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Binder, Harald, Stefan Eipeldauer, Markus Gregori, Leonard Höchtl-Lee, Anita Thomas, Thomas M. Tiefenboeck, Stefan Hajdu, and Kambiz Sarahrudi. "The Difference between Growth Factor Expression after Single and Multiple Fractures: Preliminary Results in Human Fracture Healing." Disease Markers 2015 (2015): 1–5. http://dx.doi.org/10.1155/2015/203136.
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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.
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Gajdobranski, Djordje, and Dragana Zivkovic. "Physiology of fracture healing: New aspects." Medical review 56, no. 1-2 (2003): 39–42. http://dx.doi.org/10.2298/mpns0302039g.
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Introduction Skeletal system has a great regenerative potential, but it isn't the case with other tissues. Bone fracture healing includes a complex cascade of processes at cellular and biochemical levels, ending with a complete structural and functional restoration of the damaged bone. Impaired healing occurs in 5-10% of all fractures, manifesting as delayed union or non-union Such a high incidence of impaired healing certainly presents a problem, and therefore, permanent research regarding physiology of fracture healing is justified. Phases of fracture healing In this paper we described four phases of fracture healing. They are not clearly separated, but overlap. These data are based on contemporary literature and newest achievements in the field of fracture healing. Discussion Many data regarding this phenomenon were obtained from animal studies, but they may also be applied in human medicine since there is a great similarity between fracture healing in animal models and humans. Conclusion Full and complete knowledge of mechanisms of bioregulation of normal fracture healing process certainly presents the basic prerequisite for successful surgical and orthopedic treatment.
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Moon, Myung-Sang, Sang-Yup Lee, Dong-Hyeon Kim, and Min-Geun Yoon. "HEALING PATTERN OF THE INTERLOCKING INTRAMEDULLARY NAILED CLOSED TIBIAL SHAFT FRACTURES — EFFECT OF AGE, IM NAIL AND FIBULA ON CALLUS FORMATION." Journal of Musculoskeletal Research 19, no. 04 (December 2016): 1650017. http://dx.doi.org/10.1142/s0218957716500172.
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Objectives: To assess the healing pattern of the fractured tibial shaft with or without fibula fracture, fixated with locked intramedullary (IM) standard cannulated titanium nail in a group of patients in each decade; nonosteonal versus osteonal. Summary of background data: Up to now there have been many previous clinical studies on the nailed tibial shaft fractures. However, only a few animal experiments dealt with the callus type in healing, and a little human researches on the effect of the age and fixation device on callus formation in tibia at the two bone level of the lower limb were carried out. Material and Methods: 135 out of 168 patients with normally united closed tibial shaft fractures, fixated with titanium cannulated nail which showed good quality radiograms, were subjected to this study: 10 patients at minimum in each decade from late teens to 8th decade being regularly and radiographically followed were selected. Results: The nailed fractures united primarily by periosteal callus in the teenagers, while in the patients over third decade the fractures united by the intercortical uniting callus (osteonal). Conclusion: It was found that nail in tibia could not suppress the periosteal reparative reaction in the late teenagers which was suppressed in the adults. Union of the titanium nail-fixated adult tibial shaft fractures had to be depended primarily on osteonal healing because of the suppressed reparative periosteal reaction.
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Kundu, Sujoy. "Teriparatide treatment in fracture non-union: a case report." International Journal of Research in Orthopaedics 3, no. 4 (June 23, 2017): 890. http://dx.doi.org/10.18203/issn.2455-4510.intjresorthop20172892.
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<p class="abstract">Impaired healing of fractures delays the rehabilitation process, which in turn impacts quality of life. The associated costs cause an economic burden to both the society and the patients. Till date, no systemic treatment is approved for fracture healing. Teriparatide is a synthetic polypeptide hormone consisting of the 1–34 fragment of human parathyroid hormone. Apart from its recognized indication of osteoporosis, there is a growing body of evidence suggesting its ability to accelerate fracture healing and heal non-unions. The purpose of this case report is to elucidate the Indian experience of 5 cases of use of Teriparatide for fracture healing - delayed unions and non-unions and in the setting of osteoporotic fracture. The primary observation of our case report depicts that teriparatide is a viable therapy not only to treat osteoporosis but also to accelerate fracture healing. Teriparatide therapy accelerates healing, which allows patients to return to normal life and work faster, optimizes medical resource utilization, reduces chances for future second surgery, requirement of bone graft and overall chronic morbidity associated with long-term treatment. The advantages of teriparatide therapy are that it can be prescribed in any types of fractures, including those that will be treated non-surgically; it can be commenced at any time, and can be applied through the entire healing period. Our observations are in line with other studies showing the effects of Teriparatide on delayed union and non-unions in human subjects.</p>
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Stoffel, Karl, Hanna Engler, Markus Kuster, and Walter Riesen. "Changes in Biochemical Markers after Lower Limb Fractures." Clinical Chemistry 53, no. 1 (January 1, 2007): 131–34. http://dx.doi.org/10.1373/clinchem.2006.076976.
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Abstract Background: The bone remodeling sequence after bone fracture changes the concentrations of biochemical bone markers, but the relationships of fracture size and of healing time to changes in biomarkers are unclear. The present pilot study was undertaken to determine the changes found in serum bone markers after plate osteosynthesis of closed distal tibial and malleolar fractures during a study period of 24 weeks. Methods: We measured tatrate-resistant acid phosphatase (TRACP 5b), collagen type I C-terminal telopeptide (ICTP), bone-specific alkaline phosphatase (bone ALP), osteocalcin (OC), procollagen type I C-terminal propeptide (PICP), procollagen type III N-terminal propeptide (PIIINP), and human cartilage glycoprotein 39 (YKL-40) in 20 patients with lower limb fractures (10 malleolar, 10 tibia). A physical examination and radiographs were completed to assess evidence of union. Results: All malleolar fractures healed within 6 weeks, whereas 2 tibial fractures did not show complete bone healing after 24 weeks. Changes were comparable but more pronounced in the tibia group, and marker concentrations remained increased at the end of study (bone ALP, 86 vs 74 U/L; OC, 14.9 vs 7.7 μg/L; ICTP: 5.6 vs 3.3 μg/L at day 84 after osteosynthesis, P <0.05 in tibia; 80 vs 70 U/L, 8 vs 5.2 μg/L, and 3.5 vs 3.2 μg/L, respectively, in the malleolar fracture group). Conclusions: In normal bone healing, changes in bone turnover markers were primarily dependent on the fracture size. Delayed tibia fracture healing may involve a disturbance in bone remodeling.
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Andrew, JG, JA Hoyland, AJ Freemont, and DR Marsh. "P40. PDGF expression in normally healing human fractures." Bone 15, no. 2 (March 1994): 239–40. http://dx.doi.org/10.1016/8756-3282(94)90773-0.
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Huang, Yan, Yongqiang Xu, Siyin Feng, Pan He, Bing Sheng, and Jiangdong Ni. "miR-19b enhances osteogenic differentiation of mesenchymal stem cells and promotes fracture healing through the WWP1/Smurf2-mediated KLF5/β-catenin signaling pathway." Experimental & Molecular Medicine 53, no. 5 (May 2021): 973–85. http://dx.doi.org/10.1038/s12276-021-00631-w.
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AbstractBone marrow mesenchymal stem cell (BMSC)-derived exosomes have been found to enhance fracture healing. In addition, microRNAs contributing to the healing of various bone fractures have attracted widespread attention in recent years, but knowledge of the mechanisms by which they act is still very limited. In this study, we clarified the function of altered microRNA-19b (miR-19b) expression in BMSCs in fracture healing. We modulated miR-19b expression via mimics/inhibitors in BMSCs and via agomirs in mice to explore the effects of these changes on osteogenic factors, bone cell mineralization and the healing status of modeled fractures. Through gain- and loss-of function assays, the binding affinity between miR-19b and WWP1/Smurf2 was identified and characterized to explain the underlying mechanism involving the KLF5/β-catenin signaling pathway. miR-19b promoted the differentiation of human BMSCs into osteoblasts by targeting WWP1 and Smurf2. Overexpression of WWP1 or Smurf2 degraded the target protein KLF5 in BMSCs through ubiquitination to inhibit fracture healing. KLF5 knockdown delayed fracture healing by modulating the Wnt/β-catenin signaling pathway. Furthermore, miR-19b enhanced fracture healing via the KLF5/β-catenin signaling pathway by targeting WWP1 or Smurf2. Moreover, miR-19b was found to be enriched in BMSC-derived exosomes, and treatment with exosomes promoted fracture healing in vivo. Collectively, these results indicate that mesenchymal stem cell-derived exosomal miR-19b represses the expression of WWP1 or Smurf2 and elevates KLF5 expression through the Wnt/β-catenin signaling pathway, thereby facilitating fracture healing.
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Massie, Anna, Mark Fuller, Frank Verstraete, Boaz Arzi, and Amy Kapatkin. "Outcome of nonunion fractures in dogs treated with fixation, compression resistant matrix, and recombinant human bone morphogenetic protein-2." Veterinary and Comparative Orthopaedics and Traumatology 30, no. 02 (2017): 153–59. http://dx.doi.org/10.3415/vcot-16-05-0082.
