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1.
Biomed Eng Online ; 22(1): 107, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37968671

RESUMO

BACKGROUND: Fractures are the most common orthopedic diseases. It is known that static magnetic fields (SMFs) can contribute to the maintenance of bone health. However, the effect and mechanism of SMFs on fracture is still unclear. This study is aim to investigate the effect of moderate static magnetic fields (MMFs) on bone structure and metabolism during fracture healing. METHODS: Eight-week-old male C57BL/6J mice were subjected to a unilateral open transverse tibial fracture, and following treatment under geomagnetic field (GMF) or MMF. The micro-computed tomography (Micro-CT) and three-point bending were employed to evaluate the microarchitecture and mechanical properties. Endochondral ossification and bone remodeling were evaluated by bone histomorphometric and serum biochemical assay. In addition, the atomic absorption spectroscopy and ELISA were utilized to examine the influence of MMF exposure on iron metabolism in mice. RESULTS: MMF exposure increased bone mineral density (BMD), bone volume per tissue volume (BV/TV), mechanical properties, and proportion of mineralized bone matrix of the callus during fracture healing. MMF exposure reduced the proportion of cartilage in the callus area during fracture healing. Meanwhile, MMF exposure increased the number of osteoblasts in callus on the 14th day, and reduced the number of osteoclasts on the 28th day of fracture healing. Furthermore, MMF exposure increased PINP and OCN levels, and reduced the TRAP-5b and ß-CTX levels in serum. It was also observed that MMF exposure reduced the iron content in the liver and callus, as well as serum ferritin levels while elevating the serum hepcidin concentration. CONCLUSIONS: MMF exposure could accelerate fracture healing via promote the endochondral ossification and bone formation while regulating systemic iron metabolism during fracture healing. This study suggests that MMF may have the potential to become a form of physical therapy for fractures.


Assuntos
Consolidação da Fratura , Fraturas Ósseas , Masculino , Animais , Camundongos , Consolidação da Fratura/fisiologia , Microtomografia por Raio-X , Camundongos Endogâmicos C57BL , Calo Ósseo/diagnóstico por imagem , Calo Ósseo/fisiologia , Campos Magnéticos , Ferro
2.
Nat Commun ; 12(1): 2860, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001878

RESUMO

Bone regenerates by activation of tissue resident stem/progenitor cells, formation of a fibrous callus followed by deposition of cartilage and bone matrices. Here, we show that mesenchymal progenitors residing in skeletal muscle adjacent to bone mediate the initial fibrotic response to bone injury and also participate in cartilage and bone formation. Combined lineage and single-cell RNA sequencing analyses reveal that skeletal muscle mesenchymal progenitors adopt a fibrogenic fate before they engage in chondrogenesis after fracture. In polytrauma, where bone and skeletal muscle are injured, skeletal muscle mesenchymal progenitors exhibit altered fibrogenesis and chondrogenesis. This leads to impaired bone healing, which is due to accumulation of fibrotic tissue originating from skeletal muscle and can be corrected by the anti-fibrotic agent Imatinib. These results elucidate the central role of skeletal muscle in bone regeneration and provide evidence that skeletal muscle can be targeted to prevent persistent callus fibrosis and improve bone healing after musculoskeletal trauma.


Assuntos
Regeneração Óssea/fisiologia , Calo Ósseo/fisiologia , Consolidação da Fratura/fisiologia , Fraturas Ósseas/fisiopatologia , Células-Tronco Mesenquimais/fisiologia , Músculo Esquelético/citologia , Animais , Diferenciação Celular/fisiologia , Células Cultivadas , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microscopia de Fluorescência/métodos , Osteogênese/fisiologia
3.
Int J Mol Sci ; 22(7)2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33810326

RESUMO

Musashi-1 (MSI1) is an RNA-binding protein that regulates progenitor cells in adult and developing organisms to maintain self-renewal capacities. The role of musashi-1 in the bone healing environment and its relation with other osteogenic factors is unknown. In the current study, we analyze the expression of MSI1 in an experimental model of rat femoral bone fractures. We also analyze the relation between MSI1 expression and the expression of two osteogenic markers: periostin (POSTN) and runt-related transcription factor 2 (RUNX2). We use histological, immunohistochemical, and qPCR techniques to evaluate bone healing and the expression of MSI1, POSTN, and RUNX2 over time (4, 7, and 14 days). We compare our findings with non-fractured controls. We find that in bone calluses, the number of cells expressing MSI1 and RUNX2 increase over time and the intensity of POSTN expression decreases over time. Within bone calluses, we find the presence of MSI1 expression in mesenchymal stromal cells, osteoblasts, and osteocytes but not in hypertrophic chondrocytes. After 14 days, the expression of MSI1, POSTN, and RUNX2 was significantly correlated. Thus, we conclude that musashi-1 potentially serves in the osteogenic differentiation of mesenchymal stromal cells and bone healing. Therefore, further studies are needed to determine the possibility of musashi-1's role as a clinical biomarker of bone healing and therapeutic agent for bone regeneration.


