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Sample records for accelerates fracture healing

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

    Science.gov (United States)

    2006-12-01

    MJ, Goll SR, Nichols CE, 3rd, Pollack SR: Prevention and treatment of sciatic denervation disuse osteoporosis in the rat tibia with capacitively...the healing of fractures. J Bone Joint Surg Am 83-A:259-70, 2001 40. Rubin CT, McLeod KJ, Lanyon LE: Prevention of osteoporosis by pulsed...USA Corresponding author Belinda R. Beck, Ph.D. Griffith University School of Physiotherapy and Exercise Science, PMB 50 Gold Coast Mail Centre Q

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

    Science.gov (United States)

    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.

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

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    Yinhe Wang

    2017-02-01

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

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

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    Noratep Kulachote

    2016-01-01

    Full Text Available 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.

  5. CT examinations of healing fractures

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    Nutz, V.; Uexkuell-Gueldenband, V. v.

    1988-10-01

    The CT appearances of healing fractures were studied following tibial osteotomy in a dog. Traditional radiological investigations and CT were carried out until healing was complete; CT showed callus on the ninth day, whereas radiographs only showed it after 19 days. After 32 days, callus filled nearly the entire medullary cavity. Similar observations were made in several human situations. CT demonstrates interposed material in the fracture very clearly, even if there is marked callus formation within the fracture.

  6. The science of ultrasound therapy for fracture healing.

    Science.gov (United States)

    Della Rocca, Gregory J

    2009-01-01

    Fracture healing involves a complex interplay of cellular processes, culminating in bridging of a fracture gap with bone. Fracture healing can be compromised by numerous exogenous and endogenous patient factors, and intense research is currently going on to identify modalities that can increase the likelihood of successful healing. Low-intensity pulsed ultrasound (LIPUS) has been proposed as a modality that may have a benefit for increasing reliable fracture healing as well as perhaps increasing the rate of fracture healing. We conducted a review to establish basic scince evidence of therapeutic role of lipus in fracture healing. An electronic search without language restrictions was accomplished of three databases (PubMed, Embase, Cinahl) for ultrasound-related research in osteocyte and chondrocyte cell culture and in animal fracture models, published from inception of the databases through December, 2008. Studies deemed to be most relevant were included in this review. Multiple in vitro and animal in vivo studies were identified. An extensive body of literature exists which delineates the mechanism of action for ultrasound on cellular and tissue signaling systems that may be related to fracture healing. Research on LIPUS in animal fracture models has demonstrated promising results for acceleration of fracture healing and for promotion of fracture healing in compromised tissue beds. A large body of cellular and animal research exists which reveals that LIPUS may be beneficial for accelerating normal fracture healing or for promoting fracture healing in compromised tissue beds. Further investigation of the effects of LIPUS in human fracture healing is warranted for this promising new therapy.

  7. The science of ultrasound therapy for fracture healing

    Directory of Open Access Journals (Sweden)

    Della Rocca Gregory

    2009-01-01

    Full Text Available Fracture healing involves a complex interplay of cellular processes, culminating in bridging of a fracture gap with bone. Fracture healing can be compromised by numerous exogenous and endogenous patient factors, and intense research is currently going on to identify modalities that can increase the likelihood of successful healing. Low-intensity pulsed ultrasound (LIPUS has been proposed as a modality that may have a benefit for increasing reliable fracture healing as well as perhaps increasing the rate of fracture healing. We conducted a review to establish basic scince evidence of therapeutic role of lipus in fracture healing. An electronic search without language restrictions was accomplished of three databases (PubMed, Embase, Cinahl for ultrasound-related research in osteocyte and chondrocyte cell culture and in animal fracture models, published from inception of the databases through December, 2008. Studies deemed to be most relevant were included in this review. Multiple in vitro and animal in vivo studies were identified. An extensive body of literature exists which delineates the mechanism of action for ultrasound on cellular and tissue signaling systems that may be related to fracture healing. Research on LIPUS in animal fracture models has demonstrated promising results for acceleration of fracture healing and for promotion of fracture healing in compromised tissue beds. A large body of cellular and animal research exists which reveals that LIPUS may be beneficial for accelerating normal fracture healing or for promoting fracture healing in compromised tissue beds. Further investigation of the effects of LIPUS in human fracture healing is warranted for this promising new therapy.

  8. The healing of fractured bones

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    Bacon, G.E. [Central Electricity Generating Board, Cheltenham (United Kingdom)

    1997-04-01

    A method utilising neutron beams of width 1 mm, used on D1B (2.4 A) and D20 (1.3 A) to study the healing of fractured bones is presented. It is found that the callus bone uniting the fractured tibia of a sheep, whose healing had been encouraged by daily mechanical vibration over a period of three months, showed no trace of the large preferential vertical orientation of the apatite crystals which is characteristic of the normal bone. Nevertheless the bone had regained about 60% of its mechanical strength and the callus bone, although not oriented, was well crystallized. It is considered that the new monochromator for D20, expected to give increased intensity at 2.5 A, will be of considerable advantage. (author). 2 refs.

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

    Science.gov (United States)

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

    2012-01-01

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

  10. Impaired Fracture Healing after Hemorrhagic Shock

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    Philipp Lichte

    2015-01-01

    Full Text Available 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.

  11. Management of impaired fracture healing: Historical aspects

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    Gajdobranski Đorđe

    2005-01-01

    Full Text Available Introduction Establishing continuity of long bones in cases of impaired bone healing and pseudo-arthrosis is one of the most complex problems in orthopedics. Impaired bone healing The problem of impaired fracture healing is not new. As in other areas of human life, the roots of modern treatment of impaired bone healing lie in ancient medicine. A relatively high percentage of impaired bone healing, as well as unsatisfactory results of standard therapies of impaired bone healing and pseudoarthrosis demonstrate the actuality of this problem. This paper represents an attempt to pay respect to some of those who have dedicated their work to this problem in orthopedic surgery, and it is a historical review on impaired bone fracture healing. At the same time it should be an additional stimulus and challenge for orthopedic surgeons to further study impaired bone fracture healing, improve the existing and find new methods for their adequate treatment. Conclusion The authors are certain that the number of researchers throughout the world who have contributed to treatment modalities of impaired bone healing, is much higher, but not all are mentioned in this paper. However, it does not lessen their contributions to orthopedics.

  12. Inhibition of Midkine Augments Osteoporotic Fracture Healing.

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    Melanie Haffner-Luntzer

    Full Text Available 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.

  13. Flexible fixation and fracture healing

    DEFF Research Database (Denmark)

    Schmal, Hagen; Strohm, Peter C; Jaeger, Martin

    2011-01-01

    to the bone surface than external fixator bars. External fixators have the advantage of being less expensive, highly flexible, and technically less demanding. They remain an integral part of orthopaedic surgery for emergent stabilization, for pediatric fractures, for definitive osteosynthesis in certain...

  14. Immunohistochemical localization of key arachidonic acid metabolism enzymes during fracture healing in mice.

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    Hsuan-Ni Lin

    Full Text Available 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.

  15. Indium-111 leukocyte scanning and fracture healing

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    Mead, L.P.; Scott, A.C.; Bondurant, F.J.; Browner, B.D. (Univ. of Texas Medical School, Houston (USA))

    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.

  16. Acceleration of cutaneous wound healing by brassinosteroids.

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    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 that the anabolic properties of brassinosteroids are possibly mediated through the phosphoinositide 3-kinase/protein kinase B signaling pathway. Here, we examined biological activity of homobrassinolide (HB) and its synthetic analogues in 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 days, with 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 transforming growth factor beta and intercellular adhesion molecule 1 were significantly lower, while tumor necrosis factor alpha was nearly suppressed in the wounds from treated mice. Our data suggest that topical application of brassinosteroids accelerates wound healing by positively modulating inflammatory and reepithelialization phases of the wound repair process, in part by enhancing Akt signaling in the skin at the edges of the wound and enhancing migration of fibroblasts in the wounded area. Targeting this signaling pathway with brassinosteroids may represent a promising approach to the therapy of delayed wound healing.

  17. Fracture healing: direct magnification versus conventional radiography

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    Link, T.M. [Dept. of Clinical Radiology, Westfaelische Wilhelms-Univ., Muenster (Germany); Kessler, T. [Dept. of Traumatic and Hand Surgery, Westfaelische Wilhelms-Univ., Muenster (Germany); Lange, T. [Dept. of Clinical Radiology, Westfaelische Wilhelms-Univ., Muenster (Germany); Overbeck, J. [Dept. of Traumatic and Hand Surgery, Westfaelische Wilhelms-Univ., Muenster (Germany); Fiebich, M. [Dept. of Clinical Radiology, Westfaelische Wilhelms-Univ., Muenster (Germany); Peters, P.E. [Dept. of Clinical Radiology, Westfaelische Wilhelms-Univ., Muenster (Germany)

    1994-08-01

    The aim of the study was to evaluate the potential of magnification radiography in diagnosing fracture healing and assessing its complications. Seventy-three patients with fractures or who had undergone osteotomy were radiographed with both conventional (non-magnified) and magnification (5-fold) techniques. Since 10 patients were radiographed twice and 1 three times, 83 radiographs using each technique were obtained. All radiographs were analysed and the findings correlated with the patients` follow-up studies. The microfocal X-ray unit used for magnification radiography had a focal spot size of 20-130 {mu}m. As an imaging system, digital luminescence radiography was employed with magnification, while normal film-screen systems were used with conventional radiography. Magnification radiography proved superior to conventional radiography in 47% of cases: endosteal and periosteal callus formations were seen earlier and better in 26 cases, and osseous union could be evaluated with greater certainty in 33 cases. In 49% of cases magnification radiography was equal and in 4% inferior to conventional radiography. Additionally an ``inter-observer analysis`` was carried out. Anatomical and pathological structures were classified into one of four grades. Results were significantly (P < 0.01) better using magnification radiography. We conclude that the magnification technique is a good method for monitoring fracture healing in its early stages. (orig.)

  18. Simulation of the nutrient supply in fracture healing.

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    Chen, G; Niemeyer, F; Wehner, T; Simon, U; Schuetz, M A; Pearcy, M J; Claes, L E

    2009-11-13

    The healing process for bone fractures is sensitive to mechanical stability and blood supply at the fracture site. Most currently available mechanobiological algorithms of bone healing are based solely on mechanical stimuli, while the explicit analysis of revascularization and its influences on the healing process have not been thoroughly investigated in the literature. In this paper, revascularization was described by two separate processes: angiogenesis and nutrition supply. The mathematical models for angiogenesis and nutrition supply have been proposed and integrated into an existing fuzzy algorithm of fracture healing. The computational algorithm of fracture healing, consisting of stress analysis, analyses of angiogenesis and nutrient supply, and tissue differentiation, has been tested on and compared with animal experimental results published previously. The simulation results showed that, for a small and medium-sized fracture gap, the nutrient supply is sufficient for bone healing, for a large fracture gap, non-union may be induced either by deficient nutrient supply or inadequate mechanical conditions. The comparisons with experimental results demonstrated that the improved computational algorithm is able to simulate a broad spectrum of fracture healing cases and to predict and explain delayed unions and non-union induced by large gap sizes and different mechanical conditions. The new algorithm will allow the simulation of more realistic clinical fracture healing cases with various fracture gaps and geometries and may be helpful to optimise implants and methods for fracture fixation.

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

    Science.gov (United States)

    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.

  20. Therapeutic ultrasound in fracture healing: The mechanism of osteoinduction

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    John P

    2008-01-01

    Full Text Available Background: Ultrasound has been used therapeutically for accelerating fracture healing since many years. However, the controversy on the exact mechanism of osteoinduction still continues. In this study, we try to bring out the exact biomolecular mechanism by which ultrasound induces fracture healing. Materials and Methods: The study was conducted in two phases: animal experiments and clinical study. In the first phase, we induced fractures on the left tibia of Wistar strain rats under anaesthesia. They were divided into two groups. One of the groups was given low-intensity, pulsed ultrasound (30 MW/cm 2 20 min a day for 10 days. Tissue samples and radiographs were taken weekly for 3 weeks from both the groups. In the second phase of our study, ten patients with fractures of the distal end of the radius (ten fractures were included. Five of these were treated as cases, and five were treated as controls. Ultrasound was given 30 MW/cm 2 for 20 min every day for 2 weeks. The patients were assessed radiologically and sonologically before and after ultrasound therapy. Tissue samples were studied with thymidine incorporation test with and without adding various neurotransmitter combinations. Results: Radiological findings revealed that there was an increased callus formation in the ultrasound group. At the cellular level, there was an increased thymidine incorporation in the ultrasound group. When various neurotransmitters were added to the cells, there was an increased thymidine incorporation in the ultrasound group. In the second phase of the study, radiological and sonological assessments showed that there was an increased callus formation in the ultrasound group. In cytological study, thymidine incorporation was found to be increased in the ultrasound group. Conclusions: The results of animal and clinical studies demonstrated an early and increased callus formation in the ultrasound group. Cytological studies revealed increased thymidine

  1. Ultrasound attenuation as a quantitative measure of fracture healing

    Science.gov (United States)

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

    2004-10-01

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

  2. Chitosan-alginate membranes accelerate wound healing.

    Science.gov (United States)

    Caetano, Guilherme Ferreira; Frade, Marco Andrey Cipriani; Andrade, Thiago Antônio Moretti; Leite, Marcel Nani; Bueno, Cecilia Zorzi; Moraes, Ângela Maria; Ribeiro-Paes, João Tadeu

    2015-07-01

    The purpose of this study was to evaluate the efficacy of chitosan-alginate membrane to accelerate wound healing in experimental cutaneous wounds. Two wounds were performed in Wistar rats by punching (1.5 cm diameter), treated with membranes moistened with saline solution (CAM group) or with saline only (SL group). After 2, 7, 14, and 21 days of surgery, five rats of each group were euthanized and reepithelialization was evaluated. The wounds/scars were harvested for histological, flow cytometry, neutrophil infiltrate, and hydroxyproline analysis. CAM group presented higher inflammatory cells recruitment as compared to SL group on 2(nd) day. On the 7(th) day, CAM group showed higher CD11b(+) level and lower of neutrophils than SL group. The CAM group presented higher CD4(+) cells influx than SL group on 2(nd) day, but it decreased during the follow up and became lower on 14(th) and 21(st) days. Higher fibroplasia was noticed on days 7 and 14 as well as higher collagenesis on 21(st) in the CAM group in comparison to SL group. CAM group showed faster reepithelialization on 7(th) day than SL group, although similar in other days. In conclusion, chitosan-alginate membrane modulated the inflammatory phase, stimulated fibroplasia and collagenesis, accelerating wound healing process in rats.

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

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    Ai-Yuan Wang

    2014-01-01

    Full Text Available 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.

  4. 120 Years of Accelerators that Heal

    CERN Document Server

    CERN. Geneva

    2013-01-01

    The discovery of X rays was made possible by the intelligent use of the best accelerator of the time. Since then, the development of particle accelerators has been at the root of both fundamental discoveries in physics and unforeseeable medical applications. The lecture will describe the major steps in this 120-year history of diagnostics and tumour therapy.   The first attempts to heal tumours with X rays were made only one month after Röntgen’s discovery, but the understanding of the mechanisms by which the radiation kills the cells and the introduction of dose fractionation took much longer. The use of X rays in diagnostics developed much faster and its benefits were very visible during the First World War. Today no tumour could be treated and no patient could be operated without a CT scan, which employs an X ray tube that is not very different from the one introduced by William Coolidge in 1912.   On the particle therapy frontier, more sophisticated and larger pa...

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

    Science.gov (United States)

    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

  6. Effects of anti-osteoporosis medications on fracture healing

    DEFF Research Database (Denmark)

    Jørgensen, Niklas R; Schwarz, Peter

    2011-01-01

    A number of fractures are complicated by impaired healing. This is prevalent in certain risk groups such as elderly, osteoporotics, postmenopausal women, and in people with malnutrition. At present, no pharmacologic treatments are available. Thus, there is an unmet need for medications that can...... stimulate bone healing. Parathyroid hormone (PTH) is the first bone anabolic drug approved for the treatment of osteoporosis and, intriguingly, a number of animal studies prove the ability of PTH to induce fracture healing. PTH may therefore be a potential novel treatment option in humans with impaired...

  7. Considerations on evolution and healing of vertebral fractures.

    Science.gov (United States)

    Klumpp, Raymond; Trevisan, Carlo; Nava, Veronica; Riccardi, Domenico; Recalcati, Wilmer

    2013-10-01

    Only little is known when talking about the evolution of a vertebral fracture. From the few studies available in the literature, we can deduce that the risk a vertebral compression fracture has to worsen its deformity is consistent. It is important to try to make a prognosis on how the fracture is going to heal based on the type of fracture encountered. A chapter of its own is the occurrence of a vertebral fracture non-union that is difficult to diagnose and treat, but comes along with a poor prognosis.

  8. A first order system model of fracture healing

    Institute of Scientific and Technical Information of China (English)

    WANG Xiao-ping; ZHANG Xian-long; LI Zhu-guo; YU Xin-gang

    2005-01-01

    A first order system model is proposed for simulating the influence of stress stimulation on fracture strength during fracture healing. To validate the model, the diaphyses of bilateral tibiae in 70 New Zealand rabbits were osteotomized and fixed with rigid plates and stress-relaxation plates, respectively. Stress shielding rate and ultimate bending strength of the healing bone were measured at 2 to 48 weeks postoperatively. Ratios of stress stimulation and fracture strength of the healing bone to those of intact bone were taken as the system input and output. The assumed first order system model can approximate the experimental data on fracture strength from the input of stress stimulation over time, both for the rigid plate group and the stress-relaxation plate group, with different system parameters of time constant and gain. The fitting curve indicates that the effect of mechanical stimulus occurs mainly in late stages of healing. First order system can model the stress adaptation process of fracture healing. This approach presents a simple bio-mathematical model of the relationship between stress stimulation and fracture strength, and has the potential to optimize planning of functional exercises and conduct parametric studies.

  9. Radiographic features of teriparatide-induced healing of femoral fractures

    Directory of Open Access Journals (Sweden)

    Youngwoo Kim

    2015-12-01

    Full Text Available Teriparatide is a drug that is used to increase bone remodeling, formation, and density for the treatment of osteoporosis. We present three cases of patients with a femoral insufficiency fracture. The patients were administered teripatatide in an attempt to treat severe osteoporosis and to enhance fracture healing. We found several radiographic features around the femoral fractures during the healing period. 1 Callus formation was found at a very early stage in the treatment. Teriparatide substantially increased the unusually abundant callus formation around the fracture site at 2 weeks. Moreover, this callus formation continued for 8 weeks and led to healing of the fracture. 2 Abundant callus formation was found circumferentially around the cortex with a ‘cloud-like’ appearance. 3 Remodeling of the teriparatide-induced callus formation was found to be part of the normal fracture healing process. After 1 year, normal remodeling was observed on plain radiographs. These findings indicate that teriparatide can be used as an adjuvant therapy in the management of femoral insufficiency fractures.

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

    Directory of Open Access Journals (Sweden)

    Xiong Zhao

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

  11. Stimulation of bone formation and fracture healing with pulsed electromagnetic fields: biologic responses and clinical implications.

    Science.gov (United States)

    Chalidis, B; Sachinis, N; Assiotis, A; Maccauro, G

    2011-01-01

    Pulsed electromagnetic fields (PEMF) have been used for several years to supplement bone healing. However, the mode of action of this non-invasive method is still debated and quantification of its effect on fracture healing is widely varied. At cellular and molecular level, PEMF has been advocated to promote the synthesis of extracellular matrix proteins and exert a direct effect on the production of proteins that regulate gene transcription. Electromagnetic fields may also affect several membrane receptors and stimulate osteoblasts to secrete several growth factors such as bone morphogenic proteins 2 and 4 and TGF-beta. They could also accelerate intramedullary angiogenesis and improve the load to failure and stiffness of the bone. Although healing rates have been reported in up to 87 % of delayed unions and non-unions, the efficacy of the method is significantly varied while patient or fracture related variables could not be clearly associated with a successful outcome.

  12. α-Gal Nanoparticles in Wound and Burn Healing Acceleration

    Science.gov (United States)

    Galili, Uri

    2017-01-01

    Significance: Rapid recruitment and activation of macrophages may accelerate wound healing. Such accelerated healing was observed in wounds and burns of experimental animals treated with α-gal nanoparticles. Recent Advances: α-Gal nanoparticles present multiple α-gal epitopes (Galα1-3Galβ1-4GlcNAc-R). α-Gal nanoparticles applied to wounds bind anti-Gal (the most abundant antibody in humans) and generate chemotactic complement peptides, which rapidly recruit macrophages. Fc/Fc receptor interaction between anti-Gal coating the α-gal nanoparticles and recruited macrophages activates macrophages to produce cytokines that accelerate healing. α-Gal nanoparticles applied to burns and wounds in mice and pigs producing anti-Gal, decreased healing time by 40–60%. In mice, this accelerated healing avoided scar formation. α-Gal nanoparticle-treated wounds, in diabetic mice producing anti-Gal, healed within 12 days, whereas saline-treated wounds became chronic wounds. α-Gal nanoparticles are stable for years and may be applied dried, in suspension, aerosol, ointments, or within biodegradable materials. Critical Issues: α-Gal nanoparticle therapy can be evaluated only in mammalian models producing anti-Gal, including α1,3-galactosyltransferase knockout mice and pigs or Old World primates. Traditional experimental animal models synthesize α-gal epitopes and lack anti-Gal. Future Directions: Since anti-Gal is naturally produced in all humans, it is of interest to determine safety and efficacy of α-gal nanoparticles in accelerating wound and burn healing in healthy individuals and in patients with impaired wound healing such as diabetic patients and elderly individuals. In addition, efficacy of α-gal nanoparticle therapy should be studied in healing and regeneration of internal injuries such as surgical incisions, ischemic myocardium following myocardial infarction, and injured nerves. PMID:28289553

  13. Low-intensity pulsed ultrasound affects RUNX2 immunopositive osteogenic cells in delayed clinical fracture healing

    NARCIS (Netherlands)

    Rutten, S.; Nolte, P.A.; Korstjens, C.M.; Klein-Nulend, J.

    2009-01-01

    Introduction: Osteogenic cell proliferation and differentiation play an important role in adequate fracture healing, and is target for osteoinductive therapies in delayed fracture healing. The aim of this study was to investigate whether low-intensity pulsed ultrasound enhances fracture healing at t

  14. Computational simulation of bone fracture healing under inverse dynamisation.

    Science.gov (United States)

    Wilson, Cameron J; Schütz, Michael A; Epari, Devakara R

    2017-02-01

    Adaptive finite element models have allowed researchers to test hypothetical relationships between the local mechanical environment and the healing of bone fractures. However, their predictive power has not yet been demonstrated by testing hypotheses ahead of experimental testing. In this study, an established mechano-biological scheme was used in an iterative finite element simulation of sheep tibial osteotomy healing under a hypothetical fixation regime, "inverse dynamisation". Tissue distributions, interfragmentary movement and stiffness across the fracture site were compared between stiff and flexible fixation conditions and scenarios in which fixation stiffness was increased at a discrete time-point. The modelling work was conducted blind to the experimental study to be published subsequently. The simulations predicted the fastest and most direct healing under constant stiff fixation, and the slowest healing under flexible fixation. Although low fixation stiffness promoted more callus formation prior to bridging, this conferred little additional stiffness to the fracture in the first 5 weeks. Thus, while switching to stiffer fixation facilitated rapid subsequent bridging of the fracture, no advantage of inverse dynamisation could be demonstrated. In vivo data remains necessary to conclusively test this treatment protocol and this will, in turn, provide an evaluation of the model's performance. The publication of both hypotheses and their computational simulation, prior to experimental testing, offers an appealing means to test the predictive power of mechano-biological models.

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

    Directory of Open Access Journals (Sweden)

    Abdullah Küçükalp

    2014-11-01

    Full Text Available 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.

  16. Early period of fracture healing in ovariectomized rats

    Institute of Scientific and Technical Information of China (English)

    徐少文; 喻任; 赵光锋; 王建卫

    2003-01-01

    Objective: To evaluate the effect of osteoporosis on fracture healing through observing the histomorphological changes, bone mineral density of callus and expression and distribution of transforming growth factor beta 1 (TGF-β1),basic fibroblast growth factor (bFGF) and bone morphogenetic protein-2 (BMP-2) in ovariectomized rats.Methods: Sixty female Sprague-Dawley rats (aged 12 weeks and weighing 235 g on average) were randomly divided into an ovariectomized (OVX) group (n=30) and a sham-operated (SO) group (n=30). Ovariectomy was performed in the OVX rats and same incision was made in the SO rats. Three months later, fracture of femoral shaft was made on all the rats. Then they were killed at different time points. Callus formation was observed with histological and immunohistochemical methods.Results: A reduction in callus and bone mineral density in the healing femur and a decrease of osteoblasts expressing TGF-β1 near the bone trabecula were observed in the OVX rats 3-4 weeks after fracture. Histomorphological analysis revealed a higher content of soft callus in the OVX rats than that in the SO rats. Immunohistochemistry results showed that no remarkable difference in expression and distribution of BMP-2 and bFGF between the OVX and SO groups was found.Conclusions: Osteoporosis influences the quantity and quality of callus during the early period of fracture healing. The effect of osteoporosis on fracture healing has no relationship with the expression of BMP-2 or bFGF. The decreased expression of TGF-β1 in osteoblasts may cause a decrease in quality of facture healing after osteoporosis.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  18. Muscle-bone Interactions During Fracture Healing

    Science.gov (United States)

    2015-03-01

    physical trauma31, orthopaedic surgery32, or due to disease like fibrodysplasia ossificans progressiva, which has been identified to be a result of a...responsible for bone healing may provide opportunities to develop therapies to augment normal physiologic mechanisms underlying bone regeneration. Current... osteoporosis in premenopausal and postmenopausal women. J Bone Miner Metab 2008; 26:159-64. 70. Hill M, Goldspink G. Expression and splicing of the in- sulin

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

    Liu, Pengcheng; Cai, Ming

    2017-01-01

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

  1. Excess dietary methionine does not affect fracture healing in mice

    Science.gov (United States)

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

    2012-01-01

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

  2. Locally applied Simvastatin improves fracture healing in mice

    Directory of Open Access Journals (Sweden)

    Aspenberg Per

    2007-09-01

    Full Text Available Abstract Background HMG-CoA reductase inhibitors, statins, are widely prescribed to lower cholesterol. High doses of orally administered simvastatin has previously been shown to improve fracture healing in a mouse femur fracture model. In this study, simvastatin was administered either subcutaneously or directly to the fracture area, with the goal of stimulating fracture repair at acceptable doses. Methods Femur fractures were produced in 70 mature male Balb-C mice and stabilized with marrow-nailing. Three experiments were performed. Firstly, 20 mice received subcutaneous injections of either simvastatin (20 mg or vehicle. Secondly, 30 mice were divided into three groups of 10 mice receiving continuous subcutaneous delivery of the vehicle substance, the vehicle with 5 mg or with 10 mg of simvastatin per kg bodyweight per day. Finally, in 20 mice, a silicone tube was led from an osmotic mini-pump to the fracture area. In this way, 10 mice received an approximate local dose of simvastatin of 0.1 mg per kg per day for the duration of the experiment and 10 mice received the vehicle compound. All treatments lasted until the end of the experiment. Bilateral femurs were harvested 14 days post-operative. Biomechanical tests were performed by way of three-point bending. Data was analysed with ANOVA, Scheffé's post-hoc test and Student's unpaired t-test. Results With daily simvastatin injections, no effects could be demonstrated for any of the parameters examined. Continuous systemic delivery resulted in a 160% larger force at failure. Continuous local delivery of simvastatin resulted in a 170% larger force at failure as well as a twofold larger energy uptake. Conclusion This study found a dramatic positive effect on biomechanical parameters of fracture healing by simvastatin treatment directly applied to the fracture area.

  3. A short peptide from frog skin accelerates diabetic wound healing.

    Science.gov (United States)

    Liu, Han; Duan, Zilei; Tang, Jing; Lv, Qiumin; Rong, Mingqiang; Lai, Ren

    2014-10-01

    Delayed wound healing will result in the development of chronic wounds in some diseases, such as diabetes. Amphibian skins possess excellent wound-healing ability and represent a resource for prospective wound-healing promoting compounds. A potential wound-healing promoting peptide (CW49; amino acid sequence APFRMGICTTN) was identified from the frog skin of Odorrana grahami. It promotes wound healing in a murine model with a full-thickness dermal wound in both normal and diabetic animals. In addition to its strong angiogenic ability with respect to the upregulation of some angiogenic proteins, CW49 also showed a significant anti-inflammatory effect in diabetic wounds, which was very important for healing chronic wounds. CW49 had little effect on re-epithelialization, resulting in no significant effect on wound closure rate compared to a vehicle control. Altogether, this indicated that CW49 might accelerate diabetic wound healing by promoting angiogenesis and preventing any excessive inflammatory response. Considering its favorable traits as a small peptide that significantly promotes angiogenesis, CW49 might be an excellent candidate or template for the development of a drug for use in the treatment of diabetic wounds.

  4. Association between timing of zoledronic acid infusion and hip fracture healing

    DEFF Research Database (Denmark)

    Colón-Emeric, C; Nordsletten, L; Olson, S

    2010-01-01

    Patients in the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) Recurrent Fracture Trial were assessed for evidence of delayed hip fracture healing. No association was observed between zoledronic acid (ZOL) and delayed healing. We conclude that ZOL has no clinically...... evident effect on fracture healing, even when the drug is infused in the immediate postoperative period. INTRODUCTION: Intravenous zoledronic acid 5 mg (ZOL) given after a hip fracture reduces secondary fracture rates and mortality. It has been postulated that bisphosphonates may affect healing if given...... soon after a fracture. We sought to determine whether the timing of ZOL infusion affected the risk of delayed hip fracture healing. METHODS: In the HORIZON Recurrent Fracture Trial, patients were randomized within 90 days of a low-trauma hip fracture to receive either once-yearly ZOL (n¿=¿1...

  5. CaMKK2 Inhibition in Enhancing Bone Fracture Healing

    Science.gov (United States)

    2016-05-01

    mm) retrograde through the distal condyle of the femur. Radiographic analyses were performed to confirm the location and quality of the fractures...costs, loss of productivity and most importantly, loss of patient quality of life. Prolonged healing time and non-union occur in 5-10% of these...male C57BL6 (50) were purchased from Harlan Laboratories (Indianapolis) and housed under a 12-hr light and dark cycle, with food and water provided ad

  6. Accelerated tibial fracture union in the third trimester of pregnancy: a case report

    Directory of Open Access Journals (Sweden)

    Ahmad Mudussar A

    2008-02-01

    Full Text Available Abstract Introduction We present a case of accelerated tibial fracture union in the third trimester of pregnancy. This is of particular relevance to orthopaedic surgeons, who must be made aware of the potentially accelerated healing response in pregnancy and the requirement for prompt treatment. Case presentation A 40 year old woman at 34 weeks gestational age sustained a displaced fracture of the tibial shaft. This was initially treated conservatively in plaster with view to intra-medullary nailing postpartum. Following an emergency caesarean section, the patient was able to fully weight bear without pain 4 weeks post injury, indicating clinical union. Radiographs demonstrated radiological union with good alignment and abundant callus formation. Fracture union occurred within 4 weeks, less than half the time expected for a conservatively treated tibial shaft fracture. Conclusion Long bone fractures in pregnancy require clear and precise management plans as fracture healing is potentially accelerated. Non-operative treatment is advisable provided satisfactory alignment of the fracture is achieved.

  7. Microbial symbionts accelerate wound healing via the neuropeptide hormone oxytocin.

    Directory of Open Access Journals (Sweden)

    Theofilos Poutahidis

    Full Text Available Wound healing capability is inextricably linked with diverse aspects of physical fitness ranging from recovery after minor injuries and surgery to diabetes and some types of cancer. Impact of the microbiome upon the mammalian wound healing process is poorly understood. We discover that supplementing the gut microbiome with lactic acid microbes in drinking water accelerates the wound-healing process to occur in half the time required for matched control animals. Further, we find that Lactobacillus reuteri enhances wound-healing properties through up-regulation of the neuropeptide hormone oxytocin, a factor integral in social bonding and reproduction, by a vagus nerve-mediated pathway. Bacteria-triggered oxytocin serves to activate host CD4+Foxp3+CD25+ immune T regulatory cells conveying transplantable wound healing capacity to naive Rag2-deficient animals. This study determined oxytocin to be a novel component of a multi-directional gut microbe-brain-immune axis, with wound-healing capability as a previously unrecognized output of this axis. We also provide experimental evidence to support long-standing medical traditions associating diet, social practices, and the immune system with efficient recovery after injury, sustained good health, and longevity.

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

    Science.gov (United States)

    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.

  9. Accelerated endothelial wound healing on microstructured substrates under flow.

    Science.gov (United States)

    Franco, Davide; Milde, Florian; Klingauf, Mirko; Orsenigo, Fabrizio; Dejana, Elisabetta; Poulikakos, Dimos; Cecchini, Marco; Koumoutsakos, Petros; Ferrari, Aldo; Kurtcuoglu, Vartan

    2013-02-01

    Understanding and accelerating the mechanisms of endothelial wound healing is of fundamental interest for biotechnology and of significant medical utility in repairing pathologic changes to the vasculature induced by invasive medical interventions. We report the fundamental mechanisms that determine the influence of substrate topography and flow on the efficiency of endothelial regeneration. We exposed endothelial monolayers, grown on topographically engineered substrates (gratings), to controlled levels of flow-induced shear stress. The wound healing dynamics were recorded and analyzed in various configurations, defined by the relative orientation of an inflicted wound, the topography and the flow direction. Under flow perpendicular to the wound, the speed of endothelial regeneration was significantly increased on substrates with gratings oriented in the direction of the flow when compared to flat substrates. This behavior is linked to the dynamic state of cell-to-cell adhesions in the monolayer. In particular, interactions with the substrate topography counteract Vascular Endothelial Cadherin phosphorylation induced by the flow and the wounding. This effect contributes to modulating the mechanical connection between migrating cells to an optimal level, increasing their coordination and resulting in coherent cell motility and preservation of the monolayer integrity, thus accelerating wound healing. We further demonstrate that the reduction of vascular endothelial cadherin phosphorylation, through specific inhibition of Src activity, enhances endothelial wound healing in flows over flat substrates.

  10. Thyrotropin-releasing hormone and its analogs accelerate wound healing.

    Science.gov (United States)

    Nie, Chunlei; Yang, Daping; Liu, Nan; Dong, Deli; Xu, Jin; Zhang, Jiewu

    2014-06-15

    Thyrotropin-releasing hormone (TRH) is a classical hormone that controls thyroid hormone production in the anterior pituitary gland. However, recent evidence suggested that TRH is expressed in nonhypothalamic tissues such as epidermal keratinocytes and dermal fibroblasts, but its function is not clear. This study aimed to investigate the effects of TRH and its analogs on wound healing and explore the underlying mechanisms. A stented excisional wound model was established, and the wound healing among vehicle control, TRH, and TRH analog taltirelin treatment groups was evaluated by macroscopic and histologic analyses. Primary fibroblasts were isolated from rat dermis and treated with vehicle control, TRH or taltirelin, cell migration, and proliferation were examined by scratch migration assay, MTT, and 5-ethynyl-2'- deoxyuridine (EdU) assay. The expression of α-Smooth muscle actin in fibroblasts was detected by Western blot and immunocytochemical analysis. TRH or taltirelin-treated wounds exhibited accelerated wound healing with enhanced granulation tissue formation and increased re-epithelialization and tissue formation. Furthermore, TRH or taltirelin promoted the migration and proliferation of fibroblasts and induced the expression of α-Smooth muscle actin in fibroblasts. TRH is important in upregulating the phenotypes of dermal fibroblasts and plays a role in accelerating wound healing. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Effect of early or delayed treatment upon healing of mandibular fractures: a systematic literature review

    DEFF Research Database (Denmark)

    Hermund, Niels Ulrich; Hillerup, Søren; Kofod, Thomas

    2008-01-01

    The possible relation between treatment delay and healing complications in mandibular fracture treatment (excluding condylar fractures) was reviewed systematically. Twenty-two studies were identified. No randomized studies focused on the effect of immediate or delayed treatment. The main focus...

  12. Neutrophils contribute to fracture healing by synthesizing fibronectin+ extracellular matrix rapidly after injury

    NARCIS (Netherlands)

    Bastian, Okan W.; Koenderman, Leo; Alblas, Jacqueline; Leenen, Luke P H; Blokhuis, Taco J.

    2016-01-01

    The role of inflammatory cells in bone regeneration remains unclear. We hypothesize that leukocytes contribute to fracture healing by rapidly synthesizing an "emergency extracellular matrix (ECM)" before stromal cells infiltrate the fracture hematoma (FH) and synthesize the eventual collagenous bone

  13. Modulation of inflammation by Cicaderma ointment accelerates skin wound healing.

    Science.gov (United States)

    Morin, Christophe; Roumegous, Audrey; Carpentier, Gilles; Barbier-Chassefière, Véronique; Garrigue-Antar, Laure; Caredda, Stéphane; Courty, José

    2012-10-01

    Skin wound healing is a natural and intricate process that takes place after injury, involving different sequential phases such as hemostasis, inflammatory phase, proliferative phase, and remodeling that are associated with complex biochemical events. The interruption or failure of wound healing leads to chronic nonhealing wounds or fibrosis-associated diseases constituting a major health problem where, unfortunately, medicines are not very effective. The objective of this study was to evaluate the capacity of Cicaderma ointment (Boiron, Lyon, France) to accelerate ulcer closure without fibrosis and investigate wound healing dynamic processes. We used a necrotic ulcer model in mice induced by intradermal doxorubicin injection, and after 11 days, when the ulcer area was maximal, we applied Vaseline petroleum jelly or Cicaderma every 2 days. Topical application of Cicaderma allowed a rapid recovery of mature epidermal structure, a more compact and organized dermis and collagen bundles compared with the Vaseline group. Furthermore, the expression of numerous cytokines/molecules in the ulcer was increased 11 days after doxorubicin injection compared with healthy skin. Cicaderma rapidly reduced the level of proinflammatory cytokines, mainly tumor necrosis factor (TNF)-α and others of the TNF pathway, which can be correlated to a decrease of polymorphonuclear recruitment. It is noteworthy that the modulation of inflammation through TNF-α, macrophage inflammatory protein-1α, interleukin (IL)-12, IL-4, and macrophage-colony-stimulating factor was maintained 9 days after the first ointment application, facilitating the wound closure without affecting angiogenesis. These cytokines seem to be potential targets for therapeutic approaches in chronic wounds. Our results confirm the use of Cicaderma for accelerating skin wound healing and open new avenues for sequential treatments to improve healing.

  14. Urine matrix metalloproteinases (MMPs) as biomarkers for the progression of fracture healing.

    Science.gov (United States)

    Wigner, Nathan A; Kulkarni, Nitin; Yakavonis, Mark; Young, Megan; Tinsley, Brian; Meeks, Brett; Einhorn, Thomas A; Gerstenfeld, Louis C

    2012-03-01

    Whilst the majority of fractures heal normally, it is estimated that ∼10% of fractures exhibit some level of delayed or impaired healing. Although radiography is the primary diagnostic tool to assess the progression of fracture healing, radiographic features only qualitatively correlate with tissue level increases in mineral content and do not quantitatively measure underlying biological processes that are associated with the progression of healing. Specific metaloproteinases have been shown to be essential to processes of both angiogenesis and mineralised cartilage resorption and bone remodelling at different phases of fracture healing. The aim of this study was to determine the potential of using a simple urine based assay of the activity of two MMPs as a means of assessing the biological progression of fracture healing through the endochondral phase of healing. Using a standard mid-diaphyseal murine model of femoral fracture, MMP9 and MMP13 proteins and enzymatic activity levels were quantified in the urine of mice across the time-course of fracture healing and compared to the mRNA and protein expression profiles in the calluses. Both urinary MMP9 and MMP13 protein and enzymatic activity levels, assessed by Western blot, zymogram and specific MMP fluorometric substrate assays, corresponded to mRNA expression and immunohistologic assays of the proteins within callus tissues. These studies suggest that urinary levels of MMP9 and MMP13 may have potential as metabolic markers to monitor the progression of fracture healing.

  15. Increase in bone protein components with healing rat fractures: enhancement by zinc treatment.

    Science.gov (United States)

    Igarashi, A; Yamaguchi, M

    1999-12-01

    The alteration in bone components in the femoral-diaphyseal tissues with fracture healing was investigated. Rats were sacrificed 7 and 14 days after the femoral fracture. Protein content in the femoral-diaphyseal tissues was markedly elevated by fracture healing. Analysis with sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that many protein molecules were induced in the diaphyseal tissues with fracture healing. Moreover, when the femoral-diaphyseal tissues with fracture healing were cultured for 24 and 48 h in a serum-free medium, many proteins in the bone tissues were released into the medium. Also, the culture of the diaphyseal tissues with fracture healing caused a significant increase in bone alkaline phosphatase activity and deoxyribonucleic acid (DNA) content. Meanwhile, the presence of zinc acexamate (10-5 and 10-4 M), a stimulator of bone formation, in a culture medium induced a significant elevation of protein content and alkaline phosphatase activity in the diaphyseal tissues with fracture healing. Such an effect was completely abolished by the presence of cycloheximide (10-6 M), an inhibitor of protein synthesis. The present study suggests that fracture healing induces a newly synthesized bone protein component including stimulatory factor(s) for bone formation. Zinc supplementation may stimulate the healing of femoral fracture.

  16. Suplementação de vitamina C não acelera o processo de consolidação de fratura da tíbia em ratos Supplementary vitamin C does not accelerate bone healing in a rat tibia fracture model

    Directory of Open Access Journals (Sweden)

    Vincenzo Giordano

    2012-01-01

    manually, they were not stabilized, and unprotected weight-bearing was allowed. At two, four, and six weeks post-fracture, the rats in both groups were anesthetized and sacrificed by cervical dislocation. Callus tissue was dissected, prepared, and analyzed histologically. Histomorphological analysis was performed at six weeks post-fracture and the extent of fracture healing was determined using a five-point scale. RESULTS: There were no histological and histomorphological differences between drug-treated animals and the shamin the three different stages studied. By six weeks post-fracture, the five animals of each group had a complete bone union. CONCLUSION: Under the studied conditions, intraperitoneal Vitamin C supplementation does not accelerate the fracture healing process after experimental tibia fracture in rats. Level of evidence: Level 2, individual study with experimental design.

  17. Association between timing of zoledronic acid infusion and hip fracture healing

    DEFF Research Database (Denmark)

    Colón-Emeric, C; Nordsletten, L; Olson, S

    2011-01-01

    Patients in the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) Recurrent Fracture Trial were assessed for evidence of delayed hip fracture healing. No association was observed between zoledronic acid (ZOL) and delayed healing. We conclude that ZOL has no clinical...

  18. Accelerated healing of full thickness dermal wounds by macroporous waterborne polyurethane-chitosan hydrogel scaffolds.

    Science.gov (United States)

    Bankoti, Kamakshi; Rameshbabu, Arun Prabhu; Datta, Sayanti; Maity, Priti Prasanna; Goswami, Piyali; Datta, Pallab; Ghosh, Sudip Kumar; Mitra, Analava; Dhara, Santanu

    2017-12-01

    Wound healing is a dynamic process wherein cells, and macromolecules work in consonance to facilitate tissue regeneration and restore tissue integrity. In the case of full-thickness (FT) wounds, healing requires additional support from native or synthetic matrices to aid tissue regeneration. In particular, a matrix with optimum hydrophilic-hydrophobic balance which will undergo adequate swelling as well as reduce bacterial adhesion has remained elusive. In the present study, polyurethane diol dispersion (PUD) and the anti-bacterial chitosan (Chn) were blended in different ratios which self-organized to form macroporous hydrogel scaffolds (MHS) at room temperature on drying. SEM and AFM micrographs revealed the macroporosity on top and fracture surfaces of the MHS. FTIR spectra revealed the intermolecular as well as intra-molecular hydrogen bonding interactions between the two polymers responsible for phase separation, which was also observed by micrographs of blend solutions during the drying process. The effect of phase separation on mechanical properties and in vitro degradation (hydrolytic, enzymatic and pH dependent) of MHS were studied and found to be suitable for wound healing. In vitro cytocompatibility was demonstrated by the proliferation of primary rat fibroblast cells on MHS. Selected MHS was subjected to in vivo FT wound healing study in Wistar rats and compared with an analogous polyurethane containing commercial dressing i.e. Tegaderm™. The MHS-treated wounds demonstrated accelerated healing with increased wound contraction, higher collagen synthesis, and vascularization in wound area compared to Tegaderm™. Thus, it is concluded that the developed MHS is a promising candidate for application as FT wound healing dressings. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2016-01-01

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

  20. Acacia honey accelerates in vitro corneal ulcer wound healing model.

    Science.gov (United States)

    Abd Ghafar, Norzana; Ker-Woon, Choy; Hui, Chua Kien; Mohd Yusof, Yasmin Anum; Wan Ngah, Wan Zurinah

    2016-07-29

    The study aimed to evaluate the effects of Acacia honey (AH) on the migration, differentiation and healing properties of the cultured rabbit corneal fibroblasts. Stromal derived corneal fibroblasts from New Zealand White rabbit (n = 6) were isolated and cultured until passage 1. In vitro corneal ulcer was created using a 4 mm corneal trephine onto confluent cultures and treated with basal medium (FD), medium containing serum (FDS), with and without 0.025 % AH. Wound areas were recorded at day 0, 3 and 6 post wound creation. Genes and proteins associated with wound healing and differentiation such as aldehyde dehydrogenase (ALDH), vimentin, alpha-smooth muscle actin (α-SMA), collagen type I, lumican and matrix metalloproteinase 12 (MMP12) were evaluated using qRT-PCR and immunocytochemistry respectively. Cells cultured with AH-enriched FDS media achieved complete wound closure at day 6 post wound creation. The cells cultured in AH-enriched FDS media increased the expression of vimentin, collagen type I and lumican genes and decreased the ALDH, α-SMA and MMP12 gene expressions. Protein expression of ALDH, vimentin and α-SMA were in accordance with the gene expression analyses. These results demonstrated AH accelerate corneal fibroblasts migration and differentiation of the in vitro corneal ulcer model while increasing the genes and proteins associated with stromal wound healing.

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

    Science.gov (United States)

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

    2016-03-01

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

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

    OpenAIRE

    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 ...

  3. A Feasibility study on Monitoring of Fracture Healing by Electric Stimulation-A study on 2 tibial fracture cases

    Directory of Open Access Journals (Sweden)

    S. Kumaravel

    2010-09-01

    Full Text Available Sufferings associated with broken limbs have been on an exponential increase in India, mainly due to road accidents. Conventional healing and uniting methods takes any where between 1 ½ to 6 months depending on the nature of the fracture and the speed of reporting for medical care .In an effort to speed up the healing process low voltage electric stimulation has been tried and has been found to cut down the healing time by nearly 30% depending on the fracture-history. Also the course of fracture healing has been traced and definite trends during the process identified.Two case studies of fractures of the leg bone through electric stimulation indicate identical trends in the healingprocess.

  4. Transcriptional analysis of fracture healing and the induction of embryonic stem cell-related genes.

    Directory of Open Access Journals (Sweden)

    Manish Bais

    Full Text Available 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 approximately 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

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

    Science.gov (United States)

    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. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

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

    Science.gov (United States)

    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.

  7. Comparison in bone turnover markers during early healing of femoral neck fracture and trochanteric fracture in elderly patients

    Directory of Open Access Journals (Sweden)

    Shota Ikegami

    2009-10-01

    Full Text Available Healing of fractures is different for each bone and bone turnover markers may reflect the fracture healing process. The purpose of this study was to determine the characteristic changes in bone turnover markers during the fracture healing process. The subjects were consecutive patients with femoral neck or trochanteric fracture who underwent surgery and achieved bone union. There were a total of 39 patients, including 33 women and 6 men. There were 18 patients (16 women and 2 men with femoral neck fracture and 21 patients (17 women and 4 men with trochanteric fracture. Serum bone-specific alkaline phosphatase (BAP was measured as a bone formation marker. Urine and serum levels of N-terminal telopeptide of type I collagen (NTX, as well as urine levels of C-terminal telopeptide of type I collagen (CTX and deoxypyridinoline (DPD, were measured as markers of bone resorption. All bone turnover markers showed similar changes in patients with either type of fracture, but significantly higher levels of both bone formation and resorption markers were observed in trochanteric fracture patients than in neck fracture patients. BAP showed similar levels at one week after surgery and then increased. Bone resorption markers were increased after surgery in patients with either fracture. The markers reached their peak values at three weeks (BAP and urinary NTX, five weeks (serum NTX and DPD, and 2-3 weeks (CTX after surgery. The increase in bone turnover markers after hip fracture surgery and the subsequent decrease may reflect increased bone formation and remodeling during the healing process. Both fractures had a similar bone turnover marker profile, but the extent of the changes differed between femoral neck and trochanteric fractures.

  8. Upregulation of inflammatory genes and downregulation of sclerostin gene expression are key elements in the early phase of fragility fracture healing.

    Directory of Open Access Journals (Sweden)

    Joana Caetano-Lopes

    Full Text Available BACKGROUND: Fracture healing is orchestrated by a specific set of events that culminates in the repair of bone and reachievement of its biomechanical properties. The aim of our work was to study the sequence of gene expression events involved in inflammation and bone remodeling occurring in the early phases of callus formation in osteoporotic patients. METHODOLOGY/PRINCIPAL FINDINGS: Fifty-six patients submitted to hip replacement surgery after a low-energy hip fracture were enrolled in this study. The patients were grouped according to the time interval between fracture and surgery: bone collected within 3 days after fracture (n = 13; between the 4(th and 7(th day (n = 33; and after one week from the fracture (n = 10. Inflammation- and bone metabolism-related genes were assessed at the fracture site. The expression of pro-inflammatory cytokines was increased in the first days after fracture. The genes responsible for bone formation and resorption were upregulated one week after fracture. The increase in RANKL expression occurred just before that, between the 4(th-7(th days after fracture. Sclerostin expression diminished during the first days after fracture. CONCLUSIONS: The expression of inflammation-related genes, especially IL-6, is highest at the very first days after fracture but from day 4 onwards there is a shift towards bone remodeling genes, suggesting that the inflammatory phase triggers bone healing. We propose that an initial inflammatory stimulus and a decrease in sclerostin-related effects are the key components in fracture healing. In osteoporotic patients, cellular machinery seems to adequately react to the inflammatory stimulus, therefore local promotion of these events might constitute a promising medical intervention to accelerate fracture healing.