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SummaryObjectives: To report the use of compression resistant matrix (CRM) infused with recombinant human bone morphogenetic protein (rhBMP-2) prospectively in the healing of non union long-bone fractures in dogs.Methods: A longitudinal cohort of dogs that were presented with nonunion fractures were classified and treated with CRM soaked with rhBMP-2 and fracture fixation. They were followed with serial radiographs and evaluated for healing times and complications according to the time frame and definitions previously established for orthopaedic clinical cases.Results: Eleven nonunion fractures in nine dogs were included. Median healing time was 10 weeks (range: 7–20 weeks). Major perioperative complications due to bandage morbidity were encountered in two of 11 limbs and resolved. All other complications were minor. They occurred perioperatively in eight of 11 limbs. Minor follow-up complications included short-term in one of two limbs, mid-term in one of three, and long-term in four of five limbs. Nine limbs returned to full function and two limbs returned to acceptable function at the last follow-up.Clinical significance: Nonunion fractures given a poor prognosis via standard-of-care treatment were successfully repaired using CRM with rhBMP-2 accompanying fixation. These dogs, previously at high risk of failure, returned to full or acceptable function.
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Wong, Lydia Chwang Yuh, Wing Kong Chiu, Matthias Russ, and Susan Liew. "Experimental Testing of Vibration Analysis Methods to Monitor Recovery of Stiffness of a Fixated Synthetic Pelvis: A Preliminary Study." Key Engineering Materials 558 (June 2013): 386–99. http://dx.doi.org/10.4028/www.scientific.net/kem.558.386.
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Monitoring the healing of long bones has been studied extensively to reduce the period of encumbrance and unnecessary pain for patients suffering from fractured bones. This is more critical for unstable fractures in the pelvis as the patients can bedridden for up to 12 weeks to allow proper healing to take place. Current methods employed to monitor long bone healing are insufficient for applications in the pelvis as the human pelvis presents a significant change in geometry which demands a different approach. This paper explores an approach where vibration analysis is used to provide in-situ monitoring of a healing fracture in a human pelvis. Experimental tests were conducted on 4th generation synthetic pelvises instrumented with an array of PZT sensors. The synthetic pelvises were cut at the sacrum to simulate a fractured pelvis followed by the application of araldite epoxy to simulate healing by allowing the epoxy to cure. Measurements were collected from the sensor array over the curing period to obtain the transfer functions (TFs) for various excitations. An impact hammer was utilised to obtain powerful broadband excitations while the PZT sensors were used to detect the response in the synthetic pelvis as a results of these excitation signals. A comparison of TF against cure time (healed amount) indicates the presence of a significant relationship with the stiffness recovery of the epoxy at the cut of the synthetic model.
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Pfeiffenberger, Moritz, Alexandra Damerau, Annemarie Lang, Frank Buttgereit, Paula Hoff, and Timo Gaber. "Fracture Healing Research—Shift towards In Vitro Modeling?" Biomedicines 9, no. 7 (June 28, 2021): 748. http://dx.doi.org/10.3390/biomedicines9070748.
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Fractures are one of the most frequently occurring traumatic events worldwide. Approximately 10% of fractures lead to bone healing disorders, resulting in strain for affected patients and enormous costs for society. In order to shed light into underlying mechanisms of bone regeneration (habitual or disturbed), and to develop new therapeutic strategies, various in vivo, ex vivo and in vitro models can be applied. Undeniably, in vivo models include the systemic and biological situation. However, transferability towards the human patient along with ethical concerns regarding in vivo models have to be considered. Fostered by enormous technical improvements, such as bioreactors, on-a-chip-technologies and bone tissue engineering, sophisticated in vitro models are of rising interest. These models offer the possibility to use human cells from individual donors, complex cell systems and 3D models, therefore bridging the transferability gap, providing a platform for the introduction of personalized precision medicine and finally sparing animals. Facing diverse processes during fracture healing and thus various scientific opportunities, the reliability of results oftentimes depends on the choice of an appropriate model. Hence, we here focus on categorizing available models with respect to the requirements of the scientific approach.
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Hurter, K., P. Schawalder, and H. G. Schmökel. "Percutaneous plating of tibial fractures in two dogs." Veterinary and Comparative Orthopaedics and Traumatology 16, no. 03 (July 2003): 191–95. http://dx.doi.org/10.1055/s-0038-1632776.
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SummaryA trend toward minimally invasive procedures in the treatment of fractures in human patients is apparent in recent publications. Percutaneous plating is one method of fracture fixation, conceived to minimise soft tissue damage and preserve soft tissue and bone vascularity. The use of fewer screws, in longer bridging plates, is also a relatively new technique in the stabilisation of comminuted diaphyseal fractures in human patients. A combination of these techniques was applied in two dogs with comminuted tibial fractures.The plates were passed subfascially and the screws inserted through skin incisions over the proximal and distal ends of the plate. Follow-up radiographs revealed fracture healing with callus formation after four or five weeks. Percutaneous plating seems to be a useful technique in small animals. Further studies on larger numbers of patients are needed to define the benefits and the limitations of this technique.
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Yamakawa, Daiki, Yoko Kawase-Koga, Yasuyuki Fujii, Yuki Kanno, Marika Sato, Shinsuke Ohba, Yoshiaki Kitaura, Miki Kashiwagi, and Daichi Chikazu. "Effects of Helioxanthin Derivative-Treated Human Dental Pulp Stem Cells on Fracture Healing." International Journal of Molecular Sciences 21, no. 23 (December 1, 2020): 9158. http://dx.doi.org/10.3390/ijms21239158.
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Bone defects affect patients functionally and psychologically and can decrease quality of life. To resolve these problems, a simple and efficient method of bone regeneration is required. Human dental pulp stem cells (DPSCs) have high proliferative ability and multilineage differentiation potential. In our previous study, we reported a highly efficient method to induce osteogenic differentiation using DPSC sheets treated with a helioxanthin derivative (4-(4-methoxyphenyl)pyrido[40,30:4,5]thieno[2,3-b]pyridine-2-carboxamide (TH)) in a mouse calvarial defect model. However, the localization of the DPSCs after transplantation remains unknown. Therefore, in this study, we investigated the localization of transplanted DPSCs in a mouse fracture model. DPSCs were collected from six healthy patients aged 18–29 years, cultured in normal medium (NM), osteogenic medium (OM), or OM with TH, and fabricated them into cell sheets. To evaluate the efficacy of fracture healing using DPSCs treated with OM+TH, and to clarify the localization of the transplanted DPSC sheets in vivo, we transplanted OM+TH-treated DPSC sheets labeled with PKH26 into mouse tibiae fractures. We demonstrated that transplanted OM+TH-treated DPSCs sheets were localized to the fracture site and facilitated bone formation. These results indicated that transplanted OM+TH-treated DPSCs were localized at fracture sites and directly promoted fracture healing.
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Watson, Luke, Xi Zhe Chen, Aideen E. Ryan, Áine Fleming, Aoife Carbin, Lisa O’Flynn, Paul G. Loftus, et al. "Administration of Human Non-Diabetic Mesenchymal Stromal Cells to a Murine Model of Diabetic Fracture Repair: A Pilot Study." Cells 9, no. 6 (June 3, 2020): 1394. http://dx.doi.org/10.3390/cells9061394.
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Individuals living with type 1 diabetes mellitus may experience an increased risk of long bone fracture. These fractures are often slow to heal, resulting in delayed reunion or non-union. It is reasonable to theorize that the underlying cause of these diabetes-associated osteopathies is faulty repair dynamics as a result of compromised bone marrow progenitor cell function. Here it was hypothesized that the administration of non-diabetic, human adult bone marrow-derived mesenchymal stromal cells (MSCs) would enhance diabetic fracture healing. Human MSCs were locally introduced to femur fractures in streptozotocin-induced diabetic mice, and the quality of de novo bone was assessed eight weeks later. Biodistribution analysis demonstrated that the cells remained in situ for three days following administration. Bone bridging was evident in all animals. However, a large reparative callus was retained, indicating non-union. µCT analysis elucidated comparable callus dimensions, bone mineral density, bone volume/total volume, and volume of mature bone in all groups that received cells as compared to the saline-treated controls. Four-point bending evaluation of flexural strength, flexural modulus, and total energy to re-fracture did not indicate a statistically significant change as a result of cellular administration. An ex vivo lymphocytic proliferation recall assay indicated that the xenogeneic administration of human cells did not result in an immune response by the murine recipient. Due to this dataset, the administration of non-diabetic bone marrow-derived MSCs did not support fracture healing in this pilot study.
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Zhu, Junxiong, Chenggui Zhang, Jialin Jia, Wanqiong Yuan, Min Zhang, Huijie Leng, and Chunli Song. "Effect of weekly teriparatide injections on osteoporotic fracture healing: protocol for a double-blind, randomised controlled trial." BMJ Open 11, no. 4 (April 2021): e043137. http://dx.doi.org/10.1136/bmjopen-2020-043137.