Assuntos
Consolidação da Fratura , Proteínas do Tecido Nervoso/metabolismo , Osteogênese , Proteínas de Ligação a RNA/metabolismo , Animais , Calo Ósseo/citologia , Calo Ósseo/metabolismo , Calo Ósseo/fisiologia , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Condrócitos/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Masculino , Células-Tronco Mesenquimais/metabolismo , Proteínas do Tecido Nervoso/genética , Osteoblastos/metabolismo , Osteócitos/metabolismo , Proteínas de Ligação a RNA/genética , Ratos , Ratos Wistar
4.
BMJ Case Rep ; 14(2)2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33558382

RESUMO

Fracture healing has four phases: haematoma formation, soft callus, hard callus and remodelling. Often, non-healing fractures have an arrest of one of these phases, which need resurgery. We have repurposed denosumab for impaired fracture healing cases to avoid surgical intervention. Here, we report a series of three cases of impaired fracture healing where denosumab was given 120 mg subcutaneous dosages for 3 months to enhance healing. All the three cases have shown complete bone union at a mean follow-up of 6.7 months (5-9 months) as assessed clinically and radiologically, and have observed no adverse effect of the therapy. Denosumab given in this dose aids fracture healing by increasing callus volume, density and bridges the fracture gap in recalcitrant fracture healing cases where the callus fails to consolidate.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Denosumab/uso terapêutico , Consolidação da Fratura/efeitos dos fármacos , Fraturas não Consolidadas/fisiopatologia , Fraturas não Consolidadas/terapia , Adulto , Calo Ósseo/efeitos dos fármacos , Calo Ósseo/fisiologia , Fraturas do Fêmur/fisiopatologia , Fraturas do Fêmur/terapia , Fixação Interna de Fraturas , Fraturas Fechadas/fisiopatologia , Fraturas Fechadas/terapia , Humanos , Fraturas do Úmero/fisiopatologia , Fraturas do Úmero/terapia , Masculino , Pessoa de Meia-Idade , Reoperação , Adulto Jovem
5.
J Mol Neurosci ; 71(8): 1543-1555, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31808034

RESUMO

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a naturally secreted signaling peptide and has important regulatory roles in the differentiation of the central nervous system and its absence results in disorders in femur development. PACAP has an important function in prevention of oxidative stress or mechanical stress in chondrogenesis but little is known about its function in bone regeneration. A new callus formation model was set to investigate its role in bone remodeling. Fracturing was 5 mm distal from the proximal articular surface of the tibia and the depth was 0.5 mm. Reproducibility of callus formation was investigated with CT 3, 7, and 21 days after the operation. Absence of PACAP did not alter the alkaline phosphatase (ALP) activation in PACAP KO healing process. In developing callus, the expression of collagen type I increased in wild-type (WT) and PACAP KO mice decreased to the end of healing process. Expression of the elements of BMP signaling was disturbed in the callus formation of PACAP KO mice, as bone morphogenic protein 4 (BMP4) and 6 showed an early reduction in bone regeneration. However, elevated Smad1 expression was demonstrated in PACAP KO mice. Our results indicate that PACAP KO mice show various signs of disturbed bone healing and suggest PACAP compensatory and fine tuning effects in proper bone regeneration.


Assuntos
Regeneração Óssea , Calo Ósseo/metabolismo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Animais , Proteína Morfogenética Óssea 4/genética , Proteína Morfogenética Óssea 4/metabolismo , Calo Ósseo/fisiologia , Células Cultivadas , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Camundongos , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/genética , Proteína Smad1/genética , Proteína Smad1/metabolismo
6.
Eur J Orthop Surg Traumatol ; 30(4): 643-651, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31865455