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

    OpenAIRE

    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 ...

  10. Fracture behaviour of a self-healing microcapsule-loaded epoxy system

    Directory of Open Access Journals (Sweden)

    2011-03-01

    Full Text Available The effect of temperature on the fracture behaviour of a microcapsule-loaded epoxy matrix was investigated. Microencapsulated epoxy and mercaptan-derivative healing agents were incorporated into an epoxy matrix to produce a polymer composite capable of self-healing. Maximum fracture loads were measured using the double-torsion method. Thermal aging at 55 and 110°C for 17 hours [hrs] was applied to heal the pre-cracked samples. The addition of microcapsules appeared to increase significantly the load carrying capacity of the epoxy after healing. Once healed, the composites achieved as much as 93–171% of its virgin maximum fracture load at 18, 55 and 110°C. The fracture behavior of the microcapsule- loaded epoxy matrix was influenced by the healing temperature. The high self-healing efficiency may be attributed to the result of the subsurface micro-crack pinning or deviation, and to a stronger microencapsulated epoxy and mercaptanderivative binder than that of the bulk epoxy. The results show that the healing temperature has a significant effect on recovery of load transferring capability after fracture.

  11. Low-intensity pulsed ultrasound increases bone volume, osteoid thickness and mineral apposition rate in the area of fracture healing in patients with a delayed union of the osteotomized fibula

    NARCIS (Netherlands)

    Rutten, S.; Nolte, P.A.; Korstjens, C.M.; van Duin, M.A.; Klein-Nulend, J.

    2008-01-01

    Introduction Low-intensity pulsed ultrasound (LIPUS) accelerates impaired fracture healing, but the exact mechanism is unknown. The aim of this study was to investigate how LIPUS affects bone healing at the tissue level in patients with a delayed union of the osteotomized fibula, by using histology

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

    Science.gov (United States)

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

    2015-05-01

    Low-magnitude, high-frequency vibration accelerates fracture and wound healing and prevents disuse atrophy in musculoskeletal tissues. 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. Controlled laboratory study. 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. 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 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. As low-magnitude, high-frequency vibration had no negative effects on ligament healing, vibration therapy may be a useful tool to accelerate healing of other tissues (bone) in multitrauma injuries without inhibiting ligament healing. Additionally, the enhanced gene expression in response to low-magnitude, high-frequency vibration in the intact Achilles tendon suggests

  13. AN ULTRASTRUCTURE INVESTIGATION OF OSTEOPORO-SIS FRACTURE HEALING IN OVARIECTOMIZED RAT

    Institute of Scientific and Technical Information of China (English)

    楼国祥; 张先龙

    2003-01-01

    Objective To elucidate the influence of osteoporosis on the fracture healing in ovariectomized rat. Methods 24 females 8-month-old SD rats were divided randomly into two groups.12 were sham-operated(Sham)and 12 were bilaterally ovariectomized(OVX) 3 months later.The femoral fracture model were made in both groups,the healing process was observed by transmission electron microscopy(TEM) on d3,d7,d14,d21,d28,and d42 after making fracture in control groups(Sham) and the osteoporosis group(OVX).Results According to the TEM findings,the types of fracture healing cells,their ultrastructure changes and functional states were almost identical in both groups till d21 after making fracture.In OVX group,the calcified cartilage was not resorbed and replaced by new woven bone,a lot of necrosis chondrocytes were found being embedded in a calcified chondroid matrix on d28;after this period,osteoclastic bone resorption become severe gra-dually accompanied by osteocytic osteolysis during d28 to d42 of fracture healing. Conclusion Osteoporosis greatly affect the fracture healing in the later period of healing proess.It demonstrated as endochondral bone formation delayed and increased osteoclastic bone resorption which was made even more severed by osteocytic osteolysis during the period of bone callus remodelling.

  14. Increase in bone growth factors with healing rat fractures: the enhancing effect of zinc.

    Science.gov (United States)

    Igarashi, A; Yamaguchi, M

    2001-10-01

    The effect of zinc, a stimulator of bone formation, on bone protein components in the femoral-diaphyseal tissues with fracture healing was investigated. Rats were sacrificed between 1 and 7 days after the femoral fracture, and the diaphyseal tissues were cultured in a serum-free Dulbecco's modified Eagle's medium for 24 h. Protein content in the femoral-diaphyseal tissues was markedly elevated by fracture healing. The amount of protein in the medium cultured with the diaphyseal tissues obtained from fracture healing rats was markedly elevated as compared with that of normal rats, indicating that bone protein components were secreted into culture medium. Analysis with sodium dodecyl sulfate-polyacrylamide gel elecrophoresis (SDS-PAGE) showed that many protein molecules were secreted from the diaphyseal tissues with fracture healing. Especially, protein molecule of about 66 kDa was markedly secreted by fracture healing. The presence of zinc acexamate (10(-5) and 10(-4) M) in culture medium induced a significant elevation of medium protein content; the zinc effect was enhanced by culture with the diaphyseal tissues of fracture healing rats. Also, the culture of diaphyseal tissues with fracture healing caused a significant increase in insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-beta1) in culture medium. The production of IGF-I and TGF-beta1 from bone tissues with fracture healing was significantly enhanced in the presence of zinc acexamate (10(-6)-10(-4) M). Moreover, the addition of IGF-I (10(-8) M) or TGF-beta1 (10(-10) M) in a culture medium caused a significant elevation of protein content in the medium cultured with the femoral-diaphyseal tissues from normal and fracture healing rats. The effect of IGF-I or TGF-beta1 was significantly enhanced in the presence of zinc acexamate (10(-4) M). Also, deoxyribonucleic acid (DNA) content in the diaphyseal tissues from normal and fracture healing rats was significantly raised by the

  15. Mice lacking pten in osteoblasts have improved intramembranous and late endochondral fracture healing.

    Directory of Open Access Journals (Sweden)

    Travis A Burgers

    Full Text Available 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-cre(tg/+;Pten(flox/flox . Mid-diaphyseal femoral fractures induced in wild-type and Ocn-cre(tg/+;Pten(flox/flox mice were studied via micro-computed tomography (µCT scans, biomechanical testing, histological and histomorphometric analysis, and protein expression analysis. Ocn-cre(tg/+;Pten(flox/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.

  16. Healing of multiple fractured thoracic dorsal spinous processes in a Quarter horse

    OpenAIRE

    Molnar, Rebeccah; Barber, Spencer M.; Pharr, John W.; Panizzi, Luca; Plaxton, Andrea

    2012-01-01

    A Quarter horse gelding sustained fracture and displacement of spinous processes T2–T10. Radiographic evidence of healing was seen 3 mo following injury, and at 2 years post-injury all spinous processes had healed and undergone partial re-alignment. This re-alignment has not been reported before.

  17. Healing of multiple fractured thoracic dorsal spinous processes in a Quarter horse.

    Science.gov (United States)

    Molnar, Rebeccah; Barber, Spencer M; Pharr, John W; Panizzi, Luca; Plaxton, Andrea

    2012-03-01

    A Quarter horse gelding sustained fracture and displacement of spinous processes T2-T10. Radiographic evidence of healing was seen 3 mo following injury, and at 2 years post-injury all spinous processes had healed and undergone partial re-alignment. This re-alignment has not been reported before.

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

    Directory of Open Access Journals (Sweden)

    Kemal Gökkuş

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Mohd Azri Abd Jalil

    2012-01-01

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

  20. Radiological findings and healing patterns of incomplete stress fractures of the pars interarticularis

    Energy Technology Data Exchange (ETDEWEB)

    Dunn, Andrew J.; Campbell, Robert S.D. [Royal Liverpool and Broadgreen University Teaching Hospitals, Department of Medical Imaging, Liverpool (United Kingdom); Mayor, Peter E. [Leighton Hospital, Department of Medical Imaging, Crewe, Cheshire (United Kingdom); Rees, Dai [Robert Jones and Agnes-Hunt Orthopaedic Hospital, Department of Orthopaedic Surgery, Oswestry, Shropshire (United Kingdom)

    2008-05-15

    The objective was to retrospectively record the CT and MRI features and healing patterns of acute, incomplete stress fractures of the pars interarticularis. The CT scans of 156 adolescents referred with suspected pars interarticularis stress fractures were reviewed. Patients with incomplete (grade 2) pars fractures were included in the study. Fractures were assessed on CT according to vertebral level, location of cortical involvement and direction of fracture propagation. MRI was also performed in 72 of the 156 cases. MRI images of incomplete fractures were assessed for the presence of marrow oedema and cortical integrity. Fracture healing patterns were characterised on follow-up CT imaging. Twenty-five incomplete fractures were identified in 23 patients on CT. All fractures involved the inferior or infero-medial cortex of the pars and propagated superiorly or superolaterally. Ninety-two percent of incomplete fractures demonstrated either complete or partial healing on follow-up imaging. Two (8%) cases progressed to complete fractures. Thirteen incomplete fractures in 11 patients confirmed on CT also had MRI, and 92% demonstrated oedema in the pars. Ten out of thirteen fractures (77%) showed a break in the infero-medial cortex with intact supero-lateral cortex, which correlated with the CT findings. MRI incorrectly graded one case as a complete (grade 3) fracture, and 2 cases as (grade 1) stress reaction. Six fractures had follow-up MRI, 67% showed partial or complete cortical healing, and the same number showed persistent marrow oedema. Incomplete fracture of the pars interarticularis represents a stage of the evolution of a complete stress fracture. The direction of fracture propagation is consistent, and complete healing can be achieved in most cases with appropriate clinical management. CT best demonstrates fracture size and extent, and is the most appropriate modality for follow-up. MRI is limited in its ability to fully depict the cortical integrity of

  1. Midkine-deficiency delays chondrogenesis during the early phase of fracture healing in mice.

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    Melanie Haffner-Luntzer

    Full Text Available The growth and differentiation factor midkine (Mdk plays an important role in bone development and remodeling. Mdk-deficient mice display a high bone mass phenotype when aged 12 and 18 months. Furthermore, Mdk has been identified as a negative regulator of mechanically induced bone formation and it induces pro-chondrogenic, pro-angiogenic and pro-inflammatory effects. Together with the finding that Mdk is expressed in chondrocytes during fracture healing, we hypothesized that Mdk could play a complex role in endochondral ossification during the bone healing process. Femoral osteotomies stabilized using an external fixator were created in wildtype and Mdk-deficient mice. Fracture healing was evaluated 4, 10, 21 and 28 days after surgery using 3-point-bending, micro-computed tomography, histology and immunohistology. We demonstrated that Mdk-deficient mice displayed delayed chondrogenesis during the early phase of fracture healing as well as significantly decreased flexural rigidity and moment of inertia of the fracture callus 21 days after fracture. Mdk-deficiency diminished beta-catenin expression in chondrocytes and delayed presence of macrophages during early fracture healing. We also investigated the impact of Mdk knockdown using siRNA on ATDC5 chondroprogenitor cells in vitro. Knockdown of Mdk expression resulted in a decrease of beta-catenin and chondrogenic differentiation-related matrix proteins, suggesting that delayed chondrogenesis during fracture healing in Mdk-deficient mice may be due to a cell-autonomous mechanism involving reduced beta-catenin signaling. Our results demonstrated that Mdk plays a crucial role in the early inflammation phase and during the development of cartilaginous callus in the fracture healing process.

  2. Self-assembling peptide nanofiber scaffolds accelerate wound healing.

    Directory of Open Access Journals (Sweden)

    Aurore Schneider

    Full Text Available Cutaneous wound repair regenerates skin integrity, but a chronic failure to heal results in compromised tissue function and increased morbidity. To address this, we have used an integrated approach, using nanobiotechnology to augment the rate of wound reepithelialization by combining self-assembling peptide (SAP nanofiber scaffold and Epidermal Growth Factor (EGF. This SAP bioscaffold was tested in a bioengineered Human Skin Equivalent (HSE tissue model that enabled wound reepithelialization to be monitored in a tissue that recapitulates molecular and cellular mechanisms of repair known to occur in human skin. We found that SAP underwent molecular self-assembly to form unique 3D structures that stably covered the surface of the wound, suggesting that this scaffold may serve as a viable wound dressing. We measured the rates of release of EGF from the SAP scaffold and determined that EGF was only released when the scaffold was in direct contact with the HSE. By measuring the length of the epithelial tongue during wound reepithelialization, we found that SAP scaffolds containing EGF accelerated the rate of wound coverage by 5 fold when compared to controls without scaffolds and by 3.5 fold when compared to the scaffold without EGF. In conclusion, our experiments demonstrated that biomaterials composed of a biofunctionalized peptidic scaffold have many properties that are well-suited for the treatment of cutaneous wounds including wound coverage, functionalization with bioactive molecules, localized growth factor release and activation of wound repair.

  3. Mode II fracture toughening and healing of composites using supramolecular polymer interlayers

    Directory of Open Access Journals (Sweden)

    V. Kostopoulos

    2016-11-01

    Full Text Available This study focuses on the transfer of the healing functionality of supramolecular polymers (SP to fibre reinforced composites through interleaving. SPs exhibiting self-healing based on hydrogen bonds were formed into films and were successfully incorporated into carbon fibre composites. The effect of the SP interleaves on in-plane fracture toughness and the subsequent healing capability of the hybrid composites were investigated under mode II fracture loading. The fracture toughness showed considerable increase since the maximum load (Pmax of the hybrid composite approximately doubled, and consequently the mode II interlaminar fracture toughness energy (GIIC exhibited an increase reaching nearly 100% compared to the reference composite. The healing component was activated using external heat. Pmax and GIIC recovery after activation were measured, exhibiting a healing efficiency after the first healing cycle close to 85% for Pmax and 100% for GIIC, eventually dropping to 80% for Pmax while GIIC was retained around 100% even after the fourth healing cycle. Acoustic Emission activity during the tests was monitored and was found to be strongly reduced due to the presence of the SP.

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

    Science.gov (United States)

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

    2015-10-01

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

  5. The Effect of GSM Mobile Phone Electromagnetic Field on Femur Fracture Healing in a Rat Model

    Directory of Open Access Journals (Sweden)

    Ali Kalender

    2012-10-01

    Full Text Available Aim: Biological effects of electromagnetic field (EMF and their consequences on human health have been the subject of much interest and research in recent years. The aim of this study was to investigate the effects of 900 MHz EMF on femur fracture healing in a rat model. Material and Method: After sixty male Sprague-Dawley rats were exposed to a closed right femur fracture under anesthesia, the reduction and fixation were done with a 21 g needle. Then, 900 MHz radiation (2 W peak output power and 1.04 mW/cm2 power density was applied to EM group for one hour/day for seven days. The healing was assessed using radiological (Lane and Sandhu classification, histological (Huo scale for callus evaluation, and biomechanical (3-point bending measures at 2nd, 4th and 6th weeks after fracture. Results: Fracture healing, as assessed radiologically and histopathologically, in Group EM and control animals was similar at 2nd, 4th and 6th weeks. Fracture healing, as assessed biomechanically, was significantly better in Group EM compared to controls in those sacrificed at 2nd week post-procedure (p<0.05. Biomechanical strength was not different between the groups at 4th and 6th weeks. Discussion: 900 MHz EMF from a mobile phone in this rat femur fracture model resulted in no significant difference in healing from controls not exposed to EM radiation.

  6. Strontium Is Incorporated into the Fracture Callus but Does Not Influence the Mechanical Strength of Healing Rat Fractures

    DEFF Research Database (Denmark)

    Brüel, Annemarie; Olsen, Jakob; Birkedal, Henrik

    2011-01-01

    to study fracture healing in rats after 3 and 8 weeks of healing. Two groups of rats were treated with SrR (900 mg/kg/day) mixed into the food, while two groups served as control animals. The healing fractures were investigated by three-point bending, dual energy X-ray absorptiometry, energy-dispersive X......Strontium ranelate (SrR) is a new agent used in the treatment of osteoporosis and is suggested to reduce bone resorption and increase bone formation. We investigated whether SrR influences the macro- and nanomechnical properties of healing fractures in rats. A closed tibia fracture model was used......-ray spectroscopy (EDX), and nanoindentation. There was a 100-fold increase (P\\0.001) in serum Sr after 3 and 8 weeks of SrR treatment. The callus volume was significantly higher in the SrR-treated group than in control animals (P\\0.01) after 3 weeks of healing. This was accompanied by a significant increase...

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2015-12-01

    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. 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. 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. 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. Treatment with 200 mg/kg PTX accelerated fracture healing when compared with the control group.

  9. Healing and prognosis of teeth with intra-alveolar fractures involving the cervical part of the root.

    Science.gov (United States)

    Cvek, Miomir; Mejàre, Ingegerd; Andreasen, Jens Ove

    2002-04-01

    Healing and long-term prognosis of 94 cervical root fractures were evaluated. The teeth were divided into two groups according to type of fracture: transverse fractures limited to the cervical third of the root (51 incisors) and oblique fractures involving both the cervical and middle parts of the root (43 incisors). Neither the frequency nor the type of fracture healing differed significantly between the two groups. In the material as a whole, healing of the fracture with hard tissue formation was observed in 17 teeth (18%), and healing with interposition of periodontal ligament (PDL) and, in some cases, hard tissue between the fragments in 62 teeth (66%). Fifteen teeth (16%) showed no healing and a radiolucency adjacent to the fracture. Statistical analyses revealed that incomplete root formation and a positive sensibility test at the time of injury were significantly related to both healing and hard tissue repair. The same applied to concussion or subluxation compared with dislocation of coronal fragment, as well as optimal compared with suboptimal reposition of displaced coronal fragments. The type and duration of splinting (or no splinting) appeared to be of no significance for frequency or type of healing of cervical root fractures. During the observation time (mean = 75 months), 19 (44%) of the teeth with transverse fractures and 3 (8%) of those with oblique fractures were lost after healing. In conclusion, fractures in the cervical part of the root had a healing potential and the predictive parameters identified for fractures in other parts of the root seemed to be valid for the healing of cervical root fractures. Transverse fractures appeared to have a significantly poorer long-term prognosis compared to oblique fractures, apparently due to a marked post-treatment mobility, which often led to new luxation caused by even minor impacts.

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

    Science.gov (United States)

    Colnot, C; 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.

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

    Science.gov (United States)

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

    2017-01-01

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

  12. Laboratory tests of hydraulic fracturing and swell healing

    DEFF Research Database (Denmark)

    Thunbo, Christensen Claes; Foged, Christensen Helle; Foged, Niels

    1998-01-01

    New laboratory test set-ups and test procedures are described - for testing the formation of hydraulically induced fractures as well as the potential for subsequent fracture closurefrom the relase of a swelling potential. The main purpose with the tests is to provide information on fracturing...

  13. Interface contact profiles of a novel locking plate and its effect on fracture healing in goat

    Institute of Scientific and Technical Information of China (English)

    WEI Da-cheng; ZHAO Yu-feng; XING Shu-xing; WANG Ai-min

    2010-01-01

    Objective: To evaluate the interface characteristics of the new-designed locking plate (LP) and limited contact-dynamic compression plate (LC-DCP) and compare the fracture healing between LP and LC-DCP in a goat tibia fracture model.Methods: Eight-hole LP and LC-DCP were applied to fix flesh goat tibiae in a reproducible manner. The average pressure, force and interface contact area were calculated using Fuji prescale pressure sensitive film interposed among the plate and the bone and image analysis system. Eighthole LP and LC-DCP were applied to each tibia in a goat tibia fracture model. The fracture healing was evaluated by X-ray photography at postoperative 8 weeks. The goats were sacrificed at postoperative 12 weeks. Three-point bending test was conducted in the tibiae.Results: The interface contact of LP system was smaller than that ofLC-DCP (P<0.05), while interface contact force of LP system was higher than that of LC-DCP (P<0.05). Radiographs revealed that the fracture line disappeared in the LP group, while the fracture line was visible in DCP group at postoperative 8 weeks. At postoperative 12 weeks, the bending strength and bending load of fractured tibia were higher in LP group than in DCP group, respectively.Conclusion: The new-designed locking plate can significantly decrease the contact area on the bone interface,which further provides better fracture healing than conventional plates.

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

    Science.gov (United States)

    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.

  15. Novel perfused compression bioreactor system as an in vitro model to investigate fracture healing

    Directory of Open Access Journals (Sweden)

    Waldemar eHoffmann

    2015-02-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  17. Changes in the Serum Level of Vitamin D During Healing of Tibial and Femoral Shaft Fractures

    Directory of Open Access Journals (Sweden)

    Ettehad

    2014-01-01

    Full Text Available Background: Several systemic factors and hormones are thought to regulate the fracture healing process. Vitamin D has emerged as a compound or hormone that actively participates in the regulation of calcium homeostasis and bone metabolism. Objectives: The aim of this study is to determine the serum changes in the level of vitamin D during the acute healing period of tibial and femoral shaft fractures. Patients and Methods: This cross-sectional study included of 73 patients with tibial and femoral shaft fractures referred to the Poursina Hospital between February 2011 and February 2012. Changes in the serum levels of vitamin D were assessed three times in a period of three weeks (at the first visit, end of first week, and end of the third week. Variables such as age, gender, fractured bone, concomitant fracture of tibia and fibula, type of fracture, time of measurement and serum levels of 25-hydroxyvitamin D were assessed. All statistical analyses were performed using the SPSS software. Results: Forty tibial fractures and 33 femoral fractures were recorded. Mean vitamin D levels at the time of admission, after one week and at the end of the third week for the 73 participants included in the study were 39.23, 31.49, and 28.57 ng/mL, respectively. The overall reduction of vitamin D level was significantly more evident in the first week versus the following (P < 0.0001. Conclusions: Serum levels of vitamin D in patients with tibial or femoral fractures were reduced during the curative period of the fracture. This can be related the role of vitamin D in the formation and mineralization of the callus. Patients with tibial or femoral shaft fractures may benefit from the administration of vitamin D supplements during the fracture healing process.

  18. Inhibition of indoleamine 2,3-dioxygenase activity accelerates skin wound healing.

    Science.gov (United States)

    Ito, Hiroyasu; Ando, Tatsuya; Ogiso, Hideyuki; Arioka, Yuko; Saito, Kuniaki; Seishima, Mitsuru

    2015-06-01

    Skin wound healing is a complex process involving several stages that include inflammation, proliferation, and remodeling. In the inflammatory phase, pro-inflammatory cytokines and chemokines are induced at the wound site and, they contribute to the development of wound healing. These cytokines also induce indoleamine 2,3-dioxygenase (IDO1) activity; this is the rate-limiting and first enzyme in the l-tryptophan (TRP)-l-kynurenine (KYN) pathway. This study examined the effect of IDO1 on the process of skin wound healing. The expression of the Ido1 mRNA was enhanced after creating a wound in wild-type (WT) mice. TRP concentration was simultaneously reduced at the wound site. The rate of wound healing in IDO1 knockout (IDO-KO) mice was significantly higher than that in WT mice. 1-Methyl-dl-tryptophan (1-MT), a potent inhibitor of IDO1, increased the rate of wound healing in WT mice. The administration of TRP accelerated wound healing in vivo and in an in vitro experimental model, whereas the rate of wound healing was not affected by the administration of KYN. The present study identifies the role of IDO1 in skin wound healing, and indicates that the local administration of 1-MT or TRP may provide an effective strategy for accelerating wound healing.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Boekhtiar Borhanuddin

    2012-01-01

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

  1. Enhancement of albumin expression in bone tissues with healing rat fractures.

    Science.gov (United States)

    Yamaguchi, Masayoshi; Igarashi, Aki; Misawa, Hiroyuki; Tsurusaki, Yoshinori

    2003-05-15

    The characterization of 66 kDa protein molecule, a major protein component which is produced from femoral-diaphyseal tissues with fracture healing (Igarashi and Yamaguchi [2002] Int. J. Mol. Med. 9:503-508), was investigated. Weaning rats were killed at 7 and 14 days after femoral fracture. When the femoral-diaphyseal tissues with fracture healing were cultured for 48 h in a serum-free medium, many proteins in the bone tissues were released into the medium. Analysis with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that a protein molecule of approximately 66 kDa was markedly increased in culture medium from bone tissues with fracture healing. N-terminal sequencing of 66 kDa protein indicated that its N-terminus was identical to that of rat albumin. Western blot analysis of medium 66 kDa protein showed expression of albumin. This expression was significantly enhanced by fracture healing. The expression of albumin was seen in the diaphyseal (cortical bone) and metaphyseal (trabecular bone) tissues of rat femur. When the femoral-diaphyseal tissues obtained at 7 days after femoral fracture were cultured in a serum-free medium containing either vehicle, parathyroid hormone (1-34) (10(-7) M), insulin-like growth factor-I (10(-8) M) or zinc acexamate (10(-4) M), medium albumin was significantly increased in the presence of those bone-stimulating factors. The addition of albumin (0.5 or 1.0 mg/ml of medium) caused a significant increase in calcium and deoxyribonucleic acid contents in the femoral-diaphyseal and -metaphyseal tissues obtained from normal rats in vitro. The present study demonstrates that fracture healing induces a remarkable production of albumin which is a major protein component produced from femoral-diaphyseal tissues of rats, and that albumin has an anabolic effect on bone components.

  2. AN IMMUNOCYTOCHEMICAL STUDY OF BONEMORPHOGENETIC PROTEIN IN EXPERIMENTAL FRACTURE HEALING OF THE RABBIT MANDIBLE

    Institute of Scientific and Technical Information of China (English)

    金岩; 杨连甲; FrankH.White

    1994-01-01

    A monoclonal antibody raised against bone morphogenetic protein (BMP-McAb)has been used to demonstrate the presence of bone mrphogenetic protein(BMP) in experimental fracture healing.Rabbit mandibles were frac-tured using standrdized methods and left to heal for 3,7,14,21and 24 d,respectively.The avidin-biotin com- plex(ABC)method demonstrated an accumulation of positively stained primitive mesenchyman cells at the fracture site in the hematoma stage of bone repair.These cells appeared to undergo differentiation into positively-stained chondroblasts and osteoblasts during the phase of callus formation.Undifferentiated mesenchymal cells showed a high positive reactivity in the early post-fracture stages but a much lower reactivity during the remodelling phase.The results of our study suggest that bone inductive processes are accompanied by the presence of BMP in osteopro-genitor cells during fracture healing of the mandible and that BMP may plqy a significant role in osteogenesis dur-ing bone healing.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2017-01-05

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

    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

  7. Influence of fracture gap size on the pattern of long bone healing: a computational study.

    Science.gov (United States)

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

    2005-07-07

    Following fractures, bones restore their original structural integrity through a complex process in which several cellular events are involved. Among other factors, this process is highly influenced by the mechanical environment of the fracture site. In this study, we present a mathematical model to simulate the effect of mechanical stimuli on most of the cellular processes that occur during fracture healing, namely proliferation, migration and differentiation. On the basis of these three processes, the model then simulates the evolution of geometry, distributions of cell types and elastic properties inside a healing fracture. The three processes were implemented in a Finite Element code as a combination of three coupled analysis stages: a biphasic, a diffusion and a thermoelastic step. We tested the mechano-biological regulatory model thus created by simulating the healing patterns of fractures with different gap sizes and different mechanical stimuli. The callus geometry, tissue differentiation patterns and fracture stiffness predicted by the model were similar to experimental observations for every analysed situation.

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

    Science.gov (United States)

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

    2015-12-01

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    Mawatari, Taro; Iwamoto, Yukihide

    2009-05-01

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

  11. CaMKK2 Inhibition in Enhancing Bone Fracture Healing

    Science.gov (United States)

    2014-08-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

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

    2015-09-01

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

  14. Bilateral distal radius fracture in third trimester of pregnancy with accelerated union: a rare case report.

    Science.gov (United States)

    Tv, Ravikumar; P, Rahul; Grover, Amit; Samorekar, Bheemsingh

    2015-04-01

    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.

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

    Science.gov (United States)

    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, Pbones 6 weeks after osteotomy compared with 2 weeks after osteotomy (multivariate general linear model analysis, Pbone 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.

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

    Science.gov (United States)

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

    2007-02-13

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

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

    Science.gov (United States)

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

    2013-01-01

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

  18. Effect of extracorporeal shock wave therapy on fracture healing in rat femural fractures with intact and excised periosteum.

    Science.gov (United States)

    Oktaş, Birhan; Orhan, Zafer; Erbil, Barış; Değirmenci, Erdem; Ustündağ, Nil

    2014-01-01

    The aim of this study is to compare the effect of extracorporeal shock wave therapy (ESWT) on fractures with intact periosteum and excised periosteum. Thirty-seven Wistar albino rats were randomized into four groups. Osteotomy and intramedullary Kirschner wire fixation were performed on all right femurs under ketamin anesthesia. The first group (n=10) was identified as control group. In the second group (n=10), periosteum located at the osteotomy site was excised circumferentially during surgery. In the third group (n=9), periosteum was left intact and ESWT was applied. In the forth group (n=8), periosteums of all rats were excised and ESWT was applied. All fracture lines were evaluated radiographically each two weeks and histologically at the sixth week. Results were evaluated statistically. In periosteum excised group which represents a model of open fractures with soft tissue defect, ESWT application had a significantly positive histologic effect on bone healing. However, radiological evaluation did not reveal any statistically significant difference between groups with intact and excised periosteums. According to our findings, ESWT can be used to improve fracture healing and prevent pseudoarthrosis in the treatment of open fractures with accompanying soft tissue and periosteum damage. However, further clinical studies are required to include ESWT in routine practice.

  19. Accelerated wound healing with combined NPWT and IPC: a case series.

    Science.gov (United States)

    Arvesen, Kristian; Nielsen, Camilla Bak; Fogh, Karsten

    2017-03-01

    Negative pressure wound therapy (NPWT) and intermittent pneumatic compression (IPC) have traditionally been used in patients with chronic complicated non-healing wounds. The aim of this study (retrospective case series) was to describe the use of NPWT in combination with IPC in patients with a relatively short history (2-6 months) of ulcers. All wounds showed improved healing during the treatment period with marked or moderate reduction in ulcer size, and granulation tissue formation was markedly stimulated. Oedema was markedly reduced due to IPC. Treatment was generally well tolerated. The results of this study indicate that combined NPWT and IPC can accelerate wound healing and reduce oedema, thus shortening the treatment period. Therefore, patients may have a shorter healing period and may avoid entering a chronic wound phase. However, controlled studies of longer duration are needed in order to show the long-term effect of a more accelerated treatment course.

  20. Potential of oncostatin M to accelerate diabetic wound healing.

    Science.gov (United States)

    Shin, Soo Hye; Han, Seung-Kyu; Jeong, Seong-Ho; Kim, Woo-Kyung

    2014-08-01

    Oncostatin M (OSM) is a multifunctional cytokine found in a variety of pathologic conditions, which leads to excessive collagen deposition. Current studies demonstrate that OSM is also a mitogen for fibroblasts and has an anti-inflammatory action. It was therefore hypothesised that OSM may play an important role in healing of chronic wounds that usually involve decreased fibroblast function and persist in the inflammatory stage for a long time. In a previous in vitro study, the authors showed that OSM increased wound healing activities of diabetic dermal fibroblasts. However, wound healing in vivo is a complex process involving multiple factors. Thus, the purpose of this study was to evaluate the effect of OSM on diabetic wound healing in vivo. Five diabetic mice were used in this study. Four full-thickness round wounds were created on the back of each mouse (total 20 wounds). OSM was applied on the two left-side wounds (n = 10) and phosphate-buffered saline was applied on the two right-side wounds (n = 10). After 10 days, unhealed wound areas of the OSM and control groups were compared using the stereoimage optical topometer system. Also, epithelialisation, wound contraction and reduction in wound volume in each group were compared. The OSM-treated group showed superior results in all of the tested parameters. In particular, the unhealed wound area and the reduction in wound volume demonstrated statistically significant differences (P healing of diabetic wounds. © 2012 The Authors. International Wound Journal © 2012 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  1. Pressure ulcer accelerated healing with local injections of granulocyte macrophage-colony stimulating factor.

    Science.gov (United States)

    El Saghir, N S; Bizri, A R; Shabb, N S; Husami, T W; Salem, Z; Shamseddine, A I

    1997-09-01

    This is the first report of granulocyte macrophage-colony stimulating factor (GM-CSF) inducing accelerated healing of a sacral pressure ulcer in a bedridden patient with bilateral hemiplegia. GM-CSF was diluted and injected locally around and into the ulcer bed every 2-3 days for 2 weeks, then weekly for 4 weeks until complete healing occurred. A new firm granulation tissue was noted within a few days. The ulcer showed 85% healing within 2 weeks and 100% by 2 months. Healing started from the periphery and from within the ulcer bed at sites of GM-CSF injections. It was slower at areas where there was complete necrosis and detachment of skin from underlying tissue. The ulcer remained closed until the patient's sudden death 9 months later. A biopsy of granulation tissue showed inflammatory cells and reactive fibroblasts. The potential role of GM-CSF and growth factors in pressure ulcer therapy and wound healing are discussed.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2013-01-10

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

  4. Effect of recombinant human basic fibroblast growth factor on angiogenesis during mandible fracture healing in rabbits

    Institute of Scientific and Technical Information of China (English)

    龚振宇; 周树夏; 顾晓明; 李涤尘; 孙明林

    2003-01-01

    Objective: To investigate the effect of recombinant human basic fibroblast growth factor (rhbFGF) on angiogenesis during mandible fracture healing in rabbit. Methods: Fifty adult white rabbits were used for animal model and randomly divided into a control group (25 rabbits) and an experimental group (25 rabbits). The membranous complex of rhbFGF and bovine type I collagen was prepared and implanted into the rabbit mandible fracture site under periosteum. The animals were sacrificed on 7, 14, 28, 56 and 84 days respectively after operation and the whole mandibles were harvested. The expression of factor VIII related antigen (F8-RA) in callus was examined with immunohistochemical staining. Results: The amounts of microvascular formation in calluses in the rhbFGF-treating group on days 7, 14, 28 and 56 were more than those of the control group (P<0.01).Conclusions: The results indicated that rhbFGF could stimulate microvascular formation during mandible fracture healing in rabbits.

  5. Collagen scaffolds loaded with collagen-binding NGF-beta accelerate ulcer healing.

    Science.gov (United States)

    Sun, Wenjie; Lin, Hang; Chen, Bing; Zhao, Wenxue; Zhao, Yannan; Xiao, Zhifeng; Dai, Jianwu

    2010-03-01

    Studies have shown that exogenous nerve growth factor (NGF) accelerates ulcer healing, but the inefficient growth factor delivery system limits its clinical application. In this report, we found that the native human NGF-beta fused with a collagen-binding domain (CBD) could form a collagen-based NGF targeting delivery system, and the CBD-fused NGF-beta could bind to collagen membranes efficiently. Using the rabbit dermal ischemic ulcer model, we have found that this targeting delivery system maintains a higher concentration and stronger bioactivity of NGF-beta on the collagen membranes by promoting peripheral nerve growth. Furthermore, it enhances the rate of ulcer healing through accelerating the re-epithelialization of dermal ulcer wounds and the formation of capillary lumens within the newly formed tissue area. Thus, collagen membranes loaded with collagen-targeting human NGF-beta accelerate ulcer healing efficiently.

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

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    Esther Wehrle

    2015-01-01

    Full Text Available 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

  7. Cosmos caudatus enhances fracture healing in ovariectomised rats: A preliminary biomechanical evaluation

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    Pamela Godspower Rufus

    2015-01-01

    Full Text Available Summary. Osteoporotic fractures occur in osteoporotic states and affect patients’ quality of life. Cosmos caudatus (ulam raja is a local plant known for its high calcium content and anti-oxidant properties. The present study aimed to investigate the fracture healing properties of C. caudatus water extract in ovariectomised rats by studying the biomechanical properties of tibia. Twenty-four female Sprague-Dawley rats were divided into 4 groups: (i sham operated (ii ovariectomised control (iii ovariectomised + estrogen (100µg/kg/day and (iv ovariectomised + C. caudatus (500mg/kg. Following six weeks of sham operation or ovariectomy, the right tibia of the rats were fractured. Rats were then given their respective treatment for 8 weeks with body weight monitored weekly. Biomechanical analysis indicated that the maximum load, stress and Young’s modulus of the ovariectomised control group (36.2 ± 4.7N, 10.01 ± 1.41MPa, 29.2 ± 9.39MPa respectively were significantly lower compared to sham operated (150.32 ± 32. 6N, 36.75 ± 7.98MPa, 183 ± 53.2MPa respectively and the C. caudatus treated group (136.86 ± 16.95N, 33.45 ± 4.14MPa, 155.13± 58.58MPa respectively. Therefore, C. caudatus extract improved the biomechanical property of the healed bone and may be beneficial for fracture healing in the estrogen deficient state.Industrial Relevance. Post-menopausal osteoporosis is a debilitating disease affecting women worldwide. Hormone replacement therapy (HRT, commonly used for the prevention and treatment of post-menopausal osteoporosis has been associated with several side effects. Thus, in finding alternatives in the treatment of osteoporosis, C. caudatus is a plant of interest. Previous study showed that C. caudatus improved bone histomorphometry in ovariectomized rats by increasing double-labeled surface (dLS/BS, mineral appositional rate (MAR, osteoid volume (OV/BV and osteoblast surface (Ob.S/BS. Therefore, the present study aimed to assess

  8. Experimental fracture healing: evaluation using radionuclide bone imaging: concise communication. [/sup 99m/Tc-methylene diphosphonate; rabbits

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    Gumerman, L.W.; Fogel, S.R.; Goodman, M.A.; Hanley, E.N. Jr.; Kappakas, G.S.; Rutkowski, R.; Levine, G.

    1978-12-01

    Radionuclide bone imaging was performed in a rabbit model to observe the course of fracture healing and to establish criteria for distinguishing nonunion and delayed healing from normal healing. Sequential gamma-camera images (with pinhole collimator) were collected and subjected to computer analysis. Five groups were established: (a) control--immobilization; (b) control--immobilization plus periosteal stripping; (c) simple fracture--osteotomy; (d) delayed union--osteotomy plus periosteal stripping; and (e) nonunion--osteotomy, periosteal stripping and polymethyl methacrylate interposed between fracture fragments. Histographic representation of absolute count rates along rabbit tibias followed a predictable pattern in the simple-fracture and delayed-union groups. They differed only in the time of appearance of phases. The non-union group demonstrated no recognizable sequential pattern. In this experimental model, serial bone scanning the quantitative data analysis has shown potential for indicating the course of healing in fractures and for serving as a guide to treatment.

  9. Improving Impact Strength Recovery of Fractured and Healed Rice Husks Fibre Reinforced Polypropylene Composites.

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    Odhong, O.V.E

    2016-10-01

    Full Text Available Rice husks fibre reinforced polypropylene composite (rhfrpc is a natural plant fibre reinforced polymer composite having advantages of high strength, light weight and affordability. They are commonly used for light load structural and non structural applications. They are mainly used as particle boards, for fencing post, roofing tiles, for interiors of car and aircrafts among other usages. This material once cracked by impact forces cannot be repaired using traditional repair methods for engineering materials such as metals or other composites that can be repaired by welding or by patch repair methods respectively, thus a method of repair of rice husks fibre reinforced polypropylene composites by refilling the damaged volume by injection of various healing agents has been investigated. The composite coupons were produced by injection moulding, cooled sufficiently and prepared for charpy impact tests. Test results for pristine coupons were a maximum of 48 J/mm2 . The destroyed coupons were then subjected to healing in a fabricated healing fixture. Healing agents such as epoxy resin, ethyl cyanoacrylate, and tannin gum have been investigated for their use as possible healing agents to fill the damaged volume and perform healing action at the fractured surfaces. The impact test results were recorded and compared with those of unhealed pristine coupons. The recovered strengths were a maximum of 60 J/mm2 translating into a 125% impact strength recovery, and this is good enough for the healed composites to be recommended for reuse in their second lives of their respective original functions.

  10. Tooth in the line of angle fractures: the impact in the healing process. A retrospective study of 112 patients.

    Science.gov (United States)

    Zanakis, Stylianos; Tasoulas, Jason; Angelidis, Ioannis; Dendrinos, Christos

    2015-01-01

    There is no consensus regarding the prophylactic removal of mandibular third molars (TM) in fracture lines to facilitate healing. Recent evidence suggests that poor healing is attributed to the limited use of antimicrobials, delayed care and semi-rigid fixation as a treatment method, favoring retention of TM. A retrospective cohort study of all patients presenting with mandibular angle fractures at the Hippokration General Hospital of Athens (2006-2011) was designed to examine the association between the presence versus absence of TMs in the line of mandibular fractures and the fracture healing process. Development of complications during the healing process was the outcome of interest. Additional factors considered were patient age, sex, and fracture etiology. Data were extracted from a retrospective chart review, including information from clinical and radiological examinations. The analytical sample included 112 patients with 121 angle fractures. Bivariate methods including Fisher's exact and chi-square tests were used to test the association between TM presence in the fracture line and healing complications. This study found no association between the presence of mandibular TM in the fracture line and postoperative complications and the healing process when combined with light intermaxillary fixation for 15 days. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  11. Electromagnetic stimulation as coadjuvant in the healing of diaphyseal femoral fractures: a randomized controlled trial

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    Alfredo Martinez Rondanelli

    2014-07-01

    Full Text Available Introduction: There is controversy in medical literature regarding the use of electromagnetic fields to promote bone healing.Methods: After designing and building devices capable of generating an electromagnetic field for this study, their safety was confirmed and the electromagnetic therapy was randomly allocated and compared to placebo in patients with fracture of the femoral diaphysis. Treatment began six weeks after the fracture and it was administered once a day, during 1 h, for eight consecutive weeks. Twenty devices were built, 10 of which were placebo-devices. Between June 2008 and October 2009, 64 patients were randomized in two different hospitals and were followed for 24 weeks. The mean age was 30 years (18-59 and 81% were males.Results: Healing observed at week 12 was 75% vs. 58% (p= 0.1; at week 18, it was 94% vs. 80% (p= 0.15; and at week 24, it was 94% vs. 87% (p= 0.43 for the device group and the placebo group, respectively.Discussion: This study suggests that an electromagnetic field stimulus can promote earlier bone healing compared to placebo in femoral diaphyseal fractures. Faster bone healing translates into sooner weight bearing, which – in turn – permits quicker return to normal daily activities.

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

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    Yee, Cristal Sook Ngei [Univ. of California, Merced, CA (United States)

    2016-01-01

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

  13. Vitamin D in Foot and Ankle Fracture Healing: A Literature Review and Research Design.

    Science.gov (United States)

    Bernhard, Andrew; Matuk, Jorge

    2015-10-01

    Vitamin D is a generic name for a group of essential vitamins, or secosteroids, important in calcium homeostasis and bone metabolism. Specifically, efficacy of vitamin D with regard to bone healing is in question. A literature review was performed, finding mostly large studies involving vitamin D effects on prevention of fractures and randomized animal model studies consisting of controlled fractures with vitamin D interventions. The prevention articles generally focus on at-risk populations, including menopausal women and osteoporotic patients, and also most often include calcium in the treatment group. Few studies look at vitamin D specifically. The animal model studies often focus more on vitamin D supplementation; however the results are still largely inconclusive. While recent case reports appear promising, the ambiguity of results on the topic of fracture healing suggests a need for more, higher level research. A novel study design is proposed to help determine the efficacy on vitamin D in fracture healing. Therapeutic, Level IV: Systematic Review. © 2015 The Author(s).

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

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    Julia Kemmler

    Full Text Available 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.

  15. Arginine Silicate Inositol Complex Accelerates Cutaneous Wound Healing.

    Science.gov (United States)

    Durmus, Ali Said; Tuzcu, Mehmet; Ozdemir, Oguzhan; Orhan, Cemal; Sahin, Nurhan; Ozercan, Ibrahim Hanifi; Komorowski, James Richard; Ali, Shakir; Sahin, Kazim

    2016-10-14

    Arginine silicate inositol (ASI) complex is a composition of arginine, silicon, and inositol that has been shown to have beneficial effects on vascular health. This study reports the effects of an ASI ointment on wound healing in rats. A full-thickness excision wound was created by using a disposable 5 mm diameter skin punch biopsy tool. In this placebo-controlled study, the treatment group's wound areas were covered by 4 or 10 % ASI ointments twice a day for 5, 10, or 15 days. The rats were sacrificed either 5, 10, or 15 days after the wounds were created, and biopsy samples were taken for biochemical and histopathological analysis. Granulation tissue appeared significantly faster in the ASI-treated groups than in the control groups (P B cells (NF-κB), and various cytokines (TNF-α and IL-1β) measured in this study showed a significant fall in expression level in ASI-treated wounds. The results suggest that topical application of ASI ointment (especially 4 % concentration) has beneficial effects on the healing response of an excisional wound.

  16. Stimulatory effect of zinc acexamate administration on fracture healing of the femoral-diaphyseal tissues in rats.

    Science.gov (United States)

    Igarashi, A; Yamaguchi, M

    1999-04-01

    The effect of zinc acexamate on fracture healing of the femoral-diaphyseal tissues in rats was investigated in vivo. Zinc acexamate (0.3 and 10.0 mg Zn/100 g body weight per day) was orally administered to rats (4 weeks old) surgically fractured the femoral diaphysis for 14 to 28 days. Calcium content and alkaline phosphatase activity in the femoral-diaphyseal tissues were significantly decreased in rats with fracture healing, while bone acid phosphatase activity and protein content were markedly increased. The administration of zinc acexamate (10.0 mg Zn/100 g) for 28 days caused a significant increase in calcium content, alkaline and acid phosphatases activities, protein and deoxyribonucleic acid (DNA) contents in the femoral-diaphyseal tissues of rats with fracture healing. With the lower dose (3.0 mg Zn/100 g), zinc compound had a partial effect on bone components. Femoral mineral density in rats with fracture healing was significantly increased by the administration of zinc acexamate (10.0 mg Zn/100 g) for 28 days. Femoral-diaphyseal zinc content was significantly decreased in rats with fracture healing. This decrease was completely restored by the administration of zinc acexamate (10.0 mg Zn/100 g) for 28 days. The present study suggests that the supplement of zinc compound stimulates fracture healing of the femoral-diaphyseal tissues in rats.

  17. Experimental study on healing process of rat mandibular bone fracture examined by radiological procedures

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    Iuchi, Yukio; Furumoto, Keiichi (Nippon Dental Univ., Tokyo (Japan))

    1994-06-01

    The healing process of rat mandibular fractures was stereoscopically observed daily, using plain roentgenography in the lateral-oblique and tooth axis directions and bone scintigraphy using 99m-Tc-methylene diphosphoric acid (Tc-99m-MDP). The findings were compared with microradiograms of regional polished specimens. X-ray findings included the following. Up to 3 days after bone fracture, the fracture mesiodistally showed distinct radiolucency, with sharp and irregular fracture stump. Radiopacity of the fracture site gradually increased 7 days or later, and bone trabecular formation by callus and stump bridging started to occur at 14 days. Findings similar to those in the control group were observed 49 days or later. The inside was difficult to differentiate, irrespective of the observation time. Bone scans in the mesiodistal and buccolingual planes revealed tracer uptake in the areas of mandibular and soft tissue damage one day after bone fracture. Tracer uptake began to be seen in the fracture site 3 days later, and became marked at 14 days. Then Tc-99m DMP began to be localized and returned to the findings similar to those at 49 days. Bone scanning tended to show wider areas earlier than roentgenography. Microradiographic mesiodistal examination revealed distinct radiopacy of the fracture line for 3 days after bone fracture. Seven days later, bone resorption cavity occurred in the cortical bone around the fracture stump, along with neogenesis of callus. Neogenesis and calcification began to occur gradually, and 14 days later, the fracture osteoremodeling of the internal bone trabeculae was observed. Bone trabecular formation within the bone, however, occurred later. (N.K.).

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

    Science.gov (United States)

    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.

  19. Alginate-hyaluronan composite hydrogels accelerate wound healing process.

    Science.gov (United States)

    Catanzano, O; D'Esposito, V; Acierno, S; Ambrosio, M R; De Caro, C; Avagliano, C; Russo, P; Russo, R; Miro, A; Ungaro, F; Calignano, A; Formisano, P; Quaglia, F

    2015-10-20

    In this paper we propose polysaccharide hydrogels combining alginate (ALG) and hyaluronan (HA) as biofunctional platform for dermal wound repair. Hydrogels produced by internal gelation were homogeneous and easy to handle. Rheological evaluation of gelation kinetics of ALG/HA mixtures at different ratios allowed understanding the HA effect on ALG cross-linking process. Disk-shaped hydrogels, at different ALG/HA ratio, were characterized for morphology, homogeneity and mechanical properties. Results suggest that, although the presence of HA does significantly slow down gelation kinetics, the concentration of cross-links reached at the end of gelation is scarcely affected. The in vitro activity of ALG/HA dressings was tested on adipose derived multipotent adult stem cells (Ad-MSC) and an immortalized keratinocyte cell line (HaCaT). Hydrogels did not interfere with cell viability in both cells lines, but significantly promoted gap closure in a scratch assay at early (1 day) and late (5 days) stages as compared to hydrogels made of ALG alone (p<0.01 and 0.001 for Ad-MSC and HaCaT, respectively). In vivo wound healing studies, conducted on a rat model of excised wound indicated that after 5 days ALG/HA hydrogels significantly promoted wound closure as compared to ALG ones (p<0.001). Overall results demonstrate that the integration of HA in a physically cross-linked ALG hydrogel can be a versatile strategy to promote wound healing that can be easily translated in a clinical setting.

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

    Science.gov (United States)

    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.

  1. Collagenases and gelatinases in bone healing. The focus on mandibular fractures

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    Kurzepa Jacek

    2014-06-01

    Full Text Available Due to high amount of collagen fibres in the structure of bone, the enzymes capable of collagen digestion play a key role in bone remodelling. Matrix metalloproteinases (MMPs, prevailing extracellular endopeptideses, can digest extracellularly located proteins, e.g. collagen, proteoglycans, elastin or fibronectin. Among MMPs, collagenases (MMP-1, MMP-8 and MMP-13 and gelatinases (MMP-2 and MMP-9 can cleave collagen particles to forms that are able to undergo further steps of catabolism intracellularly. In addition, activity of the gelatinases (as an activation of proinflammatory cytokines facilitates spreading inflammation that is necessary during the first stage of bone healing. Further studies related to the role of various MMPs in mandibular fractures should precisely explain their function in the bone healing and evaluate the influence of MMPs inhibitors on that process. This review provides the basic information about two groups among MMPs family, collagenases and gelatinases, and their role in repairing processes after mandibular fractures.

