cell (MG-63) migration and the subsequent healing. We found that the microgrooved substrates promoted MG-63 cells to migrate collectively into the wound gap, which serves as a fracture model, along the grooves and ridges as compared with the flat substrates. Moreover, the groove widths did not show obvious influence on the wound healing whereas the smaller groove depths tended to favor the collective cell migration and thus subsequent healing. The microgrooved substrates accelerated the wound healing by facilitating the collective cell migration into the wound gaps but not by promoting the cell proliferation. Furthermore, microgrooves were also found to promote the migration of human mesenchymal stem cells (hMSCs) to heal the fracture model. Though osteogenic differentiation of hMSCs was not improved on the microgrooved substrate, collagen I and minerals deposited by hMSCs were organized in a way similar to those in the extracellular matrix of natural bone. These findings suggest the necessity in using microgrooved implants in enhancing fracture healing in bone repair. PMID:26457873

  4. Accelerated fracture healing in transgenic mice overexpressing an anabolic isoform of fibroblast growth factor 2.

    PubMed

    Hurley, Marja M; Adams, Douglas J; Wang, Liping; Jiang, Xi; Burt, Patience Meo; Du, Erxia; Xiao, Liping

    2016-03-01

    The effect of targeted expression of an anabolic isoform of basic fibroblast growth factor (FGF2) in osteoblastic lineage on tibial fracture healing was assessed in mice. Closed fracture of the tibiae was performed in Col3.6-18 kDaFgf2-IRES-GFPsaph mice in which a 3.6 kb fragment of type I collagen promoter (Col3.6) drives the expression of only the 18 kD isoform of FGF2 (18 kDaFgf2/LMW) with green fluorescent protein-sapphire (GFPsaph) as well as Vector mice (Col3.6-IRES-GFPsaph, Vector) that did not harbor the FGF2 transgene. Radiographic, micro-CT, DEXA, and histologic analysis of fracture healing of tibiae harvested at 3, 10 and 20 days showed a smaller fracture callus but accelerated fracture healing in LMWTg compared with Vector mice. At post fracture day 3, FGF receptor 3 and Sox 9 mRNA were significantly increased in LMWTg compared with Vector. Accelerated fracture healing was associated with higher FGF receptor 1, platelet derived growth factors B, C, and D, type X collagen, vascular endothelial cell growth factor, matrix metalloproteinase 9, tartrate resistant acid phosphatase, cathepsin K, runt-related transcription factor-2, Osterix and Osteocalcin and lower Sox9, and type II collagen expression at 10 days post fracture. We postulate that overexpression of LMW FGF2 accelerated the fracture healing process due to its effects on factors that are important in chondrocyte and osteoblast differentiation and vascular invasion. PMID:26252425

  5. 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. PMID:23897412

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

    PubMed

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

    2015-10-01

    G-protein-coupled receptors (GPCRs) are key regulators of skeletal homeostasis and are likely important in fracture healing. Because GPCRs can activate multiple signaling pathways simultaneously, we used targeted disruption of G(i) -GPCR or activation of G(s) -GPCR pathways to test how each pathway functions in the skeleton. We previously demonstrated that blockade of G(i) signaling by pertussis toxin (PTX) transgene expression in maturing osteoblastic cells enhanced cortical and trabecular bone formation and prevented age-related bone loss in female mice. In addition, activation of G(s) signaling by expressing the G(s) -coupled engineered receptor Rs1 in maturing osteoblastic cells induced massive trabecular bone formation but cortical bone loss. Here, we test our hypothesis that the G(i) and G(s) pathways also have distinct functions in fracture repair. We applied closed, nonstabilized tibial fractures to mice in which endogenous G(i) signaling was inhibited by PTX, or to mice with activated G(s) signaling mediated by Rs1. Blockade of endogenous G(i) resulted in a smaller callus but increased bone formation in both young and old mice. PTX treatment decreased expression of Dkk1 and increased Lef1 mRNAs during fracture healing, suggesting a role for endogenous G(i) signaling in maintaining Dkk1 expression and suppressing Wnt signaling. In contrast, adult mice with activated Gs signaling showed a slight increase in the initial callus size with increased callus bone formation. These results show that G(i) blockade and G(s) activation of the same osteoblastic lineage cell can induce different biological responses during fracture healing. Our findings also show that manipulating the GPCR/cAMP signaling pathway by selective timing of G(s) and G(i) -GPCR activation may be important for optimizing fracture repair. PMID:25917236

  7. 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

  8. 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. PMID:27102547

  9. 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

  10. 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

  11. 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

  12. 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

  13. Fracture healing in osteoporotic bone.

    PubMed

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

    2016-06-01

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

  14. The Role of Oxygen during Fracture Healing

    PubMed Central

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

    2016-01-01

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

  15. 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

  16. Ultrasonic monitoring of bone fracture healing.

    PubMed

    Protopappas, Vasilios C; Vavva, Maria G; Fotiadis, Dimitrios I; Malizos, Konstantinos N

    2008-01-01

    Quantitative ultrasound has attracted significant interest in the evaluation of bone fracture healing. Animal and clinical studies have demonstrated that the propagation velocity across fractured bones can be used as an indicator of healing. Researchers have recently employed computational methods for modeling wave propagation in bones, aiming to gain insight into the underlying mechanisms of wave propagation and to further enhance the monitoring capabilities of ultrasound. In this paper, we review the relevant literature and present the current status of knowledge. PMID:18599412

  17. Local transplantation of osteogenic pre-differentiated autologous adipose-derived mesenchymal stem cells may accelerate non-union fracture healing with limited pro-metastatic potency.

    PubMed

    Han, Duanyang; Han, Na; Zhang, Peixun; Jiang, Baoguo

    2015-01-01

    Fracture non-union is a serious complication in orthopedic clinical practice. Mesenchymal stem cells are believed to play a vital role in fracture healing process. Among various origins of mesenchymal stem cell, adipose derived stem cells hold great promise especially in clinical milieu. However, the wide spread application of mesenchymal stem cell based therapy is impeded by the pro-metastasis nature of the mesenchymal stem cell itself. Based on the findings from previous studies, we hypothesize that local transplanted osteogenic pre-differentiatiated adipose stem cell may promote the non-union fracture healing. Moreover, the pre-differnetiation stem cells by down-regulating the expression of CCL5 and CCL2. This novel osteogenic pre-differnetiation technique may help clinical orthopedists to resolve the refractory non-union cases and shed new light on other stem cell based therapies to counteract to avoid the pro-metastasis nature of the mesenchymal stem cells. PMID:25785146

  18. 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.

  19. The effects of smoking on fracture healing.

    PubMed

    Sloan, A; Hussain, I; Maqsood, M; Eremin, O; El-Sheemy, M

    2010-04-01

    Tobacco smoking is the single most avoidable cause of premature death worldwide. In fracture healing, it has been found to be a contributory factor to delayed union, and smokers are significantly disadvantaged, as healing times are often prolonged. The orthopaedic surgeon is likely to be knowledgeable about the detrimental effects of smoking on healing bones, as the problem has been known for some time. Smoking adversely affects bone mineral density, lumbar disc degeneration, the incidences of hip fractures and the dynamics of bone and wound healing. Clinical trials and demographic studies have been more widespread than biochemical analyses, and have reported poor prognosis for fracture patients who smoke. Scientific research has elucidated some of the negative impacts of tobacco use and investigations involving several animal models in cellular and humoral analyses have shown damage caused by various toxicological processes. Cessation of the habit perioperatively, therefore, is routinely advised to improve outcomes for patients. The current review describes some of the consequences of tobacco smoking in fracture healing. PMID:20303894

  20. Role of Wnt signaling in fracture healing

    PubMed Central

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

    2014-01-01

    The Wnt signaling pathway is well known to play major roles in skeletal development and homeostasis. In certain aspects, fracture repair mimics the process of bone embryonic development. Thus, the importance of Wnt signaling in fracture healing has become more apparent in recent years. Here, we summarize recent research progress in the area, which may be conducive to the development of Wnt-based therapeutic strategies for bone repair. [BMB Reports 2014; 47(12): 666-672] PMID:25301020

  1. Fracture and healing cycles in glass

    NASA Astrophysics Data System (ADS)

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

    2014-05-01

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

  2. 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

  3. 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

  4. 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

  5. Immunohistochemical Localization of Key Arachidonic Acid Metabolism Enzymes during Fracture Healing in Mice

    PubMed Central

    Lin, Hsuan-Ni; O’Connor, J. Patrick

    2014-01-01

    This study investigated the localization of critical enzymes involved in arachidonic acid metabolism during the initial and regenerative phases of mouse femur fracture healing. Previous studies found that loss of cyclooxygenase-2 activity impairs fracture healing while loss of 5-lipoxygenase activity accelerates healing. These diametric results show that arachidonic acid metabolism has an essential function during fracture healing. To better understand the function of arachidonic acid metabolism during fracture healing, expression of cyclooxygenase-1 (COX-1), cyclooxygenase -2 (COX-2), 5-lipoxygenase (5-LO), and leukotriene A4 hydrolase (LTA4H) was localized by immunohistochemistry in time-staged fracture callus specimens. All four enzymes were detected in leukocytes present in the bone marrow and attending inflammatory response that accompanied the fracture. In the tissues surrounding the fracture site, the proportion of leukocytes expressing COX-1, COX-2, or LTA4H decreased while those expressing 5-LO remained high at 4 and 7 days after fracture. This may indicate an inflammation resolution function for 5-LO during fracture healing. Only COX-1 was consistently detected in fracture callus osteoblasts during the later stages of healing (day 14 after fracture). In contrast, callus chondrocytes expressed all four enzymes, though 5-LO appeared to be preferentially expressed in newly differentiated chondrocytes. Most interestingly, osteoclasts consistently and strongly expressed COX-2. In addition to bone surfaces and the growth plate, COX-2 expressing osteoclasts were localized at the chondro-osseous junction of the fracture callus. These observations suggest that arachidonic acid mediated signaling from callus chondrocytes or from callus osteoclasts at the chondro-osseous junction regulate fracture healing. PMID:24516658

  6. 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.

  7. Electrical stimulation to accelerate wound healing

    PubMed Central

    Thakral, Gaurav; LaFontaine, Javier; Najafi, Bijan; Talal, Talal K.; Kim, Paul; Lavery, Lawrence A.

    2013-01-01

    Background There are several applications of electrical stimulation described in medical literature to accelerate wound healing and improve cutaneous perfusion. This is a simple technique that could be incorporated as an adjunctive therapy in plastic surgery. The objective of this review was to evaluate the results of randomized clinical trials that use electrical stimulation for wound healing. Method We identified 21 randomized clinical trials that used electrical stimulation for wound healing. We did not include five studies with treatment groups with less than eight subjects. Results Electrical stimulation was associated with faster wound area reduction or a higher proportion of wounds that healed in 14 out of 16 wound randomized clinical trials. The type of electrical stimulation, waveform, and duration of therapy vary in the literature. Conclusion Electrical stimulation has been shown to accelerate wound healing and increase cutaneous perfusion in human studies. Electrical stimulation is an adjunctive therapy that is underutilized in plastic surgery and could improve flap and graft survival, accelerate postoperative recovery, and decrease necrosis following foot reconstruction. PMID:24049559

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

    PubMed Central

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

    2015-01-01

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

  9. Acceleration Of Wound Healing Ny Photodynamic Therapy

    SciTech Connect

    Hasan, Tayyaba; Hamblin, Michael R.; Trauner, Kenneth

    2000-08-22

    Disclosed is a method for accelerating wound healing in a mammal. The method includes identifying an unhealed wound site or partially-healed wound site in a mammal; administering a photosensitizer to the mammal; waiting for a time period wherein the photosensitizer reaches an effective tissue concentration at the wound site; and photoactivating the photosensitizer at the wound site. The dose of photodynamic therapy is selected to stimulate the production of one or more growth factor by cells at the wound site, without causing tissue destruction.

  10. Acceleration of cutaneous wound healing by brassinosteroids

    PubMed Central

    Esposito, Debora; Rathinasabapathy, Thirumurugan; Schmidt, Barbara; Shakarjian, Michael P.; Komarnytsky, Slavko; Raskin, Ilya

    2013-01-01

    Brassinosteroids are plant growth hormones involved in cell growth, division and differentiation. Their effects in animals are largely unknown, although recent studies showed the anabolic properties of brassinosteroids possibly mediated through the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Here we examined biological activity of homobrassinolide (HB) and its synthetic analogues on in vitro proliferation and migration assays in murine fibroblast and primary keratinocyte cell culture. HB stimulated fibroblast proliferation and migration, and weakly induced keratinocyte proliferation in vitro. The effects of topical HB administration on progression of wound closure were further tested in the mouse model of cutaneous wound healing. C57BL/6J mice were given a full thickness dermal wound, and the rate of wound closure was assessed daily for 10 d alongside adenosine receptor agonist CGS-21680 as a positive control. Topical application of brassinosteroid significantly reduced wound size and accelerated wound healing in treated animals. mRNA levels of TGF-β and ICAM-1 were significantly lower, while TNF-α was nearly suppressed in the wounds from treated mice. Our data suggest that topical brassinosteroids accelerate wound healing by positively modulating inflammatory and re-epithelialization phases of the wound-repair process, in partby enhancing Akt signaling in the skin at the edges of the wound and enhancing migration of fibroblasts in a wounded area. Targeting this signaling pathway with brassinosteroids may represent a promising approach to the therapy of delayed wound healing. PMID:23937635

  11. Pulsed electromagnetic field treatment enhances healing callus biomechanical properties in an animal model of osteoporotic fracture.

    PubMed

    Androjna, Caroline; Fort, Brian; Zborowski, Maciej; Midura, Ronald J

    2014-09-01

    Delayed bone healing has been noted in osteoporosis patients and in the ovariectomized (OVX) rat model of estrogen-depletion osteopenia. Pulsed electromagnetic field (PEMF) devices are clinically approved as an adjunct to cervical fusion surgery in patients at high risk for non-fusion and for the treatment of fracture non-unions. These bone growth stimulating devices also accelerate the healing of fresh fracture repair in skeletally mature normal rats but have not been tested for efficacy to accelerate and/or enhance the delayed bone repair process in OVX rats. The current study tested the hypothesis that daily PEMF treatments would improve the fracture healing response in skeletally mature OVX rats. By 6 weeks of healing, PEMF treatments resulted in improved hard callus elastic modulus across fibula fractures normalizing the healing process in OVX rats with respect to this mechanical property. Radiographic evidence showed an improved hard callus bridging across fibula fractures in OVX rats treated with PEMF as compared to sham treatments. These findings provide a scientific rationale for investigating whether PEMF might improve bone-healing responses in at-risk osteoporotic patients. PMID:24764277

  12. Chemokine expression is upregulated in chondrocytes in diabetic fracture healing.

    PubMed

    Alblowi, Jazia; Tian, Chen; Siqueira, Michelle F; Kayal, Rayyan A; McKenzie, Erin; Behl, Yugal; Gerstenfeld, Louis; Einhorn, Thomas A; Graves, Dana T

    2013-03-01

    Chemokines are thought to play an important role in several aspects of bone metabolism including the recruitment of leukocytes and the formation of osteoclasts. We investigated the impact of diabetes on chemokine expression in normal and diabetic fracture healing. Fracture of the femur was performed in streptozotocin-induced diabetic and matched normoglycemic control mice. Microarray analysis was carried out and chemokine mRNA levels in vivo were assessed. CCL4 were examined in fracture calluses by immunohistochemistry and the role of TNF in diabetes-enhanced expression was investigated by treatment of animals with the TNF-specific inhibitor, pegsunercept. In vitro studies were conducted with ATDC5 chondrocytes. Diabetes significantly upregulated mRNA levels of several chemokines in vivo including CCL4, CCL8, CCL6, CCL11, CCL20, CCL24, CXCL2, CXCL5 and chemokine receptors CCR5 and CXCR4. Chondrocytes were identified as a significant source of CCL4 and its expression in diabetic fractures was dependent on TNF (P<0.05). TNF-α significantly increased mRNA levels of several chemokines in vitro which were knocked down with FOXO1 siRNA (P<0.05). CCL4 expression at the mRNA and proteins levels was induced by FOXO1 over-expression and reduced by FOXO1 knockdown. The current studies point to the importance of TNF-α as a mechanism for diabetes enhanced chemokine expression by chondrocytes, which may contribute to the accelerated loss of cartilage observed in diabetic fracture healing. Moreover, in vitro results point to FOXO1 as a potentially important transcription factor in mediating this effect. PMID:23262028

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

    PubMed

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

    2016-06-01

    Growth factor delivered in combination with animal-derived collagen materials has been used to accelerate bone fracture healing in human patients. However, the introduction of bovine proteins into humans carries the risk of zoonotic and immunologic complications. Here, we developed a collagen-like polypeptide-based bone formation system consisting of poly(Pro-Hyp-Gly)10 , which mimics the triple helical conformation of collagen, and basic fibroblast growth factor (bFGF) fused to the polycystic kidney disease (PKD) domain and collagen-binding domain (CBD) of Clostridium histolyticum collagenase. Circular dichroism spectral analysis showed that when pepsin-soluble bovine type I collagen was treated at 50°C, a positive signal corresponding to the collagen triple helix at 220 nm was not detected. In contrast, poly(Pro-Hyp-Gly)10 retained the 220-nm positive peak, even when treated at 80°C. The combination of the collagen binding-bFGF fusion protein (bFGF-PKD-CBD) with poly(Pro-Hyp-Gly)10 induced greater bone formation compared to bFGF alone in mice bone fracture models. Taken together, these properties suggest that the bFGF-PKD-CBD/poly(Pro-Hyp-Gly)10 composite is a promising material for bone repair in the clinical setting. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1372-1378, 2016. PMID:26833780

  14. Are smokers a risk group for delayed healing of tibial shaft fractures?

    PubMed

    Kyrö, A; Usenius, J P; Aarnio, M; Kunnamo, I; Avikainen, V

    1993-01-01

    A total of 135 patients with a fresh tibial shaft fracture and with no other significant injuries underwent primary conservative treatment. Data on their smoking habits were obtained from hospital records and by questionnaire. Although the smokers had better prospects for healing of the fracture at the outset than non-smokers (lower mean age and less fractures caused by high-energy injuries), the smokers were found to have a significantly longer mean time to clinical union and a higher incidence of delayed union. According to a crude calculation, smokers had a 4.1-fold risk of tibial shaft fracture caused by low-energy injury, compared with non-smokers. An accelerated failure time model showed that the more comminuted or open the fracture, the higher the number of cigarettes smoked and the older the patient, the longer was the time to clinical union of the tibial shaft fracture. Female sex appeared to be a further risk factor for delayed healing. A logit model indicated that comminution of the fracture, smoking and female sex were associated with delayed union and non-union. If a patient has a markedly raised probability of delayed union of tibial shaft fracture because of many risk factors as reported in the previous literature or in this study, operative treatment should be considered as the primary alternative instead of conservative treatment. Stopping smoking during healing of tibial shaft fracture could also promote the union of the fracture. PMID:8122874

  15. Effect of Cervus and Cucumis Peptides on Osteoblast Activity and Fracture Healing in Osteoporotic Bone

    PubMed Central

    Wang, Ai-Yuan; Tian, Yue; Yuan, Mei; Zhang, Li; Chen, Ji-Feng; Xu, Wen-Jing; Meng, Hao-Ye; Yu, Xiao-Ming; Wang, Yao-Qin; Guo, Quan-Yi; Lu, Shi-Bi; Peng, Jiang; Wang, Yu

    2014-01-01

    Osteoporosis is associated with delayed and/or reduced fracture healing. As cervus and cucumis are the traditional Chinese treatments for rheumatoid arthritis, we investigated the effect of supplementation of these peptides (CCP) on bone fracture healing in ovariectomized (OVX) osteoporotic rats in vitro and in vivo. CCP enhanced osteoblast proliferation and increased alkaline phosphatase activity, matrix mineralization, and expression of runt-related transcription factor 2 (Runx2), bone morphogenetic protein 4 (BMP4), and osteopontin. In vivo, female Sprague-Dawley rats underwent ovariectomy and the right femora were fractured and fixed by intramedullary nailing 3 months later. Rats received intraperitoneal injections of either CCP (1.67 mg/kg) or physiological saline every day for 30 days. Fracture healing and callus formation were evaluated by radiography, micro-CT, biomechanical testing, and histology. At 12 weeks after fracture, calluses in CCP-treated bones showed significantly higher torsional strength and greater stiffness than control-treated bones. Bones in CCP-treated rats reunified and were thoroughly remodeled, while two saline-treated rats showed no bone union and incomplete remodeling. Taken together, these results indicate that use of CCP after fracture in osteoporotic rats accelerates mineralization and osteogenesis and improves fracture healing. PMID:25525453

  16. Lnk-dependent axis of SCF–cKit signal for osteogenesis in bone fracture healing

    PubMed Central

    Matsumoto, Tomoyuki; Ii, Masaaki; Nishimura, Hiromi; Shoji, Taro; Mifune, Yutaka; Kawamoto, Atsuhiko; Kuroda, Ryosuke; Fukui, Tomoaki; Kawakami, Yohei; Kuroda, Tomoya; Kwon, Sang Mo; Iwasaki, Hiroto; Horii, Miki; Yokoyama, Ayumi; Oyamada, Akira; Lee, Sang Yang; Hayashi, Shinya; Kurosaka, Masahiro; Takaki, Satoshi

    2010-01-01

    The therapeutic potential of hematopoietic stem cells/endothelial progenitor cells (HSCs/EPCs) for fracture healing has been demonstrated with evidence for enhanced vasculogenesis/angiogenesis and osteogenesis at the site of fracture. The adaptor protein Lnk has recently been identified as an essential inhibitor of stem cell factor (SCF)–cKit signaling during stem cell self-renewal, and Lnk-deficient mice demonstrate enhanced hematopoietic reconstitution. In this study, we investigated whether the loss of Lnk signaling enhances the regenerative response during fracture healing. Radiological and histological examination showed accelerated fracture healing and remodeling in Lnk-deficient mice compared with wild-type mice. Molecular, physiological, and morphological approaches showed that vasculogenesis/angiogenesis and osteogenesis were promoted in Lnk-deficient mice by the mobilization and recruitment of HSCs/EPCs via activation of the SCF–cKit signaling pathway in the perifracture zone, which established a favorable environment for bone healing and remodeling. In addition, osteoblasts (OBs) from Lnk-deficient mice had a greater potential for terminal differentiation in response to SCF–cKit signaling in vitro. These findings suggest that inhibition of Lnk may have therapeutic potential by promoting an environment conducive to vasculogenesis/angiogenesis and osteogenesis and by facilitating OB terminal differentiation, leading to enhanced fracture healing. PMID:20855498

  17. 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

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

    PubMed

    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

    2016-05-01

    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. Complications

  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. Local application of a proteasome inhibitor enhances fracture healing in rats.

    PubMed

    Yoshii, Toshitaka; Nyman, Jeffry S; Yuasa, Masato; Esparza, Javier M; Okawa, Atsushi; Gutierrez, Gloria E

    2015-08-01

    The ubiquitin/proteasome system plays an important role in regulating the activity of osteoblast precursor cells. Proteasome inhibitors (PSIs) have been shown to stimulate the differentiation of osteoblast precursor cells and to promote bone formation. This raises the possibility that PSIs might be useful for enhancing fracture healing. In this study, we examined the effect of the local administration of PSI on fracture repair in rats. The effects of treatment on the healing of a fractured femur were assessed based on radiographs, micro-computed tomography (μCT) analysis, biomechanical testing, and histological analysis. PSI enhanced osteogenic differentiation in bone marrow- and periosteum-derived mesenchymal progenitor cells in vitro. Moreover, the local administration of PSI in vivo promoted fracture healing in rats, as demonstrated by an increased fracture callus volume in radiographs at 2 weeks post-fracture, and improved radiographic scores. By week 4, PSI treatment had enhanced biomechanical strength and mineral density in the callus as assessed using bending tests, and μCT, respectively. Histological sections demonstrated that PSI treatment accelerated endochondral ossification during the early stages of fracture repair. Although further investigations are necessary to assess its clinical use, the local administration of PSIs might be a novel, and effective therapeutic approach for fracture repair. PMID:25683968

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

    PubMed

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

    2016-07-01

    The literature is deficient with regard to how the localized mechanical environment of skeletal tissue is altered during reduced gravitational loading and how these alterations affect fracture healing. Thus, a finite element model of the ovine hindlimb was created to characterize the local mechanical environment responsible for the inhibited fracture healing observed under experimental simulated hypogravity conditions. Following convergence and verification studies, hydrostatic pressure and strain within a diaphyseal fracture of the metatarsus were evaluated for models under both 1 and 0.25 g loading environments and compared to results of a related in vivo study. Results of the study suggest that reductions in hydrostatic pressure and strain of the healing fracture for animals exposed to reduced gravitational loading conditions contributed to an inhibited healing process, with animals exposed to the simulated hypogravity environment subsequently initiating an intramembranous bone formation process rather than the typical endochondral ossification healing process experienced by animals healing in a 1 g gravitational environment. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1206-1215, 2016. PMID:26704186

  2. 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.

  3. The crucial role of neutrophil granulocytes in bone fracture healing.

    PubMed

    Kovtun, A; Bergdolt, S; Wiegner, R; Radermacher, P; Huber-Lang, M; Ignatius, A

    2016-01-01

    Delayed bone fracture healing and the formation of non-unions represent an important clinical problem, particularly in polytrauma patients who suffer from posttraumatic systemic inflammation. However, the underlying pathomechanisms remain unclear. Neutrophil granulocytes are crucial effector cells in the systemic immune response and represent the most abundant immune cell population in the early fracture haematoma. Here we investigated the role of neutrophils in a mouse model of uncomplicated fracture healing and compromised fracture healing induced by an additional thoracic trauma. Twenty four hours before injury, 50 % of the mice were systemically treated with an anti-Ly-6G-antibody to reduce neutrophil numbers. In the isolated fracture model, Ly-6G-Ab treatment significantly increased the concentration of both pro- and anti-inflammatory cytokines, including interleukin (IL)-6 and IL-10, and chemokines, for example, C-X-C motif ligand 1 (CXCL1) and monocyte chemotactic protein-1 (MCP-1), in the fracture haematoma. Monocyte/macrophage recruitment was also significantly enhanced. After 21 d, bone regeneration was considerably impaired as demonstrated by significantly diminished bone content and impaired mechanical properties of the fracture callus. These results indicate that undisturbed neutrophil recruitment and function in the inflammatory phase after fracture is crucial to initiate downstream responses leading to bone regeneration. In the combined trauma model, the reduction of neutrophil numbers ameliorated pulmonary inflammation but did not provoke any significant effect on bone regeneration, suggesting that neutrophils may not play a crucial pathomechanistic role in compromised fracture healing induced by an additional thoracic trauma. PMID:27452963

  4. 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

  5. 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

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

    PubMed Central

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

    2015-01-01

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

  7. 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.

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

    PubMed

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

    2015-01-01

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

  9. 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

  10. 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

  11. 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

  12. Biglycan modulates angiogenesis and bone formation during fracture healing

    PubMed Central

    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.

    2014-01-01

    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

  13. 4. The Low-Intensity Pulsed Ultrasound (LIPUS) Mechanism and the Effect of Teriparatide on Fracture Healing.

    PubMed

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

    2016-08-01

    fracture models teriparatide subcutaneously 5 μg/kg three times a week from the first day after the fracture. Bone unions of the treated models were observed earlier than those of non-treated models in simple radiographs as well. In micro CT analysis, it was demonstrated that lamellar bone transforming and bone remodeling of the trabecular structure of external callus were especially accelerated. The results of these trials showed that both LIPUS and teriparatide demonstrated the effect of promoting fracture healing, and each had unique characteristics. PMID:27441765

  14. Improved Fracture Healing in Patients with Concomitant Traumatic Brain Injury: Proven or Not?

    PubMed Central

    Koopmans, Guido; Kobbe, Philipp; Poeze, Martijn; Andruszkow, Hagen; Brink, Peter R. G.; Pape, Hans-Christoph

    2015-01-01

    Over the last 3 decades, scientific evidence advocates an association between traumatic brain injury (TBI) and accelerated fracture healing. Multiple clinical and preclinical studies have shown an enhanced callus formation and an increased callus volume in patients, respectively, rats with concomitant TBI. Over time, different substances (cytokines, hormones, etc.) were in focus to elucidate the relationship between TBI and fracture healing. Until now, the mechanism behind this relationship is not fully clarified and a consensus on which substance plays the key role could not be attained in the literature. In this review, we will give an overview of current concepts and opinions on this topic published in the last decade and both clinical and pathophysiological theories will be discussed. PMID:25873754

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

    NASA Astrophysics Data System (ADS)

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

    2010-03-01

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

  16. 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

  17. Demystifying the status of fracture healing using tomosynthesis: A case report

    PubMed Central

    Roth, Eira S.; Ha, Alice S.; Chew, Felix S.

    2015-01-01

    Radiography is the most common imaging method for assessing the progress of fracture healing. However, accurate assessment may be confounded by fracture complexity in which a combination of anatomic overlay and hypertrophic callous can be visually misleading. We present just such an instance in which delayed fracture healing was further elucidated using tomosynthesis. PMID:26649112

  18. An Evaluation of the Effect of Therapeutic Ultrasound on Healing of Mandibular Fracture.

    PubMed

    Patel, Kiran; Kumar, Sanjeev; Kathiriya, Nishtha; Madan, Sonal; Shah, Ankit; Venkataraghavan, Karthik; Jani, Mehul

    2015-12-01

    subsequent weeks. No significant difference was found in clinical mobility between fracture fragments at 3-week interval. The present study provides a basis for application of therapeutic controlled ultrasound as an effective treatment modality to accelerate healing of fresh, minimally displaced mandibular fracture. PMID:26576234

  19. 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

  20. 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

  1. 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.

  2. Periodontal healing after bonding treatment of vertical root fracture.

    PubMed

    Sugaya, T; Kawanami, M; Noguchi, H; Kato, H; Masaka, N

    2001-08-01

    Vertical root fractures lead to advanced periodontal breakdown with deep periodontal pockets and vertical bone defects. The purpose of this study is to evaluate clinically the periodontal healing of root fracture treatment using adhesive resin cement. In 22 patients, 23 teeth with vertical root fractures were treated with 4-META/MMA-TBB resin cement. Eleven fractured roots were bonded through the root canal (group A) and 12 fractured roots were bonded extra-orally and replanted (group B). All teeth were then restored with full cast crowns (n=20) or coping (n=3). Mean probing depth was 6.6 mm at pre-treatment and 4.4 mm 6 months after the treatment in group A, and 7.4 mm and 4.6 mm, respectively, in group B. Bleeding scores were 100% at pre-treatment and 36.4% after 6 months in group A and 91.7% and 8.3%, respectively in group B. Radiographic bone level was 56.8% at pretreatment and 59.1% after 6 months in group A, and 18.8% and 29.2%, respectively, in group B. Two roots of group A and three roots of group B were extracted due to refracture, deterioration of periodontal inflammation, mobility, and luxation. The remaining roots (n=18) presented no discomfort to the patients and there was no deterioration of periodontal conditions over a mean period of 33 months (range 14-74 months) in group A and over a mean period of 22 months (range 6-48 months) in group B. There was no ankylosed teeth nor was any root resorption detected. The results suggested that the treatment of vertical root fracture using 4-META/MMA-TBB resin has good prognostic possibilities. PMID:11585144

  3. The Effectiveness of Human Parathyroid Hormone and Low-Intensity Pulsed Ultrasound on the Fracture Healing in Osteoporotic Bones.

    PubMed

    Mansjur, Karima Q; Kuroda, Shingo; Izawa, Takashi; Maeda, Yuichi; Sato, Minami; Watanabe, Keiichiro; Horiuchi, Shinya; Tanaka, Eiji

    2016-08-01

    Osteoporotic fracture has become a major public health problem, and until today, the treatments available are not satisfactory. While there is growing evidence to support the individual treatment of parathyroid hormone (PTH) administration and low-intensity pulsed ultrasound (LIPUS) exposure as respectively systemic and local therapies during osteoporotic fracture healing, their effects have not yet been investigated when introduced concurrently. This study aimed to evaluate the effects of combined treatment with PTH (1-34) and LIPUS on fracture healing in ovariectomized (OVX) rats. Thirty-two, 12-week-old female Sprague-Dawley rats were OVX to induce osteoporosis. After 12 weeks, the rats underwent surgery to create bilateral mid-diaphyseal fractures of proximal tibiae. All animals were randomly divided into 4 groups (n = 8 for each): control group as placebo, PTH group, LIPUS group, and combined group. PTH group had PTH administration at a dose of 30 μg/kg/day for 3 days/week for 6 weeks. LIPUS group received ultrasound 5 days/week for 20 min/day for 6 weeks and combined group had both PTH administration and LIPUS exposure for 6 weeks. Fracture healing was observed weekly by anteroposterior radiography and micro-CT. Five weeks after the fracture, the tibia were harvested to permit histological assessments and at week 6, for mechanical property of the fracture callus. Micro-CT showed that the PTH and combined groups exhibited significantly higher BMD and trabecular bone integrity than control group at weeks 4-6. Radiography, fracture healing score and mean callus area indicated that the combined group revealed better healing processes than the individual groups. Mechanically, bending moment to failure was significantly higher in LIPUS, PTH and combined groups than in control group. These data suggest that the combined treatment of PTH and LIPUS have been shown to accelerate fracture bone healing and enhance bone properties rather than single agent

  4. Immobilized thrombin receptor agonist peptide accelerates wound healing in mice.

    PubMed

    Strukova, S M; Dugina, T N; Chistov, I V; Lange, M; Markvicheva, E A; Kuptsova, S; Zubov, V P; Glusa, E

    2001-10-01

    To accelerate the healing processes in wound repair, attempts have been repeatedly made to use growth factors including thrombin and its peptide fragments. Unfortunately, the employment of thrombin is limited because of its high liability and pro-inflammatory actions at high concentrations. Some cellular effects of thrombin in wound healing are mediated by the activation of protease activated receptor-1 (PAR-1). The thrombin receptor agonist peptide (TRAP:SFLLRN) activates this receptor and mimics the effects of thrombin, but TRAP is a relatively weak agonist. We speculated that the encapsulated peptide may be more effective for PAR-1 activation than nonimmobilized peptide and developed a novel method for TRAP encapsulation in hydrogel films based on natural and synthetic polymers. The effects of an encapsulated TRAP in composite poly(N-vinyl caprolactam)-calcium alginate (PVCL) hydrogel films were investigated in a mouse model of wound healing. On day 7 the wound sizes decreased by about 60% under TRAP-chitosan-containing PVCL films, as compared with control films without TRAP. In the case of TRAP-polylysine-containing films no significant decrease in wound sizes was found. The fibroblast/macrophage ratio increased under TRAP-containing films on day 3 and on day 7. The number of proliferating fibroblasts increased to 150% under TRAP-chitosan films on day 7 as compared with control films. The number of [3H]-thymidine labeled endothelial and epithelial cells in granulation tissues was also enhanced. Thus, the immobilized TRAP to PVCL-chitosan hydrogel films were found to promote wound healing following the stimulation of fibroblast and epithelial cell proliferation and neovascularization. Furthermore, TRAP was shown to inhibit the secretion of the inflammatory mediator PAF from stimulated rat peritoneal mast cells due to augmentation of NO release from the mast cells. The encapsulated TRAP is suggested to accelerate wound healing due to the anti-inflammatory effects

  5. Trabecular bone fracture healing simulation with finite element analysis and fuzzy logic.

    PubMed

    Shefelbine, Sandra J; Augat, Peter; Claes, Lutz; Simon, Ulrich

    2005-12-01

    Trabecular bone fractures heal through intramembraneous ossification. This process differs from diaphyseal fracture healing in that the trabecular marrow provides a rich vascular supply to the healing bone, there is very little callus formation, woven bone forms directly without a cartilage intermediary, and the woven bone is remodelled to form trabecular bone. Previous studies have used numerical methods to simulate diaphyseal fracture healing or bone remodelling, however not trabecular fracture healing, which involves both tissue differentiation and trabecular formation. The objective of this study was to determine if intramembraneous bone formation and remodelling during trabecular bone fracture healing could be simulated using the same mechanobiological principles as those proposed for diaphyseal fracture healing. Using finite element analysis and the fuzzy logic for diaphyseal healing, the model simulated formation of woven bone in the fracture gap and subsequent remodelling of the bone to form trabecular bone. We also demonstrated that the trabecular structure is dependent on the applied loading conditions. A single model that can simulate bone healing and remodelling may prove to be a useful tool in predicting musculoskeletal tissue differentiation in different vascular and mechanical environments. PMID:16214492

  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. PMID:25959413

  8. TP508 accelerates fracture repair by promoting cell growth over cell death

    SciTech Connect

    Li Xinmin; Wang Hali; Touma, Edward; Qi Yuchen; Rousseau, Emma; Quigg, Richard J.; Ryaby, James T.

    2007-12-07

    TP508 is a synthetic 23-amino acid peptide representing a receptor-binding domain of human thrombin. We have previously shown that a single injection of TP508 accelerates fracture healing in a rat femoral fracture model. To understand how TP508 acts at the protein level during fracture healing, we compared the translational profiles between saline-control and fractured femur at six time points after TP508 treatment using the second generation of BD Clontech{sup TM} Antibody Microarray. Here, we demonstrate that TP508 accelerates fracture healing by modulating expression levels of proteins primarily involved in the functional categories of cell cycle, cellular growth and proliferation, and cell death. The majority of those proteins are physically interrelated and functionally overlapped. The action of those proteins is highlighted by a central theme of promoting cell growth via balance of cell survival over cell death signals. This appears to occur through the stimulation of several bone healing pathways including cell cycle-G1/S checkpoint regulation, apoptosis, JAK/STAT, NF-{kappa}B, PDGF, PI3K/AKT, PTEN, and ERK/MAPK.

  9. Substance P enhances EPC mobilization for accelerated wound healing.

    PubMed

    Um, Jihyun; Jung, Nunggum; Chin, Sukbum; Cho, Younggil; Choi, Sanghyuk; Park, Ki-Sook

    2016-03-01

    Wound healing is essential for the survival and tissue homeostasis of unicellular and multicellular organisms. The current study demonstrated that the neuropeptide substance P (SP) accelerated the wound healing process, particularly in the skin. Subcutaneous treatment of SP accelerated wound closing, increased the population of α-smooth muscle actin positive myofibroblasts, and increased extracellular matrix deposition at the wound site. Moreover, SP treatment enhances angiogenesis without a local increase in the expression levels of vascular endothelial growth factor and stromal cell-derived factor-1. Importantly, SP treatment increased both the population of circulating endothelial progenitor cells in the peripheral blood and in CD31 positive cells in Matrigel plugs. The tube forming potential of endothelial cells was also enhanced by SP treatment. The results suggested that the subcutaneous injection of SP accelerated the wound healing in the skin via better reconstitution of blood vessels, which possibly followed an increase in the systemic mobilization of endothelial progenitor cells and a more effective assembly of endothelial cells into tubes. PMID:26749197

  10. HoxD3 accelerates wound healing in diabetic mice

    SciTech Connect

    Hansen, Scott L.; Myers, Connie A.; Charboneau, Aubri; Young, David M.; and Boudreau, Nancy

    2003-12-01

    Poorly healing diabetic wounds are characterized by diminished collagen production and impaired angiogenesis. HoxD3, a homeobox transcription factor that promotes angiogenesis and collagen synthesis, is up-regulated during normal wound repair whereas its expression is diminished in poorly healing wounds of the genetically diabetic (db/db) mouse. To determine whether restoring expression of HoxD3 would accelerate diabetic wound healing, we devised a novel method of gene transfer, which incorporates HoxD3 plasmid DNA into a methylcellulose film that is placed on wounds created on db/db mice. The HoxD3 transgene was expressed in endothelial cells, fibroblasts, and keratinocytes of the wounds for up to 10 days. More importantly, a single application of HoxD3 to db/db mice resulted in a statistically significant acceleration of wound closure compared to control-treated wounds. Furthermore, we also observed that the HoxD3-mediated improvement in diabetic wound repair was accompanied by increases in mRNA expression of the HoxD3 target genes, Col1A1 and beta 3-integrin leading to enhanced angiogenesis and collagen deposition in the wounds. Although HoxD3-treated wounds also show improved re-epithelialization as compared to control db/db wounds, this effect was not due to direct stimulation of keratinocyte migration by HoxD3. Finally, we show that despite the dramatic increase in collagen synthesis and deposition in HoxD3-treated wounds, these wounds showed normal remodeling and we found no evidence of abnormal wound healing. These results indicate that HoxD3 may provide a means to directly improve collagen deposition, angiogenesis and closure in poorly healing diabetic wounds.

  11. 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

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

    PubMed

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

    2016-01-01

    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

  13. 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

  14. Transcriptional Analysis of Fracture Healing and the Induction of Embryonic Stem Cell–Related Genes

    PubMed Central

    Bais, Manish; McLean, Jody; Sebastiani, Paola; Young, Megan; Wigner, Nathan; Smith, Temple; Kotton, Darrell N.; Einhorn, Thomas A.; Gerstenfeld, Louis C.

    2009-01-01

    Fractures are among the most common human traumas. Fracture healing represents a unique temporarily definable post-natal process in which to study the complex interactions of multiple molecular events that regulate endochondral skeletal tissue formation. Because of the regenerative nature of fracture healing, it is hypothesized that large numbers of post-natal stem cells are recruited and contribute to formation of the multiple cell lineages that contribute to this process. Bayesian modeling was used to generate the temporal profiles of the transcriptome during fracture healing. The temporal relationships between ontologies that are associated with various biologic, metabolic, and regulatory pathways were identified and related to developmental processes associated with skeletogenesis, vasculogenesis, and neurogenesis. The complement of all the expressed BMPs, Wnts, FGFs, and their receptors were related to the subsets of transcription factors that were concurrently expressed during fracture healing. We further defined during fracture healing the temporal patterns of expression for 174 of the 193 genes known to be associated with human genetic skeletal disorders. In order to identify the common regulatory features that might be present in stem cells that are recruited during fracture healing to other types of stem cells, we queried the transcriptome of fracture healing against that seen in embryonic stem cells (ESCs) and mesenchymal stem cells (MSCs). Approximately 300 known genes that are preferentially expressed in ESCs and ∼350 of the known genes that are preferentially expressed in MSCs showed induction during fracture healing. Nanog, one of the central epigenetic regulators associated with ESC stem cell maintenance, was shown to be associated in multiple forms or bone repair as well as MSC differentiation. In summary, these data present the first temporal analysis of the transcriptome of an endochondral bone formation process that takes place during fracture

  15. 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.

  16. Disadvantages of interfragmentary shear on fracture healing--mechanical insights through numerical simulation.

    PubMed

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

    2014-07-01

    The outcome of secondary fracture healing processes is strongly influenced by interfragmentary motion. Shear movement is assumed to be more disadvantageous than axial movement, however, experimental results are contradictory. Numerical fracture healing models allow simulation of the fracture healing process with variation of single input parameters and under comparable, normalized mechanical conditions. Thus, a comparison of the influence of different loading directions on the healing process is possible. In this study we simulated fracture healing under several axial compressive, and translational and torsional shear movement scenarios, and compared their respective healing times. Therefore, we used a calibrated numerical model for fracture healing in sheep. Numerous variations of movement amplitudes and musculoskeletal loads were simulated for the three loading directions. Our results show that isolated axial compression was more beneficial for the fracture healing success than both isolated shearing conditions for load and displacement magnitudes which were identical as well as physiological different, and even for strain-based normalized comparable conditions. Additionally, torsional shear movements had less impeding effects than translational shear movements. Therefore, our findings suggest that osteosynthesis implants can be optimized, in particular, to limit translational interfragmentary shear under musculoskeletal loading. PMID:24648331

  17. 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.

  18. 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.

  19. 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

  20. Hyaluronidase Modulates Inflammatory Response and Accelerates the Cutaneous Wound Healing

    PubMed Central

    Fronza, Marcio; Caetano, Guilherme F.; Leite, Marcel N.; Bitencourt, Claudia S.; Paula-Silva, Francisco W. G.; Andrade, Thiago A. M.; Frade, Marco A. C.; Merfort, Irmgard; Faccioli, Lúcia H.