RESUMO

BACKGROUND: Interest around carbon/PEEK plates and nails has been raising. The elastic modulus close to the bone, the high load-carrying capacity and radiolucency make CFR/PEEK materials a potential breakthrough. In the literature, there are abundant data about CFR/PEEK plates in the treatment of proximal humerus, distal radius and distal fibula fractures. In patients affected by bone metastasis, CFR/PEEK nails were proved effective and safe with 12 months of follow-up. Very little is known about performances of CFR/PEEK nails in patients affected by other pathologies. PURPOSES: The aim of the study was to evaluate safety and efficacy of CFR/PEEK nails in the treatment of various pathological conditions. It was also investigated whatever radiolucency of this nails could lead to a more objective evaluation of bone callus or disease site. PATIENTS AND METHODS: In the study group were included 20 patients (22 bone segments) who underwent CFR/PEEK nail implantation (eight humerus, one tibia, nine femur and four knee arthrodesis). They were affected by pathological fractures, and in four cases, they required an arthrodesis of the knee. They were retrospectively evaluated considering nail failures and bone callus or disease progression (RUSH scores). Mean follow-up time was 11 months (min 6.8-max 20.3). In the control group were included patients treated with titanium nails in the same institution for the same pathologies. An interclass correlation coefficient (ICC) analysis was performed in both groups considering RUSH scores by two expert surgeon from two institution to assess whether radiolucency could lead to a more objective evaluation of disease or bone callus site. RESULTS: The ICC of mean values between RUSH scores was 0.882 (IC 95%: 0.702-0.953) in the CFR/PEEK group, while it was 0.778 (IC 95%: 0.41-0.91) in the titanium group. Observers' evaluation showed a significantly higher obscuration by titanium nails than by CFR/PEEK nails. No osteosynthesis failures were reported in both groups. CONCLUSIONS: Our results confirm the safety of CFR/PEEK nails in the short-medium term. The radiolucency of these materials led our observers to perform more objective evaluations of bone callus formation or disease progression compared to the titanium group given the higher ICC. LEVEL OF EVIDENCE: III Case-control therapeutic study.


Assuntos
Pinos Ortopédicos , Neoplasias Ósseas , Calo Ósseo , Fibra de Carbono/uso terapêutico , Fraturas do Fêmur , Fixação Intramedular de Fraturas , Fraturas do Úmero , Cetonas/uso terapêutico , Polietilenoglicóis/uso terapêutico , Fraturas da Tíbia , Artrodese/instrumentação , Artrodese/métodos , Benzofenonas , Materiais Biocompatíveis/uso terapêutico , Neoplasias Ósseas/complicações , Neoplasias Ósseas/secundário , Neoplasias Ósseas/terapia , Calo Ósseo/diagnóstico por imagem , Calo Ósseo/fisiologia , Progressão da Doença , Módulo de Elasticidade , Feminino , Fraturas do Fêmur/etiologia , Fraturas do Fêmur/patologia , Fraturas do Fêmur/cirurgia , Fixação Intramedular de Fraturas/instrumentação , Fixação Intramedular de Fraturas/métodos , Fraturas Espontâneas/cirurgia , Humanos , Fraturas do Úmero/etiologia , Fraturas do Úmero/patologia , Fraturas do Úmero/cirurgia , Articulação do Joelho/patologia , Articulação do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Osseointegração/fisiologia , Polímeros , Radioterapia/métodos , Fraturas da Tíbia/etiologia , Fraturas da Tíbia/patologia , Fraturas da Tíbia/cirurgia , Resultado do Tratamento , Suporte de Carga
7.
J Orthop Surg Res ; 14(1): 206, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31277691

RESUMO

BACKGROUND: The positive effects of grape seed proanthocyanidin extract (GSPE) on bone health, which is a potent antioxidant, are known but its effects on fracture healing are not sufficiently covered in the literature. This study aims to investigate the effects of GSPE on fracture healing and biomechanics of healing bone. MATERIALS AND METHODS: Sixty-four adult Wistar-Albino male rats were divided into 8 groups of 8 animals in each group. Osteotomy was performed to the right femurs of all groups except the negative control (G1) and positive control (G2) groups, and intramedullary Kirchner wire was used for fixation. GSPE was given to half of the rats (G2-G4-G6-G8) 100 mg/kg/day by oral gavage. The rats were sacrificed on the tenth (G3-G4), twentieth (G5-G6), and thirtieth (G1-G2-G7-G8) days, respectively, and histopathological, radiological, and biomechanical examinations were performed. RESULTS: Histopathological examination of the specimens from the callus tissues revealed that bone healing was more prominent in the groups supplemented with GSPE (G4, G6, G8). There was a statistically significant improvement in radiological recovery scores and callus volumes in groups with GSPE. When biomechanical strengths were evaluated, it was found that GSPE increased bone strength not only in fracture groups but also in the positive control group (G2). CONCLUSIONS: As a result, this study showed that GSPE, a potent anti-oxidant, had a positive effect on bone healing and improved mechanical strength of the healing bone.