  2. A review of locking compression plate biomechanics and their advantages as internal fixators in fracture healing.

    Science.gov (United States)

    Miller, Danielle L; Goswami, Tarun

    2007-12-01

    Metallic implants are often involved in the open reduction and internal fixation of fractures. Open reduction and internal fixation is commonly used in cases of trauma when the bone cannot be healed using external methods such as casting. The locking compression plate combines the conventional screw hole, which uses non-locking screws, with a locking screw hole, which uses locking head screws. This allows for more versatility in the application of the plate. There are many factors which affect the functionality of the plate (e.g., screw placement, screw choice, length of plate, distance from bone, etc.). This paper presents a review of the literature related to the biomechanics of locking compression plates and their use as internal fixators in fracture healing. Furthermore, this paper also addresses the materials used for locking compression plates and their mechanical behavior, parameters that control the overall success, as well as inherent bone quality results.

  3. To evaluate the role of platelet-rich plasma in healing of acute diaphyseal fractures of the femur

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    Roop Singh

    2017-02-01

    Conclusion: PRP has no effect on femoral shaft fracture healing treated with closed intramedullary nailing. However, PRP and matrix scaffold provided by fibrin membrane may provide an artificial hematoma effect in the initial phase of healing in open or failed closed intramedullary nailing.

  4. Effect of autocontrol micromotion intramedullary interlocking nail on fracture healing: an experimental study

    Institute of Scientific and Technical Information of China (English)

    XU Wei-zhou; GUO Xiao-dong; ZHAO Ju-cai; WANG Yi-jin

    2006-01-01

    Objective: To investigate the effect of autocontrol micromotion locking nail (AMLN) on experimental fracture healing and its mechanism.Methods: 16 goats undergoing both sides of transverse osteotomy of the femoral shafts were fixed intramedullary with AMLN and Gross-Kempf (GK) nail,respectively. The follow-up time was 7, 14, 28 and 56days. Roentgenographic, biomechanical, histological,scanning electromicroscopic and biochemical analyses were done.Results: ( 1 ) The strength of anticompression,antiflexion and antitorsion in the fractural end in the AMLN-fixed group was higher than that of GK nail-fixed group; whereas, the rate of stress shelter in the fractured end decreased significantly (P < 0.01 ). (2) The content of the total collagen, insoluble collagen, calcium and phosphate in the AMLN-fixed group was higher than that in the GK nail-fixed group ( P < 0.05 ). ( 3 ) Histological observation and quantitative analysis of calluses revealed that AMLN could promote the growth of bridge calluses and periosteum calluses. Hence the facture healing and remolding process achieved early, which was much better than traditional GK nail fixation. (P < 0.05). ( 4 ) 7-14days postoperation, the calluses of AMLN-fixed group was flourish and camellarly arranged and the collagen fibril formed constantly in the absorption lacuna of bone trabecula. 28-56 days postoperation, the collagen fibril was flourish around the absorption lacuna and was parallel to the bone's longitudinal axis. Active bony absorption and formation were seen, so was remolding and rebuilding.Haversian system was intact and the bony structural net was very tenacious because of the deposition of calcium salt.None of the above findings was observed in the GK nailfixed group.Conclusions: The design of AMLN accords well with the plastic fixation theory. As the geometry ametabolic system constituted by the intramedullary fixation instruments and the proximal and distal end of the fracture is very firm and stable

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

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    Michael J Smout

    2015-10-01

    Full Text Available 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.

  6. A synthetic uric acid analog accelerates cutaneous wound healing in mice.

    Directory of Open Access Journals (Sweden)

    Srinivasulu Chigurupati

    Full Text Available Wound healing is a complex process involving intrinsic dermal and epidermal cells, and infiltrating macrophages and leukocytes. Excessive oxidative stress and associated inflammatory processes can impair wound healing, and antioxidants have been reported to improve wound healing in animal models and human subjects. Uric acid (UA is an efficient free radical scavenger, but has a very low solubility and poor tissue penetrability. We recently developed novel UA analogs with increased solubility and excellent free radical-scavenging properties and demonstrated their ability to protect neural cells against oxidative damage. Here we show that the uric acid analog (6, 8 dithio-UA, but not equimolar concentrations of UA or 1, 7 dimethyl-UA modified the behaviors of cultured vascular endothelial cells, keratinocytes and fibroblasts in ways consistent with enhancement of the wound healing functions of all three cell types. We further show that 6, 8 dithio-UA significantly accelerates the wound healing process when applied topically (once daily to full-thickness wounds in mice. Levels of Cu/Zn superoxide dismutase were increased in wound tissue from mice treated with 6, 8 dithio-UA compared to vehicle-treated mice, suggesting that the UA analog enhances endogenous cellular antioxidant defenses. These results support an adverse role for oxidative stress in wound healing and tissue repair, and provide a rationale for the development of UA analogs in the treatment of wounds and for modulation of angiogenesis in other pathological conditions.

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

    Science.gov (United States)

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

    2005-03-01

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

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

    Science.gov (United States)

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

    2012-03-01

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

  9. Osteoporosis influences the middle and late periods of fracture healing in a rat osteoporotic model

    Institute of Scientific and Technical Information of China (English)

    WANG Jian-wei; LI Wei; XU Shao-wen; YANG Di-sheng; WANG Yun; LIN Min; ZHAO Guang-feng

    2005-01-01

    Objective: To evaluate the influence of osteoporosis on the middle and late periods of fracture healing process through observing the histomorphological changes, bone mineral density and biomechanical properties in ovariectomized rats. Methods: Eighty-four female SD rats of 4 months old were randomly divided into osteoporosis group and sham operation group, 42 in each. Rats in osteoporosis group were performed ovariectomy operation while those in sham operation group were given sham operation. A midshaft tibia fracture model was established 10 weeks after ovariectomy. Tibias were harvested 2, 4, 6, 12, 18 weeks after fracture for bone mineral density, histomorphological and biomechanical evaluation. Results: Compared with the sham operation group, callus bone mineral density was 12.8%, 18.0%, 17.0% lower in osteoporosis group 6, 12, 18 weeks after fracture, respectively (P<0.05); callus failure load was 24.3%, 31.5%, 26.6%, 28.8% lower in osteoporosis group, and callus failure stress was 23.9%, 33.6%, 19.1%, 24.9% lower in osteoporosis group 4, 6, 12, 18 weeks after fracture, respectively (P<0.05). In osteoporosis group, endochondral bone formation was delayed, more osteoclast cells could be seen around the trabecula, and the new bone trabecula arranged loosely and irregularly. Conclusions: Osteoporosis influences the middle and late periods of fracture healing in the rat osteoporotic model. The impairment is considered to be the result of combined effects of prolonged endochondral calcification, high activated osteoclast cell and the deceleration of the increase in bone mineral density.

  10. Acceleration of wound healing by growth hormone-releasing hormone and its agonists.

    Science.gov (United States)

    Dioufa, Nikolina; Schally, Andrew V; Chatzistamou, Ioulia; Moustou, Evi; Block, Norman L; Owens, Gary K; Papavassiliou, Athanasios G; Kiaris, Hippokratis

    2010-10-26

    Despite the well-documented action of growth hormone-releasing hormone (GHRH) on the stimulation of production and release of growth hormone (GH), the effects of GHRH in peripheral tissues are incompletely explored. In this study, we show that GHRH plays a role in wound healing and tissue repair by acting primarily on wound-associated fibroblasts. Mouse embryonic fibroblasts (MEFs) in culture and wound-associated fibroblasts in mice expressed a splice variant of the receptors for GHRH (SV1). Exposure of MEFs to 100 nM and 500 nM GHRH or the GHRH agonist JI-38 stimulated the expression of α-smooth muscle actin (αSMA) based on immunoblot analyses as well as the expression of an αSMA-β-galactosidase reporter transgene in primary cultures of fibroblasts isolated from transgenic mice. Consistent with this induction of αSMA expression, results of transwell-based migration assays and in vitro wound healing (scratch) assays showed that both GHRH and GHRH agonist JI-38 stimulated the migration of MEFs in vitro. In vivo, local application of GHRH or JI-38 accelerated healing in skin wounds of mice. Histological evaluation of skin biopsies showed that wounds treated with GHRH and JI-38 were both characterized by increased abundance of fibroblasts during the early stages of wound healing and accelerated reformation of the covering epithelium at later stages. These results identify another function of GHRH in promoting skin tissue wound healing and repair. Our findings suggest that GHRH may have clinical utility for augmenting healing of skin wounds resulting from trauma, surgery, or disease.

  11. IL-33 accelerates cutaneous wound healing involved in upregulation of alternatively activated macrophages.

    Science.gov (United States)

    Yin, Hui; Li, Xiangyong; Hu, Shilian; Liu, Tao; Yuan, Baohong; Gu, Hongbiao; Ni, Qian; Zhang, Xiaofan; Zheng, Fang

    2013-12-01

    IL-33 is a recently recognized member of the IL-1 family and has been best identified as a potent inducer of Th2-type immune responses. Increasing evidence, however, indicates that IL-33 also represents an important mediator of mucosal healing and epithelial restoration and repair. In this study, we further explore the potential effect of IL-33 in cutaneous wound healing. A full-thickness skin wound was generated on the back of mice and treated with IL-33 or vehicle intraperitoneally. Our results revealed that the levels of IL-33 mRNA and protein were significantly enhanced in incisional wound skin. Meantime, administration of IL-33 obviously accelerated wound healing with wounds gaping narrower and exhibiting enhanced reepithelialization. IL-33 upregulation also promoted the collagen deposition and the expression of extracellular matrix (ECM)-associated genes such as fibronectin and collagen IIIa, which implies a direct effect of IL-33 on matrix synthesis. Furthermore, IL-33 facilitated the development of alternatively activated macrophages (AAM) in incisional wound tissue, which closely related to resolution of inflammation and promotion of wound repair. Taken together, these findings suggest that IL-33 may play a pivotal role in maintenance of cutaneous homeostasis and acceleration of normal wound healing.

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

    Science.gov (United States)

    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.

  13. Accelerated healing of full-thickness wounds by genipin-crosslinked silk sericin/PVA scaffolds.

    Science.gov (United States)

    Aramwit, Pornanong; Siritienthong, Tippawan; Srichana, Teerapol; Ratanavaraporn, Juthamas

    2013-01-01

    Silk sericin has recently been studied for its advantageous biological properties, including its ability to promote wound healing. This study developed a delivery system to accelerate the healing of full-thickness wounds. Three-dimensional scaffolds were fabricated from poly(vinyl alcohol) (PVA), glycerin (as a plasticizer) and genipin (as a crosslinking agent), with or without sericin. The physical and biological properties of the genipin-crosslinked sericin/PVA scaffolds were investigated and compared with those of scaffolds without sericin. The genipin-crosslinked sericin/PVA scaffolds exhibited a higher compressive modulus and greater swelling in water than the scaffolds without sericin. Sericin also exhibited controlled release from the scaffolds. The genipin-crosslinked sericin/PVA scaffolds promoted the attachment and proliferation of L929 mouse fibroblasts. After application to full-thickness rat wounds, the wounds treated with genipin-crosslinked sericin/PVA scaffolds showed a significantly greater reduction in wound size, collagen formation and epithelialization compared with the control scaffolds without sericin but lower numbers of macrophages and multinucleated giant cells. These results indicate that the delivery of sericin from the novel genipin-crosslinked scaffolds efficiently healed the wound. Therefore, these genipin-crosslinked sericin/PVA scaffolds represent a promising candidate for the accelerated healing of full-thickness wounds.

  14. Topical simvastatin accelerates wound healing in diabetes by enhancing angiogenesis and lymphangiogenesis.

    Science.gov (United States)

    Asai, Jun; Takenaka, Hideya; Hirakawa, Satoshi; Sakabe, Jun-ichi; Hagura, Asami; Kishimoto, Saburo; Maruyama, Kazuichi; Kajiya, Kentaro; Kinoshita, Shigeru; Tokura, Yoshiki; Katoh, Norito

    2012-12-01

    Impaired wound healing is a major complication of diabetes. Recent studies have reported reduced lymphangiogenesis and angiogenesis during diabetic wound healing, which are thought to be new therapeutic targets. Statins have effects beyond cholesterol reduction and can stimulate angiogenesis when used systemically. However, the effects of topically applied statins on wound healing have not been well investigated. The present study tested the hypothesis that topical application of simvastatin would promote lymphangiogenesis and angiogenesis during wound healing in genetically diabetic mice. A full-thickness skin wound was generated on the back of the diabetic mice and treated with simvastatin or vehicle topically. Simvastatin administration resulted in significant acceleration of wound recovery, which was notable for increases in both angiogenesis and lymphangiogenesis. Furthermore, simvastatin promoted infiltration of macrophages, which produced vascular endothelial growth factor C in granulation tissues. In vitro, simvastatin directly promoted capillary morphogenesis and exerted an antiapoptotic effect on lymphatic endothelial cells. These results suggest that the favorable effects of simvastatin on lymphangiogenesis are due to both a direct influence on lymphatics and indirect effects via macrophages homing to the wound. In conclusion, a simple strategy of topically applied simvastatin may have significant therapeutic potential for enhanced wound healing in patients with impaired microcirculation such as that in diabetes.

  15. Effect of Absorbable Hydroxyapatite/Poly-DL-Lactide Rods on Experimental Fracture Healing

    Institute of Scientific and Technical Information of China (English)

    GUO Xiaodong; ZHENG Qixin; DU Jingyuan; LIU Yong

    2000-01-01

    In order to investigate the effect of a new institute-designed absorbable hydroxyapatite microparticles/poly-DL-lactide (HA/PDLLA) fracture fixation devices on experimental fracture healing, 25 rabbits with a transverse transcondylar osteotomy of the distal femur were fixed intramedullary by a HA/PDLLA rod (4.5 mm in diameter, 30-40 mm in length). The follow-up time lasted 1, 2, 4, 6 and 12 week(s). Roentgenographic, histological and ultrastructural analyses were conducted. The results showed that allosteotomies united within 6 weeks without delay.No accumulation of inflammatory cells was seen. Ultrastructural studies showed that polymorphonuclear neutrophils and macrophages were observed mainly at the 1st week, but only few were noted at the 2nd week. The inflammatory and debridement stages were not prolonged. Large amount of active fibroblasts and some chondroblasts were observed at the 2nd week, suggesting a fibrous callus stage. The main cellularity at 4th week was osteoblasts and osteocytes. Part of osteocytes had already entered the static stage at the 6th week. Our experiment showed that the HA/PDLLA had good biocompatibility, sufficient mechanical streugth and caused no delay to the fracture healing.

  16. Great increase in bone 66 kDa protein and osteocalcin at later stages with healing rat fractures: effect of zinc treatment.

    Science.gov (United States)

    Igarashi, Aki; Yamaguchi, Masayoshi

    2003-02-01

    Fracture healing has been demonstrated to increase production of bone growth factors, and this elevation has been shown to be enhanced by zinc treatment. Moreover, the effect of zinc treatment on production of bone osteocalcin, which is a kind of Ca2+-binding protein localized in bone matrix, at the later stages with bone fracture was investigated. Rats were sacrificed 7 (earlier stage) or 21 (later stage) days after fracture of femoral diaphysis. Femoral-diaphyseal tissues with fracture healing were cultured in a serum-free medium for 24 h. Many proteins in the bone tissues were released into the medium. Bone protein production was markedly elevated 21 days after bone fracture as compared with that of 7 days. A approximately 66 kDa protein molecule, a major protein component which was produced by the diaphyseal tissues during fracture healing, was predominantly increased at the later stages with fracture healing. Bone osteocalcin production was significantly increased during fracture healing. This increase was enhanced at the later stages with fracture healing. The presence of zinc acexamate (10(-4) M) in culture medium caused a significant increase in bone protein and osteocalcin production at 7 or 21 days after bone fracture. The effect of zinc acexamate in increasing bone total protein and osteocalcin production was remarkable at the later stages with fracture healing. Moreover, zinc treatment caused a significant increase in alkaline phosphatase activity, deoxyribonucleic acid (DNA) and calcium content in the femoral-diaphyseal tissues of the later stages with fracture healing in vitro. The present study demonstrates that bone protein production is markedly increased at the later stages with fracture healing, and that zinc treatment can enhance production of bone protein components including osteocalcin in vitro. Zinc treatment may stimulate the healing of femoral fracture at earlier and later stages.

  17. Skin wound healing is accelerated and scarless in the absence of commensal microbiota.

    Science.gov (United States)

    Canesso, Maria C C; Vieira, Angélica T; Castro, Tiago B R; Schirmer, Brígida G A; Cisalpino, Daniel; Martins, Flaviano S; Rachid, Milene A; Nicoli, Jacques R; Teixeira, Mauro M; Barcelos, Lucíola S

    2014-11-15

    The commensal microbiota has a high impact on health and disease by modulating the development and homeostasis of host immune system. Immune cells are involved in virtually every aspect of the wound repair process; however, the impact of commensal microbiota on skin wound healing is largely unknown. In this study, we evaluated the influence of commensal microbiota on tissue repair of excisional skin wounds by using germ-free (GF) Swiss mice. We observed that macroscopic wound closure rate is accelerated in the absence of commensal microbiota. Accordantly, histologically assessed wound epithelization was accelerated in GF in comparison with conventional (CV) Swiss mice. The wounds of GF mice presented a significant decrease in neutrophil accumulation and an increase in mast cell and macrophage infiltration into wounds. Interestingly, alternatively activated healing macrophage-related genes were highly expressed in the wound tissue of GF mice. Moreover, levels of the anti-inflammatory cytokine IL-10, the angiogenic growth factor VEGF and angiogenesis were higher in the wound tissue of those mice. Conversely, scarring and levels of the profibrogenic factor TGF-β1 were greatly reduced in GF mice wounded skin when compared with CV mice. Of note, conventionalization of GF mice with CV microbiota restored wound closure rate, neutrophil and macrophage accumulation, cytokine production, and scarring to the same extent as CV mice. Overall, our findings suggest that, in the absence of any contact with microbiota, skin wound healing is accelerated and scarless, partially because of reduced accumulation of neutrophils, increased accumulation of alternatively activated healing macrophages, and better angiogenesis at wound sites.

  18. Healing of delayed management of double traumatized incisors with complicated crown: Root fracture and apical pathosis

    Directory of Open Access Journals (Sweden)

    Abdullah M Alsaedan

    2017-01-01

    Full Text Available The present case report shows a 23-year-old male who was subjected to trauma in his maxillary right central and lateral incisors with crown and transverse apical third root fractures. Root canal therapy was started, but the patient did not complete it. After 6 years, the patient was subjected to another trauma on the same teeth and showed up after 3 weeks of the second trauma to continue his treatment. Clinical examination revealed that both incisors were sensitive to percussion and palpation with labial sinus tract and pus discharge through the open access cavity of the central incisor. Radiographic evaluation demonstrated root fracture of the central incisor with large radiolucency. Root canal treatment for both incisors and periradicular surgery was done. Histopathologic examination of the periapical lesion demonstrated tissue necrosis and fungal hyphae. Follow-up showed no symptoms with good healing. The treatment modality appears to be effective in dealing with delayed management of traumatized anterior teeth.

  19. Acemannan accelerates cell proliferation and skin wound healing through AKT/mTOR signaling pathway.

    Science.gov (United States)

    Xing, Wei; Guo, Wei; Zou, Cun-Hua; Fu, Ting-Ting; Li, Xiang-Yun; Zhu, Ming; Qi, Jun-Hua; Song, Jiao; Dong, Chen-Hui; Li, Zhuang; Xiao, Yong; Yuan, Pei-Song; Huang, Hong; Xu, Xiang

    2015-08-01

    Acemannan is a bioactive polysaccharides promoting tissue repair. However, the roles of acemannan in skin wound healing and the underlying molecular mechanisms are largely unclear. The goal of this study is to investigate the positive role of acemannan in cutaneous wound healing and its mechanism. Mouse skin wound model and skin primary fibroblasts were used to demonstrate the positive effect of acemannan on cutaneous wound healing. The expressions of cell proliferation nuclear antigen ki-67, cyclin D1 and activity of AKT/mTOR signaling were analyzed in acemannan-treated fibroblasts and mice. Rapamycin and AKT inhibitor VIII were used to determine the key role of AKT/mTOR signaling in acemannan-promoting cutaneous wound healing. We found that acemannan significantly accelerated skin wound closure and cell proliferation. Acemannan promoted the expression of cyclin D1 in cultured fibroblasts, which was mediated by AKT/mTOR signal pathway leading to enhanced activity of the eukaryotic translation initiation factor-4F (eIF4F) and increased translation of cyclin D1. In contrast, pharmaceutical blockade of AKT/mTOR signaling by mTOR inhibitor rapamycin or AKT inhibitor VIII abolished acemannan-induced cyclin D1 translation and cell proliferation. In vivo studies confirmed that the activation of AKT/mTOR by acemannan played a key role in wound healing, which could be reversed by rapamycin. Acemannan promoted skin wound healing partly through activating AKT/mTOR-mediated protein translation mechanism, which may represent an alternative therapy approach for cutaneous wound. Copyright © 2015. Published by Elsevier Ireland Ltd.

  20. Healing patterns of clavicular birth injuries as a guide to fracture dating in cases of possible infant abuse

    Energy Technology Data Exchange (ETDEWEB)

    Walters, Michele M.; Forbes, Peter W.; Buonomo, Carlo; Kleinman, Paul K. [Boston Children' s Hospital, Department of Radiology, Boston, MA (United States)

    2014-10-15

    Dating fractures is critical in cases of suspected infant abuse. There are little scientific data to guide radiologists, and dating is generally based on personal experience and conventional wisdom. Since birth-related clavicular fractures are not immobilized and their age is known, we propose that an assessment of these injuries may serve as a guide for dating inflicted fractures in young infants, acknowledging that patterns observed in the clavicle may not be entirely generalizable to other bones injured in the setting of abuse. One hundred thirty-one radiographs of presumed birth-related clavicular fractures in infants between 0 and 3 months of age were reviewed by two pediatric radiologists with 30 and 15 years' experience. Readers were asked to evaluate images based on several parameters of fracture healing, with a focus on subperiosteal new bone formation (SPNBF) and callus formation. SPNBF and callus were each evaluated with regard to presence, thickness and character. Responses were correlated with known fracture ages. SPNBF was rarely seen in fractures less than 7 days old and was most often present by 10 days. Callus formation was rarely seen in fractures less than 9 days old and was most often present by 15 days. SPNBF thickness increased with fracture age and the character of SPNBF evolved from single-layered to solid/multilayered. Callus thickness decreased with fracture age and callus matrix evolved from soft to intermediate to hard in character. There is an evolution in clavicular fracture healing in young infants that follows a predictable pattern. These findings afford the prospect that predictable patterns of infant clavicular fracture healing can provide an evidence base that may be applicable in cases of suspected infant abuse. (orig.)

  1. Effects of recombinant human growth hormone (r-hGH) on experimental osteoporotic fracture healing

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To observe the effect of recombinant human growthhormone (r-hGH) on osteoporotic fracture healing in rats, and to provide an effective therapy for osteoporotic fracture.Methods: Thirty-six female 8-month-old SD rats were randomized into two groups: therapy group and control group. After the experimental model of osteoporotic fracture was established, the therapy group was treated with r-hGH of 2.7 mg/kg body weigh/day (1 mg=3 IU) for 10 days continuously by daily subcutaneous injection; whereas the control group was treated with equivalent saline. Plasma insulin-like growth factor I concentration was detected and bone mineral density (BMD) as well as biomechanical strength of callus were measured at 2, 4, 8 weeks.Results: Plasma insulin-like growth factor I concentration in the therapy group was higher than that in the control group (P<0.005) at 2nd week and began to decline at 4th week. At 8th week, there was no significant difference between the two groups. At 4th week, callus area and BMD in therapy group were higher than those in the control group, but at 8th week, they were lower and BMD had a significant difference between the two groups (P<0.001). Biomechanical testing of callus showed that torsional strength of the therapy group was higher than that of the control group at 4th or 8th week, meanwhile maximum torsional angle had a significant difference between the two groups (P<0.005).Conclusions: The results show that exogenous r-hGH can stimulate osteoporotic fracture healing in rats.

  2. Systemic inhibition of canonical Notch signaling results in sustained callus inflammation and alters multiple phases of fracture healing.

    Directory of Open Access Journals (Sweden)

    Michael I Dishowitz

    Full Text Available 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;dnMAML(f/- 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

  3. In vivo study of microarc oxidation coated biodegradable magnesium plate to heal bone fracture defect of 3mm width.

    Science.gov (United States)

    Wu, Y F; Wang, Y M; Jing, Y B; Zhuang, J P; Yan, J L; Shao, Z K; Jin, M S; Wu, C J; Zhou, Y

    2017-06-23

    Microarc oxidation (MAO) coated magnesium (Mg) with improved corrosion resistance appeal increasing interests as a revolutionary biodegradable metal for fractured bone fixing implants application. However, the in vivo corrosion degradation of the implants and bone healing response are not well understood, which is highly required in clinic. In the present work, 10μm and 20μm thick biocompatible MAO coatings mainly composed of MgO, Mg2SiO4, CaSiO3 and Mg3(PO4)2 phases were fabricated on AZ31 magnesium alloy. The electrochemical tests indicated an improved corrosion resistance of magnesium by the MAO coatings. The 10μm and 20μm coated and uncoated magnesium plates were separately implanted into the radius bone fracture site of adult New Zealand white rabbits using a 3mm width bone fracture defect model to investigate the magnesium implants degradation and uninhibited bone healing. Taking advantage of the good biocompatibility of the MAO coatings, no adverse effects were detected through the blood test and histological examination. The implantation groups of coated and uncoated magnesium plates were both observed the promoting effect of bone fracture healing compared with the simple fracture group without implant. The releasing Mg(2+) by the degradation of implants into the fracture site improved the bone fracture healing, which is attributed to the magnesium promoting CGRP-mediated osteogenic differentiation. Mg degradation and bone fracture healing promoting must be tailored by microarc oxidation coating with different thickness for potential clinic application. Copyright © 2017. Published by Elsevier B.V.

  4. Experimental studies of healing process of rat mandibular condylar fracture, using /sup 45/Ca as tracer

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    Shimizu, Tatsuaki (Gifu Univ. (Japan). Faculty of Medicine)

    1982-09-01

    The cervical region of the mandibular condylus of young rats was fractured. The healing process was observed pathohistologically, autoradiographically using /sup 45/Ca as a tracer, and by ultra soft roentgenography. Condylectomy of the mandibular condylus was done at the same time and its regeneration observed. The results of the observation are as follows: The fractured portion is bonded with the soft tissue 1 - 2 weeks postoperatively. Histologically, new-blood vessels in the granulation tissue and the connective tissue's change into fibers are seen. On the second week chondrocytes appeared in the neck of the capitulum mandibulae and the stump of the ascending branch. On the 3rd postoperative week, the stump of the fracture of the bone is bonded with proliferated cartilaginous tissue and an osseous bond was seen in part by autoradiograph and ultra soft x-ray picture. New bone due to periosteal ossification is seen around the stump on the ascending branch side, and the bone reconstruction with osteoclasts was seen in the inside the trabeculae. On the 4th postoperative week, osseous concrescence is observed in the fractured portion. Regeneration of the capitulum mandibulae after extirpation of the capitulum mandibulae is seen in all the cases. On the postoperative 12th week, the macroscopic form of the degenerated capitulum mandibulae which seemed to be excessive becomes almost the same morphologically with that of the contralateral side and it was observed histologically that the construction of the capitulum mandibulae is completely restored.

  5. Study of stress adaptability of fracture healing%骨折愈合的应力适应性研究

    Institute of Scientific and Technical Information of China (English)

    董福慧; 关继超; 赵勇; 邹炳曾; 尚天裕

    2001-01-01

    目的 探讨骨折端受力、肌肉动力、骨痂密度与骨折愈合的关系。方法 通过传感器电测技术与X线灰度分析的方法,从三个方面对骨折愈合的应力适应性进行了研究:①分别对14只1岁龄山羊进行了断端受力与骨折愈合的关系的研究;②对10只健康成年家兔进行了肌肉动力与骨折愈合的关系的研究;③对56只健康成年家兔进行了骨痂密度与骨折愈合的关系的研究。结果与结论 ①理想的骨折愈合与最佳的应力状态相适应;②肌肉动力是应力适应的反馈调节因素;③骨痂密度是应力适应的反馈结果。%Objective To explore the relationship between local stress status,muscular motivation,callus density and fracture healing.Methods Stress adaptability of fracture healing was studied from three respects:1.the relationship between fracture local stress and fracture healing was studied in 14 one year old goats;2.the relationship between muscular motivation and fracture healing was studied in 10 health adult rabbits and 3.the relationship between callus density and fracture healing was studied in 56 healthy adult rabbits.Electric transducer technique and X-ray densitometry method were used in all the three groups of animals.Results and Conclusion 1.Ideal fracture healing should be adapted to the best stress status;2.Muscular motivation is the biofeedback regulation factor of stress adaptability of fracture healing;3.The density of callus is the result of biofeedback of stress adaptability of fracture healing.

  6. An electrospun scaffold loaded with anti-androgen receptor compound for accelerating wound healing

    Directory of Open Access Journals (Sweden)

    Cassandra Chong

    2013-09-01

    Full Text Available Current dermal regenerative scaffolds provide wound coverage, and structural support and guidance for tissue repair, but usually lack enough bio-signals needed for speeding up skin cell growth, migration, wound closure, and skin regeneration. In this study, an androgen receptor (AR inhibitor called ASC-J9 is used to demonstrate the concept and feasibility of fabricating drug-loaded scaffolds via electrospinning. Inhibition of androgen is known to promote skin wound healing. The novel ASC-J9 - loaded porous scaffold was fabricated for skin wound repair using electrospun fibers of collagen and polycaprolactone (PCL blend. Our preliminary results indicated that ASC-J9 - loaded scaffolds facilitated more efficient attachment and ingrowth of dermal fibroblasts, compared to the control collagen-PCL scaffold. A significant increase of cell proliferation was observed with the drug-loaded scaffold over a 28-day period. The drug-loaded scaffold also accelerated keratinocyte migration and wound closure in a contraction-inhibited mouse wound model over 21 days. The data indicated a sustained release of ASC-J9 from the scaffold and its potential to accelerate wound healing by promoting cell proliferation and migration over an extended period of time. More importantly, our results proved the concept and feasibility of fabricating drug-releasing or bioactive dermal scaffolds for more effective wound healing.

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

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    Toshiki Yoneda

    2014-12-01

    Full Text Available 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.

  8. Preparation and characterization of N-chitosan as a wound healing accelerator.

    Science.gov (United States)

    Tang, Fengling; Lv, Lingmei; Lu, Fei; Rong, Bao; Li, Zhiquan; Lu, Bitao; Yu, Kun; Liu, Jiawei; Dai, Fangying; Wu, Dayang; Lan, Guangqian

    2016-12-01

    Chitosan is insoluble in water due to its rigid crystalline structure, which has significantly restricted its application in wound healing. The objective of this study was to synthesize a water-soluble chitosan derivative, N-succinyl-chitosan (NSC), and evaluate its ability to accelerate the wound healing process. NSC was synthesized with succinic anhydride, hydrochloric acid, and alkaline chitosan under optimized conditions, and characterized using Fourier transform infrared, proton nuclear magnetic resonance, and X-ray diffraction spectroscopy; thermal gravimetric analysis; and a solubility test. The cytotoxicity of NSC was investigated in L929 cells, and its antibacterial activity was evaluated by the inhibition zone method and bacterial growth curves analysis. The results showed that the solubility of NSC was substantially improved compared to chitosan, and NSC was non-toxic with good antibacterial properties. An animal wound healing test indicated that NSC could significantly reduce the healing time compared to chitosan. Histopathological examination suggested that the underlying mechanisms of these effects were related to NSC's ability to promote the formation of granulation tissue and enhance epithelialization. Collectively, these results demonstrate the good potential for NSC to be applied as a wound dressing material. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Application of coenzyme Q10 for accelerating soft tissue wound healing after tooth extraction in rats.

    Science.gov (United States)

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

    2014-12-10

    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 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.

  10. The Role of Radiographs and Office Visits in the Follow-Up of Healed Intertrochanteric Hip Fractures: An Economic Analysis.

    Science.gov (United States)

    Kempegowda, Harish; Richard, Raveesh; Borade, Amrut; Tawari, Akhil; Howenstein, Abby M; Kubiak, Erik N; Suk, Michael; Horwitz, Daniel S

    2016-12-01

    The purpose of this study was to evaluate the role and the necessity of radiographs and office visits obtained during follow-up of intertrochanteric hip injuries. Retrospective study. Two level I trauma centers. Four hundred sixty-five elderly patients who were surgically treated for an intertrochanteric fracture of the femur at 2 level I trauma centers between January 2009 and August 2014 were retrospectively identified from orthopaedic trauma databases. Analysis of all healed intertrochanteric hip fractures, including demographic characteristics, quality of reduction, time of healing, number of office visits, number of radiographs obtained, and each radiograph for fracture alignment, implant position or any pathological changes. The surgical fixation of 465 fractures included 155 short nails (33%), 232 long nails (50%), 69 sliding hip screw devices (15%), 7 trochanteric stabilizing plates (1.5%), and 2 proximal femur locking plates (0.5%). The average fracture healing time was 12.8 weeks and the average follow-up was 81.2 weeks. Radiographs of any patient obtained after the fracture had healed did not reveal any changes, including fracture alignment or implant position and hardware failure. In 9 patients, pathological changes, including arthritis (3), avascular necrosis (3), and ectopic ossification (3) were noted. The average number of elective office visits and radiographs obtained after the fracture had healed were 2.8 (range: 1-8) and 2.6 (range: 1-8), respectively. According to Medicare payments to the institution, these radiographs and office visits account for a direct cost of $360.81 and $192, respectively, per patient. The current study strongly suggests that there is a negligible role for radiographs and office visits during the follow-up of a well-healed hip fracture when there is documented evidence of radiographic and clinical healing with acceptable fracture alignment and implant position. Implementation of this simple measure will help in reducing

  11. Healing

    Science.gov (United States)

    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

  12. Knockout of endothelial cell-derived endothelin-1 attenuates skin fibrosis but accelerates cutaneous wound healing.

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    Katsunari Makino

    Full Text Available Endothelin (ET-1 is known for the most potent vasoconstrictive peptide that is released mainly from endothelial cells. Several studies have reported ET-1 signaling is involved in the process of wound healing or fibrosis as well as vasodilation. However, little is known about the role of ET-1 in these processes. To clarify its mechanism, we compared skin fibrogenesis and wound repair between vascular endothelial cell-specific ET-1 knockout mice and their wild-type littermates. Bleomycin-injected fibrotic skin of the knockout mice showed significantly decreased skin thickness and collagen content compared to that of wild-type mice, indicating that bleomycin-induced skin fibrosis is attenuated in the knockout mice. The mRNA levels of transforming growth factor (TGF-β were decreased in the bleomycin-treated skin of ET-1 knockout mice. On the other hand, skin wound healing was accelerated in ET-1 knockout mice, which was indicated by earlier granulation tissue reduction and re-epithelialization in these mice. The mRNA levels of TGF-β, tumor necrosis factor (TNF-α and connective tissue growth factor (CTGF were reduced in the wound of ET-1 knockout mice. In endothelial ET-1 knockout mouse, the expression of TNF-α, CTGF and TGF-β was down-regulated. Bosentan, an antagonist of dual ET receptors, is known to attenuate skin fibrosis and accelerate wound healing in systemic sclerosis, and such contradictory effect may be mediated by above molecules. The endothelial cell-derived ET-1 is the potent therapeutic target in fibrosis or wound healing, and investigations of the overall regulatory mechanisms of these pathological conditions by ET-1 may lead to a new therapeutic approach.

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

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    Radenahmad Nisaudah

    2012-12-01

    Full Text Available Abstract 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.

  14. John Adams Lecture | 120 Years of Accelerators that Heal | 3 December

    CERN Multimedia

    2013-01-01

    120 Years of Accelerators that Heal, Dr Ugo Amaldi, Technische Universität München and TERA Foundation.     Tuesday 3 December 2013 at 2 p.m. Kjell Johnsen Auditorium, Building 30 Abstract: The discovery of X-rays was made possible by the intelligent use of the best accelerator of the time. Since then, the development of particle accelerators has been at the root of both fundamental discoveries in physics and unforeseeable medical applications. The lecture will describe the major steps in this 120-year history of diagnostics and tumour therapy. The first attempts to heal tumours with X-rays were made only one month after Röntgen’s discovery, but the understanding of the mechanisms by which the radiation kills the cells and the introduction of dose fractionation took much longer. The use of X-rays in diagnostics developed much faster and its benefits were very visible during the First World War. Today no tumour could be treated and no patient could be oper...

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

    Science.gov (United States)

    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

  16. Power Doppler assessment of the neovascularization during uncomplicated fracture healing of long bones in dogs and cats.

    Science.gov (United States)

    Risselada, Marije; Kramer, Martin; Saunders, Jimmy H; Verleyen, Piet; Van Bree, Henri

    2006-01-01

    The aims of this prospective study were to test the feasibility of assessing neovascularization with power Doppler ultrasonography and to investigate its usefulness to follow fracture healing of long bones in dogs and cats. A total of 51 patients (44 dogs and seven cats) were followed. Fracture types differed from simple to comminuted. Therapy ranged from external coaptation to plate osteosynthesis. Patients were followed with radiography, B-mode real time and power Doppler ultrasonography every 2-4 weeks until the fracture was healed. All fractures healed uneventfully. A semi-quantitative numerical score based on signal intensity, vessel area, and number of Doppler signals was assigned and the mean value was used to compare patients and examinations. Time postoperatively was divided into periods of 10 days. No Doppler signal was present during the first 10 days. The mean of the scores was highest between 11 and 20 days postoperatively and the median of the scores peaked between 21 and 30 days. A gradual decrease was seen thereafter. The mean of the scores was zero at 71-80 days and the median at 51-0 days postoperatively for the grouped results. In all positive power Doppler examinations, signals were present in and close to the callus. In seven patients (five dogs and two cats) signals were also present in the peripheral soft tissues in one of the follow up examinations. The normal healing process of fractured bones can be visualized using power Doppler ultrasonography and follows a distinctive time-dependent pattern.

  17. Accelerated wound healing phenotype in Interleukin 12/23 deficient mice

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    Matias Marie AT

    2011-12-01

    Full Text Available Abstract Background The concept that a strong inflammatory response involving the full complement of cytokines and other mediators is critical for unimpaired healing has been challenged by wound healing studies using transgenic and knockout (KO mice. The present study explored the effect of abrogation of the p40 subunit, which is shared by the pro-inflammatory cytokines interleukin (IL-12 and IL-23, on wound closure of excisional oral mucosal wounds. Methods Double IL-12 and IL-23 KO mice and C57BL ⁄ 6J wildtype mice were wounded on the dorsal surface of the tongue using a 2 mm biopsy punch. The degree of epithelialization was examined histologically. At specific timepoints wounds were examined for cellular and molecular markers for inflammation and angiogenesis using 1 immunohistochemistry; 2 analysis of RNA expression; and 3 flow cytometric analysis. Results Compared to wild type controls, KO mice displayed enhanced healing, which was driven by a greater influx of neutrophils and macrophages during the early stages of wound healing, and increased induction of messenger RNA (mRNA for endothelial derived neutrophil attractant (ENA78 chemokine and macrophage inflammatory protein-2 alpha (MIP-2α. Increased mRNA for monocyte-attracting chemokines including monocyte chemoattractant protein (MCP-1 and MCP-3 was seen from day 1, together with higher levels of IL-1β and IL-6 within 24 hours after wounding. In addition, mRNA for vascular endothelial growth factor (VEGF-A was upregulated in KO mice within 2 hours after injury, and higher expression of this mediator was confirmed by immunohistochemistry. Conclusion Overall, the accelerated oral mucosal wound healing seen in IL-12/IL-23p40 KO compared to wildtype mice was associated with the early establishment of an inflammatory response and vascularization.

  18. Boric Acid Reduces the Formation of DNA Double Strand Breaks and Accelerates Wound Healing Process.

    Science.gov (United States)

    Tepedelen, Burcu Erbaykent; Soya, Elif; Korkmaz, Mehmet

    2016-12-01

    Boron is absorbed by the digestive and respiratory system, and it was considered that it is converted to boric acid (BA), which was distributed to all tissues above 90 %. The biochemical essentiality of boron element is caused by boric acid because it affects the activity of several enzymes involved in the metabolism. DNA damage repair mechanisms and oxidative stress regulation is quite important in the transition stage from normal to cancerous cells; thus, this study was conducted to investigate the protective effect of boric acid on DNA damage and wound healing in human epithelial cell line. For this purpose, the amount of DNA damage occurred with irinotecan (CPT-11), etoposide (ETP), doxorubicin (Doxo), and H2O2 was determined by immunofluorescence through phosphorylation of H2AX((Ser139)) and pATM((Ser1981)) in the absence and presence of BA. Moreover, the effect of BA on wound healing has been investigated in epithelial cells treated with these agents. Our results demonstrated that H2AX((Ser139)) foci numbers were significantly decreased in the presence of BA while wound healing was accelerated by BA compared to that in the control and only drug-treated cells. Eventually, the results indicate that BA reduced the formation of DNA double strand breaks caused by agents as well as improving the wound healing process. Therefore, we suggest that boric acid has important therapeutical effectiveness and may be used in the treatment of inflammatory diseases where oxidative stress and wound healing process plays an important role.

  19. Reduced FOXO1 expression accelerates skin wound healing and attenuates scarring.

    Science.gov (United States)

    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

    2014-09-01

    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. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  20. Momordica charantia ointment accelerates diabetic wound healing and enhances transforming growth factor-β expression.

    Science.gov (United States)

    Hussan, F; Teoh, S Lin; Muhamad, N; Mazlan, M; Latiff, A A

    2014-08-01

    Transforming growth factor-β (TGF-β) plays an important role in wound healing. Delayed wound healing is a consequence of diabetes, leading to high morbidity and poor quality of life. Momordica charantia (MC) fruit possesses anti-diabetic and wound healing properties. This study aimed to explore the changes in TGF-β expression in diabetic wounds treated with topical MC fruit extract. Fifty-six male Sprague-Dawley rats were divided into a normal control group and five diabetic groups of ten rats each. Intravenous streptozotocin (50mg/kg) was given to induce diabetes in the diabetic groups. Full thickness excision wounds were created on the thoracodorsal region of the animals, and these wounds were then treated with vehicle, MC powder, MC ointment and povidone ointment or ointment base for ten days. Wound healing was determined by the rate of wound closure, total protein content and TGF-β expression in the wounds, and histological observation. Diabetic groups showed delayed wound closure rates compared to the control group. The wound closure rate in the MC ointment group was significantly faster than that of the untreated diabetic group (p<0.05). The MC ointment group also showed intense TGF-β expression and a high level of total protein content. MC ointment has a promising potential for use as an alternative topical medication for diabetic wounds. This work has shown that it accelerates wound healing in diabetic rats, and it is suggested here that this occurs by enhancing TGF-β expression. Further work is recommended to explore this effect.

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

    Science.gov (United States)

    2015-10-01

    Medical University of South Carolina Department of Orthopaedics 96 Jonathan Lucas Street Suite 708 MSC 622 8. PERFORMING ORGANIZATION REPORT NUMBER...analysis is completed in year 3. Nothing to report. Publications, Abstracts, and Presentations: Abstracts accepted for Orthopaedic Conferences: 1...Fracture Healing. The 32nd Annual Meeting of the Southern Orthopaedic Association, Asheville, NC. 2015. (Podium presentation) Abstract included in

  2. Characterization of the increase in bone 66 kDa protein component with healing rat fractures: stimulatory effect of zinc.

    Science.gov (United States)

    Igarashi, A; Yamaguchi, M

    2002-05-01

    The characterization of protein components produced from bone tissues with fracture healing was investigated. Weanling rats were sacrificed between 1 and 7 days after the femoral fracture. Protein content in the femoral-diaphyseal tissues was markedly elevated by fracture healing. Moreover, when the femoral-diaphyseal tissues with fracture healing were cultured for 24 h in a serum-free medium, many proteins in the bone tissues were released into the medium. Analysis with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that many protein molecules were released from the diaphyseal tissues with fracture healing. Especially, a protein molecule of approximately 66 kDa was markedly increased by fracture healing. This protein molecule was significantly increased, when the diaphyseal tissues with fracture healing were cultured in the presence of zinc acexamate (10(-6)-10(-4) M). Zinc acexamate (10(-4) M)-induced increase in medium 66 kDa protein molecule was significantly inhibited in the presence of actinomycin D (10(-7) M) or cycloheximide (10(-6) M). The zinc effect was completely blocked in the presence of PD98059 (10(-5) M), an inhibitor of MAPK kinase, or staurosporine (10(-6) M), an inhibitor of protein kinase C. The medium 66 kDa protein molecule was significantly elevated in the presence of parathyroid hormone (1-34) (10(-7) M), insulin-like growth factor-I (10(-8) M) or transforming growth factor-beta (10(-11) M), while 17beta-estradiol (10(-9) M) did not have an effect. The effect of these bone-stimulating factors was equal to the zinc effect. Zinc did not significantly enhance the effect of insulin-like growth factor-I in increasing medium 66 kDa protein molecule. The present study demonstrates that fracture healing increases production of the approximately 66 kDa protein molecule which is a major component produced from femoral-diaphyseal tissues of weanling rats, and that this elevation is enhanced by zinc treatment.

  3. Coacervate delivery of HB-EGF accelerates healing of type 2 diabetic wounds.

    Science.gov (United States)

    Johnson, Noah R; Wang, Yadong

    2015-01-01

    Chronic wounds such as diabetic ulcers pose a significant challenge as a number of underlying deficiencies prevent natural healing. In pursuit of a regenerative wound therapy, we developed a heparin-based coacervate delivery system that provides controlled release of heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) within the wound bed. In this study, we used a polygenic type 2 diabetic mouse model to evaluate the capacity of HB-EGF coacervate to overcome the deficiencies of diabetic wound healing. In full-thickness excisional wounds on NONcNZO10 diabetic mice, HB-EGF coacervate enhanced the proliferation and migration of epidermal keratinocytes, leading to accelerated epithelialization. Furthermore, increased collagen deposition within the wound bed led to faster wound contraction and greater wound vascularization. Additionally, in vitro assays demonstrated that HB-EGF released from the coacervate successfully increased migration of diabetic human keratinocytes. The multifunctional role of HB-EGF in the healing process and its enhanced efficacy when delivered by the coacervate make it a promising therapy for diabetic wounds.

  4. Umbilical Cord Mesenchymal Stem Cells Combined With a Collagenfibrin Double-layered Membrane Accelerates Wound Healing.

    Science.gov (United States)

    Nan, Wenbin; Liu, Rui; Chen, Hongli; Xu, Zhihao; Chen, Jiannan; Wang, Manman; Yuan, Zhiqing

    2015-05-01

    The aim of this study was to examine the effects of human umbilical cord mesenchymal stem cells (hUCMSCs) in combination with a collagen-fibrin double-layered membrane on wound healing in mice. A collagen-fibrin double-layered membrane was prepared, and the surface properties of the support material were investigated using a scanning electron microscope. Twenty-four mice were prepared for use as full-thickness skin wound models and randomly divided into 3 groups: group A, a control group in which the wounds were bound using a conventional method; group B, a group treated with hUCMSCs combined with a collagen membrane; and group C, a group treated with hUCMSCs combined with a collagen-fibrin double-layered membrane. The postoperative concrescence of the wounds was observed daily to evaluate the effects of the different treatments. Scanning electron microscope observation showed the collagen-fibrin scaffolds exhibited a highly porous and interconnected structure, and wound healing in the double-layered membrane group was better than in groups A or B. Treatment with hUCMSCs combined with a collagen-fibrin double-layered membrane accelerated wound healing.

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

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    Mari Kimura

    2011-01-01

    Full Text Available 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.

  6. Novel locally active estrogens accelerate cutaneous wound healing. A preliminary study.

    Science.gov (United States)

    Brufani, Mario; Ceccacci, Francesca; Filocamo, Luigi; Garofalo, Barbara; Joudioux, Roberta; La Bella, Angela; Leonelli, Francesca; Migneco, Luisa M; Bettolo, Rinaldo Marini; Farina, Paolo M; Ashcroft, Gillian S; Routley, Claire; Hardman, Matthew; Meda, Clara; Rando, Gianpaolo; Maggi, Adriana

    2009-01-01

    New 17beta-estradiol (E2) derivatives 1-11 were synthesized from an estrone derivative by addition of organometallic reagents prepared from protected alpha,omega-alkynols and further elaboration of the addition products. The estrogenic activity of these novel compounds was determined using in vitro binding competition assay and transactivation analysis. Among the E2 derivatives synthesized, compound 2 showed the highest transactivation potency and was therefore tested for its ability to modulate cutaneous wound healing in vivo. Compound 2's ability to accelerate wound healing in ovariectomized mice and decrease the production of inflammatory molecules was comparable to that of E2. However, the activity of compound 2 was not superimposable to E2 with regard to the cells involved in the wound repairing process. When locally administered, compound 2 did not show any systemic activity on ER. This class of compounds with clear beneficial effects on wound healing and suitable for topical administration may lead to the generation of innovative drugs for an area of unmet clinical need.

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

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    Sinha Shivam

    2009-01-01

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

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

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    Xinlei Wu

    2015-01-01

    Full Text Available 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.

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

    Directory of Open Access Journals (Sweden)

    Nurul 'Izzah Ibrahim

    Full Text Available 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.