    2014-01-01

    Hyaluronidases are enzymes that degrade hyaluronan an important constituent of the extracellular matrix. They have been used as a spreading agent, improving the absorption of drugs and facilitating the subcutaneous infusion of fluids. Here, we investigated the influence of bovine testes hyaluronidase (HYAL) during cutaneous wound healing in in vitro and in vivo assays. We demonstrated in the wound scratch assay that HYAL increased the migration and proliferation of fibroblasts in vitro at low concentration, e.g. 0.1 U HYAL enhanced the cell number by 20%. HYAL presented faster and higher reepithelialization in in vivo full-thickness excisional wounds generated on adult Wistar rats back skin already in the early phase at 2nd day post operatory compared to vehicle-control group. Wound closured area observed in the 16 U and 32 U HYAL treated rats reached 38% and 46% compared to 19% in the controls, respectively. Histological and biochemical analyses supported the clinical observations and showed that HYAL treated wounds exhibited increased granulation tissue, diminished edema formation and regulated the inflammatory response by modulating the release of pro and anti-inflammatory cytokines, growth factor and eicosanoids mediators. Moreover, HYAL increased gene expression of peroxisome proliferator-activated receptors (PPAR) γ and PPAR β/δ, the collagen content in the early stages of healing processes as well as angiogenesis. Altogether these data revealed that HYAL accelerates wound healing processes and might be beneficial for treating wound disorders. PMID:25393024

  1. Hyaluronidase modulates inflammatory response and accelerates the cutaneous wound healing.

    PubMed

    Fronza, Marcio; Caetano, Guilherme F; Leite, Marcel N; Bitencourt, Claudia S; Paula-Silva, Francisco W G; Andrade, Thiago A M; Frade, Marco A C; Merfort, Irmgard; Faccioli, Lúcia H

    2014-01-01

    Hyaluronidases are enzymes that degrade hyaluronan an important constituent of the extracellular matrix. They have been used as a spreading agent, improving the absorption of drugs and facilitating the subcutaneous infusion of fluids. Here, we investigated the influence of bovine testes hyaluronidase (HYAL) during cutaneous wound healing in in vitro and in vivo assays. We demonstrated in the wound scratch assay that HYAL increased the migration and proliferation of fibroblasts in vitro at low concentration, e.g. 0.1 U HYAL enhanced the cell number by 20%. HYAL presented faster and higher reepithelialization in in vivo full-thickness excisional wounds generated on adult Wistar rats back skin already in the early phase at 2nd day post operatory compared to vehicle-control group. Wound closured area observed in the 16 U and 32 U HYAL treated rats reached 38% and 46% compared to 19% in the controls, respectively. Histological and biochemical analyses supported the clinical observations and showed that HYAL treated wounds exhibited increased granulation tissue, diminished edema formation and regulated the inflammatory response by modulating the release of pro and anti-inflammatory cytokines, growth factor and eicosanoids mediators. Moreover, HYAL increased gene expression of peroxisome proliferator-activated receptors (PPAR) γ and PPAR β/δ, the collagen content in the early stages of healing processes as well as angiogenesis. Altogether these data revealed that HYAL accelerates wound healing processes and might be beneficial for treating wound disorders. PMID:25393024

  2. Topical 5-azacytidine accelerates skin wound healing in rats.

    PubMed

    Gomes, Fabiana S; de-Souza, Gabriela F; Nascimento, Lucas F; Arantes, Eva L; Pedro, Rafael M; Vitorino, Daniele C; Nunez, Carla E; Melo Lima, Maria H; Velloso, Lício A; Araújo, Eliana P

    2014-01-01

    The development of new methods to improve skin wound healing may affect the outcomes of a number of medical conditions. Here, we evaluate the molecular and clinical effects of topical 5-azacytidine on wound healing in rats. 5-Azacytidine decreases the expression of follistatin-1, which negatively regulates activins. Activins, in turn, promote cell growth in different tissues, including the skin. Eight-week-old male Wistar rats were submitted to 8.0-mm punch-wounding in the dorsal region. After 3 days, rats were randomly assigned to receive either a control treatment or the topical application of a solution containing 5-azacytidine (10 mM) once per day. Photo documentation and sample collection were performed on days 5, 9, and 15. Overall, 5-azacytidine promoted a significant acceleration of complete wound healing (99.7% ± 0.7.0 vs. 71.2% ± 2.8 on day 15; n = 10; p < 0.01), accompanied by up to threefold reduction in follistatin expression. Histological examination of the skin revealed efficient reepithelization and cell proliferation, as evaluated by the BrdU incorporation method. 5-Azacytidine treatment also resulted in increased gene expression of transforming growth factor-beta and the keratinocyte markers involucrin and cytokeratin, as well as decreased expression of cytokines such as tumor necrosis factor-alpha and interleukin-10. Lastly, when recombinant follistatin was applied to the skin in parallel with topical 5-azacytidine, most of the beneficial effects of the drug were lost. Thus, 5-azacytidine acts, at least in part through the follistatin/activin pathway, to improve skin wound healing in rodents. PMID:25039304

  3. Study on the changes of metal elemental contents in whole blood and bone during fracture healing

    NASA Astrophysics Data System (ADS)

    Yin, Sha; Guodong, Liu; Wenzheng, Lan; Pingsheng, Liu; Peiqun, Zhang; Han, Lin; Xiaoheng, Wen

    1996-04-01

    The radii of 72 rabbits were fractured by operation and the contents of elements P, S, K, Ca, Fe, Ni, Cu and Zn in whole blood of the rabbits during fracture healing were determined by proton induced X-ray emission (PIXE). The contents of Ca and Fe in whole blood were almost kept constant and the contents of other elements varied significantly during fracture healing. The contents of elements K, Ca, Mn, Fe, Cu and Zn in bone for 48 rabbits fractured in radius of limb during healing were also analyzed by PIXE. Various absorbers were tested to improve the PIXE spectra of bone samples and the spectra with much better quality were obtained using some kinds of combined absorbers. The changes of the contents of elements Sr and Fe in bone were shown as a concave shape and convex one respectively, during healing period.

  4. 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

  5. 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

  6. 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

  7. 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

  8. Hydrogen sulfide accelerates wound healing in diabetic rats

    PubMed Central

    Wang, Guoguang; Li, Wei; Chen, Qingying; Jiang, Yuxin; Lu, Xiaohua; Zhao, Xue

    2015-01-01

    Aim: The aim of this study was to explore the role of hydrogen sulfide on wound healing in diabetic rats. Methods: Experimental diabetes in rats was induced by intraperitoneal injection of streptozotocin (STZ) (in 0.1 mol/L citrate buffer, Ph 4.5) at dose of 70 mg/kg. Diabetic and age-matched non-diabetic rats were randomly assigned to three groups: untreated diabetic controls (UDC), treated diabetic administrations (TDA), and non-diabetic controls (NDC). Wound Healing Model was prepared by making a round incision (2.0 cm in diameter) in full thickness. Rats from TDA receive 2% sodium bisulfide ointment on wound, and animals from UDC and NDC receive control cream. After treatment of 21 days with sodium bisulfide, blood samples were collected for determination of vascular endothelial growth factor (VEGF), intercellular cell adhesion molecule-1 (ICAM-1), antioxidant effects. Granulation tissues from the wound were processed for histological examination and analysis of western blot. Results: The study indicated a significant increase in levels of VEGF and ICAM-1 and a decline in activity of coagulation in diabetic rats treated with sodium bisulfide. Sodium bisulfide treatment raised the activity of superoxide dismutase (SOD) and heme oxygenase-1 (HO-1) protein expression, and decreased tumor necrosis factor α (TNF-α) protein expression in diabetic rats. Conclusions: The findings in present study suggested that hydrogen sulfide accelerates the wound healing in rats with diabetes. The beneficial effect of H2S may be associated with formation of granulation, anti-inflammation, antioxidant, and the increased level of vascular endothelial growth factor (VEGF). PMID:26191204

  9. Diazoxide accelerates wound healing by improving EPC function.

    PubMed

    Li, Zhang-Peng; Xin, Ru-Juan; Yang, Hong; Jiang, Guo-Jun; Deng, Ya-Ping; Li, Dong-Jie; Shen, Fu-Ming

    2016-01-01

    Endothelial cell dysfunction is the primary cause of microvascular complications in diabetes. Diazoxide enables beta cells to rest by reversibly suppressing glucose-induced insulin secretion by opening ATP-sensitive K+ channels in the beta cells. This study investigated the role of diazoxide in wound healing in mice with streptozotocin (STZ)-induced diabetes and explored the possible mechanisms of its effect. Compared to the controls, mice with STZ-induced diabetes exhibited significantly impaired wound healing. Diazoxide treatment (30 mg/kg/d, intragastrically) for 28 days accelerated wound closure and stimulated angiogenesis in the diabetic mice. Circulating endothelial progenitor cells (EPCs) increased significantly in the diazoxide-treated diabetic mice. The adhesion, migration, and tube formation abilities of bone marrow (BM)-EPCs were impaired by diabetes, and these impairments were improved by diazoxide treatment. The expression of both p53 and TSP-1 increased in diabetic mice compared to that in the controls, and these increases were inhibited significantly by diazoxide treatment. In vitro, diazoxide treatment improved the impaired BM-EPC function and diminished the increased expression of p53 and TSP-1 in cultured BM-EPCs caused by high glucose levels. We conclude that diazoxide improved BM-EPC function in mice with STZ-induced diabetes, possibly via a p53- and TSP-1-dependent pathway. PMID:27100489

  10. 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

  11. Fracture bone healing and biodegradation of AZ31 implant in rats.

    PubMed

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

    2015-04-01

    The ideal temporary implant should offer enough mechanical support to allow healing of the fracture and then biodegrade and be resorbed by metabolic mechanisms without causing any toxic effect. The aim of this research has been to simultaneously study in situ bone healing and the biodegradation of AZ31 Mg alloy as an osteosynthesis material. The in vivo study was carried out in AZ31 implants with and without Mg-fluoride coating inserted in un-fractured and fractured femurs of Wistar rats for long experimentation time, from 1 to 13 months, by means of computed tomography, histological and histomorphometric analysis. Tomography analysis showed the bone healing and biodegradation of AZ31 implants. The fracture is healed in 100% of the animals, and AZ31 maintains its mechanical integrity throughout the healing process. Biodegradation was monitored, quantifying the evolution of gas over time by 3D composition of tomography images. In all the studied groups, gas pockets disappear with time as a result of the diffusion process through soft tissues. Histomorphometric studies reveal that after 13 months the 46.32% of AZ31 alloy has been resorbed. The resorption of the coated and uncoated AZ31 implants inserted in fractured femurs after 1, 9 and 13 months does not have statistically significant differences. There is a balance between the biodegradation of AZ31 and bone healing which allows the use of AZ31 to be proposed as an osteosynthesis material. PMID:25886380

  12. Liposome-encapsulated hemoglobin accelerates skin wound healing in mice.

    PubMed

    Fukui, Tsuyoshi; Kawaguchi, Akira T; Takekoshi, Susumu; Miyasaka, Muneo; Tanaka, Rica

    2012-02-01

    Effects of liposome-encapsulated hemoglobin with high O₂ affinity (m-LEH, P₅₀O₂ = 17 mm Hg) on skin wound healing in mice were examined. Two full-thickness dorsal wounds 6 mm in diameter encompassed by silicone stents were created in Balb/c mice. Two days later (day 2), the animals randomly received intravenous m-LEH (2 mL/kg, n = 12), homologous blood transfusion (red blood cell [RBC], n = 11), or saline (n = 12). The same treatment was repeated 4 days after wounding (day 4), and the sizes of the skin defects and ulcers were monitored on days 0, 2, 4, and 7, when all animals were euthanized for morphological studies. While the size of the skin defect in relation to the stent ring remained the same in all groups, the size of the ulcer compared with the skin defect (or silicone stent) became significantly reduced on days 4 and 7 in mice treated with m-LEH (46 ± 10% of pretreatment size, P < 0.01) compared with mice treated with RBC transfusion (73 ± 6%) or saline (76 ± 7%). m-LEH treatment significantly accelerated granulation, increased epithelial thickness, suppressed early granulocyte infiltration, and increased Ki67 expression in accordance with the ulcer size reduction, while there was no difference in surface blood flow or CD31 expression among the groups. The results suggest that m-LEH (2 mL/kg) may accelerate skin wound healing in Balb/c mice via mechanism(s) involving reduced inflammation and increased metabolism, but not by improved hemodynamics or endothelial regeneration. PMID:22339725

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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

  18. 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

  19. Absence of positive effect of black cohosh (Cimicifuga racemosa) on fracture healing in osteopenic rodent model.

    PubMed

    Kolios, Leila; Daub, Florian; Sehmisch, Stephan; Frosch, Karl-Heinz; Tezval, Mohammed; Stuermer, Klaus Michael; Wuttke, Wolfgang; Stuermer, Ewa Klara

    2010-12-01

    The healing of predominantly metaphyseal fractures in postmenopausal osteoporosis is delayed and comparatively poor. Due to the potential side effects of HRT, natural alternatives are appealing. The aim of this study was to determine whether Cimicifuga racemosa extract BNO 1055 improves metaphyseal fracture healing in severe osteopenic bone in rats. Thirty-three 12-week-old female rats developed severe osteopenia during 10 weeks after ovariectomy. After metaphyseal tibial-osteotomy and standardized T-plate-osteosynthesis, the healing periods in ovariectomized rats (C), 17-α-estradiol (E) and Cimicifuga racemosa (CR) supplemented diets were assessed for 35 days. Changes in callus morphology were evaluated qualitatively by biomechanical testing and quantitatively in microradiographies and fluorochrome-labeled histological sections. The CR-supplementation slightly improved callus quality and trabecular bone formation. It significantly enhanced the endosteal callus density compared to C group (Cl.Dn.e C: 59.08 ± 21.89, E: 45.95 ± 18.39, CR: 60.85 ± 18.66*), though most of the other morphological parameters examined showed no improvement. The time course of fracture healing did not change due to CR. Estrogen-supplementation enhanced the biomechanical properties of the fracture site. Trabecular bone was improved indicating the physiological endosteal healing process. The CR-supplementation did not exhibit positive effects in severe (senile) osteopenic fracture healing as seen in early (postmenopausal) osteoporosis in rats. Callus formation was slightly improved under CR. Estrogen improved fracture healing in severe osteopenic bone, while the extent of callus formation played a minor role. PMID:20564511

  20. 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. PMID:25298328

  1. Abductor digiti minimi muscle flap transfer to prevent wound healing complications after ORIF of calcaneal fractures

    PubMed Central

    Wang, Chao-Liang; Huang, Su-Fang; Sun, Xue-Sheng; Zhu, Tao; Lin, Chu; Li, Qiang

    2015-01-01

    Objectives: To examine the transfer of abductor digiti minimi (ADM) muscle flaps as a method for preventing wound healing complications in cases of closed calcaneal fractures treated with open reduction and internal fixation (ORIF). Method: Design: Retrospective review. Patients: Twenty-six cases of acute closed calcaneal fracture in patients at risk for serious wound complications or with serious fractures. Intervention: During the ORIF surgery, an ADM muscle flap was removed and used to cover the plate, filling the gap between the plate and skin. Main Outcome Measures: Wound healing rates, postoperative complications, and time to heal. Results: All wounds healed uneventfully, except for one case of minor superficial epithelial necrosis during the early postoperative period, which was treated conservatively. All patients regained ambulatory status with regular foot apparel. At last follow-up, the patients presented no clinical, laboratory, or radiological signs of complications. Conclusions: This ADM muscle flap transfer technique appeared to successfully prevent wound healing complications among patients undergoing ORIF for closed calcaneal fractures. This method offers a promising treatment option for calcaneal fractures in patients at high risk for serious wound complications, and future studies with greater numbers of cases are needed to further investigate its clinical application. PMID:26550221

  2. Recombinant basic fibroblast growth factor accelerates wound healing.

    PubMed

    McGee, G S; Davidson, J M; Buckley, A; Sommer, A; Woodward, S C; Aquino, A M; Barbour, R; Demetriou, A A

    1988-07-01

    Basic fibroblast growth factor (bFGF) stimulates extracellular matrix metabolism, growth, and movement of mesodermally derived cells. We have previously shown that collagen content in polyvinyl alcohol sponges increased after bFGF treatment. We hypothesized that bFGF-treated incisional wounds would heal more rapidly. After intraperitoneal pentobarbital anesthesia, male, 200- to 250-g, Sprague-Dawley rats (n = 27) each underwent two sets of paired, transverse, dorsal incisions closed with steel sutures. On Day 3 postwounding, 0.4 ml of bFGF (recombinant, 400 ng. Synergen) or normal saline was injected into one of each paired incisions. Animals were killed with ether on postwounding Days 5, 6, and 7 and their dorsal pelts were excised. Fresh or formalin-fixed wound strips were subjected to tensile strength measurements using a tensiometer. Breaking energy was calculated. Wound collagen content (hydroxyproline) was measured in wound-edge samples following hydrolysis using high-performance liquid chromatography. There was an overall significant increase in fresh wound tensile strength (13.7 +/- 1.06 vs 19.1 +/- 1.99 g/mm, P less than 0.01) and wound breaking energy (476 +/- 47 vs 747 +/- 76 mm2, P less than 0.001) in bFGF-treated incisions. There was an increase in wound collagen content which was not statistically significant and there was no difference in fixed incisional tensile strength. Histologic examination showed better organization and maturation in bFGF wounds. Recombinant bFGF accelerates normal rat wound healing. This may be due to earlier accumulation of collagen and fibroblasts and/or to greater collagen crosslinking in bFGF-treated wounds. PMID:3392988

  3. Musculoskeletal Response to Whole-Body Vibration During Fracture Healing in Intact and Ovariectomized Rats

    PubMed Central

    Stuermer, Ewa K.; Werner, Carsten; Wicke, Michael; Kolios, Leila; Sehmisch, Stephan; Tezval, Mohammad; Utesch, Clara; Mangal, Orzala; Zimmer, Sebastian; Dullin, Christian; Stuermer, Klaus M.

    2010-01-01

    This study investigated the effect of vibration on bone healing and muscle in intact and ovariectomized rats. Thirty ovariectomized (at 3 months of age) and 30 intact 5-month old female Sprague-Dawley rats underwent bilateral metaphyseal osteotomy of tibia. Five days later, half of the ovariectomized and of the intact rats were exposed to whole-body vertical vibration (90 Hz, 0.5 mm, 4 × g acceleration) for 15 min twice a day during 30 days. The other animals did not undergo vibration. After decapitation of rats, one tibia was used for computed tomographic, biomechanical, and histological analyses; the other was used for gene expression analyses of alkaline phosphatase (Alp), osteocalcin (Oc), tartrate-resistant acid phosphatase 1, and insulinlike growth factor 1. Serum Alp and Oc were measured. Mitochondrial activity, fiber area and distribution, and capillary densities were analyzed in M. gastrocnemius and M. longissimus. We found that vibration had no effect on body weight and food intake, but it improved cortical and callus densities (97 vs. 99%, 72 vs. 81%), trabecular structure (9 vs. 14 trabecular nodes), blood supply (1.7 vs. 2.1 capillaries/fiber), and oxidative metabolism (17 vs. 23 pmol O2/s/mg) in ovariectomized rats. Vibration generally increased muscle fiber size. Tibia biomechanical properties were diminished after vibration. Oc gene expression was higher in vibrated rats. Serum Alp was increased in ovariectomized rats. In ovariectomized rats, vibration resulted in an earlier bridging; in intact rats, callus bridging occurred later after vibration. The chosen vibration regimen (90 Hz, 0.5 mm, 4 × g acceleration, 15 min twice a day) was effective in improving musculoskeletal tissues in ovariectomized rats but was not optimal for fracture healing. PMID:20532877

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

    NASA Astrophysics Data System (ADS)

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

    2015-05-01

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

  5. Conditioned Media From Adipose-Derived Stromal Cells Accelerates Healing in 3-Dimensional Skin Cultures.

    PubMed

    Collawn, Sherry S; Mobley, James A; Banerjee, N Sanjib; Chow, Louise T

    2016-04-01

    Wound healing involves a number of factors that results in the production of a "closed" wound. Studies have shown, in animal models, acceleration of wound healing with the addition of adipose-derived stromal cells (ADSC). The cause for the positive effect which these cells have on wound healing has not been elucidated. We have previously shown that addition of ADSC to the dermal equivalent in 3-dimensional skin cultures accelerates reepithelialization. We now demonstrate that conditioned media (CM) from cultured ADSC produced a similar rate of healing. This result suggests that a feedback from the 3-dimensional epithelial cultures to ADSC was not necessary to effect the accelerated reepithelialization. Mass spectrometry of CM from ADSC and primary human fibroblasts revealed differences in secretomes, some of which might have roles in the accelerating wound healing. Thus, the use of CM has provided some preliminary information on a possible mode of action. PMID:26954733

  6. 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

  7. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2005-04-01

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

  9. 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

  10. 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

  11. TGFβ-2 signaling is essential for osteoblast migration and differentiation during fracture healing in medaka fish.

    PubMed

    Takeyama, Kazuhiro; Chatani, Masahiro; Inohaya, Keiji; Kudo, Akira

    2016-05-01

    TGFβ is known as a canonical coupling factor based on its effects on bone formation and bone resorption. There are 3 different isoforms of it related to bone metabolism in mammals. TGFβ function in vivo is complicated, and each isoform shows a different function. Since TGFβs are secreted during inflammation accompanied by the release of latent TGFβ from inside of the bones where they are stored in the extracellular matrix, TGFβ function is potentially related to fracture healing. Although a few reports examined the TGFβ expression during fracture healing, the function of TGFβ in this process is poorly understood. To investigate TGFβ function during fracture healing in vivo, we used the fracture healing model of the medaka fish, which enabled us to observe the behavior and function of living cells in response to a bone-specific injury. RNA in-situ hybridization analysis showed that only tgfβ-2 of the 4 TGFβ isoforms in medaka was expressed in the bone-forming region. To examine the TGFβ-2 function for bone formation by osteoblasts, we used a medaka transgenic line, Tg (type X collagen: GFP); and the results revealed that type X collagen-positive immature osteoblasts migrated to the fracture site and differentiated to osterix-positive osteoblasts. However, only a few type X collagen-positive osteoblasts exhibited BrdU incorporation after the fracture. Then we inhibited TGFβ signaling by using a chemical TGFβ receptor kinase inhibitor (SB431542), and demonstrated that inhibition of TGFβ strongly impaired osteoblast migration and differentiation. In addition, this TGFβ inhibitor reduced the RANKL expression and caused a delay of osteoclast differentiation. Our findings thus demonstrated that TGFβ-2 functioned specifically during fracture healing to stimulate the migration of osteoblasts as well as the differentiation of osteoblasts and osteoclasts. PMID:26947892

  12. 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

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

    PubMed

    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

  14. 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

  15. Ketorolac Administration Does Not Delay Early Fracture Healing in a Juvenile Rat Model

    PubMed Central

    Cappello, Teresa; Nuelle, Julia A.V.; Katsantonis, Nicolas; Nauer, Rachel K.; Lauing, Kristen L.; Jagodzinski, Jason E.; Callaci, John J.

    2014-01-01

    Background Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective at controlling pain in children, especially in the treatment of fractures. Adult animal and adult clinical studies demonstrate conflicting evidence for the inhibitory relationship between NSAIDs and fracture healing. Published pediatric orthopaedic clinical studies do not demonstrate an inhibitory effect of ketorolac on bone healing. Little is known about the effects of any NSAID on bone formation in juvenile animals. This study investigates the effects of the NSAID ketorolac on fracture healing in a juvenile rat model. Methods Unilateral surgically induced and stabilized tibial shaft fractures were created in 45 juvenile (3 to 4wk old) male Sprague-Dawley rats. Either ketorolac (5 mg/kg; n=24) or saline (0.9% normal saline; n=21) was then administered to the rats 6 d/wk by intraperitoneal injections. Animals were then randomly assigned into time groups and euthanized at 7 days (n=8 ketorolac, n=7 saline), 14 days (n=8 ketorolac, n=7 saline), or 21 days (n=8 ketorolac, n=7 saline) postfracture. Biomechanical analysis was performed using a custom-designed 4-point bending loading apparatus. Statistics for tibial stiffness and strength data were performed using software package Systat 11. Specimens were also evaluated histologically using hematoxylin and eosin staining. Results Strength and stiffness of all fractured tibiae increased over time from day 7 to day 21 regardless of treatment type. No statistical difference was found between the fractured tibiae strength or stiffness in the ketorolac or control-treated specimens at the same time point. In addition, the quality of the fracture callus was similar in both groups at each of the time points. Conclusions In this study of a juvenile rat model with a stabilized tibia fracture, fracture callus strength, stiffness, and histologic characteristics were not affected by the administration of ketorolac during the first 21 days of fracture healing

  16. 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

  17. 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

  18. Obesity does not affect the healing of femur fractures in mice.

    PubMed

    Histing, T; Andonyan, A; Klein, M; Scheuer, C; Stenger, D; Holstein, J H; Veith, N T; Pohlemann, T; Menger, M D

    2016-07-01

    Obesity is reported to be both protective and deleterious to bone. Lipotoxicity and inflammation might be responsible for bone loss through inhibition of osteoblasts and activation of osteoclasts. However, little is known whether obesity affects the process of fracture healing. Therefore, we studied the effect of high fat diet-induced (HFD) obesity on callus formation and bone remodelling in a closed femur fracture model in mice. Thirty-one mice were fed a diet containing 60kJ% fat (HFD) for a total of 20 weeks before fracture and during the entire postoperative observation period. Control mice (n=31) received a standard diet containing 10kJ% fat. Healing was analyzed using micro-CT, biomechanical, histomorphometrical, immunohistochemical, serum and protein biochemical analysis at 2 and 4 weeks after fracture. HFD-fed mice showed a higher body weight and increased serum concentrations of leptin and interleukin-6 compared to controls. Within the callus tissue Western blot analyses revealed a higher expression of transcription factor peroxisome proliferator-activated receptor y (PPARy) and a reduced expression of runt-related transcription factor 2 (RUNX2) and bone morphogenetic protein (BMP)-4. However, obesity did not affect the expression of BMP-2 and did not influence the receptor activator of nuclear factor κB (RANK)/RANK ligand/osteoprotegerin (OPG) pathway during fracture healing. Although the bones of HFD-fed animals showed an increased number of adipocytes within the bone marrow, HFD did not increase callus adiposity. In addition, radiological and histomorphometric analysis could also not detect significant differences in bone formation between HFD-fed animals and controls. Accordingly, HFD did not affect bending stiffness after 2 and 4 weeks of healing. These findings indicate that obesity does not affect femur fracture healing in mice. PMID:27156834

  19. 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

  20. [Histologic finding of fracture healing using external fixation and its clinical significance].

    PubMed

    Stürmer, K M

    1984-06-01

    The histology of bone healing under external fixation of fractures is studied in 2 human bone specimen and in the sheep's tibia. Primary bone healing occurs under absolute stable fixation. The regular course shows secundary bone healing by endosteal and periosteal callus formation, caused by motion in the fracture gap. Nonunion results, if motion is not big enough to induce callus formation and if motion is too big to allow primary bone healing. So one of the main problems in external fixation of fractures is to find out the adequate dose of stability and motion in the fracture gap. External fixation does not disturb the vascular supply of bone. Intramedullary vessels, that are cut during the osteotomy of the sheep's tibia, are perfectly regenerated 4-5 weeks later. In the surroundings of the Schanz' screws, cortical remodelling is the biomechanical response of bone to strees, which is generated by external fixation. This cortical remodelling can reduce compression, originally applied to the bone. The indication and the timing for a change to internal fixation is discussed. PMID:6474602

  1. Laboratory study of fracture healing in Topopah Spring tuff: Implications for near field hydrology

    SciTech Connect

    Lin, Wunan; Daily, W.D.

    1989-09-01

    Seven Topopah Spring tuff samples were studied to determine water permeability in this rock under pressure and temperature conditions similar to those expected in the near field of a nuclear waste package. Six of the seven samples were studied under isothermal condition; the other was subjected to a thermal gradient. Four of the six fractured samples contained a reopened, healed, natural fracture; one contained an induced tensile fracture and the other contained a saw-cut. The fracture surfaces were examined using scanning electron microscope (SEM) before and after the experiments and the water that flowed through the samples was sampled for chemical analysis. The experimental durations ranged from about 3 months to almost 6 months. Water permeability of the fractured samples was found to decrease by more than three orders of magnitude when the sample temperature increased to 150{degree}C. The sharpest decrease in permeability occurred when the temperature was increased above 90{degree}C. Permeability of the intact sample did not change significantly under the similar experimental conditions. When the temperature returned to room conditions, the water permeability did not recover. The mechanical strength of one healed sample was about half that of the intact rock. SEM studies of the fracture surfaces and water chemical analysis of the water suggested that both dissolution and deposition occurred on the fracture surfaces. Smoothing of fracture asperities because of dissolution and deposition was probably the main cause of the permeability decrease. Deposition of dissolved silica was probably the main cause of fracture healing. 12 refs., 6 figs., 1 tab.

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

    PubMed Central

    2016-01-01

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

  3. Knockout of Angiotensin AT2 receptors accelerates healing but impairs quality

    PubMed Central

    Faghih, Mahya; Hosseini, Sayed M.; Smith, Barbara; Ansari, Amir Mehdi.; Lay, Frank; Ahmed, Ali Karim; Inagami, Tedashi; Marti, Guy P.; Harmon, John W.; Walston, Jeremy D.; Abadir, Peter M.

    2015-01-01

    Wounds are among the most common, painful, debilitating and costly conditions in older adults. Disruption of the angiotensin type 1 receptors (AT1R), has been associated with impaired wound healing, suggesting a critical role for AT1R in this repair process. Biological functions of angiotensin type 2 receptors (AT2R) are less studied. We investigated effects of genetically disrupting AT2R on rate and quality of wound healing. Our results suggest that AT2R effects on rate of wound closure depends on the phase of wound healing. We observed delayed healing during early phase of wound healing (inflammation). An accelerated healing rate was seen during later stages (proliferation and remodeling). By day 12, fifty percent of AT2R−/− mice had complete wound closure as compared to none in either C57/BL6 or AT1R−/− mice. There was a significant increase in AT1R, TGFβ1 and TGFβ2 expression during the proliferative and remodeling phases in AT2R−/− mice. Despite the accelerated closure rate, AT2R−/− mice had more fragile healed skin. Our results suggest that in the absence of AT2R, wound healing rate is accelerated, but yielded worse skin quality. Elucidating the contribution of both of the angiotensin receptors may help fine tune future intervention aimed at wound repair in older individuals. PMID:26727887

  4. 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

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

    PubMed Central

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

    2015-01-01

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

  6. 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. PMID:24093748

  7. Acute phosphate restriction leads to impaired fracture healing and resistance to BMP-2.

    PubMed

    Wigner, Nathan A; Luderer, Hilary F; Cox, Megan K; Sooy, Karen; Gerstenfeld, Louis C; Demay, Marie B

    2010-04-01

    Hypophosphatemia leads to rickets and osteomalacia, the latter of which results in decreased biomechanical integrity of bones, accompanied by poor fracture healing. Impaired phosphate-dependent apoptosis of hypertrophic chondrocytes is the molecular basis for rickets. However, the underlying pathophysiology of impaired fracture healing has not been characterized previously. To address the role of phosphate in fracture repair, mice were placed on a phosphate-restricted diet 2 days prior to or 3 days after induction of a mid-diaphyseal femoral fracture to assess the effects of phosphate deficiency on the initial recruitment of mesenchymal stem cells and their subsequent differentiation. Histologic and micro-computed tomographic (microCT) analyses demonstrated that both phosphate restriction models dramatically impaired fracture healing primarily owing to a defect in differentiation along the chondrogenic lineage. Based on Sox9 and Sox5 mRNA levels, neither the initial recruitment of cells to the callus nor their lineage commitment was effected by hypophosphatemia. However, differentiation of these cells was impaired in association with impaired bone morphogenetic protein (BMP) signaling. In vivo ectopic bone-formation assays and in vitro investigations in ST2 stromal cells confirmed that phosphate restriction leads to BMP-2 resistance. Marrow ablation studies demonstrate that hypophosphatemia has different effects on injury-induced intramembranous bone formation compared with endochondral bone formation. Thus phosphate plays an important role in the skeleton that extends beyond mineralized matrix formation and growth plate maturation and is critical for endochondral bone repair. PMID:19839770

  8. 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

  9. 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

  10. 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

  11. The relationship between interfragmentary movement and cell differentiation in early fracture healing under locking plate fixation.

    PubMed

    Miramini, Saeed; Zhang, Lihai; Richardson, Martin; Mendis, Priyan; Oloyede, Adekunle; Ebeling, Peter

    2016-03-01

    Interfragmentary movement (IFM) at the fracture site plays an important role in fracture healing, particularly during its early stage, via influencing the mechanical microenvironment of mesenchymal stem cells within the fracture callus. However, the effect of changes in IFM resulting from the changes in the configuration of locking plate fixation on cell differentiation has not yet been fully understood. In this study, mechanical experiments on surrogate tibia specimens, manufactured from specially formulated polyurethane, were conducted to investigate changes in IFM of fractures under various locking plate fixation configurations and loading magnitudes. The effect of the observed IFM on callus cell differentiation was then further studied using computational simulation. We found that during the early stage, cell differentiation in the fracture callus is highly influenced by fracture gap size and IFM, which in turn, is highly sensitive to locking plate fixation configuration. The computational model predicted that a small gap size (e.g. 1 mm) under a relatively flexible configuration of locking plate fixation (larger bone-plate distances and working lengths) could experience excessive strain and fluid flow within the fracture site, resulting in excessive fibrous tissue differentiation and delayed healing. By contrast, a relatively flexible configuration of locking plate fixation was predicted to improve cartilaginous callus formation and bone healing for a relatively larger gap size (e.g. 3 mm). If further confirmed by animal and human studies, the research outcome of this paper may have implications for orthopaedic surgeons in optimising the application of locking plate fixations for fractures in clinical practice. PMID:26634603

  12. 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.

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

    PubMed Central

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

    2013-01-01

    Background Therapeutic augmentation of fracture site angiogenesis with Deferoxamine (DFO) has proven to increase vascularity, callus size and mineralization in long-bone fracture models. We posit that the addition of DFO would enhance pathological fracture healing in the setting of radiotherapy in a model where non-unions are the most common outcome. Methods Sprague-Dawley rats (n = 35) were divided into 3 groups. Fracture (Fx), radiated fracture (XFx) and radiated fracture + DFO (XFxDFO). Groups XFx and XFxDFO received a human equivalent dose of radiotherapy (7 Gy/day × 5 days = 35 Gy) 2 weeks prior to mandibular osteotomy and external fixation. The XFxDFO group received injections of DFO into the fracture callus after surgery. Following a 40-day healing period, mandibles were dissected, clinically assessed for bony-union, imaged with Micro-CT, and tension tested to failure. Results Compared to radiated fractures, metrics of callus size, mineralization and strength in DFO treated mandibles were significantly increased. These metrics were restored to a level demonstrating no statistical difference from control fractures. In addition we observed an increased rate of achieving bony unions in the XFxDFO treated group when compared to XFx (67% vs. 20% respectively). Conclusions Our data demonstrate near total restoration of callus size, mineralization, and biomechanical strength, as well as a 3-fold increase in the rate of union with the use of DFO. Our results suggest that the administration of DFO may have the potential for clinical translation as a new treatment paradigm for radiation induced pathologic fractures. Level of Evidence Animal study, not gradable for level of evidence. PMID:23629110

  14. The impact of low-magnitude high-frequency vibration on fracture healing is profoundly influenced by the oestrogen status in mice

    PubMed Central

    Wehrle, Esther; Liedert, Astrid; Heilmann, Aline; Wehner, Tim; Bindl, Ronny; Fischer, Lena; Haffner-Luntzer, Melanie; Jakob, Franz; Schinke, Thorsten; Amling, Michael; Ignatius, Anita

    2015-01-01

    Fracture healing is impaired in aged and osteoporotic individuals. Because adequate mechanical stimuli are able to increase bone formation, one therapeutical approach to treat poorly healing fractures could be the application of whole-body vibration, including low-magnitude high-frequency vibration (LMHFV). We investigated the effects of LMHFV on fracture healing in aged osteoporotic mice. Female C57BL/6NCrl mice (n=96) were either ovariectomised (OVX) or sham operated (non-OVX) at age 41 weeks. When aged to 49 weeks, all mice received a femur osteotomy that was stabilised using an external fixator. The mice received whole-body vibrations (20 minutes/day) with 0.3 g peak-to-peak acceleration and a frequency of 45 Hz. After 10 and 21 days, the osteotomised femurs and intact bones (contra-lateral femurs, lumbar spine) were evaluated using bending-testing, micro-computed tomography (μCT), histology and gene expression analyses. LMHFV disturbed fracture healing in aged non-OVX mice, with significantly reduced flexural rigidity (−81%) and bone formation (−80%) in the callus. Gene expression analyses demonstrated increased oestrogen receptor β (ERβ, encoded by Esr2) and Sost expression in the callus of the vibrated animals, but decreased β-catenin, suggesting that ERβ might mediate these negative effects through inhibition of osteoanabolic Wnt/β-catenin signalling. In contrast, in OVX mice, LMHFV significantly improved callus properties, with increased flexural rigidity (+1398%) and bone formation (+637%), which could be abolished by subcutaneous oestrogen application (0.025 mg oestrogen administered in a 90-day-release pellet). On a molecular level, we found an upregulation of ERα in the callus of the vibrated OVX mice, whereas ERβ was unaffected, indicating that ERα might mediate the osteoanabolic response. Our results indicate a major role for oestrogen in the mechanostimulation of fracture healing and imply that LMHFV might only be safe and effective in

  15. Low-Magnitude, High-Frequency Vibration Fails to Accelerate Ligament Healing but Stimulates Collagen Synthesis in the Achilles Tendon

    PubMed Central

    Thompson, William R.; Keller, Benjamin V.; Davis, Matthew L.; Dahners, Laurence E.; Weinhold, Paul S.

    2015-01-01

    Background: Low-magnitude, high-frequency vibration accelerates fracture and wound healing and prevents disuse atrophy in musculoskeletal tissues. Purpose: To investigate the role of low-magnitude, high-frequency vibration as a treatment to accelerate healing of an acute ligament injury and to examine gene expression in the intact Achilles tendon of the injured limb after low-magnitude, high-frequency vibration. Study Design: Controlled laboratory study. Methods: Complete surgical transection of the medial collateral ligament (MCL) was performed in 32 Sprague-Dawley rats, divided into control and low-magnitude, high-frequency vibration groups. Low-magnitude, high-frequency vibration started on postoperative day 2, and rats received vibration for 30 minutes a day for 12 days. All rats were sacrificed 2 weeks after the operation, and their intact and injured MCLs were biomechanically tested or used for histological analysis. Intact Achilles tendons from the injured limb were evaluated for differences in gene expression. Results: Mechanical testing revealed no differences in the ultimate tensile load or the structural stiffness between the control and vibration groups for either the injured or intact MCL. Vibration exposure increased gene expression of collagen 1 alpha (3-fold), interleukin 6 (7-fold), cyclooxygenase 2 (5-fold), and bone morphogenetic protein 12 (4-fold) in the intact Achilles tendon when compared with control tendons (P < .05). Conclusion: While no differences were observed in the mechanical or histological properties of the fully transected MCL after low-magnitude, high-frequency vibration treatment, significant enhancements in gene expression were observed in the intact Achilles tendon. These included collagen, several inflammatory cytokines, and growth factors critical for tendons. Clinical Relevance: As low-magnitude, high-frequency vibration had no negative effects on ligament healing, vibration therapy may be a useful tool to accelerate healing

  16. Acceleration of diabetic wound healing using a novel protease–anti-protease combination therapy

    PubMed Central

    Gao, Ming; Nguyen, Trung T.; Suckow, Mark A.; Wolter, William R.; Gooyit, Major; Mobashery, Shahriar; Chang, Mayland

    2015-01-01

    Nonhealing chronic wounds are major complications of diabetes resulting in >70,000 annual lower-limb amputations in the United States alone. The reasons the diabetic wound is recalcitrant to healing are not fully understood, and there are limited therapeutic agents that could accelerate or facilitate its repair. We previously identified two active forms of matrix metalloproteinases (MMPs), MMP-8 and MMP-9, in the wounds of db/db mice. We argued that the former might play a role in the body’s response to wound healing and that the latter is the pathological consequence of the disease with detrimental effects. Here we demonstrate that the use of compound ND-336, a novel highly selective inhibitor of gelatinases (MMP-2 and MMP-9) and MMP-14, accelerates diabetic wound healing by lowering inflammation and by enhancing angiogenesis and re-epithelialization of the wound, thereby reversing the pathological condition. The detrimental role of MMP-9 in the pathology of diabetic wounds was confirmed further by the study of diabetic MMP-9–knockout mice, which exhibited wounds more prone to healing. Furthermore, topical administration of active recombinant MMP-8 also accelerated diabetic wound healing as a consequence of complete re-epithelialization, diminished inflammation, and enhanced angiogenesis. The combined topical application of ND-336 (a small molecule) and the active recombinant MMP-8 (an enzyme) enhanced healing even more, in a strategy that holds considerable promise in healing of diabetic wounds. PMID:26598687

  17. Ultrasound propagation velocity and broadband attenuation can help evaluate the healing process of an experimental fracture.

    PubMed

    Barbieri, Giuliano; Barbieri, Cláudio Henrique; Mazzer, Nilton; Pelá, Carlos Alberto

    2011-03-01

    Ultrasonometry seems to have a future for the evaluation of fracture healing. Ultrasound propagation velocity (USPV) significantly decreases at the same time that bone diameter decreases as healing takes place, thus approaching normal values. In this investigation, both USPV and broadband ultrasound attenuation (BUA) were measured using a model of a transverse mid-diaphyseal osteotomy of sheep tibiae. Twenty-one sheep were operated and divided into three groups of seven, according to the follow-up period of 30, 60, and 90 days, respectively. The progress of healing of the osteotomy was checked with monthly conventional radiographs. The animals were killed at the end of the period of observation of each group, both operated-upon and intact tibiae being resected and submitted to the measurement of underwater transverse and direct contact transverse and longitudinal USPV and BUA at the osteotomy site. The intact left tibia of the 21 animals was used for control, being examined on a symmetrical diaphyseal segment. USPV increased while BUA decreased with the progression of healing, with significant differences between the operated and untouched tibiae and between the periods of observation, for most of the comparisons. There was a strong negative correlation between USPV and BUA. Both USPV and BUA directly reflect and can help predict the healing of fractures, but USPV alone can be used as a fundamental parameter. Ultrasonometry may be of use in clinical application to humans provided adequate adaptations can be developed. PMID:20882591

  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. Use of Teriparatide to improve fracture healing: What is the evidence?

    PubMed Central

    Babu, Satish; Sandiford, Nemandra A; Vrahas, Mark

    2015-01-01

    Teriparatide is a recombinant form of the biologically active component of Parathyroid hormone. It has been shown to increase bone mass and prevent fractures in osteoporotic bone. It is licensed by the Food and Drug Administration for the treatment of Osteoporosis. Over the last decade, a growing body of evidence has accumulated suggesting a role for Teriparatide in the management of fractures. Studies in both normal and delayed healing models have shown improvement in callus volume and mineralisation, bone mineral content, rate of successful union and strength at fracture sites. However most of these results have been derived from animal studies. The majority of this research on humans has comprised low level evidence, with few randomised controlled trials, many case reports and case series. Nevertheless, the results from these studies seem to support research from animal models. This has led to a growing number of clinicians using Teriparatide “off license” to treat fractures and non-unions in their patients. This review presents a critical appraisal of the current evidence supporting the use of Teriparatide for fracture healing, delayed unions and non unions and in the setting of osteoporotic fractures, the studies producing this evidence and their transferability to human beings. PMID:26191492

  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. 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

  2. miRNA-29b improves bone healing in mouse fracture model.

    PubMed

    Lee, Wayne Y; Li, Nan; Lin, Sien; Wang, Bin; Lan, Hui Y; Li, Gang

    2016-07-15

    A number of miRNAs regulates bone remodeling and their levels in circulation were associated with bone fracture, however no miRNAs have yet been shown to improve fracture healing directly. This study aimed to investigate the effect of miR-29b-3p on mice femoral fracture healing through site-specific delivery with microbubble-ultrasound system. miR-29b-3p promoted osteogenesis of mouse bone marrow-derived mesenchymal stem cells as indicated with quantitative real-time polymerase chain reaction (qPCR) and Alizarin red S staining. Animal study showed that single injection of miR-29b-3p at week 2 post fracture improved healing outcome as indicated by significant decrease of callus width and area with radiographic analysis without causing significant weight loss. Static bone histomorphometry analysis showed that miR-29b-3p increased bone volume fraction (BV/TV), and micro-computed tomography (micro-CT) measurement showed increased BV/TV of high density bone and bone mineral density (BMD) of the callus. 3 point bending mechanical test showed improved relative stiffness. However, repeated injection of miR-29b-3p at weeks 2 and 3 did not result in additive therapeutic outcome, and caused increased total tissue volume and reduced BMD of the callus. This is the first report showing significant therapeutic effect of miR-29b-3p on femoral fracture healing through site-specific delivery with microbubble-ultrasound system. Further studies are warranted to investigate the underlying mechanisms and to refine the treatment protocol. PMID:27113026

  3. 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

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

    PubMed

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

    2015-01-01

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

  5. 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

  6. Selective estrogen receptor modulators accelerate cutaneous wound healing in ovariectomized female mice.

    PubMed

    Hardman, Matthew J; Emmerson, Elaine; Campbell, Laura; Ashcroft, Gillian S

    2008-02-01

    A lack of systemic hormones in elderly postmenopausal women leads to delayed cutaneous wound healing. This effect can be reversed by systemic or topical estrogen replacement in both humans and rodent models. Over recent years selective estrogen receptor modulators have been developed in an attempt to achieve the beneficial effects of estrogen clinically, while minimizing the detrimental side effects. The effects of selective estrogen receptor modulators on the skin are poorly understood, and the effects on wound healing have not been assessed. In this study we treated 10-wk-old ovariectomized mice with estradiol, tamoxifen (TAM), raloxifene (RAL), or vehicle and examined the effect on healing of full-thickness incisional wounds. Both TAM and RAL substantially accelerate healing, associated with a dampened inflammatory response and altered inflammatory cytokine profile. In vitro TAM and RAL demonstrate antiinflammatory activity comparable to estrogen. These results have significant implications for the clinical modulation of wound healing. PMID:17974625

  7. Low level laser therapy accelerates bone healing in spinal cord injured rats.

    PubMed

    Medalha, Carla Christina; Santos, Ana Lúcia Yaeko Silva; Veronez, Suellen de Oliveira; Fernandes, Kelly Rossetti; Magri, Angela Maria Paiva; Renno, Ana Claudia Muniz

    2016-06-01

    Bone loss occurs rapidly and consistently after the occurrence of a spinal cord injury (SCI), leading to a decrease in bone mineral density (BMD) and a higher risk of fractures. In this context, the stimulatory effects of low level laser therapy (LLLT) also known as photobiomodulation (PBM) have been highlighted, mainly due to its osteogenic potential. The aim of the present study was to evaluate the effects of LLLT on bone healing using an experimental model of tibial bone defect in SCI rats. Twenty-four female Wistar rats were randomly divided into 3 groups: Sham group (SG), SCI control group (SC) and SCI laser treated group (SL). Two weeks after the induction of the SCI, animals were submitted to surgery to induce a tibial bone defect. Treatment was performed 3days a week, for 2weeks, at a single point over the area of the injury, using an 808nm laser (30mW, 100J/cm(2); 0.028cm(2), 1.7W/cm², 2.8J). The results of the histological and morphometric evaluation demonstrated that the SL group showed a larger amount of newly formed bone compared to the SC group. Moreover, a significant immunoexpression of runt-related transcription factor 2 (RUNX2) was observed in the SL group. There was no statistical difference in the biomechanical evaluation. In conclusion, the results suggest that LLLT accelerated the process of bone repair in rats with complete SCI. PMID:27077555

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

    NASA Astrophysics Data System (ADS)

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

    2008-12-01

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

  9. Nitric oxide-releasing nanoparticles accelerate wound healing by promoting fibroblast migration and collagen deposition.