Assuntos
Calo Ósseo/efeitos dos fármacos , Calo Ósseo/diagnóstico por imagem , Força Compressiva/efeitos dos fármacos , Fêmur/efeitos dos fármacos , Fêmur/diagnóstico por imagem , Extrato de Sementes de Uva/administração & dosagem , Animais , Antioxidantes/administração & dosagem , Fenômenos Biomecânicos/fisiologia , Calo Ósseo/fisiologia , Força Compressiva/fisiologia , Suplementos Nutricionais , Fêmur/lesões , Masculino , Ratos , Ratos Wistar
8.
Int J Numer Method Biomed Eng ; 35(9): e3227, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31197959

RESUMO

In silico models of distraction osteogenesis and fracture healing usually assume constant mechanical properties for the new bone tissue generated. In addition, these models do not always account for the porosity of the woven bone and its evolution. In this study, finite element analyses based on computed tomography (CT) are used to predict the stiffness of the callus until 69 weeks after surgery using 15 CT images obtained at different stages of an experiment on bone transport, technique in which distraction osteogenesis is used to correct bone defects. Three different approaches were used to assign the mechanical properties to the new bone tissue. First, constant mechanical properties of the hard callus tissue and no porosity were assumed. Nevertheless, this approach did not show good correlations. Second, random variations in the elastic modulus and porosity of the woven bone were taken from previous experimental studies. Finally, the elastic properties of each element were assigned depending on gray scale in CT images. The numerically predicted callus stiffness was compared with previous in vivo measurements. It was concluded firstly that assignment depending on gray scale is the method that provides the best results and secondly that the method that considers a random distribution of porosity and elastic modulus of the callus is also suitable to predict the callus stiffness from 15 weeks after surgery. This finding provides a method for assigning the material properties of the distraction callus, which does not require CT images and may contribute to improve current in silico models.


Assuntos
Calo Ósseo/fisiologia , Calo Ósseo/cirurgia , Modelos Biológicos , Osteogênese por Distração/estatística & dados numéricos , Animais , Fenômenos Biomecânicos , Engenharia Biomédica , Calo Ósseo/diagnóstico por imagem , Simulação por Computador , Módulo de Elasticidade , Feminino , Análise de Elementos Finitos , Consolidação da Fratura/fisiologia , Humanos , Imageamento Tridimensional , Modelos Anatômicos , Porosidade , Carneiro Doméstico , Estresse Mecânico , Tomografia Computadorizada por Raios X
9.
J Craniomaxillofac Surg ; 47(3): 454-460, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30683623

RESUMO

INTRODUCTION: In edentulous patients the form and size of the maxillary sinus vary greatly. Therefore sinus floor augmentation is a standard procedure for implantological purposes. As the sinus membrane cannot be characterized as periosteum, various augmentation materials are used. HYPOTHESIS: an artificially generated space underneath the sinus membrane in the floor of the sinus will lead to spontaneous callus forming and a stable bony consolidation without augmentation material. METHODS: Ten edentulous patients with highly atrophic maxillae were selected. Augmentation of the sinus floor was carried out in a split-mouth study design: On one side a combination of autogenous and xenogenous bone was used, and on the contralateral side a sinus membrane elevation was performed without using any substitutes. After a 6-month interval bone specimens from the test regions were harvested during implant placement. RESULTS: Clear histological evidence of new bone formation was found in all human bone specimens. An active de-novo bone formation process could be proven by the presence of Haversian systems (osteons) displaying osteoblastic and osteoclastic activity. CONCLUSION: In the maxillary sinus of edentulous patients a spontaneous callus-derived de-novo bone formation is possible by elevating the sinus membrane without using augmentation materials.


Assuntos
Regeneração Óssea/fisiologia , Substitutos Ósseos , Ílio/transplante , Seio Maxilar/cirurgia , Minerais , Boca Edêntula/cirurgia , Levantamento do Assoalho do Seio Maxilar/métodos , Transplante Ósseo/métodos , Calo Ósseo/fisiologia , Humanos , Osteogênese/fisiologia
10.
J Orthop Res ; 37(1): 35-50, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30370699

RESUMO

The biology of bone healing is a rapidly developing science. Advances in transgenic and gene-targeted mice have enabled tissue and cell-specific investigations of skeletal regeneration. As an example, only recently has it been recognized that chondrocytes convert to osteoblasts during healing bone, and only several years prior, seminal publications reported definitively that the primary tissues contributing bone forming cells during regeneration were the periosteum and endosteum. While genetically modified animals offer incredible insights into the temporal and spatial importance of various gene products, the complexity and rapidity of healing-coupled with the heterogeneity of animal models-renders studies of regenerative biology challenging. Herein, cells that play a key role in bone healing will be reviewed and extracellular mediators regulating their behavior discussed. We will focus on recent studies that explore novel roles of inflammation in bone healing, and the origins and fates of various cells in the fracture environment. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.