  10. Effect of bone marrow and low power lasers on fracture healing with destruction of both periosteum and endosteum in rabbits

    Directory of Open Access Journals (Sweden)

    M. G. Thanoon

    2010-01-01

    Full Text Available Ten mature rabbits of local breed were used in this study; weighing between 1.5 to 1.75 kg and aged about 1–2 years. These animals were divided into two equal groups; in group A destruction of both periosteum and endosteum was done one centimeter from each side of mid-shaft femoral bone fracture, then sufficient amount of autogenously bone marrow was injected directly at the fracture site after immobilization by intramedullary pin. In group B a similar procedure was achieved as in group A, but in additional to that He-Ne infrared laser therapy was used for several sessions. The result of radiological findings indicated that, the fracture healing occurred within group B at fifteen weeks, whereas in group A the healing occurred at eighteen weeks after operation. The implantation of autologous bone marrow enhanced the fracture healing, whereas using of combinations of autologous bone marrow and He-Ne infrared laser therapy hastened the healing.

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

    Energy Technology Data Exchange (ETDEWEB)

    Geiger, Adolf, E-mail: ageiger@dreirosen-pharma.com; Walker, Audrey, E-mail: awalker@dreirosen-pharma.com; Nissen, Erwin, E-mail: enissen@dreirosen-pharma.com

    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. - Highlights: • Fibrocytes have shown potent wound healing properties in vitro and in vivo. • Their clinical use is precluded by low numbers and antigen-presenting function. • We isolated exosomes with no immunogenicity potential from human fibrocytes. • Their cargo included microRNAs and proteins that are known healing promoters. • They accelerated wound closure in diabetic mice in a dose-dependent manner.

  12. Sliver nanoparticles accelerate skin wound healing in mice (Mus musculus through suppression of innate immune system

    Directory of Open Access Journals (Sweden)

    Mohammad Saeed Heydarnejad

    2013-09-01

    Full Text Available   Objective(s: This study aimed to find the effects of silver nanoparticles (Ag-NPs (40 nm on skin wound healing in mice Mus musculus when innate immune system has been suppressed.   Materials and Methods: A group of 50 BALB/c mice of about 8 weeks (weighting 24.2±3.0 g were randomly divided into two groups: Ag-NPs and control group, each with 25 mice. Once a day at the same time, a volume of 50 microliters from the nanosilver solution (10ppm was applied to the wound bed in the Ag-NPs group while in the untreated (control group no nanosilver solution was used but the wound area was washed by a physiological solution. The experiment lasted for 14. Transforming growth factor beta (TGF-β, complement component C3, and two other immune system factors involving in inflammation, namely C-reactive protein (CRP and rheumatoid factor (RF in sera of both groups were assessed and then confirmed by complement CH50 level of the blood. Results: The results show that wound healing is a complex process involving coordinated interactions between diverse immunological and biological systems and that Ag-NPs significantly accelerated wound healing and reduce scar appearance through suppression of immune system as indicated by decreasing levels of all inflammatory factors measured in this study. Conclusion: Exposure of mice to Ag-NPs can result in significant changes in innate immune function at the molecular levels. The study improves our understanding of nanoparticle interaction with components of the immune system and suggests that Ag-NPs have strong anti-inflammatory effects on skin wound healing and reduce scarring.

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

    Science.gov (United States)

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

    2011-01-01

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

  14. Open-wedge high tibial osteotomy: incidence of lateral cortex fractures and influence of fixation device on osteotomy healing.

    Science.gov (United States)

    Dexel, Julian; Fritzsche, Hagen; Beyer, Franziska; Harman, Melinda K; Lützner, Jörg

    2017-03-01

    Open-wedge high tibial osteotomy (HTO) is an established treatment for young and middle-aged patients with medial compartment knee osteoarthritis and varus malalignment. Although not intended, a lateral cortex fracture might occur during this procedure. Different fixation devices are available to repair such fractures. This study was performed to evaluate osteotomy healing after fixation with two different locking plates. Sixty-nine medial open-wedge HTO without bone grafting were followed until osteotomy healing. In patients with an intact lateral hinge, no problems were noted with either locking plate. A fracture of the lateral cortex occurred in 21 patients (30.4 %). In ten patients, the fracture was not recognized during surgery but was visible on the radiographs at the 6-week follow-up. Lateral cortex fracture resulted in non-union with the need for surgical treatment in three out of eight (37.5 %) patients using the newly introduced locking plate (Position HTO Maxi Plate), while this did not occur with a well-established locking plate (TomoFix) (0 out of 13, p = 0.023). With regard to other adverse events, no differences between both implants were observed. In cases of lateral cortex fracture, fixation with a smaller locking plate resulted in a relevant number of non-unions. Therefore, it is recommended that bone grafting, another fixation system, or an additional lateral fixation should be used in cases with lateral cortex fracture. III.

  15. Effect of 900MHz electromagnetic fields emitted from cellular phones on fracture healing: an experimental study on rats.

    Science.gov (United States)

    Aslan, Ahmet; Atay, Tolga; Gülle, Kanat; Kırdemir, Vecihi; Ozden, Ahmet; Çömlekçi, Selçuk; Aydoğan, Nevres Hürriyet

    2013-01-01

    The aim of this study was to investigate the effect of electromagnetic fields (EMFs) at 900 MHz frequencies on bone fracture healing. The study included 30 adult male Wistar albino rats (average weight: 256 g) divided into two equal groups. Transverse fracture was created manually by pressing a finger on the right tibias of all rats and fractures were fixed intramedullary using a K-wire. Rats in Group 1 were exposed to EMF at 900 MHz frequency 30 minutes a day, 5 days a week for 8 weeks. Group 2, the control group, was kept under the same experimental conditions without EMF exposure. Radiological, mechanical and histological examination of tibial fracture healing was performed. There was a significant difference between radiological, histological and manual biomechanical scores of the study and control groups (p=0.020, p=0.006 and p=0.032, respectively). All scores were lower in the study group than the control group. Results of this study demonstrate that EMF at 900 MHz of frequency emitted from cellular phones has a significantly negative effect on bone fracture healing in a rat tibia model.

  16. Relationship among bone mineral density, collagen composition, and biomechanical properties of callus in the healing of osteoporotic fracture

    Institute of Scientific and Technical Information of China (English)

    SHEN Bin; MU Jian-xiong; PEI Fu-xing

    2007-01-01

    Objective: To study the change and relationship among bone mineral density (BMD), collagen composition and biomechanical properties of the callus in the healing process of osteoporotic fracture.Methods: The osteoporotic rat model and fracture model were established through bilateral ovariectomy(OVX) and osteotomy of the middle shaft of the right hind tibiae, respectively. Ninety female SD rats were randomly divided into OVX group and sham group. With the samples of blood and callus, roentgenoraphic and histological observation were performed for the assessment of the healing progress of the fracture, and the serum concentration of TRAP-5b, proportion of type Ⅰ collagen,BMD and biomechanical properties of the callus were measured.Results: The OVX group experienced a significant delay of fracture healing. The mean serum concentration of TRAP-5b of rats in the OVX group was much higher than that in the sham group after the operation (P < 0.05), but the difference at the same time point after fracture was smaller than that before fracture (P < 0.05 ). The BMD of the callus in both groups reached the peak value at the 6 th week after fracture while the proportion of the type Ⅰ collagen and the biomechanical strength reached the peak at the 8th week.Conclusions: The deficiency of estrogen after the ovariectomy could induce the up-regulation of the osteoclasts activities, whereas the potency of further activation after fracture was depressed. Although the synthesis of collagen together with its mineralization determines the biomechanical properties of new bone, the accumulation of collagen could be assessed as an index in the prediction of biomechanical strength of bones independent of the bone mineral deposition.

  17. Effects of recombinant human basic fibroblast growth factor on cell proliferation during mandibular fracture healing in rabbits

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To investigate the effects of recombinant human basicfibroblast growth factor (rhbFGF) on the cell proliferation during mandibular fracture healing in rabbits.Methods: The complex of rhbFGF and bovine type I collagen was implanted into the mandibular fracture site under periosteum of the animal. The whole mandible was harvested at 7, 14, 28, 56 and 84 days respectively after operation. The expression of proliferating cell nuclear antigen (PCNA) in callus was examined with immunohistochemical staining.Results: PCNA-positive cells in callus in the rhbFGF-treated group on days 7 and 14 were more than that in the control group (P<0.01).Conclusions: It indicates that rhbFGF can stimulate cell proliferation during mandibular fracture healing in rabbits.

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

    Science.gov (United States)

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

    2013-03-01

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

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

    Science.gov (United States)

    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. Bisphosphonates and the fracture healing and atypical fracture%双膦酸盐与骨折愈合和非典型性骨折

    Institute of Scientific and Technical Information of China (English)

    王雪鹏; 郝永强

    2011-01-01

    Fracture healing is typically characterized by four overlapping stages that include the hematoma and inflammatory response, initial fibrocartilage callus formation, hard callus formation and bone remodeling.The remodeling process is driven by a coupled process of bone resorption and bone formation.The soft callus remodeling and hard callus remodeling are of great importance to fracture healing.Bisphosphonates act to affect fracture healing by intervening callus remodelling, based on its pharmacological action of inhibiting the osteoclast activity and bone turnover level.Long-term use of bisphosphonates does not favor the fracture healing, and has been associated with the possibility of atypical fracture of the femur.%典型的骨折愈合过程包括血肿和炎症反应、原始软骨痂形成、成熟板层骨形成以及骨板重建和塑形等4个时期.骨重建包括骨吸收和骨形成两个方面.软骨痂和硬骨痂重建对骨折愈合具有重要意义.双膦酸盐类药理基础在于抑制破骨细胞活性和骨转化水平,通过干预骨重建对骨折愈合产生影响.长期使用双膦酸盐不利于骨折愈合,有引起股骨非典型性骨折发生的危险.

  1. The effect of bisphosphonates on fracture healing and atypical fracture%双膦酸盐与骨折愈合和非典型性骨折

    Institute of Scientific and Technical Information of China (English)

    王雪鹏; 郝永强

    2011-01-01

    Fracture healing is typically characterized by four overlapping stages, including the hematoma and inflammatory response, initial fibrocartilage callus formation, hard callus formation, and bone remodeling. The remodeling process is driven by a coupled process of orderly bone resorption followed by bone formation. The soft callus remodeling and hard callus remodeling are of great importance to fracture healing. Bisphosphonates act to affect fracture healing by intervening callus remodelling, based on its pharmacological action on inhibiting osteoclast activity and bone turnover levels. The long-term use of bisphosphonates seems to be turning against fracture healing, and has been associated with the possibility of atypical fractures of the femur.%典型的骨折愈合过程包括血肿和炎症反应、原始软骨痂形成、成熟板层骨形成以及骨板重建和塑形等四个时期。骨重建包括骨吸收和骨形成两个方面。软骨痂和硬骨痂重建对骨折愈合具有重要意义。双膦酸盐类药理基础在于抑制破骨细胞活性和骨转化水平,通过干预骨重建对骨折愈合产生影响。长期使用双膦酸盐不利于骨折愈合,有引起股骨非典型性骨折发生的危险。

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Uri Galili

    2015-01-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  5. Impaired angiogenesis during fracture healing in GPCR kinase 2 interacting protein-1 (GIT1 knock out mice.

    Directory of Open Access Journals (Sweden)

    Guoyong Yin

    Full Text Available 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.

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

    Science.gov (United States)

    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.

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

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    Juan-Pablo Idrovo

    Full Text Available 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.

  8. Effect of fluvastatin on vascular endothelial growth factor in rats with osteoporosis in process of fracture healing

    Institute of Scientific and Technical Information of China (English)

    YANG Mao-wei; ZHU Yue; TU Guan-jun; L(U) Gang

    2007-01-01

    Objective: To explore the effect of fluvastatin on vascular endothelial growth factor (VEGF) in rats with osteoporosis in the process of fracture healing.Methods: Fractures at the intermediate piece of the femur were made on 72 Sprague Dawley (SD) rats (weighing initially 290-340 g and aged 6 months ) with osteoporosis after ovariectomy for three months, then these rats were divided randomly into the medication administration group (the experimental group ) and the control group, 36 rats each. In the experimental group, the rats received fluvastatin lavage (10 mg/kg per day) since the next day of operation lasting for 6 weeks, and the rats in the control group received placebo. Then the expression of VEGF and VEGF mRNA in bony callus of the two groups was measured respectively with immunohistochemistry and in situ hybridization on days of 3rd, 7th, 14th, 21st, 28th, and 42nd, and image analysis was made with real-color image analysis machine.Results: No difference was found in the cellular localization of VEGF and VEGF mRNA gene expression between the experimental group and the control group in process of fracture healing and their expression modes were almost similar. On the 14th day postoperatively, the positive extent of positive cells in the experimental group was higher than that of the control group (P < 0.05).Conclusion: Fluvastatin can promote the VEGF level in rats with osteoporosis in process of fracture healing.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  12. Bmx tyrosine kinase transgene induces skin hyperplasia, inflammatory angiogenesis, and accelerated wound healing.

    Science.gov (United States)

    Paavonen, Karri; Ekman, Niklas; Wirzenius, Maria; Rajantie, Iiro; Poutanen, Matti; Alitalo, Kari

    2004-09-01

    The Bmx gene, a member of the Tec family of nonreceptor protein tyrosine kinases, is expressed in arterial endothelium and in certain hematopoietic and epithelial cells. Previous in vitro studies have implicated Bmx signaling in cell migration and survival and suggested that it contributes to the progression of prostate carcinomas. However, the function of Bmx in normal tissues in vivo is unknown. We show here that Bmx expression is induced in skin keratinocytes during wound healing. To analyze the role of Bmx in epidermal keratinocytes in vivo, we generated transgenic mice overexpressing Bmx in the skin. We show that Bmx overexpression accelerates keratinocyte proliferation and wound reepithelialization. Bmx expression also induces chronic inflammation and angiogenesis in the skin, and gene expression profiling suggests that this occurs via cytokine-mediated recruitment of inflammatory cells. Our studies provide the first data on Bmx function in vivo and form the basis of evaluation of its role in epithelial neoplasia.

  13. Spontaneous isolated midtrimester fracture of tibia and fibula in a normal fetus with in utero healing and good long-term outcome.

    Science.gov (United States)

    Scheier, M; Peter, M; Hager, C; Lang, T; Barvinek, A; Marth, C

    2010-01-01

    We report a case of spontaneous intrauterine fracture of the right tibia and fibula in an otherwise healthy fetus at 20 weeks of gestation. The fracture healed in utero in an abnormal position. Postnatal development of the baby was normal with spontaneous correction of the angulation, and no underlying disease could be discovered. Spontaneous isolated fetal fractures are rare and need to be differentiated from fractures that occur due to trauma or underlying skeletal diseases.

  14. Hyaluronic Acid Accelerates Tendon-to-Bone Healing After Rotator Cuff Repair.

    Science.gov (United States)

    Honda, Hirokazu; Gotoh, Masafumi; Kanazawa, Tomonoshin; Ohzono, Hiroki; Nakamura, Hidehiro; Ohta, Keisuke; Nakamura, Kei-Ichiro; Fukuda, Kanji; Teramura, Takeshi; Hashimoto, Takashi; Shichijo, Shigeki; Shiba, Naoto

    2017-09-01

    tendon-to-bone healing in the rotator cuff repair model, enhancing the biomechanical strength and increasing chondroid formation and tendon maturity at the tendon-bone interface. Based on the data of in vitro experiments, HA-activated MSCs may play a crucial role in the acceleration of tendon-to-bone healing. The data suggest the relevance of clinical application of HA to accelerate tendon-to-bone healing. It may decrease the number of retears after surgery.

  15. A study of radiological features of healing in long bone fractures among infants less than a year

    Energy Technology Data Exchange (ETDEWEB)

    Warner, Christopher; Miller, Angie; Weinman, Jason; Fadell, Michael [Children' s Hospital Colorado, Department of Radiology, Aurora, CO (United States); Maguire, Sabine; Trefan, Laszlo [Cardiff University, Institute of Primary Care and Child Health, Cardiff (United Kingdom)

    2017-03-15

    To create a timetable for dating long bone fractures in infants aged less than 1 year using previously defined radiographic signs of fracture healing. A retrospective cross-sectional time series of long bone fractures in infants aged less than 1 year was conducted from 2006 to 2013. After exclusion criteria were applied 59 digital image series were available for review from 40 infants. Utilizing published criteria for dating fractures, the presence or absence of four pre-defined features of healing was scored: periosteal reaction, callus, bridging, and remodeling. Three radiologists independently scored radiographs with a 3-point scale, marking each feature as present, absent, or equivocal. The times in days when features were first seen, peaked (feature agreed present in >40% of images), and last seen were noted. Statistical analysis using free marginal kappa was conducted. The level of agreement among the three radiologists was high (0.64-0.85). The sequence in which the features were seen was: periosteal reaction range 7-130 (present in the majority of cases between 9 and 49 days); callus range 9-130 (present in the majority of cases between days 9-26); bridging range 15-130 (seen in the majority of cases between 15 and 67 days); remodeling range 51-247 days. This study provides a timetable of radiological features of long bone healing among young infants for the first time. Dating of incomplete long bone fractures is challenging, beyond the presence of periosteal reaction, but a consistent sequence of changes is present in complete fractures. (orig.)

  16. 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.

    Directory of Open Access Journals (Sweden)

    Peter Michael Prodinger

    Full Text Available 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.

  17. 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

    Science.gov (United States)

    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

  18. Antioxidant potential of bilirubin-accelerated wound healing in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Ram, Mahendra; Singh, Vishakha; Kumar, Dhirendra; Kumawat, Sanjay; Gopalakrishnan, Anu; Lingaraju, Madhu C; Gupta, Priyanka; Tandan, Surendra Kumar; Kumar, Dinesh

    2014-10-01

    Oxidative injury is markedly responsible for wound complications in diabetes mellitus. The biological actions of bilirubin may be relevant to prevent oxidant-mediated cell death, as bilirubin application at a low concentration scavenges reactive oxygen species. Hence, we hypothesized that topical bilirubin application might improve wound healing in diabetic rats. Diabetes was induced in adult male Wistar rats, which were divided into two groups, i.e., diabetic control and diabetic treated. Non-diabetic healthy rats were also taken as healthy control group. Wound area was measured on days 3, 7, 14, and 19 post-wounding. The levels of malondialdehyde (MDA) and reduced glutathione (GSH) and the activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) were estimated in the granulation tissue. There was a significant increase in percent wound closure in healthy control and diabetic treated rats on days 7, 14, and 19, as compared to diabetic control rats on days 7, 14, and 19. There was significant decrease in MDA levels on days 7, 14, and 19 in diabetic treated rats, as compared to diabetic control rats. Levels of GSH were significantly increased on days 3, 7, 14, and 19 in diabetic treated rats, as compared to diabetic control rats. GPx, SOD, and CAT activities were significantly higher on days 3, 7, and 14 in diabetic treated rats, as compared to diabetic control rats. The findings indicate that bilirubin is effective in reducing the oxidant status in wounds of diabetic rats which might have accelerated wound healing in these rats.

  19. Immediate versus delayed intramedullary nailing for open fractures of the tibial shaft: A multivariate analysis of factors affecting deep infection and fracture healing

    Directory of Open Access Journals (Sweden)

    Yokoyama Kazuhiko

    2008-01-01

    Full Text Available Background: The purpose of this study was to evaluate contributing factors affecting deep infection and fracture healing of open tibia fractures treated with locked intramedullary nailing (IMN by multivariate analysis. Materials and Methods: We examined 99 open tibial fractures (98 patients treated with immediate or delayed locked IMN in static fashion from 1991 to 2002. Multivariate analyses following univariate analyses were derived to determine predictors of deep infection, nonunion, and healing time to union. The following predictive variables of deep infection were selected for analysis: age, sex, Gustilo type, fracture grade by AO type, fracture location, timing or method of IMN, reamed or unreamed nailing, debridement time (≤6 h or> 6 h, method of soft-tissue management, skin closure time (≤1 week or> 1 week, existence of polytrauma (ISS< 18 or ISS≥18, existence of floating knee injury, and existence of superficial/pin site infection. The predictive variables of nonunion selected for analysis was the same as those for deep infection, with the addition of deep infection for exchange of pin site infection. The predictive variables of union time selected for analysis was the same as those for nonunion, excluding of location, debridement time, and existence of floating knee and superficial infection. Results: Six (6.1%; type II Gustilo n=1, type IIIB Gustilo n=5 of the 99 open tibial fractures developed deep infections. Multivariate analysis revealed that timing or method of IMN, debridement time, method of soft-tissue management, and existence of superficial or pin site infection significantly correlated with the occurrence of deep infection ( P < 0.0001. In the immediate nailing group alone, the deep infection rate in type IIIB + IIIC was significantly higher than those in type I + II and IIIA ( P = 0.016. Nonunion occurred in 17 fractures (20.3%, 17/84. Multivariate analysis revealed that Gustilo type, skin closure time, and

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

    Science.gov (United States)

    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. © 2012 by the Wound Healing Society.

  1. A cohesive elements based model to describe fracture and cohesive healing in elastomers

    NARCIS (Netherlands)

    Baldi, A.; Grande, A.M.; Bose, R.K.; Airoldi, A.; Garcia Espallargas, S.J.; Di Landro, L.; Van der Zwaag, S.

    2013-01-01

    Several polymeric systems with intrinsic Self-Healing (SH) capabilities have been reported in literature. Many of them showed healing upon contact across the crack interface. Different parameters such as contact time, temperature, pressure or chemical activity determine the degree of healing obtaine

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

    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.

  4. Novel lipoproteoplex delivers Keap1 siRNA based gene therapy to accelerate diabetic wound healing.

    Science.gov (United States)

    Rabbani, Piul S; Zhou, Anna; Borab, Zachary M; Frezzo, Joseph A; Srivastava, Nikita; More, Haresh T; Rifkin, William J; David, Joshua A; Berens, Samuel J; Chen, Raymond; Hameedi, Sophia; Junejo, Muhammad H; Kim, Camille; Sartor, Rita A; Liu, Che F; Saadeh, Pierre B; Montclare, Jin K; Ceradini, Daniel J

    2017-04-03

    Therapeutics utilizing siRNA are currently limited by the availability of safe and effective delivery systems. Cutaneous diseases, specifically ones with significant genetic components are ideal candidates for topical siRNA based therapy but the anatomical structure of skin presents a considerable hurdle. Here, we optimized a novel liposome and protein hybrid nanoparticle delivery system for the topical treatment of diabetic wounds with severe oxidative stress. We utilized a cationic lipid nanoparticle (CLN) composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and the edge activator sodium cholate (NaChol), in a 6:1 ratio of DOTAP:NaChol (DNC). Addition of a cationic engineered supercharged coiled-coil protein (CSP) in a 10:1:1 ratio of DNC:CSP:siRNA produced a stable lipoproteoplex (LPP) nanoparticle, with optimal siRNA complexation, minimal cytotoxicity, and increased transfection efficacy. In a humanized murine diabetic wound healing model, our optimized LPP formulation successfully delivered siRNA targeted against Keap1, key repressor of Nrf2 which is a central regulator of redox mechanisms. Application of LPP complexing siKeap1 restored Nrf2 antioxidant function, accelerated diabetic tissue regeneration, and augmented reduction-oxidation homeostasis in the wound environment. Our topical LPP delivery system can readily be translated into clinical use for the treatment of diabetic wounds and can be extended to other cutaneous diseases with genetic components.

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

    Science.gov (United States)

    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, ptherapy as an adjuvant treatment accelerates diabetic ulcer healing by six times in a six week period.

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

    Science.gov (United States)

    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.

  7. Acceleration of diabetic-wound healing with PEGylated rhaFGF in healing-impaired streptozocin diabetic rats.

    Science.gov (United States)

    Huang, Zhifeng; Lu, Meifei; Zhu, Guanghui; Gao, Hongchang; Xie, Liyun; Zhang, Xiaoqin; Ye, Chaohui; Wang, Yan; Sun, Chuanchuan; Li, Xiaokun

    2011-01-01

    Molecular modification with polyethylene glycol (PEGylation) is an effective approach to improve protein biostability, in vivo lifetime and therapeutic potency. In the present study, the recombinant human acid fibroblast growth factor (rhaFGF) was site-selectively PEGylated with 20 kDa mPEG-butyraldehyde. Mono-PEGylated rhaFGF was purified to near homogeneity by Sephadex G 25-gel filtration followed by a Heparin Sepharose TM CL-6B affinity chromatography. PEGylated rhaFGF has less effect than the native rhaFGF on the stimulation of 3T3 cell proliferation in vitro; however, its relative thermal stability at normal physiological temperature and structural stability were significantly enhanced, and its half-life time in vivo was significantly extended. Then, the physiological function of PEGylated rhaFGF on diabetic-wound healing was evaluated in type 1 diabetic Sprague Dawley rats. The results showed that, compared with the group of animal treated with native rhaFGF, the group treated with PEGylated rhaFGF exhibited better therapeutic efficacy with shorter healing time, quicker tissue collagen generation, earlier and higher transforming growth factor (TGF)-β expression, and dermal cell proliferation. In addition, in vivo analysis showed that both native and PEGylated rhaFGF were more effective in the wound healing in the diabetic group compared with the nondiabetic one. Taken together, these results suggest that PEGylation of rhaFGF could be a more effective approach to the pharmacological and therapeutic application of native rhaFGF.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2016-09-12

    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.

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

    Science.gov (United States)

    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

  11. Accelerated healing of skin burns by anti-Gal/alpha-gal liposomes interaction.

    Science.gov (United States)

    Galili, Uri; Wigglesworth, Kim; Abdel-Motal, Ussama M

    2010-03-01

    Topical application of alpha-gal liposomes on burns results in rapid local recruitment of neutrophils and macrophages. Recruited macrophages are pivotal for healing of burns because they secrete cytokines/growth factors that induce epidermis regeneration and tissue repair. alpha-Gal liposomes have glycolipids with alpha-gal epitopes (Galalpha1-3Galbeta1-4GlcNAc-R) which bind anti-Gal, the most abundant natural antibody in humans constituting approximately 1% of immunoglobulins. Interaction of alpha-gal liposomes with anti-Gal within the fluid film formed on burns, activates complement and generates chemotactic complement cleavage peptides which effectively recruit neutrophils and macrophages. Anti-Gal IgG coating alpha-gal liposomes further binds to Fcgamma receptors on macrophages and activates them to secrete cytokines/growth factors. Efficacy of alpha-gal liposomes treatment in accelerating burn healing is demonstrated in the experimental model of alpha1,3galactosyltransferase knockout mice. These mice are the only available nonprimate mammals that can produce anti-Gal in titers similar to those in humans. Pairs of burns in mice were covered either with a spot bandage coated with 10mg alpha-gal liposomes, or with a control spot bandage coated with saline. On Day 3 post-treatment, the alpha-gal liposomes treated burns contained approximately 5-fold as many neutrophils as control burns, whereas macrophages were found only in alpha-gal liposomes treated burns. On Day 6, 50-100% of the surface area of alpha-gal liposomes treated burns were covered with regenerating epidermis (re-epithelialization), whereas almost no epidermis was found in control burns. The extensive recruitment of macrophages by anti-Gal/alpha-gal liposomes interaction was further demonstrated in vivo with polyvinyl alcohol (PVA) sponge discs containing alpha-gal liposomes, implanted subcutaneously. Since anti-Gal is abundant in all humans, it is suggested that treatment with alpha-gal liposomes

  12. Effectiveness of combined laser-puncture and conventional wound care to accelerate diabetic foot ulcer healing

    Directory of Open Access Journals (Sweden)

    Adiningsih Srilestari

    2017-05-01

    Full Text Available Background: Impaired wound healing is a common complication of diabetes. It has complex pathophysiologic mechanisms and often necessitates amputation. Our study aimed to evaluate the effectiveness of combined laser-puncture and conventional wound care in the treatment of diabetic foot ulcers.Methods: This was a double-blind controlled randomized clinical trial on 36 patients, conducted at the Metabolic Endocrine Outpatient Clinic, Cipto Mangunkusumo Hospital, Jakarta, between May and August 2015. Stimulation by laser-puncture (the treatment group or sham stimulation (the control group were performed on top of the standard wound care. Laser-puncture or sham were done on several acupuncture points i.e. LI4 Hegu, ST36 Zusanli, SP6 Sanyinjiao and KI3 Taixi bilaterally, combined with irradiation on the ulcers itself twice a week for four weeks. The mean reduction in ulcer sizes (week 2–1, week 3–1, week 4–1 were measured every week and compared between the two groups and analyzed by Mann-Whitney test.Results: The initial median ulcer size were 4.75 (0.10–9.94 cm2 and 2.33 (0.90–9.88 cm2 in laser-puncture and sham groups, respectively (p=0.027. The median reduction of ulcer size at week 2–1 was -1.079 (-3.25 to -0.09 vs -0.36 (-0.81 to -1.47 cm2, (p=0.000; at week 3–1 was -1.70 (-3.15 to -0.01 vs -0.36 (-0.80 to -0.28 cm2, (p=0.000; and at week 4–1 was -1.22 (-2.72 to 0.00 vs -0.38 (-0.74 to -0.57 cm2, (p=0.012.Conclusion: Combined laser-puncture and conventional wound care treatment are effective in accelerating the healing of diabetic foot ulcer.

  13. Time course of 25(OHD3 vitamin D3 as well as PTH (parathyroid hormone during fracture healing of patients with normal and low bone mineral density (BMD

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    Wöfl Christoph

    2013-01-01

    Full Text Available Abstract Background Until now the exact biochemical processes during healing of metaphyseal fractures of healthy and osteoporotic bone remain unclear. Especially the physiological time courses of 25(OHD3 (Vitamin D as well as PTH (Parathyroid Hormone the most important modulators of calcium and bone homeostasis are not yet examined sufficiently. The purpose of this study was to focus on the time course of these parameters during fracture healing. Methods In the presented study, we analyse the time course of 25(OHD3 and PTH during fracture healing of low BMD level fractures versus normal BMD level fractures in a matched pair analysis. Between March 2007 and February 2009 30 patients older than 50 years of age who had suffered a metaphyseal fracture of the proximal humerus, the distal radius or the proximal femur were included in our study. Osteoporosis was verified by DEXA measuring. The time courses of 25(OHD3 and PTH were examined over an eight week period. Friedmann test, the Wilcoxon signed rank test and the Mann-Withney U test were used as post-hoc tests. A p-value ≤ 0.05 was considered significant. Results Serum levels of 25(OHD3 showed no differences in both groups. In the first phase of fracture healing PTH levels in the low BMD level group remained below those of the normal BMD group in absolute figures. Over all no significant differences between low BMD level bone and normal BMD level bone could be detected in our study. Conclusions The time course of 25(OHD3 and PTH during fracture healing of patients with normal and low bone mineral density were examined for the first time in humans in this setting and allowing molecular biological insights into fracture healing in metaphyseal bones on a molecural level. There were no significant differences between patients with normal and low BMD levels. Hence further studies will be necessary to obtain more detailed insight into fracture healing in order to provide reliable decision criteria for

  14. Role of non-mulberry silk fibroin in deposition and regulation of extracellular matrix towards accelerated wound healing.

    Science.gov (United States)

    Chouhan, Dimple; Chakraborty, Bijayshree; Nandi, Samit K; Mandal, Biman B

    2017-01-15

    Bombyx mori silk fibroin (BMSF) as biopolymer has been extensively explored in wound healing applications. However, limited study is available on the potential of silk fibroin (SF) from non-mulberry (Antheraea assama and Philosamia ricini) silk variety. Herein, we have developed non-mulberry SF (NMSF) based electrospun mats functionalized with epidermal growth factor (EGF) and ciprofloxacin HCl as potential wound dressing. The NMSF based mats exhibited essential properties of wound dressing like biocompatibility, high water retention capacity (440%), water vapor transmission rate (∼2330gm(-2)day(-1)), high elasticity (∼2.6MPa), sustained drug release and antibacterial activity. Functionalized NMSF mats enhanced the proliferation of human dermal fibroblasts and HaCaT cells in vitro as compared to non-functionalized mats (p⩽0.01) showing effective delivery of EGF. Extensive in vivo wound healing assesment demonstrated accelerated wound healing, enhanced re-epithelialization, highly vascularized granulation tissue and higher wound maturity as compared to BMSF based mats. NMSF mats treated wounds showed regulated deposition of mature elastin, collagen and reticulin fibers in the extracellular matrix of skin. Presence of skin appendages and isotropic collagen fibers in the regenerated skin also demonstrated scar-less healing and aesthetic wound repair. A facile fabrication of a ready-to-use bioactive wound dressing capable of concomitantly accelerating the healing process as well as deposition of the extracellular matrix (ECM) to circumvent further scarring complicacies has become a focal point of research. In this backdrop, our present work is based on non-mulberry silk fibroin (NMSF) electrospun antibiotic loaded semi-occlusive mats, mimicking the ECM of skin in terms of morphology, topology, microporous structure and mechanical stiffness. Regulation of ECM deposition and isotropic orientation evinced the potential of the mat as an instructive platform for skin

  15. On the continued acceleration of bomb casing fragments following casing fracture

    Institute of Scientific and Technical Information of China (English)

    Michael D.HUTCHINSON; David W.PRICE

    2014-01-01

    It has been said that, once a bomb casing has fractured,“detonation gases will then stream around the fragments or bypass them, and the acceleration process stops there.”However, while apparently copious gas flow through casing fractures indicates some pressure release, it is also an indication of significant gas drive pressure, post casing fracture. This paper shows two approaches to the problem of calculating the actual loss of drive. One presents first-order analytical calculations, in cylindrical geometry, of pressure loss to the inside surface of a fractured casing. The second shows the modelling of a selected example in the CTH code. Both approaches reveal that gas escape, while occurring at its own sound-speed relative to the adjacent casing fragments, has to compete with rapid radial expansion of the casing. Together with some historic ex-periments now publicly available, our calculations indicate that post-fracture casing fragment acceleration is, for most systems, unlikely to be reduced significantly.

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

    Directory of Open Access Journals (Sweden)

    Andrea Ode

    Full Text Available 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.

  17. The accelerating effect of chitosan-silica hybrid dressing materials on the early phase of wound healing.

    Science.gov (United States)

    Park, Ji-Ung; Jung, Hyun-Do; Song, Eun-Ho; Choi, Tae-Hyun; Kim, Hyoun-Ee; Song, Juha; Kim, Sukwha

    2017-10-01

    Commercialized dressing materials with or without silver have played a passive role in early-phase wound healing, protecting the skin defects from infections, absorbing exudate, and preventing dehydration. Chitosan (CTS)-based sponges have been developed in pure or hybrid forms for accelerating wound healing, but their wound-healing capabilities have not been extensively compared with widely used commercial dressing materials, providing limited information in a practical aspect. In this study, we have developed CTS-silica (CTS-Si) hybrid sponges with water absorption, flexibility, and mechanical behavior similar to those of CTS sponges. In vitro and in vivo tests were performed to compare the CTS-Si sponges with three commercial dressing materials [gauze, polyurethane (PU), and silver-containing hydrofiber (HF-Ag)] in addition to CTS sponges. Both in vitro and in vivo tests showed that CTS-Si sponges promoted fibroblast proliferation, leading to accelerated collagen synthesis, whereas the CTS sponges did not exhibit significant differences in fibroblast proliferation and collagen synthesis from gauze, PU, and HF-Ag sponges. In case of CTS-Si, the inflammatory cells were actively recruited to the wound by the influence of the released silicon ions from CTS-Si sponges, which, in return, led to an enhanced secretion of growth factors, particularly TGF-β during the early stage. The higher level of TGF-β likely improved the proliferation of fibroblasts, and as a result, collagen synthesis by fibroblasts became remarkably productive, thereby increasing collagen density at the wound site. Therefore, the CTS-Si hybrid sponges have considerable potential as a wound-dressing material for accelerating wound healing. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1828-1839, 2017. © 2016 Wiley Periodicals, Inc.

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

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, W.K.; Feeley, B.T.; Krenek, L.; Stout, D.B.; Chatziioannou, A.F. [David Geffen School of Medicine at UCLA, Center for Health Sciences, Department of Orthopaedic Surgery, Los Angeles, CA (United States); Lieberman, J.R. [University of Connecticut Health Center, The Musculoskeletal Institute, Department of Orthopaedic Surgery, Farmington, CT (United States)

    2007-08-15

    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 {sup 18}F-fluoride ion, which localizes in regions of high osteoblastic activity, and {sup 18}F-fluorodeoxyglucose (FDG), an indicator of cellular glucose metabolism, in assessing bone healing in a rat femur fracture model. Fractures were created in the femurs of immunocompetent 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, {sup 18}F-fluoride, and {sup 18}F-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. 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. {sup 18}F-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 {sup 18}F-FDG PET imaging at any time point. This study suggests that {sup 18}F-fluoride PET imaging, which is an indicator of osteoblastic activity in vivo, can identify fracture nonunions at an early time

  19. Rapid recruitment and activation of macrophages by anti-Gal/α-Gal liposome interaction accelerates wound healing.

    Science.gov (United States)

    Wigglesworth, Kim M; Racki, Waldemar J; Mishra, Rabinarayan; Szomolanyi-Tsuda, Eva; Greiner, Dale L; Galili, Uri

    2011-04-01

    Macrophages are pivotal in promoting wound healing. We hypothesized that topical application of liposomes with glycolipids that carry Galα1-3Galβ1-4GlcNAc-R epitopes (α-gal liposomes) on wounds may accelerate the healing process by rapid recruitment and activation of macrophages in wounds. Immune complexes of the natural anti-Gal Ab (constituting ∼1% of Ig in humans) bound to its ligand, the α-gal epitope on α-gal liposomes would induce local activation of complement and generation of complement chemotactic factors that rapidly recruit macrophages. Subsequent binding of the Fc portion of anti-Gal coating α-gal liposomes to FcγRs on recruited macrophages may activate macrophage genes encoding cytokines that mediate wound healing. We documented the efficacy of this treatment in α1,3galactosyltrasferase knockout mice. In contrast to wild-type mice, these knockout mice lack α-gal epitopes and can produce the anti-Gal Ab. The healing time of excisional skin wounds treated with α-gal liposomes in these mice is twice as fast as that of control wounds. Moreover, scar formation in α-gal liposome-treated wounds is much lower than in physiologic healing. Additional sonication of α-gal liposomes resulted in their conversion into submicroscopic α-gal nanoparticles. These α-gal nanoparticles diffused more efficiently in wounds and further increased the efficacy of the treatment, resulting in 95-100% regeneration of the epidermis in wounds within 6 d. The study suggests that α-gal liposome and α-gal nanoparticle treatment may enhance wound healing in the clinic because of the presence of high complement activity and high anti-Gal Ab titers in humans.

  20. Effect of safflower injection on lower limb fracture healing as well as blood viscosity and blood coagulation function

    Institute of Scientific and Technical Information of China (English)

    Ya-Zhong Wang; Yun Wen

    2016-01-01

    Objective:To analyze the effect of safflower injection on lower limb fracture healing as well as blood viscosity and blood coagulation function.Methods: A total of 118 patients with fracture of lower limb were randomly divided into observation group and control group (n=59), control group received conventional surgical treatment, observation group received surgery + postoperative safflower injection treatment, and then differences in serum content of bone turnover indexes and bone metabolism indexes as well as levels of thrombelastogram parameters and blood coagulation function indexes were compared between two groups after 1 month of treatment.Results:Bone turnover indexes sBAP, PINP and BGP content in serum of observation group after 1 month of treatment were higher than those of control group while sCTX, sTAP and TRAP-5b content were lower than those of control group; bone metabolism indexes Ca2+ and 25-OH-VitD content in serum were higher than those of control group while P, PTH andβ-CTX content were lower than those of control group; thrombelastogram parameters R time and K time were longer than those of control group while MA value, G value and angle level were lower than those of control group; blood coagulation function indexes PLT, FIB and D-D content in serum were lower than those of control group while PT, APTT and TT levels were higher than those of control group.Conclusions:Safflower injection can promote postoperative fracture end healing in patients with fracture of lower limb, and also plays a positive role in reducing blood viscosity and optimizing blood coagulation function.

  1. The potential role of original fracture hematoma in fracture healing%骨折愈合过程中原始骨折血肿的潜在作用

    Institute of Scientific and Technical Information of China (English)

    林梁; 唐亚辉; 吾路汗; 谢增如

    2015-01-01

    BACKGROUND:In closed fractures, the initial hematoma that is inclined to remove is seldom considered as the important reasons for bone healing. OBJECTIVE:To observe the mechanism and potential role of original fracture hematoma in fracture healing. METHODS:Ninety-six patients with closed fractures of the long bones undergoing open reduction and internal fixation were randomly divided into experimental group (n=48) and control group (n=48). In the experimental group, original fracture hematoma, 1.0-2.0 mL, was first taken out during the internal fixation and placed into a special sterile plastic bag; then, 3-4 pieces of hematomas were filed into the fracture site and sutured layer by layer. On the contrary, original fracture hematomas from the control group were discarded. Blood samples were extracted to detect the biochemical indicators at 1 month after internal fixation. X-ray examination was done at 1, 3, 6 months after internal fixation for observation of fracture healing. RESULTS AND CONCLUSION: X-ray films showed that the healing rate at 3 months after operation was 95% in the experimental group and 78% in the control group, and there was a significant difference between the two groups (P < 0.05). Levels of bone glaprotein, I-type precolagen carboxy terminus peptide and serum bone alkaline phosphatase were significantly higher in the experimental group than the control group (P < 0.01 orP < 0.05). These findings indicate that the original fracture hematoma can accelerate calus formation, promote bone induction, provide nutrition to the fracture site, and participate in revascularization. Therefore, the original fracture hematomas is one of the effectively therapeutic methods for union and nonunion of fractures.%背景:临床实践中闭合性骨折内固定过程中,骨折原始血肿很少视为骨折愈合的重要因素,常被有意清除,非常可惜。目的:对比分析骨折血肿在骨折愈合过程中所发挥的机制及作用。方

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

    Science.gov (United States)

    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.

  3. A cold plasma jet accelerates wound healing in a murine model of full-thickness skin wounds.

    Science.gov (United States)

    Schmidt, Anke; Bekeschus, Sander; Wende, Kristian; Vollmar, Brigitte; von Woedtke, Thomas

    2017-02-01

    Cold plasma has been successfully applied in several fields of medicine that require, for example, pathogen inactivation, implant functionalization or alteration of cellular activity. Previous studies have provided evidence that plasma supports the healing of wounds owing to its beneficial mixtures of reactive species and modulation of inflammation in cells and tissues. To investigate the wound healing activity of an atmospheric pressure plasma jet in vivo, we examined the cold plasma's efficacy on dermal regeneration in a murine model of dermal full-thickness ear wound. Over 14 days, female mice received daily plasma treatment. Quantitative analysis by transmitted light microscopy demonstrated a significantly accelerated wound re-epithelialization at days 3-9 in comparison with untreated controls. In vitro, cold plasma altered keratinocyte and fibroblast migration, while both cell types showed significant stimulation resulting in accelerated closure of gaps in scratch assays. This plasma effect correlated with the downregulation of the gap junctional protein connexin 43 which is thought to be important in the regulation of wound healing. In addition, plasma induced profound changes in adherence junctions and cytoskeletal dynamics as shown by downregulation of E-cadherin and several integrins as well as actin reorganization. Our results theorize cold plasma to be a beneficial treatment option supplementing existing wound therapies.

  4. [Advancement in methods of evaluation on bone fracture healing and its application in forensic medicine].

    Science.gov (United States)

    Li, Yu-fei

    2011-02-01

    It is frequently encountered to identify the time of bone fracture in forensic medicine. Hence it is important to develop the methods for evaluating the time of bone fracture. This article reviews the applications and values of the methods such as ultrasonic evaluation, impulse measurement, digital imaging technology and bone mineral density testing technology, etc. It is proposed that to use these methods jointly may provide more scientific evidence in determine the time of bone fracture.

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

    Science.gov (United States)

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

    2012-06-01

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

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

    Science.gov (United States)

    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

  7. Hydrogel and Platelet-Rich Plasma Combined Treatment to Accelerate Wound Healing in a Nude Mouse Model

    Directory of Open Access Journals (Sweden)

    Yu Gil Park

    2017-05-01

    Full Text Available BackgroundPlatelet-rich plasma (PRP contains high concentrations of growth factors involved in wound healing. Hydrogel is a 3-dimensional, hydrophilic, high-molecular, reticular substance generally used as a dressing formulation to accelerate wound healing, and also used as a bio-applicable scaffold or vehicle. This study aimed to investigate the effects of PRP and hydrogel on wound healing, in combination and separately, in an animal wound model.MethodsA total of 64 wounds, with 2 wounds on the back of each nude mouse, were classified into 4 groups: a control group, a hydrogel-only group, a PRP-only group, and a combined-treatment group. All mice were assessed for changes in wound size and photographed on scheduled dates. The number of blood vessels was measured in all specimens. Immunohistochemical staining was used for the analysis of vascular endothelial growth factor (VEGF expression.ResultsDifferences in the decrease and change in wound size in the combined-treatment group were more significant than those in the single-treatment groups on days 3, 5, 7, and 10. Analysis of the number of blood vessels through histological examination showed a pattern of increase over time that occurred in all groups, but the combined-treatment group exhibited the greatest increase on days 7 and 14. Immunohistochemical staining showed that VEGF expression in the combined-treatment group exhibited its highest value on day 7.ConclusionsThis experiment demonstrated improved wound healing using a PRP–hydrogel combined treatment compared to either treatment individually, resulting in a decrease in wound size and a shortening of the healing period.

  8. Research progress in mechanism of traumatic brain injury affecting speed of fracture healing

    Institute of Scientific and Technical Information of China (English)

    ZHAO Xiao-gang; ZHAO Guang-feng; MA Yue-feng; JIANG Guan-yu

    2007-01-01

    @@ In patients who have sustained traumatic brain injury with associated extremity fracture, there is often a clinical perception that the rate of new bone formation around the fracture site increases. 1 An overgrowth of callus is observed and ectopic ossification even occurs in the muscle,2 but the mechanism remains unclear.

  9. Inhibition of Prostaglandin Transporter (PGT Promotes Perfusion and Vascularization and Accelerates Wound Healing in Non-Diabetic and Diabetic Rats.

    Directory of Open Access Journals (Sweden)

    Zhongbo Liu

    Full Text Available Peripheral ischemia, resulting from diminished arterial flow and defective local vascularization, is one of the main causes of impaired wound healing in diabetes. Vasodilatory prostaglandins (PGs, including PGE2 and PGI2, regulate blood flow in peripheral tissues. PGs also stimulate angiogenesis by inducing vascular endothelial growth factor. However, PG levels are reduced in diabetes mainly due to enhanced degradation. We hypothesized that inhibition of the prostaglandin transporter (PGT (SLCO2A1, which mediates the degradation of PGs, would increase blood flow and stimulate vascularization, thereby mitigating peripheral ischemia and accelerating wound healing in diabetes. Here we report that inhibiting PGT with intravenously injected PGT inhibitor, T26A, increased blood flow in ischemic hind limbs created in non-diabetic rats and streptozotocin induced diabetic rats. Systemic, or combined with topical, T26A accelerated closure of cutaneous wounds. Immunohistochemical examination revealed that inhibition of PGT enhanced vascularization (marked by larger numbers of vessels formed by CD34+ cells, and accelerated re-epithelialization of cutaneous wounds. In cultured primary human bone marrow CD34+ cells and human epidermal keratinocytes (HEKs either inhibiting or silencing PGT increased migration in both cell lines. Thus PGT directly regulates mobilization of endothelial progenitor cells (EPCs and HEKs, which could contribute to PGT-mediated vascularization and re-epithelialization. At the molecular level, systemic inhibition of PGT raised circulating PGE2. Taken together, our data demonstrate that PGT modulates arterial blood flow, mobilization of EPCs and HEKs, and vascularization and epithelialization in wound healing by regulating vasodilatory and pro-angiogenic PGs.

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

    Science.gov (United States)

    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.

  11. Exosomes derived from human amniotic epithelial cells accelerate wound healing and inhibit scar formation.

    Science.gov (United States)

    Zhao, Bin; Zhang, Yijie; Han, Shichao; Zhang, Wei; Zhou, Qin; Guan, Hao; Liu, Jiaqi; Shi, Jihong; Su, Linlin; Hu, Dahai

    2017-04-01

    Wound healing is a highly orchestrated physiological process consisting of a complex events, and scarless wound healing is highly desired for the development and application in clinical medicine. Recently, we have demonstrated that human amniotic epithelial cells (hAECs) promoted wound healing and inhibited scar formation through a paracrine mechanism. However, exosomes (Exo) are one of the most important paracrine factors. Whether exosomes derived from human amniotic epithelial cells (hAECs-Exo) have positive effects on scarless wound healing have not been reported yet. In this study, we examined the role of hAECs-Exo on wound healing in a rat model. We found that hAECs, which exhibit characteristics of both embryonic and mesenchymal stem cells, have the potential to differentiate into all three germ layers. hAECs-Exo ranged from 50 to 150 nm in diameter, and positive for exosomal markers CD9, CD63, CD81, Alix, TSG101 and HLA-G. Internalization of hAECs-Exo promoted the migration and proliferation of fibroblasts. Moreover, the deposition of extracellular matrix (ECM) were partly abolished by the treatment of high concentration of hAECs-Exo (100 μg/mL), which may be through stimulating the expression of matrix metalloproteinase-1 (MMP-1). In vivo animal experiments showed that hAECs-Exo improved the skin wound healing with well-organized collagen fibers. Taken together, These findings represent that hAECs-Exo can be used as a novel hope in cell-free therapy for scarless wound healing.

  12. Effects of " vitex agnus castus" extract and magnesium supplementation, alone and in combination, on osteogenic and angiogenic factors and fracture healing in women with long bone fracture

    Directory of Open Access Journals (Sweden)

    Mohammad Hassan Eftekhari

    2014-01-01

    Full Text Available Background: The purpose of this study was to investigate the effects of the combination of vitex agnus castus extract, as a source of phytoestrogens, plus magnesium supplementation on osteogenic and angiogenic factors and callus formation in women with long bone fracture. Material and Methods: In a double-blind randomized placebo controlled trial, 64 women with long bone fracture, 20-45 years old, were randomly allocated to receive 1 one Agnugol tablet (4 mg dried fruit extract of vitex agnus castus plus 250 mg magnesium oxide (VAC + Mg group (n = 10, 2 one Agnugol tablet plus placebo (VAC group (n = 15, 3 placebo plus 250 mg magnesium oxide (Mg group (n = 12, or 4 placebo plus placebo (placebo group (n = 14 per day for 8 weeks. At baseline and endpoint of the trial, serum alkaline phosphatase, osteocalcin, and vascular endothelial growth factor (VEGF were measured together with radiological bone assessment. Results: There were no significant differences in the characteristic aspects of concern between the four groups at baseline. Despite the increased level of alkaline phosphatase in the VAC group (188.33 ± 16.27 to 240.40 ± 21.49, P = 0.05, administration of VAC + Mg could not increase alkaline phosphatase activity. However, treatment with VAC + Mg significantly enhanced the osteocalcin level. The serum concentration of VEGF was increased in the VAC group (269.04 ± 116.63 to 640.03 ± 240.16, P < 0.05. Callus formation in the VAC + Mg group was higher than the other groups but the differences between the four groups were not significant (P = 0.39. No relevant side effect was observed in patients in each group. Conclusion : Our results suggest that administration of vitex agnus castus plus magnesium may promote fracture healing. However, more studies need to further explore the roles of vitex agnus castus in fracture repair processes.