    PubMed

    Han, George; Nguyen, Long N; Macherla, Chitralekha; Chi, Yuling; Friedman, Joel M; Nosanchuk, Joshua D; Martinez, Luis R

    2012-04-01

    Wound healing is a complex process that involves coordinated interactions between diverse immunological and biological systems. Long-term wounds remain a challenging clinical problem, affecting approximately 6 million patients per year, with a high economic impact. To exacerbate the problem, these wounds render the individual susceptible to life-threatening microbial infections. Because current therapeutic strategies have proved suboptimal, it is imperative to focus on new therapeutic approaches and the development of technologies for both short- and long-term wound management. In recent years, nitric oxide (NO) has emerged as a critical molecule in wound healing, with NO levels increasing rapidly after skin damage and gradually decreasing as the healing process progresses. In this study, we examined the effects of a novel NO-releasing nanoparticle technology on wound healing in mice. The results show that the NO nanoparticles (NO-np) significantly accelerated wound healing. NO-np modified leukocyte migration and increased tumor growth factor-β production in the wound area, which subsequently promoted angiogenesis to enhance the healing process. By using human dermal fibroblasts, we demonstrate that NO-np increased fibroblast migration and collagen deposition in wounded tissue. Together, these data show that NO-releasing nanoparticles have the ability to modulate and accelerate wound healing in a pleiotropic manner. PMID:22306734

  10. Adipose derived pericytes rescue fractures from a failure of healing - non-union.

    PubMed

    Tawonsawatruk, T; West, C C; Murray, I R; Soo, C; Péault, B; Simpson, A H R W

    2016-01-01

    Atrophic non-union is attributed to biological failure of the fracture repair process. It occurs in up to 10% of fractures, results in significant morbidity to patients, and treatment often requires complex reconstructive procedures. We tested the ability of human bone derived marrow mesenchymal stem cells (MSC), and human adipose derived pericytes (the native ancestor of the MSC) delivered percutaneously to the fracture gap to prevent the formation of atrophic non-union in a rat model. At eight weeks, 80% of animals in the cell treatment groups showed evidence of bone healing compared to only 14% of those in the control group. Radiographic parameters showed significant improvement over the eight-week period in the cell treatment groups, and histology confirmed bone bridges at the fracture gap in the both treatment groups. The quality of bone produced and its biomechanical properties were significantly enhanced in both treatment groups. The results from this study demonstrate that MSC and pericytes have significant bone regeneration potential in an atrophic non-union model. These cells may have a role in the prevention of atrophic non-union and could enable a paradigm shift in the treatment of fractures at high risk of failing to heal and developing non-union. PMID:26997456

  11. Adipose derived pericytes rescue fractures from a failure of healing – non-union

    PubMed Central

    Tawonsawatruk, T.; West, C. C.; Murray, I. R.; Soo, C.; Péault, B.; Simpson, A. H. R. W.

    2016-01-01

    Atrophic non-union is attributed to biological failure of the fracture repair process. It occurs in up to 10% of fractures, results in significant morbidity to patients, and treatment often requires complex reconstructive procedures. We tested the ability of human bone derived marrow mesenchymal stem cells (MSC), and human adipose derived pericytes (the native ancestor of the MSC) delivered percutaneously to the fracture gap to prevent the formation of atrophic non-union in a rat model. At eight weeks, 80% of animals in the cell treatment groups showed evidence of bone healing compared to only 14% of those in the control group. Radiographic parameters showed significant improvement over the eight-week period in the cell treatment groups, and histology confirmed bone bridges at the fracture gap in the both treatment groups. The quality of bone produced and its biomechanical properties were significantly enhanced in both treatment groups. The results from this study demonstrate that MSC and pericytes have significant bone regeneration potential in an atrophic non-union model. These cells may have a role in the prevention of atrophic non-union and could enable a paradigm shift in the treatment of fractures at high risk of failing to heal and developing non-union. PMID:26997456

  12. Postural control and torque of the knee joint after healed tibial shaft fracture.

    PubMed

    Karladani, A H; Svantesson, U; Granhed, H; Styf, J

    2001-01-01

    Muscular atrophy occurs as a consequence of trauma and immobilisation. This cohort comparison study was conducted to evaluate the limb function after healed tibial shaft fractures, which were treated by casting versus nailing. Balance (as centre of pressure) and muscle strength (as torque of the knee joint during knee extension) have been measured in 27 patients with tibial shaft fractures with a mean age of 39 (19-73) years, 1 year after fracture healing. Fourteen patients were treated by intramedullary nailing 'nailed group' and 13 by plaster cast with or without minimal internal fixation 'casted group'. Centre of pressure was measured on a force platform. Knee extension torque was measured during isometric and concentric muscle actions by an isokinetic dynamometer. Centre of pressure tended to be more towards the uninjured leg in patients who had been treated by plaster cast (P<0.05). Side-to-side differences for isometric torque were significantly higher within the casted group (P<0.05). Patients with tibial shaft fractures treated by intramedullary nailing showed better postural control, one-leg standing test, and side-to-side differences for isometric muscle strength compared with patients treated by cast. Therefore, we recommend intramedullary nailing as a better method of treatment for tibial shaft fractures, with regard to recovery of muscle function. PMID:11164404

  13. 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.

  14. A numerical model of the fracture healing process that describes tissue development and revascularisation.

    PubMed

    Simon, U; Augat, P; Utz, M; Claes, L

    2011-01-01

    A dynamic model was developed to simulate complex interactions of mechanical stability, revascularisation and tissue differentiation in secondary fracture healing. Unlike previous models, blood perfusion was included as a spatio-temporal state variable to simulate the revascularisation process. A 2D, axisymmetrical finite element model described fracture callus mechanics. Fuzzy logic rules described the following biological processes: angiogenesis, intramembranous ossification, chondrogenesis, cartilage calcification and endochondral ossification, all of which depended on local strain state and local blood perfusion. In order to evaluate how the predicted revascularisation depended on the mechanical environment, we simulated two different healing cases according to two groups of transverse metatarsal osteotomies in sheep with different axial stability. The model predicted slower revascularisation and delayed bony bridging for the less stable case, which corresponded well to the experimental observations. A revascularisation sensitivity analysis demonstrated the potential of the model to account for different conditions regarding the blood supply. PMID:21086207

  15. 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

  16. 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

  17. Efficacy of minimally invasive techniques for enhancement of fracture healing: evidence today

    PubMed Central

    Pountos, Ippokratis; Georgouli, Theodora; Kontakis, George

    2009-01-01

    The successful treatment of nonunions represents a major challenge for orthopaedic surgeons. Lately, ongoing advances made in the field of molecular medicine and molecular biology have increased our understanding of the pathways and involvement of mediators surrounding the bone healing process. As a result, the surgeon’s armamentarium has been increased in terms of options for intervention. This article aims to provide an overview of minimally invasive techniques applicable in the treatment of nonunions of fractures. PMID:19844709

  18. 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

  19. Microarray Analysis of Gene Expression Reveals that Cyclo-oxygenase-2 Gene Therapy Up-regulates Hematopoiesis and Down-regulates Inflammation During Endochondral Bone Fracture Healing

    PubMed Central

    Lau, K.-H. William; Popa, Nicoleta L.

    2014-01-01

    Background Cyclo-oxygenase-2 (Cox-2) is an inflammatory mediator that is necessary for the tissue repair, including bone fracture healing. Although the application of Cox-2 gene therapy to a murine closed femoral fracture has accelerated bony union, but the beneficial effect was not observed until the endochondral stage of bone repair that is well after the inflammatory stage normally subsides. Methods To identify the molecular pathways through which Cox-2 regulates fracture healing, we examined gene expression profile in fracture tissues in response to Cox-2 gene therapy during the endochondral bone repair phase. Cox-2 gene therapy was applied to the closed murine femur fracture model. Microarray analysis was performed at 10 days post-fracture to examine global gene expression profile in the fracture tissues during the endochondral bone repair phase. The entire repertoire of significantly expressed genes was examined by gene set enrichment analysis, and the most up-regulated individual genes were evaluated further. Results The genes that normally promote inflammation were under-represented in the microarray analysis, and the expression of several inflammatory chemokines was significantly down-regulated. There was an up-regulation of two key transcription factor genes that regulate hematopoiesis and erythropoiesis. More surprisingly, there was no significant up-regulation in the genes that are normally involved in angiogenesis or bone formation. However, the expression of two tissue remodeling genes was up-regulated. Conclusions The down-regulation of the inflammatory genes in response to Cox-2 gene therapy was unexpected, given the pro-inflammatory role of prostaglandins. Cox-2 gene therapy could promote bony union through hematopoietic precursor proliferation during endochondral bone repair and thereby enhances subsequently fracture callus remodeling that leads to bony union of the fracture gap. PMID:25247155

  20. Optimization of coil geometries for bone fracture healing via dielectrophoretic force stimulation - a simulation study.

    PubMed

    Kibritoğlu, Erman; Gülçür, Halil Özcan

    2015-08-01

    In this paper we propose a novel technique for shortening fracture healing times based on the use of dielectrophoretic forces (DEPFs). If a non-uniform electromagnetic field is applied around a fracture site, red blood cells within the blood will be polarized; creating electrical dipoles. The dielectrophoretic forces resulting from the interaction of these dipoles and the electromagnetic field, can be used to manipulate blood flow at a fracture site, promote vascularization, increase transmembrane signaling, increase supply of nutrients, necessary hormones and growth factors at the fracture site and thus may help bone healing. For the generation of non-uniform fields we considered three different coil designs (linear, parabolic and square root) and using Mathcad numerically studied the dielectrophoretic forces for a long bone fracture where the main arteries are vertically-oriented and the blood flow is downward. The gravitational force and the drag force on the red blood cells determine the steady state blood flow. The dielectrophoretic force added to the force balance is functional in increasing the blood flow. The ratio of the velocity in the presence of dielectrophoresis to the velocity without dielectrophoresis (called here as the Dielectrophoretic Force Factor, K(DEpF)) is a good measure of the performance of the dielectrophoresis, since it indicates the increase in blood flow. It was found that the dielectorophoretic force reaches peak levels at a frequency range between 5-15 Hz. At 5 Hz, the average value of dielectrophoretic force factor is 1.90, 2.51 and 1.61 for the linear, parabolic and the square root coils, respectively. The parabolic coil results in the best DEPF and therefore would be the configuration to use in an experimental study to determine if DEPF is useful for bone healing. PMID:26737886

  1. 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

  2. Bilateral Distal Radius Fracture in Third Trimester of Pregnancy with Accelerated Union: A Rare Case Report

    PubMed Central

    TV, Ravikumar; P, Rahul; Samorekar, Bheemsingh

    2015-01-01

    Bilateral distal radius fracture is a rare entity. There is no literature reporting a bilateral distal radius fracture in pregnancy. Fracture healing is influenced by hormones. Hormonal changes of pregnancy will affect the healing of a fracture. A 28-year-old female at 34 wk of pregnancy sustained a bilateral distal radius fracture after a self fall. One side was managed conservatively and open reduction was done for the other side. Both fractures united at four weeks. This case is unique in three ways. First distal radius fractures commonly occur in elderly postmenopausal females due to oestrogen deficiency. In this case a distal radius fracture occurred following a self fall in third trimester of pregnancy – a hyperestrogenic state. Second the time taken for union was only four weeks signifying the hormonal effects on pregnancy on fracture healing. Third the occurrence of bilateral distal radius fracture itself is very rare in adults. In pregnancy there is a faster rate of fracture healing due to effects of oestrogen and increased cardiac output. Fractures in pregnancy require special attention. Surgical intervention should be done with a multidisciplinary approach. While management of fractures in pregnancy, effect of hormonal and physiological changes should be kept in mind. PMID:26023611

  3. 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.

  4. 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

  5. Potential use of blood bank platelet concentrates to accelerate wound healing of diabetic ulcers.

    PubMed

    Han, Seung-Kyu; Kim, Deok-Woo; Jeong, Seong-Ho; Hong, Yong-Taek; Woo, Hong-Suh; Kim, Woo-Kyung; Gottrup, Finn

    2007-11-01

    Many clinical trials have shown the effectiveness of platelet releasates on diabetic wound healing, but large volumes of blood must be aspirated from patients and a platelet separator is required. This study was undertaken to investigate the potential of blood bank platelet concentrate (BBPC) for accelerating diabetic wound healing. Platelet-derived growth factor-BB (PDGF-BB) contents in BBPC were determined by enzyme-linked immunosorbent assay in vitro, and the in vivo study involved comparing extents of wound healing in BBPC-treated and control groups using diabetic mouse wound models. In the in vitro study, 5.2 +/- 1.2 pg of PDGF-BB was found to be released by 1 million platelets in fresh BBPC, and adding thrombin to BBPC significantly increased the levels of PDGF-BB released. Our in vivo study in diabetic mice revealed that BBPC treatment greatly accelerated wound healing. Our results suggest that BBPC has potential to accelerate the healing of diabetic ulcers. PMID:17992147

  6. Sodium humate accelerates cutaneous wound healing by activating TGF-β/Smads signaling pathway in rats

    PubMed Central

    Ji, Yuanyuan; Zhang, Aijun; Chen, Xiaobin; Che, Xiaoxia; Zhou, Kai; Wang, Zhidong

    2016-01-01

    Sodium humate (HA-Na) has been topically used as a wound healing and anti-inflammatory agent in folk medicine. In the present study, HA-Na was investigated for cutaneous wound healing in Sprague–Dawley rats. HA-Na solution (1.0%, w/v) was topically administered to rats undergoing excision wound models. Healing was assessed with a recombinant bovine basic fibroblast growth factor for external use as positive control. Wound healing rates were calculated on Day 3, 6, 9, 14 and 21 after injury, and tissues were also harvested after the same intervals for histological analysis. In addition, tissue hydroxyproline levels were measured. Furthermore, mRNA levels and protein expressions of transforming growth factor-β1, 2, 3 (TGF-β1, 2, 3) were determined by RT-PCR and western blot. Protein expression levels of Smad-2, -3, -4 and -7 were also detected by western blot. Our study demonstrates that HA-Na has the capacity to promote wound healing in rats via accelerated wound contraction and increased hydroxyproline content. More importantly, these wound healing effects of HA-Na might be mediated through the TGF-β/Smad signaling pathway. HA-Na may be an effective agent for enhanced wound healing. PMID:27006897

  7. Acceleration of healing of gastric ulcers induced in rats by liquid diet: importance of tissue contraction.

    PubMed

    Tsukimi, Y; Okabe, S

    1994-12-01

    We examined the effect of a liquid diet or a combined diet of liquid plus cellulose on the healing of gastric ulcers induced in rats in comparison with that of solid chow. Ulcers were induced in the fundus of the stomach by luminal application of an acetic acid solution. The healing of ulcers could be divided into two phases based on the healing rate: early phase (days 1 to 10) and late phase (days 10 to 20). The liquid diet, but not the combined one, administered for 10 days significantly accelerated ulcer healing in both the early and late phases. The length of the ruptured muscularis mucosa decreased only in the liquid diet group in both phases. Regeneration of the ulcerated mucosa in the chow diet group was observed only in the late phase, it being markedly inhibited in the liquid diet group. The serum gastrin level significantly decreased in the liquid and combined diet groups in contrast to that in the chow group. The liquid and combined diets significantly reduced gastric mucosal DNA synthesis. We conclude that 1) the healing in this gastric ulcer model comprises two phases, and 2) tissue contraction is a major factor for the healing of gastric ulcers in the early phase, while both tissue contraction and regeneration of the ulcerated mucosa are involved in the healing in the late phase. PMID:7723215

  8. Engineered human vascularized constructs accelerate diabetic wound healing.

    PubMed

    Shen, Yu-I; Cho, Hongkwan; Papa, Arianne E; Burke, Jacqueline A; Chan, Xin Yi; Duh, Elia J; Gerecht, Sharon

    2016-09-01

    Stem cell-based therapy is emerging as a promising approach for chronic diabetic wounds, but strategies for optimizing both cellular differentiation and delivery remain as major obstacles. Here, we study bioengineered vascularized constructs as a therapeutic modality for diabetic wound healing. We developed a wound model in immunodeficient rodent and treated it with engineered vascularized constructs from endothelial progenitors or early vascular cells-derived from human induced pluripotent stem cells (hiPSCs) reprogrammed either from healthy donor or type-1 diabetic patient. We found that all vascularized constructs expedited wound closure and reperfusion, with endothelial progenitor constructs having the earliest maximum closure rate followed closely by healthy and diabetic hiPSC-derivative constructs. This was accompanied by rapid granulation layer formation and regression in all vascularized construct groups. Macrophage infiltration into the hydrogel matrix occurred during early stages of healing, seeming to facilitate rapid neovascularization of the wound that could then better persist in the vascularized constructs. Blood perfusion of the human vasculature could be detected after three days, indicating rapid integration with the host vasculature. Overall, we propose a potential therapeutic strategy using allograft or autologous vascularized constructs to treat type-1 diabetic wounds. This approach highlights the unprecedented prospects of designing patient-specific stem cell therapy. PMID:27328431

  9. 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

  10. Accelerated healing of excisional skin wounds by PL 14736 in alloxan-hyperglycemic rats.

    PubMed

    Seveljević-Jaran, D; Cuzić, S; Dominis-Kramarić, M; Glojnarić, I; Ivetić, V; Radosević, S; Parnham, M J

    2006-01-01

    PL 14736 is a synthetic peptide, originally isolated from human gastric juice, that has anti-inflammatory and tissue-protective actions in experimental models of gastrointestinal inflammation. To investigate its possible benefit in poorly healing skin wounds, the effects of the topical application of PL 14736 in a gel formulation have been studied on full-thickness excisional wounds in rats, either healthy or made hyperglycemic by alloxan (175 mg/kg s.c.) 5 days previously. The effects of becaplermin gel (platelet-derived growth factor, PDGF-BB, Regranex, a standard therapy for diabetic foot ulcers, were investigated for comparison. Healing was evaluated for up to 7 days after wounding, using digital planimetry analysis, macroscopic scoring and histology. While healing was too rapid in healthy rats to observe enhancement by either treatment, in the hyperglycemic rats which exhibited delayed healing, PL 14736 (10-1,000 microg/wound) produced a dose-dependent acceleration of wound healing (determined by macroscopic scoring) equivalent at the highest doses to that observed with becaplermin. The beneficial effect on healing was associated with increased deposition of organized granulation tissue by day 7 for both PL 14736 and becaplermin, as determined histologically. PL 14736 tended to have a greater effect than becaplermin on the formation of granulation tissue containing mature collagen. Wound contraction, as measured by planimetry, was not significantly affected. In conclusion, topical PL 14736 produces a dose-dependent acceleration of deficient skin wound healing in hyperglycemic rats by facilitating granulation tissue formation, similar to the response seen with topical becaplermin, the standard therapy for diabetic skin wounds. PL 14736 may represent an alternative therapy for delayed wound healing, such as that seen with diabetic foot ulcers, without the proliferative concerns or immunogenicity associated with growth factors. PMID:16785777

  11. Calcium-Based Nanoparticles Accelerate Skin Wound Healing

    PubMed Central

    Ishise, Hisako; Carre, Antoine Lyonel; Nishimoto, Soh; Longaker, Michael; Lorenz, H. Peter

    2011-01-01

    Introduction Nanoparticles (NPs) are small entities that consist of a hydroxyapatite core, which can bind ions, proteins, and other organic molecules from the surrounding environment. These small conglomerations can influence environmental calcium levels and have the potential to modulate calcium homeostasis in vivo. Nanoparticles have been associated with various calcium-mediated disease processes, such as atherosclerosis and kidney stone formation. We hypothesized that nanoparticles could have an effect on other calcium-regulated processes, such as wound healing. In the present study, we synthesized pH-sensitive calcium-based nanoparticles and investigated their ability to enhance cutaneous wound repair. Methods Different populations of nanoparticles were synthesized on collagen-coated plates under various growth conditions. Bilateral dorsal cutaneous wounds were made on 8-week-old female Balb/c mice. Nanoparticles were then either administered intravenously or applied topically to the wound bed. The rate of wound closure was quantified. Intravenously injected nanoparticles were tracked using a FLAG detection system. The effect of nanoparticles on fibroblast contraction and proliferation was assessed. Results A population of pH-sensitive calcium-based nanoparticles was identified. When intravenously administered, these nanoparticles acutely increased the rate of wound healing. Intravenously administered nanoparticles were localized to the wound site, as evidenced by FLAG staining. Nanoparticles increased fibroblast calcium uptake in vitro and caused contracture of a fibroblast populated collagen lattice in a dose-dependent manner. Nanoparticles also increased the rate of fibroblast proliferation. Conclusion Intravenously administered, calcium-based nanoparticles can acutely decrease open wound size via contracture. We hypothesize that their contraction effect is mediated by the release of ionized calcium into the wound bed, which occurs when the p

  12. 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

  13. Healing

    PubMed Central

    Ventres, William B.

    2016-01-01

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

  14. 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

  15. Targeted Delivery of Lovastatin and Tocotrienol to Fracture Site Promotes Fracture Healing in Osteoporosis Model: Micro-Computed Tomography and Biomechanical Evaluation

    PubMed Central

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

    2014-01-01

    Osteoporosis is becoming a major health problem that is associated with increased fracture risk. Previous studies have shown that osteoporosis could delay fracture healing. Although there are potential agents available to promote fracture healing of osteoporotic bone such as statins and tocotrienol, studies on direct delivery of these agents to the fracture site are limited. This study was designed to investigate the effects of two potential agents, lovastatin and tocotrienol using targeted drug delivery system on fracture healing of postmenopausal osteoporosis rats. The fracture healing was evaluated using micro CT and biomechanical parameters. Forty-eight Sprague-Dawley female rats were divided into 6 groups. The first group was sham-operated (SO), while the others were ovariectomized (OVx). After two months, the right tibiae of all rats were fractured at metaphysis region using pulsed ultrasound and were fixed with plates and screws. The SO and OVxC groups were given two single injections of lovastatin and tocotrienol carriers. The estrogen group (OVx+EST) was given daily oral gavages of Premarin (64.5 µg/kg). The Lovastatin treatment group (OVx+Lov) was given a single injection of 750 µg/kg lovastatin particles. The tocotrienol group (OVx+TT) was given a single injection of 60 mg/kg tocotrienol particles. The combination treatment group (OVx+Lov+TT) was given two single injections of 750 µg/kg lovastatin particles and 60 mg/kg tocotrienol particles. After 4 weeks of treatment, the fractured tibiae were dissected out for micro-CT and biomechanical assessments. The combined treatment group (OVx+Lov+TT) showed significantly higher callus volume and callus strength than the OVxC group (p<0.05). Both the OVx+Lov and OVx+TT groups showed significantly higher callus strength than the OVxC group (p<0.05), but not for callus volume. In conclusion, combined lovastatin and tocotrienol may promote better fracture healing of osteoporotic bone. PMID:25526611

  16. 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

  17. Effects of Sclerostin Antibody on the Healing of Femoral Fractures in Ovariectomised Rats.

    PubMed

    Liu, Yang; Rui, Yunfeng; Cheng, Tin Yan; Huang, Shuo; Xu, Liangliang; Meng, Fanbiao; Lee, Wayne Yuk Wai; Zhang, Ting; Li, Nan; Li, Chaoyang; Ke, Huazhu; Li, Gang

    2016-03-01

    The inhibition of sclerostin by the systemic administration of a monoclonal antibody (Scl-Ab) significantly increased bone mass and strength in fractured bones in animal models and non-fractured bones in ovariectomised (OVX) rats. In this study, the effects of Scl-Ab on healing were examined in a closed fracture model in OVX rats. Sixty Sprague-Dawley rats underwent an ovariectomy or a sham operation at 4 months of age, and a closed fracture of the right femur was performed 3 months later. Subcutaneous injections with Scl-Ab (25 mg/kg) or saline were then administered on day 1 after the fracture and twice a week for 8 weeks (n = 20 per group), at which time the fractured femurs were harvested for micro-computed tomography analysis, four-point bending mechanical testing and histomorphometric analysis to examine bone mass, bone strength and dynamic bone formation at the fracture site. The angiogenesis at the fracture site was also examined. Bone marrow stem cells were also isolated from the fractured bone to perform a colony-forming unit (CFU) assay and an alkaline phosphatase-positive (ALP(+)) CFU assay. OVX rats treated with Scl-Ab for 8 weeks had significantly increased bone mineral density and relative bone volume compared with OVX rats treated with saline. Similarly, maximum loading, energy to maximum load and stiffness in Scl-Ab-treated OVX rats were significantly higher than those in saline controls. The mineral apposition rate (MAR), mineralising surface (MS/BS) and bone formation rate (BFR/BS) were also significantly increased in Scl-Ab-treated group compared with the saline-treated group in OVX rats. Furthermore, the Scl-Ab-treated group had more CFUs and ALP(+) CFUs than the saline-treated group in OVX rats. No significant difference in angiogenesis at the fracture site was found between the groups. Our study demonstrated that Scl-Ab helped to increase bone mass, bone strength and bone formation at the fracture site in a closed femoral fracture

  18. Carcinogenic Parasite Secretes Growth Factor That Accelerates Wound Healing and Potentially Promotes Neoplasia.

    PubMed

    Smout, Michael J; Sotillo, Javier; Laha, Thewarach; Papatpremsiri, Atiroch; Rinaldi, Gabriel; Pimenta, Rafael N; Chan, Lai Yue; Johnson, Michael S; Turnbull, Lynne; Whitchurch, Cynthia B; Giacomin, Paul R; Moran, Corey S; Golledge, Jonathan; Daly, Norelle; Sripa, Banchob; Mulvenna, Jason P; Brindley, Paul J; Loukas, Alex

    2015-10-01

    Infection with the human liver fluke Opisthorchis viverrini induces cancer of the bile ducts, cholangiocarcinoma (CCA). Injury from feeding activities of this parasite within the human biliary tree causes extensive lesions, wounds that undergo protracted cycles of healing, and re-injury over years of chronic infection. We show that O. viverrini secreted proteins accelerated wound resolution in human cholangiocytes, an outcome that was compromised following silencing of expression of the fluke-derived gene encoding the granulin-like growth factor, Ov-GRN-1. Recombinant Ov-GRN-1 induced angiogenesis and accelerated mouse wound healing. Ov-GRN-1 was internalized by human cholangiocytes and induced gene and protein expression changes associated with wound healing and cancer pathways. Given the notable but seemingly paradoxical properties of liver fluke granulin in promoting not only wound healing but also a carcinogenic microenvironment, Ov-GRN-1 likely holds marked potential as a therapeutic wound-healing agent and as a vaccine against an infection-induced cancer of major public health significance in the developing world. PMID:26485648

  19. Carcinogenic Parasite Secretes Growth Factor That Accelerates Wound Healing and Potentially Promotes Neoplasia

    PubMed Central

    Smout, Michael J.; Sotillo, Javier; Laha, Thewarach; Papatpremsiri, Atiroch; Rinaldi, Gabriel; Pimenta, Rafael N.; Chan, Lai Yue; Johnson, Michael S.; Turnbull, Lynne; Whitchurch, Cynthia B.; Giacomin, Paul R.; Moran, Corey S.; Golledge, Jonathan; Daly, Norelle; Sripa, Banchob; Mulvenna, Jason P.

    2015-01-01

    Abstract Infection with the human liver fluke Opisthorchis viverrini induces cancer of the bile ducts, cholangiocarcinoma (CCA). Injury from feeding activities of this parasite within the human biliary tree causes extensive lesions, wounds that undergo protracted cycles of healing, and re-injury over years of chronic infection. We show that O. viverrini secreted proteins accelerated wound resolution in human cholangiocytes, an outcome that was compromised following silencing of expression of the fluke-derived gene encoding the granulin-like growth factor, Ov-GRN-1. Recombinant Ov-GRN-1 induced angiogenesis and accelerated mouse wound healing. Ov-GRN-1 was internalized by human cholangiocytes and induced gene and protein expression changes associated with wound healing and cancer pathways. Given the notable but seemingly paradoxical properties of liver fluke granulin in promoting not only wound healing but also a carcinogenic microenvironment, Ov-GRN-1 likely holds marked potential as a therapeutic wound-healing agent and as a vaccine against an infection-induced cancer of major public health significance in the developing world. PMID:26485648

  20. Combination of low level light therapy and nitrosyl-cobinamide accelerates wound healing

    PubMed Central

    Spitler, Ryan; Ho, Hsiang; Norpetlian, Frederique; Kong, Xiangduo; Jiang, Jingjing; Yokomori, Kyoko; Andersen, Bogi; Boss, Gerry R.; Berns, Michael W.

    2015-01-01

    Abstract. Low level light therapy (LLLT) has numerous therapeutic benefits, including improving wound healing, but the precise mechanisms involved are not well established; in particular, the underlying role of cytochrome C oxidase (C-ox) as the primary photoacceptor and the associated biochemical mechanisms still require further investigation. We previously showed the nitric oxide (NO) donating drug nitrosyl-cobinamide (NO-Cbi) enhances wound healing through a cGMP/cGMP-dependent protein kinase/ERK1/2 mechanism. Here, we show that the combination of LLLT and NO-Cbi markedly improves wound healing compared to either treatment alone. LLLT-enhanced wound healing proceeded through an electron transport chain-C-ox-dependent mechanism with a reduction of reactive oxygen species and increased adenosine triphosphate production. C-ox was validated as the primary photoacceptor by three observations: increased oxygen consumption, reduced wound healing in the presence of sodium azide, and disassociation of cyanide, a known C-ox ligand, following LLLT. We conclude that LLLT and NO-Cbi accelerate wound healing through two independent mechanisms, the electron transport chain-C-ox pathway and cGMP signaling, respectively, with both resulting in ERK1/2 activation. PMID:25562608

  1. Epidermal stem cells (ESCs) accelerate diabetic wound healing via the Notch signalling pathway

    PubMed Central

    Yang, Rong-Hua; Qi, Shao-Hai; Shu, Bin; Ruan, Shu-Bin; Lin, Ze-Peng; Lin, Yan; Shen, Rui; Zhang, Feng-Gang; Chen, Xiao-Dong; Xie, Ju-Lin

    2016-01-01

    Chronic, non-healing wounds are a major complication of diabetes. Recently, various cell therapies have been reported for promotion of diabetic wound healing. Epidermal stem cells (ESCs) are considered a powerful tool for tissue therapy. However, the effect and the mechanism of the therapeutic properties of ESCs in the diabetic wound healing are unclear. Herein, to determine the ability of ESCs to diabetic wound healing, a dorsal skin defect in a streptozotocin (STZ)-induced diabetes mellitus (DM) mouse model was used. ESCs were isolated from mouse skin. We found that both the mRNA and protein levels of a Notch ligand Jagged1 (Jag1), Notch1 and Notch target gene Hairy Enhancer of Split-1 (Hes1) were significantly increased at the wound margins. In addition, we observed that Jag1 was high expressed in ESCs. Overexpression of Jag1 promotes ESCs migration, whereas knockdown Jag1 resulted in a significant reduction in ESCs migration in vitro. Importantly, Jag1 overexpression improves diabetic wound healing in vivo. These results provide evidence that ESCs accelerate diabetic wound healing via the Notch signalling pathway, and provide a promising potential for activation of the Notch pathway for the treatment of diabetic wound. PMID:27129289

  2. Epidermal stem cells (ESCs) accelerate diabetic wound healing via the Notch signalling pathway.

    PubMed

    Yang, Rong-Hua; Qi, Shao-Hai; Shu, Bin; Ruan, Shu-Bin; Lin, Ze-Peng; Lin, Yan; Shen, Rui; Zhang, Feng-Gang; Chen, Xiao-Dong; Xie, Ju-Lin

    2016-08-01

    Chronic, non-healing wounds are a major complication of diabetes. Recently, various cell therapies have been reported for promotion of diabetic wound healing. Epidermal stem cells (ESCs) are considered a powerful tool for tissue therapy. However, the effect and the mechanism of the therapeutic properties of ESCs in the diabetic wound healing are unclear. Herein, to determine the ability of ESCs to diabetic wound healing, a dorsal skin defect in a streptozotocin (STZ)-induced diabetes mellitus (DM) mouse model was used. ESCs were isolated from mouse skin. We found that both the mRNA and protein levels of a Notch ligand Jagged1 (Jag1), Notch1 and Notch target gene Hairy Enhancer of Split-1 (Hes1) were significantly increased at the wound margins. In addition, we observed that Jag1 was high expressed in ESCs. Overexpression of Jag1 promotes ESCs migration, whereas knockdown Jag1 resulted in a significant reduction in ESCs migration in vitro Importantly, Jag1 overexpression improves diabetic wound healing in vivo These results provide evidence that ESCs accelerate diabetic wound healing via the Notch signalling pathway, and provide a promising potential for activation of the Notch pathway for the treatment of diabetic wound. PMID:27129289

  3. Combination of low level light therapy and nitrosyl-cobinamide accelerates wound healing

    NASA Astrophysics Data System (ADS)

    Spitler, Ryan; Ho, Hsiang; Norpetlian, Frederique; Kong, Xiangduo; Jiang, Jingjing; Yokomori, Kyoko; Andersen, Bogi; Boss, Gerry R.; Berns, Michael W.

    2015-05-01

    Low level light therapy (LLLT) has numerous therapeutic benefits, including improving wound healing, but the precise mechanisms involved are not well established; in particular, the underlying role of cytochrome C oxidase (C-ox) as the primary photoacceptor and the associated biochemical mechanisms still require further investigation. We previously showed the nitric oxide (NO) donating drug nitrosyl-cobinamide (NO-Cbi) enhances wound healing through a cGMP/cGMP-dependent protein kinase/ERK1/2 mechanism. Here, we show that the combination of LLLT and NO-Cbi markedly improves wound healing compared to either treatment alone. LLLT-enhanced wound healing proceeded through an electron transport chain-C-ox-dependent mechanism with a reduction of reactive oxygen species and increased adenosine triphosphate production. C-ox was validated as the primary photoacceptor by three observations: increased oxygen consumption, reduced wound healing in the presence of sodium azide, and disassociation of cyanide, a known C-ox ligand, following LLLT. We conclude that LLLT and NO-Cbi accelerate wound healing through two independent mechanisms, the electron transport chain-C-ox pathway and cGMP signaling, respectively, with both resulting in ERK1/2 activation.

  4. Combination of low level light therapy and nitrosyl-cobinamide accelerates wound healing.

    PubMed

    Spitler, Ryan; Ho, Hsiang; Norpetlian, Frederique; Kong, Xiangduo; Jiang, Jingjing; Yokomori, Kyoko; Andersen, Bogi; Boss, Gerry R; Berns, Michael W

    2015-05-01

    Low level light therapy (LLLT) has numerous therapeutic benefits, including improving wound healing, but the precise mechanisms involved are not well established; in particular, the underlying role of cytochrome C oxidase (C-ox) as the primary photoacceptor and the associated biochemical mechanisms still require further investigation. We previously showed the nitric oxide (NO) donating drug nitrosyl-cobinamide (NO-Cbi) enhances wound healing through a cGMP/cGMP-dependent protein kinase/ERK1/2 mechanism. Here, we show that the combination of LLLT and NO-Cbi markedly improves wound healing compared to either treatment alone. LLLT-enhanced wound healing proceeded through an electron transport chain-C-ox-dependent mechanism with a reduction of reactive oxygen species and increased adenosine triphosphate production. C-ox was validated as the primary photoacceptor by three observations: increased oxygen consumption, reduced wound healing in the presence of sodium azide, and disassociation of cyanide, a known C-ox ligand, following LLLT. We conclude that LLLT and NO-Cbi accelerate wound healing through two independent mechanisms, the electron transport chain-C-ox pathway and cGMP signaling, respectively, with both resulting in ERK1/2 activation. PMID:25562608

  5. C5aR-antagonist significantly reduces the deleterious effect of a blunt chest trauma on fracture healing.

    PubMed

    Recknagel, Stefan; Bindl, Ronny; Kurz, Julian; Wehner, Tim; Schoengraf, Philipp; Ehrnthaller, Christian; Qu, Hongchang; Gebhard, Florian; Huber-Lang, Markus; Lambris, John D; Claes, Lutz; Ignatius, Anita

    2012-04-01

    Confirming clinical evidence, we recently demonstrated that a blunt chest trauma considerably impaired fracture healing in rats, possibly via the interaction of posttraumatic systemic inflammation with local healing processes, the underlying mechanisms being unknown. An important trigger of systemic inflammation is the complement system, with the potent anaphylatoxin C5a. Therefore, we investigated whether the impairment of fracture healing by a severe trauma resulted from systemically activated complement. Rats received a blunt chest trauma and a femur osteotomy stabilized with an external fixator. To inhibit the C5a-dependent posttraumatic systemic inflammation, half of the rats received a C5aR-antagonist intravenously immediately and 12 h after the thoracic trauma. Compared to the controls (control peptide), the treatment with the C5aR-antagonist led to a significantly increased flexural rigidity (three-point-bending test), an improved bony bridging of the fracture gap, and a slightly larger and qualitatively improved callus (µCT, histomorphometry) after 35 days. In conclusion, immunomodulation by a C5aR-antagonist could abolish the deleterious effects of a thoracic trauma on fracture healing, possibly by influencing the function of inflammatory and bone cells locally at the fracture site. C5a could possibly represent a target to prevent delayed bone healing in patients with severe trauma. PMID:21922535

  6. Biodegradable nanocomposite coatings accelerate bone healing: In vivo evaluation

    PubMed Central

    Mehdikhani-Nahrkhalaji, Mehdi; Fathi, Mohammad Hossein; Mortazavi, Vajihesadat; Mousavi, Sayed Behrouz; Akhavan, Ali; Haghighat, Abbas; Hashemi-Beni, Batool; Razavi, Sayed Mohammad; Mashhadiabbas, Fatemeh

    2015-01-01

    Background: The aim of this study was to evaluate the interaction of bioactive and biodegradable poly (lactide-co-glycolide)/bioactive glass/hydroxyapatite (PBGHA) and poly (lactide-co-glycolide)/bioactive glass (PBG) nanocomposite coatings with bone. Materials and Methods: Sol-gel derived 58S bioactive glass nanoparticles, 50/50 wt% poly (lactic acid)/poly (glycolic acid) and hydroxyapatite nanoparticles were used to prepare the coatings. The nanocomposite coatings were characterized by scanning electron microscopy, X-ray diffraction and atomic force microscopy. Mechanical stability of the prepared nanocomposite coatings was studied during intramedullary implantation of coated Kirschner wires (K-wires) into rabbit tibia. Titanium mini-screws coated with nanocomposite coatings and without coating were implanted intramedullary in rabbit tibia. Bone tissue interaction with the prepared nanocomposite coatings was evaluated 30 and 60 days after surgery. The non-parametric paired Friedman and Kruskal-Wallis tests were used to compare the samples. For all tests, the level of significance was P < 0.05. Results: The results showed that nanocomposite coatings remained stable on the K-wires with a minimum of 96% of the original coating mass. Tissue around the coated implants showed no adverse reactions to the coatings. Woven and trabecular bone formation were observed around the coated samples with a minimum inflammatory reaction. PBG nanocomposite coating induced more rapid bone healing than PBGHA nanocomposite coating and titanium without coating (P < 0.05). Conclusion: It was concluded that PBG nanocomposite coating provides an ideal surface for bone formation and it could be used as a candidate for coating dental and orthopedic implants. PMID:25709681

  7. Histopathologic and Radiographic evaluation of the electroacupuncture effects on ulna fracture healing in dogs

    PubMed Central

    Naddaf, H.; Baniadam, A.; Esmaeilzadeh, S.; Ghadiri, A.R.; Pourmehdi, M.; Falah, H.; Hosseini, O.; Farmani, F.; Sabiza, S.

    2014-01-01

    Acupuncture can affect bone healing by stimulation of sensory nerves and releasing of local and systemic neuropeptides. The purpose of this experimental study was to evaluate the effects of electroacupuncture on ulna fracture healing in dogs. In this study, 12 healthy dogs were randomly divided in to four equal groups, where group 1 was kept as control group and evaluated for 45 days, group 2: treatment group and evaluated for 45 days, group3: control group of 90 days and group 4: treatment group of 90 days. After induction of anesthesia, the ulna was cut with Gigli wire saw in each groups, 10 days after operation, the treatment (acupuncture) group was treated with 10 minutes electroacupuncture stimulations on the acupoints Kid1, Kid3, Kid6 and Kid7, for 10 days. Histopathologic samples of all dogs were harvested from bone osteotomized site in 45 and 90 days after surgery. Indices like, count of inflammatory cells, cartilaginous tissue, fibrotic tissue and deposition of collagen were evaluated on samples and classified with 0, 1, 2, and 3 degrees. Also, radiographic evaluation of the patients was applied using radiographic scoring system on days: 7, 15, 30, 45, 60 and 90 after surgery. This study revealed that, acupuncture had no effect on bone healing (p>0.05). Cause of non-significant difference changes between the control and treatment groups, and lack of complete healing in both groups may be due to lack of ulna bone fixation. Alternatively, selection of other acupoints in acupuncture could have a better healing role. PMID:26623337

  8. Evaluation of fracture healing and subimplant bone response following fixation with a locking miniplate and screw system for mandibular angle fractures in a sheep model.

    PubMed

    Poon, C C H; Verco, S

    2013-06-01

    This study aims to establish a mandible fracture model, and to review fracture healing following fixation with a locking miniplate system. Eighteen 2-year-old sheep were divided into three groups of six. Each animal had a single fracture that was anatomically reduced and internally fixed by a single 4-hole plate with two monocortical screws each side of the fracture. The fractures were internally fixed with poorly contoured conventional miniplates or poorly contoured mini-locking plate or well contoured conventional miniplates. Two sheep in each of the three groups were killed at 2, 4 and 8 weeks after surgery. The mandibles were radiographed then decalcified specimens were reviewed microscopically. No clinical difference was observed between the groups. All fractures were at an advanced stage of bony union by 4 weeks. Fracture union appeared radiographically more advanced with the locking plate system. This study established a protocol for simulating a fracture model for the study of fracture healing. A more advanced stage of union was seen for fractures internally fixed with locking plates/screws than with a conventional system. The observations suggest the purported biological benefits of locking miniplate system do exist. PMID:23374732

  9. 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

  10. 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

  11. He-Ne laser irradiation acceleration of healing process of open gingival wounds in cats

    NASA Astrophysics Data System (ADS)

    Abramovici, Armand; Roisman, P.; Hirsch, A.; Segal, S.; Fischer, J.

    1994-09-01

    A histopathological study on the effect of He-Ne laser treatment on the evolution of cat gingiva open wounds is presented. The irradiation initiates first a massive inflammatory cell exudate together with an antiedematic effect after the second postoperative day. A substantial acceleration of the healing process is noted on the sixth day among irradiated tissues as compared to the operated gingiva which still shows, at this period of time, inflammatory exudate and isolated fibroblasts. The persistence of inflammatory exudate and edema among the untreated gingiva seemed to have a delaying effect upon the healing process. The biostimulatory effect of soft laser seems to act photodynamically both at the intracellular level and extracellular millieu, thus promoting the proliferative capacity of fibroblasts and capillary buds formation necessary for a rapid differentiation of connective tissue. The controlled application of He-Ne laser treatment is suggested in dental healing procedures.

  12. 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

  13. 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

  14. Bilateral first rib anomalous articulations with pseudarthroses mimicking healing fractures in an infant with abusive head injury.