Assuntos
Consolidação da Fratura/imunologia , Osteogênese , Transdução de Sinais , Animais , Calo Ósseo/fisiologia , Condrócitos/fisiologia , Células Progenitoras Endoteliais/fisiologia , Humanos , Células-Tronco Mesenquimais/fisiologia , Neovascularização Fisiológica , Osteoblastos/fisiologia , Osteoclastos/fisiologia
11.
Musculoskelet Surg ; 103(3): 257-262, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30536224

RESUMO

BACKGROUND: Elongation in patients with achondroplasia provides better overall skeletal proportionality and significantly improves such individuals' access to their perineal region to self-manage personal hygiene. This paper describes our surgical technique and outcomes for bilateral humeral lengthening in achondroplasia patients over 26 years. METHODS: Ours was a retrospective study of 55 patients with achondroplasia-related short stature, in whom bilateral humeral lengthening was performed from 1990 to 2016. We describe the surgical technique and analyze mean gain in humeral length, days using an external fixator, mean percentage of lengthening, external fixation index, type of callus, and complications. Pre- and postoperative radiographic measurements were obtained. Patients also were contacted by telephone and asked about their ability to perform peri-anal self-hygiene and about their overall satisfaction. RESULTS: In total, 110 humeri were lengthened (28 males and 27 females) with medium elongation of 9.5 cm on the right and 9.6 cm on the left, while averaging 220 days in an external fixator. We observed 14 minor complications. There was no significant association between pin position and type of callus, and elongation most often external and in the presence of a straight callus. Before elongation, 77.1% of patients reported difficulties with perineal hygiene and 85.4% could not put their hands in their pockets. Upon completion of lengthening, 100% could perform both tasks and 94.5% were very satisfied. CONCLUSIONS: Bilateral humeral elongation yields significant improvements in patient autonomy, with a relatively low complication rate and very high patient satisfaction.


Assuntos
Acondroplasia/cirurgia , Alongamento Ósseo/métodos , Úmero/cirurgia , Acondroplasia/diagnóstico por imagem , Adolescente , Adulto , Alongamento Ósseo/efeitos adversos , Alongamento Ósseo/psicologia , Calo Ósseo/fisiologia , Criança , Fixadores Externos , Feminino , Humanos , Úmero/anatomia & histologia , Úmero/diagnóstico por imagem , Higiene , Masculino , Satisfação do Paciente , Complicações Pós-Operatórias , Estudos Retrospectivos , Autocuidado , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
12.
Acta cir. bras ; 34(1): e20190010000002, 2019. graf
Artigo em Inglês | LILACS | ID: biblio-983685

RESUMO

Abstract Purpose: To evaluate the effects of food restriction on fracture healing in growing rats. Methods: Sixty-eight male Wistar rats were assigned to two groups: (1) Control and (2) Dietary restriction. After weaning the dietary restricted animals were fed ad libitum for 42 days with 50% of the standard chow ingested by the control group. Subsequently, the animals underwent bone fracture at the diaphysis of the right femur, followed by surgical stabilization of bone fragments. On days 14 and 28 post-fracture, the rats were euthanized, and the fractured femurs were dissected, the callus was analyzed by dual-energy X-ray absorptiometry, micro-computed tomography, histomorphometry, mechanical tests, and gene expression. Results: Dietary restriction decreased body mass gain and resulted in several phenotypic changes at the bone callus (a delay in cell proliferation and differentiation, lower rate of newly formed bone and collagen deposition, reductions in bone callus density and size, decrease in tridimensional callus volume, deterioration in microstructure, and reduction in bone callus strength), together with the downregulated expression of osteoblast-related genes. Conclusion: Dietary restriction had detrimental effects on osseous healing, with a healing delay and a lower quality of bone callus formation.