  13. Topical Application of Sadat-Habdan Mesenchymal Stimulating Peptide (SHMSP Accelerates Wound Healing in Diabetic Rabbits

    Directory of Open Access Journals (Sweden)

    Abdulmohsen H. Al-Elq

    2012-01-01

    Full Text Available Objective. Diminished wound healing is a common problem in diabetic patients due to diminished angiogenesis. SHMSP was found to promote angiogenesis. The present study was carried out to examine the effect of this peptide in healing of wounds in diabetic rabbits. Materials and Methods. Twenty male New Zealand rabbits were used in this study. Diabetes mellitus was induced and the rabbits were randomly divided into two equal groups: control group and peptide group. A-full thickness punch biopsy was made to create a wound of about 10 mm on the right ears of all rabbits. Every day, the wound was cleaned with saline in control groups. In the peptide group, 15 mg of SHMSP was applied after cleaning. On day 15th, all animals were sacrificed, and the wounds were excised with a rim of 5 mm of normal surrounding tissue. Histo-pathological assessment of wound healing, inflammatory cell infiltration, blood vessel proliferation, and collagen deposition was performed. Results. There were no deaths among the groups. There was significant increase in wound healing, blood vessel proliferation and collagen deposition, and significant decrease in inflammatory cell infiltration in the peptide group compared to the control group. Conclusion. Topical application of SHMSP improves wound healing in diabetic rabbits.

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

    Directory of Open Access Journals (Sweden)

    Anica Eschler

    2016-01-01

    Full Text Available 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.

  15. Radiographic evaluation of fracture healing after rigid plate fixation. Experiments in the rabbit

    Energy Technology Data Exchange (ETDEWEB)

    Paavolainen, P.; Karaharju, E.; Slaetis, P.; Waris, P. (Helsinki Univ. Central Hospital (Finland). Meilahti Clinic)

    1981-01-01

    Experimental osteotomies were made in 35 rabbit tibio-fibular bones and fixed with rigid stainless steel osteosynthesis plates (DCP/ASIF). The radiographic and histopathologic appearances in the healing osteotomies and adjacent bone were analysed at intervals from 3 up to 24 weeks postoperatively. Radiologically the osteotomy had closed at 9 weeks and microscopically this could be confirmed as longitudinal orientation of the cutter heads across the osteotomy gap with longitudinal orientation of the bone structure. The healing of the osteotomy was accompanied by gross structural changes in the adjacent cortical bone with loss of intracortical and subendosteal osteons, cementing lines and intermediate tissue between the osteons. This was characterized by decreasing attenuation of the cortical bone after healing of the osteotomy and should clinically be regarded as an indication for removal of the implant.

  16. The effect of PTH(1-34) on fracture healing during different loading conditions

    DEFF Research Database (Denmark)

    Ellegaard, Maria; Kringelbach, Tina; Syberg, Susanne

    2013-01-01

    . Five days before fracture, half of the animals received Botulinum Toxin A injections in the muscles of the fractured leg to induce muscle paralysis (unloaded group), whereas the other half received saline injections (control group). For the following 8 weeks, half of the animals in each group received...... and control animals. PTH(1-34) treatment increased ultimate force of the fracture by 63% in both control and unloaded animals and no interaction of the two interventions could be detected. PTH(1-34) was able to stimulate bone formation in normally loaded as well as unloaded intact bone. In conclusion...

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

    KAUST Repository

    Seow, Wei Yang

    2016-09-07

    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.

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

    Science.gov (United States)

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

    2016-09-01

    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.

  19. Fracture healing and transport properties of wellbore cement in the presence of supercritical CO2

    NARCIS (Netherlands)

    Liteanu, E.; Spiers, C.J.

    2011-01-01

    This paper investigates the process and rate of carbonation reaction of Class A wellbore cement exposed to CO2-saturated solution at confined conditions similar to those employed in geological storage of CO2. The main goal was to investigate whether reaction improves or degrades the sealing/healing

  20. Pharmacological agents and impairment of fracture healing: what is the evidence?

    NARCIS (Netherlands)

    Pountos, I.; Georgouli, T.; Blokhuis, T.J.; Pape, H.C.; Giannoudis, P.V.

    2008-01-01

    Bone healing is an extremely complex process which depends on the coordinated action of several cell lineages on a cascade of biological events, and has always been a major medical concern. The use of several drugs such as corticosteroids, chemotherapeutic agents, non-steroidal anti-inflammatory dru

  1. Accelerated in vivo wound healing evaluation of microbial glycolipid containing ointment as a transdermal substitute.

    Science.gov (United States)

    Gupta, Sonam; Raghuwanshi, Navdeep; Varshney, Ritu; Banat, I M; Srivastava, Amit Kumar; Pruthi, Parul A; Pruthi, Vikas

    2017-10-01

    A potent biosurfactant (BS) producing Bacillus licheniformis SV1 (NCBI GenBank Accession No. KX130852) was isolated from oil contaminated soil sample. Physicochemical investigations (TLC, HPLC, FTIR, GC-MS and NMR) revealed it to be glycolipid in nature. Fibroblast culture assay showed cytocompatibility and increased cell proliferation of 3T3/NIH fibroblast cells treated with this biosurfactant when checked using MTT assay and DAPI fluorescent staining. To evaluate the wound healing potential, BS ointment was formulated and checked for its spreadability and viscosity consistency. In vivo wound healing examination of full thickness skin excision wound rat model demonstrated the prompt re-epithelialization and fibroblast cell proliferation in the early phase while quicker collagen deposition in later phases of wound healing when BS ointment was used. These results validated the potential usage of BS ointment as a transdermal substitute for faster healing of impaired skin wound. Biochemical evaluation also substantiated the highest concentration of hydroxyproline (32.18±0.46, p<0.001) in the BS ointment treated animal tissue samples compared to the control. Hematoxylin-Eosin (H&E) and Masson's Trichrome staining validated the presence of increased amount of collagen fibers and blood vessels in the test animals treated with BS ointment. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  2. The Probiotic Mixture VSL#3 Accelerates Gastric Ulcer Healing by Stimulating Vascular Endothelial Growth Factor

    Science.gov (United States)

    Dharmani, Poonam; De Simone, Claudio; Chadee, Kris

    2013-01-01

    Studies assessing the effect and mechanism of probiotics on diseases of the upper gastrointestinal tract (GI) including gastric ulcers are limited despite extensive work and promising results of this therapeutic option for other GI diseases. In this study, we investigated the mechanisms by which the probiotic mixture VSL#3 (a mixture of eight probiotic bacteria including Lactobacilli, Bifidobacteria and Streptococcus species) heals acetic acid induced gastric ulcer in rats. VSL#3 was administered orally at low (6×109 bacteria) or high (1.2×1010 bacteria) dosages from day 3 after ulcer induction for 14 consecutive days. VSL#3 treatments significantly enhanced gastric ulcer healing in a dose-dependent manner. To assess the mechanism(s) whereby VSL#3 exerted its protective effects, we quantified the gene expression of several pro-inflammatory cytokines, protein and expression of stomach mucin-Muc5ac, regulatory cytokine-IL-10, COX-2 and various growth factors. Of all the components examined, only expression and protein production of VEGF was increased 332-fold on day 7 in the ulcerated tissues of animals treated with VSL#3. Predictably, animals treated with VEGF neutralizing antibody significantly delayed gastric ulcer healing in VSL#3 treated animals. This is the first report to demonstrate high efficacy of the probiotic mixture VSL#3 in enhancing gastric ulcer healing. Probiotic efficacy was effective at higher concentrations of VSL#3 by specifically increasing the expression and production of angiogenesis promoting growth factors, primarily VEGF. PMID:23484048

  3. Acarbose Accelerates Wound Healing via Akt/eNOS Signaling in db/db Mice

    Directory of Open Access Journals (Sweden)

    Xue Han

    2017-01-01

    Full Text Available Refractory wound is a dreaded complication of diabetes and is highly correlated with EPC dysfunction caused by hyperglycemia. Acarbose is a widely used oral glucose-lowering drug exclusively for T2DM. Previous studies have suggested the beneficial effect of acarbose on improving endothelial dysfunction in patients with T2DM. However, no data have been reported on the beneficial efficacy of acarbose in wound healing impairment caused by diabetes. We herein investigated whether acarbose could improve wound healing in T2DM db/db mice and the possible mechanisms involved. Acarbose hastened wound healing and enhanced angiogenesis, accompanied by increased circulating EPC number in db/db mice. In vitro, a reversed BM-EPC dysfunction was observed after the administration of acarbose in db/db mice, as reflected by tube formation assay. In addition, a significantly increased NO production was also witnessed in BM-EPCs from acarbose treated db/db mice, with decreased O2 levels. Akt inhibitor could abolish the beneficial effect of acarbose on high glucose induced EPC dysfunction in vitro, accompanied by reduced eNOS activation. Acarbose displayed potential effect in promoting wound healing and improving angiogenesis in T2DM mice, which was possibly related to the Akt/eNOS signaling pathway.

  4. The effects of glycyrrhizic acid and glabridin in the regulation of CXCL5 inflammation gene on acceleration of wound healing

    Institute of Scientific and Technical Information of China (English)

    Hong Yung Yip; Melissa Su Wei Poh; Yoke Yin Chia

    2016-01-01

    Objective: To evaluate the anti-inflammatory property of both glycyrrhizic acid(GA)and glabridin in reducing inflammation to accelerate wound regeneration on 3T3-L1 and NIH-3T3 fibroblast cell lines.Methods: Cell proliferation and viability assay(MTT assay), scratch wound healing assays,and quantitative real-time PCR were conducted to investigate the effects on cell proliferation,cell migration, and expression of CXC chemokine ligand 5 inflammation gene respectively.Results: Results showed that at a low concentration of 1 × 10-8mol/L, glabridin down regulated cell proliferation in NIH-3T3 significantly, suggesting its involvement in ERK1/2 signaling pathway. GA and glabridin significantly accelerated cell migration through wound healing in both 3T3-L1 and NIH-3T3 and significantly down regulated the expression of CXC chemokine ligand 5 in 3T3-L1 at concentration 1 × 10-8mol/L,indicating the possible involvement of nuclear factor-k B and cyclooxygenase 2 transcriptions modulation.Conclusions: Both GA and glabridin can serve as potential treatment for chronic inflammatory disease, and glabridin as an oncogenic inhibitor due to its anti-proliferative property.

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

    Science.gov (United States)

    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

  6. Downregulation of PTEN at Corneal Wound Sites Accelerates Wound Healing through Increased Cell Migration

    Science.gov (United States)

    Cao, Lin; Graue-Hernandez, Enrique O.; Tran, Vu; Reid, Brian; Pu, Jin; Mannis, Mark J.

    2011-01-01

    Purpose. The PI3K/Akt pathway is required for cell polarization and migration, whereas the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) has inhibitory effects on the PI3K/Akt pathway. The authors therefore hypothesized that wounding would downregulate PTEN and that this downregulation would enhance wound healing. Methods. In human corneal epithelial (HCE) cell monolayer and rat cornea scratch wound models, the authors investigated PTEN and Akt expression using Western blot and immunofluorescence analyses. The effects of PTEN and PI3K inhibitors dipotassium bisperoxo (picolinato) oxovanadate (bpv(pic)) and LY294002 on cell migration and wound closure were investigated using time-lapse imaging. Finally, the authors investigated the effect of PTEN inhibition on wound healing in whole rat eyes. Results. In HCE cell monolayer and rat cornea, PTEN was downregulated at the wound edges within 30 minutes of wounding. The downregulation of PTEN was causal in a simultaneous increase in Akt activation, which was responsible for a significant increase in individual cell migration rate from 8.8 μm/h to 17.3 μm/h. An increased migration rate was maintained for 20 hours. PTEN inhibition significantly enhanced the wound healing rate in the HCE cell monolayer from 10 minutes onward after treatment and reduced the healing time in eye organ culture from 30 to 20 hours. Conclusions. Injury to the corneal epithelium downregulates the expression of PTEN at wound edges, allowing increased PI3K/Akt signaling, thereby contributing to a significant enhancement of cell migration and wound healing. These results suggest that PTEN inhibition may be an effective treatment for corneal injury. PMID:21212174

  7. Topical Application of Aloe vera Accelerated Wound Healing, Modeling, and Remodeling: An Experimental Study.

    Science.gov (United States)

    Oryan, Ahmad; Mohammadalipour, Adel; Moshiri, Ali; Tabandeh, Mohammad Reza

    2016-01-01

    Treatment of large wounds is technically demanding and several attempts have been taken to improve wound healing. Aloe vera has been shown to have some beneficial roles on wound healing but its mechanism on various stages of the healing process is not clear. This study was designed to investigate the effect of topical application of A. vera on cutaneous wound healing in rats. A rectangular 2 × 2-cm cutaneous wound was created in the dorsum back of rats. The animals were randomly divided into 3 groups of control (n = 20), low-dose (n = 20), and high-dose (n = 20) A. vera. The control and treated animals were treated daily with topical application of saline, low-dose (25 mg/mL), and high-dose (50 mg/mL) A. vera gel, up to 10 days, respectively. The wound surface, wound contraction, and epithelialization were monitored. In each group, the animals were euthanized at 10 (n = 5), 20 (n = 5), and 30 (n = 10) days post injury (DPI). At 10, 20, and 30 DPI, the skin samples were used for histopathological and biochemical investigations; and at 30 DPI, the skin samples were also subjected for biomechanical studies. Aloe vera modulated the inflammation, increased wound contraction and epithelialization, decreased scar tissue size, and increased alignment and organization of the regenerated scar tissue. A dose-dependent increase in the tissue level of dry matter, collagen, and glycosaminoglycans' content was seen in the treated lesions, compared to the controls. The treated lesions also demonstrated greater maximum load, ultimate strength, and modulus of elasticity compared to the control ones (P vera improved the biochemical, morphological, and biomechanical characteristics of the healing cutaneous wounds in rats. This treatment option may be valuable in clinical practice.

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

    Science.gov (United States)

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

    2014-06-01

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

  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

    Science.gov (United States)

    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. Acceleration of wound healing by growth hormone-releasing hormone and its agonists

    OpenAIRE

    Dioufa, Nikolina; Schally, Andrew V.; Chatzistamou, Ioulia; Moustou, Evi; Block, Norman L.; Owens, Gary K.; Papavassiliou, Athanasios G; Kiaris, Hippokratis

    2010-01-01

    Despite the well-documented action of growth hormone-releasing hormone (GHRH) on the stimulation of production and release of growth hormone (GH), the effects of GHRH in peripheral tissues are incompletely explored. In this study, we show that GHRH plays a role in wound healing and tissue repair by acting primarily on wound-associated fibroblasts. Mouse embryonic fibroblasts (MEFs) in culture and wound-associated fibroblasts in mice expressed a splice variant of the receptors for GHRH (SV1). ...

  11. Propranolol attenuates hemorrhage and accelerates wound healing in severely burned adults

    OpenAIRE

    Ali, Arham; Herndon, David N.; Mamachen, Ashish; Hasan, Samir; Andersen, Clark R; Grogans, Ro-Jon; Brewer, Jordan L.; Lee, Jong O.; Heffernan, Jamie; Suman, Oscar E.; Finnerty, Celeste C

    2015-01-01

    Introduction Propranolol, a nonselective β-blocker, exerts an indirect effect on the vasculature by leaving α-adrenergic receptors unopposed, resulting in peripheral vasoconstriction. We have previously shown that propranolol diminishes peripheral blood following burn injury by increasing vascular resistance. The purpose of this study was to investigate whether wound healing and perioperative hemodynamics are affected by propranolol administration in severely burned adults. Methods Sixty-nine...

  12. Bmx Tyrosine Kinase Transgene Induces Skin Hyperplasia, Inflammatory Angiogenesis, and Accelerated Wound Healing

    OpenAIRE

    2004-01-01

    The Bmx gene, a member of the Tec family of nonreceptor protein tyrosine kinases, is expressed in arterial endothelium and in certain hematopoietic and epithelial cells. Previous in vitro studies have implicated Bmx signaling in cell migration and survival and suggested that it contributes to the progression of prostate carcinomas. However, the function of Bmx in normal tissues in vivo is unknown. We show here that Bmx expression is induced in skin keratinocytes during wound healing. To analy...

  13. BMP-7 stimulates early diaphyseal fracture healing in estrogen deficient rats

    NARCIS (Netherlands)

    Blokhuis, T.J.; Buma, P.; Verdonschot, N.J.J.; Gotthardt, M.; Hendriks, T.

    2012-01-01

    Estrogen deficiency causes postmenopausal osteoporosis. The relationship between estrogen deficiency and the high failure rate after osteoporotic fracture treatment is unclear, as is the effect of possible interventions, either with anti-resorptive agents or with anabolic agents such as bone morphog

  14. BMP-7 stimulates early diaphyseal fracture healing in estrogen deficient rats.

    NARCIS (Netherlands)

    Blokhuis, T.J.; Buma, P.; Verdonschot, N.J.; Gotthardt, M.; Hendriks, T.

    2012-01-01

    Estrogen deficiency causes postmenopausal osteoporosis. The relationship between estrogen deficiency and the high failure rate after osteoporotic fracture treatment is unclear, as is the effect of possible interventions, either with anti-resorptive agents or with anabolic agents such as bone morphog

  15. Means of enhancing bone fracture healing : Optimal cell source, isolation methods and acoustic stimulation

    NARCIS (Netherlands)

    Ghebes, Corina Adriana; Braham, Maaike Vera Jasmijn; Zeegers, Adelgunde Veronica Clemens Maria; Renard, Auke Jan Sijbe; Fernandes, Hugo; Saris, Daniel B F

    2016-01-01

    Background: The human body has an extensive capacity to regenerate bone tissue after trauma. However large defects such as long bone fractures of the lower limbs cannot be restored without intervention and often lead to nonunion. Therefore, the aim of the present study was to assess the pool and

  16. Observations concerning different patterns of bone healing using the Point Contact Fixator (PC-Fix) as a new technique for fracture fixation.

    Science.gov (United States)

    Hofer, H P; Wildburger, R; Szyszkowitz, R

    2001-09-01

    The recent trend in all surgical disciplines has been the development of techniques in minimally invasive surgery and the optimal maintenance of the blood supply to the bone fragments during osteosynthesis. Currently, the Point Contact Fixator (PC-Fix) has been introduced as a new implant for the stabilization of forearm bones. This plate-like splint and screw fixation system, which actually acts as an internal fixator, is characterized by minimized isolated contacts to the bone and proven angular stability of the monocortically locked screws. By using the PC-Fix, a further reduction of damage to the blood supply to the bone is achieved. Since 1994, 38 patients have been treated with this new device; we have reviewed the radiographs of 52 consolidated forearm fractures/osteotomies in accordance with the patterns of bone healing associated with the different methods of implant application according to the fracture type. In the groups in which traditionally precise reduction, interfragmentary compression and stable fixation was achieved (N=31), we found in 71% an absence of periosteal callus (direct bone healing). In the groups in which compression and adaptation were combined, or even main fragments adapted without compression, with wedges remaining unreduced in soft tissue connection (N=21), we found a visible external callus in 81% (indirect healing) (P = 0.002). Indirect healing after internal fixation is no longer regarded as a disturbance to healing, but is a goal in itself. The appearance of callus is a welcome sign indicating a prompt and positive reaction in the course of bone union which will lead to progressive fracture immobilization. When using the PC-Fix in a "biological way", callus formation and solid union take place earlier than in conventional plating. The new internal fixator offers substantial technical and mechanical advantages in fracture treatment. Therefore, it is an ideal implant to satisfy the requirements of modern biological

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

    Directory of Open Access Journals (Sweden)

    Hong Huang

    2016-01-01

    Full Text Available 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.

  18. Endothelium-specific GTP cyclohydrolase I overexpression accelerates refractory wound healing by suppressing oxidative stress in diabetes.

    Science.gov (United States)

    Tie, Lu; Li, Xue-Jun; Wang, Xian; Channon, Keith M; Chen, Alex F

    2009-06-01

    Refractory wound is a severe complication that leads to limb amputation in diabetes. Endothelial nitric oxide synthase (eNOS) plays a key role in normal wound repair but is uncoupled in streptozotocin (STZ)-induced type 1 diabetes because of reduced cofactor tetrahydrobiopterin (BH(4)). We tested the hypothesis that overexpression of GTP cyclohydrolase I (GTPCH I), the rate-limiting enzyme for de novo BH(4) synthesis, retards NOS uncoupling and accelerates wound healing in STZ mice. Blood glucose levels were significantly increased in both male endothelium-specific GTPCH I transgenic mice (Tg-GCH; via a tie-2 promoter) and wild-type (WT) littermates 5 days after STZ regimen. A full-thickness excisional wound was created on mouse dorsal skin by a 4-mm punch biopsy. Wound closure was delayed in STZ mice, which was rescued in STZ Tg-GCH mice. Cutaneous BH(4) level was significantly reduced in STZ mice vs. WT mice, which was maintained in STZ Tg-GCH mice. In STZ mice, constitutive NOS (cNOS) activity and nitrite levels were decreased compared with WT mice, paralleled by increased superoxide anion (O(2)(-)) level and inducible NOS (iNOS) activity. In STZ Tg-GCH mice, nitrite level and cNOS activity were potentiated and O(2)(-) level and iNOS activity were suppressed compared with STZ mice. Thus endothelium-specific BH(4) overexpression accelerates wound healing in type 1 diabetic mice by enhancing cNOS activity and suppressing oxidative stress.

  19. Transcutaneous electrical nerve stimulation (TENS) accelerates cutaneous wound healing and inhibits pro-inflammatory cytokines.

    Science.gov (United States)

    Gürgen, Seren Gülşen; Sayın, Oya; Cetin, Ferihan; Tuç Yücel, Ayşe

    2014-06-01

    The purpose of this study was to evaluate transcutaneous electrical nerve stimulation (TENS) and other common treatment methods used in the process of wound healing in terms of the expression levels of pro-inflammatory cytokines. In the study, 24 female and 24 male adult Wistar-Albino rats were divided into five groups: (1) the non-wounded group having no incision wounds, (2) the control group having incision wounds, (3) the TENS (2 Hz, 15 min) group, (4) the physiological saline (PS) group and (5) the povidone iodine (PI) group. In the skin sections, interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were assessed with enzyme-linked immunosorbent assay and immunohistochemical methods. In the non-wounded group, the expression of IL-1β, IL-6, and TNF-α signaling molecules was weaker in the whole tissue; however, in the control group, significant inflammatory response occurred, and strong cytokine expression was observed in the dermis, granulation tissue, hair follicles, and sebaceous glands (P TENS group, the decrease in TNF-α, IL-1β, and IL-6 immunoreaction in the skin was significant compared to the other forms of treatment (P TENS group suggest that TENS shortened the healing process by inhibating the inflammation phase.

  20. Human amniotic membrane, best healing accelerator, and the choice of bone induction for vestibuloplasty technique (an animal study

    Directory of Open Access Journals (Sweden)

    Ahad Khoshzaban

    2010-12-01

    Full Text Available Mohammad H Samandari1, Shahriar Adibi2, Ahad Khoshzaban3, Sara Aghazadeh5, Parviz Dihimi4, Siamak S Torbaghan6, Saeed H Keshel5, Zohreh Shahabi71Department of Oral and Maxillofacial Surgery, Dentistry Faculty, 2Dental Research of Torabinejad Research Centre, 3Iranian Tissue Bank Research and Preparation Centre, Imam Khomeini Hospital Complex, 4Department of Oral and Maxillofacial Pathology, Dentistry Faculty, Isfahan University of Medical Sciences, Isfahan, Iran; 5Stem Cells Preparation Unit, Eye Research Center, Farabi Hospital, 6Department of Pathology, Imam Khomeini Medical Centre, 7BMT Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, IranObjective: To investigate the effects of amniotic membrane (AM in bone induction and wound healing after vestibuloplasty surgery on animal samples while receptacle proteins such as growth factors were considered as accelerators for wound healing and bone induction after these operations.Material and methods: Ten adult dogs (5 females, 5 males; race, Iranian mixed; weight, 44 pounds were included, which underwent surgery for transplantation on mandible and maxillary. AM was used for promoting bone induction and healing.Results: The tissue samples were obtained after 2, 8, and 12 weeks for histology survey. No significant differences were observed between male and female or left and right jaws. AM decreased fibrinoleukocytic exudates and inflammation in the experimental group, had significant effects on bone formation, considerably improves wound healing, and gives rise to bone induction (P < 0.0001.Conclusions: Our study findings indicate that the AM is a suitable cover for different injuries and acellular AM has the potential for rapid improvement and bone induction. The AM contains collagen, laminin, and fibronectin, which provide an appropriate substrate for bone induction. This substrate promoted bone induction and might contribute to induction of the progenitor cells and/or stem

  1. Modeling of a self-healing process in blast furnace slag cement exposed to accelerated carbonation

    NARCIS (Netherlands)

    Zemskov, S.V.; Ahmad, B.; Copuroglu, O.; Vermolen, F.J.

    2013-01-01

    In the current research, a mathematical model for the post-damage improvement of the carbonated blast furnace slag cement (BFSC) exposed to accelerated carbonation is constructed. The study is embedded within the framework of investigating the effect of using lightweight expanded clay aggregate, whi

  2. Bone stimulation for fracture healing: What′s all the fuss?

    Directory of Open Access Journals (Sweden)

    Victoria Galkowski

    2009-01-01

    Full Text Available Approximately 10% of the 7.9 million annual fracture patients in the United States experience nonunion and/or delayed unions, which have a substantial economic and quality of life impact. A variety of devices are being marketed under the name of "bone growth stimulators." This article provides an overview of electrical and electromagnetic stimulation, ultrasound, and extracorporeal shock waves. More research is needed for knowledge of appropriate device configurations, advancement in the field, and encouragement in the initiation of new trials, particularly large multicenter trials and randomized control trials that have standardized device and protocol methods.

  3. Effects of low-dose microwave on healing of fractures with titanium alloy internal fixation: an experimental study in a rabbit model.

    Directory of Open Access Journals (Sweden)

    Dongmei Ye

    Full Text Available 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.

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

    Directory of Open Access Journals (Sweden)

    M.T. Xu

    2016-01-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

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

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    Naofumi Tamaki

    2016-01-01

    Full Text Available 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.

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

    Science.gov (United States)

    Tamaki, Naofumi; 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.

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

    Science.gov (United States)

    Lu, Yanfei; Lekszycki, Tomasz

    2016-10-01

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

  9. Root fractures

    DEFF Research Database (Denmark)

    Andreasen, Jens Ove; Christensen, Søren Steno Ahrensburg; Tsilingaridis, Georgios

    2012-01-01

    The purpose of this study was to analyze tooth loss after root fractures and to assess the influence of the type of healing and the location of the root fracture. Furthermore, the actual cause of tooth loss was analyzed.......The purpose of this study was to analyze tooth loss after root fractures and to assess the influence of the type of healing and the location of the root fracture. Furthermore, the actual cause of tooth loss was analyzed....

  10. The effect of PDGFmRNA and IGFmRNA in the platelet concentrated liquid on ulna fracture healing in rabbit%血小板浓缩液中血小板源性生长因子及胰岛素样生长因子对兔尺骨骨折愈合的影响

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective By hybridization in situ and biomechanical approach of platelet derived growth fator mRNA(PDGFmRNA) and insulin like growth factor mRNA(IGFmRNA),we discussed the influence of the platelet concentrated liquid on the healing of rabbit ulna fracture.Method We selected 24 New Zealand rabbits,divided them into 4 groups randomly (blank group, serum control group, group with platelet concentrated liquid and group with bone graft and platelet concentrated liquid), and then made the fracture model on the middle of ulna which was fixed by finger armor plate.Before the operation, we drew out 6 ml blood from femoral artery, performed anti coagulation with the Sodium Citrate and centrifugated by low and the followed high speed.We purified the white blood plate and injected it into the fracture position.The rabbits were killed at 1st, 2nd, 4th and 6th week.Qualitative analysis by hybridization in situ of PDGFmRNA and IGFmRNA and biomechanical measurement on the 6th week sample were made.Result Bone callus could be seen on the radius specimen in various degrees when the rabbits were killed at 1st,2nd,4th and 6th week, particularly in the last week.The average maximum destructive load on the fracture tip is higher to the control, and there is significant difference(P< 0.01). Conclusion The local application of platelet concentration on the fracture tip can accelerate its healing.

  11. The 9/11 Decade: Social Imaginary and Healing Virtual Community Fracture

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    Charles A. Hays

    2011-01-01

    Full Text Available The initial events of 9/11 broke upon the awareness of people who turned first to traditional media for information, then to their networks of distant others when traditional media could not meet their needs. This study looks at two online community groups on Usenet. Though other technologies have supplanted Usenet to some degree, it provided a vibrant means of asynchronously connecting people interested in online discussion. As community members expressed their shock and horror, they also acted out the process of repairing the radical fracture to their virtual communal identity. The process by which they enacted this repair embodies a social imaginary, and is generally called “community repair”. This study finds that the process of community repair is very much driven by the culture inherent in the sodality represented by the participants to each newsgroup, reflecting the values that participants have communally agreed to hold valuable.

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

    Science.gov (United States)

    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.

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

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    Aleksandra Matuszyk

    2016-09-01

    Full Text Available 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.

  14. The use of MTA/blood mixture to induce hard tissue healing in a root fractured maxillary central incisor. Case report and treatment considerations.

    Science.gov (United States)

    Chaniotis, A

    2014-10-01

    To report the use of MTA/blood mixture for the induction of hard tissue healing of multiple horizontal root fractures in a maxillary incisor. An 18-year-old male patient was referred after suffering trauma to the anterior maxilla. Radiographic evaluation revealed multiple horizontal fractures in the middle and cervical third of his maxillary right central incisor. Clinical evaluation revealed third grade mobility of the coronal segment. The patient's accompanying radiographs revealed that root canal treatment of all segments had been previously initiated and both segments had been rendered pulpless. The coronal segment was repositioned and stabilized. A bi-antibiotic mixture, containing equal parts of ciprofloxacin and metronidazole, was used for the disinfection of the root canal segments. A blood clot was induced from the periapical area and MTA powder was mixed with the blood creating a bioceramic mixture covering all the fractures. Thick MTA was placed as a coronal barrier and the tooth was restored. Recall examination after 24 months revealed healing of the horizontal fractures. The MTA mixed with the blood lost its radio-opacity over time. Tooth mobility returned to normal limits. A low range of 5-25% of all horizontally root fractured cases develop pulp necrosis, confined in the coronal segment, leaving the apical segment with vital tissue. In the unfortunate situation that the pulp of both segments becomes necrotic or the entire pulp tissue is removed, the use of MTA/blood mixture may be beneficial for the induction of hard tissue healing. MTA when mixed with blood seems to lose its radio-opacity over time. © 2013 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  15. Ascorbic Acid Promotes the Stemness of Corneal Epithelial Stem/Progenitor Cells and Accelerates Epithelial Wound Healing in the Cornea.

    Science.gov (United States)

    Chen, Jialin; Lan, Jie; Liu, Dongle; Backman, Ludvig J; Zhang, Wei; Zhou, Qingjun; Danielson, Patrik

    2017-03-09

    High concentration of ascorbic acid (vitamin C) has been found in corneal epithelium of various species. However, the specific functions and mechanisms of ascorbic acid in the repair of corneal epithelium are not clear. In this study, it was found that ascorbic acid accelerates corneal epithelial wound healing in vivo in mouse. In addition, ascorbic acid enhanced the stemness of cultured mouse corneal epithelial stem/progenitor cells (TKE2) in vitro, as shown by elevated clone formation ability and increased expression of stemness markers (especially p63 and SOX2). The contribution of ascorbic acid on the stemness enhancement was not dependent on the promotion of Akt phosphorylation, as concluded by using Akt inhibitor, nor was the stemness found to be dependent on the regulation of oxidative stress, as seen by the use of two other antioxidants (GMEE and NAC). However, ascorbic acid was found to promote extracellular matrix (ECM) production, and by using two collagen synthesis inhibitors (AzC and CIS), the increased expression of p63 and SOX2 by ascorbic acid was decreased by around 50%, showing that the increased stemness by ascorbic acid can be attributed to its regulation of ECM components. Moreover, the expression of p63 and SOX2 was elevated when TKE2 cells were cultured on collagen I coated plates, a situation that mimics the in vivo situation as collagen I is the main component in the corneal stroma. This study shows direct therapeutic benefits of ascorbic acid on corneal epithelial wound healing and provides new insights into the mechanisms involved. © Stem Cells Translational Medicine 2017.

  16. The acceleration of garlic (Allium sativum L ethanolic extract on gingival wound healing process in Wistar rats

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    Indra Bramanti Ngatidjan Setyo Purwono

    2014-04-01

    Full Text Available Garlic (Allium sativum L is a medicinal plant traditionally used to relieve pain. Garlic’s active constituents, allicin and triacremonone, have been proven to have antibacterial and antiinflammatory activity. The aim of this study was to investigate the effect of garlic ethanolic extract gel in gingival wound healing process of rats. Thirty male Wistar rats aged 10 weeks with with body weight 200-250 g were subjected in this study. Rats were divided randomly into five groups with six rats in each group. Group I as negative control was given sodium carboxymethyl cellulose (Na CMC base gel. Group II as positive control was given Benzydamine® gel and Group IV-V were given garlic ethanolic extract gel at dose of 20, 40 and 80%, respectively. Each group was subdivided into two sub groups of three rats according to the decapitation period which were 5th (D-5 and 7th (D-7 day after the garlic extract gel application. Excisional wounds using punch biopsy, 2.5 mm in diameter, were created at the mandibular labial gingiva between right and left incisor teeth of the rats. The garlic extract gel of each preparation dose was then applied on the wound three times a day, starting at 0 day until 7th day. The decapitation was conducted on the D-5 and D-7. Histological slides of wounded tissue were prepared. Epithelial thickness, new blood vessel, and number of fibroblast were examined. The results showed that the epithelial thickness of garlic ethanolic extract gel groups was significantly higher than control group (p<0.05, especially after 5thday application. However, the number of new blood vessels and the amount of fibroblast of those groups were not significantly higher than control group (p>0.05. In conclusion, topical application of garlic ethanolic extract gel accelerates the gingival wound healing process in rats by increasing epithelial thickness.     Keywords: garlic ethanolic extract - gingival wound healing - epithelium thickness

  17. Healing acceleration of acetic acid-induced colitis by marigold (Calendula officinalis in male rats

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    Nader Tanideh

    2016-01-01

    Full Text Available 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.

  18. Healing acceleration of acetic acid-induced colitis by marigold (Calendula officinalis) in male rats.

    Science.gov (United States)

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

    2016-01-01

    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. 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. 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). 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.

  19. Accelerated Wound Healing Device Using Light Emitting Diodes (LEDs) Biostimulation to Support Long Term Human Exploration of Space Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Several cases of minor cuts in microgravity have been reported not being able to heal until return to Earth. While the exact cause for the slow healing in space...

  20. 6-Formylindolo[3,2-b]Carbazole Accelerates Skin Wound Healing via Activation of ERK, but Not Aryl Hydrocarbon Receptor.

    Science.gov (United States)

    Morino-Koga, Saori; Uchi, Hiroshi; Mitoma, Chikage; Wu, Zhouwei; Kiyomatsu, Mari; Fuyuno, Yoko; Nagae, Konosuke; Yasumatsu, Mao; Suico, Mary Ann; Kai, Hirofumi; Furue, Masutaka

    2017-10-01

    Wound healing is an elaborate process composed of overlapping phases, such as proliferation and remodeling, and is delayed in several circumstances, including diabetes. Although several treatment strategies for chronic wounds, such as growth factors, have been applied, further alternatives are required. The skin, especially keratinocytes, is continually exposed to UV rays, which impairs wound healing. 6-Formylindolo[3,2-b]carbazole (FICZ) is a tryptophan photoproduct formed by UV exposure, indicating that FICZ might be one of the effectors of UV radiation. In contrast, treatment with tryptophan, the precursor for FICZ, promoted wound closure in keratinocytes. Therefore, the aim of our study was to determine the role of FICZ in wound healing. Here we showed that FICZ enhanced keratinocyte migration through mitogen-activated protein kinase/extracellular signal-regulated kinase activation, and promoted wound healing in various mouse models, including db/db mice, which exhibit wound healing impairments because of type 2 diabetes. Moreover, FICZ, the endogenous ligand of an aryl hydrocarbon receptor, accelerated migration even in the aryl hydrocarbon receptor knockdown condition and also promoted wound healing in DBA/2 mice, bearing a low-affinity aryl hydrocarbon receptor, suggesting that FICZ enhanced keratinocyte migration in a mitogen-activated protein kinase/extracellular signal-regulated kinase-dependent, but aryl hydrocarbon receptor-independent, manner. The function of FICZ might indicate the possibility of its clinical use for intractable chronic wounds. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  1. A mutein of human basic fibroblast growth factor TGP-580 accelerates colonic ulcer healing by stimulating angiogenesis in the ulcer bed in rats.

    Science.gov (United States)

    Satoh, H; Szabo, S

    2015-10-01

    Previously, we reported that TGP-580, a mutein of human basic fibroblast growth factor (bFGF), accelerated the healing of gastric and duodenal ulcers in rats. In the present study, we examined the effect of TGP-580 on the healing of colonic ulcers. In male Sprague Dawley rats, ulcers were induced in the colon 6 cm from the anus by enema of 50 μl of 3% N-ethylmaleimide, a sulfhydryl alkylator. The lesions were examined under a dissecting microscope (x10). The concentration of bFGF in the ulcerated colon was measured by enzyme immunoassay, and both the distribution of bFGF and the density of microvessels in the ulcer bed were examined by immunohistochemical staining. The content of bFGF in the ulcerated colon was markedly increased associated with ulcer healing, and ulcer healing was significantly delayed by intravenous administration of a monoclonal antibody for bFGF (MAb 3H3) once daily for 10 days. In the ulcer bed, many cells such as fibroblasts, vascular endothelial cells and macrophages were positively stained with bFGF antiserum. TGP-580, human bFGF or dexamethasone was given intracolonally twice daily for 10 days, starting the day after ulcer induction. TGP-580 (0.2 - 20 μg/ml, 200 μl/rat) dose-dependently accelerated ulcer healing, and its effect was more than 10 times stronger than that of human bFGF. Density (μm/0.01 mm(2)) of microvessels in the ulcer bed was significantly increased by treatment with TGP-580, and there was a good correlation between the density of microvessels and the decrease of ulcerated area (R(2) = 0.633). On the other hand dexamethasone (20 μg/ml) inhibited angiogenesis in the ulcer bed and delayed ulcer healing. These results suggest that angiogenesis in the ulcer bed plays an important role in ulcer healing, and that bFGF mutein TGP-580 accelerated colonic ulcer healing, at least in part, by stimulating angiogenesis, whereas glucocorticoids may delay the healing by inhibiting angiogenesis.

  2. EXPERIMENTAL ANALYSIS OF THE HEALING PROCESS IN THE AREA OF TIBIAL BONE FRACTURE

    Directory of Open Access Journals (Sweden)

    I. F. Аkhtyamov

    2016-01-01

    Full Text Available Purpose. To quantify the density of the cortical bone of the tibia in the area of reparative regeneration and the state of the vascular bed (hemodynamics of the operated limb under intramedullary osteosynthesis using pins coated with titanium and hafnium nitrides. Materials and methods. In the experiment, changes in the bone density and the characteristics of the local blood supply were studied on 40 outbred rabbits which underwent intramedullary osteosynthesis by the use of pins with a nanocoating based on superhard compounds which consist of titanium and hafnium nitrides and pins without a coating. Using color Doppler mode helped to evaluate the condition of the vascular bed proximally to the fracture site. Results. It is noted that the use of pins with the described coating above did not violate the osteoregeneration staging. The density of the cortical bone in the test group exceeded that of the comparison group by an average of 30%. Bone remodeling processes in the test group completed at an earlier date, as determined by the higher rates of its density. In the study of the vascular bed of the operated limb, it was found that on the 10th day of the experiment, an increase in the maximal velocity of the blood flow was recorded (TAMAX. In animals of the test group this index approached preoperative values on the 30th day, while in animals of the comparison group this index approached the initial values only by the 60th day. Conclusion. The use of implants coated with titanium and hafnium nitrides which are characterized by high strength, thermal and chemical stability is accompanied by the formation of a cortical bone in the area of osteotomy with higher density characteristics. The changes which are typical of the vasodilatation in the area of injury in the early postoperative period can be regarded as a positive factor in the formation of primary bone union. In the group where implants coated with titanium and hafnium nitrides were used

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

    Energy Technology Data Exchange (ETDEWEB)

    Walter, M.N.M. [Institute for Science and Technology in Medicine, Keele University RJAH Orthopaedic Hospital, Oswestry, SY10 7AG (United Kingdom); School of Life and Health Science, Aston University, Aston Triangle, Birmingham, B4 7EJ (United Kingdom); Wright, K.T.; Fuller, H.R. [Institute for Science and Technology in Medicine, Keele University RJAH Orthopaedic Hospital, Oswestry, SY10 7AG (United Kingdom); MacNeil, S. [Kroto Research Institute and Centre for Nanoscience and Technology, Sheffield University, Sheffield, S1 2UE (United Kingdom); Johnson, W.E.B., E-mail: w.e.johnson@aston.ac.uk [School of Life and Health Science, Aston University, Aston Triangle, Birmingham, B4 7EJ (United Kingdom)

    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.

  4. Sesame oil accelerates healing of 2,4,6-trinitrobenzenesulfonic acid-induced acute colitis by attenuating inflammation and fibrosis.

    Science.gov (United States)

    Periasamy, Srinivasan; Hsu, Dur-Zong; Chandrasekaran, Victor Raj Mohan; Liu, Ming-Yie

    2013-09-01

    Sesame oil is a component of traditional health food in Asian countries. Acute colitis is a form of inflammatory bowel disease (IBD) with chronic inflammatory disorder of the bowel. The precise etiology of IBD remains unknown, but it is believed that an abnormal host response to endogenous antigens causes initial tissue injury with amplification of the immune response. We investigated the protective effect of sesame oil against 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute colitis in rats. Rats were intracolonically instilled with TNBS (120 mg/kg) using a cannula to induce colitis and then orally gavaged with sesame oil (4 mL/kg for 7 days) to attenuate TNBS-induced acute colitis. The acute colitis activity index (ACAI) was assessed using the colon weight/length ratio (mg/cm), thickness, extension of lesion, diarrhea, and macroscopic and microscopic damage scores. In addition, the degree of inflammation, mucins, and fibrosis was assessed by measuring mast cells, CD68(+) cells, neutral mucin, acidic mucin, collagen, and laminin on day 8 after inducing acute colitis. All tested parameters except neutral mucins were significantly higher in TNBS-induced acute colitis. Sesame oil significantly decreased the degree of inflammation, fibrosis, and acidic mucin and increased neutral mucin. We conclude that sesame oil accelerates the healing of an inflamed colon by inhibiting inflammation, acidic mucin, and fibrosis in TNBS-induced acute colitis in rats.

  5. Low dose erythropoietin stimulates bone healing in mice.

    Science.gov (United States)

    Garcia, P; Speidel, V; Scheuer, C; Laschke, M W; Holstein, J H; Histing, T; Pohlemann, T; Menger, M D

    2011-02-01

    Beyond its classical role in regulation of erythropoiesis, erythropoietin (EPO) has been shown to exert protective and regenerative actions in a variety of non-hematopoietic tissues. However, little is known about potential actions in bone regeneration. To analyze fracture healing in mice, a femoral 0.25 mm osteotomy gap was stabilized with a pin-clip technique. Animals were treated with 500 U EPO/kg bw per day or with vehicle only. After 2 and 5 weeks, fracture healing was analyzed biomechanically, radiologically and histologically. Expression of PCNA and NFκB was examined by Western blot analysis. Vascularization was analyzed by immunohistochemical staining of PECAM-1. Circulating endothelial progenitor cells were measured by flow-cytometry. Herein, we demonstrate that EPO-treatment significantly accelerates bone healing in mice. This is indicated by a significantly greater biomechanical stiffness and a higher radiological density of the periosteal callus at 2 and 5 weeks after fracture and stabilization. Histological analysis demonstrated significantly more bone and less cartilage and fibrous tissue in the periosteal callus. Endosteal vascularization was significantly increased in EPO-treated animals when compared to controls. The number of circulating endothelial progenitor cells was significantly greater in EPO-treated animals. The herein shown acceleration of healing by EPO may represent a promising novel treatment strategy for fractures with delayed healing and non-union formation.

  6. Topical treatment with the opioid antagonist naltrexone accelerates the remodeling phase of full-thickness wound healing in type 1 diabetic rats.

    Science.gov (United States)

    Immonen, Jessica A; Zagon, Ian S; Lewis, Gregory S; McLaughlin, Patricia J

    2013-10-01

    Wound repair involves a series of overlapping phases that include inflammation, proliferation, and tissue remodeling, with the latter phase requiring months for proper healing. Delays in any of these processes can result in infection, chronic ulceration, and possible amputation. Diabetes is a major risk factor for improper wound repair, and impaired wound healing is a major complication for more than 26 million people in the US diagnosed with diabetes. Previous studies have demonstrated that the opioid antagonist naltrexone (NTX) dissolved in moisturizing cream reverses delays in wound closure in streptozotocin-induced type 1 diabetic (T1D) rats. NTX accelerated DNA synthesis and increased the number of epithelial and mast cells, as well as new blood vessel formation. In this study, remodeling was evaluated in T1D rats up to eight weeks after initial wounding. Twenty days following wounding, diabetic rats treated with vehicle had elevated numbers of MMP-2+ fibroblasts, suggesting delayed healing processes; birefringence of granulation tissue stained with Sirius red revealed diminished collagen formation and maturation. Wound tissue from NTX-treated T1D rats had comparable numbers of MMP-2+ fibroblasts to control specimens, as well as accelerated maturation of granulation tissue. The integrity of wounded skin was evaluated by tensile strength measurements. T1D resulted in delayed wound healing, and wounded skin that displayed reduced tensile strength relative to normal rats. Topical NTX applied to wounds in T1D rats resulted in enhanced collagen formation and maturation over a 60-day period of time. Moreover, the force required to tear skin of NTX-treated T1D rats was elevated relative to the force necessary to tear the skin of vehicle-treated T1D rats, and comparable to that for normal rats. These data reveal that complications in wound healing associated with T1D involve the novel OGF-OGFr pathway, and that topical NTX is an effective treatment to enhance wound

  7. Allogeneic Transplantation of an Adipose-Derived Stem Cell Sheet Combined With Artificial Skin Accelerates Wound Healing in a Rat Wound Model of Type 2 Diabetes and Obesity.

    Science.gov (United States)

    Kato, Yuka; Iwata, Takanori; Morikawa, Shunichi; Yamato, Masayuki; Okano, Teruo; Uchigata, Yasuko

    2015-08-01

    One of the most common complications of diabetes is diabetic foot ulcer. Diabetic ulcers do not heal easily due to diabetic neuropathy and reduced blood flow, and nonhealing ulcers may progress to gangrene, which necessitates amputation of the patient's foot. This study attempted to develop a new cell-based therapy for nonhealing diabetic ulcers using a full-thickness skin defect in a rat model of type 2 diabetes and obesity. Allogeneic adipose-derived stem cells (ASCs) were harvested from the inguinal fat of normal rats, and ASC sheets were created using cell sheet technology and transplanted into full-thickness skin defects in Zucker diabetic fatty rats. The results indicate that the transplantation of ASC sheets combined with artificial skin accelerated wound healing and vascularization, with significant differences observed 2 weeks after treatment. The ASC sheets secreted large amounts of several angiogenic growth factors in vitro, and transplanted ASCs were observed in perivascular regions and incorporated into the newly constructed vessel structures in vivo. These results suggest that ASC sheets accelerate wound healing both directly and indirectly in this diabetic wound-healing model. In conclusion, allogeneic ASC sheets exhibit potential as a new therapeutic strategy for the treatment of diabetic ulcers.

  8. Bony healing of unstable thoracolumbar burst fractures in the elderly using percutaneously applied titanium mesh cages and a transpedicular fixation system with expandable screws.

    Directory of Open Access Journals (Sweden)

    Anica Eschler

    Full Text Available There is a high incidence of vertebral burst fractures following low velocity trauma in the elderly. Treatment of unstable vertebral burst fractures using the same principles like in stable vertebral burst fractures may show less favourable results in terms of fracture reduction, maintenance of reduction and cement leakage. In order to address these shortcomings this study introduces cementless fixation of unstable vertebral burst fractures using internal fixators and expandable intravertebral titanium mesh cages in a one-stage procedure via minimum-invasive techniques.A total of 16 consecutive patients (median age 76 years, range 58-94 with unstable thoracolumbar burst fractures and concomitant osteoporosis were treated by an internal fixator inserted via minimum invasive technique one level above and below the fractured vertebra. Fracture reduction was achieved and maintained by transpedicular placement of two titanium mesh cages into the fractured vertebral body during the same procedure. Intra- and postoperative safety of the procedure as well as analysis of reduction quality was analysed by 3D C-arm imaging or CT, respectively. Clinical and radiographic follow-up averaged 10.4 months (range 4.5-24.5.Stabilization of the collapsed vertebral body was achieved in all 16 cases without any intraoperative complication. Surgical time averaged 102 ± 6.6 minutes (71-194. The postoperative kyphotic angle (KA and Cobb angle revealed significant improvements (KA 13.7° to 7.4°, p < 0.001; Cobb 9.6° to 6.0°, p < 0.002 with partial loss of reduction at final follow-up (KA 8.3°, Cobb 8.7°. VAS (Visual Analogue Scale improved from 7.6 to 2.6 (p < 0.001. Adjacent fractures were not observed. One minor (malposition of pedicle screw complication was encountered.Cementless fixation of osteoporotic burst fractures revealed substantial pain relief, adequate maintenance of reduction and a low complication rate. Bony healing after unstable osteoporotic burst

  9. Dehydrated Human Amnion/Chorion Grafts May Accelerate the Healing of Ulcers on Free Flaps in Patients With Venous Insufficiency and/or Lymphedema

    OpenAIRE

    Miranda, Edward P.; Friedman, Alex

    2016-01-01

    Objective: Ulceration of free flaps in patients with venous insufficiency and/or lymphedema is an uncommon but challenging problem. We hypothesized that dehydrated human amnion/chorion membrane (Epifix) grafts would accelerate healing of these challenging ulcers. Methods: Retrospective analysis of prospectively acquired data identified 8 lower extremity free flaps with ulcerations in the context of venous insufficiency and/or lymphedema. The first 4 were flaps that had been treated with conse...