    PubMed

    Pasquale-Styles, Melissa A; Crowder, Christian M; Fridie, Jeannette; Milla, Sarah S

    2014-11-01

    Bilateral symmetric bone nodules were observed in the anterolateral first ribs of an infant with shaking injuries at autopsy. The location prompted diagnostic considerations of healing fractures versus anomalous articulations with pseudarthroses. The forensic pathologist worked with forensic anthropologists and pediatric radiologists to evaluate autopsy findings and compare premortem and postmortem X-rays. Gross examination of the bones by the pathologist and anthropologists confirmed bilateral, callus-like bone nodules in first-rib locations associated with pseudarthroses. Histologic examination of one of the bones further showed features most consistent with pseudarthrosis, not a healing fracture. Radiologists then compared multiple premortem and postmortem radiographs that showed no remodeling of the bone over a 2-week interval between the time of injury and death, which would be unexpected for a healing fracture in an infant. This multidisciplinary approach resulted in the appropriate diagnosis of pseudarthroses due to anomalous articulations, an uncommon finding in forensic pathology. PMID:25382601

  15. Biafine topical emulsion accelerates excisional and burn wound healing in mice.

    PubMed

    Krausz, Aimee E; Adler, Brandon L; Landriscina, Angelo; Rosen, Jamie M; Musaev, Tagai; Nosanchuk, Joshua D; Friedman, Adam J

    2015-09-01

    Macrophages play a fundamental role in wound healing; therefore, employing a strategy that enhances macrophage recruitment would be ideal. It was previously suggested that the mechanism by which Biafine topical emulsion improves wound healing is via enhanced macrophage infiltration into the wound bed. The purpose of this study was to confirm this observation through gross and histologic assessments of wound healing using murine full-thickness excisional and burn wound models, and compare to common standards, Vaseline and silver sulfadiazine (SSD). Full-thickness excisional and burn wounds were created on two groups of 60 mice. In the excisional arm, mice were divided into untreated control, Biafine, and Vaseline groups. In the burn arm, mice were divided into untreated control, Biafine, and SSD groups. Daily treatments were administered and healing was measured over time. Wound tissue was excised and stained to appropriately visualize morphology, collagen, macrophages, and neutrophils. Collagen deposition was measured and cell counts were performed. Biafine enhanced wound healing in murine full-thickness excisional and burn wounds compared to control, and surpassed Vaseline and SSD in respective wound types. Biafine treatment accelerated wound closure clinically, with greater epidermal/dermal maturity, granulation tissue formation, and collagen quality and arrangement compared to other groups histologically. Biafine application was associated with greater macrophage and lower neutrophil infiltration at earlier stages of healing when compared to other study groups. In conclusion, Biafine can be considered an alternative topical therapy for full-thickness excisional and burn wounds, owing to its advantageous biologically based wound healing properties. PMID:25794496

  16. A bioengineered drug-Eluting scaffold accelerated cutaneous wound healing In diabetic mice.

    PubMed

    Yin, Hao; Ding, Guoshan; Shi, Xiaoming; Guo, Wenyuan; Ni, Zhijia; Fu, Hong; Fu, Zhiren

    2016-09-01

    Hyperglycemia in diabetic patients can greatly hinder the wound healing process. In this study we investigated if the engagement of F4/80(+) murine macrophages could accelerate the cutaneous wound healing in streptozotocin induced diabetic mice. To facilitate the engagement of macrophages, we engineered a drug-eluting electrospun scaffold with a payload of monocyte chemoattractant protein-1 (MCP-1). MCP-1 could be readily released from the scaffold within 3 days. The electrospun scaffold showed no cytotoxic effects on human keratinocytes in vitro. Full-thickness excisional cutaneous wound was created in diabetic mice. The wound fully recovered within 10 days in mice treated with the drug-eluting scaffold. In contrast, the wound took 14 days to fully recover in control groups. The use of drug-eluting scaffold also improved the re-epithelialization. Furthermore, we observed a larger population of F4/80(+) macrophages in the wound bed of mice treated with drug-eluting scaffolds on day 3. This marked increase of macrophages in the wound bed could have contributed to the accelerated wound healing. Our study shed new light on an immuno-engineering solution for wound healing management in diabetic patients. PMID:27187186

  17. Reduced FOXO1 Expression Accelerates Skin Wound Healing and Attenuates Scarring

    PubMed Central

    Mori, Ryoichi; Tanaka, Katsuya; de Kerckhove, Maiko; Okamoto, Momoko; Kashiyama, Kazuya; Tanaka, Katsumi; Kim, Sangeun; Kawata, Takuya; Komatsu, Toshimitsu; Park, Seongjoon; Ikematsu, Kazuya; Hirano, Akiyoshi; Martin, Paul; Shimokawa, Isao

    2015-01-01

    The forkhead box O (FOXO) family has been extensively investigated in aging and metabolism, but its role in tissue-repair processes remains largely unknown. Herein, we clarify the molecular aspect of the FOXO family in skin wound healing. We demonstrated that Foxo1 and Foxo3a were both up-regulated during murine skin wound healing. Partial knockout of Foxo1 in Foxo1+/− mice throughout the body led to accelerated skin wound healing with enhanced keratinocyte migration, reduced granulation tissue formation, and decreased collagen density, accompanied by an attenuated inflammatory response, but we observed no wound phenotype in Foxo3a−/− mice. Fibroblast growth factor 2, adiponectin, and notch1 genes were significantly increased at wound sites in Foxo1+/− mice, along with markedly altered extracellular signal–regulated kinase 1/2 and AKT phosphorylation. Similarly, transient knockdown of Foxo1 at the wound site by local delivery of antisense oligodeoxynucleotides enhanced skin wound healing. The link between FOXO1 and scarring extends to patients, in particular keloid scars, where we see FOXO1 expression markedly increased in fibroblasts and inflammatory cells within the otherwise normal dermis. This occurs in the immediate vicinity of the keloid by comparison to the center of the mature keloid, indicating that FOXO1 is associated with the overgrowth of this fibrotic response into adjacent normal skin. Overall, our data indicate that molecular targeting of FOXO1 may improve the quality of healing and reduce pathological scarring. PMID:25010393

  18. 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

  19. 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

  20. 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

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

    PubMed

    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

  2. Odanacatib increases mineralized callus during fracture healing in a rabbit ulnar osteotomy model.

    PubMed

    Pennypacker, Brenda L; Gilberto, David; Gatto, Nicholas T; Samadfam, Rana; Smith, Susan Y; Kimmel, Donald B; Duong, Le Thi

    2016-01-01

    The effects of the cathepsin K inhibitor odanacatib (ODN) on fracture healing were monitored for ~6 and 15 weeks post-fracture in two separate studies using the unilateral transverse mid-ulnar osteotomy model in skeletally mature female rabbits. Rabbits were pre-treated for 3-4 weeks with vehicle (Veh), ODN (2 mg/kg, po, daily), or alendronate (ALN) (0.3 mg/kg, sc, twice-weekly) prior to osteotomy. In Study 1, the animals were maintained on the same respective treatment for ~6 weeks. In Study 2, the animals were also continued on the same therapy or switched from Veh to ODN or ODN to Veh for 15 weeks. No treatment-related impairment of fracture union was seen by qualitative histological assessments in the first study. Cartilage retention was detected in the calluses of ALN-treated rabbits at week-6, while calluses in the ODN and Veh groups contained bony tissue with significantly less residual cartilage. ODN treatment also markedly increased the number of cathepsin K-(+) osteoclasts in the callus, indicating enhanced callus remodeling. From the second study, ex vivo DXA and pQCT confirmed that ODN treatment pre- and post-osteotomy increased callus bone mineral content and bone mineral density (BMD) versus Veh (p < 0.001) and discontinuation of ODN post-surgery returned callus BMD to Veh. Peak load of ODN- or ALN-treated calluses were comparable to Veh. ODN increased callus yield load (20%, p = 0.056) and stiffness (26%, p < 0.05) versus Veh. These studies demonstrated that ODN increased mineralized callus during the early phase of fracture repair without impairing callus formation or biomechanical integrity at the fracture site. PMID:26178170

  3. Tobacco extract but not nicotine impairs the mechanical strength of fracture healing in rats.

    PubMed

    Skott, Martin; Andreassen, Troels T; Ulrich-Vinther, Michael; Chen, X; Keyler, Dan E; LeSage, Mark G; Pentel, Paul R; Bechtold, Joan E; Soballe, Kjeld

    2006-07-01

    The influence of nicotine and tobacco extract (without nicotine) alone and in combination on and mechanical strength of closed femoral fractures in rats was investigated. One hundred four male Sprague-Dawley rats were divided into four groups receiving: nicotine, tobacco extract, tobacco extract plus nicotine, and saline. One week prior to fracture, osmotic pumps were implanted subcutaneously in all animals to administer nicotine equivalent to the serum level of nicotine observed in a smoker consuming one to two packs of cigarettes daily. An equivalent volume of saline was administered to the control animals. Tobacco extract was administered orally. A closed transverse femoral diaphysial fracture was performed, and stabilized with an intramedullary pin. The fractures were mechanically tested after 21 days of healing. Tobacco extract alone decreased the mechanical strength. Ultimate torque and torque at yield point of the tobacco extract group were decreased by 21% (p=0.010) and 23% (p=0.056), respectively, compared with the vehicle (saline) group, and by 20% (p=0.023) and 26% (p=0.004), respectively, compared with the nicotine group. No difference was found between the tobacco extract and tobacco extract plus nicotine groups. An 18% (p=0.013) reduction in torque at yield point was observed in the tobacco extract plus nicotine group compared with the nicotine group. No differences in ultimate stiffness, energy absorption, and callus bone mineral content at the fracture line were found between any of the groups. Serum levels of nicotine were between 40-50 ng/mL in the group given nicotine alone and the group given tobacco extract plus nicotine (equivalent to serum levels observed in persons smoking one to two packs of cigarettes per day). PMID:16705735

  4. 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

  5. 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

  6. 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

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

    PubMed Central

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

    2015-01-01

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

  8. Application of Coenzyme Q10 for Accelerating Soft Tissue Wound Healing after Tooth Extraction in Rats

    PubMed Central

    Yoneda, Toshiki; Tomofuji, Takaaki; Kawabata, Yuya; Ekuni, Daisuke; Azuma, Tetsuji; Kataoka, Kota; Kunitomo, Muneyoshi; Morita, Manabu

    2014-01-01

    Accelerating wound healing after tooth extraction is beneficial in dental treatment. Application of antioxidants, such as reduced coenzyme Q10 (rCoQ10), may promote wound healing after tooth extraction. In this study, we examined the effects of topical application of rCoQ10 on wound healing after tooth extraction in rats. After maxillary first molars were extracted, male Fischer 344 rats (8 weeks old) (n = 27) received topical application of ointment containing 5% rCoQ10 (experimental group) or control ointment (control group) to the sockets for 3 or 8 days (n = 6–7/group). At 3 days after extraction, the experimental group showed higher collagen density and lower numbers of polymorphonuclear leukocytes in the upper part of socket, as compared to the control group (p < 0.05). Gene expression of interleukin-1β, tumor necrosis factor-α and nuclear factor-κB were also lower in the experimental group than in the control group (p < 0.05). At 8 days after tooth extraction, there were no significant differences in collagen density, number of polymorphonuclear leukocytes and bone fill between the groups. Our results suggest that topical application of rCoQ10 promotes wound healing in the soft tissue of the alveolar socket, but that rCoQ10 has a limited effect on bone remodeling in rats. PMID:25514392

  9. Blumea balsamifera Oil for the Acceleration of Healing of Burn Injuries.

    PubMed

    Fan, Zuo-Wang; Pang, Yu-Xin; Wang, Kai; Yu, Fu-Lai; Wang, Dan; Yang, Quan; Ma, Qing-Song; Li, Xiao-Ting; Zou, Jin; Zhang, Wen-Qing; Wu, Li-Fen

    2015-01-01

    Blumea balsamifera oil (BBO) is a main extract obtained from Blumea balsamifera (L.) DC (Ainaxiang) leaves, which are widely used as a traditional medicine by the Miao and Li Nations to promote skin trauma or burn injury healing. This study was initiated to investigate the healing efficacy in deep second-degree burn model in rats. The rats were treated by BBO for 21 consecutive days. The rate of healing, scabs dropped time and re-epithelialization time were observed every three days for 21 days after burn injury. The samples were collected from different treated rats by sacrificing the animals on the 1st, 2nd, 5th, 9th, 14th, and 21st day post-burn creation. Then, the water content of burn tissue was measured. Plasma interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α) levels were evaluated, and the tissue expressions of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and transforming growth factor-beta (TGF-β) were determined along with skin histopathology. The results showed that the water content of tissue was significantly reduced, the scabs dropped time shortened, and healing accelerated after treatment with BBO in the burn injury rats. Furthermore, the expressions of growth factors were significantly increased in the tissue; however, the levels of inflammatory factors on plasma decreased. This study confirms the efficacy of BBO consumption on burn injuries. PMID:26393555

  10. Potential Activity of 3-(2-Chlorophenyl)-1-phenyl-propenonein Accelerating Wound Healing in Rats

    PubMed Central

    Dhiyaaldeen, Summaya M.; Alshawsh, Mohammed A.; Salama, Suzy M.; Alwajeeh, Nahla S. I.

    2014-01-01

    Wound healing involves inflammation followed by granular tissue development and scar formation. In this study, synthetic chalcone 3-(2-Chlorophenyl)-1-phenyl-propenone (CPPP) was investigated for a potential role in enhancing wound healing and closure. Twenty-four male rats were divided randomly into 4 groups: carboxymethyl cellulose (CMC) (0.2 mL), Intrasite gel, and CPPP (25 or 50 mg/mL). Gross morphology, wounds treatment with the CPPP, and Intrasite gel accelerate the rate of wound healing compared to CMC group. Ten days after surgery, the animals were sacrificed. Histological assessment revealed that the wounds treated with CPPP showed that wound closure site contained little amount of scar and the granulation tissue contained more collagen and less inflammatory cells than wound treated with CMC. This finding was confirmed with Masson's trichrome staining. The antioxidant defence enzymes catalase (CAT) and superoxide dismutase (SOD) were significantly increased in the wound homogenates treated with CPPP (P < 0.05) compared to CMC treated group. However, in the CPPP treatment group, lipid peroxidation (MDA) was significantly decreased (P < 0.05), suggesting that the CPPP also has an important role in protection against lipid peroxidation-induced skin injury after ten days of treatment with CPPP, which is similar to the values of cytokines TGF-β and TNF-α in tissue homogenate. Finally the administration of CPPP at a dosage of 25 and 50 mg/kg was suitable for the stimulation of wound healing. PMID:24587992

  11. In Vivo Hypobaric Hypoxia Performed During the Remodeling Process Accelerates Bone Healing in Mice

    PubMed Central

    Durand, Marjorie; Collombet, Jean-Marc; Frasca, Sophie; Begot, Laurent; Lataillade, Jean-Jacques; Le Bousse-Kerdilès, Marie-Caroline

    2014-01-01

    We investigated the effects of respiratory hypobaric hypoxia on femoral bone-defect repair in mice because hypoxia is believed to influence both mesenchymal stromal cell (MSC) and hematopoietic stem cell mobilization, a process involved in the bone-healing mechanism. To mimic conditions of non-weight-bearing limb immobilization in patients suffering from bone trauma, our hypoxic mouse model was further subjected to hind-limb unloading. A hole was drilled in the right femur of adult male C57/BL6J mice. Four days after surgery, mice were subjected to hind-limb unloading for 1 week. Seven days after surgery, mice were either housed for 4 days in a hypobaric room (FiO2 at 10%) or kept under normoxic conditions. Unsuspended control mice were housed in either hypobaric or normoxic conditions. Animals were sacrificed on postsurgery day 11 to allow for collection of both contralateral and lesioned femurs, blood, and spleen. As assessed by microtomography, delayed hypoxia enhanced bone-healing efficiency by increasing the closing of the cortical defect and the newly synthesized bone volume in the cavity by +55% and +35%, respectively. Proteome analysis and histomorphometric data suggested that bone-repair improvement likely results from the acceleration of the natural bone-healing process rather than from extended mobilization of MSC-derived osteoprogenitors. Hind-limb unloading had hardly any effect beyond delayed hypoxia-enhanced bone-healing efficiency. PMID:24944208

  12. 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

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

    PubMed Central

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

    2011-01-01

    fracture healing, as assessed by the reduced callus volumes and reduced callus scores. This extract is beneficial for fractures in osteoporotic states. PMID:21789393

  14. Young coconut juice can accelerate the healing process of cutaneous wounds

    PubMed Central

    2012-01-01

    Background Estrogen has been reported to accelerate cutaneous wound healing. This research studies the effect of young coconut juice (YCJ), presumably containing estrogen-like substances, on cutaneous wound healing in ovairectomized rats. Methods Four groups of female rats (6 in each group) were included in this study. These included sham-operated, ovariectomized (ovx), ovx receiving estradiol benzoate (EB) injections intraperitoneally, and ovx receiving YCJ orally. Two equidistant 1-cm full-thickness skin incisional wounds were made two weeks after ovariectomy. The rats were sacrificed at the end of the third and the fourth week of the study, and their serum estradiol (E2) level was measured by chemiluminescent immunoassay. The skin was excised and examined in histological sections stained with H&E, and immunostained using anti-estrogen receptor (ER-α an ER-β) antibodies. Results Wound healing was accelerated in ovx rats receiving YCJ, as compared to controls. This was associated with significantly higher density of immunostaining for ER-α an ER-β in keratinocytes, fibroblasts, white blood cells, fat cells, sebaceous gland, skeletal muscles, and hair shafts and follicles. This was also associated with thicker epidermis and dermis, but with thinner hypodermis. In addition, the number and size of immunoreactive hair follicles for both ER-α and ER-β were the highest in the ovx+YCJ group, as compared to the ovx+EB group. Conclusions This study demonstrates that YCJ has estrogen-like characteristics, which in turn seem to have beneficial effects on cutaneous wound healing. PMID:23234369

  15. Serpina3n accelerates tissue repair in a diabetic mouse model of delayed wound healing

    PubMed Central

    Hsu, I; Parkinson, L G; Shen, Y; Toro, A; Brown, T; Zhao, H; Bleackley, R C; Granville, D J

    2014-01-01

    Chronic, non-healing wounds are a major complication of diabetes and are characterized by chronic inflammation and excessive protease activity. Although once thought to function primarily as a pro-apoptotic serine protease, granzyme B (GzmB) can also accumulate in the extracellular matrix (ECM) during chronic inflammation and cleave ECM proteins that are essential for proper wound healing, including fibronectin. We hypothesized that GzmB contributes to the pathogenesis of impaired diabetic wound healing through excessive ECM degradation. In the present study, the murine serine protease inhibitor, serpina3n (SA3N), was administered to excisional wounds created on the dorsum of genetically induced type-II diabetic mice. Wound closure was monitored and skin wound samples were collected for analyses. Wound closure, including both re-epithelialization and contraction, were significantly increased in SA3N-treated wounds. Histological and immunohistochemical analyses of SA3N-treated wounds revealed a more mature, proliferative granulation tissue phenotype as indicated by increased cell proliferation, vascularization, fibroblast maturation and differentiation, and collagen deposition. Skin homogenates from SA3N-treated wounds also exhibited greater levels of full-length intact fibronectin compared with that of vehicle wounds. In addition, GzmB-induced detachment of mouse embryonic fibroblasts correlated with a rounded and clustered phenotype that was prevented by SA3N. In summary, topical administration of SA3N accelerated wound healing. Our findings suggest that GzmB contributes to the pathogenesis of diabetic wound healing through the proteolytic cleavage of fibronectin that is essential for normal wound closure, and that SA3N promotes granulation tissue maturation and collagen deposition. PMID:25299783

  16. Drug loaded composite oxidized pectin and gelatin networks for accelerated wound healing.

    PubMed

    Tummalapalli, Mythili; Berthet, Morgane; Verrier, Bernard; Deopura, B L; Alam, M S; Gupta, Bhuvanesh

    2016-05-30

    Biocomposite interactive wound dressings have been designed and fabricated using oxidized pectin (OP), gelatin and nonwoven cotton fabric. Due to their inherent virtues of antimicrobial activity and cytocompatibility, these composite structures are capable of redirecting the healing cascade and influencing cell attachment and proliferation. A novel in situ reduction process has been followed to synthesize oxidized pectin-gelatin-nanosilver (OP-Gel-NS) flower like nanohydrocolloids. This encapsulation technology controls the diffusion and permeation of nanosilver into the surrounding biological tissues. Ciprofloxacin hydrochloride has also been incorporated into the OP-Gel matrix to produce OP-Gel-Cipro dressings. While OP-Gel-NS dressings exhibited 100% antimicrobial activity at extremely low loadings of 3.75μg/cm(2), OP-Gel-Cipro dressings were highly antimicrobial at 1% drug loading. While NIH3T3 mouse fibroblasts proliferated remarkably well when cultured with OP-Gel and OP-Gel-Cipro dressings, OP-Gel-NS hindered cell growth and Bactigras(®) induced complete lysis. Full thickness excisional wounds were created on C57BL/6J mice and the wound healing potential of the OP-Gel-NS dressings led to accelerated healing within 12days, while OP-Gel-Cipro dressings healed wounds at a rate similar to that of Bactigras(®). Histological examination revealed that OP-Gel-NS and OP-Gel-Cipro treatment led to organized collagen deposition, neovascularization and nuclei migration, unlike Bactigras(®). Therefore, the OP-Gel-NS and OP-Gel-Cipro biocomposite dressings exhibiting good hydrophilicity, sustained antimicrobial nature, promote cell growth and proliferation, and lead to rapid healing, can be considered viable candidates for effective management. PMID:27063849

  17. Accelerated reepithelialization by triterpenes: proof of concept in the healing of surgical skin lesions.

    PubMed

    Metelmann, Hans-Robert; Brandner, Johanna M; Schumann, Hauke; Bross, Felix; Fimmers, Rolf; Böttger, Kerstin; Scheffler, Armin; Podmelle, Fred

    2015-01-01

    The acceleration of wound healing is a major surgical concern. A triterpene extract from birch bark (Betulae cortex) experimentally enhances keratinocyte differentiation in vitro and accelerates wound healing ex vivo. We conducted an open, blind-evaluated, controlled, prospective, randomized (1:1) phase II clinical trial in patients requiring split-thickness skin graft transplantation at two university hospitals in Germany. Donor sites on the upper legs were covered with a moist silicone-coated dressing. Oleogel-S10 ointment containing 10% birch bark extract was randomly applied to the distal or proximal half of the wound, with the other half serving as an intraindividual control, for 14 days after the skin graft surgery. The primary efficacy variable was faster reepithelialization as determined from macrophotographs by independent, blinded experts. Twenty-four patients were randomized and completed the trial. After the 14-day test period, the planned interim analysis revealed a highly significant (p < 0.0001) superiority of Oleogel-S10 in the primary efficacy variable and the trial was terminated early due to ethical concerns. The treatment side was also better reepithelialized and more similar to normal skin after 3 months. In conclusion, Oleogel-S10 significantly accelerated reepithelialization at split-thickness skin graft donor sites. Treatment with Oleogel-S10 was safe and well tolerated. PMID:25034442

  18. Healing of 400 intra-alveolar root fractures. 2. Effect of treatment factors such as treatment delay, repositioning, splinting type and period and antibiotics.

    PubMed

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

    2004-08-01

    This is the second part of a retrospective study of 400 root-fractured permanent incisors. In this article, the effect of various treatment procedures is analyzed. Treatment delay, i.e. treatment later than 24 h after injury, did not change the root fracture healing pattern, healing with hard tissue between fragments (HH1), interposition of bone and/or periodontal ligament (PDL) or pulp necrosis (NEC). When initial displacement did not exceed 1 mm, optimal repositioning appeared to significantly enhance both the likelihood of pulpal healing and hard tissue repair (HH1). Significant differences in healing were found among the different splinting techniques. The lowest frequency of healing was found with cap splints and the highest with fiberglass or Kevlar splints. The latter splinting procedure showed almost the same healing result as non-splinting. Comparison between non-splinting and splinting for non-displaced teeth was found to reveal no benefit from splinting. With respect to root fractures with displacement, too few cases were available for analysis. No beneficial effect of splinting periods greater than 4 weeks could be demonstrated. The administration of antibiotics had the paradoxical effect of promoting both HH1 and NEC. No explanation could be found. It was concluded that, optimal repositioning seems to favor healing. Furthermore, the chosen splinting method appears to be related to healing of root fractures, with a preference to pulp healing and healing fusion of fragments to a certain flexibility of the splint and possibly also non-traumatogenic splint application. Splinting for more than 4 weeks was not found to influence the healing pattern. A certain treatment delay (a few days) appears not to result in inferior healing. The role of antibiotics upon fracture healing is questionable. PMID:15245519

  19. Accelerated healing of cutaneous leishmaniasis in non-healing BALB/c mice using water soluble amphotericin B-polymethacrylic acid

    PubMed Central

    Corware, Karina; Harris, Debra; Teo, Ian; Rogers, Matthew; Naresh, Kikkeri; Müller, Ingrid; Shaunak, Sunil

    2011-01-01

    Cutaneous leishmaniasis (CL) is a neglected tropical disease that causes prominent skin scaring. No water soluble, non-toxic, short course and low cost treatment exists. We developed a new water soluble amphotericin B-polymethacrylic acid (AmB-PMA) using established and scalable chemistries. AmB-PMA was stable for 9 months during storage. In vitro, it was effective against Leishmania spp. promastigotes and amastigote infected macrophages. It was also less toxic and more effective than deoxycholate-AmB, and similar to liposomal AmB. Its in vivo activity was determined in both early and established CL lesion models of Leishmania major infection in genetically susceptible non-healing BALB/c mice. Intradermal AmB-PMA at a total dose of 18 mg of AmB/kg body weight led to rapid parasite killing and lesion healing. No toxicity was seen. No parasite relapse occurred after 80 days follow-up. Histological studies confirmed rapid parasite clearance from macrophages followed by accelerated fibroblast mediated tissue repair, regeneration and cure of the infection. Quantitative mRNA studies of the CL lesions showed that accelerated healing was associated with increased Tumor Necrosis Factor-α and Interferon-γ, and reduced Interleukin-10. These results suggest that a cost-effective AmB-PMA could be used to pharmacologically treat and immunotherapeutically accelerate the healing of CL lesions. PMID:21807409

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

    PubMed Central

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

    2014-01-01

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

  1. 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. PMID:25801536

  2. Magnetic Resonance Imaging of Postoperative Fracture Healing Process without Metal Artifact: A Preliminary Report of a Novel Animal Model.

    PubMed

    Jin, Zhe; Guan, Yuheng; Yu, Guibo; Sun, Yu

    2016-01-01

    Background. Early radiological diagnosis and continual monitoring are of ultimate importance for timely treatment of delayed union, nonunion, and infection after bone fracture surgery. Although magnetic resonance imaging (MRI) could provide superior detailed images compared with X-ray and computed tomography (CT) without ionizing radiation, metal implants used for fracture fixation lead to abundant artifacts on MRI and thus prohibit accurate interpretation. The authors develop a novel intramedullary fixation model of rat femoral fracture using polyetheretherketone (PEEK) threaded rods and investigate its feasibility for in vivo MRI monitoring of the fracture healing process without artifact. Methods. Femoral fractures of 3 adult male Sprague-Dawley rats were fixed with intramedullary PEEK threaded rods. X-ray and MRI examinations were performed at day 7 postoperatively. Radiological images were analyzed for the existence of artifact interruption and postoperative changes in bone and peripheral soft tissue. Results. Postoperative plain film revealed no loss of reduction. MRI images illustrated the whole length of femur and peripheral tissue without artifact interruption, and the cortical bone, implanted PEEK rod, and soft tissue were clearly illustrated. Conclusion. This preliminary study introduced a novel rat model for in vivo MRI monitoring of the fracture healing process without metal artifact, by using intramedullary fixation of femur with PEEK threaded rod. PMID:27123442

  3. Magnetic Resonance Imaging of Postoperative Fracture Healing Process without Metal Artifact: A Preliminary Report of a Novel Animal Model

    PubMed Central

    Jin, Zhe; Guan, Yuheng; Yu, Guibo

    2016-01-01

    Background. Early radiological diagnosis and continual monitoring are of ultimate importance for timely treatment of delayed union, nonunion, and infection after bone fracture surgery. Although magnetic resonance imaging (MRI) could provide superior detailed images compared with X-ray and computed tomography (CT) without ionizing radiation, metal implants used for fracture fixation lead to abundant artifacts on MRI and thus prohibit accurate interpretation. The authors develop a novel intramedullary fixation model of rat femoral fracture using polyetheretherketone (PEEK) threaded rods and investigate its feasibility for in vivo MRI monitoring of the fracture healing process without artifact. Methods. Femoral fractures of 3 adult male Sprague-Dawley rats were fixed with intramedullary PEEK threaded rods. X-ray and MRI examinations were performed at day 7 postoperatively. Radiological images were analyzed for the existence of artifact interruption and postoperative changes in bone and peripheral soft tissue. Results. Postoperative plain film revealed no loss of reduction. MRI images illustrated the whole length of femur and peripheral tissue without artifact interruption, and the cortical bone, implanted PEEK rod, and soft tissue were clearly illustrated. Conclusion. This preliminary study introduced a novel rat model for in vivo MRI monitoring of the fracture healing process without metal artifact, by using intramedullary fixation of femur with PEEK threaded rod. PMID:27123442

  4. Traditional Japanese Formula Kigikenchuto Accelerates Healing of Pressure-Loading Skin Ulcer in Rats

    PubMed Central

    Kimura, Mari; Shibahara, Naotoshi; Hikiami, Hiroaki; Yoshida, Toshiko; Jo, Michiko; Kaneko, Maria; Nogami, Tatsuya; Fujimoto, Makoto; Goto, Hirozo; Shimada, Yutaka

    2011-01-01

    We evaluated the effect of kigikenchuto (KKT), a traditional Japanese formula, in a modified rat pressure-loading skin ulcer model. Rats were divided into three groups, KKT extract orally administered (250 or 500 mg/kg/day for 35 days) and control. KKT shortened the duration until healing. Immunohistochemically, KKT increased CD-31-positive vessels in early phase and increased α-smooth muscle actin-(α-SMA-) positive fibroblastic cells in early phase and decreased them in late phase of wound healing. By Western blotting, KKT showed the potential to decrease inflammatory cytokines (MCP-1, IL-1β, and TNF-α) in early phase, decrease vascular endothelial growth factor in early phase and increase it in late phase, and modulate the expression of extracellular protein matrix (α-SMA, TGF-β1, bFGF, collagen III, and collagen I). These results suggested the possibility that KKT accelerates pressure ulcer healing through decreases of inflammatory cytokines, increase of angiogenesis, and induction of extracellular matrix remodeling. PMID:21660308

  5. Cinnamtannin B-1 Promotes Migration of Mesenchymal Stem Cells and Accelerates Wound Healing in Mice.

    PubMed

    Fujita, Kosuke; Kuge, Katsunori; Ozawa, Noriyasu; Sahara, Shunya; Zaiki, Kaori; Nakaoji, Koichi; Hamada, Kazuhiko; Takenaka, Yukiko; Tanahashi, Takao; Tamai, Katsuto; Kaneda, Yasufumi; Maeda, Akito

    2015-01-01

    Substances that enhance the migration of mesenchymal stem cells to damaged sites have the potential to improve the effectiveness of tissue repair. We previously found that ethanol extracts of Mallotus philippinensis bark promoted migration of mesenchymal stem cells and improved wound healing in a mouse model. We also demonstrated that bark extracts contain cinnamtannin B-1, a flavonoid with in vitro migratory activity against mesenchymal stem cells. However, the in vivo effects of cinnamtannin B-1 on the migration of mesenchymal stem cells and underlying mechanism of this action remain unknown. Therefore, we examined the effects of cinnamtannin B-1 on in vivo migration of mesenchymal stem cells and wound healing in mice. In addition, we characterized cinnamtannin B-1-induced migration of mesenchymal stem cells pharmacologically and structurally. The mobilization of endogenous mesenchymal stem cells into the blood circulation was enhanced in cinnamtannin B-1-treated mice as shown by flow cytometric analysis of peripheral blood cells. Whole animal imaging analysis using luciferase-expressing mesenchymal stem cells as a tracer revealed that cinnamtannin B-1 increased the homing of mesenchymal stem cells to wounds and accelerated healing in a diabetic mouse model. Additionally, the cinnamtannin B-1-induced migration of mesenchymal stem cells was pharmacologically susceptible to inhibitors of phosphatidylinositol 3-kinase, phospholipase C, lipoxygenase, and purines. Furthermore, biflavonoids with similar structural features to cinnamtannin B-1 also augmented the migration of mesenchymal stem cells by similar pharmacological mechanisms. These results demonstrate that cinnamtannin B-1 promoted mesenchymal stem cell migration in vivo and improved wound healing in mice. Furthermore, the results reveal that cinnamtannin B-1-induced migration of mesenchymal stem cells may be mediated by specific signaling pathways, and the flavonoid skeleton may be relevant to its effects on

  6. Cinnamtannin B-1 Promotes Migration of Mesenchymal Stem Cells and Accelerates Wound Healing in Mice

    PubMed Central

    Fujita, Kosuke; Kuge, Katsunori; Ozawa, Noriyasu; Sahara, Shunya; Zaiki, Kaori; Nakaoji, Koichi; Hamada, Kazuhiko; Takenaka, Yukiko; Tanahashi, Takao; Tamai, Katsuto; Kaneda, Yasufumi; Maeda, Akito

    2015-01-01

    Substances that enhance the migration of mesenchymal stem cells to damaged sites have the potential to improve the effectiveness of tissue repair. We previously found that ethanol extracts of Mallotus philippinensis bark promoted migration of mesenchymal stem cells and improved wound healing in a mouse model. We also demonstrated that bark extracts contain cinnamtannin B-1, a flavonoid with in vitro migratory activity against mesenchymal stem cells. However, the in vivo effects of cinnamtannin B-1 on the migration of mesenchymal stem cells and underlying mechanism of this action remain unknown. Therefore, we examined the effects of cinnamtannin B-1 on in vivo migration of mesenchymal stem cells and wound healing in mice. In addition, we characterized cinnamtannin B-1-induced migration of mesenchymal stem cells pharmacologically and structurally. The mobilization of endogenous mesenchymal stem cells into the blood circulation was enhanced in cinnamtannin B-1-treated mice as shown by flow cytometric analysis of peripheral blood cells. Whole animal imaging analysis using luciferase-expressing mesenchymal stem cells as a tracer revealed that cinnamtannin B-1 increased the homing of mesenchymal stem cells to wounds and accelerated healing in a diabetic mouse model. Additionally, the cinnamtannin B-1-induced migration of mesenchymal stem cells was pharmacologically susceptible to inhibitors of phosphatidylinositol 3-kinase, phospholipase C, lipoxygenase, and purines. Furthermore, biflavonoids with similar structural features to cinnamtannin B-1 also augmented the migration of mesenchymal stem cells by similar pharmacological mechanisms. These results demonstrate that cinnamtannin B-1 promoted mesenchymal stem cell migration in vivo and improved wound healing in mice. Furthermore, the results reveal that cinnamtannin B-1-induced migration of mesenchymal stem cells may be mediated by specific signaling pathways, and the flavonoid skeleton may be relevant to its effects on

  7. 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

  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. 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.

  10. Localization of submicron inclusion re-equilibration at healed fractures in host garnet

    NASA Astrophysics Data System (ADS)

    Griffiths, T. A.; Habler, G.; Rhede, D.; Wirth, R.; Ram, F.; Abart, R.

    2014-12-01

    Microstructures in Permian inclusion-bearing metapegmatite garnets from the Koralpe (Eastern Alps, Austria) reveal re-equilibration by coarsening of abundant submicron-sized inclusions (1 μm-2 nm diameter) at the site of healed brittle cracks. The microstructures developed during Cretaceous eclogite-facies deformation and the related overprinting of the host-inclusion system. Trails of coarsened inclusions (1-10 μm diameter) crosscut the garnet, defining traces of former fractures with occasional en-echelon overlaps. Trails are flanked by 10- to 100-μm-wide `bleaching zones' characterized by the absence of ≤1-μm-sized inclusions in optical and SE images. FEG-microprobe data show that trails and bleaching zones can form isochemically, although some trails exhibit non-isochemical coarsening. Cross-correlation-based EBSD analysis reveals garnet lattice rotation of up to 0.45°, spatially correlated with bleaching zones. The garnet lattice in the center of trails is misoriented around different axes with respect to the lattice either side of the trail. Elevated dislocation density within bleaching zones is confirmed by TEM observations. Dislocations represent a plastic wake formed by crystal plastic deformation at the crack tip. Fracture enhanced diffusion rates in the lattice adjacent to crack planes by introducing dislocations, priming these areas to behave differently to the bulk of the garnet during Cretaceous metamorphism and facilitating localized coarsening of inclusions. Diffusion within the bleaching zone was enhanced by a minimum factor of 102. The partially closed host-inclusion system records the influence of deformation mechanisms on re-equilibration and contributes to understanding of the interaction between deformation and chemical reaction during metamorphism.

  11. Gene gun transferring-bone morphogenetic protein 2 (BMP-2) gene enhanced bone fracture healing in rabbits

    PubMed Central

    Li, Wenju; Wei, Haifeng; Xia, Chunmei; Zhu, Xiaomeng; Hou, Guozhu; Xu, Feng; Song, Xinghua; Zhan, Yulin

    2015-01-01

    Purpose: Transferring the bone morphogenetic protein 2 (BMP-2) genes into the tissues or cells can improve the bone healing of the fracture has been widely accepted. We evaluated the efficiency of using gene gun to transfer the BMP-2 gene thereby affected the healing of a fractured bone. Methods: The vector coding for BMP-2 was constructed by a non-replicating encephalo-myocarditis virus (ECMV)-based vector. The segmental bone defect (1.5 cm) model was created by a wire-saw at the middle part of the radius bone of the New Zealand white rabbits. Then either BMP-2 gene or control vector without BMP-2 gene was injected into the tissues around the fracture site. Healing of the defects was monitored radiographically for 9 weeks, bone consolidation was determined by the Lane-Sandhu score pre- and post-operatively, which can evaluated bone formation, bone connect and bone plasticity. Results: The radiographic score and bone consolidation rates were significantly higher in animals injected with BMP-2 gene group as compared with control vector-injected animals (P<0.05). The control group still showed no radiological signs of stable healing. Western-blot and RT-PCR showed BMP-2 expression was significant increase in the tissues around the site of osseous lesions in comparison with the control vector-injected animals (P<0.05). Conclusions: Our results suggested that BMP-2 gene transferred by gene gun could increase the expression of BMP-2 protein and improved the bone callus formation therefore shortened the time of bone defect healing. PMID:26884910

  12. 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

  13. 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

  14. 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

  15. 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

  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. Prediction of the Time Course of Callus Stiffness as a Function of Mechanical Parameters in Experimental Rat Fracture Healing Studies - A Numerical Study

    PubMed Central

    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

  18. Acceleration of Wound Healing by α-gal Nanoparticles Interacting with the Natural Anti-Gal Antibody

    PubMed Central

    Galili, Uri

    2015-01-01

    Application of α-gal nanoparticles to wounds and burns induces accelerated healing by harnessing the natural anti-Gal antibody which constitutes ~1% of human immunoglobulins. α-gal nanoparticles present multiple α-gal epitopes (Galα1-3Galβ1-4GlcNAc-R), the carbohydrate ligand of anti-Gal. Studied α-gal nanoparticles were comprised of glycolipids with α-gal epitopes, phospholipids, and cholesterol. Binding of anti-Gal to α-gal nanoparticles in wounds activates the complement cascade, resulting in formation of chemotactic complement cleavage peptides that induce rapid recruitment of many macrophages. The Fc/Fcγ receptors interaction between anti-Gal coating α-gal nanoparticles and the recruited macrophages activates macrophages to produce cytokines/growth factors that promote wound healing and recruit stem cells. Studies of wound healing by α-gal nanoparticles were feasible in α1,3galactosyltransferase knockout mice and pigs. In contrast to other nonprimate mammals, these mice and pigs lack the α-gal epitope, and thus they are not immunotolerant to it and produce anti-Gal. Treatment of skin wounds and burns with α-gal nanoparticles resulted in 40–60% decrease in healing time in comparison with control wounds treated with saline. This accelerated healing is associated with increased recruitment of macrophages and extensive angiogenesis in wounds, faster regrowth of epidermis, and regeneration of the dermis. The accelerated healing further decreases and may completely eliminate fibrosis and scar formation in wounds. Since healing of internal injuries is mediated by mechanisms similar to those in external wound healing, it is suggested that α-gal nanoparticles treatment may also improve regeneration and restoration of biological function following internal injuries such as surgical incisions, myocardial ischemia following infarction, and nerve injuries. PMID:25922849

  19. Acceleration of wound healing by α-gal nanoparticles interacting with the natural anti-Gal antibody.

    PubMed

    Galili, Uri

    2015-01-01

    Application of α-gal nanoparticles to wounds and burns induces accelerated healing by harnessing the natural anti-Gal antibody which constitutes ~1% of human immunoglobulins. α-gal nanoparticles present multiple α-gal epitopes (Galα1-3Galβ1-4GlcNAc-R), the carbohydrate ligand of anti-Gal. Studied α-gal nanoparticles were comprised of glycolipids with α-gal epitopes, phospholipids, and cholesterol. Binding of anti-Gal to α-gal nanoparticles in wounds activates the complement cascade, resulting in formation of chemotactic complement cleavage peptides that induce rapid recruitment of many macrophages. The Fc/Fcγ receptors interaction between anti-Gal coating α-gal nanoparticles and the recruited macrophages activates macrophages to produce cytokines/growth factors that promote wound healing and recruit stem cells. Studies of wound healing by α-gal nanoparticles were feasible in α1,3galactosyltransferase knockout mice and pigs. In contrast to other nonprimate mammals, these mice and pigs lack the α-gal epitope, and thus they are not immunotolerant to it and produce anti-Gal. Treatment of skin wounds and burns with α-gal nanoparticles resulted in 40-60% decrease in healing time in comparison with control wounds treated with saline. This accelerated healing is associated with increased recruitment of macrophages and extensive angiogenesis in wounds, faster regrowth of epidermis, and regeneration of the dermis. The accelerated healing further decreases and may completely eliminate fibrosis and scar formation in wounds. Since healing of internal injuries is mediated by mechanisms similar to those in external wound healing, it is suggested that α-gal nanoparticles treatment may also improve regeneration and restoration of biological function following internal injuries such as surgical incisions, myocardial ischemia following infarction, and nerve injuries. PMID:25922849

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

    PubMed

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

    2015-09-01

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

  1. Qualitative and quantitative assessment of bone fragility and fracture healing using conventional radiography and advanced imaging technologies--focus on wrist fracture.

    PubMed

    Firoozabadi, Reza; Morshed, Saam; Engelke, Klaus; Prevrhal, Sven; Fierlinger, Anke; Miclau, Theodore; Genant, Harry K

    2008-09-01

    Fractures of the distal radius are one of the most common injuries presented to orthopaedic surgeons. A variety of treatment options are available for the vast array of fracture patterns. Research that explores bone fragility and fracture healing has led to new treatment modalities. As new products and methods are derived to aid in fracture healing it is essential to develop noninvasive and/or nondestructive techniques to assess structural information about bone. Quantitative assessment of macro-structural characteristics such as geometry, and microstructural features such as relative trabecular volume, trabecular spacing, and connectivity may improve our ability to estimate bone strength. Methods for quantitatively assessing macrostructure include (besides conventional radiographs) dual x-ray absorptiometry (DXA) and computed tomography (CT), particularly volumetric quantitative computed tomography (vQCT). Methods for assessing microstructure of trabecular bone include high resolution computed tomography (hrCT), micro computed tomography (microCT), high resolution magnetic resonance (hrMR), and micro magnetic resonance microMR. Volumetric QCT, hrCT and hrMR are generally applicable in vivo; microCT and microMR are principally applicable in vitro. Clinically, the challenges for bone imaging include balancing the advantages of simple bone densitometry versus the more complex architectural features of bone, or the deeper research requirements versus the broader clinical needs. PMID:18753895

  2. The Effects of RANKL Inhibition on Fracture Healing and Bone Strength in a Mouse Model of Osteogenesis Imperfecta

    PubMed Central

    Delos, D.; Yang, X.; Ricciardi, B.F.; Myers, E.R.; Bostrom, M.P.G.; Pleshko Camacho, N.

    2009-01-01

    Summary Currently, the standard treatment for osteogenesis imperfecta (OI) is bisphosphonate therapy. Recent studies, however, have shown delayed healing of osteotomies in a subset of OI patients treated with such agents. The current study sought to determine the effects of another therapy, RANKL inhibition, on bone healing and bone strength in the growing oim/oim mouse, a model of moderate-to-severe OI. Mice (73 oim/oim and 69 wildtype (WT)) were injected twice weekly with either soluble murine RANK (RANK-Fc) (1.5mg/kg) or saline beginning at 6 weeks of age. At 8 weeks of age, the animals underwent transverse mid-diaphyseal osteotomies of the right femur. Therapy was continued until sacrifice at 2, 3, 4 or 6 weeks post-fracture. At 6 weeks post-fracture, greater callus area (6.59±3.78mm2 vs 2.67±2.05mm2, p=0.003) and increased radiographic intensity (mineral density) (0.48 ± 0.14 vs. 0.30 ± 0.80, p=0.005) were found in the RANK-Fc vs saline oim/oim group, indicating a delay in callus remodeling. Despite this delay, mechanical tests at 6 weeks post-fracture revealed no significant differences in whole bone properties of stiffness and failure moment. Further, RANKL inhibition resulted in a greater failure moment and greater work to failure for the non-fractured contralateral WT bones compared to the non-fractured saline WT bones. Together, these results demonstrate that RANKL-inhibition does not adversely affect the mechanical properties of healing bone in the oim/oim mice, and is associated with increased strength in intact bone in the WT mice. PMID:17729310

  3. Prolonged Survival of Transplanted Osteoblastic Cells Does Not Directly Accelerate the Healing of Calvarial Bone Defects.