Assuntos
Animais , Masculino , Ratos , Calo Ósseo/fisiologia , Densidade Óssea/fisiologia , Consolidação da Fratura/fisiologia , Desnutrição , Fraturas do Fêmur/fisiopatologia , Fraturas Fechadas/fisiopatologia , Osteoporose/prevenção & controle , Ratos Wistar , Fraturas do Fêmur/diagnóstico por imagem , Fixação Intramedular de Fraturas , Fraturas Fechadas/diagnóstico por imagem
13.
Clin Biomech (Bristol, Avon) ; 58: 62-68, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30036852

RESUMO

BACKGROUND: Circulating mesenchymal stem cells contribute to bone repair. Their incorporation in fracture callus is correlated to their bioavailability. In addition, Granulocyte-colony stimulating factor induces the release of vascular and mesenchymal progenitors. We hypothesized that this glycoprotein stimulates fracture healing, and analyzed the effects of its administration at low doses on bone healing. METHODS: 27 adult male Sprague-Dawley rats underwent mid-femur osteotomy stabilized by centromedullar pinning. In a post (pre) operative group, rats were subcutaneously injected with 5 µg/kg per day of Granulocyte-colony stimulating factor for 5 days after (before) surgery. In a control group, rats were injected with saline solution for 5 days immediately after surgery. A radiographic consolidation score was calculated. At day 35, femurs were studied histologically and underwent biomechanical tests. FINDINGS: 5 weeks after surgery, mean radiographic scores were significantly higher in the Preop group 7.75 (SD 0.42) and in the Postop group 7.67 (SD 0.52) than in the control group 6.75 (SD 0.69). Biomechanical tests showed femur stiffness to be more than three times higher in both the Preop 109.24 N/mm (SD 51.86) and Postop groups 100.05 N/mm (SD 60.24) than in control 32.01 N/mm (SD 15.78). Mean maximal failure force was twice as high in the Preop group 68.66 N (SD 27.78) as in the control group 34.21 N (SD 11.79). Histological results indicated a later consolidation process in control than in treated groups. INTERPRETATION: Granulocyte-colony stimulating factor injections strongly stimulated early femur fracture healing, indicating its potential utility in human clinical situations such as programmed osteotomy and fracture.


Assuntos
Consolidação da Fratura/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Animais , Pinos Ortopédicos , Calo Ósseo/fisiologia , Fraturas do Fêmur/fisiopatologia , Fraturas do Fêmur/cirurgia , Fixação Intramedular de Fraturas , Consolidação da Fratura/fisiologia , Humanos , Masculino , Osteotomia , Ratos , Ratos Sprague-Dawley
14.
PLoS One ; 13(4): e0195466, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29624608

RESUMO

The mechanical environment is a primary factor in the success of distraction osteogenesis. It is known that the interfragmentary movement during the distraction and maturation phase effects the callus formation. In addition to cyclic compression, other movements like shear and bending influence the bone formation process as shown in previous callus distraction studies. Reports of cartilage presence and endochondral ossification in the regenerative zone have been associated with a lack of fixation stability and delayed healing. So far the effects of the direction of interfragmentary movements could not be studied separately. By means of a unique lateral callus distraction model, we investigated the effects of small (0.1 mm) and moderate (0.6 mm), purely axial compression on ossification during callus maturation in sheep. A distraction device incorporating a mobile titanium plate was mounted on the tibia. Following lateral callus distraction, electromechanically controlled movements allowed purely axial cyclic compression of the tissue regenerate. Seven weeks post-operatively, the tissue regenerates were investigated using µCT, histology and immunohistochemistry. The larger amplitude significantly increased bone formation (Fractional bone volume: 19.4% vs. 5.2%, p = 0.03; trabecular thickness: 0.1 mm vs. 0.06 mm, p = 0.006; mean spicule height: 2.6 mm vs. 1.1 mm, p = 0.02) however, no endochondral ossification occurred. The elimination of shear movement, unimpaired neovascularization as well as the tensile strain stimuli during the distraction phase suppressing chondrogenic differentiation may all contribute to the absence of cartilage. In clinical application of distraction osteogenesis, moderate axial interfragmentary movement augments intramembranous ossification provided shear strain is minimized.


Assuntos
Calo Ósseo/fisiologia , Calo Ósseo/cirurgia , Osteogênese por Distração/métodos , Animais , Fenômenos Biomecânicos , Calo Ósseo/diagnóstico por imagem , Colágeno Tipo II/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Desenho de Equipamento , Fixadores Externos , Feminino , Imuno-Histoquímica , Modelos Animais , Osteogênese , Osteogênese por Distração/instrumentação , Fatores de Transcrição SOX9/metabolismo , Carneiro Doméstico , Estresse Mecânico , Tíbia/diagnóstico por imagem , Tíbia/fisiologia , Tíbia/cirurgia , Microtomografia por Raio-X
15.
Orthopedics ; 41(1): 54-58, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29257188