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IntroductionBoth animal studies and clinical trials have shown that daily parathyroid hormone administration promotes bone fracture healing. We previously found that weekly injections of the recombinant human parathyroid hormone teriparatide at a dosage of 20 μg/kg promoted tibial fracture healing to the same extent as daily injections of teriparatide at a dosage of 10 μg/kg in a rodent model. However, the effect of weekly teriparatide administration on human fracture healing is unreported. This protocol describes a randomised controlled clinical trial designed to evaluate whether weekly administration of teriparatide accelerates fracture repair in humans.Methods and analysisThis single-centre, double-blind, randomised controlled trial will be conducted in Peking University Third Hospital. Eligible patients with Colles’ fracture incurred within 48 hours will be randomly divided into two groups (n=40 per group) that will receive 14 weekly subcutaneous injections of either saline or teriparatide (40 μg/week). The primary outcome will be the time taken to achieve radiographic healing, as assessed using the modified radiographic union scale for tibial fractures. The secondary outcomes will be functional assessments, including the self-administered Patient-Rated Wrist Evaluation questionnaire, grip strength and rate of fracture non-union.Ethics and disseminationEthical approval has been obtained from the Peking University Third Hospital Medical Science Research Ethics Committee (M2020207). The findings will be disseminated in peer-reviewed publications.Trial registration numberNCT04473989: protocol version: 1.
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Starlinger, Julia, Georg Kaiser, Anita Thomas, and Kambiz Sarahrudi. "The impact of nonosteogenic factors on the expression of osteoprotegerin and RANKL during human fracture healing." Bone & Joint Research 8, no. 7 (July 2019): 349–56. http://dx.doi.org/10.1302/2046-3758.87.bjr-2018-0116.r3.
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Objectives The osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL) balance is of the utmost importance in fracture healing. The aim of this study was therefore to investigate the impact of nonosteogenic factors on OPG and RANKL levels. Methods Serum obtained from 51 patients with long bone fractures was collected over 48 weeks. The OPG and serum sRANKL (soluble RANKL) concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Smoking habit, diabetes, and alcohol consumption were recorded. Results Age and sex greatly influenced preoperative serum levels of OPG and sRANKL but differences were even more pronounced during fracture healing. Statistical significance was observed for overall serum levels of OPG (p = 0.001) and sRANKL (p < 0.001) in older men and women (age greater than 50 years). Interestingly, OPG levels increased over time in older women but decreased over time in older men. Conclusion These data suggest that nonosteogenic factors, most significantly age and sex, have a major impact on sRANKL and OPG levels. Given the established association of OPG and sRANKL levels and nonunion, these findings seem to be of clinical relevance. Cite this article: J. Starlinger, G. Kaiser, A. Thomas, K. Sarahrudi. The impact of nonosteogenic factors on the expression of osteoprotegerin and RANKL during human fracture healing. Bone Joint Res 2019;8:349–356. DOI: 10.1302/2046-3758.87.BJR-2018-0116.R3.
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Dyachenko, Denis, Alexander Vorobyev, Yuliya Makedonova, Svetlana Dyachenko, Svetlana Vargina, and Oksana Kurkina. "EXOSKELETON FOR LOWER JAW FRACTURES TREATMENT." Archiv Euromedica 11, no. 3 (July 3, 2021): 68–70. http://dx.doi.org/10.35630/2199-885x/2021/11/3/16.
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The aim of this study was to study the possibility of the lower jaw exoskeleton as a means of treating its fractures. The analysis took into account the ability of the extrafocal osteosynthesis apparatus to maintain the spatial orientation of bone fragments under load. For this, the apparatus was analyzed by the finite element method on 3D models and a study was carried out in a special stand on the bones of the human lower jaw. As a result of the analysis, it was revealed that the lower jaw exoskeleton makes it possible to qualitatively fix the fragments of the lower jaw for the period of fracture healing.
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Otoni, C. C., O. C. M. Pereira-Júnior, A. L. L. Blum, L. C. Vulcano, and C. Rahal. "Synthesis Pengo System plates for the treatment of long-bone diaphyseal fractures in dogs." Veterinary and Comparative Orthopaedics and Traumatology 21, no. 01 (2008): 59–63. http://dx.doi.org/10.3415/vcot-07-05-0049.
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SummaryA Brazilian orthopaedic company designed a stainless steel plate called Synthesis Pengo System (S.P.S.), which has one fixed and one changeable extremity. According to the assembly of the changeable extremity, it is possible to obtain dynamization or neutralization of the fracture site. Since the S.P.S. plate was developed for use in human patients, the aim of this study was to evaluate this system in long-bone diaphyseal fractures in dogs. Eight dogs with closed diaphyseal fractures of the femur (n= 1), radius and ulna (n=5), and tibia (n=2) were used. Patients were aged seven months to three years and weighed 18 to 31.2 kg. The S.P.S. plate was assembled with one fixed extremity and one changeable extremity in dynamization mode. The trail bar was positioned for synthesis modules with holes for cortical screws. The modules were positioned close to one another in two fractures and far away from the fracture site in the others. The bone healing occurred by external callus. Since motion at the fracture site determines the amount of callus required, the secondary bone healing that was observed in all of the cases indicated less rigid fixation of this system. A potential benefit of this system was a lesser interface contact with the bone since it was only done by trail bar. The major disadvantage was the prominence of the implant. It was possible to conclude that the S.P.S. plate appears to be a suitable method for the treatment of diaphyseal fractures in dogs.
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Illukka, E., and R. J. Boudrieau. "Surgical repair of a severely comminuted maxillary fracture in a dog with a titanium locking plate system." Veterinary and Comparative Orthopaedics and Traumatology 27, no. 05 (2014): 398–404. http://dx.doi.org/10.3415/vcot-14-03-0044.
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SummaryA four-year old male Labrador Retriever was admitted with head trauma after being hit by a car. The dog had sustained multiple nasal, maxillary, and frontal bone fractures that resulted in separation of the maxilla from the base of the skull. A severely comminuted left zygomatic arch fracture was also present. These fractures were all repaired using a point contact, locking titanium plate system, in a single procedure that resulted in excellent postoperative occlusion and immediate function. Healing was uneventful. Full function and excellent cosmetic appearance were evident 13 months after surgery. This case illustrates the ease of repair and the success of treatment of severely comminuted maxillofacial fractures by conforming to basic biomechanical principles taken directly from the human experience and successfully applied to the dog; these included multiple plate application along the buttresses and trusses of the facial skeleton. The plate fixation was applied to bridge the multiple fractures along the most appropriate lines of stress. The small size of the plates, and the ability to easily contour them to adapt to the bone surface in threedimensions, allowed their placement in the most appropriate positions to achieve sufficient rigidity and lead to uncomplicated healing without any postoperative complications.
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Jones, Stephen C., Daniel D. Lewis, and Matthew D. Winter. "Fluoroscopic-Assisted Olecranon Fracture Repair in Three Dogs." Case Reports in Veterinary Medicine 2015 (2015): 1–11. http://dx.doi.org/10.1155/2015/542842.
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Olecranon fractures in dogs are often both comminuted and intra-articular. Anatomic reduction and stable internal fixation are thus paramount to achieving primary bone healing and mitigating the development of posttraumatic osteoarthritis. Intraoperative fluoroscopy can be useful to confirm accurate fracture reduction and facilitate precise implant placement, potentially reducing the surgical exposure required and additional trauma. Despite widespread use in human surgery, reports of fluoroscopic-assisted fracture repair in dogs are limited. Presented here are three dogs in which intraoperative fluoroscopy was used to facilitate accurate olecranon fracture reduction and implant positioning. The olecranon fractures appeared to heal by primary bone union, although the anconeal process failed to obtain osseous union in one dog. Despite the development of mild-to-moderate osteoarthritis in all three dogs, and the nonunion of the anconeal process in one dog, the clinical outcome was considered successful with all dogs subjectively free of lameness at long-term follow-up evaluation. Intraoperative fluoroscopy was found to be a useful modality during fracture reduction and implant placement in dogs with olecranon fractures.
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Hernigou, J., and F. Schuind. "Tobacco and bone fractures." Bone & Joint Research 8, no. 6 (June 2019): 255–65. http://dx.doi.org/10.1302/2046-3758.86.bjr-2018-0344.r1.
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Objectives The aim of this study was to review the impact of smoking tobacco on the musculoskeletal system, and on bone fractures in particular. Methods English-language publications of human and animal studies categorizing subjects into smokers and nonsmokers were sourced from MEDLINE, The Cochrane Library, and SCOPUS. This review specifically focused on the risk, surgical treatment, and prevention of fracture complications in smokers. Results Smokers have an increased risk of fracture and experience more complications with delayed bone healing, even if they have already stopped smoking, because some adverse effects persist for a prolonged period. Some risks can be reduced during and after surgery by local and general prevention, and smoking cessation is an important factor in lessening this risk. However, if a patient wants to stop smoking at the time of a fracture, the cessation strategies in reducing tobacco use are not easy to implement. The patient should also be warned that using e-cigarettes or other tobaccos does not appear to reduce adverse effects on health. Conclusion The evidence reviewed in this study shows that smoking has a negative effect in terms of the risk and treatment of fractures. Cite this article: J. Hernigou, F. Schuind. Tobacco and bone fractures: A review of the facts and issues that every orthopaedic surgeon should know. Bone Joint Res 2019;8:255–265. DOI: 10.1302/2046-3758.86.BJR-2018-0344.R1.