    PubMed

    Kitami, Megumi; Kaku, Masaru; Rocabado, Juan Marcelo Rosales; Ida, Takako; Akiba, Nami; Uoshima, Katsumi

    2016-09-01

    Considering the increased interest in cell-based bone regeneration, it is necessary to reveal the fate of transplanted cells and their substantive roles in bone regeneration. The aim of this study was to analyze the fate of transplanted cells and the effect of osteogenic cell transplantation on calvarial bone defect healing. An anti-apoptotic protein, heat shock protein (HSP) 27, was overexpressed in osteoblasts. Then, the treated osteoblasts were transplanted to calvarial bone defect and their fate was analyzed to evaluate the significance of transplanted cell survival. Transient overexpression of Hsp27 rescued MC3T3-E1 osteoblastic cells from H2 O2 -induced apoptosis without affecting osteoblastic differentiation in culture. Transplantation of Hsp27-overexpressing cells, encapsulated in collagen gel, showed higher proliferative activity, and fewer apoptotic cells in comparison with control cells. After 4-week of transplantation, both control cell- and Hsp27 overexpressed cell-transplanted groups showed significantly higher new bone formation in comparison with cell-free gel-transplantation group. Interestingly, the prolonged survival of transplanted osteoblastic cells by Hsp27 did not provide additional effect on bone healing. The transplanted cells in collagen gel survived for up to 4-week but did not differentiate into bone-forming osteoblasts. In conclusion, cell-containing collagen gel accelerated calvarial bone defect healing in comparison with cell-free collagen gel. However, prolonged survival of transplanted cells by Hsp27 overexpression did not provide additional effect. These results strongly indicate that cell transplantation-based bone regeneration cannot be explained only by the increment of osteogenic cells. Further studies are needed to elucidate the practical roles of transplanted cells that will potentiate successful bone regeneration. J. Cell. Physiol. 231: 1974-1982, 2016. © 2016 Wiley Periodicals, Inc. PMID:26754153

  4. Combination of adrenomedullin with its binding protein accelerates cutaneous wound healing.

    PubMed

    Idrovo, Juan-Pablo; Yang, Weng-Lang; Jacob, Asha; Ajakaiye, Michael A; Cheyuo, Cletus; Wang, Zhimin; Prince, Jose M; Nicastro, Jeffrey; Coppa, Gene F; Wang, Ping

    2015-01-01

    Cutaneous wound continues to cause significant morbidity and mortality in the setting of diseases such as diabetes and cardiovascular diseases. Despite advances in wound care management, there is still an unmet medical need exists for efficient therapy for cutaneous wound. Combined treatment of adrenomedullin (AM) and its binding protein-1 (AMBP-1) is protective in various disease conditions. To examine the effect of the combination treatment of AM and AMBP-1 on cutaneous wound healing, full-thickness 2.0-cm diameter circular excision wounds were surgically created on the dorsum of rats, saline (vehicle) or AM/AMBP-1 (96/320 μg kg BW) was topically applied to the wound daily and wound size measured. At days 3, 7, and 14, skin samples were collected from the wound sites. AM/AMBP-1 treated group had significantly smaller wound surface area than the vehicle group over the 14-day time course. At day 3, AM/AMBP-1 promoted neutrophil infiltration (MPO), increased cytokine levels (IL-6 and TNF-α), angiogenesis (CD31, VEGF and TGFβ-1) and cell proliferation (Ki67). By day 7 and 14, AM/AMBP-1 treatment decreased MPO, followed by a rapid resolution of inflammation characterized by a decrease in cytokines. At the matured stage, AM/AMBP-1 treatment increased the alpha smooth muscle actin expression (mature blood vessels) and Masson-Trichrome staining (collagen deposition) along the granulation area, and increased MMP-9 and decreased MMP-2 mRNA expressions. TGFβ-1 mRNA levels in AM/AMBP-1 group were 5.3 times lower than those in the vehicle group. AM/AMBP-1 accelerated wound healing by promoting angiogenesis, collagen deposition and remodeling. Treatment also shortened the days to reach plateau for wound closure. Thus, AM/AMBP-1 may be further developed as a therapeutic for cutaneous wound healing. PMID:25781901

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

    PubMed

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

    2004-08-01

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

  6. Topical Aloe Vera (Aloe barbadensis Miller) Extract Does Not Accelerate the Oral Wound Healing in Rats.

    PubMed

    Coelho, Fernanda Hack; Salvadori, Gabriela; Rados, Pantelis Varvaki; Magnusson, Alessandra; Danilevicz, Chris Krebs; Meurer, Luise; Martins, Manoela Domingues

    2015-07-01

    The effect of topical application of Aloe Vera (Aloe barbadensis Miller) extract was assessed on the healing of rat oral wounds in an in vivo model using 72 male Wistar rats divided into three groups (n = 24): control, placebo and Aloe Vera (0.5% extract hydroalcoholic). Traumatic ulcers were caused in the dorsum of the tongue using a 3-mm punch tool. The Aloe Vera and placebo group received two daily applications. The animals were sacrificed after 1, 5, 10 and 14 days. Clinical analysis (ulcer area and percentage of repair) and histopathological analysis (degree of re-epithelialization and inflammation) were performed. The comparison of the differences between scores based on group and experimental period, both in quantitative and semi-quantitative analyses, was performed using the Kruskal-Wallis test. The significance level was 5%. On day 1, all groups showed predominantly acute inflammatory infiltrate. On day 5, there was partial epithelialization and chronic inflammatory infiltrate. On the days 10 and 14 total repair of ulcers was observed. There was no significant difference between groups in the repair of mouth ulcers. It is concluded that treatment using Aloe Vera as an herbal formulation did not accelerate oral wound healing in rats. PMID:25891093

  7. Electrospun tilapia collagen nanofibers accelerating wound healing via inducing keratinocytes proliferation and differentiation.

    PubMed

    Zhou, Tian; Wang, Nanping; Xue, Yang; Ding, Tingting; Liu, Xin; Mo, Xiumei; Sun, Jiao

    2016-07-01

    The development of biomaterials with the ability to induce skin wound healing is a great challenge in biomedicine. In this study, tilapia skin collagen sponge and electrospun nanofibers were developed for wound dressing. The collagen sponge was composed of at least two α-peptides. It did not change the number of spleen-derived lymphocytes in BALB/c mice, the ratio of CD4(+)/CD8(+) lymphocytes, and the level of IgG or IgM in Sprague-Dawley rats. The tensile strength and contact angle of collagen nanofibers were 6.72±0.44MPa and 26.71±4.88°, respectively. They also had good thermal stability and swelling property. Furthermore, the nanofibers could significantly promote the proliferation of human keratinocytes (HaCaTs) and stimulate epidermal differentiation through the up-regulated gene expression of involucrin, filaggrin, and type I transglutaminase in HaCaTs. The collagen nanofibers could also facilitate rat skin regeneration. In the present study, electrospun biomimetic tilapia skin collagen nanofibers were succesfully prepared, were proved to have good bioactivity and could accelerate rat wound healing rapidly and effectively. These biological effects might be attributed to the biomimic extracellular matrix structure and the multiple amino acids of the collagen nanofibers. Therefore, the cost-efficient tilapia collagen nanofibers could be used as novel wound dressing, meanwhile effectively avoiding the risk of transmitting animal disease in the future clinical apllication. PMID:27037778

  8. Obestatin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats

    PubMed Central

    Matuszyk, Aleksandra; Ceranowicz, Piotr; Warzecha, Zygmunt; Cieszkowski, Jakub; Bonior, Joanna; Jaworek, Jolanta; Kuśnierz-Cabala, Beata; Konturek, Peter; Ambroży, Tadeusz; Dembiński, Artur

    2016-01-01

    Obestatin, a 23-amino acid peptide derived from the proghrelin, has been shown to exhibit some protective and therapeutic effects in the gut. The aim of present study was to determine the effect of obestatin administration on the course of acetic acid-induced colitis in rats. Materials and Methods. Studies have been performed on male Wistar rats. Colitis was induced by a rectal enema with 3.5% acetic acid solution. Obestatin was administered intraperitoneally twice a day at a dose of 8 nmol/kg, starting 24 h after the induction of colitis. Seven or 14 days after the induction of colitis, the healing rate of the colon was evaluated. Results. Treatment with obestatin after induction of colitis accelerated the healing of colonic wall damage and this effect was associated with a decrease in the colitis-evoked increase in mucosal activity of myeloperoxidase and content of interleukin-1β. Moreover, obestatin administration significantly reversed the colitis-evoked decrease in mucosal blood flow and DNA synthesis. Conclusion. Administration of exogenous obestatin exhibits therapeutic effects in the course of acetic acid-induced colitis and this effect is related, at least in part, to the obestatin-evoked anti-inflammatory effect, an improvement of local blood flow, and an increase in cell proliferation in colonic mucosa. PMID:26798415

  9. 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 Central

    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. PMID:24260576

  10. 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

  11. 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

  12. 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. PMID:1201463

  13. Effects of black cohosh (Cimicifuga racemosa) and estrogen on metaphyseal fracture healing in the early stage of osteoporosis in ovariectomized rats.

    PubMed

    Kolios, Leila; Schumann, Jacob; Sehmisch, Stephan; Rack, Thomas; Tezval, Mohammed; Seidlova-Wuttke, Dana; Frosch, Karl-Heinz; Stuermer, Klaus Michael; Stuermer, Ewa Klara

    2010-06-01

    Osteoporosis and its accompanying, predominantly metaphyseal, fractures are a major health problem. Black cohosh (Cimicifuga racemosa) and estrogen positively influence osteoporotic bone. Both substances may improve fracture healing in early osteoporosis as well. In 48 twelve-week-old ovariectomized or, respectively, sham-operated (SHAM) rats, a standardized metaphyseal tibia osteotomy with bridging T-plate fixation was performed. During the healing process of 35 days, rats received soy-free (SHAM, osteopenic C), estrogen- (E) or Cimicifuga racemosa- (CR) supplemented diets. After sacrifice, the callus formation was analyzed with regard to biomechanical quality, morphology, quantity, time course of new bone built and gene expression. CR induced a high rate of metaphyseal callus formation. The biomechanical properties and the amount of new callus formation indicated that fracture healing was still in progress. Therefore, gene expression of osteoblasts was comparatively high. Body weight and the trabecular structure were influenced little by CR. Estrogen improved the biomechanical properties of the callus. Resistance to microfracturing was significantly enhanced in the E group and even superior to SHAM. Remodeling of the callus formation had already begun. The trabecular network and the typical endosteal fracture healing were especially improved. Osteoporotic metaphyseal fracture healing was improved by estrogen more than by Cimicifuga racemosa. The process of fracture healing occurred nearly physiologically. The generation of callus formation was supported by Cimicifuga racemosa as well, but the five-week duration of application was too short for Cimicifuga racemosa to show its complete potential. Already-initiated Cimicifuga racemosa therapy for menopausal symptoms could be continued during fracture healing without hesitation. PMID:20104444

  14. Accelerating skin wound healing by M-CSF through generating SSEA-1 and -3 stem cells in the injured sites

    PubMed Central

    Li, Yunyuan; Jalili, Reza Baradar; Ghahary, Aziz

    2016-01-01

    Wound healing is a complicated process requiring the collaborative efforts of different cell lineages. Our recent studies have found that one subset of hematopoietic cells can be induced to dedifferentiate into multipotent stem cells by means of a proliferating fibroblast releasable factor, M-CSF. Understanding the importance of stem cells on skin wound healing, here we evaluate the biological significance of M-CSF on skin wound healing. In an in vivo mouse skin excisional wound model, we found that SSEA-positive stem cells were present in wounded but not normal skin. After isolating skin cells from either normal or wounded skin by collagenase digestion, and analyzing the SSEA-1 positive cells by flow cytometry, we found a significant increase in the number of SSEA-1 positive cells in wounded skin. Topical application of M-CSF in skin wounds accelerated healing remarkably, while application of M-CSF-neutralizing antibody slowed wound healing. Furthermore, injection of EGFP-labeled hematopoietic cell-derived stem cells generated from M-CSF treated splenocytes resulted in EGFP-labeled cells being enriched in the skin wound site and further differentiated into functional organ-specific cells. Together, these data demonstrated that M-CSF makes a significant contribution to the healing process by inducing hematopoietic cell dedifferentiation into stem cells. PMID:27363517

  15. 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

  16. 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

  17. Systemically delivered insulin-like growth factor-I enhances mesenchymal stem cell-dependent fracture healing

    PubMed Central

    MYERS, TIMOTHY J.; YAN, YUN; GRANERO-MOLTO, FROILAN; WEIS, JARED A.; LONGOBARDI, LARA; LI, TIESHI; LI, YING; CONTALDO, CLARA; OZKHAN, HUSEYIN; SPAGNOLI, ANNA

    2013-01-01

    In this study, we examined the effectiveness of systemic subcutaneous delivery of recombinant Insulin-like growth factor (IGF)-I concurrently with primary cultured bone marrow-derived mesenchymal stem cell (MSC) transplant on fracture repair. We found that the fracture callus volume increased in mice with a stabilized tibia fracture that received IGF-I + MSC when compared with that in either untreated or MSC alone treated mice. In evaluating the callus tissue components, we found that the soft and new bone tissue volumes were significantly increased in IGF-I + MSC recipients. Histological and in-situ hybridization analyses confirmed a characteristic increase of newly forming bone in IGF-I + MSC recipients and that healing progressed mostly through endochondral ossification. The increase in soft and new bone tissue volumes correlated with increased force and toughness as determined by biomechanical testing. In conclusion, MSC transplant concurrent with systemic delivery of IGF-I improves fracture repair suggesting that IGF-I + MSC could be a novel therapeutic approach in patients who have inadequate fracture repair. PMID:22559791

  18. Interaction of Age and Mechanical Stability on Bone Defect Healing: An Early Transcriptional Analysis of Fracture Hematoma in Rat

    PubMed Central

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

    2014-01-01

    Among other stressors, age and mechanical constraints significantly influence regeneration cascades in bone healing. Here, our aim was to identify genes and, through their functional annotation, related biological processes that are influenced by an interaction between the effects of mechanical fixation stability and age. Therefore, at day three post-osteotomy, chip-based whole-genome gene expression analyses of fracture hematoma tissue were performed for four groups of Sprague-Dawley rats with a 1.5-mm osteotomy gap in the femora with varying age (12 vs. 52 weeks - biologically challenging) and external fixator stiffness (mechanically challenging). From 31099 analysed genes, 1103 genes were differentially expressed between the six possible combinations of the four groups and from those 144 genes were identified as statistically significantly influenced by the interaction between age and fixation stability. Functional annotation of these differentially expressed genes revealed an association with extracellular space, cell migration or vasculature development. The chip-based whole-genome gene expression data was validated by q-RT-PCR at days three and seven post-osteotomy for MMP-9 and MMP-13, members of the mechanosensitive matrix metalloproteinase family and key players in cell migration and angiogenesis. Furthermore, we observed an interaction of age and mechanical stimuli in vitro on cell migration of mesenchymal stromal cells. These cells are a subpopulation of the fracture hematoma and are known to be key players in bone regeneration. In summary, these data correspond to and might explain our previously described biomechanical healing outcome after six weeks in response to fixation stiffness variation. In conclusion, our data highlight the importance of analysing the influence of risk factors of fracture healing (e.g. advanced age, suboptimal fixator stability) in combination rather than alone. PMID:25187955

  19. Effect of isolated fractures on accelerated flow in unsaturated porous rock

    USGS Publications Warehouse

    Su, G.W.; Nimmo, J.R.; Dragila, M.I.

    2003-01-01

    Fractures that begin and end in the unsaturated zone, or isolated fractures, have been ignored in previous studies because they were generally assumed to behave as capillary barriers and remain nonconductive. We conducted a series of experiments using Berea sandstone samples to examine the physical mechanisms controlling flow in a rock containing a single isolated fracture. The input fluxes and fracture orientation were varied in these experiments. Visualization experiments using dyed water in a thin vertical slab of rock were conducted to identify flow mechanisms occurring due to the presence of the isolated fracture. Two mechanisms occurred: (1) localized flow through the rock matrix in the vicinity of the isolated fracture and (2) pooling of water at the bottom of the fracture, indicating the occurrence of film flow along the isolated fracture wall. These mechanisms were observed at fracture angles of 20 and 60 degrees from the horizontal, but not at 90 degrees. Pooling along the bottom of the fracture was observed over a wider range of input fluxes for low-angled isolated fractures compared to high-angled ones. Measurements of matrix water pressures in the samples with the 20 and 60 degree fractures also demonstrated that preferential flow occurred through the matrix in the fracture vicinity, where higher pressures occurred in the regions where faster flow was observed in the visualization experiments. The pooling length at the terminus of a 20 degree isolated fracture was measured as a function of input flux. Calculations of the film flow rate along the fracture were made using these measurements and indicated that up to 22% of the flow occurred as film flow. These experiments, apparently the first to consider isolated fractures, demonstrate that such features can accelerate flow through the unsaturated zone and should be considered when developing conceptual models.

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

    PubMed

    Zhang, Leiming; Wang, Hongsheng; Wang, Tian; Jiang, Na; Yu, Pengfei; Liu, Feiyan; Chong, Yating; Fu, Fenghua

    2012-04-01

    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

  1. 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

  2. Healing Sacral Fracture Masquerading as Metastatic Bone Disease on a 68Ga-PSMA PET/CT.

    PubMed

    Gykiere, Pieterjan; Goethals, Lode; Everaert, Hendrik

    2016-07-01

    Prostate-specific membrane antigen (PSMA) is a cell surface glycoprotein, which is frequently overexpressed on prostate cancer cells. A Ga-PSMA PET/CT can be used for early detection of lymph node or bone metastases after radical prostatectomy when there is biochemical recurrence. This report describes PSMA uptake in a healing fracture masquerading as metastatic bone disease in a patient with a history of prostate adenocarcinoma. Clinicians reporting Ga-PSMA PET/CT should be aware of this potential important pitfall. PMID:27055135

  3. The use of low output laser therapy to accelerate healing of diabetic foot ulcers: a randomized prospective controlled trial

    NASA Astrophysics Data System (ADS)

    Naidu, S. V. L. G.; Subapriya, S.; Yeoh, C. N.; Soosai, S.; Shalini, V.; Harwant, S.

    2005-11-01

    The aim of this study was to assess the effects of low output laser therapy as an adjuvant treatment in grade 1 diabetic foot ulcers. Methods: Sixteen patients were randomly divided equally into two groups. Group A had daily dressing only, while group B had low output laser therapy instituted five days a week in addition to daily dressing. Serial measurement of the ulcer was done weekly using digital photography and analyzed. Results: The rate of healing in group A was 10.42 mm2/week, and in group B was 66.14mm2/week. The difference in the rate of healing was statistically significant, p<0.05. Conclusion: Laser therapy as an adjuvant treatment accelerates diabetic ulcer healing by six times in a six week period.

  4. Combined nitric oxide-releasing poly(vinyl alcohol) film/F127 hydrogel for accelerating wound healing.

    PubMed

    Schanuel, Fernanda Seabra; Raggio Santos, Karen Slis; Monte-Alto-Costa, Andréa; de Oliveira, Marcelo G

    2015-06-01

    Nitric oxide (NO) releasing biomaterials represent a potential strategy for use as active wound dressings capable of accelerating wound healing. Topical NO-releasing poly(vinyl alcohol) (PVA) films and Pluronic F127 hydrogels (F127) have already exhibited effective skin vasodilation and wound healing actions. In this study, we functionalized PVA films with SNO groups via esterification with a mixture of mercaptosucinic acid (MSA) and thiolactic acid (TLA) followed by S-nitrosation of the SH moieties. These films were combined with an underlying layer of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), i.e., PEO-PPO-PEO (Pluronic F127) hydrogel and used for the topical treatment of skin lesions in an animal model. The mixed esterification of PVA with MSA and TLA led to chemically crosslinked PVA-SNO films with a high swelling capacity capable of spontaneously releasing NO. Real time NO-release measurements revealed that the hydrogel layer reduces the initial NO burst from the PVA-SNO films. We demonstrate that the combination of PVA-SNO films with F127 hydrogel accelerates wound contraction, decreases wound gap and cellular density and accelerates the inflammatory phase of the lesion. These results were reflected in an increase in myofibroblastic differentiation and collagen type III expression in the cicatricial tissue. Therefore, PVA-SNO films combined with F127 hydrogel may represent a new approach for active wound dressings capable of accelerating wound healing. PMID:25907598

  5. The use of 18F-fluoride and 18F-FDG PET scans to assess fracture healing in a rat femur model

    PubMed Central

    Hsu, W. K.; Feeley, B. T.; Krenek, L.; Stout, D. B.; Chatziioannou, A. F.; Lieberman, J. R.

    2011-01-01

    Purpose Currently available diagnostic techniques can be unreliable in the diagnosis of delayed fracture healing in certain clinical situations, which can lead to increased complication rates and costs to the health care system. This study sought to determine the utility of positron emission tomography (PET) scanning with 18F-fluoride ion, which localizes in regions of high osteoblastic activity, and 18F-fluorodeoxyglucose (FDG), an indicator of cellular glucose metabolism, in assessing bone healing in a rat femur fracture model. Methods Fractures were created in the femurs of immuno-competent rats. Animals in group I had a fracture produced via a manual three-point bending technique. Group II animals underwent a femoral osteotomy with placement of a 2-mm silastic spacer at the fracture site. Fracture healing was assessed with plain radiographs, 18F-fluoride, and 18F-FDG PET scans at 1, 2, 3, and 4-week time points after surgery. Femoral specimens were harvested for histologic analysis and manual testing of torsional and bending strength 4 weeks after surgery. Results All fractures in group I revealed abundant callus formation and bone healing, while none of the nonunion femurs were healed via assessment with manual palpation, radiographic, and histologic evaluation at the 4-week time point. 18F-fluoride PET images of group I femurs at successive 1-week intervals revealed progressively increased signal uptake at the union site during fracture repair. In contrast, minimal tracer uptake was seen at the fracture sites in group II at all time points after surgery. Data analysis revealed statistically significant differences in mean signal intensity between groups I and II at each weekly interval. No significant differences between the two groups were seen using 18F-FDG PET imaging at any time point. Conclusion This study suggests that 18F-fluoride PET imaging, which is an indicator of osteoblastic activity in vivo, can identify fracture nonunions at an early time point

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

    PubMed

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

    2012-04-01

    Damaged bone is sensitive to mechanical stimulation throughout the remodeling phase of bone healing. Muscle damage and muscular atrophy associated with open fractures and subsequent fixation are not beneficial to maintaining optimum conditions for mechanical stability. The aim of this study was to investigate whether local muscle atrophy and dysfunction affect fracture healing in a rat femur fracture model. We combined the rat model of a short period atrophy of the quadriceps with femur fracture. Forty-four-month-old male Wistar rats were adopted for this study. Two units of botulinum toxin-A (BXTA) were administered locally into the right side of the quadriceps of each rat, while the same dose of saline was injected into the contralateral quadriceps. After BXTA had been fully absorbed by the quadriceps, osteotomy was performed in both femurs with intramedullary fixation. Gross observation and weighing of muscle tissue, X-ray analysis, callus histology, and bone biomechanical testing were performed at different time points up to 8 weeks post-surgery. Local injection of BXTA led to a significant decrease in the volume and weight of the quadriceps compared to the control side. At the eighth week, the left side femurs of the saline-injected quadriceps almost reached bony union, and fibrous calluses were completely calcified into woven bone. However, a gap was still visible in the BXTA-treated side on X-ray images. As showed by bone histology, there were no mature osseous calluses or woven bone on the BXTA-treated side, but a resorption pattern was evident. Biomechanical testing indicated that the femurs of the BXTA-treated side exhibited inferior mechanical properties compared with the control side. The inferior outcome following BXTA injection, compared with saline injection, in terms of callus resistance may be the consequence of unexpected load and mechanical unsteadiness caused by muscle atrophy and dysfunction. PMID:21919046

  7. 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

  8. Human fibrocyte-derived exosomes accelerate wound healing in genetically diabetic mice.

    PubMed

    Geiger, Adolf; Walker, Audrey; Nissen, Erwin

    2015-11-13

    Diabetic ulcers represent a substantial societal and healthcare burden worldwide and scarcely respond to current treatment strategies. This study was addressed to evaluate the therapeutic potential of exosomes secreted by human circulating fibrocytes, a population of mesenchymal progenitors involved in normal wound healing via paracrine signaling. The exosomes released from cells sequentially stimulated with platelet-derived growth factor-BB and transforming growth factor-β1, in the presence of fibroblast growth factor 2, did not show potential immunogenicity. These exosomes exhibited in-vitro proangiogenic properties, activated diabetic dermal fibroblasts, induced the migration and proliferation of diabetic keratinocytes, and accelerated wound closure in diabetic mice in vivo. Important components of the exosomal cargo were heat shock protein-90α, total and activated signal transducer and activator of transcription 3, proangiogenic (miR-126, miR-130a, miR-132) and anti-inflammatory (miR124a, miR-125b) microRNAs, and a microRNA regulating collagen deposition (miR-21). This proof-of-concept study demonstrates the feasibility of the use of fibrocytes-derived exosomes for the treatment of diabetic ulcers. PMID:26454169

  9. 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

  10. Expectation-induced placebo responses fail to accelerate wound healing in healthy volunteers: results from a prospective controlled experimental trial.

    PubMed

    Vits, Sabine; Dissemond, Joachim; Schadendorf, Dirk; Kriegler, Lisa; Körber, Andreas; Schedlowski, Manfred; Cesko, Elvir

    2015-12-01

    Placebo responses have been shown to affect the symptomatology of skin diseases. However, expectation-induced placebo effects on wound healing processes have not been investigated yet. We analysed whether subjects' expectation of receiving an active drug accelerates the healing process of experimentally induced wounds. In 22 healthy men (experimental group, n = 11; control group, n = 11) wounds were induced by ablative laser on both thighs. Using a deceptive paradigm, participants in the experimental group were informed that an innovative 'wound gel' was applied on one of the two wounds, whereas a 'non-active gel' was applied on the wound of the other thigh. In fact, both gels were identical hydrogels without any active components. A control group was informed to receive a non-active gel on both wounds. Progress in wound healing was documented via planimetry on days 1, 4 and 7 after wound induction. From day 9 onwards wound inspections were performed daily accompanied by a change of the dressing and a new application of the gel. No significant differences could be observed with regard to duration or process of wound healing, either by intraindividual or by interindividual comparisons. These data document no expectation-induced placebo effect on the healing process of experimentally induced wounds in healthy volunteers. PMID:24373522

  11. Green light emitting diodes accelerate wound healing: characterization of the effect and its molecular basis in vitro and in vivo.

    PubMed

    Fushimi, Tomohiro; Inui, Shigeki; Nakajima, Takeshi; Ogasawara, Masahiro; Hosokawa, Ko; Itami, Satoshi

    2012-01-01

    Because light-emitting diodes (LEDs) are low-coherent, quasimonochromatic, and nonthermal, they are an alternative for low level laser therapy, and have photobiostimulative effects on tissue repair. However, the molecular mechanism(s) are unclear, and potential effects of blue and/or green LEDs on wound healing are still unknown. Here, we investigated the effects of red (638 nm), blue (456 nm), and green (518 nm) LEDs on wound healing. In an in vivo study, wound sizes in the skin of ob/ob mice were significantly decreased on day 7 following exposure to green LEDs, and complete reepithelialization was accelerated by red and green LEDs compared with the control mice. To better understand the molecular mechanism(s) involved, we investigated the effects of LEDs on human fibroblasts in vitro by measuring mRNA and protein levels of cytokines secreted by fibroblasts during the process of wound healing and on the migration of HaCat keratinocytes. The results suggest that some cytokines are significantly increased by exposure to LEDs, especially leptin, IL-8, and VEGF, but only by green LEDs. The migration of HaCat keratinocytes was significantly promoted by red or green LEDs. In conclusion, we demonstrate that green LEDs promote wound healing by inducing migratory and proliferative mediators, which suggests that not only red LEDs but also green LEDs can be a new powerful therapeutic strategy for wound healing. PMID:22380691

  12. Exosomes derived from human adipose mensenchymal stem cells accelerates cutaneous wound healing via optimizing the characteristics of fibroblasts.

    PubMed

    Hu, Li; Wang, Juan; Zhou, Xin; Xiong, Zehuan; Zhao, Jiajia; Yu, Ran; Huang, Fang; Zhang, Handong; Chen, Lili

    2016-01-01

    Prolonged healing and scar formation are two major challenges in the treatment of soft tissue trauma. Adipose mesenchymal stem cells (ASCs) play an important role in tissue regeneration, and recent studies have suggested that exosomes secreted by stem cells may contribute to paracrine signaling. In this study, we investigated the roles of ASCs-derived exosomes (ASCs-Exos) in cutaneous wound healing. We found that ASCs-Exos could be taken up and internalized by fibroblasts to stimulate cell migration, proliferation and collagen synthesis in a dose-dependent manner, with increased genes expression of N-cadherin, cyclin-1, PCNA and collagen I, III. In vivo tracing experiments demonstrated that ASCs-Exos can be recruited to soft tissue wound area in a mouse skin incision model and significantly accelerated cutaneous wound healing. Histological analysis showed increased collagen I and III production by systemic administration of exosomes in the early stage of wound healing, while in the late stage, exosomes might inhibit collagen expression to reduce scar formation. Collectively, our findings indicate that ASCs-Exos can facilitate cutaneous wound healing via optimizing the characteristics of fibroblasts. Our results provide a new perspective and therapeutic strategy for the use of ASCs-Exos in soft tissue repair. PMID:27615560

  13. 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

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

    PubMed

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

    2016-05-01

    Interpersonal violence (IPV) and heavy alcohol consumption are major problems in the Western Cape Province of South Africa. Cranio-maxillofacial fractures, particularly nasal and zygomatic bone fractures, as well as isolated radial fractures (Colles fractures) and ulnar shaft fractures (parry fractures), are indicative of IPV, while alcoholic liver disease (ALD) is the consequence of chronic alcohol abuse. We therefore aim to investigate whether a significant association exists between the prevalence of cranio-maxillofacial fractures and parry fractures and ALD in a Western Cape population. Embalmed cadavers (n = 124) used for medical students' anatomy training at the Division of Anatomy and Histology, Faculty of Medicine and Health Sciences, Stellenbosch University were studied. The cadavers were dissected according to departmental protocol. The liver of each cadaver was investigated for macroscopic pathology lesions. Tissue samples were removed, processed to wax, and sectioned and stained with hematoxylin and eosin (H&E). All soft tissue was removed from the skulls, radii, and ulnae, which were then investigated for healed skeletal trauma. The results showed 37/124 (29.8%) cadavers had healed cranio-maxillofacial fractures and 24/124 (19.4%) cadavers had morphologic features of ALD. A total of 12/124 (9.7%) cadavers showed signs of both ALD and healed cranio-maxillofacial trauma. More males were affected than females, and left-sided facial fractures were statistically more common compared to the right side. This study illustrated a significant trend between alcohol abuse and cranio-maxillofacial fractures in individuals from communities with a low socio-economic status (SES) where IPV is a major problem. PMID:27139236

  15. 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

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

    PubMed

    Eschler, Anica; 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

  17. 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

  18. 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

  19. Chitosan-based copper nanocomposite accelerates healing in excision wound model in rats.

    PubMed

    Gopal, Anu; Kant, Vinay; Gopalakrishnan, Anu; Tandan, Surendra K; Kumar, Dinesh

    2014-05-15

    Copper possesses efficacy in wound healing which is a complex phenomenon involving various cells, cytokines and growth factors. Copper nanoparticles modulate cells, cytokines and growth factors involved in wound healing in a better way than copper ions. Chitosan has been shown to be beneficial in healing because of its antibacterial, antifungal, biocompatible and biodegradable polymeric nature. In the present study, chitosan-based copper nanocomposite (CCNC) was prepared by mixing chitosan and copper nanoparticles. CCNC was applied topically to evaluate its wound healing potential and to study its effects on some important components of healing process in open excision wound model in adult Wistar rats. Significant increase in wound contraction was observed in the CCNC-treated rats. The up-regulation of vascular endothelial growth factor (VEGF) and transforming growth factor-beta1(TGF-β1) by CCNC-treatment revealed its role in facilitating angiogenesis, fibroblast proliferation and collagen deposition. The tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) were significantly decreased and increased, respectively, in CCNC-treated rats. Histological evaluation showed more fibroblast proliferation, collagen deposition and intact re-epithelialization in CCNC-treated rats. Immunohistochemistry of CD31 revealed marked increase in angiogenesis. Thus, we concluded that chitosan-based copper nanocomposite efficiently enhanced cutaneous wound healing by modulation of various cells, cytokines and growth factors during different phases of healing process. PMID:24632085

  20. Accelerated care versus standard care among patients with hip fracture: the HIP ATTACK pilot trial

    PubMed Central

    2014-01-01

    Background: A hip fracture causes bleeding, pain and immobility, and initiates inflammatory, hypercoagulable, catabolic and stress states. Accelerated surgery may improve outcomes by reducing the duration of these states and immobility. We undertook a pilot trial to determine the feasibility of a trial comparing accelerated care (i.e., rapid medical clearance and surgery) and standard care among patients with a hip fracture. Methods: Patients aged 45 years or older who, during weekday, daytime working hours, received a diagnosis of a hip fracture requiring surgery were randomly assigned to receive accelerated or standard care. Our feasibility outcomes included the proportion of eligible patients randomly assigned, completeness of follow-up and timelines of accelerated surgery. The main clinical outcome, assessed by data collectors and adjudicators who were unaware of study group allocations, was a major perioperative complication (i.e., a composite of death, preoperative myocardial infarction, myocardial injury after noncardiac surgery, pulmonary embolism, pneumonia, stroke, and life-threatening or major bleeding) within 30 days of randomization. Results: Of patients eligible for inclusion, 80% consented and were randomly assigned to groups (30 to accelerated care and 30 to standard care) at 2 centres in Canada and 1 centre in India. All patients completed 30-day follow-up. The median time from diagnosis to surgery was 6.0 hours in the accelerated care group and 24.2 hours in the standard care group (p < 0.001). A major perioperative complication occurred in 9 (30%) of the patients in the accelerated care group and 14 (47%) of the patients in the standard care group (hazard ratio 0.60, 95% confidence interval 0.26–1.39). Interpretation: These results show the feasibility of a trial comparing accelerated and standard care among patients with hip fracture and support a definitive trial. Trial registration: ClinicalTrials.gov, no. NCT01344343. PMID:24246589

  1. Low-intensity pulsed ultrasonography versus electrical stimulation for fracture healing: a systematic review and network meta-analysis

    PubMed Central

    Ebrahim, Shanil; Mollon, Brent; Bance, Sheena; Busse, Jason W.; Bhandari, Mohit

    2014-01-01

    Background To best inform evidence-based patient care, it is often desirable to compare competing therapies. We performed a network meta-analysis to indirectly compare low intensity pulsed ultrasonography (LIPUS) with electrical stimulation (ESTIM) for fracture healing. Methods We searched the reference lists of recent reviews evaluating LIPUS and ESTIM that included studies published up to 2011 from 4 electronic databases. We updated the searches of all electronic databases up to April 2012. Eligible trials were those that included patients with a fresh fracture or an existing delayed union or nonunion who were randomized to LIPUS or ESTIM as well as a control group. Two pairs of reviewers, independently and in duplicate, screened titles and abstracts, reviewed the full text of potentially eligible articles, extracted data and assessed study quality. We used standard and network meta-analytic techniques to synthesize the data. Results Of the 27 eligible trials, 15 provided data for our analyses. In patients with a fresh fracture, there was a suggested benefit of LIPUS at 6 months (risk ratio [RR] 1.17, 95% confidence interval [CI] 0.97–1.41). In patients with an existing nonunion or delayed union, ESTIM had a suggested benefit over standard care on union rates at 3 months (RR 2.05, 95% CI 0.99–4.24). We found very low-quality evidence suggesting a potential benefit of LIPUS versus ESTIM in improving union rates at 6 months (RR 0.76, 95% CI 0.58–1.01) in fresh fracture populations. Conclusion To support our findings direct comparative trials with safeguards against bias assessing outcomes important to patients, such as functional recovery, are required. PMID:24869616

  2. Fibrin biomatrix-conjugated platelet-derived growth factor AB accelerates wound healing in severe thermal injury.

    PubMed

    Mittermayr, Rainer; Branski, Ludwik; Moritz, Martina; Jeschke, Marc G; Herndon, David N; Traber, Daniel; Schense, Jason; Gampfer, Jörg; Goppelt, Andreas; Redl, Heinz

    2016-05-01

    Controlled delivery of growth factors from biodegradable biomatrices could accelerate and improve impaired wound healing. The study aim was to determine whether platelet-derived growth factor AB (PDGF.AB) with a transglutaminase (TG) crosslinking substrate site released from a fibrin biomatrix improves wound healing in severe thermal injury. The binding and release kinetics of TG-PDGF.AB were determined in vitro. Third-degree contact burns (dorsum of Yorkshire pigs) underwent epifascial necrosectomy 24 h post-burn. Wound sites were covered with autologous meshed (3:1) split-thickness skin autografts and either secured with staples or attached with sprayed fibrin sealant (FS; n = 8/group). TG-PDGF.AB binds to the fibrin biomatrix using the TG activity of factor XIIIa, and is subsequently released through enzymatic cleavage. Three doses of TG-PDGF.AB in FS (100 ng, 1 µg and 11 µg/ml FS) were tested. TG-PDGF.AB was bound to the fibrin biomatrix as evidenced by western blot analysis and subsequently released by enzymatic cleavage. A significantly accelerated and improved wound healing was achieved using sprayed FS containing TG-PDGF.AB compared to staples alone. Low concentrations (100 ng-1 µg TG-PDGF.AB/ml final FS clot) demonstrated to be sufficient to attain a nearly complete closure of mesh interstices 14 days after grafting. TG-PDGF.AB incorporated in FS via a specific binding technology was shown to be effective in grafted third-degree burn wounds. The adhesive properties of the fibrin matrix in conjunction with the prolonged growth factor stimulus enabled by this binding technology could be favourable in many pathological situations associated with wound-healing disturbances. Copyright © 2013 John Wiley & Sons, Ltd. PMID:23723146

  3. Topical N-Acetylcysteine Accelerates Wound Healing in Vitro and in Vivo via the PKC/Stat3 Pathway

    PubMed Central

    Tsai, Min-Ling; Huang, Hui-Pei; Hsu, Jeng-Dong; Lai, Yung-Rung; Hsiao, Yu-Ping; Lu, Fung-Jou; Chang, Horng-Rong

    2014-01-01

    N-Acetylcysteine (Nac) is an antioxidant administered in both oral and injectable forms. In this study, we used Nac topically to treat burn wounds in vitro and in vivo to investigate mechanisms of action. In vitro, we monitored glutathione levels, cell proliferation, migration, scratch-wound healing activities and the epithelialization-related proteins, matrixmetalloproteinase-1 (MMP-1) and proteins involved in regulating the expression of MMP-1 in CCD-966SK cells treated with Nac. Various Nac concentrations (0.1, 0.5, and 1.0 mM) increased glutathione levels, cell viability, scratch-wound healing activities and migration abilities of CCD-966SK cells in a dose-dependent manner. The MMP-1 expression of CCD-966SK cells treated with 1.0 mM Nac for 24 h was significantly increased. Levels of phosphatidylinositol 3-kinase (PI3K), protein kinase C (PKC), janus kinase 1 (Jak1), signal transducer and activator of transcription 3 (Stat3), c-Fos and Jun, but not extracellular signal-regulated protein kinases 1 and 2 (Erk1/2), were also significantly increased in a dose-dependent manner compared to the controls. In addition, Nac induced collagenous expression of MMP-1 via the PKC/Stat3 signaling pathway. In vivo, a burn wound healing rat model was applied to assess the stimulation activity and histopathological effects of Nac, with 3.0% Nac-treated wounds being found to show better characteristics on re-epithelialization. Our results demonstrated that Nac can potentially promote wound healing activity, and may be a promising drug to accelerate burn wound healing. PMID:24798751

  4. A deficiency in cold-inducible RNA-binding protein accelerates the inflammation phase and improves wound healing.

    PubMed

    Idrovo, Juan Pablo; Jacob, Asha; Yang, Weng Lang; Wang, Zhimin; Yen, Hao Ting; Nicastro, Jeffrey; Coppa, Gene F; Wang, Ping

    2016-02-01

    Chronic or non-healing wounds are a major concern in clinical practice and these wounds are mostly associated with diabetes, and venous and pressure ulcers. Wound healing is a complex process involving overlapping phases and the primary phase in this complex cascade is the inflammatory state. While inflammation is necessary for wound healing, a prolonged inflammatory phase leads to impaired healing. Cold-inducible RNA-binding protein (CIRP) belongs to a family of cold-shock proteins that are expressed in high levels under stress conditions. Recently, we demonstrated that a deficiency in CIRP led to decreased inflammation and mortality in an experimental model of hemorrhagic shock. Thus, we hypothesized that a deficiency in CIRP would accelerate the inflammatory phase and lead to an improvement in cutaneous wound healing. In this study, to examine this hypothesis, a full-thickness wound was created on the dorsum of wild-type (WT) and CIRP-/- mice. The wound size was measured every other day for 14 days. The wound area was significantly decreased in the CIRP-/- mice by day 9 and continued to decrease until day 14 compared to the WT mice. In a separate cohort, mice were sacrificed on days 3 and 7 after wounding and the skin tissues were harvested for histological analysis and RNA measurements. On day 3, the mRNA expression of tumor necrossis factor (TNF)-α in the skin tissues was increased by 16-fold in the WT mice, whereas these levels were increased by 65-fold in the CIRP-/- mice. Of note on day 7, while the levels of TNF-α remained high in the WT mice, these levels were significantly decreased in the CIRP-/- mice. The histological analysis of the wounded skin tissue indicated an improvement as early as day 3 in the CIRP-/- mice, whereas in the WT mice, infiltrated immune cells were still present on day 7. On day 7 in the CIRP-/- mice, Gr-1 expression was low and CD31 expression was high, whereas in the WT mice, Gr-1 expression was high and CD31 expression was low

  5. 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

  6. Deletion of the α2A/α2C-adrenoceptors accelerates cutaneous wound healing in mice.

    PubMed

    Romana-Souza, Bruna; Nascimento, Adriana P; Brum, Patricia C; Monte-Alto-Costa, Andréa

    2014-10-01

    The α2-adrenoceptors regulate the sympathetic nervous system, controlling presynaptic catecholamine release. However, the role of the α2-adrenoceptors in cutaneous wound healing is poorly understood. Mice lacking both the α2A/α2C-adrenoceptors were used to evaluate the participation of the α2-adrenoceptor during cutaneous wound healing. A full-thickness excisional lesion was performed on the dorsal skin of the α2A/α2C-adrenoceptor knockout and wild-type mice. Seven or fourteen days later, the animals were euthanized and the lesions were formalin-fixed and paraffin-embedded or frozen. Murine skin fibroblasts were also isolated from α2A/α2C-adrenoceptor knockout and wild-type mice, and fibroblast activity was evaluated. The in vivo study demonstrated that α2A/α2C-adrenoceptor depletion accelerated wound contraction and re-epithelialization. A reduction in the number of neutrophils and macrophages was observed in the α2A/α2C-adrenoceptor knockout mice compared with wild-type mice. In addition, α2A/α2C-adrenoceptor depletion enhanced the levels of nitrite and hydroxyproline, and the protein expression of transforming growth factor-β and vascular endothelial growth factor. Furthermore, α2A/α2C-adrenoceptor depletion accelerated blood vessel formation and myofibroblast differentiation. The in vitro study demonstrated that skin fibroblasts isolated from α2A/α2C-adrenoceptor knockout mice exhibited enhanced cell migration, α-smooth muscle actin _protein expression and collagen deposition compared with wild-type skin fibroblasts. In conclusion, α2A/α2C-adrenoceptor deletion accelerates cutaneous wound healing in mice. PMID:25186490

  7. The Use of Growth Factors and Other Humoral Agents to Accelerate and Enhance Burn Wound Healing

    PubMed Central

    Ching, Yiu-Hei; Sutton, Thomas L.; Pierpont, Yvonne N.; Robson, Martin C.; Payne, Wyatt G.

    2011-01-01

    Objective: Certain cytokines, especially those known as growth factors, have been demonstrated to mediate or modulate burn wound healing. Experimental and clinical evidence suggests that there are therapeutic advantages to the wound healing process when these agents are utilized. Positive effects have been reported for 4 types of wounds seen in the burn patient: partial-thickness wounds, full-thickness wounds, interstices of meshed skin grafts, and skin graft donor sites. Methods: A comprehensive literature search was performed using the MEDLINE, Ovid, and Web of Science databases to identify pertinent articles regarding growth factors and other cytokines in burns and wound healing. Results: The current knowledge about cytokine growth factors and their potential therapeutic applications in burn wound healing are discussed and reviewed. Conclusions: Platelet-derived growth factor, fibroblast growth factors, epidermal growth factors, transforming growth factor alpha, vascular endothelial growth factor, insulin-like growth factor I, nerve growth factor, transforming growth factor beta, granulocyte-macrophage colony-stimulating factor, and amnion-derived cellular cytokine solution have all been suggested to enhance the rate and quality of healing in 1 or more of these wounds encountered in burn care. PMID:22084646

  8. Accelerated bone mineral loss following a hip fracture: a prospective longitudinal study.

    PubMed

    Dirschl, D R; Henderson, R C; Oakley, W C

    1997-07-01

    The purpose of this prospective study was to monitor the bone mineral density (BMD) of the lumbar spine and contralateral femoral neck in the first year following an osteoporosis-related fracture of the hip. Eighty-three elderly patients (mean age 77 years) who had sustained a hip fracture had determinations of BMD made at the time of fracture; 49 of these patients were available for reassessment of BMD 1 year later. The change in BMD was correlated with pre- and postinjury variables, such as ambulatory ability, dietary intake of calcium, serum vitamin D levels, mental status, and routine serologies. The mean decrease in BMD in the year following fracture was 5.4% from the contralateral femoral neck and 2.4% from the lumbar spine. Calcium intake correlated with the loss of BMD from the femoral neck (p = 0.015), but not the lumbar spine. Patients with daily calcium intakes of less than 500 mg/day had a more than 10% decrease in femoral neck BMD in the year following their hip fracture. Serum 1,25-dihydroxy vitamin D level correlated with loss of MBD from the lumbar spine (p = 0.001), but not from the femoral neck. There was no correlation between the loss of bone mineral from either measurement site and age, sex, level of ambulation, or mental status. The loss of BMD from the femoral neck in the year following a hip fracture is more than five times that reported in the nonfractured population. This accelerated rate of loss can have drastic consequences in an elderly population already exhibiting osteopenia and propensity to fall. Investigation of pharmacologic or other interventions in the first critical year following a hip fracture may potentially blunt this accelerated rate of bone loss and lessen the risk of subsequent fractures. PMID:9213011

  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. 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

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

    PubMed

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

    2013-09-01

    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

  12. Transparent crosslinked ultrashort peptide hydrogel dressing with high shape-fidelity accelerates healing of full-thickness excision wounds.