RESUMO

Evaluation of callus maturation and the decision to remove an external fixator depend on radiographic and clinical findings, which are subjective. Callus fracture or recurrent deformity may occur after premature removal of a fixator. The authors applied a technique to measure bioelectrical impedance to assess callus maturation. This study included 27 limbs that underwent deformity correction or callus distraction using a fixator. Mean patient age at the time of surgery was 17.2 years. Overall impedance during callus maturation was measured from after completion of correction or distraction to removal of the fixator. Temporal changes in impedance values were measured, and maximum and final values were compared with initial values. The resistance rates were compared by age (<15 or ≥15 years), correction site (femur or tibia), and treatment method (noncontact or contact). Mean overall impedance increased gradually. Compared with initial values, maximum and final impedance values were 1.21 times and 1.15 times higher, respectively. Resistance rates by age, correction site, and treatment method were significantly higher in patients 15 years and older, in the tibia, and in the contact group, respectively. Overall impedance tended to increase during callus maturation but varied among patients. Therefore, resistance rates were calculated to classify differences for individual patients. Age and treatment method were important predictors of resistance rates. These data by age, correction site, and treatment method, which assume overall impedance from after completion of correction or distraction, can serve as a useful index to determine when a fixator should be removed. [Orthopedics. 2018; 41(1):54-58.].


Assuntos
Calo Ósseo/fisiologia , Fixadores Externos , Fêmur/cirurgia , Fixação de Fratura , Fraturas Ósseas/cirurgia , Tíbia/cirurgia , Adolescente , Adulto , Calosidades , Criança , Impedância Elétrica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteogênese por Distração , Adulto Jovem
16.
Int J Nanomedicine ; 12: 8443-8457, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29225463

RESUMO

Treatment for fractures requires internal fixation devices, which are mainly produced from stainless steel or titanium alloy without biological functions. Therefore, we developed a novel nano-copper-bearing stainless steel with nano-sized copper-precipitation (317L-Cu SS). Based on previous studies, this work explores the effect of 317L-Cu SS on fracture healing; that is, proliferation, osteogenic differentiation, osteogenesis-related gene expression, and lysyl oxidase activity of human bone mesenchymal stem cells were detected in vitro. Sprague-Dawley rats were used to build an animal fracture model, and fracture healing and callus evolution were investigated by radiology (X-ray and micro-CT), histology (H&E, Masson, and safranin O/fast green staining), and histomorphometry. Further, the Cu2+ content and Runx2 level in the callus were determined, and local mechanical test of the fracture was performed to assess the healing quality. Our results revealed that 317L-Cu SS did not affect the proliferation of human bone mesenchymal stem cells, but promoted osteogenic differentiation and the expression of osteogenesis-related genes. In addition, 317L-Cu SS upregulated the lysyl oxidase activity. The X-ray and micro-CT results showed that the callus evolution efficiency and fracture healing speed were superior for 317L-Cu SS. Histological staining displayed large amounts of fibrous tissues at 3 weeks, and cartilage and new bone at 6 weeks. Further, histomorphometric analysis indicated that the callus possessed higher osteogenic efficiency at 6 weeks, and a high Cu2+ content and increased Runx2 expression were observed in the callus for 317L-Cu SS. Besides, the mechanical strength of the fracture site was much better than that of the control group. Overall, we conclude that 317L-Cu SS possesses the ability to increase Cu2+ content and promote osteogenesis in the callus, which could accelerate the callus evolution process and bone formation to provide faster and better fracture healing.


Assuntos
Calo Ósseo/efeitos dos fármacos , Cobre/farmacologia , Consolidação da Fratura/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Aço Inoxidável/farmacologia , Animais , Calo Ósseo/diagnóstico por imagem , Calo Ósseo/fisiologia , Cartilagem/efeitos dos fármacos , Cartilagem/crescimento & desenvolvimento , Diferenciação Celular/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Humanos , Implantes Experimentais , Células-Tronco Mesenquimais/citologia , Nanoestruturas/química , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Ratos , Ratos Sprague-Dawley , Aço Inoxidável/química , Microtomografia por Raio-X
17.
Acta cir. bras ; 32(11): 924-934, Nov. 2017. graf
Artigo em Inglês | LILACS | ID: biblio-886184

RESUMO

Abstract Purpose: To evaluate the influence of nandrolone decanoate on fracture healing and bone quality in normal rats. Methods: Male rats were assigned to four groups (n=28/group): Control group consisting of animals without any intervention, Nandrolone decanoate (DN) group consisting of animals that received intramuscular injection of nandrolone decanoate, Fracture group consisting of animals with a fracture at the mid-diaphysis of the femur, and Fracture and nandrolone decanoate group consisting of animals with a femur fracture and treatment with nandrolone decanoate. Fractures were created at the mid-diaphysis of the right femur by a blunt trauma and internally fixed using an intramedullary steel wire. The DN was injected intramuscularly twice per week (10 mg/kg of body mass). The femurs were measured and evaluated by densitometry and mechanical resistance after animal euthanasia. The newly formed bone and collagen type I levels were quantified in the callus. Results: The treated animals had longer femurs after 28 days. The quality of the intact bone was not significantly different between groups. The bone callus did show a larger mass in the treated rats. Conclusion: The administration of nandrolone decanoate did not affect the quality of the intact bone, but might have enhanced the bone callus formation.