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Lee, Si Young, Jun Young Choi, Hyun Il Lee, Jung Min Lee, and Jin Ho Cho. "The Comparison of Postoperative Outcomes Open and Closed Reduction for Patellar Fractures." Journal of Knee Surgery 33, no. 01 (December 21, 2018): 073–77. http://dx.doi.org/10.1055/s-0038-1676515.
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AbstractPatellar fractures account for approximately 1% of all human body fractures. This study aimed to compare the surgical outcomes of open reduction and closed reduction for patellar fractures. This retrospective study included 62 patients (63 cases) who underwent surgical treatment of patellar fractures from 2008 to 2013. Of the 63 cases, open and closed reductions were performed in 42 and 21 cases, respectively. Plain radiography was used to assess fracture healing. Comminuted patellar fracture was the most common fracture type in both groups. Tension band wiring and cannulated screw fixation were mainly used in the open and closed reduction groups, respectively. There was no significant difference in the modified hospital for special surgery score, visual analog scale score for pain, and range of motion between the two groups. The mean union time was 3.2 and 3.0 months in open and closed reductions, respectively. Postoperative knee stiffness was noted in five cases of open reduction and in three cases of closed reduction. One patient in the open reduction group had a refracture. There were no notable differences in treatment outcomes between open and closed reductions. Thus, closed reduction may not be inferior to open reduction as a surgical treatment for patellar fractures.
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Pfeiffenberger, M., A. Damerau, P. Hoff, A. Lang, F. Buttgereit, and T. Gaber. "OP0244 A PRECLINICAL TESTING TOOL: THE IN VITRO 3D FRACTURE GAP MODEL." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 154.1–154. http://dx.doi.org/10.1136/annrheumdis-2020-eular.3546.
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Background:Approximately 10% of fractures lead to significant fracture healing disorders, with a tendency to further increase due to the aging population. Of note, especially immunosuppressed patients with ongoing inflammation show difficulties in the correct course of fracture healing leading to fracture healing disorders. Most notably, invading immune cells and secreted cytokines are considered to provide an inflammatory microenvironment within the fracture gap, primarily during the initial phase of fracture healing. Current research has the focus on small animal models, facing the problem of translation towards the human system. In order to improve the therapy of fracture healing disorders, we have developed a human cell-basedin vitromodel to mimic the initial phase of fracture healing adequately. This model will be used for the development of new therapeutic strategies.Objectives:Our aim is to develop anin vitro3D fracture gap model (FG model) which mimics thein vivosituation in order to provide a reliable preclinical test system for fracture healing disorders.Methods:To assemble our FG model, we co-cultivated coagulated peripheral blood and primary human mesenchymal stromal cells (MSCs) mimicking the fracture hematoma (FH model) together with a scaffold-free bone-like construct mimicking the bony part of the fracture gap for 48 h under hypoxic conditions (n=3), in order to reflect thein vivosituation after fracture most adequately. To analyze the impact of the bone-like construct on thein vitroFH model with regard to its osteogenic induction capacity, we cultivated the fracture gap models in either medium with or without osteogenic supplements. To analyze the impact of Deferoxamine (DFO, known to foster fracture healing) on the FG model, we further treated our FG models with either 250 µmol DFO or left them untreated. After incubation and subsequent preparation of the fracture hematomas, we evaluated gene expression of osteogenic (RUNX2,SPP1), angiogenic (VEGF,IL8), inflammatory markers (IL6,IL8) and markers for the adaptation towards hypoxia (LDHA,PGK1) as well as secretion of cytokines/chemokines using quantitative PCR and multiplex suspension assay, respectively.Results:We found via histology that both the fracture hematoma model and the bone-like construct had close contact during the incubation, allowing the cells to interact with each other through direct cell-cell contact, signal molecules or metabolites. Additionally, we could show that the bone-like constructs induced the upregulation of osteogenic markers (RUNX2, SPP1) within the FH models irrespective of the supplementation of osteogenic supplements. Furthermore, we observed an upregulation of hypoxia-related, angiogenic and osteogenic markers (RUNX2,SPP1) under the influence of DFO, and the downregulation of inflammatory markers (IL6,IL8) as compared to the untreated control. The latter was also confirmed on protein level (e.g. IL-6 and IL-8). Within the bone-like constructs, we observed an upregulation of angiogenic markers (RNA-expression ofVEGF,IL8), even more pronounced under the treatment of DFO.Conclusion:In summary, our findings demonstrate that our establishedin vitroFG model provides all osteogenic cues to induce the initial bone healing process, which could be enhanced by the fracture-healing promoting substance DFO. Therefore, we conclude that our model is indeed able to mimic correctly the human fracture gap situation and is therefore suitable to study the influence and efficacy of potential therapeutics for the treatment of bone healing disorders in immunosuppressed patients with ongoing inflammation.Disclosure of Interests:Moritz Pfeiffenberger: None declared, Alexandra Damerau: None declared, Paula Hoff: None declared, Annemarie Lang: None declared, Frank Buttgereit Grant/research support from: Amgen, BMS, Celgene, Generic Assays, GSK, Hexal, Horizon, Lilly, medac, Mundipharma, Novartis, Pfizer, Roche, and Sanofi., Timo Gaber: None declared
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Törnkvist, H., and J. R. Field. "Biological fracture fixation: a perspective." Veterinary and Comparative Orthopaedics and Traumatology 14, no. 04 (2001): 169–78. http://dx.doi.org/10.1055/s-0038-1632694.
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The concept of biological fracture fixation encompasses a reduction in soft-tissue trauma at the time of surgery, usually involving percutaneous application of plates. This is combined with the implantation of reduced amounts of hardware; the desired result is a fracture that repairs through indirect bone union with the formation of callus. The end result is a fracture that heals faster and is stronger, at least in the healing phase.Biological fixation is not uncommonly utilized in human orthopaedics, particularly for diaphyseal fractures which involve a number (>2) of fragments with articular disruption. This methodology may also have application in veterinary orthopaedics, particularly small animals or the juvenile equid.
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Locatelli, Vittorio, and Vittorio E. Bianchi. "Effect of GH/IGF-1 on Bone Metabolism and Osteoporsosis." International Journal of Endocrinology 2014 (2014): 1–25. http://dx.doi.org/10.1155/2014/235060.
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Background. Growth hormone (GH) and insulin-like growth factor (IGF-1) are fundamental in skeletal growth during puberty and bone health throughout life. GH increases tissue formation by acting directly and indirectly on target cells; IGF-1 is a critical mediator of bone growth. Clinical studies reporting the use of GH and IGF-1 in osteoporosis and fracture healing are outlined.Methods. A Pubmed search revealed 39 clinical studies reporting the effects of GH and IGF-1 administration on bone metabolism in osteopenic and osteoporotic human subjects and on bone healing in operated patients with normal GH secretion. Eighteen clinical studies considered the effect with GH treatment, fourteen studies reported the clinical effects with IGF-1 administration, and seven related to the GH/IGF-1 effect on bone healing.Results. Both GH and IGF-1 administration significantly increased bone resorption and bone formation in the most studies. GH/IGF-1 administration in patients with hip or tibial fractures resulted in increased bone healing, rapid clinical improvements. Some conflicting results were evidenced.Conclusions. GH and IGF-1 therapy has a significant anabolic effect. GH administration for the treatment of osteoporosis and bone fractures may greatly improve clinical outcome. GH interacts with sex steroids in the anabolic process. GH resistance process is considered.
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Lawton, M., J. A. Hoyland, D. R. Marsh, A. J. Freemont, and J. G. Andrew. "A study of collagen gene expression in normally and abnormally healing human fractures." Bone 17, no. 6 (December 1995): 557. http://dx.doi.org/10.1016/8756-3282(96)87785-4.
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Guillot, Pascale V., Oyebode Abass, J. H. Duncan Bassett, Sandra J. Shefelbine, George Bou-Gharios, Jerry Chan, Hitoshi Kurata, Graham R. Williams, Julia Polak, and Nicholas M. Fisk. "Intrauterine transplantation of human fetal mesenchymal stem cells from first-trimester blood repairs bone and reduces fractures in osteogenesis imperfecta mice." Blood 111, no. 3 (February 1, 2008): 1717–25. http://dx.doi.org/10.1182/blood-2007-08-105809.
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Abstract The inherited skeletal dysplasia osteogenesis imperfecta (OI) results in multiple fractures and is currently treated empirically. We transplanted human first-trimester fetal blood mesenchymal stem cells (MSCs) into homozygous oim mice in utero. This resulted in a two-thirds reduction in long bone fractures (P < .01), with fewer fractures per mouse (median 1, range 0-2 in mice that received transplants vs median 3, range 1-5 in mice that did not receive transplants by 12 weeks, P < .01). Nearly all mice that did not receive transplants had fractures (47 [97.9%] of 48), in contrast to 17 (58.6%) of 29 4- to 12-week-old mice that received transplants (P < .01). Transplantation was associated with increased bone strength (P < .01), thickness (P < .01), and length (P < .01), and normalization/reduction of growth plate height in 4- to 12-week-old oim was reduced in mice that underwent transplantion (P < .001). More donor cells were found in bone tissues compared with other organs (P < .001), with cells clustered in areas of active bone formation and remodeling, and at sites of fracture healing. Donor cells found in the bone expressed osteoblast lineage genes, and produced the extracellular bone structural protein osteopontin. Finally, MSC transplantation decreased bone hydroxyproline content. In conclusion, intrauterine transplantation of fetal MSCs markedly reduced fracture rates and skeletal abnormalities in a mouse model of the intermediate severity type III OI, suggesting a scientific basis for MSC treatment of affected human fetuses.