    PubMed

    Seow, Wei Yang; Salgado, Giorgiana; Lane, E Birgitte; Hauser, Charlotte A E

    2016-01-01

    Wound healing is a major burden of healthcare systems worldwide and hydrogel dressings offer a moist environment conducive to healing. We describe cysteine-containing ultrashort peptides that self-assemble spontaneously into hydrogels. After disulfide crosslinking, the optically-transparent hydrogels became significantly stiffer and exhibited high shape fidelity. The peptide sequence (LIVAGKC or LK6C) was then chosen for evaluation on mice with full-thickness excision wounds. Crosslinked LK6C hydrogels are handled easily with forceps during surgical procedures and offer an improvement over our earlier study of a non-crosslinked peptide hydrogel for burn wounds. LK6C showed low allergenic potential and failed to provoke any sensitivity when administered to guinea pigs in the Magnusson-Kligman maximization test. When applied topically as a dressing, the medium-infused LK6C hydrogel accelerated re-epithelialization compared to controls. The peptide hydrogel is thus safe for topical application and promotes a superior rate and quality of wound healing. PMID:27600999

  13. Transparent crosslinked ultrashort peptide hydrogel dressing with high shape-fidelity accelerates healing of full-thickness excision wounds

    PubMed Central

    Seow, Wei Yang; Salgado, Giorgiana; Lane, E. Birgitte; Hauser, Charlotte A. E.

    2016-01-01

    Wound healing is a major burden of healthcare systems worldwide and hydrogel dressings offer a moist environment conducive to healing. We describe cysteine-containing ultrashort peptides that self-assemble spontaneously into hydrogels. After disulfide crosslinking, the optically-transparent hydrogels became significantly stiffer and exhibited high shape fidelity. The peptide sequence (LIVAGKC or LK6C) was then chosen for evaluation on mice with full-thickness excision wounds. Crosslinked LK6C hydrogels are handled easily with forceps during surgical procedures and offer an improvement over our earlier study of a non-crosslinked peptide hydrogel for burn wounds. LK6C showed low allergenic potential and failed to provoke any sensitivity when administered to guinea pigs in the Magnusson-Kligman maximization test. When applied topically as a dressing, the medium-infused LK6C hydrogel accelerated re-epithelialization compared to controls. The peptide hydrogel is thus safe for topical application and promotes a superior rate and quality of wound healing. PMID:27600999

  14. Biofunctionalized electrospun silk mats as a topical bioactive dressing for accelerated wound healing

    PubMed Central

    Schneider, A.; Wang, X.Y.; Kaplan, D.L.; Garlick, J.A.; Egles, C.

    2010-01-01

    Materials able to deliver topically bioactive molecules represent a new generation of biomaterials. In this article, we describe the use of silk mats, made of electrospun nanoscale silk fibers containing epidermal growth factor (EGF), for the promotion of wound healing processes. In our experiments, we demonstrated that EGF is incorporated into the silk mats and slowly released in a time-dependent manner (25% EGF release in 170 h). We tested these materials using a new model of wounded human skin-equivalents displaying the same structure as human skin and able to heal using the same molecular and cellular mechanisms found in vivo. This human three-dimensional model allows us to demonstrate that the biofunctionalized silk mats, when placed on the wounds as a dressing, aid the healing by increasing the time of wound closure by the epidermal tongue by 90%. The preservation of the structure of the mats during the healing period as demonstrated by electronic microscopy, the biological action of the dressing, as well as the biocompatibility of the silk demonstrate that this biomaterial is a new and very promising material for medical applications, especially for patients suffering from chronic wounds. PMID:19162575

  15. Curcuma purpurascens BI. rhizome accelerates rat excisional wound healing: involvement of Hsp70/Bax proteins, antioxidant defense, and angiogenesis activity

    PubMed Central

    Rouhollahi, Elham; Moghadamtousi, Soheil Zorofchian; Hajiaghaalipour, Fatemeh; Zahedifard, Maryam; Tayeby, Faezeh; Awang, Khalijah; Abdulla, Mahmood Ameen; Mohamed, Zahurin

    2015-01-01

    Purpose Curcuma purpurascens BI. is a member of Zingiberaceae family. The purpose of this study is to investigate the wound healing properties of hexane extract of C. purpurascens rhizome (HECP) against excisional wound healing in rats. Materials and methods Twenty four rats were randomly divided into 4 groups: A) negative control (blank placebo, acacia gum), B) low dose of HECP, C) high dose of HECP, and D) positive control, with 6 rats in each group. Full-thickness incisions (approximately 2.00 cm) were made on the neck area of each rat. Groups 1–4 were treated two-times a day for 20 days with blank placebo, HECP (100 mg/kg), HECP (200 mg/kg), and intrasite gel as a positive control, respectively. After 20 days, hematoxylin and eosin and Masson’s trichrome stainings were employed to investigate the histopathological alterations. Protein expressions of Bax and Hsp70 were examined in the wound tissues using immunohistochemistry analysis. In addition, levels of enzymatic antioxidants and malondialdehyde representing lipid peroxidation were measured in wound tissue homogenates. Results Macroscopic evaluation of wounds showed conspicuous elevation in wound contraction after topical administration of HECP at both doses. Moreover, histopathological analysis revealed noteworthy reduction in the scar width correlated with the enhanced collagen content and fibroblast cells, accompanied by a reduction of inflammatory cells in the granulation tissues. At the molecular level, HECP facilitates wound-healing process by downregulating Bax and upregulating Hsp70 protein at the wound site. The formation of new blood vessel was observed in Masson’s trichrome staining of wounds treated with HECP (100 and 200 mg/kg). In addition, HECP administration caused a significant surge in enzymatic antioxidant activities and a decline in lipid peroxidation. Conclusion These findings suggested that HECP accelerated wound-healing process in rats via antioxidant activity, angiogenesis

  16. Osteoporotic fracture healing: potential use of medicinal plants from the tropics.

    PubMed

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

    2013-12-01

    With improvements in living standards and healthcare, life expectancy has been increasing dramatically in most parts of the world. These situations lead to the increase in the reported cases of geriatrics-related diseases such as hypogonadal osteoporosis with skeletal fracture being the ultimate outcome, which eventually causes significant morbidity and mortality. The deficient gonadal hormones, which are the main cause of hypogonadal osteoporosis, could be substituted with hormone replacement therapy to hinder bone loss. However, the artificial hormonal therapy has been linked to grievous conditions such as breast and prostate cancers. In view of the various adverse effects associated with conventional treatment, many researchers are now focusing on finding alternative remedies from nature. This article explores the possibilities of certain medicinal plants native to Malaysia that possess androgenic and antioxidant properties to potentially be used in the treatment of fracture due to osteoporosis in ageing people. PMID:24354586

  17. 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

  18. 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.

  19. Method for detecting moment connection fracture using high-frequency transients in recorded accelerations

    USGS Publications Warehouse

    Rodgers, J.E.; Elebi, M.

    2011-01-01

    The 1994 Northridge earthquake caused brittle fractures in steel moment frame building connections, despite causing little visible building damage in most cases. Future strong earthquakes are likely to cause similar damage to the many un-retrofitted pre-Northridge buildings in the western US and elsewhere. Without obvious permanent building deformation, costly intrusive inspections are currently the only way to determine if major fracture damage that compromises building safety has occurred. Building instrumentation has the potential to provide engineers and owners with timely information on fracture occurrence. Structural dynamics theory predicts and scale model experiments have demonstrated that sudden, large changes in structure properties caused by moment connection fractures will cause transient dynamic response. A method is proposed for detecting the building-wide level of connection fracture damage, based on observing high-frequency, fracture-induced transient dynamic responses in strong motion accelerograms. High-frequency transients are short (<1 s), sudden-onset waveforms with frequency content above 25 Hz that are visually apparent in recorded accelerations. Strong motion data and damage information from intrusive inspections collected from 24 sparsely instrumented buildings following the 1994 Northridge earthquake are used to evaluate the proposed method. The method's overall success rate for this data set is 67%, but this rate varies significantly with damage level. The method performs reasonably well in detecting significant fracture damage and in identifying cases with no damage, but fails in cases with few fractures. Combining the method with other damage indicators and removing records with excessive noise improves the ability to detect the level of damage. ?? 2010 Elsevier B.V. All rights reserved.

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

    PubMed Central

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

    2015-01-01

    Transforming growth factor beta 1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2) are important regulators of bone repair and regeneration. In this study, we examined whether TGF-β1 and BMP-2 expressions were delayed during bone healing in type 1 diabetes mellitus. Tibial fractures were created in 95 diabetic and 95 control adult male Wistar rats of 10 weeks of age. At 1, 2, 3, 4, and 5 weeks after fracture induction, five rats were sacrificed from each group. The expressions of TGF-β1 and BMP2 in the fractured tibias were measured by immunohistochemistry and quantitative reverse-transcription polymerase chain reaction, weekly for the first 5 weeks post-fracture. Mechanical parameters (bending rigidity, torsional rigidity, destruction torque) of the healing bones were also assessed at 3, 4, and 5 weeks post-fracture, after the rats were sacrificed. The bending rigidity, torsional rigidity and destruction torque of the two groups increased continuously during the healing process. The diabetes group had lower mean values for bending rigidity, torsional rigidity and destruction torque compared with the control group (P<0.05). TGF-β1 and BMP-2 expression were significantly lower (P<0.05) in the control group than in the diabetes group at postoperative weeks 1, 2, and 3. Peak levels of TGF-β1 and BMP-2 expression were delayed by 1 week in the diabetes group compared with the control group. Our results demonstrate that there was a delayed recovery in the biomechanical function of the fractured bones in diabetic rats. This delay may be associated with a delayed expression of the growth factors TGF-β1 and BMP-2. PMID:26628397

  1. 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

  2. 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

  3. 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.

  4. Formulated collagen gel accelerates healing rate immediately after application in patients with diabetic neuropathic foot ulcers

    PubMed Central

    Blume, Peter; Driver, Vickie R; Tallis, Arthur J; Kirsner, Robert S; Kroeker, Roy; Payne, Wyatt G; Wali, Soma; Marston, William; Dove, Cyaandi; Engler, Robert L; Chandler, Lois A; Sosnowski, Barbara K

    2011-01-01

    We assessed the safety and efficacy of Formulated Collagen Gel (FCG) alone and with Ad5PDGF-B (GAM501) compared with Standard of Care (SOC) in patients with 1.5–10.0 cm2 chronic diabetic neuropathic foot ulcers that healed <30% during Run-in. Wound size was assessed by planimetry of acetate tracings and photographs in 124 patients. Comparison of data sets revealed that acetate tracings frequently overestimated areas at some sites. For per-protocol analysis, 113 patients qualified using acetate tracings but only 82 qualified using photographs. Prior animal studies suggested that collagen alone would have little effect on healing and would serve as a negative control. Surprisingly trends for increased incidence of complete closure were observed for both GAM501 (41%) and FCG (45%) vs. Standard of Care (31%). By photographic data, Standard of Care had no significant effect on change in wound radius (mm/week) from during Run-in to Week 1 (−0.06±0.32 to 0.78±1.53, p=ns) but both FCG (−0.08±0.61 to 1.97±1.77, p<0.002) and GAM501 (−0.02±0.58 to 1.46±1.37, p<0.002) significantly increased healing rates that gradually declined over subsequent weeks. Both GAM501 and FCG appeared to be safe and well tolerated, and alternate dosing schedules hold promise to improve overall complete wound closure in adequately powered trials. PMID:21371164

  5. PEDF promotes self-renewal of limbal stem cell and accelerates corneal epithelial wound healing.

    PubMed

    Ho, Tsung-Chuan; Chen, Show-Li; Wu, Ju-Yun; Ho, Mei-Ying; Chen, Lee-Jen; Hsieh, Jui-Wen; Cheng, Huey-Chuan; Tsao, Yeou-Ping

    2013-09-01

    Limbal epithelial stem cell (LSC) transplantation is a prevalent therapeutic method for patients with LSC deficiency. The maintenance of stem cell characteristics in the process of culture expansion is critical for the success of ocular surface reconstruction. Pigment epithelial-derived factor (PEDF) increased the numbers of holoclone in LSC monolayer culture and preserved the stemness of LSC in suspension culture by evidence of ΔNp63α, Bmi-1, and ABCG2 expression. BrdU pulse-labeling assay also demonstrated that PEDF stimulated LSCs proliferation. In air-lift culture of limbal equivalent, PEDF was capable of increasing the numbers of ΔNp63α-positive cells. The mitogenic effect of PEDF was found to be mediated by the phosphorylations of p38 MAPK and STAT3 in LSCs. Synthetic 44-mer PEDF (residues 78-121) was as effective as the full length PEDF in LSC expansion in suspension culture and limbal equivalent formation, as well as the activation of p38 MAPK and STAT3. In mice subjecting to mechanical removal of cornea epithelium, 44-mer PEDF facilitated corneal wound healing. Microscopically, 44-mer PEDF advanced the early proliferative response in limbus, increased the proliferation of ΔNp63α-positive cells both in limbus and in epithelial healing front, and assisted the repopulation of limbus in the late phase of wound healing. In conclusion, the capability of expanding LSC in cell culture and in animal indicates the potential of PEDF and its fragment (e.g., 44-mer PEDF) in ameliorating limbal stem cell deficiency; and their uses as therapeutics for treating corneal wound. PMID:23553951

  6. G-CSF Administration after the Intraosseous Infusion of Hypertonic Hydroxyethyl Starches Accelerating Wound Healing Combined with Hemorrhagic Shock

    PubMed Central

    Huang, Hong; Liu, Jiejie; Hao, Haojie; Tong, Chuan; Ti, Dongdong; Liu, Huiling; Song, Haijing; Jiang, Chaoguang; Fu, Xiaobing; Han, Weidong

    2016-01-01

    Objective. To evaluate the therapeutic effects of G-CSF administration after intraosseous (IO) resuscitation in hemorrhagic shock (HS) combined with cutaneous injury rats. Methods. The rats were randomly divided into four groups: (1) HS with resuscitation (blank), (2) HS with resuscitation + G-CSF (G-CSF, 200 μg/kg body weight, subcutaneous injection), (3) HS with resuscitation + normal saline solution injection (normal saline), and (4) HS + G-CSF injection without resuscitation (Unres/G-CSF). To estimate the treatment effects, the vital signs of alteration were first evaluated, and then wound closure rates and homing of MSCs and EPCs to the wound skins and vasculogenesis were measured. Besides, inflammation and vasculogenesis related mRNA expressions were also examined. Results. IO infusion hypertonic hydroxyethyl starch (HHES) exhibited beneficial volume expansion roles and G-CSF administration accelerated wound healing 3 days ahead of other groups under hemorrhagic shock. Circulating and the homing of MSCs and EPCs at wound skins were significantly elevated at 6 h after G-CSF treatment. Inflammation was declined since 3 d while angiogenesis was more obvious in G-CSF treated group on day 9. Conclusions. These results suggested that the synergistical application of HHES and G-CSF has life-saving effects and is beneficial for improving wound healing in HS combined with cutaneous injury rats. PMID:26989687

  7. Hydrogen-Rich Water Intake Accelerates Oral Palatal Wound Healing via Activation of the Nrf2/Antioxidant Defense Pathways in a Rat Model

    PubMed Central

    Orihuela-Campos, Rita Cristina; Fukui, Makoto; Ito, Hiro-O

    2016-01-01

    The wound healing process attempts to restore the integrity and function of the injured tissue. Additionally, proinflammatory cytokines, growth factors, and oxidative stress play important roles in wound healing. The aim of this study was to determine whether hydrogen-rich water intake induces the activation of the Nrf2/antioxidant defense pathway in rat palatal tissue, thereby reducing systemic oxidative stress and proinflammatory cytokine levels and promoting healing-associated genes. A circular excisional wound was created in the oral palatal region, and the wound healing process was observed. The rats were divided into two experimental groups in which either hydrogen-rich water or distilled water was consumed. In the drinking hydrogen-rich water, the palatal wound healing process was accelerated compared to that in the control group. As molecular hydrogen upregulated the Nrf2 pathway, systemic oxidative stresses were decreased by the activation of antioxidant activity. Furthermore, hydrogen-rich water intake reduced proinflammatory cytokine levels and promoted the expression of healing-associated factors in rat palatal tissue. In conclusion, hydrogen-rich water intake exhibited multiple beneficial effects through activation of the Nrf2/antioxidant defense pathway. The results of this study support the hypothesis that oral administration of hydrogen-rich water benefits the wound healing process by decreasing oxidative stress and inflammatory responses. PMID:26798423

  8. Loss of epithelial hypoxia-inducible factor prolyl hydroxylase 2 accelerates skin wound healing in mice.

    PubMed

    Kalucka, Joanna; Ettinger, Andreas; Franke, Kristin; Mamlouk, Soulafa; Singh, Rashim Pal; Farhat, Katja; Muschter, Antje; Olbrich, Susanne; Breier, Georg; Katschinski, Dörthe M; Huttner, Wieland; Weidemann, Alexander; Wielockx, Ben

    2013-09-01

    Skin wound healing in mammals is a complex, multicellular process that depends on the precise supply of oxygen. Hypoxia-inducible factor (HIF) prolyl hydroxylase 2 (PHD2) serves as a crucial oxygen sensor and may therefore play an important role during reepithelialization. Hence, this study was aimed at understanding the role of PHD2 in cutaneous wound healing using different lines of conditionally deficient mice specifically lacking PHD2 in inflammatory, vascular, or epidermal cells. Interestingly, PHD2 deficiency only in keratinocytes and not in myeloid or endothelial cells was found to lead to faster wound closure, which involved enhanced migration of the hyperproliferating epithelium. We demonstrate that this effect relies on the unique expression of β3-integrin in the keratinocytes around the tip of the migrating tongue in an HIF1α-dependent manner. Furthermore, we show enhanced proliferation of these cells in the stratum basale, which is directly related to their attenuated transforming growth factor β signaling. Thus, loss of the central oxygen sensor PHD2 in keratinocytes stimulates wound closure by prompting skin epithelial cells to migrate and proliferate. Inhibition of PHD2 could therefore offer novel therapeutic opportunities for the local treatment of cutaneous wounds. PMID:23798557

  9. Loss of Epithelial Hypoxia-Inducible Factor Prolyl Hydroxylase 2 Accelerates Skin Wound Healing in Mice

    PubMed Central

    Kalucka, Joanna; Ettinger, Andreas; Franke, Kristin; Mamlouk, Soulafa; Singh, Rashim Pal; Farhat, Katja; Muschter, Antje; Olbrich, Susanne; Breier, Georg; Katschinski, Dörthe M.; Huttner, Wieland; Weidemann, Alexander

    2013-01-01

    Skin wound healing in mammals is a complex, multicellular process that depends on the precise supply of oxygen. Hypoxia-inducible factor (HIF) prolyl hydroxylase 2 (PHD2) serves as a crucial oxygen sensor and may therefore play an important role during reepithelialization. Hence, this study was aimed at understanding the role of PHD2 in cutaneous wound healing using different lines of conditionally deficient mice specifically lacking PHD2 in inflammatory, vascular, or epidermal cells. Interestingly, PHD2 deficiency only in keratinocytes and not in myeloid or endothelial cells was found to lead to faster wound closure, which involved enhanced migration of the hyperproliferating epithelium. We demonstrate that this effect relies on the unique expression of β3-integrin in the keratinocytes around the tip of the migrating tongue in an HIF1α-dependent manner. Furthermore, we show enhanced proliferation of these cells in the stratum basale, which is directly related to their attenuated transforming growth factor β signaling. Thus, loss of the central oxygen sensor PHD2 in keratinocytes stimulates wound closure by prompting skin epithelial cells to migrate and proliferate. Inhibition of PHD2 could therefore offer novel therapeutic opportunities for the local treatment of cutaneous wounds. PMID:23798557

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

    NASA Astrophysics Data System (ADS)

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

    2014-11-01

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

  11. Non-union of an undisplaced radial styloid fracture in a heavy smoker: revisiting the association of smoking and bone healing.

    PubMed

    Sarraf, Khaled M; Tavare, Aniket; Somashekar, Naresh; Langstaff, Ronald J

    2011-01-01

    Isolated radial styloid fractures occur relatively infrequently, with non-union of such fractures, especially when undisplaced, being highly unusual. Smoking of tobacco, a common habit which is decreasing in prevalence in the developed world, has been proven to exert many adverse effects on tissue healing including bone union. We present a case of non-union of an undisplaced radial styloid fracture in the dominant hand of a young and healthy heavy smoker, emphasising the negative impact of tobacco smoke and its association with bone repair. We suggest that heavy tobacco users should also be followed up more vigilantly with this complication in mind, with smoking cessation modalities being offered on presentation. PMID:21348035

  12. 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

  13. Exogenous Ghrelin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats.

    PubMed

    Matuszyk, Aleksandra; Ceranowicz, Piotr; Warzecha, Zygmunt; Cieszkowski, Jakub; Ceranowicz, Dagmara; Gałązka, Krystyna; Bonior, Joanna; Jaworek, Jolanta; Bartuś, Krzysztof; Gil, Krzysztof; Olszanecki, Rafał; Dembiński, Artur

    2016-01-01

    Previous studies have shown that ghrelin reduces colonic inflammation induced by trinitrobenzene sulfonic acid and dextran sodium sulfate. In the present study we determined the effect of treatment with ghrelin on the course of acetic acid-induced colitis in rats. Rectal administration of 3% acetic acid solution led to induction of colitis in all animals. Damage of the colonic wall was accompanied by an increase in mucosal concentration of pro-inflammatory interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), as well mucosal activity of myeloperoxidase. Moreover, induction of colitis led to a reduction in colonic blood flow and DNA synthesis. Administration of ghrelin after induction of colitis led to faster regeneration of the colonic wall and reduction in colonic levels of IL-1β, TNF-α, and myeloperoxidase. In addition, treatment with ghrelin improved mucosal DNA synthesis and blood flow. Our study disclosed that ghrelin exhibits a strong anti-inflammatory and healing effect in acetic acid-induced colitis. Our current observation in association with previous findings that ghrelin exhibits curative effect in trinitrobenzene sulfonic acid- and dextran sodium sulfate-induced colitis suggest that therapeutic effect of ghrelin in the colon is universal and independent of the primary cause of colitis. PMID:27598133

  14. The PHSRN sequence induces extracellular matrix invasion and accelerates wound healing in obese diabetic mice

    PubMed Central

    Livant, Donna L.; Brabec, R. Kaye; Kurachi, Kotoku; Allen, David L.; Wu, Yanling; Haaseth, Ronald; Andrews, Philip; Ethier, Stephen P.; Markwart, Sonja

    2000-01-01

    The PHSRN sequence of the plasma fibronectin (pFn) cell-binding domain induces human keratinocytes and fibroblasts to invade the naturally serum-free extracellular matricies of sea urchin embryos. The potency of acetylated, amidated PHSRN (Ac-PHSRN-NH2) is significantly increased, making it more active on a molar basis than the 120-kDa cell-binding domain of pFn. Arginine is important to this activity because PHSAN and PHSEN are inactive, as is a randomized sequence peptide, Ac-HSPNR-NH2. One treatment with Ac-PHSRN-NH2 stimulates reepithelialization and contraction of dermal wounds in healing-impaired, obese diabetic C57BL6/KsJ db/db mice. Wound closure is equally rapid in treated db/db and db/+ mice and may be more rapid than in untreated nondiabetic db/+ littermates. In contrast, treatment with either Ac-HSPNR-NH2 or normal saline (NS) has no effect. Analysis of sectioned db/db wounds shows that, in contrast to treatment with Ac-HSPNR-NH2 or NS, a single Ac-PHSRN-NH2 treatment stimulates keratinocyte and fibroblast migration into wounds, enhances fibroplasia and vascularization in the provisional matrix, and stimulates the formation of prominent fibers that may be associated with wound contraction. PMID:10841512

  15. Loss of CAR promotes migration and proliferation of HaCaT cells, and accelerates wound healing in rats via Src-p38 MAPK pathway

    PubMed Central

    Su, Linlin; Fu, Lanqing; Li, Xiaodong; Zhang, Yue; Li, Zhenzhen; Wu, Xue; Li, Yan; Bai, Xiaozhi; Hu, Dahai

    2016-01-01

    The coxsackie and adenovirus receptor (CAR) is a cell adhesion molecule mostly localized to cell-cell contacts in epithelial and endothelial cells. CAR is known to regulate tumor progression, however, its physiological role in keratinocyte migration and proliferation, two essential steps in re-epithelialization during wound healing, has less been investigated. Here we showed that CAR was predominantly expressed in the epidermis of human skin, CAR knockdown by RNAi significantly accelerated HaCaT cell migration and proliferation. In addition, knockdown of CAR in vitro increased p-Src, p-p38, and p-JNK protein levels; however, Src inhibitor PP2 prevented the increase of p-Src and p-p38 induced by CAR RNAi, but not p-JNK, and decelerated cell migration and proliferation. More intriguingly, in vivo CAR RNAi on the skin area surrounding the wounds on rat back visually accelerated wound healing and re-epithelialization process, while treatment with PP2 or p38 inhibitor SB203580 obviously inhibited these effects. By contrast, overexpressing CAR in HaCaT cells significantly decelerated cell migration and proliferation. Above results demonstrate that suppression of CAR could accelerate HaCaT cell migration and proliferation, and promote wound healing in rat skin, probably via Src-p38 MAPK pathway. CAR thus might serve as a novel therapeutic target for facilitating wound healing. PMID:26804208

  16. Bony Healing of Unstable Thoracolumbar Burst Fractures in the Elderly Using Percutaneously Applied Titanium Mesh Cages and a Transpedicular Fixation System with Expandable Screws

    PubMed Central

    Eschler, Anica; Ender, Stephan Albrecht; Schiml, Katharina; Mittlmeier, Thomas; Gradl, Georg

    2015-01-01

    . Bony healing after unstable osteoporotic burst fractures is possible. Trial Registration www.germanctr.de DRKS00005657 PMID:25706642

  17. Healing Acceleration of Acetic Acid-induced Colitis by Marigold (Calendula officinalis) in Male Rats

    PubMed Central

    Tanideh, Nader; Jamshidzadeh, Akram; Sepehrimanesh, Masood; Hosseinzadeh, Masood; Koohi-Hosseinabadi, Omid; Najibi, Asma; Raam, Mozhdeh; Daneshi, Sajad; Asadi-Yousefabad, Seyedeh-Leili

    2016-01-01

    Background/Aim: Ulcerative colitis (UC) is a type of chronic inflammatory bowel disease with unknown etiology. Several therapeutic strategies such as consumption of medicinal plants have been used for its treatment. The aim of this study was to evaluate healing effects of Calendula officinalis hydroalcoholic extract in experimentally induced UC in rat. Materials and Methods: Ninety-six rats, weighing 200 ± 20 g, were randomly divided into eight equal groups. UC induced by 3% acetic acid and oral doses of C. officinalis extract, 1500 and 3000 mg/kg, and enema (gel 10% and 20%) were given. Two groups as positive controls were given asacol (enema) and oral mesalamine. Negative control groups were given normal saline and base gel. On days 3 and 7, intestinal histopathology and weight changes, plus oxidative stress indices including malondialdehyde (MDA) level and myeloperoxidase (MPO) activity were assayed. Results: A significant increase in the body weight of rats was seen in the group given C. officinalis extract 3000 mg/kg orally, oral mesalamine, and 20% intracolonic gel form of marigold extract compared with negative control and base gel groups during the experimental period. Acute inflammation and granular atrophy after UC induction were resolved completely completely by both 20% intracolonic gel and 3000 mg/kg orally. An increase in MPO activity and a decrease in MDA level in response to oral and intracolonic gel form of C. officinalis were observed 3 and and 7 days after treatment (P < 0.05). Conclusion: Our results indicate that oral and enema forms of hydroalcoholic extract of C. officinalis can be offered as are potential therapeutic agents for UC induced in rats. PMID:26831607

  18. Bioprinted Amniotic Fluid-Derived Stem Cells Accelerate Healing of Large Skin Wounds

    PubMed Central

    Skardal, Aleksander; Mack, David; Kapetanovic, Edi; Atala, Anthony; Jackson, John D.; Yoo, James

    2012-01-01

    Stem cells obtained from amniotic fluid show high proliferative capacity in culture and multilineage differentiation potential. Because of the lack of significant immunogenicity and the ability of the amniotic fluid-derived stem (AFS) cells to modulate the inflammatory response, we investigated whether they could augment wound healing in a mouse model of skin regeneration. We used bioprinting technology to treat full-thickness skin wounds in nu/nu mice. AFS cells and bone marrow-derived mesenchymal stem cells (MSCs) were resuspended in fibrin-collagen gel and “printed” over the wound site. At days 0, 7, and 14, AFS cell- and MSC-driven wound closure and re-epithelialization were significantly greater than closure and re-epithelialization in wounds treated by fibrin-collagen gel only. Histological examination showed increased microvessel density and capillary diameters in the AFS cell-treated wounds compared with the MSC-treated wounds, whereas the skin treated only with gel showed the lowest amount of microvessels. However, tracking of fluorescently labeled AFS cells and MSCs revealed that the cells remained transiently and did not permanently integrate in the tissue. These observations suggest that the increased wound closure rates and angiogenesis may be due to delivery of secreted trophic factors, rather than direct cell-cell interactions. Accordingly, we performed proteomic analysis, which showed that AFS cells secreted a number of growth factors at concentrations higher than those of MSCs. In parallel, we showed that AFS cell-conditioned media induced endothelial cell migration in vitro. Taken together, our results indicate that bioprinting AFS cells could be an effective treatment for large-scale wounds and burns. PMID:23197691

  19. Mesenchymal stem cell-conditioned medium accelerates skin wound healing: An in vitro study of fibroblast and keratinocyte scratch assays

    SciTech Connect

    Walter, M.N.M.; Wright, K.T.; Fuller, H.R.; MacNeil, S.; Johnson, W.E.B.

    2010-04-15

    We have used in vitro scratch assays to examine the relative contribution of dermal fibroblasts and keratinocytes in the wound repair process and to test the influence of mesenchymal stem cell (MSC) secreted factors on both skin cell types. Scratch assays were established using single cell and co-cultures of L929 fibroblasts and HaCaT keratinocytes, with wound closure monitored via time-lapse microscopy. Both in serum supplemented and serum free conditions, wound closure was faster in L929 fibroblast than HaCaT keratinocyte scratch assays, and in co-culture the L929 fibroblasts lead the way in closing the scratches. MSC-CM generated under serum free conditions significantly enhanced the wound closure rate of both skin cell types separately and in co-culture, whereas conditioned medium from L929 or HaCaT cultures had no significant effect. This enhancement of wound closure in the presence of MSC-CM was due to accelerated cell migration rather than increased cell proliferation. A number of wound healing mediators were identified in MSC-CM, including TGF-{beta}1, the chemokines IL-6, IL-8, MCP-1 and RANTES, and collagen type I, fibronectin, SPARC and IGFBP-7. This study suggests that the trophic activity of MSC may play a role in skin wound closure by affecting both dermal fibroblast and keratinocyte migration, along with a contribution to the formation of extracellular matrix.

  20. The accelerating effect of negative pressure wound therapy with Prevena™ on the healing of a closed wound with persistent serous secretion.

    PubMed

    Altintas, Burak; Biber, Roland; Brem, Matthias H

    2015-12-01

    Negative pressure wound therapy has been lately used on closed incisions in the immediate postoperative period to accelerate wound healing. However, there are no data in the literature regarding the use of this type of therapy for wounds with persistent secretion in the early postoperative care. We present the first report of persistent postoperative serous wound secretion in a patient after femoral nailing treated successfully with Prevena™ (KCI), a closed incision negative pressure management system (CINPWT). PMID:24393137

  1. Recombinant growth factor mixtures induce cell cycle progression and the upregulation of type I collagen in human skin fibroblasts, resulting in the acceleration of wound healing processes.

    PubMed

    Lee, Do Hyun; Choi, Kyung-Ha; Cho, Jae-We; Kim, So Young; Kwon, Tae Rin; Choi, Sun Young; Choi, Yoo Mi; Lee, Jay; Yoon, Ho Sang; Kim, Beom Joon

    2014-05-01

    Application of growth factor mixtures has been used for wound healing and anti-wrinkles agents. The aim of this study was to evaluate the effect of recombinant growth factor mixtures (RGFM) on the expression of cell cycle regulatory proteins, type I collagen, and wound healing processes of acute animal wound models. The results showed that RGFM induced increased rates of cell proliferation and cell migration of human skin fibroblasts (HSF). In addition, expression of cyclin D1, cyclin E, cyclin-dependent kinase (Cdk)4, and Cdk2 proteins was markedly increased with a growth factor mixtures treatment in fibroblasts. Expression of type I collagen was also increased in growth factor mixtures-treated HSF. Moreover, growth factor mixtures-induced the upregulation of type I collagen was associated with the activation of Smad2/3. In the animal model, RGFM-treated mice showed accelerated wound closure, with the closure rate increasing as early as on day 7, as well as re-epithelization and reduced inflammatory cell infiltration than phosphate-buffered saline (PBS)-treated mice. In conclusion, the results indicated that RGFM has the potential to accelerate wound healing through the upregulation of type I collagen, which is partly mediated by activation of Smad2/3-dependent signaling pathway as well as cell cycle progression in HSF. The topical application of growth factor mixtures to acute and chronic skin wound may accelerate the epithelization process through these molecular mechanisms. PMID:24626875

  2. 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

  3. Angiopoietin-like 4 Stimulates STAT3-mediated iNOS Expression and Enhances Angiogenesis to Accelerate Wound Healing in Diabetic Mice

    PubMed Central

    Chong, Han Chung; Chan, Jeremy Soon Kiat; Goh, Chi Qin; Gounko, Natalia V; Luo, Baiwen; Wang, Xiaoling; Foo, Selin; Wong, Marcus Thien Chong; Choong, Cleo; Kersten, Sander; Tan, Nguan Soon

    2014-01-01

    Impaired wound healing is a major source of morbidity in diabetic patients. Poor outcome has, in part, been related to increased inflammation, poor angiogenesis, and deficiencies in extracellular matrix components. Despite the enormous impact of these chronic wounds, effective therapies are lacking. Here, we showed that the topical application of recombinant matricellular protein angiopoietin-like 4 (ANGPTL4) accelerated wound reepithelialization in diabetic mice, in part, by improving angiogenesis. ANGPTL4 expression is markedly elevated upon normal wound injury. In contrast, ANGPTL4 expression remains low throughout the healing period in diabetic wounds. Exogenous ANGPTL4 modulated several regulatory networks involved in cell migration, angiogenesis, and inflammation, as evidenced by an altered gene expression signature. ANGPTL4 influenced the expression profile of endothelial-specific CD31 in diabetic wounds, returning its profile to that observed in wild-type wounds. We showed ANGPTL4-induced nitric oxide production through an integrin/JAK/STAT3-mediated upregulation of inducible nitric oxide synthase (iNOS) expression in wound epithelia, thus revealing a hitherto unknown mechanism by which ANGPTL4 regulated angiogenesis via keratinocyte-to-endothelial-cell communication. These data show that the replacement of ANGPTL4 may be an effective adjunctive or new therapeutic avenue for treating poor healing wounds. The present finding also confirms that therapeutic angiogenesis remains an attractive treatment modality for diabetic wound healing. PMID:24903577

  4. Hierarchically micro-patterned nanofibrous scaffolds with a nanosized bio-glass surface for accelerating wound healing

    NASA Astrophysics Data System (ADS)

    Xu, He; Lv, Fang; Zhang, Yali; Yi, Zhengfang; Ke, Qinfei; Wu, Chengtie; Liu, Mingyao; Chang, Jiang

    2015-11-01

    A composite scaffold with a controlled micro-pattern, nano-sized fiber matrix and surface-modified nanobioglass component was successfully prepared for skin wound healing by combining the patterning electrospinning with pulsed laser deposition strategies, and the hierarchical micro/nano structures and nano-sized bioglass in the scaffolds could synergistically improve the efficiency and re-epithelialization of wound healing.A composite scaffold with a controlled micro-pattern, nano-sized fiber matrix and surface-modified nanobioglass component was successfully prepared for skin wound healing by combining the patterning electrospinning with pulsed laser deposition strategies, and the hierarchical micro/nano structures and nano-sized bioglass in the scaffolds could synergistically improve the efficiency and re-epithelialization of wound healing. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr04802h

  5. Hierarchically micro-patterned nanofibrous scaffolds with a nanosized bio-glass surface for accelerating wound healing.

    PubMed

    Xu, He; Lv, Fang; Zhang, Yali; Yi, Zhengfang; Ke, Qinfei; Wu, Chengtie; Liu, Mingyao; Chang, Jiang

    2015-11-28

    A composite scaffold with a controlled micro-pattern, nano-sized fiber matrix and surface-modified nanobioglass component was successfully prepared for skin wound healing by combining the patterning electrospinning with pulsed laser deposition strategies, and the hierarchical micro/nano structures and nano-sized bioglass in the scaffolds could synergistically improve the efficiency and re-epithelialization of wound healing. PMID:26503372

  6. Enhanced growth of endothelial precursor cells on PCG-matrix facilitates accelerated, fibrosis-free, wound healing: a diabetic mouse model.

    PubMed

    Kanitkar, Meghana; Jaiswal, Amit; Deshpande, Rucha; Bellare, Jayesh; Kale, Vaijayanti P

    2013-01-01

    Diabetes mellitus (DM)-induced endothelial progenitor cell (EPC) dysfunction causes impaired wound healing, which can be rescued by delivery of large numbers of 'normal' EPCs onto such wounds. The principal challenges herein are (a) the high number of EPCs required and (b) their sustained delivery onto the wounds. Most of the currently available scaffolds either serve as passive devices for cellular delivery or allow adherence and proliferation, but not both. This clearly indicates that matrices possessing both attributes are 'the need of the day' for efficient healing of diabetic wounds. Therefore, we developed a system that not only allows selective enrichment and expansion of EPCs, but also efficiently delivers them onto the wounds. Murine bone marrow-derived mononuclear cells (MNCs) were seeded onto a PolyCaprolactone-Gelatin (PCG) nano-fiber matrix that offers a combined advantage of strength, biocompatibility wettability; and cultured them in EGM2 to allow EPC growth. The efficacy of the PCG matrix in supporting the EPC growth and delivery was assessed by various in vitro parameters. Its efficacy in diabetic wound healing was assessed by a topical application of the PCG-EPCs onto diabetic wounds. The PCG matrix promoted a high-level attachment of EPCs and enhanced their growth, colony formation, and proliferation without compromising their viability as compared to Poly L-lactic acid (PLLA) and Vitronectin (VN), the matrix and non-matrix controls respectively. The PCG-matrix also allowed a sustained chemotactic migration of EPCs in vitro. The matrix-effected sustained delivery of EPCs onto the diabetic wounds resulted in an enhanced fibrosis-free wound healing as compared to the controls. Our data, thus, highlight the novel therapeutic potential of PCG-EPCs as a combined 'growth and delivery system' to achieve an accelerated fibrosis-free healing of dermal lesions, including diabetic wounds. PMID:23922871

  7. Low-intensity pulsed ultrasound for bone healing: an overview.

    PubMed

    Malizos, Konstantinos N; Hantes, Michael E; Protopappas, Vassilios; Papachristos, Athanasios

    2006-04-01

    Low-intensity ultrasound is a biophysical form of intervention in the fracture-repair process, which through several mechanisms accelerates healing of fresh fractures and enhances callus formation in delayed unions and nonunions. The goal of this review is to present the current knowledge obtained from basic science and animal studies, as well as existing evidence from clinical trials and case series with the different applications of ultrasound in the management of fractures, delayed unions, nonunions and distraction osteogenesis. Low-intensity pulsed ultrasound is currently applied transcutaneously, although recent experimental studies have proven the efficacy of a trans-osseous application for both enhancement and monitoring of the bone healing process with modern smart implant technologies. PMID:16581076

  8. Cryptotanshinone downregulates the profibrotic activities of hypertrophic scar fibroblasts and accelerates wound healing: A potential therapy for the reduction of skin scarring.

    PubMed

    Li, Yan; Shi, Shan; Gao, Jianxin; Han, Shichao; Wu, Xue; Jia, Yanhui; Su, Linlin; Shi, Jihong; Hu, Dahai

    2016-05-01

    Hypertrophic scar (HS) is a skin fibrotic disease that causes major clinically problematic symptoms. Cryptotanshinone (CT) is an important ingredient of Danshen (Salvia miltiorrhiza Bunge extract) that has been used to treat cardio-cerebral vascular diseases. Its clinical efficacy in HS remains unclear. To investigate whether CT can inhibit HS fibrosis, HS-derived fibroblastic cells (HSFs) were established and treated with or without CT. Type-collagen-I (Col1), type-collagen-III (Col3) and α-smooth muscle actin (α-SMA) expression were measured by western blot and real-time quantitative polymerase chain reaction. HSFs migration and contraction were assessed with the scratch assay and the fibroblast-populated collagen lattice (FPCL) contraction assay, respectively. Wound healing in CT-treated Balb/c mice was assessed by immunohistochemical analysis of collagen expression and Masson's trichrome staining analysis of collagen deposition. CT treatment of HSFs down-regulated Col1, Col3 and α-SMA mRNA and protein expression, HSFs migration, and HSFs contraction, and improved FPCL architecture. In mice, CT treatment accelerated wound healing: the scar margins were narrow and there was less collagen deposition in the regenerated tissue. Thus, CT promotes wound healing and decreases excessive deposition of extracellular matrix components. CT may help to prevent and reduce scarring. PMID:27133042

  9. An Immunomodulatory Protein (Ling Zhi-8) from a Ganoderma lucidum Induced Acceleration of Wound Healing in Rat Liver Tissues after Monopolar Electrosurgery

    PubMed Central

    Lin, Hao-Jan; Chang, Yushan-Sophie; Lin, Li-Hsiang; Haung, Chiung-Fang; Wu, Chia-Yu; Ou, Keng-Liang

    2014-01-01

    The purpose of this study was to investigate the effect of an immunomodulatory protein (Ling Zhi-8, LZ-8) on wound healing in rat liver tissues after monopolar electrosurgery. Animals were sacrificed for evaluations at 0, 3, 7, and 28 days postoperatively. It was found that the wound with the LZ-8 treatment significantly increases wound healing. Western blot analysis clearly indicated that the expression of NF-κB was decreased at 3, 7, and 28 days when liver tissues were treated with LZ-8. Moreover, caspase-3 activity of the liver tissue also significantly decreases at 7 and 28 days, respectively. DAPI staining and TUNEL assays revealed that only a minimal dispersion of NF-κB was found on the liver tissue treated with LZ-8 at day 7 as compared with day 3 and tissues without LZ-8 treatment. Similarly, apoptosis was decreased on liver tissues treated with LZ-8 at 7 days when compared to the control (monopolar electrosurgery) tissues. Therefore, the analytical results demonstrated that LZ-8 induced acceleration of wound healing in rat liver tissues after monopolar electrosurgery. PMID:24883073

  10. Polysaccharides-Rich Extract of Ganoderma lucidum (M.A. Curtis:Fr.) P. Karst Accelerates Wound Healing in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Cheng, Poh-Guat; Sabaratnam, Vikineswary; Kuppusamy, Umah Rani

    2013-01-01

    Ganoderma lucidum (M.A. Curtis:Fr.) P. Karst is a popular medicinal mushroom. Scientific reports had shown that the wound healing effects of G. lucidum were partly attributed to its rich polysaccharides. However, little attention has been paid to its potential effects on wounds associated with diabetes mellitus. In this study, we evaluated the wound healing activity of the hot aqueous extract of G. lucidum in streptozotocin-induced diabetic rats. The extract of G. lucidum was standardised based on chemical contents (w/w) of total polysaccharides (25.1%), ganoderic acid A (0.45%), and adenosine (0.069%). Six groups of six rats were experimentally wounded in the posterior neck region. Intrasite gel was used as a positive control and aqueous cream as the placebo. Topical application with 10% (w/w) of mushroom extract-incorporated aqueous cream was more effective than that with Intrasite gel in terms of wound closure. The antioxidant activity in serum of rats treated with aqueous extract of G. lucidum was significantly higher; whereas the oxidative protein products and lipid damage were lower when compared to those of the controls. These findings strongly support the beneficial effects of standardised aqueous extract of G. lucidum in accelerating wound healing in streptozotocin-induced diabetic rats. PMID:24348715

  11. Polysaccharides-Rich Extract of Ganoderma lucidum (M.A. Curtis:Fr.) P. Karst Accelerates Wound Healing in Streptozotocin-Induced Diabetic Rats.