  10. Why most traumatic brain injuries are not caused by linear acceleration but skull fractures are.

    Directory of Open Access Journals (Sweden)

    Svein eKleiven

    2013-11-01

    Full Text Available Injury statistics have found the most common accident situation to be an oblique impact. An oblique impact will give rise to both linear and rotational head kinematics. The human brain is most sensitive to rotational motion. The bulk modulus of brain tissue is roughly five to six orders of magnitude larger than the shear modulus so that for a given impact it tends to deform predominantly in shear. This gives a large sensitivity of the strain in the brain to rotational loading and a small sensitivity to linear kinematics. Therefore, rotational kinematics should be a better indicator of traumatic brain injury risk than linear acceleration. To illustrate the difference between radial and oblique impacts, perpendicular impacts through the center of gravity of the head and 45o oblique impacts were simulated. It is obvious that substantially higher strain levels in the brain are obtained for an oblique impact, compared to a corresponding perpendicular one, when impacted into the same padding using an identical impact velocity. It was also clearly illustrated that the radial impact causes substantially higher stresses in the skull with an associated higher risk of skull fractures, and traumatic brain injuries secondary to those.

  11. Rotary self-locking intramedullary nail for long tubular bone fractures

    Institute of Scientific and Technical Information of China (English)

    HUANG Zhong-lian; YANG Hai-long; XU Jian-kun; XIA Xue; WANG Xin-jia; SONG Jian-xin; HU Jun

    2013-01-01

    Background Intramedullary nails had been widely used in the treatment of long-bone fractures because of less interference of fractures and center bearing biomechanical advantage.However,it had been also found many shortcomings such as broken nails,delayed healing and was modified in order to achieve better efficacy and reduce complications.The aim of the present study is to compare the efficacy of rotary self-locking intramedullary nails (RSIN) with that of interlocking intramedullary nails (IIN) in the treatment of long-bone fractures.Methods A retrospective study investigated 129 cases with long-bone fractures (36 with femoral fracture,81 with tibial fracture,and 12 with humeral fracture).The fractures were fixed using either an RSIN or IIN.All patients underwent followup for 12-30 months.Results All patients in both groups achieved a clinical fracture healing standard and the postoperative affected limb muscle strength and joint function were well restored.The RSIN group required a shorter operative time and the fracture healed faster.There was no significant difference in the hospital stay,intraoperative blood loss or postoperative complications between the two groups.Conclusions RSIN is used to treat long-bone fractures.Its healing efficacy is equivalent to the IIN.Moreover,the RSIN method is simpler and causes less tissue damage than the IIN,therefore having the advantage of accelerated healing.

  12. Acceleration of tendon healing using US guided intratendinous injection of bevacizumab: First pre-clinical study on a murine model

    Energy Technology Data Exchange (ETDEWEB)

    Dallaudière, Benjamin, E-mail: bendallau64@hotmail.fr [Service de Radiologie, Hôpital universitaire Bichat, Paris (France); Inserm U698, Hôpital universitaire Bichat, Paris (France); Université de Médecine Paris Diderot (France); Lempicki, Marta [Service de Radiologie, Hôpital universitaire Bichat, Paris (France); Université de Médecine Paris Diderot (France); Pesquer, Lionel [Centre d’Imagerie Ostéo Articulaire, Clinique du Sport de Bordeaux-Mérignac (France); Louedec, Liliane [Inserm U698, Hôpital universitaire Bichat, Paris (France); Preux, Pierre Marie [Laboratoire de Biostatistiques, Faculté de médecine, Limoges (France); Meyer, Philippe [Centre d’Imagerie Ostéo Articulaire, Clinique du Sport de Bordeaux-Mérignac (France); Hess, Agathe [Service de Radiologie, Hôpital universitaire Bichat, Paris (France); Université de Médecine Paris Diderot (France); Durieux, Marie Hèlène Moreau [Centre d’Imagerie Ostéo Articulaire, Clinique du Sport de Bordeaux-Mérignac (France); Hummel, Vincent; Larbi, Ahmed [Service de Radiologie, Hôpital universitaire Bichat, Paris (France); Deschamps, Lydia [Service d’ Anatomopathologie, Hôpital universitaire Bichat, Paris (France); and others

    2013-12-01

    Purpose: Tendinopathy shows early disorganized collagen fibers with neo-angiogenesis on histology. Peri-tendinous injection of corticosteroid is the commonly accepted strategy despite the abscence of inflammation in tendinosis. The aim of our study was to assess the potential of intratendinous injection of an anti-angiogenic drug (bevacizumab, AA) to treat tendinopathy in a murine model of patellar and Achilles tendinopathy, and to evaluate its local toxicity. Materials and method: Forty rats (160 patellar and Achilles tendons) were used for this study. We induced tendinosis (T+) in 80 tendons by injecting under ultrasonography (US) guidance Collagenase 1{sup ®} (day 0 = D0, patellar = 40 and Achilles = 40). Clinical examination and tendon US were performed at D3, immediately followed by either AA (AAT+, n = 40) or physiological serum (PST+, n = 40, control) US-guided intratendinous injection. Follow-up at D6 and D13 using clinical, US and histology, and comparison between the 2 groups were performed. To study AA toxicity we compared the 80 remaining normal tendons (T−) after injecting AA in 40 (AAT−). Results: All AAT+ showed a better joint mobilization compared to PST+ at D6 (p = 0.004) with thinner US tendon diameters (p < 0.004), and less disorganized collagen fibers and neovessels on histology (p < 0.05). There was no difference at D13 regarding clinical status, US tendon diameter and histology (p > 0.05). Comparison between AAT− and T− showed no AA toxicity on tendon (p = 0.18). Conclusion: Our study suggests that high dose mono-injection of AA in tendinosis, early after the beginning of the disease, accelerates tendon's healing, with no local toxicity.

  13. Effect of Combined Calcium Hydroxide and Accelerated Portland Cement on Bone Formation and Soft Tissue Healing in Dog Bone Lesions

    Directory of Open Access Journals (Sweden)

    Khorshidi H

    2015-09-01

    Full Text Available Statement of Problem: Recent literatures show that accelerated Portland cement (APC and calcium hydroxide Ca (OH2 may have the potential to promote the bone regeneration. However, certain clinical studies reveal consistency of Ca (OH2, as one of the practical drawbacks of the material when used alone. To overcome such inconvenience, the combination of the Ca (OH2 with a bone replacement material could offer a convenient solution. Objectives: To evaluate the soft tissue healing and bone regeneration in the periodontal intrabony osseous defects using accelerated Portland cement (APC in combination with calcium hydroxide Ca (OH2, as a filling material. Materials and Methods: Five healthy adult mongrel dogs aged 2-3 years old (approximately 20 kg in weight with intact dentition and healthy periodontium were selected for this study. Two one-wall defects in both mesial and distal aspects of the 3rd premolars of both sides of the mandible were created. Therefore, four defects were prepared in each dog. Three defects in each dog were randomly filled with one of the following materials: APC alone, APC mixed with Ca (OH2, and Ca (OH2 alone. The fourth defect was left empty (control. Upon clinical examination of the sutured sites, the amount of dehiscence from the adjacent tooth was measured after two and eight weeks, using a periodontal probe mesiodistally. For histometric analysis, the degree of new bone formation was estimated at the end of the eighth postoperative week, by a differential point-counting method. The percentage of the defect volume occupied by new osteoid or trabecular bone was recorded. Results: Measurement of wound dehiscence during the second week revealed that all five APCs had an exposure of 1-2 mm and at the end of the study all samples showed 3-4 mm exposure across the surface of the graft material, whereas the Ca (OH2, control, and APC + Ca (OH2 groups did not show any exposure at the end of the eighth week of the study. The most

  14. The effect of calcium and vitamin D3 supplementation on the healing of the proximal humerus fracture: a randomized placebo-controlled study

    DEFF Research Database (Denmark)

    Doetsch, A M; Faber, J; Lynnerup, N

    2004-01-01

    scan, WHO criteria), and not taking any drugs related to bone formation, including calcium or vitamin D supplementation, were randomly assigned to either oral 800 IU vitamin D3 plus 1 g calcium or placebo, in a double-blind prospective study. We measured biochemical, radiographic, and bone mineral......The purpose of this study was to (1) quantify the healing process of the human osteoporotic proximal humerus fracture (PHF) expressed in terms of callus formation over the fracture region using BMD scanning, and (2) quantify the impact of medical intervention with vitamin D3 and calcium......, with peak levels in week 6. By week 6 BMD levels were higher in the active group (0.623 g/cm2) compared with the placebo group (0.570 g/cm2, P = 0.006). Thirty seven percent of the patients presented with vitamin D levels below 30 nmol/l, indicative of mild vitamin D insufficiency. In conclusion, we have...

  15. Aloesin from Aloe vera accelerates skin wound healing by modulating MAPK/Rho and Smad signaling pathways in vitro and in vivo.

    Science.gov (United States)

    Wahedi, Hussain Mustatab; Jeong, Minsun; Chae, Jae Kyoung; Do, Seon Gil; Yoon, Hyeokjun; Kim, Sun Yeou

    2017-05-15

    Cutaneous wound healing is a complex process involving various regulatory factors at the molecular level. Aloe vera is widely used for cell rejuvenation, wound healing, and skin moisturizing. This study aimed to investigate the effects of aloesin from Aloe vera on cutaneous wound healing and mechanisms involved therein. This study consisted of both in vitro and in vivo experiments involving skin cell lines and mouse model to demonstrate the wound healing effects of aloesin by taking into account several parameters ranging from cultured cell migration to wound healing in mice. The activities of Smad signaling molecules (Smad2 and Smad3), MAPKs (ERK and JNK), and migration-related proteins (Cdc42, Rac1, and α-Pak) were assessed after aloesin treatment in cultured cells (1, 5 and 10µM) and mouse skin (0.1% and 0.5%). We also monitored macrophage recruitment, secretion of cytokines and growth factors, tissue development, and angiogenesis after aloesin treatment using IHC analysis and ELISAs. Aloesin increased cell migration via phosphorylation of Cdc42 and Rac1. Aloesin positively regulated the release of cytokines and growth factors (IL-1β, IL-6, TGF-β1 and TNF-α) from macrophages (RAW264.7) and enhanced angiogenesis in endothelial cells (HUVECs). Aloesin treatment accelerated wound closure rates in hairless mice by inducing angiogenesis, collagen deposition and granulation tissue formation. More importantly, aloesin treatment resulted in the activation of Smad and MAPK signaling proteins that are key players in cell migration, angiogenesis and tissue development. Aloesin ameliorates each phase of the wound healing process including inflammation, proliferation and remodeling through MAPK/Rho and Smad signaling pathways. These findings indicate that aloesin has the therapeutic potential for treating cutaneous wounds. Copyright © 2017 Elsevier GmbH. All rights reserved.

  16. Hyperforin/HP-β-Cyclodextrin Enhances Mechanosensitive Ca2+ Signaling in HaCaT Keratinocytes and in Atopic Skin Ex Vivo Which Accelerates Wound Healing

    Science.gov (United States)

    Takada, Hiroya; Yonekawa, Jun; Matsumoto, Masami; Sokabe, Masahiro

    2017-01-01

    Cutaneous wound healing is accelerated by mechanical stretching, and treatment with hyperforin, a major component of a traditional herbal medicine and a known TRPC6 activator, further enhances the acceleration. We recently revealed that this was due to the enhancement of ATP-Ca2+ signaling in keratinocytes by hyperforin treatment. However, the low aqueous solubility and easy photodegradation impede the topical application of hyperforin for therapeutic purposes. We designed a compound hydroxypropyl-β-cyclodextrin- (HP-β-CD-) tetracapped hyperforin, which had increased aqueous solubility and improved photoprotection. We assessed the physiological effects of hyperforin/HP-β-CD on wound healing in HaCaT keratinocytes using live imaging to observe the ATP release and the intracellular Ca2+ increase. In response to stretching (20%), ATP was released only from the foremost cells at the wound edge; it then diffused to the cells behind the wound edge and activated the P2Y receptors, which caused propagating Ca2+ waves via TRPC6. This process might facilitate wound closure, because the Ca2+ response and wound healing were inhibited in parallel by various inhibitors of ATP-Ca2+ signaling. We also applied hyperforin/HP-β-CD on an ex vivo skin model of atopic dermatitis and found that hyperforin/HP-β-CD treatment for 24 h improved the stretch-induced Ca2+ responses and oscillations which failed in atopic skin. PMID:28210627

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

    Science.gov (United States)

    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 (Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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

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

    OpenAIRE

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

    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 mi...

  20. 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.

    Science.gov (United States)

    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.

  1. Acceleration of fibroblast number and FGF-2 expression using Channa striata extract induction during wound healing process: in vivo studies in wistar rats

    Directory of Open Access Journals (Sweden)

    Gunawan Oentaryo

    2017-03-01

    Full Text Available Background: Wound healing is a biological process associated with tissue growth and regeneration. Wound healing process, is important to repair damaged tissue. Wound healing process consists of coagulation and hemostasis, inflammation, proliferation, as well as remodeling phases. The process can be accelerated by taking synthetic or non synthetic drugs. One of them is Channa striata extract. The extract contains albumin, copper, and zinc, which can be assumed to increase inflammatory cell infiltration, fibroblast proliferation, and collagen secretion. Purpose: This study aimed to reveal the effects of Channa striata extracts on fibroblast number and FGF-2 expression in mucosal wound healing process of the Wistar rats’ lower lip. Method: This research was a true laboratory experimental research with randomized post test only control group design. Samples of experiment were devided to experiment and control group that consist five samples each. Experimental group was treted with Channa striata extract and ethanol at concentration of 25%, 50%, and 100%. The fibroblast number and FGF-2 expresion were examined. Result: The number of fibroblasts in the treatment groups receiving Channa striata extract at concentrations of 25%, 50%, and 100% was higher than in the control group. The highest number of fibroblasts was found on day 3 at the concentration of 100% (p<0.05. Similarly, FGF-2 expression in the treatment groups receiving Channa striata at concentrations of 25%, 50%, and 100% was higher than in the control group. The highest expression of FGF-2 was found on day 3 at the concentration of 50% (p<0.05. Conclusion: Channa striata extract increased fibroblast number and FGF-2 expression in mucosa wound healing process.

  2. Effect of Simvastatin on Fracture Healing in Osteoporotic Rats%辛伐他汀对大鼠骨质疏松性骨折愈合的影响

    Institute of Scientific and Technical Information of China (English)

    田发明; 张柳; 骆阳; 宋亚琪; 杨方

    2012-01-01

    目的 观察骨质疏松对大鼠骨折愈合的影响及辛伐他汀对骨质疏松性骨折愈合的作用.方法 12周龄雌性Sprague-Dawley大鼠40只随机分成5组,每组8只:假手术组(A);卵巢切除组(B);正常骨折组(C);骨质疏松性骨折组(D);骨质疏松性骨折+辛伐他汀组(E).除A、C组外,其余各组大鼠行双侧卵巢切除术,C、D、E组于卵巢切除术4周后制作右股骨中段骨折模型;E组给予辛伐他汀灌胃干预(20 mg·kg-1·d-1),C、D组给等量生理盐水.A、B组于术后4周处死,测量右股骨骨密度;其余3组于骨折后6周处死,完整取出右侧股骨,行CR摄片并评分、骨密度测定、HE染色并镜下组织学观察.结果 ①卵巢切除后4周,B组骨密度(BMD)显著低于A组(P<0.05);②各骨折组右股骨骨密度:D、E组tBMD、mBMD和dBMD均显著低于C组(P<0.05),E组各段骨密度均高于D组,但差异无统计学意义(P>0.05);③CR摄片:D组与E组整体愈合情况较C组差,多数标本骨折线清晰,X线评分均显著低于C组,E组高于D组,但差别无统计学意义;④组织学观察:C组大鼠骨痂组织更为成熟,可见板层骨形成,D组、E组软骨成分比例明显较高,均未见板层骨形成.结论 骨质疏松大鼠骨折愈合较正常延迟,辛伐他汀可部分阻止去卵巢大鼠骨量丢失并表现出一定的促进骨折愈合的作用趋势,但效果并不显著.%OBJECTIVE To verify the delayed process of fracture healing in osteoporosis rats, as well as to investigate the effect of simvastatin on osteoprotic fracture healing. METHODS Fouty 12-week old female Sprague-Dawley rats were randomly divided into 5 groups with 8 animals in each group. All rats except those in group A and C rats received bilateral ovariectomy. The rats in group A received sham operation. The rats in group C, D and E underwent an operation 4 weeks after ovariectomy to establish the midshaft femur fracture model all fractured rats were

  3. 胫骨骨折不愈合28例临床分析%Analyses of 28 tibia fracture cases not healed

    Institute of Scientific and Technical Information of China (English)

    张庆凯

    2014-01-01

    目的:通过对28例胫骨骨折不愈合患者的临床治疗研究,分析造成其不愈合的原因。方法:收集我院自2005年6月至2013年5月8年间所收治的胫骨骨折不愈合患者28例,其中,男性16例,女性12例,年龄从12岁到73岁,平均38.7岁。交通事故所致17例,重物砸伤所致6例,摔伤所致4例,被别人打伤1例。闭合性骨折9例,开放性骨折19例。患者从首次治疗出院到再次入院时间在0.6—2年,均进行2次手术治疗,术后随访,并根据其症状、体征及影像学资料进行评估分析。结果:术后随访3-24个月,平均14个月,患者切口愈合良好,无感染,无皮肤坏死。全部患者未见骨不愈合、感染、畸形及再骨折发生。结论:胫骨骨折不愈合可以有胫骨本身解剖及生理特点,外伤程度及部位,手术治疗及术后功能锻炼等几个方面原因。%Objective:Through the clinic analyses of 20 cases of tibia fracture, found the reasons which caused the tibia fracture not healed Method:From Jane 2005 to May 2013, In the 8 Months, 28 cases with tibia fracture not healed were col ected. Including 16 males and 12 females , with an average of 38.7 years old .(range,12 to 73 years old).17 cases were caused by the traffic accident ,6 cases were caused by heavy parts ,4 cases were caused by fal damage,1 case was caused by a fight;9 closed fractures ,19 open fractures .It was about 0.6-2 years from the time that the patients left hospital after first treated to the time that the patients returned .Through the second operations, al the patients was fol owed up, According to the symptoms、signs and images, we carried a evaluate and analyses .Result:Al the cases were fol owed up for an average of 14 months (range, 3 to 24 months). The fractures of al the cases were recovered .There were no complications such as infection of wound , skin necrosis , yet infection of bone didn't healed, deformity and broken

  4. Antioxidant and anti-inflammatory potential of curcumin accelerated the cutaneous wound healing in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Kant, Vinay; Gopal, Anu; Pathak, Nitya N; Kumar, Pawan; Tandan, Surendra K; Kumar, Dinesh

    2014-06-01

    Prolonged inflammation and increased oxidative stress impairs healing in diabetics and application of curcumin, a well known antioxidant and anti-inflammatory agent, could be an important strategy in improving impaired healing in diabetics. So, the present study was conducted to evaluate the cutaneous wound healing potential of topically applied curcumin in diabetic rats. Open excision skin wound was created in streptozotocin induced diabetic rats and wounded rats were divided into three groups; i) control, ii) gel-treated and iii) curcumin-treated. Pluronic F-127 gel (25%) and curcumin (0.3%) in pluronic gel were topically applied in the gel- and curcumin-treated groups, respectively, once daily for 19 days. Curcumin application increased the wound contraction and decreased the expressions of inflammatory cytokines/enzymes i.e. tumor necrosis factor-alpha, interleukin (IL)-1beta and matrix metalloproteinase-9. Curcumin also increased the levels of anti-inflammatory cytokine i.e. IL-10 and antioxidant enzymes i.e. superoxide dismutase, catalase and glutathione peroxidase. Histopathologically, the curcumin-treated wounds showed better granulation tissue dominated by marked fibroblast proliferation and collagen deposition, and wounds were covered by thick regenerated epithelial layer. These findings reveal that the anti-inflammatory and antioxidant potential of curcumin caused faster and better wound healing in diabetic rats and curcumin could be an additional novel therapeutic agent in the management of impaired wound healing in diabetics.

  5. Parathyroid hormone and bone healing

    DEFF Research Database (Denmark)

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

    2010-01-01

    , no pharmacological treatments are available. There is therefore an unmet need for medications that can stimulate bone healing. Parathyroid hormone (PTH) is the first bone anabolic drug approved for the treatment of osteoporosis, and intriguingly a number of animal studies suggest that PTH could be beneficial...... in the treatment of fractures and could thus be a potentially new treatment option for induction of fracture healing in humans. Furthermore, fractures in animals with experimental conditions of impaired healing such as aging, estrogen withdrawal, and malnutrition can heal in an expedited manner after PTH treatment...

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

    Directory of Open Access Journals (Sweden)

    Sabrina Valente

    2016-01-01

    Full Text Available 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.

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

    Science.gov (United States)

    Valente, Sabrina; Ciavarella, Carmen; Pasanisi, Emanuela; Ricci, Francesca; Stella, Andrea; Pasquinelli, Gianandrea

    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.

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

    Directory of Open Access Journals (Sweden)

    Poh-Guat Cheng

    2013-01-01

    Full Text Available 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.

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

    Directory of Open Access Journals (Sweden)

    Hao-Jan Lin

    2014-01-01

    Full Text Available 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.

  10. Alveolar process fractures in the permanent dentition. Part 2. The risk of healing complications in teeth involved in an alveolar process fracture

    DEFF Research Database (Denmark)

    Lauridsen, Eva; Gerds, Thomas; Andreasen, Jens Ove

    2016-01-01

    for PN (age, fracture in relation to apex, displacement, gingival injury, degree of repositioning, type of splint, duration of splinting, treatment delay, and antibiotics) were analyzed for mature teeth using Cox regression. The level of significance was 5%. RESULTS: Immature: No severe complications (PN.......3-3.5), P = 0.003), and age >30 years (HR: 2.3 (95% CI: 1.1-4.6), P = 0.02). The type of splint (rigid or flexible), the duration of splinting (more or less than 4 weeks), and the administration of antibiotics did not affect the risk of PN. CONCLUSION: Teeth involved in alveolar process fractures appear......AIM: To analyze the risk of pulp canal obliteration (PCO), pulp necrosis (PN), repair-related resorption (RRR), infection-related resorption (IRR), ankylosis-related resorption (ARR), marginal bone loss (MBL), and tooth loss (TL) for teeth involved in an alveolar process fracture and to identify...

  11. Comparison of laser and diode sources for acceleration of in vitro wound healing by low-level light therapy.

    Science.gov (United States)

    Spitler, Ryan; Berns, Michael W

    2014-03-01

    Low-level light therapy has been shown to improve in vitro wound healing. However, well-defined parameters of different light sources for this therapy are lacking. The goal of this study was (1) to determine if the wavelengths tested are effective for in vitro wound healing and (2) to compare a laser and a light-emitting diode (LED) source at similar wavelengths. We show four wavelengths, delivered by either a laser or LED array, improved in vitro wound healing in A549, U2OS, and PtK2 cells. Improved wound healing occurred through increased cell migration demonstrated through scratch wound and transwell assays. Cell proliferation was tested by the (3-(4,5-dimethylthiazol-2-yl)-5-(3-car-boxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS) assay and was found generally not to be involved in the wound healing process. The laser and LED sources were found to be comparable when equal doses of light were applied. The biological response measured was similar in most cases. We conclude that the laser at 652 (5.57  mW/cm2, 10.02  J/cm2) and 806 nm (1.30  mW/cm2, 2.334  J/cm2) (full bandwidth 5 nm), and LED at 637 (5.57  mW/cm2, 10.02  J/cm2) and 901 nm (1.30  mW/cm2, 2.334  J/cm2) (full bandwidth 17 and 69 nm respectively) induce comparable levels of cell migration and wound closure.

  12. Rectal prolapse associated with a healed pelvic fracture in a pregnant free-ranging African black rhinoceros (Diceros bicornis. Part 2 : surgery and necropsy : case report

    Directory of Open Access Journals (Sweden)

    A. Olivier

    2001-07-01

    Full Text Available The oedematous and traumatised protruding section of the rectal tissue of an adult free-ranging female African black rhinoceros (Diceros bicornis was surgically amputated. Immediately before completion of surgery, the rhinoceros died of anaesthetic-related cardiac arrest. At necropsy a deformed pelvis and sacrum associated with a healed fracture of the left ileal wing were noted. New bone formation in and around the left ventral sacral foramina may have resulted in neuropathy of particularly the 3rd and 4th left ventral sacral nerves, which (in the horse supply the majority of the nerve fibres innervating the caudal rectum and anus. The cause of the injury is not known, although back injuries, presumably sustained during mating by bulls, have been recorded in white rhinoceros. An encounter with elephants could also have been responsible for the injury in this case.

  13. Arnebin-1 promotes the angiogenesis of human umbilical vein endothelial cells and accelerates the wound healing process in diabetic rats.

    Science.gov (United States)

    Zeng, Zhi; Zhu, Bang-Hao

    2014-07-03

    Zicao is a traditional wound healing herbal medicine that has been used for several hundred years in China. A survey of the published literatures revealed that arnebin-1, one of the naphthoquinone derivatives, played the most important role in wound healing property of this plant. However, whether arnebin-1 affects angiogenesis in vitro and has an effect on wound healing process in diabetic rats remains enigmatic. To investigate the effect of arnebin-1 with or without VEGF on proliferation, migration and tube formation of HUVECs in vitro and the effect of its topical application in the form of ointment on wound healing in a cutaneous punch wound model of alloxan-induced diabetic rats in vivo. The pro-angiogenic functions of arnebin-1 on HUVECs including proliferation, migration and angiogenesis were evaluated through MTT assay, wound healing assay, transwell assay and tube formation assay in vitro. Male Sprague-Dawley rats were injected intraperitoneally with alloxan to induce type І diabetic rats. Three wounds were created in each rat on the dorsal surface, and then divided to be basement treated, arnebin-1 ointment treated and untreated group correspondingly. The indicators including wound closure rate and histological evaluation were investigated on day 4 and 7 post-wounding. Without VEGF, arnebin-1 did not affect the proliferation of HUVECs significantly, but had a positive effect on cell migration and tube formation. However, in the presence of minimal VEGF, Arnebin-1 could increase the proliferation, enhance the migration and promote the tube formation of HUVECs significantly. The wound closure rate was increased significantly in arnebin-1 treated group compared to that of untreated and basement treated groups in diabetic rats, and the histological evaluation also showed well organized dermal layer, reduced number of macrophages, increased number of fibroblasts, remarkable degree of neovascularization and epithelization in arnebin-1 treated group. These

  14. Changes in the ultimate load and static bone histomorphometery parameters during the fracture healing process of denervated rats with tibial fracture%胫骨骨折大鼠失神经支配条件下骨折愈合过程中最大载荷及静态骨计量学参数变化

    Institute of Scientific and Technical Information of China (English)

    苗军; 刘春蓉; 夏群; 张继东; 金鸿宾

    2006-01-01

    背景:临床观察表明,截瘫患者骨折常常愈合加快或在下肢有异位骨化形成,表明周围神经系统对骨折愈合有重要的调节作用.目的:观察一侧下肢失神经胫骨骨折愈合过程中骨计量学参数及骨痂形成和生物力学的变化.设计:自身对照动物实验.单位:天津医院.材料:健康雄性Wistar大鼠36只,6个月龄,平均体质量210 g.方法:实验于2001-03/2004-03在天津医院动物实验中心完成.将大鼠一侧下肢制成失神经胫骨骨折模型,对侧制成正常神经支配骨折模型.骨折后2周、4周麻醉状态下处死大鼠,取双侧胫骨,拍X射线片、测定生物力学强度,制备不脱钙切片,进行骨计量学观察.主要观察指标:①两组大鼠骨折后双侧胫骨和骨痂湿质量比较.②X射线平片计分.③胫骨标本生物力学测试结果.④骨折愈合组织形态学观察.结果:①两组大鼠骨折后双侧胫骨和骨痂湿质量比较:骨折后2,4周失神经组重量远大于正常神经支配组[(0.94±0.15)比(0.76±0.14)g,(1.06±0.26)比(0.81±0.10)g,P<0.05].②X射线平片计分结果:失神经组骨痂形成量明显增多(P<0.01).③胫骨标本三点弯曲生物力学测试结果:骨折后2,4周失神经组骨痂的强度明显低于正常神经支配组[(9.88±8.49)比(16.62±13.38)N,(12.77±7.55)比(20.19±10.60)N,P<0.05].④骨计量学检测结果:静态参数与正常神经支配组比较,失神经组矿化骨小梁宽度明显减小(P<0.05),类骨质宽度增加,破骨细胞指数及骨吸收表面明显增大(P<0.05),成骨细胞指数及骨形成表面两组无差别;动态参数与正常神经支配组比较,失神经组矿化沉积率明显变小(P<0.05),类骨质成熟时间延长(P<0.05).结论:周围神经在骨折愈合早、中期起重要的调节作用,完整的神经支配是骨折愈合所必需的.%BACKGROUND: Clinical observation demonstrates that accelerated fracture healing or lower limb

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Abu Bakar Mohd Hilmi

    2013-01-01

    Full Text Available 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.

  17. Early changes of fracture healing on MRI%骨折愈合早期磁共振成像的实验研究

    Institute of Scientific and Technical Information of China (English)

    殷耀斌; 张力丹; 腾星; 程晓光; 王满宜

    2010-01-01

    Objective To observe MRI presentations of fracture healing process in the early stage.Methods Six New Zealand rabbits were used in the experiment. A union model of long oblique fracture of 1 mm in bone defect and 10 mm in vertical length was created on the right radius. A model of 10 mm bone defect was created on the left radius. X-ray and MRI examinations were performed in 1 w, 2 w, 4 w, 6 w, 8 w, 12 wafter the surgery and CT examination was performed in 4 w, 12 w after the surgery. The imaging presentations at the fracture sites were observed on T1, T2, FS-T2, PD, FS-PD sequences. Results The soft tissue around the fracture site presented high signals on T2, FS-T2, PD, FS-PD sequences in the early stage of fracture healing. The signals decreased as time went on, but turned intermediate at 6 w after surgery. The signals of bone marrow turned from high to intermediate on T1, T2 and PD sequences early after the surgery,but turned high again with the healing of medullary cavity. On FS-T2 and FS-PD sequences, bone marrow presented intermediate signals mixed with high signals, but the high signals subsided as time went by. Early changes of callus formation could be observed by MRI. Callus formation at the site of fracture showed intermediate signals in FS-T2 and FS-PD images obtained at 2 w after the surgery in the fracture union model. The changes above could not be observed in the bone defect model. Conclusions Callus formation may be predicted earlier by MRI than by X ray, especially on FS-T2 and FS-PD sequences. The MRI presentations of early fracture healing are to be confirmed by pathological examinations.%目的 探讨骨折愈合过程中磁共振成像(MRI)的表现及变化规律.方法 6只新西兰白兔右侧桡骨中段制造垂直长度为10 mm、断端间隙为1 mm的长斜形骨折愈合模型.左侧桡骨中段制造10 mm骨质缺损模型.于术后1、2、4、6、8、12周对动物模型行X线及MRI扫描,于术后4 周及12周行螺旋CT扫描,

  18. Multi-factors analysis on the healing of open fracture of tibia and fibula%影响胫腓骨开放性骨折愈合的多因素分析

    Institute of Scientific and Technical Information of China (English)

    赵国平; 苏伟; 赵劲民; 唐建东; 秦汉兴

    2012-01-01

    [Objective] To discuss the main factors affecting the healing of open fracture of tibia and fibula. [ Method ] Retrospective analysis of our hospital from May 2005 to February 201031 cases of treated open fractures of tibia and fibula information were gathered. Univariate logistic regression analysis were used including patients age,sex,cause of injury,associated injuries, fractures of other limbs,fracture type,the time from injury to debridement,fixation,the timing of the soft tissue closure, and the application of VSD etc. Above 10 factors were analyzed on the relationship to the healing rate. The binary logistic regression analysis of multiple factors was carried out. [ Result ] Univariate logistic regression revealed that causes of injury, fracture type, the time from injury to debridement, and the timing of the soft tissue closure were correlated with the healing rate of open fracture of tibia and fibula. Logistic regression analysis of multiple factors revealed that causes of injury, fracture type and the timing of the soft tissue closure were associated independently with the healing of open fracture of tibia and fibula, while the other factors were not statistically significant. [ Conclusion ] High-energy injuries is the risk factor of affecting healing of open fracture of tibia and fibula. There is a connection between the type and severity of fracture to the healing rate of open fractures of tibia and fibula. Early repair of soft tissue does have a benefit in the healing of open fractures of tibia and fibula.%[目的]探讨影响胫腓骨开放性骨折愈合的主要因素.[方法]回顾性分析本院从2005年5月~2010年2月5年间收治的81例胫腓骨开放性骨折的病历资料.采用单因素分析患者年龄、性别、致伤原因、合并伤、骨折肢别、骨折分型、从受伤至开始清创的时间、固定方式、软组织修复时机、VSD的应用等10项因素与骨折愈合率的关系,对以上有意义的因素进行二

  19. Porous microspheres as promising vehicles for the topical delivery of poorly soluble asiaticoside accelerate wound healing and inhibit scar formation in vitro &in vivo.

    Science.gov (United States)

    Zhang, Chen-Zhen; Niu, Jie; Chong, Yee-Song; Huang, Yan-Fen; Chu, Yang; Xie, Sheng-Yang; Jiang, Zhi-Hong; Peng, Li-Hua

    2016-12-01

    Asiaticoside is a natural compound possessing diverse pharmacological effects with great potential for clinical use. However, the low solubility and oil-water partition coefficient of asiaticoside lead to reduced effect and limited application. This study aims to construct a porous microsphere for the sustained release of asiaticoside to improve its absorption and enhance the therapeutic effects. Parameters of the formulations, including the drug to polymer ratio, solvent amounts of the inner and external phases, the stirring speed for preparation, and the drug entrapment efficiency were investigated and optimized. Particle size, morphology, pores structure, and Fourier transform infrared spectrum of the microsphere were characterized. The release kinetics and cellular uptake profiles of the asiaticoside-microspheres were examined. The therapeutic effects of asiaticoside-microspheres on wound healing and skin appendages regeneration were investigated in vitro & in vivo. Results showed that the optimized asiaticoside-microspheres possess spherical spongy structure with cylindrical holes. Asiaticoside can be loaded in the microsphere with high efficiency and released with sustained manner. The cellular uptake of asiaticoside from the microspheres was increased with 9.1 folds higher than that of free solution. Asiaticoside-microspheres expressed the strong promotion in the proliferation, migration of keratinocytes and wound scratching healing in vitro. More importantly, they significantly accelerated the re-epithelization, collagen synthesis and pro-angiogenesis in the rat full-skin wound healing. Porous microsphere was shown a novel carrier for the sustained delivery of poorly soluble asiaticoside, with absorption and therapeutic effects improved. Asiaticoside-microsphere is a promising topical preparation with excellent regenerative effects for the wound therapy.

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

    Science.gov (United States)

    2012-09-01

    protein for tooth enamel . Teeth and bones are related structures but have distinct components and cellular components Surgical results- animal...A fibrin adhesive seal for the repair of osteochondral fracture fragments. Clin Orthop Relat Res, 1984(182): p. 258-63. 33. Kim, S.S. and B.S. Kim...needle, and held in place while the needle was 158 retracted. The catheter was secured in place using tissue adhesive and transparent adhesive 159

  1. Combined application of low-intensity pulsed ultrasound and functional electrical stimulation accelerates bone-tendon junction healing in a rabbit model.

    Science.gov (United States)

    Hu, Jianzhong; Qu, Jin; Xu, Daqi; Zhang, Tao; Qin, Ling; Lu, Hongbin

    2014-02-01

    The objective of this study was to elucidate the combined use of low-intensity pulsed ultrasound (LIPUS) and functional electrical stimulation (FES) on patella-patellar tendon (PPT) junction healing using a partial patellectomy model in rabbits. LIPUS was delivered continuously starting day 3 postoperative until week 6. FES was applied on quadriceps muscles to induce tensile force to the repaired PPT junction 5 days per week for 6 weeks since week 7 postoperatively. Forty rabbits with partial patellectomy were randomly divided into four groups: control, LIPUS alone, FES alone, and LIPUS + FES groups. At week 12, the PPT complexes were harvested for histology, radiographs, peripheral quantitative computed tomography, and biomechanical testing. There was better remodeling of newly formed bone and fibrocartilage zone in the three treatment groups compared with the control group. LIPUS and/or FES treatments significantly increased the area and bone mineral content of new bone. The failure load and ultimate strength of PPT complex were also highly improved in the three treatment groups. More new bone formed and higher tensile properties were showed in the LIPUS + FES group compared with the LIPUS or FES alone groups. Early LIPUS treatment and later FES treatment showed the additive effects of accelerating PPT junction healing.

  2. alpha-Lipoic acid supplementation inhibits oxidative damage, accelerating chronic wound healing in patients undergoing hyperbaric oxygen therapy.

    Science.gov (United States)

    Alleva, Renata; Nasole, Emanuele; Di Donato, Ferruccio; Borghi, Battista; Neuzil, Jiri; Tomasetti, Marco

    2005-07-29

    Hyperbaric oxygen (HBO) therapy is successfully used for the treatment of a variety of conditions. However, prolonged exposure to high concentrations of oxygen induces production of reactive oxygen species, causing damage to the cells. Thus, antioxidant supplementation has been proposed as an adjuvant to attenuate such deleterious secondary effects. We evaluated the effects of alpha-lipoic acid (LA) in patients affected by chronic wounds undergoing HBO treatment. LA supplementation efficiently reduces both the lipid and DNA oxidation induced by oxygen exposure. LA exerted its antioxidant activity by directly interacting with free radicals or by recycling vitamin E. An inhibitory effect of LA on the pro-inflammatory cytokine interleukin-6 was observed. Taken together, we demonstrated an adjuvant effect of LA in HBO therapy used for impaired wound healing treatment. We propose that LA may be used to further promote the beneficial effects of HBO therapy.

  3. Thrombin related peptide TP508 promoted fracture repair in a mouse high energy fracture model

    Directory of Open Access Journals (Sweden)

    Pan Xiao-Hua

    2009-01-01

    Full Text Available Abstract Background Thrombin related peptide (TP508 is a 23 amino-acid synthetic peptide that represents a portion of the receptor-binding domain of thrombin molecule. Previous studies have shown that TP508 can accelerate musculoskeletal tissue repair including fracture healing. Objectives The aim of this study was to investigate the effect of TP508 on fracture healing in a murine fracture model representing high energy fracture situation. Methods Eighty CD 1 mice underwent controlled quadriceps muscle crush and open transverse mid diaphyseal femoral fracture that was then fixed with an external fixator. Animals were randomised into four groups to receive an intra-operative dose of either 100 μg TP508 into the fracture gap; 100 μg TP508 into the surrounding damaged muscle tissues; 10 μg TP508 into the fracture gap, or control equal amount of saline into the fracture gap. Radiographic assessment was performed weekly for 5 weeks; histological analysis was at 3 and 5 weeks post fracture and biomechanical testing of the fractured bone was performed at 5 weeks post fracture. Results Mechanical testing data showed that the fracture stiffness was significantly higher in the group receiving 100 μg TP508 into the fracture gap than other groups. Histological and radiographic analysis revealed a trend of increase in bone formation in the 100 μg TP508 injected into the fracture gap group compared to the saline control group. It was noted that the scar tissues was significantly less in Group II comparing with the saline control group and there was increased blood vessel formation in the crushed muscles and fracture gap areas in the groups receiving TP508 comparing to the saline control group. Conclusion The results from this study demonstrated the use of thrombin related peptide TP508 in the situation of a high energy fracture can promote fracture healing and reduce the potential complications such as muscle fibrosis and fracture delayed or non-union.

  4. Bone healing in 2016

    Science.gov (United States)

    Buza, John A.; Einhorn, Thomas

    2016-01-01

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

  5. 失神经对大鼠胫骨骨折愈合影响作用的实验研究%Experimental Study of Denervation of Rat Tibial Fracture Healing Effect

    Institute of Scientific and Technical Information of China (English)

    王永红; 汪玉良; 吴卓; 康学文; 康鑫

    2015-01-01

    目的:通过观察失神经后大鼠胫骨骨折的愈合情况,探讨中枢神经系统影响失神经骨折愈合的作用机制。方法将64只 SD 成熟雌性大鼠随机分为失神经骨折组、单纯骨折组,每组各32只。分别于术后第7、14、21、28天进行 BBB 评分,观察骨折愈合情况,并行左下肢骨折部位 X 线检查、胫骨湿重称量、骨痂体积测量,进行相关统计学分析。结果 BBB 行为学评分提示两组大鼠在术后各时间点具有统计学意义(P <0.05)。通过比较失神经骨折组与单纯骨折组 BBB 评分结果,提示在术后各时间点,失神经骨折组大鼠运动功能恢复速度明显减慢。X 线片提示失神经骨折组大鼠骨折处有大量骨痂生成,且愈合速度明显加快。在术后7天,两组大鼠胫骨湿重称量、骨痂体积测量则无统计学意义(P >0.05),而在术后14至28天,失神经骨折组与单纯骨折组相比,胫骨湿重称量、骨痂体积测量分别具有统计学意义(P <0.05),提示在失神经骨折中晚期会生成过量骨痂。结论中枢神经系统在骨折愈合中起重要的调节作用,完整的神经支配是骨折愈合的必要条件。%Objective By observing the healing after denervation of rat tibial fractures to investigate the mechanism of the central nervous system denervation affect fracture healing.Methods The 64 mature female SD rats were randomly divided into 2 groups including denervation fractures and fracture group,32 in each group.7,14,21 and 28 days after surgery,re-spectively,to assess the BBB score,fracture healing was observed,and in the left lower limb fracture site X-ray examination, tibia wet weighing callus volume measurement,the related statistical analysis was carried.Results The BBB behavioral scores showed two groups of rats at various time points after surgery have statistically significant (P 0.05),and in 14 to 28 days after surgery

  6. Degradation of impact fracture during accelerated aging of weld metal on microalloyed steel; Degradacion de la tenacidad al impacto durante el envejecimiento acelerado de soldadura en acero microaleado

    Energy Technology Data Exchange (ETDEWEB)

    Vargas-Arista, B.; Hallen, J. M.; Albiter, A.; Angeles-Chavez, C.

    2008-07-01

    The effect of accelerated aging on the toughness and fracture of the longitudinal weld metal on an API5L-X52 line pipe steel was evaluated by Charpy V-notch impact test, fracture analysis and transmission electron microscopy. Aging was performed at 250 degree centigrade for 100 to 1000 h. The impact results indicated a significant reduction in the fracture energy and impact toughness as a function of aging time, which were achieved by the scanning electron microscope fractography that showed a decrease in the vol fraction of microvoids by Charpy ductile failure with the aging time, which favored the brittle fracture by transgranular cleavage. The minimum vol fraction of microvoids was reached at 500 h due to the peak aged. The microstructural analysis indicated the precipitation of transgranular iron nano carbides in the aged specimens, which was related to the deterioration of toughness and change in the ductile to brittle behavior. (Author) 15 refs.

  7. Open or closed repositioning of mandibular fractures: is there a difference in healing outcome? A systematic review

    DEFF Research Database (Denmark)

    Andreasen, Jens Ove; Storgård Jensen, Simon; Kofod, Thomas

    2008-01-01

    The clinical outcome of closed vs open reduction and rigid fixation was compared based on a systematic review of the literature. Ten non-randomized retrospective studies were found. In six of these ten studies, the complication rate was significantly increased when open reduction and plating...... or wires. Nerve injuries were slightly increased when open reduction was found (although not significant). With regard to occlusal disturbances, no difference was found in the open and closed reduction group. Concerning overall complication problems, six of seven studies showed more problems after open...... in case of more complicated fractures cannot be excluded, which might explain the differences found between the two procedures. Prospective, randomized clinical trials are needed to illuminate this problem....

  8. 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

    Directory of Open Access Journals (Sweden)

    Xiao-na Zhang

    2016-01-01

    Full Text Available 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.

  9. 促进跟骨骨折内固定术后切口愈合的护理对策%Nursing Strategy of Promoting Incision Healing After Internal Fixation of Calcaneal Fractures

    Institute of Scientific and Technical Information of China (English)

    吴惠冰; 杜雪莲

    2014-01-01

    Objective To investigate nursing strategy of promoting incision healing after internal fixation of calcaneal fractures. Methods 121 patients with internal fixation of calcaneal fractures were divided into two groups. 60 cases of control group received routine nursing, while 61 cases of observation group received swelling care, pain care and wound care on the basis of routine nursing. The clinical outcomes were compared. Results Among 61 cases of observation group, there were 56 cases of incision healing within 14 days, 4 cases of poor partial involution (healing after one month of treatment) and one case of unhealed incision (caused by allograft rejection). Among 60 cases of control group, there were 39 cases of incision healing within 14 days, 15 cases of poor partial involution (healed after one month of treatment) and 6 cases of necrosis of local skin of incision (healing at 2 months after treatment). Conclusions Nursing intervention can promote the incision healing of calcaneal fractures surgery.%目的:探讨促进跟骨骨折内固定术后切口愈合的护理对策。方法将121例跟骨骨折内固定手术患者分为观察组及对照组,观察组在常规护理基础上,加强肿胀护理、疼痛护理、伤口护理,对照组予常规护理,比较两组的临床效果。结果观察组61例患者有56例切口14天愈合,4例切口局部对合差,经治疗1月内愈合,1例伤口不愈,为异体骨排斥引起;对照组60例患者有39例切口14天愈合,15例患者切口局部对合差,经治疗1月内愈合,6例患者伤口局部皮肤坏死,术后2个月愈合。结论护理干预可以促进跟骨骨折术后切口的愈合。

  10. The Effects of One Chinese Herbal Medicine on Fracture Healing of Rabbits%一剂复方中药对家兔骨骼愈合的影响

    Institute of Scientific and Technical Information of China (English)

    曲伟杰; 李进军; 王生奎

    2011-01-01

    The pathways of Chinese herbal medicine in fracture healing are not very well understood. Therefore, the objective of the present study was to evaluate the effects of one compound Chinese herbal medicine on rabbits radius fracture healing using indexes(such as the serum Ca. P, serum ALP, and X-ray of bone fracture). 48 healthy mature rabbits were selected to build standard defect models, and randomly divided into experimental groups and control groups. The control rabbits were given standard diet. Experimental rabbits were fed with standard diet plus Chinese herbal medicine (2. 5 g/kg) every day. The detection was performed on the 2,4,6 and 8 weeks after operation. The results of the study showed that the level of serum Ca, P, the activity of AKP and X-ray appearances for taking Chinese herbal medicine after fracture were significantly higher than that of the control. In conclusion, composite Chinese herbs might shorten the time to union, improve the quality of fracture healing and be beneficial to the fracture healing.%复方中药对骨折愈合的作用机制目前尚不明确,本试验通过观察复方中药对家兔桡骨骨折后血清钙、磷、碱性磷酸酶和X线影像学等指标的影响,分析该中药促骨愈合的效能及其可能作用机理.试验选用48只成年家兔,制成骨缺损标准模型,随机分为试验组和空白对照组,试验组每日在饲料中添加复方中药2.5 g/kg饲喂,对照组给予普通饲料.分别于术后2、4、6、8周进行生化指标和X线影像学检测.试验结果表明,试验组血清钙、血清磷、血清碱性磷酸酶及X线片评分骨折后明显高于对照组.该复方中药能缩短骨折愈合过程所需时间,提高骨折愈合质量,有利于骨折愈合.

  11. Bisphosphonate long-term treatment related bilateral subtrochanteric femoral fracture. Can teriparatide be useful?

    Science.gov (United States)

    Tarazona-Santabalbina, Francisco José; Aguilella-Fernández, Luis

    2013-10-01

    Long-term treatment with bisphosphonates has been related to atypical femoral fractures. We report the clinical case of a woman who suffered a proximal diaphyseal oblique fracture of the left femur after uninterrupted 13-year treatment with alendronate. Shortly after surgery, a painful lytic image in the external cortex of her right femur diaphysis was detected. Some papers have suggested surgical treatment to repair femur fractures after long-term treatment with bisphosphonates. Otherwise, two studies have shown healing acceleration of bone fractures with teriparatide. A lytic lesion was treated with teriparatide obtaining progressive disappearance of symptoms as well as bone healing. This outcome may suggest a way of prevention of complete fractures in symptomatic patients with long-term treatment with bisphosphonates.

  12. Anti-alpha-toxin monoclonal antibody and antibiotic combination therapy improves disease outcome and accelerates healing in a Staphylococcus aureus dermonecrosis model.

    Science.gov (United States)

    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; Sellman, Bret R

    2015-01-01

    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.