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Ma, Xue, Jian Yang, Ting Liu, Jing Li, Yanyu Lan, Yonglin Wang, Aimin Wang, Ye Tian, and Yongjun Li. "Gukang Capsule Promotes Fracture Healing by Activating BMP/SMAD and Wnt/β-Catenin Signaling Pathways." Evidence-Based Complementary and Alternative Medicine 2020 (September 29, 2020): 1–12. http://dx.doi.org/10.1155/2020/7184502.
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Background. Gukang capsule (GKC) is a traditional Chinese medicine formulation which has been used extensively in the clinical treatment of bone fractures. However, the mechanisms underlying its effects on fracture healing remain unclear. Methods. In this study we used a rabbit radius fracture model, and we measured the serum content of bone alkaline phosphatase (ALP), calcium, and phosphorus and examined pathology of the fracture site as indicators of the fracture healing effects of GKC. SaOS-2 human osteosarcoma cells were used to measure (i) ALP activity, (ii) ornithine transcarbamylase (OTC), calcium, and mineralization levels, (iii) the expression of osteogenic-related genes, that is, runt-related transcription factor 2 (RUNX2), bone morphogenetic protein 2 (BMP2), collagen I (COL-I), osteopontin (OPN), OTC, and osterix (Osx), and (iv) the expression of key proteins in the Wnt/β-catenin and BMP/SMAD signaling pathways to study the mechanisms by which GKC promotes fracture healing. Results. We found that GKC effectively promotes radius fracture healing in rabbits and enhances ALP activity, increases OTC and calcium levels, and stimulates the formation of mineralized nodules in SaOS-2 cells. Moreover, COL-I, OTC, Osx, BMP2, and OPN expression levels were higher in SaOS-2 cells treated with GKC than control cells. GKC upregulates glycogen synthase kinase 3β (GSK3β) phosphorylation and Smad1/5 and β-catenin protein levels, thereby activating Wnt/β-catenin and BMP/Smad signaling pathways. Inhibitors of the Wnt/β-catenin and BMP/Smad signaling pathways (DKK1 and Noggin, respectively) suppress the osteogenic effects of GKC. Conclusions. GKC promotes fracture healing by activating the Wnt/β-catenin and BMP/Smad signaling pathways and increasing osteoprotegerin (OPG) secretion by osteoblasts (OBs), which prevents receptor activator of nuclear factor kappa B ligand (RANKL) binding to RANK.
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Rodríguez-Merchán, Emerito Carlos. "A Review of Recent Developments in the Molecular Mechanisms of Bone Healing." International Journal of Molecular Sciences 22, no. 2 (January 14, 2021): 767. http://dx.doi.org/10.3390/ijms22020767.
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Between 5 and 10 percent of fractures do not heal, a condition known as nonunion. In clinical practice, stable fracture fixation associated with autologous iliac crest bone graft placement is the gold standard for treatment. However, some recalcitrant nonunions do not resolve satisfactorily with this technique. For these cases, biological alternatives are sought based on the molecular mechanisms of bone healing, whose most recent findings are reviewed in this article. The pro-osteogenic efficacy of morin (a pale yellow crystalline flavonoid pigment found in old fustic and osage orange trees) has recently been reported, and the combined use of bone morphogenetic protein-9 (BMP9) and leptin might improve fracture healing. Inhibition with methyl-piperidino-pyrazole of estrogen receptor alpha signaling delays bone regeneration. Smoking causes a chondrogenic disorder, aberrant activity of the skeleton’s stem and progenitor cells, and an intense initial inflammatory response. Smoking cessation 4 weeks before surgery is therefore highly recommended. The delay in fracture consolidation in diabetic animals is related to BMP6 deficiency (35 kDa). The combination of bioceramics and expanded autologous human mesenchymal stem cells from bone marrow is a new and encouraging alternative for treating recalcitrant nonunions.
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Hatten, H. P., and M. J. Voor. "Bone Healing Using a Bi-Phasic Ceramic Bone Substitute Demonstrated in Human Vertebroplasty and with Histology in a Rabbit Cancellous Bone Defect Model." Interventional Neuroradiology 18, no. 1 (March 2012): 105–13. http://dx.doi.org/10.1177/159101991201800114.
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A non-exothermic material that demonstrates clinical pain relief comparable to polymethylacrylate (PMMA) for vertebroplasty and promotes bone healing is desirable. The purpose of this investigation is to demonstrate clinical pain score improvement and bone healing following vertebroplasty with a novel bi-phasic ceramic cement. Twenty patients were prospectively treated for compression fractures in a single center in the USA with the injectable bi-phasic ceramic bone substitute. Statistical comparison of pain scores was made during a 12 month follow-up retrospectively against a matched cohort of patients treated with PMMA vertebroplasty by the same neuroradiologist (HPH) in the same setting. The bone remodeling material was also evaluated with histology in a New Zealand white rabbit model. The bi-phasic material demonstrated a preoperative mean VAS score of 8.5 (± 1.6) with a significant post-operative pain relief mean VAS score of 1.8 (± 2.5) after one week, which was maintained throughout the 12 month follow-up period. These data are in line with the pain scores for the PMMA treated cohort. CT scans six and 12 months after surgery with the bi-phasic cement showed healing of the osteoporotic fractures. In the rabbit model, histology with the study material showed evidence of incorporation, new bone growth and bone healing in a cancellous bone defect. Both the clinical results and the histologic evidence of bone healing and new bone growth support the application of this new bioinjectable material as an alternative to the use of PMMA for vertebroplasty.
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Bak, B., P. H. Jørgensen, and T. T. Andreassen. "Increased mechanical strength of healing rat tibial fractures treated with biosynthetic human growth hormone." Bone 11, no. 4 (1990): 233–39. http://dx.doi.org/10.1016/8756-3282(90)90075-a.
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Alinejad, Yasaman, Marc-Antoine Lauzon, Guillaume Grenier, Frédéric Balg, and Nathalie Faucheux. "Both Human Hematoma Punctured from Pelvic Fractures and Serum Increase Muscle Resident Stem Cells Response to BMP9: A Multivariate Statistical Approach." Journal of Clinical Medicine 9, no. 4 (April 19, 2020): 1175. http://dx.doi.org/10.3390/jcm9041175.
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Hematoma and skeletal muscles play a crucial role in bone fracture healing. The muscle resident mesenchymal stromal cells (mrSCs) can promote bone formation by differentiating into osteoblasts upon treatment by bone morphogenetic proteins (BMP), such as BMP9. However, the influence of hematoma fracture extracts (Hema) on human mrSC (hmrSC) response to BMP9 is still unknown. We therefore determined the influence of Hema, human healthy serum (HH), and fetal bovine serum (FBS, control) on BMP9-induced osteoblast commitment of hmrSC by measuring alkaline phosphatase activity. Multiplex assays of 90 cytokines were performed to characterize HH and Hema composition and allow their classification by a multivariate statistical approach depending on their expression levels. We confirmed that BMP9 had a greater effect on osteoblastic differentiation of hmrSCs than BMP2 in presence of FBS. The hmrSCs response to BMP9 was enhanced by both Hema and HH, even though several cytokines were upregulated (IL-6, IL-8, MCP-1, VEGF-A and osteopontin), downregulated (BMP9, PDGF) or similar (TNF-alpha) in Hema compared with HH. Thus, hematoma may potentiate BMP9-induced osteogenic differentiation of hmrSCs during bone fracture healing. The multivariate statistical analyses will help to identify the cytokines involved in such phenomenon leading to normal or pathological bone healing.
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Sehmisch, S., F. Daub, M. Komrakova, M. Tezval, K. M. Stuermer, and E. K. Stuermer. "Raloxifene supports early fracture healing more than estrogen in ovariectomized rats." Osteologie 22, no. 04 (2013): 290–97. http://dx.doi.org/10.1055/s-0038-1630130.
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Summary Objectives: Most people suffering from osteoporosis are undiagnosed: the first osteopenic fracture strikes an untreated organism. Therefore implant fixation often fails and bone healing is disturbed. In this basic research project, we explore possibilities to improve the quality of the osteopenic bone immediately after a fracture to avoid these complications. Methods: Thirty-six female rats, which developed osteopenia within ten weeks duration after ovariectomy (OVX), underwent a standardized metaphyseal osteotomy with a bridging T-plate-fixation. After that rats were divided into three groups, which received soyfree food supplemented with raloxifene (R: 2.02 mg/d) or estradiol-17β-benzoate (E: 0.09 mg/d), orally, or soyfree food (SF) only. During fracture healing the rats were subcutaneously injected with fluorescent agents to help label and visualize the process of bone formation. Bones were analyzed using a three-point bending test, histological sections and microradiographs. Results: Raloxifene and estradiol have exerted anabolic effects on the trabecular bone. Both substances induced fracture healing mainly via endosteal callus formation (R: 2.08 ± 0.66 mm2, E: 2.02 ± 0.75 mm2 vs. SF: 1.78 ± 0.74 mm2). Due to early bridging and advanced fracture healing, less bone occurred in the later stages after application of test substances. The biomechanical features of the callus formations determined by the Yield load of R- (100.3 ± 28.4 N) were at the level of E-treated bone (93.8 ± 29.7 N) being higher in both comparing to the osteopenic bones (SF: 76.4 ± 18.8 N). Conclusions: Raloxifene and estrogen had supporting effects in the therapy of fractures of osteopenic bone. They improved not only the bone, but also the callus structure. The raloxifene- and estradiol-treatment enhanced the mechanical properties of the osteopenic bone, which probably lead to (micro) fracture risk reduction. Taking into account all the results there is an advantage for raloxifene; additionally its negative side effects detected in human settings, with respect to e. g. breast cancer propagation, are less than that of estrogens.