    PubMed

    Cheng, Poh-Guat; Phan, Chia-Wei; Sabaratnam, Vikineswary; Abdullah, Noorlidah; Abdulla, Mahmood Ameen; Kuppusamy, Umah Rani

    2013-01-01

    Ganoderma lucidum (M.A. Curtis:Fr.) P. Karst is a popular medicinal mushroom. Scientific reports had shown that the wound healing effects of G. lucidum were partly attributed to its rich polysaccharides. However, little attention has been paid to its potential effects on wounds associated with diabetes mellitus. In this study, we evaluated the wound healing activity of the hot aqueous extract of G. lucidum in streptozotocin-induced diabetic rats. The extract of G. lucidum was standardised based on chemical contents (w/w) of total polysaccharides (25.1%), ganoderic acid A (0.45%), and adenosine (0.069%). Six groups of six rats were experimentally wounded in the posterior neck region. Intrasite gel was used as a positive control and aqueous cream as the placebo. Topical application with 10% (w/w) of mushroom extract-incorporated aqueous cream was more effective than that with Intrasite gel in terms of wound closure. The antioxidant activity in serum of rats treated with aqueous extract of G. lucidum was significantly higher; whereas the oxidative protein products and lipid damage were lower when compared to those of the controls. These findings strongly support the beneficial effects of standardised aqueous extract of G. lucidum in accelerating wound healing in streptozotocin-induced diabetic rats. PMID:24348715

  12. Hepatocyte Growth Factor Effects on Mesenchymal Stem Cells Derived from Human Arteries: A Novel Strategy to Accelerate Vascular Ulcer Wound Healing

    PubMed Central

    Valente, Sabrina; Pasanisi, Emanuela; Ricci, Francesca; Stella, Andrea

    2016-01-01

    Vascular ulcers are a serious complication of peripheral vascular disease, especially in diabetics. Several approaches to treat the wounds are proposed but they show poor outcomes and require long healing times. Hepatocyte Growth Factor/Scatter Factor (HGF/SF) is a pleiotropic cytokine exerting many biological activities through the c-Met receptor. This study was aimed at verifying whether HGF/SF influences proliferation, migration, and angiogenesis on mesenchymal stem cells isolated from human arteries (hVW-MSCs). hVW-MSCs were exposed to NIBSC HGF/SF (2.5, 5, 10, and 70 ng/mL) from 6 hrs to 7 days. HGF and c-MET mRNA and protein expression, cell proliferation (Alamar Blue and Ki–67 assay), migration (scratch and transwell assays), and angiogenesis (Matrigel) were investigated. hVW-MSCs displayed stemness features and expressed HGF and c-MET. HGF/SF did not increase hVW-MSC proliferation, whereas it enhanced the cell migration, the formation of capillary-like structures, and the expression of angiogenic markers (vWF, CD31, and KDR). The HGF/SF effects on hVW-MSC migration and angiogenic potential are of great interest to accelerate wound healing process. Local delivery of HGF/SF could therefore improve the healing of unresponsive vascular ulcers. PMID:26788066

  13. The Absence of Beta-3 Integrin Accelerates Early Skeletal Repair

    PubMed Central

    Hu, Diane; Lu, Chuanyong; Sapozhnikova, Anna; Barnett, Michael; Sparrey, Carolyn; Miclau, Theodore; Marcucio, Ralph S.

    2010-01-01

    Integrins are heterodimeric transmembrane proteins that mediate cell-matrix interactions and modulate cell behavior. β3 subunit is a component of αII β 3 and αv β3 integrins. In this study, we first determined that β3 transcripts are expressed by cells within fracture calluses at 7 and 10 days after injury in a mouse model. We then analyzed fracture healing in mice deficient of β3 integrin with molecular, histomorphometric, and biomechanical techniques. We found that lack ofβ3 integrin results in an extended bleeding time and leads to more bone formation and accelerated cartilage maturation at 7 days after injury. However, β3 deficiency does not appear to affect later fracture healing. At days 14 and 21, histological appearance or biomechanical properties of fracture calluses are similar between wild type and mutant mice. We also found that altered fracture healing in β3 null mice is not associated with accelerated angiogenesis, since no significant difference of length density and surface density of blood vessels in fracture limbs was detected at 3 days after injury between wild type and β3 null mice. In conclusion, our findings demonstrate that β3 integrin plays an important role during early fracture healing. Further research is required to determine the underlying mechanisms. PMID:19637214

  14. Evaluation of the effectiveness of early or delayed treatment upon healing of mandibular fractures: A retrospective study

    PubMed Central

    Gazal, Giath

    2015-01-01

    Objectives: This study was aimed to assess the impacts of delay treatment of mandibular fracture and its complications. In addition risk variables related such as time to repair, fracture types, substance abuse, causes, surgical management, muddling or complications and duration of clinic stay were also evaluated. Materials and Methods: The data of patients attending the Newcastle General Hospital, UK for the management of mandibular fractures were probed. This retrospective clinical trial conducted over 6 months, included 91 patients attending trauma operating theatre during weekdays or weekends. Data were analyzed for time to admission and treatment and its relationships to various factors using SPSS version 20 (SPSS Inc., Chicago, IL). Results: Time to treatment from the point of admission was 31.50 ± 3.83 h during week days that has been significantly more for patients attending the hospital at weekends or nights. Similar trend was observed for total summative time from the incident to treatment analysis. Conclusions: This investigation has demonstrated that the rate of infection and postoperative complications following surgical treatment of mandible fractures can be eased off by reducing the waiting time from presentation to the emergency and to the operating theater. PMID:25713490

  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. 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 ...

  17. Fractures

    MedlinePlus

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

  18. Collagen Hydrogel Scaffold and Fibroblast Growth Factor-2 Accelerate Periodontal Healing of Class II Furcation Defects in Dog

    PubMed Central

    Momose, Takehito; Miyaji, Hirofumi; Kato, Akihito; Ogawa, Kosuke; Yoshida, Takashi; Nishida, Erika; Murakami, Syusuke; Kosen, Yuta; Sugaya, Tsutomu; Kawanami, Masamitsu

    2016-01-01

    Objective: Collagen hydrogel scaffold exhibits bio-safe properties and facilitates periodontal wound healing. However, regenerated tissue volume is insufficient. Fibroblast growth factor-2 (FGF2) up-regulates cell behaviors and subsequent wound healing. We evaluated whether periodontal wound healing is promoted by application of collagen hydrogel scaffold in combination with FGF2 in furcation defects in beagle dogs. Methods: Collagen hydrogel was fabricated from bovine type I collagen with an ascorbate-copper ion cross-linking system. Collagen hydrogel was mingled with FGF2 and injected into sponge-form collagen. Subsequently, FGF2 (50 µg)/collagen hydrogel scaffold and collagen hydrogel scaffold alone were implanted into class II furcation defects in dogs. In addition, no implantation was performed as a control. Histometric parameters were assessed at 10 days and 4 weeks after surgery. Result: FGF2 application to scaffold promoted considerable cell and tissue ingrowth containing numerous cells and blood vessel-like structure at day 10. At 4 weeks, reconstruction of alveolar bone was stimulated by implantation of scaffold loaded with FGF2. Furthermore, periodontal attachment, consisting of cementum-like tissue, periodontal ligament-like tissue and Sharpey’s fibers, was also repaired, indicating that FGF2-loaded scaffold guided self-assembly and then re-established the function of periodontal organs. Aberrant healing, such as ankylosis and root resorption, was not observed. Conclusion: FGF2-loaded collagen hydrogel scaffold possessed excellent biocompatibility and strongly promoted periodontal tissue engineering, including periodontal attachment re-organization. PMID:27583044

  19. Ciliary neurotrophic factor promotes the activation of corneal epithelial stem/progenitor cells and accelerates corneal epithelial wound healing.

    PubMed

    Zhou, Qingjun; Chen, Peng; Di, Guohu; Zhang, Yangyang; Wang, Yao; Qi, Xia; Duan, Haoyun; Xie, Lixin

    2015-05-01

    Ciliary neurotrophic factor (CNTF), a well-known neuroprotective cytokine, has been found to play an important role in neurogenesis and functional regulations of neural stem cells. As one of the most innervated tissue, however, the role of CNTF in cornea epithelium remains unclear. This study was to explore the roles and mechanisms of CNTF in the activation of corneal epithelial stem/progenitor cells and wound healing of both normal and diabetic mouse corneal epithelium. In mice subjecting to mechanical removal of corneal epithelium, the corneal epithelial stem/progenitor cell activation and wound healing were promoted by exogenous CNTF application, while delayed by CNTF neutralizing antibody. In cultured corneal epithelial stem/progenitor cells, CNTF enhanced the colony-forming efficiency, stimulated the mitogenic proliferation, and upregulated the expression levels of corneal epithelial stem/progenitor cell-associated transcription factors. Furthermore, the promotion of CNTF on the corneal epithelial stem/progenitor cell activation and wound healing was mediated by the activation of STAT3. Moreover, in diabetic mice, the content of CNTF in corneal epithelium decreased significantly when compared with that of normal mice, and the supplement of CNTF promoted the diabetic corneal epithelial wound healing, accompanied with the advanced activation of corneal epithelial stem/progenitor cells and the regeneration of corneal nerve fibers. Thus, the capability of expanding corneal epithelial stem/progenitor cells and promoting corneal epithelial wound healing and nerve regeneration indicates the potential application of CNTF in ameliorating limbal stem cell deficiency and treating diabetic keratopathy. PMID:25546438

  20. Mesenchymal stromal cells form vascular tubes when placed in fibrin sealant and accelerate wound healing in vivo.

    PubMed

    Mendez, Julio J; Ghaedi, Mahboobe; Sivarapatna, Amogh; Dimitrievska, Sashka; Shao, Zhen; Osuji, Chinedum O; Steinbacher, Derek M; Leffell, David J; Niklason, Laura E

    2015-02-01

    Non-healing, chronic wounds are a growing public health problem and may stem from insufficient angiogenesis in affected sites. Here, we have developed a fibrin formulation that allows adipose-derived mesenchymal stromal cells (ADSCs) to form tubular structures in vitro. The tubular structures express markers of endothelium, including CD31 and VE-Cadherin, as well as the pericyte marker NG2. The ability for the MSCs to form tubular structures within the fibrin gels was directly dependent on the stoichiometric ratios of thrombin and fibrinogen and the resulting gel concentration, as well as on the presence of bFGF. Fibrin gel formulations that varied in stiffness were tested. ADSCs that are embedded in a stiff fibrin formulation express VE-cadherin and CD31 as shown by PCR, FACS and immunostaining. Confocal imaging analysis demonstrated that tubular structures formed, containing visible lumens, in the stiff fibrin gels in vitro. There was also a difference in the amounts of bFGF secreted by ADSCs grown in the stiffer gels as compared to softer gels. Additionally, hAT-MSCs gave rise to perfusable vessels that were VE-cadherin positive after subcutaneous injection into mice, whereas the softer fibrin formulation containing ADSCs did not. The application of ADSCs delivered in the stiff fibrin gels allowed for the wounds to heal more quickly, as assessed by wound size, amount of granulation tissue and collagen content. Interestingly, following 5 days of healing, the ADSCs remained within the fibrin gel and did not integrate into the granulation tissue of healing wounds in vivo. These data show that ADSCs are able to form tubular structures within fibrin gels, and may also contribute to faster wound healing, as compared with no treatment or to wounds treated with fibrin gels devoid of ADSCs. PMID:25433608

  1. Chitosan Dermal Substitute and Chitosan Skin Substitute Contribute to Accelerated Full-Thickness Wound Healing in Irradiated Rats

    PubMed Central

    Mohd Hilmi, Abu Bakar; Halim, Ahmad Sukari; Jaafar, Hasnan; Asiah, Abu Bakar; Hassan, Asma

    2013-01-01

    Wounds with full-thickness skin loss are commonly managed by skin grafting. In the absence of a graft, reepithelialization is imperfect and leads to increased scar formation. Biomaterials can alter wound healing so that it produces more regenerative tissue and fewer scars. This current study use the new chitosan based biomaterial in full-thickness wound with impaired healing on rat model. Wounds were evaluated after being treated with a chitosan dermal substitute, a chitosan skin substitute, or duoderm CGF. Wounds treated with the chitosan skin substitute showed the most re-epithelialization (33.2 ± 2.8%), longest epithelial tongue (1.62 ± 0.13 mm), and shortest migratory tongue distance (7.11 ± 0.25 mm). The scar size of wounds treated with the chitosan dermal substitute (0.13 ± 0.02 cm) and chitosan skin substitute (0.16 ± 0.05 cm) were significantly decreased (P < 0.05) compared with duoderm (0.45 ± 0.11 cm). Human leukocyte antigen (HLA) expression on days 7, 14, and 21 revealed the presence of human hair follicle stem cells and fibroblasts that were incorporated into and surviving in the irradiated wound. We have proven that a chitosan dermal substitute and chitosan skin substitute are suitable for wound healing in full-thickness wounds that are impaired due to radiation. PMID:24324974

  2. Chitosan dermal substitute and chitosan skin substitute contribute to accelerated full-thickness wound healing in irradiated rats.

    PubMed

    Mohd Hilmi, Abu Bakar; Halim, Ahmad Sukari; Jaafar, Hasnan; Asiah, Abu Bakar; Hassan, Asma

    2013-01-01

    Wounds with full-thickness skin loss are commonly managed by skin grafting. In the absence of a graft, reepithelialization is imperfect and leads to increased scar formation. Biomaterials can alter wound healing so that it produces more regenerative tissue and fewer scars. This current study use the new chitosan based biomaterial in full-thickness wound with impaired healing on rat model. Wounds were evaluated after being treated with a chitosan dermal substitute, a chitosan skin substitute, or duoderm CGF. Wounds treated with the chitosan skin substitute showed the most re-epithelialization (33.2 ± 2.8%), longest epithelial tongue (1.62 ± 0.13 mm), and shortest migratory tongue distance (7.11 ± 0.25 mm). The scar size of wounds treated with the chitosan dermal substitute (0.13 ± 0.02 cm) and chitosan skin substitute (0.16 ± 0.05 cm) were significantly decreased (P < 0.05) compared with duoderm (0.45 ± 0.11 cm). Human leukocyte antigen (HLA) expression on days 7, 14, and 21 revealed the presence of human hair follicle stem cells and fibroblasts that were incorporated into and surviving in the irradiated wound. We have proven that a chitosan dermal substitute and chitosan skin substitute are suitable for wound healing in full-thickness wounds that are impaired due to radiation. PMID:24324974

  3. Clinical evaluation of Cissus quadrangularis as osteogenic agent in maxillofacial fracture: A pilot study

    PubMed Central

    Brahmkshatriya, Hemal R.; Shah, Kruti A.; Ananthkumar, G. B.; Brahmkshatriya, Mansi H.

    2015-01-01

    Introduction: Cissus quadrangularis Linn. is an indigenous medicinal plant, grown in India, which helps to increase healing process of fractured bone. Fracture of maxillofacial skeletal takes reasonably long time to heal. Many attempts have been made till today to reduce the healing period of 6–8 weeks, by means of improved surgical technology or by inhibiting the physiological mechanism of bone healing. Aim: To evaluate the effect of C. quadrangularis in healing process of maxillofacial fracture. Materials and Methods: All the patients were treated by open reduction internal fixation method and in postoperative management, antibiotics, and analgesics. Patients were divided into two groups. In Group 1, one capsule of C. quadrangularis (500 mg) thrice a day for 6 weeks was administered (n = 5), and in Group 2 (control group), no supplementary medication was administered (n = 4). Pain, swelling, fragment mobility, serum calcium, and serum phosphorus were evaluated pre- and post-operatively on day-1, -21, and -45. Results: Pain, swelling, and fragment mobility were low in Group 1 compared to Group 2. Serum calcium and serum phosphorus were also high, and healing of bone was clearly seen in Group 1 on day 21 as compared to control group. Conclusion: C. quadrangularis helps in reducing pain, swelling, and fracture mobility and accelerate the healing of fracture jaw bones. PMID:27011718

  4. 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

  5. Local release of pioglitazone (a peroxisome proliferator-activated receptor γ agonist) accelerates proliferation and remodeling phases of wound healing.

    PubMed

    Sakai, Shigeki; Sato, Keisuke; Tabata, Yasuhiko; Kishi, Kazuo

    2016-01-01

    Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor superfamily known for its anti-inflammatory and macrophage differentiation effects, as well as its ability to promote fat cell differentiation and reduce insulin resistance. Pioglitazone (Pio) is a PPARγ agonist used clinically as an anti-diabetic agent for improving insulin sensitivity in patients with diabetes. The objective of this study was to develop a drug delivery system (DDS) for the local release of Pio to promote wound healing. Pio of low aqueous solubility was water-solubilized by micelles formed from gelatin grafted with L-lactic acid oligomers, and incorporated into a biodegradable gelatin hydrogel. An 8-mm punch biopsy tool was used to prepare two skin wounds on either side of the midline of 8-week-old mice. Wounds were treated by the hydrogels with (Pio-hydrogel group) or without (control group) Pio, and the wound area were observed 1, 4, 7, and 14 days after treatment. In addition, a protein assay and immunohistological stain were performed to determine the effects of the Pio-hydrogel on inflammation and macrophage differentiation. The Pio-hydrogels promote wound healing. Moreover, Western blotting analysis demonstrated that treatment with Pio-hydrogels resulted in decreased levels of the cytokines MIP-2 and TGF-β, and increased levels of glucose-regulating adiponectin. It is concluded that Pio-incorporated hydrogels promote the proliferation and remodeling phases of wound healing, and may prove to be effective as wound dressings. PMID:26710090

  6. Gastric pentadecapeptide BPC 157 accelerates healing of transected rat Achilles tendon and in vitro stimulates tendocytes growth.

    PubMed

    Staresinic, M; Sebecic, B; Patrlj, L; Jadrijevic, S; Suknaic, S; Perovic, D; Aralica, G; Zarkovic, N; Borovic, S; Srdjak, M; Hajdarevic, K; Kopljar, M; Batelja, L; Boban-Blagaic, A; Turcic, I; Anic, T; Seiwerth, S; Sikiric, P

    2003-11-01

    In studies intended to improve healing of transected Achilles tendon, effective was a stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W. 1419). Currently in clinical trials for inflammatory bowel disease (PLD-116, PL 14736, Pliva), it ameliorates internal and external wound healing. In rats, the right Achilles tendon transected (5 mm proximal to its calcaneal insertion) presents with a large tendon defect between cut ends. Agents (/kg b.w., i.p., once time daily) (BPC 157 (dissolved in saline, with no carrier addition) (10 microg, 10 ng or 10 pg) or saline (5.0 ml)), were firstly applied at 30 min after surgery, the last application at 24 h before autopsy. Achilles functional index (AFI) was assessed once time daily. Biomechanical, microscopical and macroscopical assessment was on day 1, 4, 7, 10 and 14. Controls generally have severely compromised healing. In comparison, pentadecapeptide BPC 157 fully improves recovery: (i) biomechanically, increased load of failure, load of failure per area and Young's modulus of elasticity; (ii) functionally, significantly higher AFI-values; (iii) microscopically, more mononuclears and less granulocytes, superior formation of fibroblasts, reticulin and collagen; (iv) macroscopically, smaller size and depth of tendon defect, and subsequently the reestablishment of full tendon integrity. Likewise, unlike TGF-beta, pentadecapeptide BPC 157, presenting with no effect on the growth of cultured cell of its own, consistently opposed 4-hydroxynonenal (HNE), a negative modulator of the growth. HNE-effect is opposed in both combinations: BPC 157+HNE (HNE growth inhibiting effect reversed into growth stimulation of cultured tendocytes) and HNE+BPC 157(abolished inhibiting activity of the aldehyde), both in the presence of serum and serum deprived conditions. In conclusion, these findings, particularly, Achilles tendon transection fully recovered in rats, peptide stability suitable delivery, usefully favor gastric

  7. Comparison between Different Methods for Biomechanical Assessment of Ex Vivo Fracture Callus Stiffness in Small Animal Bone Healing Studies

    PubMed Central

    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

  8. Dinitrosyl iron complexes with glutathione incorporated into a collagen matrix as a base for the design of drugs accelerating skin wound healing.

    PubMed

    Shekhter, Anatoly B; Rudenko, Tatyana G; Istranov, Leonid P; Guller, Anna E; Borodulin, Rostislav R; Vanin, Anatoly F

    2015-10-12

    Composites of a collagen matrix and dinitrosyl iron complexes with glutathione (DNIC-GS) (in a dose of 4.0 μmoles per item) in the form of spongy sheets (DNIC-Col) were prepared and then topically applied in rat excisional full-thickness skin wound model. The effects of DNIC-Col were studied in comparison with spontaneously healing wounds (SpWH) and wounds treated with collagen sponges (Col) without DNIC-GS. The composites induced statistically and clinically significant acceleration of complete wound closure (21±1 day versus 23±1 day and 26±1 day for DNIC-Col, Col and SpWH, respectively). Histological examination of wound tissues on days 4, 14, 18 and 21 after surgery demonstrated that this improvement was supported by enhanced growth, maturation and fibrous transformation of granulation tissue and earlier epithelization of the injured area in rats treated with DNIC-Col composites benchmarked against Col and SpWH. It is suggested that the positive effect of the new pharmaceutical material on wound healing is based on the release of NO from decomposing DNIC. This effect is believed to be potentiated by the synergy of DNIC and collagen. PMID:26066410

  9. Osteogenic gene regulation and relative acceleration of healing by adenoviral-mediated transfer of human BMP-2 or -6 in equine osteotomy and ostectomy models.

    PubMed

    Ishihara, Akikazu; Shields, Kathleen M; Litsky, Alan S; Mattoon, John S; Weisbrode, Steven E; Bartlett, Jeffrey S; Bertone, Alicia L

    2008-06-01

    This study evaluated healing of equine metatarsal osteotomies and ostectomies in response to percutaneous injection of adenoviral (Ad) bone morphogenetic protein (BMP)-2, Ad-BMP-6, or beta-galactosidase protein vector control (Ad-LacZ) administered 14 days after surgery. Radiographic and quantitative computed tomographic assessment of bone formation indicated greater and earlier mineralized callus in both the osteotomies and ostectomies of the metatarsi injected with Ad-BMP-2 or Ad-BMP-6. Peak torque to failure and torsional stiffness were greater in osteotomies treated with Ad-BMP-2 than Ad-BMP-6, and both Ad-BMP-2- and Ad-BMP-6-treated osteotomies were greater than Ad-LacZ or untreated osteotomies. Gene expression of ostectomy mineralized callus 8 weeks after surgery indicated upregulation of genes related to osteogenesis compared to intact metatarsal bone. Expression of transforming growth factor beta-1, cathepsin H, and gelsolin-like capping protein were greater in Ad-BMP-2- and Ad-BMP-6-treated callus compared to Ad-LacZ-treated or untreated callus. Evidence of tissue biodistribution of adenovirus in distant organs was not identified by quantitative PCR, despite increased serum antiadenoviral vector antibody. This study demonstrated a greater relative potency of Ad-BMP-2 over Ad-BMP-6 in accelerating osteotomy healing when administered in this regimen, although both genes were effective at increasing bone at both osteotomy and ostectomy sites. PMID:18241059

  10. 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

  11. 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.

  12. Hypoxic Conditioned Medium from Human Amniotic Fluid-Derived Mesenchymal Stem Cells Accelerates Skin Wound Healing through TGF-β/SMAD2 and PI3K/Akt Pathways

    PubMed Central

    Jun, Eun Kyoung; Zhang, Qiankun; Yoon, Byung Sun; Moon, Jai-Hee; Lee, Gilju; Park, Gyuman; Kang, Phil Jun; Lee, Jung Han; Kim, Areee; You, Seungkwon

    2014-01-01

    In a previous study, we isolated human amniotic fluid (AF)-derived mesenchymal stem cells (AF-MSCs) and utilized normoxic conditioned medium (AF-MSC-norCM) which has been shown to accelerate cutaneous wound healing. Because hypoxia enhances the wound healing function of mesenchymal stem cell-conditioned medium (MSC-CM), it is interesting to explore the mechanism responsible for the enhancement of wound healing function. In this work, hypoxia not only increased the proliferation of AF-MSCs but also maintained their constitutive characteristics (surface marker expression and differentiation potentials). Notably, more paracrine factors, VEGF and TGF-β1, were secreted into hypoxic conditioned medium from AF-MSCs (AF-MSC-hypoCM) compared to AF-MSC-norCM. Moreover, AF-MSC-hypoCM enhanced the proliferation and migration of human dermal fibroblasts in vitro, and wound closure in a skin injury model, as compared to AF-MSC-norCM. However, the enhancement of migration of fibroblasts accelerated by AF-MSC-hypoCM was inhibited by SB505124 and LY294002, inhibitors of TGF-β/SMAD2 and PI3K/AKT, suggesting that AF-MSC-hypoCM-enhanced wound healing is mediated by the activation of TGF-β/SMAD2 and PI3K/AKT. Therefore, AF-MSC-hypoCM enhances wound healing through the increase of hypoxia-induced paracrine factors via activation of TGF-β/SMAD2 and PI3K/AKT pathways. PMID:24398984

  13. The Four-Herb Chinese Medicine Formula Tuo-Li-Xiao-Du-San Accelerates Cutaneous Wound Healing in Streptozotocin-Induced Diabetic Rats through Reducing Inflammation and Increasing Angiogenesis

    PubMed Central

    Zhang, Xiao-na; Ma, Ze-jun; Wang, Ying; Li, Yu-zhu; Sun, Bei; Guo, Xin; Pan, Cong-qing; Chen, Li-ming

    2016-01-01

    Impaired wound healing in diabetic patients is a serious complication that often leads to amputation or even death with limited effective treatments. Tuo-Li-Xiao-Du-San (TLXDS), a traditional Chinese medicine formula for refractory wounds, has been prescribed for nearly 400 years in China and shows good efficacy in promoting healing. In this study, we explored the effect of TLXDS on healing of diabetic wounds and investigated underlying mechanisms. Four weeks after intravenous injection of streptozotocin, two full-thickness excisional wounds were created with a 10 mm diameter sterile biopsy punch on the back of rats. The ethanol extract of TLXDS was given once daily by oral gavage. Wound area, histological change, inflammation, angiogenesis, and collagen synthesis were evaluated. TLXDS treatment significantly accelerated healing of diabetic rats and improved the healing quality. These effects were associated with reduced neutrophil infiltration and macrophage accumulation, enhanced angiogenesis, and increased collagen deposition. This study shows that TLXDS improves diabetes-impaired wound healing. PMID:27057551

  14. Acceleration of diabetic wound healing by a cryopreserved living dermal substitute created by micronized amnion seeded with fibroblasts

    PubMed Central

    Zheng, Yongjun; Ji, Shizhao; Wu, Haibin; Tian, Song; Wang, Xingtong; Luo, Pengfei; Fang, He; Wang, Zhihong; Wang, Junjie; Wang, Zhongshan; Xiao, Shichu; Xia, Zhaofan

    2015-01-01

    Bioengineered dermal substitutes have been used for the treatment of diabetic ulcers in clinics and achieved satisfactory results. However, constructing traditional tissue engineered dermal substitutes with two-step method is high-cost, time-consuming and greatly decreases fibroblast proliferative activity because of repeated trypsinization. Inthisstudy, we created a 3D micronized amniotic membrane (mAM) and used it as a natural microcarrier for ex vivo culture and amplification of human dermal fibroblasts (HDF) combined with the rotary cell culture system (RCCS). This one-step mAM-RCCS method couldamplify HDF quickly and construct a dermal substitute HDF-mAM simultaneously. To facilitate the clinical application of mAM-RCCS, anoptimized storage method was used.Post-thawing HDF-mAM retained high cell viability, intact cell morphology and active peptide secretion. When transplanted to the wounds of db/db mice, cryopreserved HDF-mAM promoted vascularization and diabetic wound healing significantly. These results demonstrate the potential application of cryopreserved HDF-mAM as a living dermal substitutefor treating diabetic ulcers and other chronic wounds in clinics. PMID:26885266

  15. Anti-Alpha-Toxin Monoclonal Antibody and Antibiotic Combination Therapy Improves Disease Outcome and Accelerates Healing in a Staphylococcus aureus Dermonecrosis Model

    PubMed Central

    Hilliard, Jamese J.; Datta, Vivekananda; Tkaczyk, Christine; Hamilton, Melissa; Sadowska, Agnieszka; Jones-Nelson, Omari; O'Day, Terrence; Weiss, William J.; Szarka, Szabolcs; Nguyen, Vien; Prokai, Laszlo; Suzich, JoAnn; Stover, C. Kendall

    2014-01-01

    Alpha-toxin (AT) is a major virulence determinant in Staphylococcus aureus skin and soft tissue infection models. We previously demonstrated that prophylactic administration of 2A3, an AT-neutralizing monoclonal antibody (MAb), prevents S. aureus disease in a mouse dermonecrosis model by neutralizing AT-mediated tissue necrosis and immune evasion. In the present study, MEDI4893*, an affinity-optimized version of 2A3, was characterized for therapeutic activity in the dermonecrosis model as a single agent and in combination with two frontline antibiotics, vancomycin and linezolid. MEDI4893* postinfection therapy was found to exhibit a therapeutic treatment window similar to that for linezolid but longer than that for vancomycin. Additionally, when combined with either vancomycin or linezolid, MEDI4893* resulted in reduced tissue damage, increased neutrophil and macrophage infiltration and abscess formation, and accelerated healing relative to those with the antibiotic monotherapies. These data suggest that AT neutralization with a potent MAb holds promise for both prophylaxis and adjunctive therapy with antibiotics and may be a valuable addition to currently available options for the treatment of S. aureus skin and soft tissue infections. PMID:25348518

  16. 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 ...

  17. Platelet-Rich Fibrin Promotes an Accelerated Healing of Achilles Tendon When Compared to Platelet-Rich Plasma in Rat

    PubMed Central

    Dietrich, Franciele; L. Duré, Gustavo; P. Klein, Caroline; F. Bampi, Vinícius; V. Padoin, Alexandre; D. Silva, Vinícius; Braga-Silva, Jefferson

    2015-01-01

    BACKGROUND Autologous platelet concentrate has been used to improve the function and regeneration of injured tissues. Tendinopathies are common in clinical practice, although long-term treatment is required. On the basis of lead time, we compared the effect of using platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) in repairing rat Achilles tendon. METHODS The effectiveness of using PRP and PRF was evaluated after 14 and 28 postoperative days by histological analysis. The quantification of collagen types I and III was performed by Sirius red staining. Qualitatively, the data were verified with hematoxylin-eosin (H&E) staining. RESULTS In Sirius red staining, no significant treatment differences were found between groups. Statistical difference was observed only between PRP (37.2% collagen) and the control group (16.2%) 14 days after treatment. Intra-groups compared twice showed a difference for collagen I (27.8% and 47.7%) and III (66.9% and 46.0%) in the PRF group. The control group showed differences only in collagen I (14.2% and 40.9%) and no other finding was observed in the PRP group. In H&E staining, PRF showed a better cellular organization when compared to the other groups at 28 days. CONCLUSION Our study suggests that PRF promotes accelerated regeneration of the Achilles tendon in rats, offering promising prospects for future clinical use. PMID:26284178

  18. Development of an Electromagnetic Acceleration Facility for Impact and Fracture Studies at High Strain Rates

    NASA Astrophysics Data System (ADS)

    Pahari, S.; Suryaprasad, I. V. V.; Shiv, N.; Madhavan, S.; Sijoy, C. D.; Chaturvedi, S.

    2011-07-01

    Experimental studies of strain time history and fracture & penetration resulting from the high velocity impact of solid projectiles on solid targets have been initiated. Design, fabrication, testing and commissioning of an electromagnetic impact facility driven by a capacitor bank have been carried out in this regard. The facility presently has an induction coil gun driving a cylindrical hollow/solid projectile on to a target. 3-7 kJ capacitor banks have been used to drive the launchers. The parameters of the coil gun are in consonance with a computer code developed in-house for the validation and optimization of the coil dimension and bank parameters. Systematic studies have been carried out for validation of code and understanding and benchmarking coil performance. Reproducible velocities of the order of 100 m/s have been successfully achieved with projectiles of masses 20 gm. Preliminary impact studies carried out on Alumnium target plates have given the strain time history.

  19. 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. PMID:23878824

  20. Inhibition of pathogenic bacterial growth on excision wound by green synthesized copper oxide nanoparticles leads to accelerated wound healing activity in Wistar Albino rats.

    PubMed

    Sankar, Renu; Baskaran, Athmanathan; Shivashangari, Kanchi Subramanian; Ravikumar, Vilwanathan

    2015-07-01

    An impaired wound healing is one of the major health related problem in diabetic and non-diabetic patients around the globe. The pathogenic bacteria play a predominant role in delayed wound healing, owing to interaction in the wound area. In our previous work we developed green chemistry mediated copper oxide nanoparticles using Ficus religiosa leaf extract. In the present study we make an attempt to evaluate the anti-bacterial, and wound healing activity of green synthesized copper oxide nanoparticles in male Wistar Albino rats. The agar well diffusion assay revealed copper oxide nanoparticles have substantial inhibition activity against human pathogenic strains such as Klebsiella pneumoniae, Shigella dysenteriae, Staphylococcus aureus, Salmonella typhimurium and Escherichia coli, which were responsible for delayed wound healing process. Furthermore, the analyses results of wound closure, histopathology and protein profiling confirmed that the F. religiosa leaf extract tailored copper oxide nanoparticles have enhanced wound healing activity in Wistar Albino rats. PMID:26194977

  1. Pediatric Open Fractures.

    PubMed

    Trionfo, Arianna; Cavanaugh, Priscilla K; Herman, Martin J

    2016-07-01

    Open fractures in children are rare and are typically associated with better prognoses compared with their adult equivalents. Regardless, open fractures pose a challenge because of the risk of healing complications and infection, leading to significant morbidity even in the pediatric population. Therefore, the management of pediatric open fractures requires special consideration. This article comprehensively reviews the initial evaluation, classification, treatment, outcomes, and controversies of open fractures in children. PMID:27241379

  2. 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).

  3. 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

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

    PubMed

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

    2015-09-01

    We have previously obtained compelling proof-of-principle evidence for COX2 gene therapy for fracture repair using integrating retroviral vectors. For this therapy to be suitable for patient uses, a suitable vector with high safety profile must be used. Accordingly, this study sought to evaluate the feasibility of AAV as the vector for this COX2 gene therapy, because AAV raises less safety issues than the retroviral vectors used previously. However, an appropriate AAV serotype is required to provide early increase in and adequate level of COX2 expression that is needed for fracture repair. Herein, we reported that AAV-DJ, an artificial AAV pseudoserotype, is highly effective in delivering COX2 gene to fracture sites in a mouse femoral fracture model. Compared with AAV-2, the use of AAV-DJ led to ~5-fold increase in infectivity in mesenchymal stem cells (MSCs) and provided an earlier and significantly higher level of transgene expression at the fracture site. Injection of this vector at a dose of 7.5 × 10(11) genomic copies led to high COX2 level at the fracture site on day 3 after injections and significantly promoted fracture union at 21 days, as analyzed by radiography and μ-CT. The therapeutic effect appears to involve enhanced osteoblastic differentiation of MSCs and remodeling of callus tissues to laminar bone. This interpretation is supported by the enhanced expression of several key genes participating in the fracture repair process. In conclusion, AAV-DJ is a promising serotype for the AAV-based COX2 gene therapy of fracture repair in humans. PMID:25965395

  5. 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 ...

  6. 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

  7. 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.

  8. Spontaneous calcaneal fracture in patients with diabetic foot ulcer: Four cases report and review of literature.

    PubMed

    Evran, Mehtap; Sert, Murat; Tetiker, Tamer; Akkuş, Gamze; Biçer, Ömer Sunkar

    2016-07-16

    Spontaneous calcaneal fractures in diabetic patients without obvious trauma may occur, sometimes accompanying diabetic foot ulcers. In the current study we report four cases who were hospitalized for diabetic foot ulcer with concomitant calcaneal fractures. There were four diabetic patients (one type 1 and three type 2) who registered with diabetic foot ulcers with coexisting calcaneal fractures, all of which were classified as Type A according to Essex Lopresti Calcaneal Fracture Classification. Two of the patients with renal failure were in a routine dialysis program, as well as vascular compromise and osteomyelitis in all of the patients. The diabetic foot ulcer of the 61 years old osteoporotic female patient healed with local debridement, vacuum assisted closure and then epidermal growth factor while the calcaneal fracture was then followed by elastic bandage. In two patients could not prevent progression of diabetic foot ulcers and calcaneal fractures to consequent below-knee amputation. The only patient with type 1 diabetes mellitus improved with antibiotic therapy and split thickness skin grafting, while the calcaneal fracture did not heal. In the current study we aimed to emphasize the spontaneous calcaneal fractures as possible co-existing pathologies in patients with diabetic foot ulcers. After all the medical treatment, amputation below knee had to be performed in 2 patients. It should be noted that other accompanying conditions such as impaired peripheral circulation, osteomyelitis, chronic renal failure, and maybe osteoporosis is a challenge of the recovery of calcaneal fractures and accelerate the progress to amputation in diabetic patients. PMID:27458594

  9. Spontaneous calcaneal fracture in patients with diabetic foot ulcer: Four cases report and review of literature

    PubMed Central

    Evran, Mehtap; Sert, Murat; Tetiker, Tamer; Akkuş, Gamze; Biçer, Ömer Sunkar

    2016-01-01

    Spontaneous calcaneal fractures in diabetic patients without obvious trauma may occur, sometimes accompanying diabetic foot ulcers. In the current study we report four cases who were hospitalized for diabetic foot ulcer with concomitant calcaneal fractures. There were four diabetic patients (one type 1 and three type 2) who registered with diabetic foot ulcers with coexisting calcaneal fractures, all of which were classified as Type A according to Essex Lopresti Calcaneal Fracture Classification. Two of the patients with renal failure were in a routine dialysis program, as well as vascular compromise and osteomyelitis in all of the patients. The diabetic foot ulcer of the 61 years old osteoporotic female patient healed with local debridement, vacuum assisted closure and then epidermal growth factor while the calcaneal fracture was then followed by elastic bandage. In two patients could not prevent progression of diabetic foot ulcers and calcaneal fractures to consequent below-knee amputation. The only patient with type 1 diabetes mellitus improved with antibiotic therapy and split thickness skin grafting, while the calcaneal fracture did not heal. In the current study we aimed to emphasize the spontaneous calcaneal fractures as possible co-existing pathologies in patients with diabetic foot ulcers. After all the medical treatment, amputation below knee had to be performed in 2 patients. It should be noted that other accompanying conditions such as impaired peripheral circulation, osteomyelitis, chronic renal failure, and maybe osteoporosis is a challenge of the recovery of calcaneal fractures and accelerate the progress to amputation in diabetic patients. PMID:27458594

  10. Use of a strontium-enriched calcium phosphate cement in accelerating the healing of soft-tissue tendon graft within the bone tunnel in a rabbit model of anterior cruciate ligament reconstruction.

    PubMed

    Kuang, G M; Yau, W P; Lu, W W; Chiu, K Y

    2013-07-01

    We investigated whether strontium-enriched calcium phosphate cement (Sr-CPC)-treated soft-tissue tendon graft results in accelerated healing within the bone tunnel in reconstruction of the anterior cruciate ligament (ACL). A total of 30 single-bundle ACL reconstructions using tendo Achillis allograft were performed in 15 rabbits. The graft on the tested limb was treated with Sr-CPC, whereas that on the contralateral limb was untreated and served as a control. At timepoints three, six, nine, 12 and 24 weeks after surgery, three animals were killed for histological examination. At six weeks, the graft-bone interface in the control group was filled in with fibrovascular tissue. However, the gap in the Sr-CPC group had already been completely filled in with new bone, and there was evidence of the early formation of Sharpey fibres. At 24 weeks, remodelling into a normal ACL-bone-like insertion was found in the Sr-CPC group. Coating of Sr-CPC on soft tissue tendon allograft leads to accelerated graft healing within the bone tunnel in a rabbit model of ACL reconstruction using Achilles tendon allograft. PMID:23814244

  11. 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

  12. How wounds heal

    MedlinePlus

    ... How puncture wounds heal; How burns heal; How pressure sores heal; How lacerations heal ... bleed. For example, burns, some puncture wounds, and pressure sores don't bleed. Once the scab forms, your ...

  13. Slow release delivery of rioprostil by an osmotic pump inhibits the formation of acute aspirin-induced gastric lesions in dogs and accelerates the healing of chronic lesions without incidence of side effects.

    PubMed

    Katz, L B; Shriver, D A

    1989-10-01

    Rioprostil, a primary alcohol prostaglandin E1 analog, inhibits gastric acid secretion and prevents gastric lesions induced by a variety of irritants in experimental animals. Because rioprostil is relatively short-acting, it would be of significant benefit clinically if its duration of action could be extended to allow once daily dosing. This investigation demonstrates that when administered via an osmotically driven pump (Osmet, Alza Corp.), rioprostil prevents the acute effects of aspirin on the gastric mucosa of dogs, accelerates the healing of aspirin-induced gastric lesions, and heals preexisting aspirin-induced gastric lesions during chronic administration of aspiring. The potency of rioprostil against acute gastric lesion formation was greatest when delivered from a 24-hr release pump (ED50 = 0.77 micrograms/kg/24 hr) and was 37 times greater than when administered as a single oral bolus. In addition, this activity occurred at doses which had little or no gastric antisecretory activity in betazole-stimulated Heidenhain pouch dogs. When delivered from a 24-hr pump, rioprostil (100 micrograms/kg/24 hr) healed preexisting aspirin-induced gastric lesions within 8 days after removal of aspirin, or after 15 days during continued daily aspirin administration. Additional studies determined that administration of rioprostil at doses of 720, 1440, or 2160 micrograms/kg/24 hr (935-2805 times the gastroprotective ED50 in 24 hr pumps) was well tolerated, with only slight, transient increases in body temperature, softening of the stools, and mild sedation at the highest dose. Administration of rioprostil daily for 5 days at 960 micrograms/kg/24 hr from 24-hr release pumps was also well tolerated by all dogs with no evidence of any accumulation of effect of rioprostil. In summary, administration of rioprostil via an osmotic pump increases its potency and duration of action against the gastric lesion-inducing effect of aspirin, and maintains a wide ratio of safety. PMID

  14. [Healing "booster" dressings].

    PubMed

    Fromantin, Isabelle; Téot, Luc; Meaume, Sylvie

    2011-09-01

    The relationship between the dressing and the wound is vital to clinical effectiveness. The more-or-less standard wound-surface coverings have been replaced with initial dressings, referred to as modern dressings, which contain an oily and sticky compound. They provide a moist medium by applying the basic mechanistic principles (liquid absorption and release). Other types of products and techniques modify the behaviour of wound cells by acting directly through irritation, biochemical stimulation or genetic modification of the cells, which accelerates the healing process. PMID:22003786

  15. Progress in corneal wound healing.

    PubMed

    Ljubimov, Alexander V; Saghizadeh, Mehrnoosh

    2015-11-01

    Corneal wound healing is a complex process involving cell death, migration, proliferation, differentiation, and extracellular matrix remodeling. Many similarities are observed in the healing processes of corneal epithelial, stromal and endothelial cells, as well as cell-specific differences. Corneal epithelial healing largely depends on limbal stem cells and remodeling of the basement membrane. During stromal healing, keratocytes get transformed to motile and contractile myofibroblasts largely due to activation of transforming growth factor-β (TGF-β) system. Endothelial cells heal mostly by migration and spreading, with cell proliferation playing a secondary role. In the last decade, many aspects of wound healing process in different parts of the cornea have been elucidated, and some new therapeutic approaches have emerged. The concept of limbal stem cells received rigorous experimental corroboration, with new markers uncovered and new treatment options including gene and microRNA therapy tested in experimental systems. Transplantation of limbal stem cell-enriched cultures for efficient re-epithelialization in stem cell deficiency and corneal injuries has become reality in clinical setting. Mediators and course of events during stromal healing have been detailed, and new treatment regimens including gene (decorin) and stem cell therapy for excessive healing have been designed. This is a very important advance given the popularity of various refractive surgeries entailing stromal wound healing. Successful surgical ways of replacing the diseased endothelium have been clinically tested, and new approaches to accelerate endothelial healing and suppress endothelial-mesenchymal transformation have been proposed including Rho kinase (ROCK) inhibitor eye drops and gene therapy to activate TGF-β inhibitor SMAD7. Promising new technologies with potential for corneal wound healing manipulation including microRNA, induced pluripotent stem cells to generate corneal

  16. Multifunctional composites: Healing, heating and electromagnetic integration

    NASA Astrophysics Data System (ADS)

    Plaisted, Thomas Anthony John

    2007-12-01

    Multifunctional materials, in the context of this research, integrate other functions into materials that foremost have outstanding structural integrity. Details of the integration of electromagnetic, heating, and healing functionalities into fiber-reinforced polymer composites are presented. As a result of fiber/wire integration through textile braiding and weaving, the dielectric constant of a composite may be tuned from negative to positive values. These wires are further leveraged to uniformly heat the composite through resistive heating. A healing functionality is introduced by utilizing a polymer matrix with the ability to heal internal cracking through thermally-reversible covalent bonds based on Diels-Alder cycloaddition. The Double Cleavage Drilled Compression (DCDC) specimen is applied to study the fracture and healing characteristics of the neat polymer. This method allows for quantitative evaluation of incremental crack growth, and ensures that the cracked sample remains in one piece after the test, improving the ability to re-align the fracture surfaces prior to healing. Initially, the fracture strength of PMMA is studied with various DCDC geometries to develop a model of the propagation of a crack within this type of specimen. Applied to the healable polymer (2MEP4F), repeated fracture-healing cycles demonstrate that treatment at temperatures between 85 to 95°C results in full fracture toughness recovery and no dimensional changes due to creep. The fracture toughness after each fracturing and healing cycle has been calculated, using the model, to yield a fracture toughness of about 0.71 MPa·m1/2 for this material at room temperature. Glass and carbon fiber-reinforced composites have been fabricated with the 2MEP4F polymer, and the ability of this polymer to heal microcracks in fiber-reinforced composites is demonstrated. Microcracks have been introduced into the composites by cryogenic cycling in liquid nitrogen, causing a reduction in the storage

  17. 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

  18. Ghrelin accelerates wound healing through GHS-R1a-mediated MAPK-NF-κB/GR signaling pathways in combined radiation and burn injury in rats.