  13. Study of the impact of PDLLA in fracture healing%PDLLA可吸收材料髓内固定对骨折愈合的影响

    Institute of Scientific and Technical Information of China (English)

    凌卓彦; 史高龙; 陈礼; 董启榕

    2015-01-01

    Objective To compare the different effect of PDLLA absorbable materials and traditional metal fixation products for post-traumatic bone healing and osteogenesis/osteoclast.Methods The project will establish an open osteotomy model of SD rats using traditional metal internal fixation products (Kirschner) and PDLLA absorbable intramedullary rod fixation.We compared the osteoblasts/osteoclasts effects of the two materials by dynamic monitoring of relevant indicators of bone repair in wound healing process.Furthermore, wehaveanalyzed the signaling pathways and transcription factor expression levels of osteoblast/osteoclast differentiation and maturation in healing process.We thoroughly studied the differenceof the cellular and molecular mechanisms in the treatment of traumatic fractures by PDLLA intramedullary rod fixation and traditional metal products.We measured the soluble receptor activateor of nuclear factors-κB ligand (sRANKL), osteoprotegerin (OPG), RANKL, OPG by the enzyme linked immunosorbent assay (ELISA) to evaluate the fracture healing.We compared the osteoblasts/osteoclasts effects of the two materials by X-ray and MicroCT.We observed the protein of Wnt OPG and RANKL by histology method.Compared the expression of mRNA of Wnt OPG and RANKL by real-time quantitative polymerase chain reaction (Real-time PCR).Results At 4 and 6 weeks after surgery, compared to that of metal intramedullary fixation products, after using the PDLLA absorbable material for intramedullary fixation, the growth of trabecula in callus was significantly promoted [4 W: (0.522 ± 0.06) 1/mm;6 W: (0.709 ±0.06) 1/mm];The serum concentrations of sRANKL [4 W: (132.66 ± 2.87) ng/L;6 W: (131.08 ±2.09) ng/L], OPG [4W: (42.68 ± 3.99) ng/L;6 W: (44.88 ± 3.90) ng/L], and the ratio of OPG/sRANKL (4 W:0.34 ±0.06;6W:0.34 ±0.08) were significantly increased;The serum concentrations of TRACP-5b[4 W:(86.48 ±5.11) ng/L;6 W:(90.05 ±5.13) ng/L]was decreased(P <0.05).At 4 and 6 weeks after

  14. Experimental study and clinical observation of minimum-contact plate in long bone fracture

    Institute of Scientific and Technical Information of China (English)

    YANG Xin-jian; FEI Jun; WANG Zheng-guo; YU Hong-jun; SUN Jun

    2005-01-01

    Objective: To sutdy the mechanical properties and the clinical results of minimum-contact plate in the treatment of fractures. Methods: Four-point bending and torsion tests were conducted to compare the new minimum contact plate (MCP) with dynamic compression plate (DCP) and limited contact dynamic compression plate (LC-DCP). The fracture healing time and growth of bony callus were observed in 29 cases of long bone fracture fixed with MCP to evaluate the advantages of this kind of plate. Results: The 29 patients who underwent MCP were followed up from 6 to 14 months. The average healing time for femoral, tibial and humeral fractures was 12, 13 and 10 weeks, respectively. All fractures were healed. No displacement of fracture, screw pullout, deformation or break of the plate were found. Conclusions: The bending stiffness of MCP is significantly greater than that of DCP and LC-DCP (P<0.05). MCP can protect the periosteal blood supply against avascular osseous necrosis and accelerate bone healing. It is a kind of reliable and effective plate in treatment of fractures.

  15. Comparative study of the effect of ultrasound and electrostimulation on bone healing in rats.

    Science.gov (United States)

    Zorlu, U; Tercan, M; Ozyazgan, I; Taşkan, I; Kardaş, Y; Balkar, F; Oztürk, F

    1998-01-01

    This study was performed to compare the effects of direct current with ultrasound on fracture healing. Thirty-two rats were subjected to the experiment. Each rat's right legs were used as the experimental sample, and their left legs were used as the control. Four groups were formed, each consisting of 16 ultrasound, 16 electrostimulation, 16 ultrasound control, and 16 electrostimulation control animals. Fibular osteotome was applied to the rats under anesthesia. In the electrostimulation and electrostimulation control groups, a stainless steel cathode electrode was installed in the fractured side. In the electrostimulation group, 10 microA of direct current for 30 min, using a semi-invasive method, was given one day after fracture, for 15 days. On the control side, the aforementioned protocol was followed but sham treated. The ultrasound group was treated with 0.1 W/cm2 ultrasound for 2 min every second day for 6 days after fracture (4 times). Rats were killed on the 7th and 14th days to investigate the macroscopic, radiologic, and histopathologic parameters of fracture healing. There was a difference (P electrostimulation and the electrostimulation control groups on the 7th day. There was a difference (P electrostimulation groups, the fracture healing had been accelerated more so than in the control groups. There was no observed statistical difference between ultrasound and electrostimulation effects.

  16. Ultrasound stimulation of maxillofacial bone healing

    NARCIS (Netherlands)

    Schortinghuis, J; Stegenga, B; Raghoebar, GM; de Bont, LGM

    2003-01-01

    A substantial part of the maxillofacial surgery practice deals with maxillofacial bone healing. In the past decades, low-intensity ultrasound treatment has been shown to reduce the healing time of fresh fractures of the extremities up to 38%, and to heal delayed and non-unions up to 90% and 83%, res

  17. 丹参和内固定对胫骨远端骨折愈合的影响研究%Study on the Effect of Salvia Miltiorrhiza and Internal Fixation on the Healing of Distal Tibial Fractures

    Institute of Scientific and Technical Information of China (English)

    董晓强; 王海涛

    2016-01-01

    Objective To discuss the effect of different internal fixation treatment combined with Salvia miltiorrhiza for distal tibial fractures and defining the value of Salvia miltiorrhiza for fracture healing.Methods A retrospective analysis of therapeutic efficacy was made in Department of orthopedics of Chenggang Steel Hospital where there were 226 cases of emergency patients with internal fixation of distal tibial fractures according to the use of Salvia miltiorrhiza. They were divided into the Salvia miltiorrhiza group 114 cases (Salvia miltiorrhiza and pressure plate sub group, Salvia miltiorrhiza and LCP group, Salvia miltiorrhiza and intramedullary nail group) and the internal fixation group 112 cases(compression ifxation group, locking compression plate and intramedullary fixation sub group), in 1 week, 2 weeks, 4 weeks and 8 weeks after the treatment, comparison of callus formation, the postoperative hospitalization time and fracture healing made among groups. ResultsAt the same time after 2 weeks, the callus score of Salvia miltiorrhiza group was significantly better than the internal fixation group, and fracture healing time, postoperative hospitalization time were signiifcantly lower than those of the internal fixation group. The indicators of salvia miltiorrhiza and locking compression plate group were better than other groups,P<0.05, so the difference was significant. Conclusion Salvia miltiorrhiza combined with internal ifxation can signiifcantly improve fracture healing, and Salvia miltiorrhiza combined with locking pressurized plate internal fixation can be the best choice of tibial fractures treatment. The treatment effect is remarkable and fast healing.%目的:探讨丹参结合不同内固定方案治疗胫骨远端骨折的效果,明确丹参对于骨折愈合的价值。方法回顾性分析承钢医院骨科226例胫骨远端骨折患者急诊内固定手术的治疗效果,根据丹参使用分为丹参组114例(丹参与加压板亚组、

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

    Directory of Open Access Journals (Sweden)

    Eun Kyoung Jun

    2014-01-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  20. Effects of ultrashortwave and low frequency pulsed electromagnetic fields on the expression of vascular endothelial growth factor in fracture healing%超短波及低频脉冲磁疗对骨折愈合中血管内皮生长因子的影响

    Institute of Scientific and Technical Information of China (English)

    王珊珊; 毕然然; 崔宝娟; 代仁涛; 孙强三

    2009-01-01

    Objective To study the effects of uhrashortwave and low frequency pulsed electromagnetic fields on the expression of vascular endothelial growth factor(VEGF) in fracture healing. Methods Fifty-six New Zeal-and rabbits with artificial fractures were randomly divided into 4 groups:a control group,an ultrashortwave group,a low frequency pulsed electromagnetic field group and an ultrashortwave combined with low frequency pulsed electro-magnetic field group(combined group),with 14 in each group.Radiographic evaluation of callus formation and frac-ture healing,pathohistological examination and detection of VEGF expression through immunohistochemical staining were performed at the 1 st,2nd,4th and 6th week after the operation. Results Radiographic examination showed that there was significantly greater callus formation in the combined group than in the other groups throughout the healing process. Pathohistological examination also revealed significantly more cartilage islets and callus formation in the combined group.At the 1 st,2nd and 4th week after the operation,VEGF positive indexes in the combined group were significantly higher than in the other groups. Conclusion Uhrashortwave combined with low frequency pulsed electromagnetic field exposure can up-regulate the expression of VEGF and thus can accelerate fracture healing.%目的 观察超短波及低频脉冲磁疗对骨折愈合过程中血管内皮生长因子(VEGF)表达的影响.方法 选用新西兰大白兔56只,随机分为对照组、超短波治疗组(超短波组)、低频脉冲磁疗组(磁疗组)和超短波+低频脉冲磁疗组(联合组),每组14只.各组分别制备桡骨横断骨折模型.对照组不予干预,其余各组分别给予超短波及低频脉冲磁疗治疗.分别于术后第1,2,4,6周拍摄X线片,评价骨痂以及骨折愈合情况;于术后第1,2,4,6周取材行病理学检查,观察骨折愈合情况,并行免疫组织化学染色检测VEGF蛋白表达水平.结果 X

  1. Topical insulin accelerates wound healing in diabetes by enhancing the AKT and ERK pathways: a double-blind placebo-controlled clinical trial.

    Directory of Open Access Journals (Sweden)

    Maria H M Lima

    Full Text Available BACKGROUND: Wound healing is impaired in diabetes mellitus, but the mechanisms involved in this process are virtually unknown. Proteins belonging to the insulin signaling pathway respond to insulin in the skin of rats. OBJECTIVE: The purpose of this study was to investigate the regulation of the insulin signaling pathway in wound healing and skin repair of normal and diabetic rats, and, in parallel, the effect of a topical insulin cream on wound healing and on the activation of this pathway. RESEARCH DESIGN AND METHODS: We investigated insulin signaling by immunoblotting during wound healing of control and diabetic animals with or without topical insulin. Diabetic patients with ulcers were randomized to receive topical insulin or placebo in a prospective, double-blind and placebo-controlled, randomized clinical trial (NCT 01295177 of wound healing. RESULTS AND CONCLUSIONS: Expression of IR, IRS-1, IRS-2, SHC, ERK, and AKT are increased in the tissue of healing wounds compared to intact skin, suggesting that the insulin signaling pathway may have an important role in this process. These pathways were attenuated in the wounded skin of diabetic rats, in parallel with an increase in the time of complete wound healing. Upon topical application of insulin cream, the wound healing time of diabetic animals was normalized, followed by a reversal of defective insulin signal transduction. In addition, the treatment also increased expression of other proteins, such as eNOS (also in bone marrow, VEGF, and SDF-1α in wounded skin. In diabetic patients, topical insulin cream markedly improved wound healing, representing an attractive and cost-free method for treating this devastating complication of diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01295177.

  2. Mandibular Condyle Fractures and Treatment Modalities

    Directory of Open Access Journals (Sweden)

    Halil ibrahim Kisa

    2014-08-01

    Full Text Available Maxillofacial injuries are most commonly associated with falls, motor and vehicle accidents, sports-related trauma, and interpersonel violence. The complexity of mandibular condyle region and its anatomic proximity to other craniofacial structures complicate diagnosis and treatment. Thus, treatment approaches of mandibular condyle fracture are still controversial. In the literature, different success rates are reported about observation versus treatment, closed reduction versus open reduction and fixation methods. In the present article, controversial issues related to mandibular condyle fractures were reviewed under the light of current literature. In conclusion, the simplest way that can be done with the least risk of complication should be chosen during treatment planning. In addition, current adjunctive treatment methods accelerating healing of fracture should be considered. [Archives Medical Review Journal 2014; 23(4.000: 658-671

  3. Saliva and wound healing.

    Science.gov (United States)

    Brand, Henk S; Ligtenberg, Antoon J M; Veerman, Enno C I

    2014-01-01

    Oral wounds heal faster and with less scar formation than skin wounds. One of the key factors involved is saliva, which promotes wound healing in several ways. Saliva creates a humid environment, thus improving the survival and functioning of inflammatory cells that are crucial for wound healing. In addition, saliva contains several proteins which play a role in the different stages of wound healing. Saliva contains substantial amounts of tissue factor, which dramatically accelerates blood clotting. Subsequently, epidermal growth factor in saliva promotes the proliferation of epithelial cells. Secretory leucocyte protease inhibitor inhibits the tissue-degrading activity of enzymes like elastase and trypsin. Absence of this protease inhibitor delays oral wound healing. Salivary histatins in vitro promote wound closure by enhancing cell spreading and cell migration, but do not stimulate cell proliferation. A synthetic cyclic variant of histatin exhibits a 1,000-fold higher activity than linear histatin, which makes this cyclic variant a promising agent for the development of a new wound healing medication. Conclusively, recognition of the many roles salivary proteins play in wound healing makes saliva a promising source for the development of new drugs involved in tissue regeneration.

  4. Ephrin-B2 is differentially expressed in the intestinal epithelium in Crohn's disease and contributes to accelerated epithelial wound healing in vitro

    Institute of Scientific and Technical Information of China (English)

    Christian Hafner; Michael Landthaler; Thomas Vogt; Stefanie Meyer; Thomas Langmann; Gerd Schmitz; Frauke Bataille; Ilja Hagen; Bernd Becker; Alexander Roesch; Gerhard Rogler

    2005-01-01

    AIM: Eph receptor tyrosine kinases and their membrane bound receptor-like ligands, the ephrins, represent a bi-directional cell-cell contact signaling system that directs epithelial movements in development. The meaning of this system in the adult human gut is unknown. We investigated the Eph/ephrin mRNA expression in the intestinal epithelium of healthy controls and patients with inflammatory bowel disease (IBD).METHODS: mRNA expression profiles of all Eph/ephrin family members in normal small intestine and colon were established by real-time RT-PCR. In addition, differential expression in IBD was investigated by cDNA array technology, and validated by both real-time RT-PCR and immunohistochemistry. Potential effects of enhanced EphB/ephrin-B signaling were analyzed in an in vitro IEC-6 cell scratch wound model.RESULTS: Human adult intestinal mucosa exhibits a complex pattern of Eph receptors and ephrins. Beside the known prominent co-expression of EphA2 and ephrinA1,we found abundantly co-expressed EphB2 and ephrin-B1/2.Interestingly, cDNA array data, validated by real-time PCR and immunohistochemistry, showed upregulation of ephrin-B2 in both perilesional and lesional intestinal epithelial cells of IBD patients, suggesting a role in epithelial homeostasis. Stimulation of ephrin-B signaling in ephrinB1/2 expressing rat IEC-6-cells with recombinant EphB1Fc resulted in a significant dose-dependent acceleration of wound closure. Furthermore, fluorescence microscopy showed that EphB1-Fc induced coordinated migration of wound edge cells is associated with enhanced formation of lamellipodial protrusions into the wound, increased actin stress fiber assembly and production of laminin at the wound edge.CONCLUSION: EphB/ephrin-B signaling might represent a novel protective mechanism that promotes intestinal epithelial wound healing, with potential impact on epithelial restitution in IBD.

  5. The Waywardness of Knee Joint Affect Fracture Healing(annexal three Example Clinical Analysis)%膝关节不稳对骨折愈合的影响(附3例临床分析)

    Institute of Scientific and Technical Information of China (English)

    黄枫; 曾志奎; 黄学员; 曾展鹏

    2011-01-01

    Objective: To investigate the waywardness of knee joint affect fracture Healing. Methods: To review our hospital adduct three patients who because of fail to make a definite diagnosis of the Cruciate ligaments of knee joint injuries,which induce the homonymy Fracture of shaft of femur postoperative disunion. Author from the biomechanics point of view to analyze,cruciate ligament is very important to the steady of knee joint,conversely after the injuries of knee joint to mean a certain degree loss of physiological move-ment,as well as load conduction disturbance Followed by,which lead to the waywardness of knee joint. The waywardness of knee joint cause the stress of broken ends of fractured bone modify,which will bring what influence to fracture healing. Results: If we do not repair the injured cruciate ligament in time.when the patient who is postoperative of Fracture of shaft of femur is doing contineous passive motion or contineous passive motion working, there will be one shearing and revolving stress transmit to broken ends of fractured bone, meanwhile Vertical compressive stress of legs is hard to transmit to broken ends of fractured bone.which is likely to induce Fracture of shaft of femur to defer union even disunion. Conclusion: The waywardness of knee joint cause the stress of broken ends of fractured bone in homonymy limbs modify,which is likely to induce fracture to defer union even disunion.%目的:探讨膝关节不稳对骨折愈合的影响.方法:回顾性分析我院收治3例患者因早期未能准确诊治膝关节交叉韧带损伤,而导致同侧股骨干骨折术后不愈合的临床资料.我们从生物力学角度分析,交叉韧带对膝关节生理性制导及稳定作用,反之损伤后膝关节的生理运动一定程度的丧失,以及随之而来的载荷传导紊乱,从而导致膝关节不稳.膝关节不稳所引起骨折端应力改变,其对骨折愈合将产生怎样的影响.结果:如未能及时修复交叉韧带在患者

  6. Thermo-mechanical, Wear and Fracture Behavior of High-density Polyethylene/Hydroxyapatite Nano Composite for Biomedical Applications:Effect of Accelerated Ageing

    Institute of Scientific and Technical Information of China (English)

    H.Fouad; R.Elleithy; Othman Y.Alothman

    2013-01-01

    The objective of this work is to demonstrate how the viscoelastic,thermal,rheological,hardness,wear resistance and fracture behavior of bioinert high-density polyethylene (HDPE) can be changed by the addition of hydroxyapatite (HAP) nano particles.Also the effects of accelerated thermal ageing on the composite properties have been investigated.Different weight fractions of HAP nano particles up to 30 wt% have been incorporated in HDPE matrix by using melt blending in co-rotating intermeshing twin screw extruder.The fracture toughness results showed a remarkable decrease in proportion to the HAP content.The differential scanning calorimetry results indicated that the melting temperature and crystallinity were affected by the addition of HAP nano particles into the matrix.The complex viscosity increased as the percentage of HAP increased due to the restriction of the molecular mobility.The dynamic mechanical analysis results revealed that higher storage modulus (8.3 1011 Pa) could be obtained in the developed HDPE/HAP in 30 wt% compared to neat HDPE (5.1 1011 Pa).Finally,the hardness and wear resistance of HDPE were improved significantly due to the addition of HAP nano particles.The changes in the HDPE and its nano composite properties due to ageing showed that the HDPE and its hang composites crystallinity increased while the fracture toughness,hardness,wear resistance,storage and loss modulus decreased.

  7. Limited open reduction is better for simple- distal tibial shaft fractures than minimally invasive plate osteosynthesis.

    Science.gov (United States)

    Li, Q; Zeng, B F; Luo, C F; Song, S; Zhang, C Q; Kong, W Q

    2014-07-24

    The aim of this study was to compare the effects and indications of minimally invasive plate osteosynthesis (MIPO) and limited open reduction (LOR) for managing distal tibial shaft fractures. A total of 79 cases of distal tibial shaft fractures were treated surgically in our trauma center. The 79 fracture cases were classified into type A, B, and C (C1) according to the Arbeitsgemeinschaft für Osteosynthesefragen (AO) classification, with 28, 32, and 19 cases, respectively. Among the 79 fracture cases, 52 were closed fractures and 27 were open fractures (GUSTILO, I-II). After adequate preparation, 48 cases were treated with LOR and 31 cases were treated with MIPO. All cases were followed up for 12 to 18 months, with an average of 16.4 months. During the follow-up period, 76 fracture cases were healed in the first stage, whereas the 3 cases that developed non-union were treated by changing the fixation device and autografting. For types A, B, and some of C simple fractures (C1), LOR accelerated the fracture healing and lowered the non-union rate. One case suffered from regional soft tissue infection, which was controlled by wound dressing and intravenous antibiotics. Another case that developed local skin necrosis underwent local flap transplant. LOR promoted bone healing and lowered the non-union rate of several simple-distal tibial shaft fractures. Thereafter, the incidence of soft tissue complication was not significantly increased. However, for complex and comminuted fractures, MIPO was the preferred method for correcting bone alignment and protecting soft tissue, leading to functional recovery.

  8. TSG-6 released from intradermally injected mesenchymal stem cells accelerates wound healing and reduces tissue fibrosis in murine full-thickness skin wounds.

    Science.gov (United States)

    Qi, Yu; Jiang, Dongsheng; Sindrilaru, Anca; Stegemann, Agatha; Schatz, Susanne; Treiber, Nicolai; Rojewski, Markus; Schrezenmeier, Hubert; Vander Beken, Seppe; Wlaschek, Meinhard; Böhm, Markus; Seitz, Andreas; Scholz, Natalie; Dürselen, Lutz; Brinckmann, Jürgen; Ignatius, Anita; Scharffetter-Kochanek, Karin

    2014-02-01

    Proper activation of macrophages (Mφ) in the inflammatory phase of acute wound healing is essential for physiological tissue repair. However, there is a strong indication that robust Mφ inflammatory responses may be causal for the fibrotic response always accompanying adult wound healing. Using a complementary approach of in vitro and in vivo studies, we here addressed the question of whether mesenchymal stem cells (MSCs)-due to their anti-inflammatory properties-would control Mφ activation and tissue fibrosis in a murine model of full-thickness skin wounds. We have shown that the tumor necrosis factor-α (TNF-α)-stimulated protein 6 (TSG-6) released from MSCs in co-culture with activated Mφ or following injection into wound margins suppressed the release of TNF-α from activated Mφ and concomitantly induced a switch from a high to an anti-fibrotic low transforming growth factor-β1 (TGF-β1)/TGF-β3 ratio. This study provides insight into what we believe to be a previously undescribed multifaceted role of MSC-released TSG-6 in wound healing. MSC-released TSG-6 was identified to improve wound healing by limiting Mφ activation, inflammation, and fibrosis. TSG-6 and MSC-based therapies may thus qualify as promising strategies to enhance tissue repair and to prevent excessive tissue fibrosis.

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

    NARCIS (Netherlands)

    Chong, H.C.; Goh, C.Q.; Gounko, N.V.; Luo, B.; Wang, X.; Kersten, A.H.

    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.

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

    NARCIS (Netherlands)

    Chong, H.C.; Goh, C.Q.; Gounko, N.V.; Luo, B.; Wang, X.; Kersten, A.H.

    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.

  11. 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.

    Science.gov (United States)

    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.

  12. Treatment of diabetic mice with undenatured whey protein accelerates the wound healing process by enhancing the expression of MIP-1α, MIP-2, KC, CX3CL1 and TGF-β in wounded tissue

    Directory of Open Access Journals (Sweden)

    Badr Gamal

    2012-06-01

    Full Text Available Abstract Background Continuous diabetes-associated complications are a major source of immune system exhaustion and an increased incidence of infection. Diabetes can cause poor circulation in the feet, increasing the likelihood of ulcers forming when the skin is damaged and slowing the healing of the ulcers. Whey proteins (WPs enhance immunity during childhood and have a protective effect on some immune disorders. Therefore, in this study, we investigated the effects of camel WP on the healing and closure of diabetic wounds in a streptozotocin (STZ-induced type I diabetic mouse model. Results Diabetic mice exhibited delayed wound closure characterized by a significant decrease in an anti-inflammatory cytokine (namely, IL-10 and a prolonged elevation of the levels of inflammatory cytokines (TNF-α, IL-1β and IL-6 in wound tissue. Moreover, aberrant expression of chemokines that regulate wound healing (MIP-1α, MIP-2, KC and CX3CL1 and growth factors (TGF-β were observed in the wound tissue of diabetic mice compared with control nondiabetic mice. Interestingly, compared with untreated diabetic mice, supplementation with WP significantly accelerated the closure of diabetic wounds by limiting inflammatory stimuli via the restoration of normal IL-10, TNF-α, IL-1β and IL-6 levels. Most importantly, the supplementation of diabetic mice with WP significantly modulated the expression of MIP-1α, MIP-2, KC, CX3CL1 and TGF-β in wound tissue compared with untreated diabetic mice. Conclusion Our data demonstrate the benefits of WP supplementation for improving the healing and closure of diabetic wounds and restoring the immune response in diabetic mice.

  13. Improved Transplanted Stem Cell Survival in a Polymer Gel Supplemented With Tenascin C Accelerates Healing and Reduces Scarring of Murine Skin Wounds.

    Science.gov (United States)

    Yates, Cecelia C; Nuschke, Austin; Rodrigues, Melanie; Whaley, Diana; Dechant, Jason J; Taylor, Donald P; Wells, Alan

    2017-01-24

    Mesenchymal stem cells (MSCs) remain of great interest in regenerative medicine because of their ability to home to sites of injury, differentiate into a variety of relevant lineages, and modulate inflammation and angiogenesis through paracrine activity. Many studies have found that despite the promise of MSC therapy, cell survival upon implant is highly limited and greatly reduces the therapeutic utility of MSCs. The matrikine tenascin C, a protein expressed often at the edges of a healing wound, contains unique EGF-like repeats that are able to bind EGFR at low affinities and induce downstream prosurvival signaling without inducing receptor internalization. In this study, we utilized tenascin C in a collagen/GAG-based polymer (TPolymer) that has been shown to be beneficial for skin wound healing, incorporating human MSCs into the polymer prior to application to mouse punch biopsy wound beds. We found that the TPolymer was able to promote MSC survival for 21 days in vivo, leading to associated improvements in wound healing such as dermal maturation and collagen content. This was most marked in a model of hypertrophic scarring, in which the scar formation was limited. This approach also reduced the inflammatory response in the wound bed, limiting CD3e+ cell invasion by approximately 50% in the early wound-healing process, while increasing the numbers of endothelial cells during the first week of wound healing as well. Ultimately, this matrikine-based approach to improving MSC survival may be of great use across a variety of cell therapies utilizing matrices as delivery vehicles for cells.

  14. Toe and Metatarsal Fractures (Broken Toes)

    Science.gov (United States)

    ... rest is the only treatment needed to promote healing of a stress or traumatic fracture of a metatarsal bone. Avoid the offending activity. Because stress fractures result from repetitive stress, it ...

  15. 信号选择性甲状旁腺素模拟肽促进去势雄性小鼠的骨折愈合%Effects of signaling-selective parathyroid hormone peptide analog on fracture healing in orchiectomized mouse models

    Institute of Scientific and Technical Information of China (English)

    袁亮; 林振; 付兆宗; 孟越; 黄志平; 吴秀华; 杨德鸿; 江建明

    2013-01-01

    Objective To assess the effect of intermittent subcutaneous injections of signal-selective parathyroid hormone (PTH) peptide analog on fracture healing in orchiectomized mouse models. Methods Thirty-six 7-week-old C57/BL male mice were orchiectomized and injected with hPTH(l-34), the signal-selective PTH peptide analog [Gly1, Arg19]hPTH (1-34), or an identical volume of vehicle 1 week after induction of femoral fracture. At 14 and 28 days after the operation, the mice were sacrificed for measurement of bone mineral density (BMD) and bone mineral content (BMC) of the callus using by dual energy X-ray absorptiometry. The bone healing was evaluated by radiography, biomechanical testing, micro-computed tomography (Micro-CT) and histological examination. Results At 14 days after the operation, BMD in PTH peptide analog group was significantly increased (P<0.05). The mouse models treated with the PTH peptide analog showed significantly lower ultimate bending force and bending rigidity than those with hPTH(l-34) treatment. X-ray and Micro-CT scanning showed that callus transformation and remodeling was better in PTH peptide analog group than in the vehicle control group but poorer than in hPTH(l-34) group. Conclusion The signaling-selective PTH peptide analog G1, R19 (1-28) can accelerate fracture healing in orchiectomized mouse models, in which process cAMP/PKA pathway plays an important role.%目的 观察间断皮下注射信号选择性甲状旁腺素(PTH)模拟肽对去势雄性小鼠骨折愈合的影响.方法 36只7周龄C57/BL雄性小鼠去势,1周后制作股骨中段骨折模型,术后用人重组甲状旁腺素(hPTH(1-34)),信号选择性PTH模拟肽[Gly1,Arg19] hPTH (1-34)(G1,R19(1-28))和等量溶解剂注射,于术后14d和28 d处死,双能X线骨密度仪测量骨痂区骨密度以及骨矿物含量;术侧骨折愈合情况通过X线、显微CT、生物力学和组织学显示.结果 术后14d,G1,R19(1-28)组骨密度显著高于对照组(P<0.05).

  16. Effect of different hemostasis methods on operative incision healing of calcaneal fracture%不同止血方法对跟骨骨折手术切口愈合的影响

    Institute of Scientific and Technical Information of China (English)

    代灿; 苟景跃; 邓子龙; 张晓星

    2016-01-01

    目的:观察和对比分析电凝止血、钳夹止血及压迫止血对跟骨骨折手术切口愈合的影响。方法收集2012年12月~2015年12月收治的60例66足跟骨骨折患者临床资料,其中男性48例,女性12例;年龄18~59岁,平均36.6岁。均经跟骨外侧L形切口行切开复位钛板内固定术,术中止血方法分别采用电凝止血、钳夹止血及压迫止血。记录三组患者年龄、骨折分型、伤后至手术时间、手术时间、切口干燥时间、切口愈合时间、切口并发症发生率及足部功能Maryland评分等,并进行统计学分析。结果在切口干燥时间、切口愈合时间及切口并发症等方面钳夹止血组显著优于电凝止血组和压迫止血组(P<0.05),而电凝止血组和压迫止血组之间无显著性差异(P>0.05),三组足部功能Maryland评分无显著性差异(P>0.05)。结论跟骨骨折术中行钳夹止血可明显降低切口并发症的发生率。%Objective To observe and compare the effects of electrocoagulation hemostasis, forceps hemo-stasis and compression hemostasis on the operative incision healing in calcaneal fracture patients.Methods From Dec.2012 to Dec.2015,60 patients with calcaneal fracture were treated.Among them 48 were male and 12 were fe-male ranged from 18 to 59 years(average,36.6 years).All cases (66 calcaneal fractures) were treated by open re-duction and internal fixation through L-type calcaneal lateral incision.Intra-operative hemostasis methods included the electrocoagulation hemostasis, forceps hemostasis and compression hemostasis. Indexes such as age, fracture classification,time from injury to operation,operation time,drying time and healing time of the incision,incidence of incision-related complications and Maryland foot function score among the 3 groups were recorded and statistically analyzed.Results The forceps hemostasis group was significantly better than the electrocoagulation

  17. Effect of He-Ne Laser and CO2 Laser on Bone Fracture Healing%He-Ne激光与扩束CO2激光照射对骨折愈合的影响

    Institute of Scientific and Technical Information of China (English)

    崔建胜; 章萍

    2011-01-01

    目的 比较相同剂量的He-Ne激光与CO激光照射对骨折的疗效.方法 36只健康雄性兔制成骨折模型,随机分为三组,每组12只.He-Ne激光组:He-Ne激光扩束照射骨折区;CO激光组:CO激光扩束照射骨折组;对照组:常规治疗.通过X片,观察骨折愈合情况,测定骨痂中钙和胶原含量及生物力学抗扭性能,比较三组的疗效.结果 (1)骨折愈合效果:两激光组均优于对照组(P激光组优于He-Ne激光组(P激光组好于He-Ne激光组(P)和瞬间扭矩(T)均高于对照组(P激光组T高于He-Ne激光组.结论 He-Ne激光与CO激光照射对骨折愈合均有促进作用,且CO激光更好于He-Ne激光.%Objective To obsere and compare the discrepancy of curative effect of He-Ne laser and CO2 laser irradiation under the same dosage.Methods The bone fracture pattern was made to 36 healthy male rabbits, who were randomly divided into 3 groups ( each 12) : He-Ne laser group: expanding a bunch of the He-Ne laser project light upon the bone fracture zone, CO2 laser group: expanding a bunch of the CO2 laser irradiation, and matched control group:the routine cures.The different therapy impact was observed on the bone fracture healing.Observed X-ray, detected the contents of collagen and calcium in the callus, and measured the biomechanics anti-torsion strength to evaluate curative effect.Results ( 1 ) Fracture healing effect: the two laser groups were better than the control group (P <0.05 or <0.01 ), and 25 days after treatment, CO2 laser group was better than He-Ne laser group ( P < 0.04 ).(2) Collagen and calcium content: two laser groups were higher than control group (P < 0.05), and CO2 laser group was better than He-Ne laser group ( P < 0.05 ).(3) Biomechanics anti-torsion strength: the minimum torque ( T8°) and instantaneous torque (Tmax) of both laser groups were higher than that of control group (P <0.01 ), and the Tmax of CO2 laser group was higher than that of He-Ne laser group

  18. 接骨木总苷片促进骨折愈合与抗炎作用研究Ⅰ%Study on Effects of Sambucus williamsii Total Glycosides Tablets on Fracture Healing and Inflammation: Part Ⅰ

    Institute of Scientific and Technical Information of China (English)

    杨炳友; 何娅雯; 朱晓清; 韩华; 杨柳; 王秋红; 匡海学

    2014-01-01

    目的:研究接骨木总苷片促进骨折愈合与抗炎作用.方法:复制兔骨折模型.60只新西兰大白兔随机均分为正常对照(等容生理盐水)组、模型(等容生理盐水)组、跌打丸(0.28 g/kg)组与接骨木总苷片高、中、低剂量(0.22、0.11、0.06 g/kg)组,以药物加入饲料给药,连续36 d.骨密度仪测定骨密度(BMD)、骨矿含量(BMC)、骨痂面积(Area),通过X光片观察兔骨折愈合程度.采用小鼠耳肿胀和大鼠足肿胀模型观察其抗炎作用,热板法观察其镇痛作用.结果:高、中、低剂量接骨木总苷片可增加模型大白兔BMD、BMC,使模型大白兔骨折断端接近消失,骨膜反应密度加深,骨痂量增多、增深;中剂量组接骨木总苷片可增加模型大白兔Area.高、中、低剂量接骨木总苷片可减轻模型小鼠耳肿胀度,降低模型大鼠足肿胀率,提高1h内模型小鼠痛阈值.结论:接骨木总苷片有较好的抵抗急性炎症和镇痛的作用,并能促进骨折愈合.%OBJECTIVE:To study the effects of Sambucus williamsii total glycosides tablets on fracture healing and inflammation.METHODS:Rabbit fracture model was induced.50 New Zealand white rabbits were randomly divided into normal control group (constant volume of normal saline),model group (constant volume of normal saline),Dieda pills group (0.28 g/kg),S.williamsii total glycosides tablets high-dose,medium-dose and low-dose groups(0.22,0.11,0.06 g/kg).They were given medicine via feedingstuff for consecutive 36 d.The bone mineral density (BMD),bone mineral content (BMC) and callus area (Area) were determined by dual energy X-ray absorptioumetry (DXA).The degree of fracture healing was observed by X-ray film.Anti-inflammatory effects were observed by mice ear swelling and rat foot swelling experiments; analgesic action was observed by hot plate method.RESULTS:High-dose,medium-dose and low-dose of S.williamsii total glycosides tablets could increase BMD and BMC in model group

  19. 掌侧入路与背侧入路对腕舟骨骨折愈合率的影响%Effect of volar approach versus dorsal approach on the healing rate of scaphoid bone fractures

    Institute of Scientific and Technical Information of China (English)

    喻永新; 尚如国

    2014-01-01

    目的:探讨掌侧入路与背侧入路对腕舟骨骨折愈合率的影响。方法:中文数据库以“腕舟骨骨折”与“掌侧入路”和“背侧入路”的布尔逻辑搭配结果作为检索词,英文数据库以“scaphoid fractures”与“dorsal”、“volar”及“palmar”的布尔逻辑搭配结果作为检索词。用计算机检索中国知网、万方学术期刊数据库、维普中文期刊数据库、中国生物医学文献服务系统、中国生物医学期刊网引文数据库、Pubmed及Sciencedirect数据库建库至2013年11月收录的所有相关文献。利用Revman5.2统计软件进行统计分析。结果:共纳入9篇文献,涉及435例患者,其中随机对照实验2篇,非随机对照实验7篇;中文文献4篇,外文文献5篇。漏斗图显示文献不存在发表偏倚。掌侧入路组与背侧入路组总的骨折愈合率比较,差异无统计学意义[Z=149,P=0.140;OR=0.420,95%CI(0.140,1.310)];掌侧入路组术后6~8个月的骨折愈合率优于背侧入路组[Z=2.840,P=0.004;OR=6.930,95%CI(1.820,26.320)]。掌侧入路组与背侧入路组术后并发症发生率比较,差异无统计学意义[Z=0.590,P=0.560;OR=0.760,95%CI(0.310,1.890)]。掌侧入路组与背侧入路组术后腕部活动功能比较,差异无统计学意义[Z=0.990,P=0.320;OR=1.900,95%CI(-1.840,5.840)]。结论:掌侧入路与背侧入路治疗腕舟骨骨折对骨折愈合率的影响没有差异,但经掌侧入路固定的患者骨折愈合更快。%Objective:To explore the effect of volar approach versus dorsal approach on the healing rate of scaphoid bone fractures. Methods:The Boolean logical combination of Scaphoid fractures,Dorsal,Volar and Palmar were used as index terms.All the literatures of controlled trial included from database establishing to November 2013 were retrieved from

  20. Acceleration of wound healing in acute full-thickness skin wounds using a collagen-binding peptide with an affinity for MSCs

    Directory of Open Access Journals (Sweden)

    Huili Wang

    2014-10-01

    Full Text Available Mesenchymal stem cells (MSCs have been accepted as a promising cell source in tissue repair and regeneration. However, the inability to enrich MSCs in target areas limits their wide application. As a result, it has been a major goal to induce MSCs to be abundantly and specifically recruited to the injury site. In this study, a peptide with a specific affinity for MSCs (E7 peptide was immobilized to a collagen scaffold via a collagen-binding domain (CBD to construct a functional collagen scaffold. In addition, the hypothesis that this method could recruit MSCs specifically was evaluated in a porcine model. In vivo investigations indicated that due to the immunoreaction, the CBD-MSC-peptide collagen scaffold enhanced MSC adhesion and infiltration and promoted wound healing. At day 7 after surgery, we found more infiltrating cells and capillaries in the Collagen/CBD-E7 peptide group compared to the Scaffold group. At day 14, 21 and 28, a faster healing process was observed in the Collagen/CBD-E7 peptide group, with significant differences compared with the other groups (P < 0.05, P < 0.01. The results demonstrate the potential use of targeted therapy to rapidly heal skin wounds.

  1. Topical application of Acalypha indica accelerates rat cutaneous wound healing by up-regulating the expression of Type I and III collagen.

    Science.gov (United States)

    Ganeshkumar, Moorthy; Ponrasu, Thangavel; Krithika, Rajesh; Iyappan, Kuttalam; Gayathri, Vinaya Subramani; Suguna, Lonchin

    2012-06-26

    Acalypha indica Linn. (Acalypha indica) vernacularly called Kuppaimeni in Tamil, has been used as a folklore medicine since ages for the treatment of wounds by tribal people of Tamil Nadu, Southern India. The present study investigates the biochemical and molecular rationale behind the healing potential of Acalypha indica on dermal wounds in rats. Acalypha indica extract (40 mg/kg body weight) was applied topically once a day on full-thickness excision wounds created on rats. The wound tissue was removed and used for estimation of various biochemical and biophysical analyses and to observe histopathological changes with and with-out extract treatment. The serum levels of pro-inflammatory cytokine tumor necrosis factor (TNF-α) was measured at 12 h, 24 h, 48 h and 72 h post-wounding using ELISA. Reverse transcription-polymerase chain reaction (RT-PCR) analysis was performed to study the expression pattern of transforming growth factor [TGF-β1], collagen 1 α (I) [Col 1 α (I)] and collagen 3 α (I) [Col 3 α (I)]. Likewise, linear incision wounds were created and treated with the extract and used for tensile strength measurements. Wound healing in control rats was characterized by less inflammatory cell infiltration, lack of granulation tissue formation, deficit of collagen and significant decrease in biomechanical strength of wounds. Acalypha indica treatment mitigated the oxidative stress and decreased lipid peroxidation with concomitant increase in ascorbic acid levels. It also improved cellular proliferation, increased TNF-α levels during early stages of wound healing, up-regulated TGF-β1 and elevated collagen synthesis by markedly increasing the expression of Col 1 α (I) and Col 3 α (I). Increased rates of wound contraction, epithelialization, enhanced shrinkage temperature and high tensile strength were observed in the extract treated rats. Acalypha indica extract was shown to augment the process of dermal wound healing by its ability to increase collagen

  2. 龙血竭提取物促进创面愈合的实验研究%Application of Resina Draconis Extract on Accelerating Animal Wound Healing

    Institute of Scientific and Technical Information of China (English)

    刘辉辉; 肖丹; 郑晓; 顾岩; 郭善禹

    2013-01-01

    Objective To investigate the effects of ethanolic extract of Resina Draconis (RDEE) in animal wound healing. Methods Forty-eight SD rats were randomly divided into three groups: control group, MEBO group (treated with MEBO) and RDEE group (treated with RDEE). Wound healing rates and healing time were calculated 3, 7, 11 and 15 days after treatment, and tissues were harvested at the same time for histological, immunohistochemical analysis and MVD calculation. The expression of VEGF was determined by real-time PCR and western blot. Results Wound healing time in RDEE group was shorter than in control group (P<0.05). There was no difference of would healing time between RDEE group and MEBO group. Wound healing rates, MVD number (3, 7, 11 days after treatment) and the expression of VEGF were significantly higher in RDEE group and MEBO group than in control group (P<0.05). Histological results showed more well-organized bands of collagen, more fibrob-lasts and less inflammatory cells in RDEE group compared with control group. Conclusion The extract from Resina Draconis possesses wound healing activity, and is worthy of clinical application.%目的探讨龙血竭乙醇提取物(Ethanolic extract of Resina Draconis, RDEE)促进创面愈合的疗效。方法将48只SD大鼠随机分为对照组、湿润烧伤膏组(MEBO组)和龙血竭乙醇提取物组(RDEE组)。测量和计算伤后第3、7、11和15天创面面积,计算创面愈合率和愈合时间;采用HE、Masson染色和CD31免疫组织化学染色,观察创面肉芽组织结构改变、胶原分布,并计算微血管密度(Microvessel density,MVD);采用荧光定量PCR和Western Blot,检测创面肉芽组织中VEGF表达的变化。结果 RDEE组创面愈合时间明显比对照组短(P<0.05),MEBO组和RDEE组之间无显著性差异;RDEE组、MEBO组创面愈合率和伤后第3、7、11天的MVD、VEGF 表达量均高于对照组,差异显著(P<0.05);RDEE组创面

  3. Self-healing polymers

    Science.gov (United States)

    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.

  4. Effect of Zoledronic Acid on the Healing of Distal Radial Fracture%唑来膦酸对老年桡骨远端骨折术后疗效观察

    Institute of Scientific and Technical Information of China (English)

    尹自龙; 石磊; 王林; 刘驰; 郑念野; 纪泉; 张华俦; 良元; 薛庆云

    2014-01-01

    ,and a conventional calcium and calcitriol supplement,4 week and 3 month follow-up of fractures heal-ing and postoperative 1 year follow-up of bone mineral density. Results The fracture healing in elderly patients with no obvi-ous effect of zoledronic acid anti osteoporosis medicine after distal radius fracture,callus in A group is more than callus in group B,postoperative bone mineral density increased over one year ago. Conclusion The effect of osteoporosis treatment with zoledronic acid medicine in elderly patients with distal radius fractures is significant,while no obvious negative effect on the healing of the osteoporotic distal radius fracture.

  5. The Experimental Study of the Sound field of Low Intensity Pulsed Ultrasound Promoting Fracture Healing%低强度脉冲超声促进骨愈合的声场研究

    Institute of Scientific and Technical Information of China (English)

    王迪龙; 张冀; 菅喜岐

    2013-01-01

    目的 通过对圆形平面超声换能器近声场的实验测量,研究低强度脉冲超声(low intensity pulsed ultrasound,LIPUS)治疗骨折愈合时,骨组织的厚度和裂缝位置、形状等对近声场的影响,为LIPUS促进骨愈合治疗方案的制定提供理论依据.方法 选取圆形平面超声换能器近声场声轴上的一个声压极大值和极小值端点处作为参考位置,分别对这两个位置上垂直于声轴断面的声压分布进行测试,分析讨论不同功率、骨组织厚度、水体深度、骨折裂缝宽度及其位置,对垂直于声轴断面上的声压分布的影响.结果 近场声压随功率的增大而非线性增大;骨组织厚度在1~5 mm范围时,在声轴上极大值点处的声压随骨组织厚度增厚明显减小,但在极小值点变化较小;声压受骨组织和换能器之间水体的影响较小;随骨折裂缝宽度增大,声压在裂缝处增大.结论 骨组织厚度以及骨折裂缝的位置、形状等对声场分布均有影响,且对近声场内极大值和极小值处的声压影响程度不同;在进行LIPUS促进骨折愈合治疗时,需要根据骨折位置等不同条件设定不同的治疗参数.%Objective To study the effect of the thickness,the shape and location of the bone tissue on the near sound field of the circular plane ultrasonic transducer by experimentally measuring the near sound field,during the fracture healing treated by the low intensity pulsed ultrasound (LIPUS),which can provide theoretical basis for making the treatment plan of the fracture healing promoted by the LIPUS.Methods Select a maximum and minimum point of near field pressure on acoustic axis as the reference positions.Then,respectively obtain the axial pressure distribution of the two positions perpendicular to the cross-section of the acoustic axis.Analyze and discuss the effects of different power,the bone tissue thickness,the depth of water,the width of the fracture crack and the

  6. Randomised controlled trial evaluating the efficacy of wrap therapy for wound healing acceleration in patients with NPUAP stage II and III pressure ulcer

    Science.gov (United States)

    Mizuhara, Akihiro; Oonishi, Sandai; Takeuchi, Kensuke; Suzuki, Masatsune; Akiyama, Kazuhiro; Kobayashi, Kazuyo; Matsunaga, Kayoko

    2012-01-01

    Objectives To evaluate if ‘wrap therapy’ using food wraps, which is widely used in Japanese clinical sites, is not inferior when compared to guideline adhesion treatments. Design Multicentre, prospective, randomised, open, blinded endpoint clinical trial. Setting 15 hospitals in Japan. Patients 66 older patients with new National Pressure Ulcer Advisory Panel stage II or III pressure ulcers. Interventions Of these 66 patients, 31 were divided into the conventional treatment guidelines group and 35 into the wrap therapy group. Main outcome measures The primary end point was the period until the pressure ulcers were cured. The secondary end point was a comparison of the speed of change in the Pressure Ulcer Scale for Healing score. Results 64 of the 66 patients were analysed. The estimated mean period until healing was 57.5 days (95% CI 45.2 to 69.8) in the control group as opposed to 59.8 days (95% CI 49.7 to 69.9) in the wrap therapy group. By the extent of pressure ulcer infiltration, the mean period until healing was 16.0 days (95% CI 8.1 to 23.9) in the control group as opposed to 18.8 days (95% CI 10.3 to 27.2) in the wrap therapy group with National Pressure Ulcer Advisory Panel stage II ulcers, and 71.8 days (95% CI 61.4 to 82.3) as opposed to 63.2 days (95% CI 53.0 to 73.4), respectively, with stage III ulcers. There is no statistical significance in difference in Pressure Ulcer Scale for Healing scores. Conclusions It might be possible to consider wrap therapy as an alternative choice in primary care settings as a simple and inexpensive dressing care. Clinical Trial registration UMIN Clinical Trials Registry UMIN000002658. Summary protocol is available on https://upload.umin.ac.jp/cgi-bin/ctr/ctr.cgi?function=brows&action=brows&type=detail&recptno=R000003235&admin=0&language=J PMID:22223842

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

    Science.gov (United States)

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

    2015-06-01

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

  8. A follow-up study of the in-practice results of pulsed electromagnetic field therapy in the management of nonunion fractures

    Directory of Open Access Journals (Sweden)

    Murray HB

    2016-12-01

    Full Text Available Hallie B Murray,1 Brian A Pethica1,2 1EBI, LLC (a Zimmer Biomet company, Parsippany, NJ, USA; 2Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ, USA Abstract: During normal fracture repair, healing occurs within a few months. However, for a minority of patients, the processes of bone repair are compromised or interrupted leading to the development of delayed union and nonunion fractures. Noninvasive bone growth stimulators using pulsed electromagnetic field (PEMF technology are currently in widespread use by patients with impaired fracture healing. This article reports the results of a follow-up study of 1,382 patients treated with PEMF stimulation to evaluate success rates and the relationship between average daily use and the clinical outcomes of therapy as reported by their prescribing physicians. The reported overall success rate for the 1,382 patients was 89.6%. The results were analyzed in audited subsets comparing days of treatment time and average daily use of the electrical bone growth stimulator, using several statistical methods. Linear regression analysis indicated a 6-day reduction in time to heal with each additional hour of average daily use. Survival analysis concluded that the median heal time was reduced by 35%–60%, depending on the different fracture characteristics of patients who complied with the recommended daily use of 10 hours per day. A third statistical analysis indicated that patients treated with the PEMF device for 9 hours or more per day had a significant reduction in time to heal, achieving successful fracture repair an average of 76 days earlier than patients treated with the PEMF device for an average of 3 hours or less per day. Overall, these different methods of statistical analysis indicate that PEMF therapy correlates with an acceleration in the healing of nonunion fractures. Keywords: PEMF, pulsed electromagnetic field, dose–response, nonunion, time to heal

  9. Vibration acceleration promotes bone formation in rodent models

    Science.gov (United States)

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

    2017-01-01

    All living tissues and cells on Earth are subject to gravitational acceleration, but no reports have verified whether acceleration mode influences bone formation and healing. Therefore, this study was to compare the effects of two acceleration modes, vibration and constant (centrifugal) accelerations, on bone formation and healing in the trunk using BMP 2-induced ectopic bone formation (EBF) mouse model and a rib fracture healing (RFH) rat model. Additionally, we tried to verify the difference in mechanism of effect on bone formation by accelerations between these two models. Three groups (low- and high-magnitude vibration and control-VA groups) were evaluated in the vibration acceleration study, and two groups (centrifuge acceleration and control-CA groups) were used in the constant acceleration study. In each model, the intervention was applied for ten minutes per day from three days after surgery for eleven days (EBF model) or nine days (RFH model). All animals were sacrificed the day after the intervention ended. In the EBF model, ectopic bone was evaluated by macroscopic and histological observations, wet weight, radiography and microfocus computed tomography (micro-CT). In the RFH model, whole fracture-repaired ribs were excised with removal of soft tissue, and evaluated radiologically and histologically. Ectopic bones in the low-magnitude group (EBF model) had significantly greater wet weight and were significantly larger (macroscopically and radiographically) than those in the other two groups, whereas the size and wet weight of ectopic bones in the centrifuge acceleration group showed no significant difference compared those in control-CA group. All ectopic bones showed calcified trabeculae and maturated bone marrow. Micro-CT showed that bone volume (BV) in the low-magnitude group of EBF model was significantly higher than those in the other two groups (3.1±1.2mm3 v.s. 1.8±1.2mm3 in high-magnitude group and 1.3±0.9mm3 in control-VA group), but BV in the

  10. Retracted: Exosomes secreted by human urine-derived stem cells accelerate skin wound healing by promoting angiogenesis in rat by Yuan H, Guan J, Zhang J, Zhang R, Li M.