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Howard, N. E., M. Phaff, J. Aird, L. Wicks, and P. Rollinson. "Does human immunodeficiency virus status affect early wound healing in open surgically stabilised tibial fractures?" Bone & Joint Journal 95-B, no. 12 (December 2013): 1703–7. http://dx.doi.org/10.1302/0301-620x.95b12.32083.
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Andrew, JG, JA Hoyland, AJ Freemont, and DR Marsh. "O7. Sequential expression of cartilage and bone phenotypes by cells in normally healing human fractures." Bone 15, no. 2 (March 1994): 230. http://dx.doi.org/10.1016/8756-3282(94)90733-1.
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Tsuji, Tsuakasa, Hideaki Kitada, and Sinnosuke Abe. "The use of bioabsorbable poly-L-lactide acid miniplate and screw (FIXSORB®-MX ) for bone fixation in mandibular fracture: cases reports." Journal of Dentomaxillofacial Science 3, no. 1 (April 1, 2018): 46. http://dx.doi.org/10.15562/jdmfs.v3i1.681.
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Objective: This report aims to elucidate the degree of degradation of bioabsorbable poly-L-lactide acid (PLLA) devices and the influence of these materials on the surrounding tissues in the human body.Methods: Two patients with fractured mandibles underwent treatment using a biodegradable fixation system. In the first case, the plates and screws were removed along with extraction of an impacted wisdom tooth at 6 months after surgery, and in the second case, the same procedure was performed 12 months after surgery. Changes in the physical properties of the materials and histologic alterations in the periosteum and bone associated with the bioabsorbable plates were assessed.Results: The materials demonstrated adequate degradation in the human body, and skeletal stability proved sufficient for the duration of mandibular bone healing without complications after surgery.Conclusion: On the basis these findings, it can be concluded that PLLA implants are useful for the fixation of human mandibular fractures.
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Pavarotti, Greta, and Randy Boudrieau. "Treatment of a Paediatric Distal Femoral Malunion Deformity." Veterinary and Comparative Orthopaedics and Traumatology 31, no. 03 (April 16, 2018): 222–28. http://dx.doi.org/10.1055/s-0038-1637754.
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Objective The aim of this article was to describe the surgical re-alignment technique and stabilization of a distal femoral deformity in a 6-week-old, male, Foxhound. Methods A healing metaphyseal fracture, resulting in a valgus deformity with internal rotation, was observed just proximal to the distal femoral physis. The deformity was treated by an opening wedge osteotomy with lateral translation and external rotation of the distal epiphysis using a guide-wire technique; a corticocancellous allograft bridged the defect, which was stabilized with a 2.0-mm locking Y-plate designed for human phalangeal fractures. Results Successful deformity correction was obtained with subsequent healing of the osteotomy and maintained longitudinal bone growth. Sciatic neurapraxia developed as a result of a migrating adjunct pin (9 days post-operatively), which was removed. At long-term follow-up (4 years), a 12% shortening of the femur did result in addition to an asymptomatic grade 2 medial patellar luxation (MPL). The cause of the MPL was not evident; the owners declined treatment and the dog continued to function as an active hunting dog. Clinical Significance Prior to ossification of the epiphyses in very young animals, which precludes effective radiographic pre-planning, the guide-wire technique can be utilized as the primary tool for performing angular deformity correction. Adequate fixation and stabilization can be obtained with small human specialty locking plates.
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Alqahtani, Mohammed S., Abdulsalam Abdulaziz Al-Tamimi, Mohamed H. Hassan, Fengyuan Liu, and Paulo Bartolo. "Optimization of a Patient-Specific External Fixation Device for Lower Limb Injuries." Polymers 13, no. 16 (August 10, 2021): 2661. http://dx.doi.org/10.3390/polym13162661.
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The use of external fixation devices is considered a valuable approach for the treatment of bone fractures, providing proper alignment to fractured fragments and maintaining fracture stability during the healing process. The need for external fixation devices has increased due to an aging population and increased trauma incidents. The design and fabrication of external fixations are major challenges since the shape and size of the defect vary, as well as the geometry of the human limb. This requires fully personalized external fixators to improve its fit and functionality. This paper presents a methodology to design personalized lightweight external fixator devices for additive manufacturing. This methodology comprises data acquisition, Computer tomography (CT) imaging analysis and processing, Computer Aided Design (CAD) modelling and two methods (imposed predefined patterns and topology optimization) to reduce the weight of the device. Finite element analysis with full factorial design of experiments were used to determine the optimal combination of designs (topology optimization and predefined patterns), materials (polylactic acid, acrylonitrile butadiene styrene, and polyamide) and thickness (3, 4, 5 and 6 mm) to maximize the strength and stiffness of the fixator, while minimizing its weight. The optimal parameters were found to correspond to an external fixator device optimized by topology optimization, made in polylactic acid with 4 mm thickness.
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Lin, Chun-Cheng, Shih-Chieh Lin, Chao-Ching Chiang, Ming-Chau Chang, and Oscar Kuang-Sheng Lee. "Reconstruction of Bone Defect Combined with Massive Loss of Periosteum Using Injectable Human Mesenchymal Stem Cells in Biocompatible Ceramic Scaffolds in a Porcine Animal Model." Stem Cells International 2019 (November 23, 2019): 1–8. http://dx.doi.org/10.1155/2019/6832952.
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Clinically, in patients who sustain severe open fractures, there is not only a segmental bone defect needed to be reconstructed but also insufficient healing capacity due to concomitant damages to the periosteum and surrounding soft tissues. For studying the reconstruction of bone defects associated with massive loss of periosteum and surrounding soft tissues, there are no well-established preclinical models in large animals in the literature. The purpose of the study was to generate a large animal model of bone defect with massive periosteum loss and to adopt a tissue engineering approach to achieve rapid bony union with stem cells and biomaterials. In this study, a bone defect with massive periosteum stripping was generated in pigs, which was followed by emptying nearby canal marrow including fat and cancellous bone. The stripped periosteum was a mimic to the situation in the Gustilo type 3 open fractures. Bone defects were then reconstructed by impacting the biocompatible ceramic scaffold, morselized tricalcium phosphate (TCP) loaded with human adipose tissue-derived mesenchymal stem cells (hMSCs). Radiological and pathological assessments indicated that TCP and hMSCs synergistically promoted bone healing with increased lamination and ingrowth of vessels. Both bridging periosteum formation and gap filling were induced rapidly. In conclusion, a porcine model of segmental bone loss with damage of surrounding periosteum was created. Reconstruction of such defects with hMSCs and TCP achieved rapid union of bone defects associated with massive periosteal stripping.
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Chen, Lin, Lei Liu, Cai Li, Wen Luo, Yinghui Tan, and Gang Zhang. "Nanospheres of Recombinant Human Bone Morphogenetic-2 and Polylactic Acid Promote the Healing of Bone Fractures In Vivo." Advanced Science Letters 6, no. 1 (March 15, 2012): 56–62. http://dx.doi.org/10.1166/asl.2012.2035.
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Mad Jin, Rashid, and Naznin Sultana. "Osteoblast adhesion and proliferation on porous chitosan/polycaprolactone scaffolds for bone tissue engineering application." Malaysian Journal of Fundamental and Applied Sciences 14, no. 4 (January 6, 2019): 495–99. http://dx.doi.org/10.11113/mjfas.v14n4.1200.
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Tissue engineering is an evolving technique to reduce the limitations of the bone graft. It provides diversity to improve the healing process of bone fractures and defect by combining the use of 3D scaffolds, healing promoting factors, gene therapy and different drugs. Flexibility to use a different technique to fabricate scaffolds lead to the new insight into bone healing future. A bone graft is defined as promoted bone healing through osteogenesis, osteoinduction, and osteoconduction by the implanted material alone or with other materials. Ideal bone graft depends on several factors such as biomechanical characteristic, tissue viability, the morphological structure as well as biological characteristics. In this work, we have investigated adhesion, proliferation, and differentiation of poly (ɛ-caprolactone) / chitosan scaffolds with the incorporation of hydroxyapatite and tetracycline HCl on normal human osteoblast cells. Both of the polymers were blended without a cross-linking agent to form porous scaffolds by freeze-drying technique. From the results, it was observed that the compressive modulus increased from 4.0 MPa to 12.5 MPa and the yield strength increased from 0.48 MPa to 0.75 MPa for the PCL/CS scaffold and nHA/PCL/CS scaffold, respectively. Scanning electron microscopy study revealed that the cells successfully adhered to the surface of scaffolds after 24 hours incubation. Proliferation analysis exhibited the increasing trend of growth of cells. This study indicated that the scaffold fabricated using this technique was able to promote adhesion, proliferation, and differentiation of normal human osteoblast cells.