    PubMed

    Liu, Cong; Huang, Jiawei; Li, Hong; Yang, Zhangyou; Zeng, Yiping; Liu, Jing; Hao, Yuhui; Li, Rong

    2016-01-01

    The therapeutic effect of ghrelin on wound healing was assessed using a rat model of combined radiation and burn injury (CRBI). Rat ghrelin, anti-rat tumor necrosis factor (TNF) α polyclonal antibody (PcAb), or selective antagonists of p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), and growth hormone secretagogue receptor (GHS-R) 1a (SB203580, SP600125, and [D-Lys3]-GHRP-6, respectively), were administered for seven consecutive days. Levels of various signaling molecules were assessed in isolated rat peritoneal macrophages. The results showed that serum ghrelin levels and levels of macrophage glucocorticoid receptor (GR) decreased, while phosphorylation of p38MAPK, JNK, and p65 nuclear factor (NF) κB increased. Ghrelin inhibited the serum induction of proinflammatory mediators, especially TNF-α, and promoted wound healing in a dose-dependent manner. Ghrelin treatment decreased phosphorylation of p38MAPK, JNK, and p65NF-κB, and increased GR levels in the presence of GHS-R1a. SB203580 or co-administration of SB203580 and SP600125 decreased TNF-α level, which may have contributed to the inactivation of p65NF-κB and increase in GR expression, as confirmed by western blotting. In conclusion, ghrelin enhances wound recovery in CRBI rats, possibly by decreasing the induction of TNF-α or other proinflammatory mediators that are involved in the regulation of GHS-R1a-mediated MAPK-NF-κB/GR signaling pathways. PMID:27271793

  19. Ghrelin accelerates wound healing through GHS-R1a-mediated MAPK-NF-κB/GR signaling pathways in combined radiation and burn injury in rats

    PubMed Central

    Liu, Cong; Huang, Jiawei; Li, Hong; Yang, Zhangyou; Zeng, Yiping; Liu, Jing; Hao, Yuhui; Li, Rong

    2016-01-01

    The therapeutic effect of ghrelin on wound healing was assessed using a rat model of combined radiation and burn injury (CRBI). Rat ghrelin, anti-rat tumor necrosis factor (TNF) α polyclonal antibody (PcAb), or selective antagonists of p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), and growth hormone secretagogue receptor (GHS-R) 1a (SB203580, SP600125, and [D-Lys3]-GHRP-6, respectively), were administered for seven consecutive days. Levels of various signaling molecules were assessed in isolated rat peritoneal macrophages. The results showed that serum ghrelin levels and levels of macrophage glucocorticoid receptor (GR) decreased, while phosphorylation of p38MAPK, JNK, and p65 nuclear factor (NF) κB increased. Ghrelin inhibited the serum induction of proinflammatory mediators, especially TNF-α, and promoted wound healing in a dose-dependent manner. Ghrelin treatment decreased phosphorylation of p38MAPK, JNK, and p65NF-κB, and increased GR levels in the presence of GHS-R1a. SB203580 or co-administration of SB203580 and SP600125 decreased TNF-α level, which may have contributed to the inactivation of p65NF-κB and increase in GR expression, as confirmed by western blotting. In conclusion, ghrelin enhances wound recovery in CRBI rats, possibly by decreasing the induction of TNF-α or other proinflammatory mediators that are involved in the regulation of GHS-R1a-mediated MAPK-NF-κB/GR signaling pathways. PMID:27271793

  20. 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 ...

  1. Ethanolic extract of roots from Arctium lappa L. accelerates the healing of acetic acid-induced gastric ulcer in rats: Involvement of the antioxidant system.

    PubMed

    da Silva, Luisa Mota; Allemand, Alexandra; Mendes, Daniel Augusto G B; Dos Santos, Ana Cristina; André, Eunice; de Souza, Lauro Mera; Cipriani, Thales Ricardo; Dartora, Nessana; Marques, Maria Consuelo Andrade; Baggio, Cristiane Hatsuko; Werner, Maria Fernanda

    2013-01-01

    We evaluate the curative efficacy of the ethanolic extract (EET) of roots from Arctium lappa (bardana) in healing of chronic gastric ulcers induced by 80% acetic acid in rats and additionally studies the possible mechanisms underlying this action. Oral administration of EET (1, 3, 10 and 30mg/kg) reduced the gastric lesion area in 29.2%, 41.4%, 59.3% and 38.5%, respectively, and at 10mg/kg promoted significant regeneration of the gastric mucosa, which was confirmed by proliferating cell nuclear antigen immunohistochemistry. EET (10mg/kg) treatment did not increase the gastric mucus content but restored the superoxide dismutase activity, prevented the reduction of glutathione levels, reduced lipid hydroperoxides levels, inhibited the myeloperoxidase activity and reduced the microvascular permeability. In addition, EET reduced the free radical generation and increased scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals in vitro. Furthermore, intraduodenal EET (10 and 30mg/kg) decreased volume and acidity of gastric secretion. Total phenolic compounds were high in EET (Folin-Ciocalteau assay) and the analysis by liquid chromatography-mass spectrometry revealed that the main compounds present in EET were a serie of hydroxycinnamoylquinic acid isomers. In conclusion, these data reveal that EET promotes regeneration of damaged gastric mucosa, probably through its antisecretory and antioxidative mechanisms. PMID:23036453

  2. Systemic treatment with strontium ranelate accelerates the filling of a bone defect and improves the material level properties of the healing bone.

    PubMed

    Zacchetti, Giovanna; Dayer, Romain; Rizzoli, René; Ammann, Patrick

    2014-01-01

    Rapid bone defect filling with normal bone is a challenge in orthopaedics and dentistry. Strontium ranelate (SrRan) has been shown to in vitro decrease bone resorption and increase bone formation, and represents a potential agent with the capacity to accelerate bone defect filling. In this study, bone tibial defects of 2.5 mm in diameter were created in 6-month-old female rats orally fed SrRan (625 mg/kg/d; 5/7 days) or vehicle for 4, 8, or 12 weeks (10 rats per group per time point) from the time of surgery. Tibias were removed. Micro-architecture was determined by micro-computed tomography (µCT) and material level properties by nanoindentation analysis. µCT analysis showed that SrRan administration significantly improved microarchitecture of trabecular bone growing into the defect after 8 and 12 weeks of treatment compared to vehicle. SrRan treatment also accelerated the growth of cortical bone over the defect, but with different kinetics compared to trabecular bone, as the effects were already significant after 4 weeks. Nanoindentation analysis demonstrated that SrRan treatment significantly increased material level properties of both trabecular bone and cortical bone filling the defect compared to vehicle. SrRan accelerates the filling of bone defect by improving cortical and trabecular bone microarchitecture both quantitatively and qualitatively. PMID:25243150

  3. 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

  4. Stress fracture of the medial malleolus.

    PubMed

    Orava, S; Karpakka, J; Taimela, S; Hulkko, A; Permi, J; Kujala, U

    1995-03-01

    We studied eight patients who had a stress fracture of the medial malleolus. The main symptom was localized pain on the medial side of the ankle. The initial radiographs revealed the lesion for only three patients; for the other patients, the diagnosis was made with the use of isotope scans and was confirmed with computerized tomography scans, magnetic resonance images, or subsequent plain radiographs. One vertical fracture was treated initially with compression with AO screws. On the basis of our experience with stress fractures in other bones, drilling was performed to enhance the formation of bone in two patients who had delayed healing and who had had symptoms for eight and twelve months. The fractures healed four and five months after the drilling. The five patients who were managed non-operatively had to avoid running and jumping for at least three months (average, four months) so that healing could take place. All five of these fractures healed within five months. PMID:7890784

  5. Autonomic healing of polymer composites

    NASA Astrophysics Data System (ADS)

    Sottos, N. R.; Geubelle, P. H.; Moore, J. S.; Kessler, M. R.; Sriram, S. R.; Brown, E. N.; Viswanathan, S.

    2001-02-01

    Structural polymers are susceptible to damage in the form of cracks, which form deep within the structure where detection is difficult and repair is almost impossible. Cracking leads to mechanical degradation of fibre-reinforced polymer composites; in microelectronic polymeric components it can also lead to electrical failure. Microcracking induced by thermal and mechanical fatigue is also a long-standing problem in polymer adhesives. Regardless of the application, once cracks have formed within polymeric materials, the integrity of the structure is significantly compromised. Experiments exploring the concept of self-repair have been previously reported, but the only successful crack-healing methods that have been reported so far require some form of manual intervention. Here we report a structural polymeric material with the ability to autonomically heal cracks. The material incorporates a microencapsulated healing agent that is released upon crack intrusion. Polymerization of the healing agent is then triggered by contact with an embedded catalyst, bonding the crack faces. Our fracture experiments yield as much as 75% recovery in toughness, and we expect that our approach will be applicable to other brittle materials systems (including ceramics and glasses).

  6. Mechanisms and Management of Stress Fractures in Physically Active Persons

    PubMed Central

    Romani, William A.; Gieck, Joe H.; Perrin, David H.; Saliba, Ethan N.; Kahler, David M.

    2002-01-01

    Objective: To describe the anatomy of bone and the physiology of bone remodeling as a basis for the proper management of stress fractures in physically active people. Data Sources: We searched PubMed for the years 1965 through 2000 using the key words stress fracture, bone remodeling, epidemiology, and rehabilitation. Data Synthesis: Bone undergoes a normal remodeling process in physically active persons. Increased stress leads to an acceleration of this remodeling process, a subsequent weakening of bone, and a higher susceptibility to stress fracture. When a stress fracture is suspected, appropriate management of the injury should begin immediately. Effective management includes a cyclic process of activity and rest that is based on the remodeling process of bone. Conclusions/Recommendations: Bone continuously remodels itself to withstand the stresses involved with physical activity. Stress fractures occur as the result of increased remodeling and a subsequent weakening of the outer surface ofthe bone. Once a stress fracture is suspected, a cyclic management program that incorporates the physiology of bone remodeling should be initiated. The cyclic program should allow the physically active person to remove the source of the stress to the bone, maintain fitness, promote a safe return to activity, and permit the bone to heal properly. PMID:16558676

  7. 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 usually occurs after an injury and often occurs with ...

  8. CT scan-evaluated outcome of pulsed electromagnetic fields in the treatment of acute scaphoid fractures: a randomised, multicentre, double-blind, placebo-controlled trial.

    PubMed

    Hannemann, P F W; van Wezenbeek, M R; Kolkman, K A; Twiss, E L L; Berghmans, C H J; Dirven, P A M G M; Brink, P R G; Poeze, M

    2014-08-01

    We hypothesised that the use of pulsed electromagnetic field (PEMF) bone growth stimulation in acute scaphoid fractures would significantly shorten the time to union and reduce the number of nonunions in a randomised, double-blind, placebo-controlled multicentre trial. A total of 102 patients (78 male, 24 female; mean age 35 years (18 to 77)) from five different medical centres with a unilateral undisplaced acute scaphoid fracture were randomly allocated to PEMF (n = 51) or placebo (n = 51) and assessed with regard to functional and radiological outcomes (multiplanar reconstructed CT scans) at 6, 9, 12, 24 and 52 weeks. The overall time to clinical and radiological healing did not differ significantly between the active PEMF group and the placebo group. We concluded that the addition of PEMF bone growth stimulation to the conservative treatment of acute scaphoid fractures does not accelerate bone healing. PMID:25086123

  9. Stress fractures in athletes.

    PubMed

    Hulkko, A; Orava, S

    1987-06-01

    During the 14-year period of 1971-1985, 368 stress fractures in 324 athletes were treated. The series contained 268 fractures in males and 100 fractures in females; 32 fractures occurred in children (less than 16 years), 117 in adolescents (16-19 years), and 219 in adults. Forty-six fractures were incurred by athletes at an international level, 274 by athletes at a national or district level and 48 by recreational athletes. Of the total cases, 72% occurred to runners and a further 12% to athletes in other sports after running exercises. The distribution of the stress fractures by site was: tibia 182, metatarsal bones 73, fibula 44, big toe sesamoid bones 15, femoral shaft 14, femoral neck 9, tarsal navicular 9, pelvis 7, olecranon 5 and other bones 10. Of the total fractures, 342 were treated conservatively and 26 fractures required surgical treatment. The operative indication was dislocation in 5 cases and delayed union/nonunion in 21 cases. The sites most often affected by delayed union were: anterior midtibia, sesamoid bones of the big toe, base of the fifth metatarsal, olecranon, and tarsal navicular. The athletes at an international level experienced the greatest risk of multiple separate fractures, protracted healing, or fractures requiring surgery. PMID:3623785

  10. Skull fracture

    MedlinePlus

    Basilar skull fracture; Depressed skull fracture; Linear skull fracture ... Skull fractures may occur with head injuries . The skull provides good protection for the brain. However, a severe impact ...

  11. 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.

  12. 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.

  13. Acceleration of aneurysm healing by P(DLLA-co-TMC)-coated coils enabling the controlled release of vascular endothelial growth factor.

    PubMed

    Wang, Qiujing; Gao, Yuyuan; Sun, Xinlin; Ji, Bin; Cui, Xubo; Liu, Yaqi; Zheng, Tao; Chen, Chengwei; Jiang, Xiaodan; Zhu, Aiping; Quan, Daping

    2014-08-01

    Since the introduction of the detachable coil in endovascular treatment of intracranial aneurysms, the in-hospital mortality rate has been significantly decreased. Recurrence of the aneurysm remains the major drawback of using detachable coils. We prepared a bioactive coil coated with poly(d,l-lactide)-7co-(1,3-trimethylene carbonate) (P(DLLA-co-TMC)), a novel copolymer for controlling the release of vascular endothelial growth factor (VEGF). Platinum coils were prepared by successive coating with cationic P(DLLA-co-TMC) and anionic heparin. Then, recombinant human VEGF-165 (rhVEGF) was immobilized by affinity binding to heparin. The morphological characteristics and sustained in vitro release of rhVEGF were examined using scanning electron microscopy and enzyme-linked immunosorbent assay, respectively. The efficacy of these novel coils modified by P(DLLA-co-TMC)/rhVEGF was tested using a common carotid artery aneurysm model in rats. Experimental aneurysms were embolized with unmodified, P(DLLA-co-TMC)/heparin-coated or P(DLLA-co-TMC)/rhVEGF-coated platinum coils (n = 18). The coils were removed on days 15, 30 and 90 after insertion, and the histological and immunohistochemical analysis of factor VIII was performed to confirm the presence of endothelial cells in the organized area. In addition, the controlled in vivo release of VEGF was confirmed by Western blotting analysis. The release of VEGF tended to increase during the whole period and no burst release was observed. In the group treated with P(DLLA-co-TMC)/rhVEGF-coated platinum coils, clot organization and endothelial cell proliferation were accelerated. The immunohistochemistry study showed that the expression of factor VIII was found in the P(DLLA-co-TMC)/rhVEGF-coated coil group but not in the other two groups. Furthermore, Western blotting analysis confirmed that the major released VEGF in the aneurysm sac was from the P(DLLA-co-TMC)/VEGF-coated coil. P(DLLA-co-TMC)/rhVEGF-coated platinum coils can

  14. Analogy between fluid cavitation and fracture mechanics

    NASA Technical Reports Server (NTRS)

    Hendricks, R. C.; Mullen, R. L.; Braun, M. J.

    1983-01-01

    When the stresses imposed on a fluid are sufficiently large, rupture or cavitation can occur. Such conditions can exist in many two-phase flow applications, such as the choked flows, which can occur in seals and bearings. Nonspherical bubbles with large aspect ratios have been observed in fluids under rapid acceleration and high shear fields. These bubbles are geometrically similar to fracture surface patterns (Griffith crack model) existing in solids. Analogies between crack growth in solid and fluid cavitation are proposed and supported by analysis and observation (photographs). Healing phenomena (void condensation), well accepted in fluid mechanics, have been observed in some polymers and hypothesized in solid mechanics. By drawing on the strengths of the theories of solid mechanics and cavitation, a more complete unified theory can be developed.

  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. 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

  17. Thyroid Hormone and Wound Healing

    PubMed Central

    Safer, Joshua D.

    2013-01-01

    Although thyroid hormone is one of the most potent stimulators of growth and metabolic rate, the potential to use thyroid hormone to treat cutaneous pathology has never been subject to rigorous investigation. A number of investigators have demonstrated intriguing therapeutic potential for topical thyroid hormone. Topical T3 has accelerated wound healing and hair growth in rodents. Topical T4 has been used to treat xerosis in humans. It is clear that the use of thyroid hormone to treat cutaneous pathology may be of large consequence and merits further study. This is a review of the literature regarding thyroid hormone action on skin along with skin manifestations of thyroid disease. The paper is intended to provide a context for recent findings of direct thyroid hormone action on cutaneous cells in vitro and in vivo which may portend the use of thyroid hormone to promote wound healing. PMID:23577275

  18. [Trochanteric femoral fractures].

    PubMed

    Douša, P; Čech, O; Weissinger, M; Džupa, V

    2013-01-01

    At the present time proximal femoral fractures account for 30% of all fractures referred to hospitals for treatment. Our population is ageing, the proportion of patients with post-menopausal or senile osteoporosis is increasing and therefore the number of proximal femoral fractures requiring urgent treatment is growing too. In the age category of 50 years and older, the incidence of these fractures has increased exponentially. Our department serves as a trauma centre for half of Prague and part of the Central Bohemia Region with a population of 1 150 000. Prague in particular has a high number of elderly citizens. Our experience is based on extensive clinical data obtained from the Register of Proximal Femoral Fractures established in 1997. During 14 years, 4280 patients, 3112 women and 1168 men, were admitted to our department for treatment of proximal femoral fractures. All patients were followed up until healing or development of complications. In the group under study, 82% were patients older than 70 years; 72% of those requiring surgery were in their seventies and eighties. Men were significantly younger than women (p<0.001) and represented 30% of the group. The fractures were 2.3-times more frequent in women than in men. In the category under 60 years, men significantly outnumbered women (p<0.001). The patients with pertrochanteric fractures were, on the average, eight years older than the patients with intertrochanteric fractures, which is a significant difference (p<0.001). The mortality rate within a year of injury was about 30%. Trochanteric fractures accounted for 54.7% and femoral neck fractures for 45.3% of all fractures. The inter-annual increase was 5.9%, with more trochanteric than femoral neck fractures. There was a non-significant decrease in intertrochanteric (AO 31-A3) fractures. On the other hand, the number of pertrochanteric (AO 31-A1+2) fractures increased significantly (p<0.001). A total of 1 394 fractures were treated with a proximal

  19. 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. PMID:20966434

  20. 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

  1. Small molecule GS-nitroxide ameliorates ionizing irradiation-induced delay in bone wound healing in a novel murine model.

    PubMed

    Gokhale, Abhay; Rwigema, Jean-Claude; Epperly, Michael W; Glowacki, Julie; Wang, Hong; Wipf, Peter; Goff, Julie P; Dixon, Tracy; Patrene, Ken; Greenberger, Joel S

    2010-01-01

    We studied radioprotection and mitigation by mitochondrial-targeted Tempol (GS-nitroxide, JP4-039), in a mouse injury/irradiation model of combined injury (fracture/irradiation). Right hind legs of control C57BL/6NHsd female mice, mice pretreated with MnSOD-PL, JP4-039, or with amifostine were irradiated with single and fractionated doses of 0 to 20 Gy. Twenty-four hours later, unicortical holes were drilled into the tibiae of both hind legs; at intervals, tibias were excised, radiographed, and processed for histology. Bone wounds irradiated to 20 or 30 Gy showed delayed healing at 21 to 28 days. Treatment with JP4-039 MnSOD-PL or amifostine, before or after single fraction 20 Gy or during fractionated irradiation followed by drilling accelerated wound healing at days 21 and 28. Orthotopic 3LL tumors were not protected by JP4-039 or amifostine. In nonirradiated mice, pretreatment with JP4-039 accelerated bone wound healing. This test system should be useful for the development of new small molecule radioprotectors. PMID:20668303

  2. Pulsed Electromagnetic Fields in the treatment of fresh scaphoid fractures. A multicenter, prospective, double blind, placebo controlled, randomized trial

    PubMed Central

    2011-01-01

    Background The scaphoid bone is the most commonly fractured of the carpal bones. In the Netherlands 90% of all carpal fractures is a fracture of the scaphoid bone. The scaphoid has an essential role in functionality of the wrist, acting as a pivot. Complications in healing can result in poor functional outcome. The scaphoid fracture is a troublesome fracture and failure of treatment can result in avascular necrosis (up to 40%), non-union (5-21%) and early osteo-arthritis (up to 32%) which may seriously impair wrist function. Impaired consolidation of scaphoid fractures results in longer immobilization and more days lost at work with significant psychosocial and financial consequences. Initially Pulsed Electromagnetic Fields was used in the treatment of tibial pseudoarthrosis and non-union. More recently there is evidence that physical forces can also be used in the treatment of fresh fractures, showing accelerated healing by 30% and 71% reduction in nonunion within 12 weeks after initiation of therapy. Until now no double blind randomized, placebo controlled trial has been conducted to investigate the effect of this treatment on the healing of fresh fractures of the scaphoid. Methods/Design This is a multi center, prospective, double blind, placebo controlled, randomized trial. Study population consists of all patients with unilateral acute scaphoid fracture. Pregnant women, patients having a life supporting implanted electronic device, patients with additional fractures of wrist, carpal or metacarpal bones and pre-existing impairment in wrist function are excluded. The scaphoid fracture is diagnosed by a combination of physical and radiographic examination (CT-scanning). Proven scaphoid fractures are treated with cast immobilization and a small Pulsed Electromagnetic Fields bone growth stimulating device placed on the cast. Half of the devices will be disabled at random in the factory. Study parameters are clinical consolidation, radiological consolidation

  3. Autologous keratinocyte suspension in platelet concentrate accelerates and enhances wound healing – a prospective randomized clinical trial on skin graft donor sites: platelet concentrate and keratinocytes on donor sites

    PubMed Central

    2013-01-01

    Background Wound healing involves complex mechanisms, which, if properly chaperoned, can enhance patient recovery. The abilities of platelets and keratinocytes may be harnessed in order to stimulate wound healing through the formation of platelet clots, the release of several growth factors and cytokines, and cell proliferation. The aim of the study was to test whether autologous keratinocyte suspensions in platelet concentrate would improve wound healing. The study was conducted at the Lausanne University Hospital, Switzerland in 45 patients, randomized to three different topical treatment groups: standard treatment serving as control, autologous platelet concentrate (PC) and keratinocytes suspended in autologous platelet concentrate (PC + K). Split thickness skin graft donor sites were chosen on the anterolateral thighs of patients undergoing plastic surgery for a variety of defects. Wound healing was assessed by the duration and quality of the healing process. Pain intensity was evaluated at day five. Results Healing time was reduced from 13.9 ± 0.5 days (mean ± SEM) in the control group to 7.2 ± 0.2 days in the PC group (P < 0.01). An addition of keratinocytes in suspension further reduced the healing time to 5.7 ± 0.2 days. Pain was reduced in both the PC and PC + K groups. Data showed a statistically detectable advantage of using PC + K over PC alone (P < 0.01). Conclusion The results demonstrate the positive contribution of autologous platelets combined with keratinocytes in stimulating wound healing and reducing pain. This strikingly simple approach could have a significant impact on patient care, especially critically burned victims for whom time is of the essence. Clinical trial registry information Protocol Record Identification Number: 132/03 Registry URL: http://www.clinicaltrials.gov PMID:23570605

  4. Inverse Dynamics Model for the Ankle Joint with Applications in Tibia Malleolus Fracture

    NASA Astrophysics Data System (ADS)

    Budescu, E.; Merticaru, E.; Chirazi, M.

    The paper presents a biomechanical model of the ankle joint, in order to determine the force and the torque of reaction into the articulation, through inverse dynamic analysis, in various stages of the gait. Thus, knowing the acceleration of the foot and the reaction force between foot and ground during the gait, determined by experimental measurement, there was calculated, for five different positions of the foot, the joint reaction forces, on the basis of dynamic balance equations. The values numerically determined were compared with the admissible forces appearing in the technical systems of osteosynthesis of tibia malleolus fracture, in order to emphasize the motion restrictions during bone healing.

  5. 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

  6. 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.

  7. 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.

  8. Authenticity and healing.

    PubMed

    McGee, Michael D

    2014-06-01

    Caring and compassion cannot be faked. These are not actions we perform mechanically but states of being that flow from within to make healing connection with others in need. To be authentically healing requires that we live authentic lives. This paper describes what it means to be authentic from a psychospiritual perspective, discusses the components of authentic caring and ends with an exploration of ways to cultivate the authenticity of our lives in general and in our efforts to heal others. PMID:24526471

  9. Placenta Growth Factor in Diabetic Wound Healing

    PubMed Central

    Cianfarani, Francesca; Zambruno, Giovanna; Brogelli, Laura; Sera, Francesco; Lacal, Pedro Miguel; Pesce, Maurizio; Capogrossi, Maurizio C.; Failla, Cristina Maria; Napolitano, Monica; Odorisio, Teresa

    2006-01-01

    Reduced microcirculation and diminished expression of growth factors contribute to wound healing impairment in diabetes. Placenta growth factor (PlGF), an angiogenic mediator promoting pathophysiological neovascularization, is expressed during cutaneous wound healing and improves wound closure by enhancing angiogenesis. By using streptozotocin-induced diabetic mice, we here demonstrate that PlGF induction is strongly reduced in diabetic wounds. Diabetic transgenic mice overexpressing PlGF in the skin displayed accelerated wound closure compared with diabetic wild-type littermates. Moreover, diabetic wound treatment with an adenovirus vector expressing the human PlGF gene (AdCMV.PlGF) significantly accelerated the healing process compared with wounds treated with a control vector. The analysis of treated wounds showed that PlGF gene transfer improved granulation tissue formation, maturation, and vascularization, as well as monocytes/macrophages local recruitment. Platelet-derived growth factor, fibroblast growth factor-2, and vascular endothelial growth factor mRNA levels were increased in AdCMV.PlGF-treated wounds, possibly enhancing PlGF-mediated effects. Finally, PlGF treatment stimulated cultured dermal fibroblast migration, pointing to a direct role of PlGF in accelerating granulation tissue maturation. In conclusion, our data indicate that reduced PlGF expression contributes to impaired wound healing in diabetes and that PlGF gene transfer to diabetic wounds exerts therapeutic activity by promoting different aspects of the repair process. PMID:17003476

  10. Self-healing materials.

    PubMed

    Hager, Martin D; Greil, Peter; Leyens, Christoph; van der Zwaag, Sybrand; Schubert, Ulrich S

    2010-12-14

    Self-healing materials are able to partially or completely heal damage inflicted on them, e.g., crack formation; it is anticipated that the original functionality can be restored. This article covers the design and generic principles of self-healing materials through a wide range of different material classes including metals, ceramics, concrete, and polymers. Recent key developments and future challenges in the field of self-healing materials are summarised, and generic, fundamental material-independent principles and mechanism are discussed and evaluated. PMID:20839257

  11. Biomechanical assessment and clinical analysis of different intramedullary nailing systems for oblique fractures.

    PubMed

    Alierta, J A; Pérez, M A; Seral, B; García-Aznar, J M

    2016-09-01

    The aim of this study is to evaluate the fracture union or non-union for a specific patient that presented oblique fractures in tibia and fibula, using a mechanistic-based bone healing model. Normally, this kind of fractures can be treated through an intramedullary nail using two possible configurations that depends on the mechanical stabilisation: static and dynamic. Both cases are simulated under different fracture geometries in order to understand the effect of the mechanical stabilisation on the fracture healing outcome. The results of both simulations are in good agreement with previous clinical experience. From the results, it is demonstrated that the dynamization of the fracture improves healing in comparison with a static or rigid fixation of the fracture. This work shows the versatility and potential of a mechanistic-based bone healing model to predict the final outcome (union, non-union, delayed union) of realistic 3D fractures where even more than one bone is involved. PMID:26712100

  12. 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

  13. [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

  14. Analysis of 429 fractures in 189 battered children.

    PubMed

    King, J; Diefendorf, D; Apthorp, J; Negrete, V F; Carlson, M

    1988-01-01

    To assess empirically the radiologic appearance of fractures among victims of child abuse, the charts and radiographs of 189 battered children exhibiting fractures (n = 429 total fractures) were studied. Approximately one-half of the patients had a single fracture. Bones most commonly fractured were the humerus, femur, and tibia; transverse fractures were the most common type. Of long bone fractures, the middle third (50%) and distal third (41%) locations were most prominent. Age, race, and gender were not associated with any particular long bone fracture type. Skull fractures were the only type more likely to be present in children aged less than 1 year than in older children (p less than 0.05, one-tailed). In the past, emphasis has been placed on corner fractures, fractures at different stages of healing, and injuries at several sites. Our results suggest that fresh single diaphyseal fractures are more common. PMID:3170740

  15. 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

  16. Factors Affecting Wound Healing

    PubMed Central

    Guo, S.; DiPietro, L.A.

    2010-01-01

    Wound healing, as a normal biological process in the human body, is achieved through four precisely and highly programmed phases: hemostasis, inflammation, proliferation, and remodeling. For a wound to heal successfully, all four phases must occur in the proper sequence and time frame. Many factors can interfere with one or more phases of this process, thus causing improper or impaired wound healing. This article reviews the recent literature on the most significant factors that affect cutaneous wound healing and the potential cellular and/or molecular mechanisms involved. The factors discussed include oxygenation, infection, age and sex hormones, stress, diabetes, obesity, medications, alcoholism, smoking, and nutrition. A better understanding of the influence of these factors on repair may lead to therapeutics that improve wound healing and resolve impaired wounds. PMID:20139336

  17. 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.

  18. 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

  19. Stem Cells for Cutaneous Wound Healing

    PubMed Central

    Kirby, Giles T. S.; Mills, Stuart J.; Cowin, Allison J.; Smith, Louise E.

    2015-01-01

    Optimum healing of a cutaneous wound involves a well-orchestrated cascade of biological and molecular processes involving cell migration, proliferation, extracellular matrix deposition, and remodelling. When the normal biological process fails for any reason, this healing process can stall resulting in chronic wounds. Wounds are a growing clinical burden on healthcare systems and with an aging population as well as increasing incidences of obesity and diabetes, this problem is set to increase. Cell therapies may be the solution. A range of cell based approaches have begun to cross the rift from bench to bedside and the supporting data suggests that the appropriate administration of stem cells can accelerate wound healing. This review examines the main cell types explored for cutaneous wound healing with a focus on clinical use. The literature overwhelmingly suggests that cell therapies can help to heal cutaneous wounds when used appropriately but we are at risk of clinical use outpacing the evidence. There is a need, now more than ever, for standardised methods of cell characterisation and delivery, as well as randomised clinical trials. PMID:26137471

  20. Diagnosis and treatment of scaphoid fractures.

    PubMed

    Patrick, Cynthia N

    2010-01-01

    The scaphoid bone in the wrist is the most frequently fractured carpal bone. This Directed Reading discusses types of scaphoid fractures, issues of special concern (eg, the risk of avascular necrosis and delayed union or non-union), steps involved in bone fracture healing and various imaging modalities used for scaphoid fracture diagnosis. Types of fracture management such as casting and surgical intervention are examined. Factors that can negatively influence bone healing, such as certain disease processes and tobacco use, are also investigated. This article is a Directed Reading. Your access to Directed Reading quizzes for continuing education credit is determined by your area of interest. For access to other quizzes, go to www.asrt.org/store. PMID:21048065

  1. Wound Healing Activity of Elaeis guineensis Leaf Extract Ointment

    PubMed Central

    Sasidharan, Sreenivasan; Logeswaran, Selvarasoo; Latha, Lachimanan Yoga

    2012-01-01

    Elaeis guineensis of the Arecaceae family is widely used in the traditional medicine of societies in West Africa for treating various ailments. To validate the ethnotherapeutic claims of the plant in skin diseases, wound healing activity was studied. The results showed that E. guineensis leaf extract had potent wound healing capacity as evident from the better wound closure (P < 0.05), improved tissue regeneration at the wound site, and supporting histopathological parameters pertaining to wound healing. Matrix metalloproteinases expression correlated well with the results thus confirming efficacy of E. guineensis in the treatment of the wound. E. guineensis accelerated wound healing in rats, thus supporting its traditional use. The result of this study suggested that, used efficiently, oil palm leaf extract is a renewable resource with wound healing properties. PMID:22312255

  2. [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

  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. Chitosan as a starting material for wound healing applications.

    PubMed

    Patrulea, V; Ostafe, V; Borchard, G; Jordan, O

    2015-11-01

    Chitosan and its derivatives have attracted great attention due to their properties beneficial for application to wound healing. The main focus of the present review is to summarize studies involving chitosan and its derivatives, especially N,N,N-trimethyl-chitosan (TMC), N,O-carboxymethyl-chitosan (CMC) and O-carboxymethyl-N,N,N-trimethyl-chitosan (CMTMC), used to accelerate wound healing. Moreover, formulation strategies for chitosan and its derivatives, as well as their in vitro, in vivo and clinical applications in wound healing are described. PMID:26614560

  5. Diabetes primes neutrophils to undergo NETosis, which impairs wound healing.

    PubMed

    Wong, Siu Ling; Demers, Melanie; Martinod, Kimberly; Gallant, Maureen; Wang, Yanming; Goldfine, Allison B; Kahn, C Ronald; Wagner, Denisa D

    2015-07-01

    Wound healing is impaired in diabetes, resulting in significant morbidity and mortality. Neutrophils are the main leukocytes involved in the early phase of healing. As part of their anti-microbial defense, neutrophils form extracellular traps (NETs) by releasing decondensed chromatin lined with cytotoxic proteins. NETs, however, can also induce tissue damage. Here we show that neutrophils isolated from type 1 and type 2 diabetic humans and mice were primed to produce NETs (a process termed NETosis). Expression of peptidylarginine deiminase 4 (PAD4, encoded by Padi4 in mice), an enzyme important in chromatin decondensation, was elevated in neutrophils from individuals with diabetes. When subjected to excisional skin wounds, wild-type (WT) mice produced large quantities of NETs in wounds, but this was not observed in Padi4(-/-) mice. In diabetic mice, higher levels of citrullinated histone H3 (H3Cit, a NET marker) were found in their wounds than in normoglycemic mice and healing was delayed. Wound healing was accelerated in Padi4(-/-) mice as compared to WT mice, and it was not compromised by diabetes. DNase 1, which disrupts NETs, accelerated wound healing in diabetic and normoglycemic WT mice. Thus, NETs impair wound healing, particularly in diabetes, in which neutrophils are more susceptible to NETosis. Inhibiting NETosis or cleaving NETs may improve wound healing and reduce NET-driven chronic inflammation in diabetes. PMID:26076037

  6. Bee Venom Accelerates Wound Healing in Diabetic Mice by Suppressing Activating Transcription Factor-3 (ATF-3) and Inducible Nitric Oxide Synthase (iNOS)-Mediated Oxidative Stress and Recruiting Bone Marrow-Derived Endothelial Progenitor Cells.

    PubMed

    Badr, Gamal; Hozzein, Wael N; Badr, Badr M; Al Ghamdi, Ahmad; Saad Eldien, Heba M; Garraud, Olivier

    2016-10-01

    Multiple mechanisms contribute to impaired diabetic wound healing including impaired neovascularization and deficient endothelial progenitor cell (EPC) recruitment. Bee venom (BV) has been used as an anti-inflammatory agent for the treatment of several diseases. Nevertheless, the effect of BV on the healing of diabetic wounds has not been studied. Therefore, in this study, we investigated the impact of BV on diabetic wound closure in a type I diabetic mouse model. Three experimental groups were used: group 1, non-diabetic control mice; group 2, diabetic mice; and group 3, diabetic mice treated with BV. We found that the diabetic mice exhibited delayed wound closure characterized by a significant decrease in collagen production and prolonged elevation of inflammatory cytokines levels in wounded tissue compared to control non-diabetic mice. Additionally, wounded tissue in diabetic mice revealed aberrantly up-regulated expression of ATF-3 and iNOS followed by a marked elevation in free radical levels. Impaired diabetic wound healing was also characterized by a significant elevation in caspase-3, -8, and -9 activity and a marked reduction in the expression of TGF-β and VEGF, which led to decreased neovascularization and angiogenesis of the injured tissue by impairing EPC mobilization. Interestingly, BV treatment significantly enhanced wound closure in diabetic mice by increasing collagen production and restoring the levels of inflammatory cytokines, free radical, TGF-β, and VEGF. Most importantly, BV-treated diabetic mice exhibited mobilized long-lived EPCs by inhibiting caspase activity in the wounded tissue. Our findings reveal the molecular mechanisms underlying improved diabetic wound healing and closure following BV treatment. J. Cell. Physiol. 231: 2159-2171, 2016. © 2016 Wiley Periodicals, Inc. PMID:26825453

  7. Metalloproteinases and Wound Healing

    PubMed Central

    Caley, Matthew P.; Martins, Vera L.C.; O'Toole, Edel A.

    2015-01-01

    Significance: Matrix metalloproteinases (MMPs) are present in both acute and chronic wounds. They play a pivotal role, with their inhibitors, in regulating extracellular matrix degradation and deposition that is essential for wound reepithelialization. The excess protease activity can lead to a chronic nonhealing wound. The timed expression and activation of MMPs in response to wounding are vital for successful wound healing. MMPs are grouped into eight families and display extensive homology within these families. This homology leads in part to the initial failure of MMP inhibitors in clinical trials and the development of alternative methods for modulating the MMP activity. MMP-knockout mouse models display altered wound healing responses, but these are often subtle phenotypic changes indicating the overlapping MMP substrate specificity and inter-MMP compensation. Recent Advances: Recent research has identified several new MMP modulators, including photodynamic therapy, protease-absorbing dressing, microRNA regulation, signaling molecules, and peptides. Critical Issues: Wound healing requires the controlled activity of MMPs at all stages of the wound healing process. The loss of MMP regulation is a characteristic of chronic wounds and contributes to the failure to heal. Future Directions: Further research into how MMPs are regulated should allow the development of novel treatments for wound healing. PMID:25945285

  8. Strontium-impregnated bioabsorbable composite for osteoporotic fracture fixation.

    PubMed

    Wu, Chang-Chin; Kuo, Chih-Lin; Fan, Fang-Yu; Yang, Kai-Chiang

    2015-10-01

    Osteoporosis impairs the bone-healing process as well as bone fracture fixation. The intervention of osteoporosis is considered to be one part of bone fracture treatment. Thus, orthopedic fixators impregnated with antiosteoporosis regimens will improve fracture fixation in osteoporotic bone. In this study, the strontium (Sr) and calcium phosphate ceramic (CPC) were mixed first and then mixed with poly(ε-caprolactone) (PCL) to fabricate a bioactive and bioabsorbable bone fixators. The prepared Sr-CPC/PCL screws were implanted into the distal femur of ovariectomized rabbits. The results showed that Sr-CPC/PCL composite had the appropriate mechanical properties, good biocompatibility, and radio-opacity. The Sr addition created a porous structure and accelerated the degradation of bone screws, but the degradation products did not acidify the surrounding environment. For osteoporotic animals, favorable osteointegration around the Sr-CPC/PCL screws was found, and the total porosity of trabecular bone was decreased under the inspections of micro-computerized tomography. Compared with PCL or CPC/PCL screw, animals which received Sr-CPC/PCL were found to have better results in terms of trabecular number, thickness, and separation. This study reveals that the Sr-impregnated bone fixator improves osseointegration in osteoporotic animals. Sr-CPC/PCL composite is a good candidate material for osteofixation in osteoporotic patients. PMID:25847487

  9. Intra-oral PTH Administration Promotes Tooth Extraction Socket Healing

    PubMed Central

    Kuroshima, S.; Kovacic, B.L.; Kozloff, K.M.; McCauley, L.K.; Yamashita, J.

    2013-01-01

    Intermittent parathyroid hormone (PTH) administration increases systemic and craniofacial bone mass. However, the effect of PTH therapy on healing of tooth extraction sites is unknown. The aims of this study were to determine the effect of PTH therapy on tooth extraction socket healing and to examine whether PTH intra-oral injection promotes healing. The mandibular first molars were extracted in rats, and subcutaneous PTH was administered intermittently for 7, 14, and 28 days. In a second study, maxillary second molars were extracted, and PTH was administered by either subcutaneous or intra-oral injection to determine the efficacy of intra-oral PTH administration. Healing was assessed by micro-computed tomography and histomorphometric analyses. PTH therapy accelerated the entire healing process and promoted both hard- and soft-tissue healing by increasing bone fill and connective tissue maturation. PTH therapy by intra-oral injection was as effective as subcutaneous injection in promoting tooth extraction socket healing. The findings suggest that PTH therapy promotes tooth extraction socket healing and that intra-oral injections can be used to administer PTH. PMID:23611925

  10. 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

  11. Current Options for Determining Fracture Union

    PubMed Central

    Morshed, Saam

    2014-01-01

    Determining whether a bone fracture is healed is one of the most important and fundamental clinical determinations made in orthopaedics. However, there are currently no standardized methods of assessing fracture union, which in turn has created significant disagreement among orthopaedic surgeons in both clinical and research settings. An extensive amount of research has been dedicated to finding novel and reliable ways of determining healing with some promising results. Recent advancements in imaging techniques and introduction of new radiographic scores have helped decrease the amount of disagreement on this topic among physicians. The knowledge gained from biomechanical studies of bone healing has helped us refine our tools and create more efficient and practical research instruments. Additionally, a deeper understanding of the molecular pathways involved in the bone healing process has led to emergence of serologic markers as possible candidates in assessment of fracture union. In addition to our current physician centered methods, patient-centered approaches assessing quality of life and function are gaining popularity in assessment of fracture union. Despite these advances, assessment of union remains an imperfect practice in the clinical setting. Therefore, clinicians need to draw on multiple modalities that directly and indirectly measure or correlate with bone healing when counseling patients. PMID:26556422

  12. Cutaneous wound healing through paradoxical MAPK activation by BRAF inhibitors.

    PubMed

    Escuin-Ordinas, Helena; Li, Shuoran; Xie, Michael W; Sun, Lu; Hugo, Willy; Huang, Rong Rong; Jiao, Jing; de-Faria, Felipe Meira; Realegeno, Susan; Krystofinski, Paige; Azhdam, Ariel; Komenan, Sara Marie D; Atefi, Mohammad; Comin-Anduix, Begoña; Pellegrini, Matteo; Cochran, Alistair J; Modlin, Robert L; Herschman, Harvey R; Lo, Roger S; McBride, William H; Segura, Tatiana; Ribas, Antoni

    2016-01-01

    BRAF inhibitors are highly effective therapies for the treatment of BRAF(V600)-mutated melanoma, with the main toxicity being a variety of hyperproliferative skin conditions due to paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway in BRAF wild-type cells. Most of these hyperproliferative skin changes improve when a MEK inhibitor is co-administered, as it blocks paradoxical MAPK activation. Here we show how the BRAF inhibitor vemurafenib accelerates skin wound healing by inducing the proliferation and migration of human keratinocytes through extracellular signal-regulated kinase (ERK) phosphorylation and cell cycle progression. Topical treatment with vemurafenib in two wound-healing mice models accelerates cutaneous wound healing through paradoxical MAPK activation; addition of a mitogen-activated protein kinase kinase (MEK) inhibitor reverses the benefit of vemurafenib-accelerated wound healing. The same dosing regimen of topical BRAF inhibitor does not increase the incidence of cutaneous squamous cell carcinomas in mice. Therefore, topical BRAF inhibitors may have clinical applications in accelerating the healing of skin wounds. PMID:27476449

  13. Cutaneous wound healing through paradoxical MAPK activation by BRAF inhibitors

    PubMed Central

    Escuin-Ordinas, Helena; Li, Shuoran; Xie, Michael W.; Sun, Lu; Hugo, Willy; Huang, Rong Rong; Jiao, Jing; de-Faria, Felipe Meira; Realegeno, Susan; Krystofinski, Paige; Azhdam, Ariel; Komenan, Sara Marie D.; Atefi, Mohammad; Comin-Anduix, Begoña; Pellegrini, Matteo; Cochran, Alistair J.; Modlin, Robert L.; Herschman, Harvey R.; Lo, Roger S.; McBride, William H.; Segura, Tatiana; Ribas, Antoni

    2016-01-01

    BRAF inhibitors are highly effective therapies for the treatment of BRAFV600-mutated melanoma, with the main toxicity being a variety of hyperproliferative skin conditions due to paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway in BRAF wild-type cells. Most of these hyperproliferative skin changes improve when a MEK inhibitor is co-administered, as it blocks paradoxical MAPK activation. Here we show how the BRAF inhibitor vemurafenib accelerates skin wound healing by inducing the proliferation and migration of human keratinocytes through extracellular signal-regulated kinase (ERK) phosphorylation and cell cycle progression. Topical treatment with vemurafenib in two wound-healing mice models accelerates cutaneous wound healing through paradoxical MAPK activation; addition of a mitogen-activated protein kinase kinase (MEK) inhibitor reverses the benefit of vemurafenib-accelerated wound healing. The same dosing regimen of topical BRAF inhibitor does not increase the incidence of cutaneous squamous cell carcinomas in mice. Therefore, topical BRAF inhibitors may have clinical applications in accelerating the healing of skin wounds. PMID:27476449

  14. 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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-01-01

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

  17. Stress fractures of the olecranon in javelin throwers.

    PubMed

    Hulkko, A; Orava, S; Nikula, P

    1986-08-01

    Between the years 1977 and 1984, four javelin throwers with a stress fracture of the olecranon were seen and treated. In one patient, acute painful dislocation of the fracture occurred during a competitive throw. Two patients had stress fracture of the tip. The fracture treated conservatively healed in 18 months. The patient treated by excision of the tip was able to throw after 2 months. Two patients had slightly oblique, more distally located stress fractures, which were treated with a tension band and 2 Kirschner wires. The fractures healed in 4 months. One of the patients had a refracture 11 months after the primary operation. It was successfully treated with a compression screw and two bone pegs. Because of the high risk of delayed union and nonunion, stress fractures of the olecranon should be treated operatively in javelin throwers. PMID:3759300

  18. [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 instrumen