    Science.gov (United States)

    2017-08-01

    The above article, published online on 21 April 2016 in Wiley Online Library (http://onlinelibrary.wiley.com/doi/10.1002/cbin.10615/full), has been retracted by agreement between the authors, the journal Editor, Sergio Schenkman, and John Wiley & Sons Ltd. The retraction has been agreed because the authors discovered inconsistent results in repeated tests. The authors and publisher apologise for any inconvenience. Reference Yuan H, Guan J, Zhang J, Zhang R, LiM(2016) Exosomes secreted by human urine-derived stem cells accelerate skin wound healing by promoting angiogenesis in rat. Cell Biol Int, Accepted Author Manuscript. https://doi.org/10.1002/cbin.10615. © 2017 International Federation for Cell Biology.

  11. 罂粟碱促进跟骨骨折手术切口愈合的疗效评价%Evaluation of promotive effect on incision healing after the operation of calcaneus fractures by using papaverine

    Institute of Scientific and Technical Information of China (English)

    汤俊君; 张建; 吴克俭; 刘亭茹; 张永刚

    2015-01-01

    Objective To evaluate the promotive effect on incision healing after the operation of calcaneus fractures by using papaverine. Methods From 2010 to 2013, 52 patients with calcaneus fractures were divided into 2 groups according to whether papaverine was used or not after the operation. There were 29 patients ( 33 feet ) in treatment group and 23 patients ( 25 feet ) in control group. All the patients underwent open reduction and internal ifxation with L-type calcaneal lateral incision, and the time of regular drainage lasted for 48 hours after the operation. The clinical data were recorded in all the patients, including gender, age, degree of soft tissue injury, classiifcation of fracture, time from injury to operation, operation time, intraoperative amount of bleeding, drying time and healing time of the incision, length of unhealthy skin and incidence of complications of the incision and function score of the foot at 1 year after the operation. Statistical analysis was performed. Results There were no statistically signiifcant differences in gender, age, degree of soft tissue injury, classiifcation of fracture, time from injury to operation, operation time, intraoperative amount of bleeding and function score of the foot at 1 year after the operation between the 2 groups. In control group, the average time of incision drying was ( 6.2±1.9 ) days and the average time of incision healing was ( 17.8±3.1 ) days. The good ratio of incision health degree was 64.0%. While in treatment group, the average time of incision drying was ( 5.1±1.2 ) days and the average time of incision healing was ( 15.7±2.6 ) days. The good ratio of incision health degree was 84.8%. The differences between the 2 groups were statistically signiifcant ( P<0.0355, 0.0063, 0.0328 ). Conclusions Papaverine can promote incision healing and decrease complications after the operation of calcaneus fractures.%目的:评价跟骨骨折术后使用罂粟碱对手术切口

  12. Hydroethanolic Extract of Strychnos pseudoquina Accelerates Skin Wound Healing by Modulating the Oxidative Status and Microstructural Reorganization of Scar Tissue in Experimental Type I Diabetes

    Directory of Open Access Journals (Sweden)

    Mariáurea M. Sarandy

    2017-01-01

    Full Text Available The effect of topical application of ointment based on Strychnos pseudoquina hydroethanolic extract in the cutaneous wounds healing in diabetic rats was evaluated. Samples of S. pseudoquina were submitted to phytochemical prospection and in vitro antioxidant assay. Thirty Wistar rats were divided into 5 groups: Sal-wounds treated with 0.9% saline solution; VH-wounds treated with 0.6 g of lanolin cream (vehicle; SS-wounds treated with silver sulfadiazine cream (10 mg/g; ES5- and ES10-wounds treated with an ointment of S. pseudoquina extract, 5% and 10%, respectively. Fragments of wounds were removed for histological and biochemical analysis every 7 days during 21 days. ES showed equivalent levels per gram of extract of total phenols and flavonoids equal to 122.04 mg for TAE and 0.60 mg for RE. The chlorogenic acid was one of the major constituents. S. pseudoquina extract presented high antioxidant potential in vitro. ES5 and ES10 showed higher wound healing rate and higher amount of cells, blood vessels, and type III and I collagen. The oxidative stress markers were lower in the ES5 and ES10 groups, while the antioxidants enzymes levels were higher. Ointment based on S. pseudoquina extract promotes a fast and efficient cutaneous repair in diabetic rats.

  13. Dynamical effect of fractures combined with brain injury on the bone healing and bone metabolism%骨折合并脑损伤对骨愈合和骨代谢的影响

    Institute of Scientific and Technical Information of China (English)

    周青; 刘进炼; 刘超群; 周耀东; 陈豪

    2015-01-01

    BACKGROUND:Peri-fracture nerve injury can inhibit osteoclast activity and promote early fracture healing. OBJECTIVE:To investigate dynamical y the effects of traumatic brain injury on the bone mineral density, microstructure, biomechanics property and bone metabolism in rat models of fractures. METHODS:Sixty-three male rats were randomly divided into three groups:sham group, simple fracture group and fracture combined with brain injury group. After 3, 6, and 3 months, the animals were sacrificed in batches under anesthesia, and then, the bones and serum specimens were used to detect the bone mineral density, microstructure, biomechanics property, serum cross-linked N-telopeptide of col agen type I and osteocalcin levels. RESULTS AND CONCLUSION:Compared with the simple fracture group, the fracture combined brain injury group had significantly increased bone mineral density of the proximal tibia, bone volume fraction of the cancel ous bone, trabecular thickness, cross-sectional area of tibial cortical bone and total area of the bone marrow, ultimate load and stress of the tibia, serum cross-linked N-telopeptide of col agen type I and osteocalcin levels at 3 and 6 weeks after modeling (P  目的:观察了大鼠肢体骨折合并脑损伤对骨密度、骨微结构、骨生物力学特征和骨代谢影响。  方法:63只大鼠随机分为假手术组、单纯骨折组和脑损伤合并骨折组。在术后3周、6周和3个月分批麻醉处死动物保存骨骼和血清标本,检测骨密度、骨微结构和生物力学性能以及血清Ⅰ型胶原氨基末端肽和骨钙素水平的变化。  结果与结论:与单纯骨折组相比,在造模3周和6周后,脑损伤合并骨折组胫骨近端的骨密度、松质骨微结构骨体积分数、骨小梁厚度、胫骨皮质骨截面总面积和骨髓腔面积、胫骨极限载荷和极限应力、血清原氨基末端肽和骨钙素水平均显著增高(P<0.05),造模后3个月,3组间

  14. Navigating in Foldonia: Using Accelerated Molecular Dynamics to Explore Stability, Unfolding and Self-healing of the β-Solenoid Structure Formed by a Silk-like Polypeptide

    NARCIS (Netherlands)

    Cohen Stuart, M.A.; Hall, Carol K.

    2017-01-01

    The β roll molecules with sequence (GAGAGAGQ)10 stack via hydrogen bonding to form fibrils which have been themselves been used to make viral capsids of DNA strands, supramolecular nanotapes and pH-responsive gels. Accelerated molecular dynamics (aMD) simulations are used to investigate the

  15. Dynamic expression of several grow factors in process of osteoblasts grafts to promote healing of osteoporotic fracuture%几种生长因子在成骨细胞移植促进骨质疏松性骨折愈合过程中的动态表达

    Institute of Scientific and Technical Information of China (English)

    曾敬; 徐栋梁; 张惠忠; 丘钜世; 张萌; 梁惠珍

    2003-01-01

    AIM: To study the biological function of transforming growth factor β1(TGF-β1), vascular endothelial growth factor(VEGF), basic fibroblast growth factor(bFGF) during the process of osteoblasts allografts to accelerate faceture healing of osteoporosis rats. METHODS: Set up the fracture models of osteoporosis rats and do osteoblasts grafts; during different periods in the process of fracture healing by using immunnohistochemistry to detect the expression of TGF-β1, VEGF, bFGF and in situ hybridization to study the expression of bFGFmRNA, VEGFmRNA, TGF-β1 mRNA, also using image analysis to deal with it. RESULTS: In experimental group, Osteoblasts can survive, even proliferate in fracture areas; VEGF, bFGF could be seen positive after 7 days of after osteoblast grafts, and there have the highest quantites about 14 days of post-transplantation. TGF-β1 could be seen positiveafter 3 days of post-transplantation, and there have the highest quantities about 7 - 10 days of post-transplantation. However there are not obviously high quantities in control. CONCLUSION: Osteoblasts grafts enhance bone fracture healing of osteoporosis rats. TGF-β1, VEGF and bFGF play very important roles in accelerating fracture healing of osteoporosis rats.

  16. Reconsiderações sobre o tempo de consolidação das fraturas na picnodisostose Reconsiderations regarding time of fracture healing in Pycnodysostosis

    Directory of Open Access Journals (Sweden)

    Flávio Dorcilo Rabelo

    2010-01-01

    Full Text Available OBJETIVO: Discutir o que vem sendo descrito na literatura até então a respeito do tempo de consolidação das fraturas na picnodisostose. MÉTODOS: Treze novos casos foram estudados por questão de disponibilidade de prontuários e exames radiográficos, totalizando 44 fraturas englobando pacientes avaliados no período de novembro de 1970 a agosto de 2004, no Hospital Ortopédico de Goiânia. Pesquisa em campo, acompanhamento clínico simultâneo, por novas fraturas, de duas pacientes e avaliação retrospectiva de prontuários foram feitos, com base em se determinar o número de fraturas totais de cada paciente e quais destas tinham viabilidade para esta pesquisa. O grupo de pacientes compõe-se de três mulheres e dois homens com idade média de 51,4 anos. A tíbia foi o osso mais acometido, seguido pelo fêmur. Foram excluídas as fraturas cujo acompanhamento tenha sido feito em outro serviço. RESULTADOS: Das 12 fraturas consideradas plenas para o estudo, nove aconteceram em fêmures (seis no fêmur E e três no fêmur D; uma em tíbia (D; uma em clavícula (D e uma em ulna (E. Dentre as 12 fraturas, oito evoluíram com pseudartrose em um tempo médio de 29,25 meses; três consolidaram bem em uma média de 5,83 meses e um paciente evoluiu com retardo de consolidação em apenas dois meses. CONCLUSÃO: Associadas à pesquisa gênica e estudos micromorfológicos, aguarda-se novos estudos para reconfirmação diagnóstica numa entidade clínica tão rara.OBJECTIVE: To discuss what has been described so far in the literature regarding the time of consolidation of fractures in Pycnodysostosis. MATERIALS AND METHODS: Thirteen new cases were studied, as a matter of the availability of medical records and radiographic examinations, totaling 44 patients in the period from November 1970 to August 2004 in the Hospital Ortopédico de Goiânia. Field research and simultaneous clinical monitoring for new fractures in two patients, and the retrospective

  17. 鲑鱼降钙素联合恒古骨伤愈合剂治疗腰椎OPF疗效分析%The study on treatment of vertebral osteoporotic fracture by salmon calcitonin and Heng Gu bone healing reagent

    Institute of Scientific and Technical Information of China (English)

    罗德军; 赵宏斌; 周旭; 董锡亮; 李林芝; 王文志; 熊海

    2011-01-01

    Objective To study effects of salmon calcitonin and Heng Gu bone healing reagent on vertebral osteoporotic fracture(OPF).Methods From Nov.2007 to Dec.2009,82 cases of vertebral OPF were treated.These cases were randomly divided into treatment group and control group.The treatment group(42 cascs)were treated with salmon calcitonin and Heng Gu bone healing reagent.The control group(40 cases)received salmon calcitonin only.Pain relief of the 2 groups wag compared.Results Before treatment,the 82 patients were scored 6-9 points by visual analogue scales(VAS)and pain scores of the 2 groups were similar (P>0.05).3 days,5 days,8 days and 15 days after treatment,VAS scores of the 2 groups were significantly different(P0.05).治疗后3、5、8、15 d,2组疼痛VAS评分分别经秩和检验差异有统计学意义(P<0.01).治疗组不但疼痛缓解快,3个月后复查骨矿物密度改善程度亦明显优于对照组.结论 鲑鱼降钙素联合恒古骨伤愈合剂治疗腰椎骨质疏松性骨折具有良好止痛和促进成骨作用,是一种安全、有效的方法.

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

    Science.gov (United States)

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

    2016-06-07

    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.

  19. Influência do componente protéico na consolidação de fraturas: trabalho experimental em ratos Influence of the protein component upon fracture healing: an experimental study in rats

    Directory of Open Access Journals (Sweden)

    Roberto Guarniero

    2003-12-01

    Full Text Available Os autores estudaram a influência da nutrição protéica na consolidação de fraturas em 40 ratos Lewis divididos em 4 grupos de 10. Durante 6 semanas os grupos 1, 2 e 3 receberam respectivamente dietas com 0, 19% e 36% de proteínas. O grupo 4 recebeu dieta sem proteínas durante as 2 primeiras semanas e com 36% de proteínas nas 4 semanas seguintes. Foram realizadas fraturas nas tíbias esquerdas ao final de 2 semanas e após 4 semanas das fraturas os animais foram sacrificados para estudo dos calos ósseos. Para a avaliação dos resultados foram utilizadas medidas clínicas, bioquímicas, radiográficas, densitométricas, e histomorfométricas. Concluiu-se que a dieta hiperprotéica alterou a consolidação óssea produzindo um calo maior e mais resistente, mas não alterou a qualidade em concentração de cálcio e em porcentagem a quantidade de tecido ósseo.The authors investigated the influence of a protein diet on fracture healing in 40 Lewis rats divided into four groups of ten. During 6 weeks, Groups 1, 2 and 3 were fed diets containing, respectively, 0.19% and 36% protein. Group 4 was fed a proteinless diet during the first two weeks and a 36%-protein diet during the next 4 weeks. At two weeks, fractures were performed in the left tibias; all animals were killed 4 weeks later so that the bone calluses could be investigated. Clinical, biochemical, radiographic, densitometry and histomorphometry measurements were performed to evaluate the findings. The conclusion was that the hyperprotein diet altered bone healing by producing a larger, more resistant callus, although it did not change quality as regards calcium levels and the percentage amount of bone tissue.

  20. Effect of Jieguqili chip and simvastatin in promoting fracture Healing: An animal experiment%接骨七厘片、辛伐他汀对促进骨折愈合的动物实验研究

    Institute of Scientific and Technical Information of China (English)

    张勇妹; 丁妍; 郭贵宾; 陈邦元

    2013-01-01

    目的 探讨接骨七厘片和辛伐他汀对促进骨折愈合的机制,并分析联合应用接骨七厘片和辛伐他汀与单独应用接骨七厘片或辛伐他汀对促进骨折愈合的差异.方法 用蒸馏水将接骨七厘片和辛伐他汀片分别溶解,配成一定浓度的溶解液.将实验大鼠随机分成4组,将双侧尺桡骨中1/3段徒手折断,造成闭合性完全性骨折,不给予外固定.术后接骨七厘片组给予接骨七厘片溶液,1次/d,连续28 d;辛伐他汀片组给予辛伐他汀溶液,1次/d,连续28d;联合应用组同时给予接骨七厘片溶液及辛伐他汀溶液,1次/d,连续28d;对照组灌胃给予生理盐水1 mL,1次/d,连续28d.结果 在一般行为表现、X线表现、组织形态学、骨痂干重等方面,接骨七厘片组和(或)辛伐他汀组与联合应用接骨七厘片和辛伐他汀组相比,差异有统计学意义(P<0.05).结论 本实验研究发现接骨七厘片及辛伐他汀在骨折愈合的过程中,均能增加成骨细胞的活性,使成骨细胞大量增生,促进骨痂的形成,提高骨痂的质量,而联合应用接骨七厘片及辛伐他汀比单纯使用接骨七厘片或辛伐他汀片作用更明显,骨折愈合较快.%Objective To analyze the mechanism of Jieguqili chip and simvastatin in promoting fracture healing, and to compare the difference between the combined use of the Jieguqili chip and simvastatin and single use of Jieguqili chip or simvastatin in promoting fracture healing. Methods The Jieguqili chip and simvastatin tablets were dissolved with distilled, dubbed a certain concentration of solvent. Rats were randomly divided into 4 groups, and their bilateral radius and ulna 1/3 of unarmed were broken, which created the closed complete bone fracture. No external fixation was done. After the technique, the 1st group was treated the Jieguqili chip solution, once a day, continually 28 days. The second group was treated with simvastatin solution, once a day

  1. Scaphoid fractures in children

    Directory of Open Access Journals (Sweden)

    Gajdobranski Đorđe

    2014-01-01

    Full Text Available Introduction. Scaphoid fractures are rare in childhood. Diagnosis is very difficult to establish because carpal bones are not fully ossified. In suspected cases comparative or delayed radiography is used, as well as computerized tomography, magnetic resonance imaging, ultrasound and bone scintigraphy. Majority of scaphoid fractures are treated conservatively with good results. In case of delayed fracture healing various types of treatment are available. Objective. To determine the mechanism of injury, clinical healing process, types and outcome of treatment of scaphoid fractures in children. Methods. We retrospectively analyzed patients with traumatic closed fracture of the scaphoid bone over a ten-year period (2002-2011. The outcome of the treatment of “acute” scaphoid fracture was evaluated using the Mayo Wrist Score. Results. There were in total 34 patients, of mean age 13.8 years, with traumatic closed fracture of the scaphoid bone, whose bone growth was not finished yet. Most common injury mechanism was fall on outstretched arm - 76% of patients. During the examined period 31 children with “acute” fracture underwent conservative treatment, with average immobilization period of 51 days. Six patients were lost to follow-up. In the remaining 25 patients, after completed rehabilitation, functional results determined by the Mayo Wrist Score were excellent. Conclusion. Conservative therapy of “acute” scaphoid fractures is an acceptable treatment option for pediatric patients with excellent functional results.

  2. Systemic Treatment with Strontium Ranelate Accelerates the Filling of a Bone Defect and Improves the Material Level Properties of the Healing Bone

    Directory of Open Access Journals (Sweden)

    Giovanna Zacchetti

    2014-01-01

    Full Text Available 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.

  3. Healing Architecture

    DEFF Research Database (Denmark)

    Folmer, Mette Blicher; Mullins, Michael; Frandsen, Anne Kathrine

    2012-01-01

    The project examines how architecture and design of space in the intensive unit promotes or hinders interaction between relatives and patients. The primary starting point is the relatives. Relatives’ support and interaction with their loved ones is important in order to promote the patients healing...... process. Therefore knowledge on how space can support interaction is fundamental for the architect, in order to make the best design solutions. Several scientific studies document that the hospital's architecture and design are important for human healing processes, including how the physical environment...... architectural and design solutions in order to improve quality of interaction between relative and patient in the hospital's intensive unit....

  4. MicroRNA miR-27b rescues bone marrow-derived angiogenic cell function and accelerates wound healing in type 2 diabetes mellitus.

    Science.gov (United States)

    Wang, Jie-Mei; Tao, Jun; Chen, Dan-Dan; Cai, Jing-Jing; Irani, Kaikobad; Wang, Qinde; Yuan, Hong; Chen, Alex F

    2014-01-01

    Vascular precursor cells with angiogenic potentials are important for tissue repair, which is impaired in diabetes mellitus. MicroRNAs are recently discovered key regulators of gene expression, but their role in vascular precursor cell-mediated angiogenesis in diabetes mellitus is unknown. We tested the hypothesis that the microRNA miR-27b rescues impaired bone marrow-derived angiogenic cell (BMAC) function in vitro and in vivo in type 2 diabetic mice. BMACs from adult male type 2 diabetic db/db and from normal littermate db/+ mice were used. miR-27b expression was decreased in db/db BMACs. miR-27b mimic improved db/db BMAC function, including proliferation, adhesion, tube formation, and delayed apoptosis, but it did not affect migration. Elevated thrombospondin-1 (TSP-1) protein in db/db BMACs was suppressed on miR-27b mimic transfection. Inhibition of miR-27b in db/+ BMACs reduced angiogenesis, which was reversed by TSP-1 small interfering RNA (siRNA). miR-27b suppressed the pro-oxidant protein p66(shc) and mitochondrial oxidative stress, contributing to its protection of BMAC function. miR-27b also suppressed semaphorin 6A to improve BMAC function in diabetes mellitus. Luciferase binding assay suggested that miR-27b directly targeted TSP-1, TSP-2, p66(shc), and semaphorin 6A. miR-27b improved topical cell therapy of diabetic BMACs on diabetic skin wound closure, with a concomitant augmentation of wound perfusion and capillary formation. Normal BMAC therapy with miR-27b inhibition demonstrated reduced efficacy in wound closure, perfusion, and capillary formation. Local miR-27b delivery partly improved wound healing in diabetic mice. miR-27b rescues impaired BMAC angiogenesis via TSP-1 suppression, semaphorin 6A expression, and p66shc-dependent mitochondrial oxidative stress and improves BMAC therapy in wound healing in type 2 diabetic mice.

  5. Allium stipitatum Extract Exhibits In Vivo Antibacterial Activity against Methicillin-Resistant Staphylococcus aureus and Accelerates Burn Wound Healing in a Full-Thickness Murine Burn Model

    Science.gov (United States)

    Karunanidhi, Arunkumar; Jeevajothi Nathan, Jayakayatri; van Belkum, Alex

    2017-01-01

    The in vivo antibacterial and burn wound healing potency of Persian shallot bulbs (Allium stipitatum) were explored in a mice burn model infected with methicillin-resistant Staphylococcus aureus (MRSA). Hexane (ASHE) and dichloromethane (ASDE) extracts were tested. Female BALB/c mice were inflicted with third-degree thermal injury followed by infection with MRSA. ASHE and ASDE formulated with simple ointment base (SOB) at concentrations of 1%, 2%, and 5% (w/w) were topically applied to burn wounds twice a day for 20 days. Silver sulfadiazine (1%) served as drug positive control. Microbiological analysis was carried out on 1, 2, 3, 4, and 5 days postwounding (dpw) and histopathological analysis at the end of the experiment (20 dpw). Both ointments demonstrated strong antibacterial activity with complete elimination of MRSA at 48–72 h after infection. The rate of wound contraction was higher (95–100%) in mice groups treated with ASHE and ASDE ointments after 15 dpw. Histological analysis revealed significant increase (p antibacterial as well as promising alternatives in managing thermal injuries. PMID:28321262

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

    Science.gov (United States)

    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.

  7. 鲑鱼降钙素促进老年转子间骨折愈合的疗效观察%Efficacy Observation of Salmon Calcitonin for Femoral Intertrochanteric Fractures Healing in Elderly Patients

    Institute of Scientific and Technical Information of China (English)

    谭美云; 郭杏; 税巍; 王远辉; 张忠杰

    2011-01-01

    目的:观察鲑鱼降钙素促进老年转子问骨折愈合的疗效.方法:将40例老年患者随机分为2组:治疗组20例,肌肉注射鲑鱼降钙素;对照组20例,在相同的部位肌肉注射等量注射用生理盐水.自术后第1天开始,2组均连续用药3个月.用药后的第1、3个月复查X线片,观察骨痂生长情况.治疗前和治疗后3个月检测患者腰椎(L4)骨密度(BMD)及血清钙、磷、碱性磷酸酶等浓度.结果:所有患者均得到随访.术后第1、3个月x线评估发现,治疗组比同时期对照组的骨痂生成量多.治疗后3个月,治疗组腰椎(L4)BMD明显高于对照组(P0.05),治疗组碱性磷酸酶明显高于对照组(P<0.05).治疗组1例出现恶心、呕吐等胃肠道症状,2例出现面颈部潮红.结论:鲑鱼降钙素能显著促进老年转子间骨折的愈合.%OBJECTIVE: To observe the therapeutic efficacy of salmon calcitonin for femoral intertrochanteric fractures healing in elderly patients. METHODS: A total of 40 elderly patients with femoral intertrochanteric fractures were randomly divided into 2 groups. 20 cases in treatment group received intramuscular injection of salmon calcitonin and 20 cases in control group received equal dose of normal saline at the same site. Both groups were given medicine after operation for 3 months. The X-ray plate of 2 groups was examined at 1 and 3 months after treatment to investigate the condition of bony callus. The BMD of the lumbar spine at LA, the concentration of serum calcium, serum phosphorus and alkaline phosphate were measured before treament and 3 months after treatment. RESULTS: All patients were followed up. The X-ray plate showed that the bony callus in treatment group was more abundant than in control group at 1 and 3 months after treatment. 3 months after treatment, the BMD of the lumbar spine at L4 in treatment group was significantly higher than in control group (P<0.05). The concentration of serum calcium in treatment group was

  8. Biomechanics Significance of Femoral Head and Neck of Grafting-bone Group After Femoral Neck Fracture-healing%股骨颈骨折愈合后钉道植骨的生物力学意义

    Institute of Scientific and Technical Information of China (English)

    唐洪涛; 仝允辉; 杨茹萍; 朱太永; 张美超; 赵卫东

    2011-01-01

    Objective To study biomechanical performance of fracture-healing femoral head and neck after the hollow compressionb screws are taken out in ungrafting-bone group, grafting-bone group, normal group, and provide theoretical basis for the treatment of necrosis of the femoral head by bone grafting in the channel of screws. Methods Nine femurs fixed and preserved by formalin were used in this test. They were randomly divided into three groups: normal group, ungrafting-bone group, grafting-bone group. According to inversed-triangle, at the range of physiological load, it tested the defixed bias-value of three group femoral head at different load. The data were collected and analyzed. The three-dimension finite element model of the femoral head and neck was calculated. Nodal solution of stress value and max-offset was calculated at area of femoral head and neck, then the data were compared and analyzed.Results Compared with the mean of load-offset about the femoral head and neck, biomechanical capability of ungrafting-bone group was lowest with regard to other two groups , the influence was very hard, P <0.05. But there was no singnificant difference between normal group and graflng-bone group, P >0.05. Analysis of the three-dimension finite element model showed that the massive stress was concentrated at weight loading region of ungrafting-bone group's femoral head, it was an dangerous chance to lead to femoral head collapse. Conclusion For the treatment of femur neck fractures with cannulated compression screws, bone grafting in the channel of screw should be used to improve biomechanical integrity after fracture healed and cannulated compression screws are taken out. This is of benefit to loading in early stage and to preventing the collapse of femoral head, etc.%目的 探讨股骨颈骨折愈合后取出空心加压螺钉遗留钉道不植骨、植骨及正常的股骨头颈部的生物力学特性,为临床提供实验依据.方法 收集9付股骨标本测量

  9. Displaced patella fractures.

    Science.gov (United States)

    Della Rocca, Gregory J

    2013-10-01

    Displaced patella fractures often result in disruption of the extensor mechanism of the knee. An intact extensor mechanism is a requirement for unassisted gait. Therefore, operative treatment of the displaced patella fracture is generally recommended. The evaluation of the patella fracture patient includes examination of extensor mechanism integrity. Operative management of patella fractures normally includes open reduction with internal fixation, although partial patellectomy is occasionally performed, with advancement of quadriceps tendon or patellar ligament to the fracture bed. Open reduction with internal fixation has historically been performed utilizing anterior tension band wiring, although comminution of the fracture occasionally makes this fixation construct inadequate. Supplementation or replacement of the tension band wire construct with interfragmentary screws, cerclage wire or suture, and/or plate-and-screw constructs may add to the stability of the fixation construct. Arthrosis of the patellofemoral joint is very common after healing of patella fractures, and substantial functional deficits may persist long after fracture healing has occurred. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  10. [Extracorporeal shock wave therapy as a treatment of a non-healing chronic leg ulcer].

    Science.gov (United States)

    Stieger, M; Schmid, J-P; Bajrami, S; Hunziker, T

    2013-06-01

    Extracorporeal shock waves are defined as a sequence of sonic pulses characterized by high peak pressure over 100 MPa, fast pressure rise, and short lifecycle. In the 1980s extracorporeal shock wave lithotripsy (ESWL) was first used for the treatment of urolithiasis. Orthopedic surgeons use extracorporeal shock wave therapy (ESWT) to treat non-union fractures, tendinopathies and osteonecrosis. The first application of ESWT in dermatology was for recalcitrant skin ulcers. Several studies in the last 10 years have shown that ESWT promotes angiogenesis, increases perfusion in ischemic tissues, decreases inflammation, enhances cell differentiation and accelerates wound healing. We successfully treated a non-healing chronic venous leg ulcer with ESWT. Furthermore we observed an improvement of the lymphatic drainage after application of ESWT. We are confident that ESWT is a non-invasive, practical, safe and efficient physical treatment modality for recalcitrant leg ulcers.

  11. Study on the Effects of Differrent Compatibility of Traditonal Chinese Medicine on VEGF Expression at Fracture Site and Healing of Early Radius Fracture of Rats%桃仁、木香、黄芪分别与红花配伍对大鼠早期桡骨骨折愈合及VEGF表达的影响

    Institute of Scientific and Technical Information of China (English)

    王轩; 李引刚

    2009-01-01

    Objective:To observe the effect of different compatibility of herbs on VEGF expression at fracture site and thickness of callus of early radius fracture rat models. Methods:256 SD rats were divided into four groups randomly,model group,Semen Persicae and Flos Carthami group,Radix Aucklandiae and Flos Carthami group,Radix Astragali and Flos Carthami group.Left radius fracture rat models were established. Conventional haematoxylin and eosin staining and im-munostaining for bone section were carried out on clays 3,7,10 and 14 after model establishment. Results:On days 7,10 and 14 after model establishment, compared with model group, VEGF positive cells at fracture site and thickness of callus were significantly increased in all the treatment groups;compared with Radix Aucklandiae and Flos Carthami group,VEGF positive cells at fracture site and thickness of callus were significantly decreased in Semen Persicae and Flos Carthami group,Radix Astragali and Flos Carthami group. Conclusions:Radix Aucklandiae and Flos Carthami can increase obvi-ously VEGF expression at fracture site and thickness of callus in the healing of early radius fracture rats.We can get a con-clusion that the therapy of regulating the flow of qi and promoting the circulation of blood is an effective therapy on early extremities closed fracture from this experiment.%目的:观察桃仁、木香、黄芪分别与红花配伍对成年SD大鼠早期桡骨骨折愈合过程中骨痂厚度及VEGF表达的影响,为理气活血法用于四肢闭合性骨折早期临床治疗提供实验支持.方法:256只SD大鼠随机分为模型组、桃仁红花组、木香红花组、黄芪红花组4组,每组各64只,各组大鼠均造成左侧桡骨骨折模型.于造模后第3天、第7天、第10天、第14天,各组大鼠分4次处死,每次每组处死16只,取材进行常规HE染色观察骨痂厚度,VEGF-DAB显色计数观察VEGF阳性细胞数.结果:造模后第3天,各给药组与模型组比较,标本VEGF

  12. Effects of different compatibility of TCM on BMP-2 expression at fracture site and healing of early radius fracture of rats%桃仁、木香、黄芪分别与红花配伍对大鼠早期桡骨骨折愈合过程中BMP-2表达的影响

    Institute of Scientific and Technical Information of China (English)

    王轩; 潘琪; 张慧萍; 李引刚

    2011-01-01

    Carthami group, BMP-2 positive cells at fracture site and thickness of callus were significantly decreased in Semen Persicae and Flos Carthami group, Radix Astragali and Flos Carthami group.Conclusions: Radix Aueklandiae and Flos Carthami can increase obviously BMP-2 expression at fracture site and thickness of callus in the healing of early radius fracture rats. We can get a conclusion that the therapy of regulating the flow of qi and promoting the circulation of blood was an effective therapy on early extremities closed fracture from this experiment.

  13. Tooth mobility changes subsequent to root fractures

    DEFF Research Database (Denmark)

    Andreasen, Jens Ove; Christensen, Søren Steno Ahrensburg; Tsilingaridis, Georgios

    2012-01-01

    The purpose of this study was to analyze tooth mobility changes in root-fractured permanent teeth and relate this to type of interfragment healing (hard tissue healing (HT), interfragment healing with periodontal ligament (PDL) and nonhealing with interposition of granulation tissue (GT) because...... of pulp necrosis in the coronal fragment. Furthermore, the effect of age, location of the fracture on the root, and observation period on mobility values was analyzed. Mobility values were measured for 44 of 95 previous reported root-fractured permanent incisors. Mobility changes were measured...... after 3 months and 1 year, and a normalization of mobility value was usually found after 5 and 10 years. In 17 cases of PDL healing, generally a higher mobility was found in comparison with root fractures healing with hard tissue, and a consistent decrease in mobility value was found in the course...

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

    Directory of Open Access Journals (Sweden)

    Tracy K. Kovach

    2015-01-01

    Full Text Available 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.

  15. Carbon Dots as Fillers Inducing Healing/Self-Healing and Anticorrosion Properties in Polymers.

    Science.gov (United States)

    Zhu, Cheng; Fu, Yijun; Liu, Changan; Liu, Yang; Hu, Lulu; Liu, Juan; Bello, Igor; Li, Hao; Liu, Naiyun; Guo, Sijie; Huang, Hui; Lifshitz, Yeshayahu; Lee, Shuit-Tong; Kang, Zhenhui

    2017-08-01

    Self-healing is the way by which nature repairs damage and prolongs the life of bio entities. A variety of practical applications require self-healing materials in general and self-healing polymers in particular. Different (complex) methods provide the rebonding of broken bonds, suppressing crack, or local damage propagation. Here, a simple, versatile, and cost-effective methodology is reported for initiating healing in bulk polymers and self-healing and anticorrosion properties in polymer coatings: introduction of carbon dots (CDs), 5 nm sized carbon nanocrystallites, into the polymer matrix forming a composite. The CDs are blended into polymethacrylate, polyurethane, and other common polymers. The healing/self-healing process is initiated by interfacial bonding (covalent, hydrogen, and van der Waals bonding) between the CDs and the polymer matrix and can be optimized by modifying the functional groups which terminate the CDs. The healing properties of the bulk polymer-CD composites are evaluated by comparing the tensile strength of pristine (bulk and coatings) composites to those of fractured composites that are healed and by following the self-healing of scratches intentionally introduced to polymer-CD composite coatings. The composite coatings not only possess self-healing properties but also have superior anticorrosion properties compared to those of the pure polymer coatings. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Multifunctional composites: Healing, heating and electromagnetic integration

    Science.gov (United States)

    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. Forearm Fractures in Children

    Science.gov (United States)

    ... secure them in place. Your doctor may recommend surgery if: Casts support and protect broken bones while they heal. Reproduced from Pring M, Chambers H: Pediatric forearm fractures. Orthopaedic Knowledge Online Journal 2007; 5(5). Accessed October 2014. • The bone ...

  18. Progress in corneal wound healing.

    Science.gov (United States)

    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

  19. Progress in corneal wound healing

    Science.gov (United States)

    Ljubimov, Alexander V.; Saghizadeh, Mehrnoosh

    2015-01-01

    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 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 epithelium, and

  20. Dating fractures in infants

    Energy Technology Data Exchange (ETDEWEB)

    Halliday, K.E., E-mail: kath.halliday@nuh.nhs.uk [Department of Radiology, Nottingham University Hospitals, Queen' s Medical Centre, Nottingham (United Kingdom); Broderick, N.J.; Somers, J.M. [Department of Radiology, Nottingham University Hospitals, Queen' s Medical Centre, Nottingham (United Kingdom); Hawkes, R. [Department of Radiology, Paul O' Gorman Building, Bristol (United Kingdom)

    2011-11-15

    Aim: To document the timing of the appearance of the radiological features of fracture healing in a group of infants in which the date of injury was known and to assess the degree of interobserver agreement. Materials and methods: Three paediatric radiologists independently assessed 161 images of 37 long bone fractures in 31 patients aged 0-44 months. The following features were assessed: soft-tissue swelling, subperiosteal new bone formation (SPNBF), definition of fracture line, presence or absence of callus, whether callus was well or ill defined, and the presence of endosteal callus. Results: Agreement between observers was only moderate for all discriminators except SPNBF. SPNBF was invariably seen after 11 days but was uncommon before this time even in the very young. In one case SPNBF was seen at 4 days. Conclusion: With the exception of SPNBF, the criteria relied on to date fractures are either not reproducible or are poor discriminators of fracture age.

  1. Growth hormone does not stimulate early healing in rat tendons

    OpenAIRE

    2012-01-01

    Growth Hormone stimulates bone growth and fracture repair. It acts mainly by increasing the systemic levels of IGF-1. Local treatment with IGF-1 appears to stimulate tendon healing. We therefore hypothesized that systemic treatment with Growth Hormone would also stimulate tendon healing. Rat Achilles tendons were transected and left to heal. 4 groups were studied. Intramuscular injections of botulinum toxin A (Botox) were used to reduce loading in 2 groups. The animals were randomized to twic...

  2. El trasplante autólogo de células mesoteliales como acelerador y modificador de la cicatrización cutánea en ratas Autologous mesothelial cells transplantation as accelerator and skin healing modifier in rats

    Directory of Open Access Journals (Sweden)

    R. Esparza Iturbide

    2013-03-01

    retraction, data support a proliferative phase of healing. In the Group II or experimental were found less inflammation and fibrosis, increased collagen and data consistent with a remodeling phase. In conclusion, we found that autologous peritoneal mesothelial cells in full thickness wounds accelerates the normal skin healing in rats by decreasing inflammation, fibrosis and increased collagen.

  3. Pedicular stress fracture in the lumbar spine

    Energy Technology Data Exchange (ETDEWEB)

    Chong, V.F.H.; Htoo, M.M. [Singapore General Hospital, Singapore, (Singapore). Department of Diagnostic Radiology

    1997-08-01

    Spondylolisthesis with or without spondylolysis is common in the lumbar spine. Associated fracture in the pedicle (`pediculolysis`) is unusual. The margins of pedicular stress fractures, like spondylolysis, usually appear sclerotic. A patient with a pedicular stress fracture with minimal marginal sclerosis suggesting an injury of recent onset is presented here. There was associated bilateral spondylolysis. The findings in this patient suggest that established pediculolysis probably represents a stress fracture that has failed to heal. (authors). 10 refs., 2 figs.

  4. Analogy between fluid cavitation and fracture mechanics

    Science.gov (United States)

    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.

  5. Effect of local application of simvastatin in biodegradable coating of osteosynthetic implants on osteoporotic fracture healing in rats%高生物涂层局部应用辛伐他汀对大鼠骨质疏松性骨折愈合的影响

    Institute of Scientific and Technical Information of China (English)

    张俊山; 田发明; 康玉川; 骆阳; 刘冠华; 张柳

    2013-01-01

    Objective To evaluate the effect of local application of simvastatin in a biodegradable coating of osteosynthetic implants on osteoporotic fracture healing in ovariectomized (OVX) rats.Methods Thirty female SD rats of 3 months old were randomly divided into 3 groups (n =10),group A,group B and group C.The rats of group B and group C underwent ovariectomy,while those in group A received sham operation.Midshaft femur fracture model was established at 6 weeks after ovariectomy.Intramedullary stabilization was achieved without coating in group A,with polymer coating in group B,and with polymer plus simvastatin coating in group C.The right femurs were harvested at 6 weeks after fracture operation,and radiographic evaluation,bone mineral density (BMD) measurement,HE staining,and immunohistochemical staining for VEGF and BMP-2 detection were performed.Restlts Radiographic results demonstrated the proportion of complete and incomplete ridging callus in group A and C was markedly higher than that in group B (P < 0.05).The BMD of total femur and BMD of callus in group A and group C were significantly higher than those in group B (P < 0.05).The results of immunohistochemical staining showed that the mean absorbance of VEGF and BMP-2 in group A and group C was significantly higher than that in group B (P < 0.05).Conclusion Local application of simvastatin as a biodegradable coating of osteosynthetic implants can accelerate the fracture healing process in osteoporotic rats,which may rely on increasing BMD and up-regulating the expression of BMP-2 and VEGF in callus.%目的 研究局部应用辛伐他汀对卵巢切除大鼠骨质疏松性骨折愈合的影响.方法 30只3月龄雌性SD大鼠,随机数字表法分为假手术+骨折组(A组)、卵巢切除+骨折组(B组)、卵巢切除+骨折+辛伐他汀缓释干预组(C组),每组10只.A组仅暴露腹腔,其余2组行卵巢切除术,术后6周,实验大鼠均制作右侧股骨骨折模型.A组行无涂层的髓内固

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  8. Scaphoid fractures in the athlete.

    Science.gov (United States)

    Winston, Mark J; Weiland, Andrew J

    2017-03-01

    Scaphoid fractures are a common wrist injury, especially in athletes. Clinicians should have a high index of suspicion for a scaphoid fracture in any patient complaining of radial-sided wrist pain after a fall on an outstretched hand. Advanced imaging, including CT and MRI scans, may be useful in diagnosis and classification of fracture patterns. Treatment varies based on the fracture location, stability of the fracture, and predictability of the fracture to heal. Treatment involves either non-operative management with a thumb spica cast or brace, or operative fixation with a headless compression screw, k-wires, or scaphoid-specific plates. Return to play is dependent on many variables, including sport, fracture union, and ability to play with cast.

  9. Medicinal plants and bone healing.

    Science.gov (United States)

    Singh, Vibha

    2017-01-01

    Fracture is defined as complete or incomplete separation in the continuity of bone Fracture healing is a complex physiological process that involves the coordinated participation of hematopoietic and immune cells within bone marrow. It conjunction with vascular and skeletal cell precursors it also includes mesenchymal stem cells which are recruited from the circulation and the surrounding tissues. It is estimated that 80% of the population in developing countries still rely on the traditional herbal medicines. Healing is practiced by people from all levels of society, who live and work in intimate relation with their environment. They range from bone setting, treatment of snake bite and mental disorders. Knowledge of Medicinal plants and their identification should be gain with the help of cowherds, hermits, hunters, forest dwellers and those who gather plants of forest for food. Sushruta Samita Sutrasthanam 36 V.10. Herbs can effective in reducing swelling pain and soreness of the fracture and al so speedy recovery of function. In last few decades there has been growing In alternative forms of therapy globally. Herbal medicines are currently in demand and their popularity is increasing.

  10. Clinical analysis of the rap stress stimulator applied for crus fracture after skeletal external fixation

    OpenAIRE

    Zhuang, Ping; Hong, Jiayuan; Chen, Wei; Wu, Jin; Ding, Zhenqi

    2015-01-01

    Introduction Open crus fracture is still difficult in clinical treatment because of the delayed fracture union and high rate of nonunion after the operation. A consensus has been reached that mechanical stress can promote fracture healing. We independently developed a stress stimulator, which can provide longitudinal pressure for the fixed fracture end of the lower legs to promote fracture healing. The purpose of this study is to explore the advantages and clinical effect of the rap stress st...

  11. Effects of Traditional Chinese Medicine Formula for Nourishing Kidney-Essence on Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells in Rabbits in Different Phases of Fracture Healing%补肾填精法对兔骨折后不同时相骨髓间充质干细胞成骨分化的影响

    Institute of Scientific and Technical Information of China (English)

    王斌; 罗毅文; 胡年宏

    2013-01-01

    目的 观察补肾填精中药对兔骨折后不同时点骨髓间充质干细胞(bone marrow mesenchymal stem cells,BMSCs)分化为成骨细胞的影响.方法 将20只白兔随机分成4组,即正常对照组、骨折模型组、中药治疗组、西药治疗组.分离培养骨折端BMSCs,取P3代BMSCs并向成骨细胞诱导分化,分别采用碱性磷酸酶(alkaline phosphatase,ALP)试剂盒、骨钙素(osteocalcin,OCN)试剂盒检测ALP活性、OCN水平.结果 随着用药时间的延长,各骨折组ALP活性和OCN水平均逐渐增强.在骨折后第14、21天,中药治疗组ALP活性、OCN水平均高于其他3组.结论 补肾填精法可促进兔骨折后不同时点BMSCs向成骨细胞分化.%Objective To observe the effects of traditional Chinese medicine (TCM) formula for nourishing kidney-essence on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in rabbits in different phases of fracture healing. Methods Twenty white rabbits were divided into normal control group, fracture model group, TCM treatment group, and Western medicine (WM) treatment group. The BMSCs at the fracture ends were isolated and cultured, and the passage 3 cells were collected and then induced to differentiate into osteoblasts. Alkaline phosphatase (ALP) assay kit and osteocalcin (OCN) assay kit were used to measure the ALP activity and OCN level, respectively. Results After fracture, the ALP activity and OCN level increased gradually in the fracture model group, TCM treatment group, and WM treatment group. At 14 and 21 days after fracture, the TCM treatment group had significantly higher ALP activity and OCN level than the other three groups (P<0. 05 or P<0. 01). Conclusion TCM formula for nourishing kidney-essence can promote the osteogenic differentiation of BMSCs in rabbits in different phases of fracture healing.

  12. Re-evaluation of low intensity pulsed ultrasound in treatment of tibial fractures (TRUST): randomized clinical trial

    Science.gov (United States)

    Bhandari, Mohit; Einhorn, Thomas A; Schemitsch, Emil; Heckman, James D; Tornetta, Paul; Leung, Kwok-Sui; Heels-Ansdell, Diane; Makosso-Kallyth, Sun; Della Rocca, Gregory J; Jones, Clifford B; Guyatt, Gordon H

    2016-01-01

    Objective To determine whether low intensity pulsed ultrasound (LIPUS), compared with sham treatment, accelerates functional recovery and radiographic healing in patients with operatively managed tibial fractures. Design A concealed, randomized, blinded, sham controlled clinical trial with a parallel group design of 501 patients, enrolled between October 2008 and September 2012, and followed for one year. Setting 43 North American academic trauma centers. Participants Skeletally mature men or women with an open or closed tibial fracture amenable to intramedullary nail fixation. Exclusions comprised pilon fractures, tibial shaft fractures that extended into the joint and required reduction, pathological fractures, bilateral tibial fractures, segmental fractures, spiral fractures >7.5 cm in length, concomitant injuries that were likely to impair function for at least as long as the patient’s tibial fracture, and tibial fractures that showed 1 cm gap after surgical fixation. 3105 consecutive patients who underwent intramedullary nailing for tibial fracture were assessed, 599 were eligible and 501 provided informed consent and were enrolled. Interventions Patients were allocated centrally to self administer daily LIPUS (n=250) or use a sham device (n=251) until their tibial fracture showed radiographic healing or until one year after intramedullary fixation. Main outcome measures Primary registry specified outcome was time to radiographic healing within one year of fixation; secondary outcome was rate of non-union. Additional protocol specified outcomes included short form-36 (SF-36) physical component summary (PCS) scores, return to work, return to household activities, return to ≥80% of function before injury, return to leisure activities, time to full weight bearing, scores on the health utilities index (mark 3), and adverse events related to the device. Results SF-36 PCS data were acquired from 481/501 (96%) patients, for whom we had 2303/2886 (80

  13. Acceleration of Ligament Healing with Cellular Attractants

    Science.gov (United States)

    2008-07-01

    70. [5] Chen Q, Fitch J, Gibney E, Linsenmayer TF. Type II collagen during cartilage and corneal development: immunohistochemical analyses with an...McCarthy, D.M., Kwak, S.D., Legrand, P., Fo- garosi, F., Ciaccio, E.J., and Ateshian, G.A. Knee cartilage topography , thickness, and contact areas from

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

    Directory of Open Access Journals (Sweden)

    Poeze Martijn

    2011-05-01

    Full Text Available Abstract 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

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

    Science.gov (United States)

    Hannemann, Pascal; Göttgens, Kevin W A; van Wely, Bob J; Kolkman, Karel A; Werre, Andries J; Poeze, Martijn; Brink, Peter R G

    2011-05-06

    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. 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 evaluated by CT-scanning, functional

  16. 动机性访谈对儿童小腿创伤慢性伤口愈合的影响%Effect of motivational interview on accelerating chronic wound healing in children with calf injury

    Institute of Scientific and Technical Information of China (English)

    蒋雪飞; 林梅; 傅强; 谭伟欣; 欧会芝

    2016-01-01

    Objective:To explore the effect of motivational interview on accelerating chronic wound healing in children with calf injury. Methods:Selected 140 children with traumatic chronic wounds from January 2015 to December 2015 and randomly divided them into control group and intervention group. The control group was given routine health education. The intervention group established the motivational interview intervention model based on the cross - theo-retical model. The treatment effect was evaluated by wound score and average dressing treatment time. Results:Compared with the situation before the inter-vention,the wound scores of the two groups were decreased at some degree,however the decreased degree of the intervention group was more significant than that of the control group(P < 0. 05). The average time of dressing change of the intervention group was significantly shorter than that of the control group(P < 0. 05). No significant difference was found between the cure rates of the two groups(P ﹥ 0. 05). Conclusion:Motivational interview can relieve children’s depression and tension caused by trauma through motivating inner behavioral change willing,improve children’s compliance and promote the healing of chronic wounds effectively.%目的:探讨动机性访谈对促进儿童小腿创伤慢性伤口愈合的效果。方法:将2015年1~12月140例儿童小腿创伤性慢性伤口患儿随机等分为对照组和干预组,对照组进行常规健康教育;干预组基于跨理论模型建立动机性访谈干预模式。采用伤口疮面评分、平均换药治疗时间评价干预效果。结果:干预前后两组患儿疮面评分均有不同程度降低,但干预组下降程度较对照组更加明显(P <0.05),且平均换药治疗时间明显短于对照组(P <0.05),伤口疮面的痊愈率两组无明显差异(P ﹥0.05)。结论:动机性访谈可通过激发患儿内在行为改变意愿,消除患儿因创伤造成的

  17. Complications of mandibular fractures.

    Science.gov (United St