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Shokouhimehr, Mohammadreza, Andrea S. Theus, Archana Kamalakar, Liqun Ning, Cong Cao, Martin L. Tomov, Jarred M. Kaiser, et al. "3D Bioprinted Bacteriostatic Hyperelastic Bone Scaffold for Damage-Specific Bone Regeneration." Polymers 13, no. 7 (March 30, 2021): 1099. http://dx.doi.org/10.3390/polym13071099.
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Current strategies for regeneration of large bone fractures yield limited clinical success mainly due to poor integration and healing. Multidisciplinary approaches in design and development of functional tissue engineered scaffolds are required to overcome these translational challenges. Here, a new generation of hyperelastic bone (HB) implants, loaded with superparamagnetic iron oxide nanoparticles (SPIONs), are 3D bioprinted and their regenerative effect on large non-healing bone fractures is studied. Scaffolds are bioprinted with the geometry that closely correspond to that of the bone defect, using an osteoconductive, highly elastic, surgically friendly bioink mainly composed of hydroxyapatite. Incorporation of SPIONs into HB bioink results in enhanced bacteriostatic properties of bone grafts while exhibiting no cytotoxicity. In vitro culture of mouse embryonic cells and human osteoblast-like cells remain viable and functional up to 14 days on printed HB scaffolds. Implantation of damage-specific bioprinted constructs into a rat model of femoral bone defect demonstrates significant regenerative effect over the 2-week time course. While no infection, immune rejection, or fibrotic encapsulation is observed, HB grafts show rapid integration with host tissue, ossification, and growth of new bone. These results suggest a great translational potential for 3D bioprinted HB scaffolds, laden with functional nanoparticles, for hard tissue engineering applications.
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Sloan, Andrew, Issam Hussain, Mohamed El-Sheemy, Mohammad Maqsood, Latif Mubasher, Vikas Sharma, and Oleg Eremin. "In Vitro effect of Bone Morphogenetic Protein-2 (BMP-2) and Cigarette Smoke Extract (CSE) on Osteoblastic Mesenchymal Stem Cells: Beneficial Biological Effects of BMP-2 Negated By CSE." Journal of Bone Biology and Osteoporosis 4, no. 1 (December 20, 2018): 110–20. http://dx.doi.org/10.18314/jbo.v4i1.1387.
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Introduction: Clinical and demographic studies have shown that tobacco smoking is a major contributor to non- and delayed-union in fracture healing. The cellular and molecular basis for this is poorly understood, and few studies in human fractures have been undertaken.Aims: To analyse the in vitro biological effects of tobacco smoking at the cellular level within the human fracture microenvironment, with specific regard to mesenchymal stem cell (MSC) proliferation and to ascertain whether the application of bone morphogenetic factor-2 (BMP-2) could be used therapeutically to improve fracture healing.Methods: Fracture haematomas (n=10) were collected from anaesthetised, non-smoking patients who had sustained a tibial fracture, and who were undergoing surgical operative fixation. The semi-solid material was dissected and explanted into tissue culture flasks. Complete culture media was introduced, and cultures were incubated at 37oC in a humidified 5% CO2 environment. Cigarette smoke extract (CSE) was produced and infused into the cell cultures to establish an in vitro smoking environment. A control group (n=10) was set-up and left ntreated by CSE. Harvested, spindle-shaped adherent cells were characterised by immunocytochemistry. Cell populations were counted via flow cytometry to assess and compare proliferation rates between CSE-treated and untreated cell cultures. BMP-2 concentrations (10 and 100 ng/mL (an additional dose of 500 ng/mL in CSE- reated cells)) were infused into cell cultures to enhance in vitro cellular viability, which was analysed by means of the MTT assay.Results: There was a significant reduction in the rate of proliferation of osteoblastic MSCs in CSE-treated cells after 5 days of culture (p < 0.05). At a dose of 100 ng/mL, BMP-2 augmented cellular growth and improved cellular viability in cultures not treated with CSE (p < 0.0001). No significant improvement was seen in CSE-treated cell cultures.Summary: The effect of smoking on bone fracture healing appears to contribute to the inhibition of osteoblast proliferation, which may not be reversible with the therapeutic use of exogenous BMP-2. Moreover, the improvement seen in non-smokers does strengthen the case for smokers to cease using tobacco in the perioperative setting in order that such treatments are rendered more effective.
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Dehghanghadikolaei, Amir, and Behzad Fotovvati. "Coating Techniques for Functional Enhancement of Metal Implants for Bone Replacement: A Review." Materials 12, no. 11 (June 3, 2019): 1795. http://dx.doi.org/10.3390/ma12111795.
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To facilitate patient healing in injuries and bone fractures, metallic implants have been in use for a long time. As metallic biomaterials have offered desirable mechanical strength higher than the stiffness of human bone, they have maintained their place. However, in many case studies, it has been observed that these metallic biomaterials undergo a series of corrosion reactions in human body fluid. The products of these reactions are released metallic ions, which are toxic in high dosages. On the other hand, as these metallic implants have different material structures and compositions than that of human bone, the process of healing takes a longer time and bone/implant interface forms slower. To resolve this issue, researchers have proposed depositing coatings, such as hydroxyapatite (HA), polycaprolactone (PCL), metallic oxides (e.g., TiO2, Al2O3), etc., on implant substrates in order to enhance bone/implant interaction while covering the substrate from corrosion. Due to many useful HA characteristics, the outcome of various studies has proved that after coating with HA, the implants enjoy enhanced corrosion resistance and less metallic ion release while the bone ingrowth has been increased. As a result, a significant reduction in patient healing time with less loss of mechanical strength of implants has been achieved. Some of the most reliable coating processes for biomaterials, to date, capable of depositing HA on implant substrate are known as sol-gel, high-velocity oxy-fuel-based deposition, plasma spraying, and electrochemical coatings. In this article, all these coating methods are categorized and investigated, and a comparative study of these techniques is presented.
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Eckardt, Henrik, Knud S. Christensen, Martin Lind, Ebbe S. Hansen, David W. R. Hall, and Ivan Hvid. "Recombinant human bone morphogenetic protein 2 enhances bone healing in an experimental model of fractures at risk of non-union." Injury 36, no. 4 (April 2005): 489–94. http://dx.doi.org/10.1016/j.injury.2004.10.019.
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Mohamed Haneef, Intan Najwa Humaira, Norhashimah Shaffiar, Yose Fachmi Buys, and Abdul Malek Abd. Hamid. "Finite element analysis (FEA) of polylactic acid/polypropylene carbonate (PLA/PPC) blends fixation plate for craniomaxillofacial surgery." International Journal of Structural Integrity 10, no. 5 (October 7, 2019): 678–91. http://dx.doi.org/10.1108/ijsi-05-2019-0048.
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Purpose The internal fixation plate of bone fractures by using polylactic acid (PLA) has attracted the attention of many researchers, as it is biodegradable and biocompatible to the human body. However, its brittleness has led to implant fracture. On the contrary, polypropylene carbonate (PPC), which is also biodegradable and biocompatible, has an excellent elongation at break. The purpose of this paper is to compare the PLA fixation plate with the new fixation plate made up of PLA/PPC blends by using finite element analysis (FEA). Design/methodology/approach The mandible bone from CT data set and fixation plate was designed by using the MIMICS, Amira and Solidworks softwares. Abaqus software was used for FEA of PLA/PPC fixation plate applied on the fractured mandible bone. A model of mandibular bone with a fracture in the body was subjected to incisor load. The analysis was run to determine the von Mises stress, elongation of the fixation plate and the displacement of the fractured gap of PLA/PPC blends fixation plate. Findings The von Mises stress predicted that all the blend compositions were safe to be used as a fixation plate since the stress values were less than the yield strength. In addition, the stress value of the fixation plate was gradually decreased up to 20 percent when the amount of PPC increased to 30 percent. This indicates that the stress shielding effect was successfully reduced. The elongation of the fixation plate was gradually increased from 11.54 to 12.55 µm as the amount of PPC in the blends increased from 0 to 30 percent, thereby illustrating that the flexibility of the fixation plate was improved by the addition of PPC. Finally, the measured displacement of the fractured gap for all compositions of PLA/PPC blends fixation plate is less than 150 µm, which proves the likely success of fracture fixation by using the PLA/PPC blends. Research limitations/implications An optimum solution of PLA/PPC blends and another new material such as compatibilizer need to be introduced in the blends in order to improve the performance of PLA/PPC blends as a new material for a fixation plate. Besides, by using the same method of producing PLA/PPC blends, longer durations for in vitro degradation of PLA/PPC blends are essential to further understand the degradation behavior of the blends applied in the human body. Finally, it is also important to further test the mechanical strength of PLA/PPC blends during the degradation period to know the current strength of the implant in the healing process of the bone. Practical implications PLA fixation plate and screw can commercially be used in CMF surgery since they reduce cost because of the elimination of secondary surgery to remove the fixation plate and screw after the healing process. Social implications It is hoped that the advantages of this research will ensure the market of PLA product to continue expanding in medical application. Originality/value This study is one of the alternative ways for the biomedical researchers to improve the elongation break of PLA. Currently, many researchers focus on polymeric materials such as PLA, poly(glycolic) acid and polydioxanone blends, which were extensively being used in CMF surgery. However, the work on PLA/PPC blends to be used as one of the materials for the CMF fixation plate is very limited, if any. PPC, the proposed material for this research, will improve the mechanical performance of PLA fixation plate and screw to become more sustainable and flexible when applied on human mandible bone.
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Yu, Qing, Robin DiFeo Jacquet, and William J. Landis. "Characterization of Tissue-Engineered Human Periosteum and Allograft Bone Constructs: The Potential of Periosteum in Bone Regenerative Medicine." Cells Tissues Organs 209, no. 2–3 (2020): 128–43. http://dx.doi.org/10.1159/000509036.
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Delayed-union or non-union between a host bone and a graft is problematic in clinical treatment of segmental bone defects in orthopedic cases. Based on a preliminary study of human periosteum allografts from this laboratory, the present work has extensively investigated the use of human cadaveric tissue-engineered periosteum-allograft constructs as an approach to healing such serious orthopedic surgical situations. In this current report, human cadaveric periosteum-wrapped bone allografts and counterpart controls without periosteum were implanted subcutaneously in athymic mice (<i>nu/nu</i>) for 10, 20, and, for the first time, 40 weeks. Specimens were then harvested and assessed by histological and gene expression analyses. Compared to controls, the presence of new bone formation and resorption in periosteum-allograft constructs was indicated in both histology and gene expression results over 40 weeks of implantation. Of several genes also examined for the first time, <i>RANKL</i> and <i>SOST</i> expression levels increased in a statistically significant manner, data suggesting that bone formation and the presence of increasing numbers of osteocytes in bone matrices had increased with time. The tissue-engineering strategy described in this study provides a possible means of improving delayed-union or non-union at the healing sites of segmental bone defects or bone fractures. The potential of periosteum and its resident cells could thereby be utilized effectively in tissue-engineering methods and tissue regenerative medicine.
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Rushikesh Thakre, Ketaki Harne, Pradip Tekade, and Shweta Parve. "Role of Ajan Vruksha/Khandu Chakka Plant (Ehretia Laevis Roxb.) in Covid-19 Pandemic." International Journal of Research in Pharmaceutical Sciences 11, SPL1 (August 3, 2020): 224–33. http://dx.doi.org/10.26452/ijrps.v11ispl1.2703.
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Ehretia Laevis Roxb. plant has many compounds useful in wound healing, fractures, UTI, aphrodisiac, headache, antihelminthics, diuretic, demulcent, expectorant, RTI, fever, fungal infections, hepato-protective , cytotoxic, insecticidal, anti-inflammatory, anti-apoptotic, anti-carcinogenic, weight gain, diabetes , muscles wasting, anti viral activity, preventing viral mutations, blood clotting, reduce the serum lipid level, immunity booster, promotes neural crest cell survival, sedation , anti-Alzheimer,antinociceptive , thyroid uptake promotion, anticoagulant, antiplatelet aggregatory, peptic ulcer, antiasthmatic, antiosteoporotic & antiosteopenic , anticataract & ophthalmic effect, decongestant, skin protective, nephroprotective, anti fatigue effect, protection of human sperm, protection of testicular tissue , larvicidal, antimalarial, antiretroviral, cosmetics product, atopic dermatitis, anti fatigue, neuroprotective, retinoprotective, lung tissue protection, heart protection , prevention of splenocyte apoptosis, relieve stress and improve sleep, hepatic encephalopathy , anti-secretory, neurotransmitter, myelin sheath maintenance, gastric acid secretion & regulation, metal ions chelator, anemia, psychiatric disorders, collagen formation, reduce the recurrence, severity, healing period of herpes simplex virus infections, calcium absorption , muscle protein, post surgery recovery, sports injuries, hormones , aging, used in psychotropic drugs.
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de la Mora-Ramírez, T., M. A. Doñu Ruiz, N. López Perrusquia, D. Sánchez Huerta, and J. V. Cortes-Suarez. "Analysis of Bone Plate with Different Material in Terms of Stress Distribution." Defect and Diffusion Forum 371 (February 2017): 18–24. http://dx.doi.org/10.4028/www.scientific.net/ddf.371.18.
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One of the most used in the field of medicine for the treatment of tibial shaft fractures internal fixation methods is by osteosynthesis plates, the most common plate limited contact dynamic compression (DCP-LC) [1]. This paper presents the results of the fracture site grade 1, where the contact plate and the bone callus area on plates made of bone (LVM stainless steel, titanium alloy different biomedical materials and cobalt alloy), in recovery conditions 1% (one week of recovery), 50% (three weeks of recovery), 75% (six weeks of recovery) and 100%. The fractured tibia bone was modeled with an ideal geometry in CAD [2], modeling of commercial DCP-LC plate was obtained by parameterization of the part using a coordinate machine equipment for the exact geometry. The finite element method for the analysis of each case under the same loads and boundary conditions is used, the results were used to determine stress concentrations in the displacement plate and the fracture callus in the load direction, to have a starting point in the optimization of the geometry from a commercial plate minimizing mass while determining that the material has faster and better biocompatibility with the human body recovery. The results obtained show that the plate under the conditions of three different types of biomaterials has a greater stress concentration in the part located in the fracture zone from stage with 1% recovery between the surfaces of the bone callus upper and lower, keeping this a significant effect on the recovery of the fracture. The compression and tension strength that occur in the intact part of the bone and the tibial fracture interface at different stages of osseous healing have been investigated, The results were compared and presented, showing that the stress distribution in the callus to 1% recovery in the stainless steel plate indicate considerable compression in the area of the callus with this causing deterioration in the area fracture because the callus is not strengthened by contact between fractured bone by increasing the recovery time, the results also indicate that the titanium plate is the one with the lower shielding effect [3] according to the distribution of contact stresses according to the recovery period in the part of callus, making it the material of which the best adaptability to the bone is obtained.
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Gómez-Barrena, Enrique, Norma G. Padilla-Eguiluz, Cristina Avendaño-Solá, Concepción Payares-Herrera, Ana Velasco-Iglesias, Ferran Torres, Philippe Rosset, et al. "A Multicentric, Open-Label, Randomized, Comparative Clinical Trial of Two Different Doses of Expanded hBM-MSCs Plus Biomaterial versus Iliac Crest Autograft, for Bone Healing in Nonunions after Long Bone Fractures: Study Protocol." Stem Cells International 2018 (2018): 1–13. http://dx.doi.org/10.1155/2018/6025918.
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ORTHOUNION is a multicentre, open, comparative, three-arm, randomized clinical trial (EudraCT number 2015-000431-32) to compare the efficacy, at one and two years, of autologous human bone marrow-derived expanded mesenchymal stromal cell (hBM-MSC) treatments versus iliac crest autograft (ICA) to enhance bone healing in patients with diaphyseal and/or metaphysodiaphyseal fracture (femur, tibia, and humerus) status of atrophic or oligotrophic nonunion (more than 9 months after the acute fracture, including recalcitrant cases after failed treatments). The primary objective is to determine if the treatment with hBM-MSCs combined with biomaterial is superior to ICA in obtaining bone healing. If confirmed, a secondary objective is set to determine if the dose of 100 × 106 hBM-MSCs is noninferior to that of 200 × 106 hBM-MSCs. The participants (n=108) will be randomly assigned to either the experimental low dose (n=36), the experimental high dose (n=36), or the comparator arm (n=36) using a central randomization service. The trial will be conducted in 20 clinical centres in Spain, France, Germany, and Italy under the same clinical protocol. The confirmation of superiority for the proposed ATMP in nonunions may foster the future of bone regenerative medicine in this indication. On the contrary, absence of superiority may underline its limitations in clinical use.
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Chen, Gongfa, Zongchao Liu, Yong Zhang, Jiqiao Zhang, Fangsen Cui, and Minglong Xu. "Biomechanical Assessment for Healing Progression of Fractured Long Bones: Comparisons of Various Methods Using Beam Models." International Journal of Applied Mechanics 08, no. 06 (September 2016): 1650074. http://dx.doi.org/10.1142/s1758825116500745.
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Measurements of various effective stiffnesses have been suggested as non-invasive biomechanical methods to assess healing status of a fractured long bone. This paper has compared the sensitivities of five assessment methods for fracture healing of long bones: torsion, compression, 3-point bending, 4-point bending and cantilever bending. A fractured human femur is modeled by an Euler beam and Castigliano’s theorem is used to obtain the effective stiffnesses of the fractured bone. The variations of the effective stiffnesses of the fractured bone with the healing status of the callus have been investigated. The healing process of the callus is represented by gradual increases of the Young’s modulus. The callus is divided into multiple regions. The narrowing process of the fracture gap is characterized by assigning different Young’s modulus for different regions. Our findings showed that torsional, compressional, and bending stiffnesses all perform similarly with respect to the healing process. Before the rapid increase, all effective stiffness curves show a substantial creeping stage which corresponds to the narrowing process of the fracture gap. A higher value of them indicates bony bridging of healing callus. The effective stiffnesses for cantilever bending and 3-point bending are more sensitive to the fracture location, while torsional and compressional stiffness are independent from the fracture location.