Assuntos
Animais , Masculino , Ratos , Calo Ósseo/fisiologia , Consolidação da Fratura/efeitos dos fármacos , Fraturas do Fêmur/tratamento farmacológico , Anabolizantes/farmacologia , Nandrolona/análogos & derivados , Densidade Óssea/fisiologia , Ratos Wistar , Consolidação da Fratura/fisiologia , Nandrolona/farmacologia
18.
J Mech Behav Biomed Mater ; 74: 236-244, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28623826

RESUMO

Nanoindentation has been used successfully in the determination of the mechanical properties of bone. Its application in fracture healing provides information on the evolution of material properties of the woven bone during regeneration process. However, this technique has not been applied in assessing the mechanical properties of woven bone during distraction osteogenesis. Therefore, the aim of this work is to evaluate the spatial and temporal variations of the elastic modulus of the woven bone generated during the bone transport process. Callus samples were harvested from intervened animals at different time points during the bone transport process (35, 50, 79, 98, 161 and 525 days after surgery) for nanoindentation measurements. Results clearly showed that the mean elastic modulus of the woven bone increased during the bone transport process reaching 77% of value for cortical bone after 525 days (from 7GPa 35 days after surgery to 14GPa 525 days after surgery approximately). Woven bone generated during bone transport seems to present similar evolution of elastic modulus with time as values reported for fracture healing. Furthermore, different spatial variations of elastic modulus within the callus were found for different stages of the process.


Assuntos
Regeneração Óssea , Calo Ósseo/fisiologia , Consolidação da Fratura , Osteogênese por Distração , Animais , Módulo de Elasticidade , Ovinos , Análise Espaço-Temporal
19.
J Bone Joint Surg Am ; 98(4): 276-84, 2016 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-26888675

RESUMO

BACKGROUND: Mechanotransduction is theorized to influence fracture-healing, but optimal fracture-site motion is poorly defined. We hypothesized that three-dimensional (3-D) fracture-site motion as estimated by finite element (FE) analysis would influence callus formation for a clinical series of supracondylar femoral fractures treated with locking-plate fixation. METHODS: Construct-specific FE modeling simulated 3-D fracture-site motion for sixty-six supracondylar femoral fractures (OTA/AO classification of 33A or 33C) treated at a single institution. Construct stiffness and directional motion through the fracture were investigated to assess the validity of construct stiffness as a surrogate measure of 3-D motion at the fracture site. Callus formation was assessed radiographically for all patients at six, twelve, and twenty-four weeks postoperatively. Univariate and multivariate linear regression analyses examined the effects of longitudinal motion, shear (transverse motion), open fracture, smoking, and diabetes on callus formation. Construct types were compared to determine whether their 3-D motion profile was associated with callus formation. RESULTS: Shear disproportionately increased relative to longitudinal motion with increasing bridge span, which was not predicted by our assessment of construct stiffness alone. Callus formation was not associated with open fracture, smoking, or diabetes at six, twelve, or twenty-four weeks. However, callus formation was associated with 3-D fracture-site motion at twelve and twenty-four weeks. Longitudinal motion promoted callus formation at twelve and twenty-four weeks (p = 0.017 for both). Shear inhibited callus formation at twelve and twenty-four weeks (p = 0.017 and p = 0.022, respectively). Titanium constructs with a short bridge span demonstrated greater longitudinal motion with less shear than did the other constructs, and this was associated with greater callus formation (p < 0.001). CONCLUSIONS: In this study of supracondylar femoral fractures treated with locking-plate fixation, longitudinal motion promoted callus formation, while shear inhibited callus formation. Construct stiffness was found to be a poor surrogate of fracture-site motion. Future implant design and operative fixation strategies should seek to optimize 3-D fracture-site motion rather than rely on surrogate measures such as axial stiffness.


Assuntos
Calo Ósseo/fisiologia , Fraturas do Fêmur/cirurgia , Fixação Interna de Fraturas , Consolidação da Fratura/fisiologia , Movimento/fisiologia , Idoso , Fenômenos Biomecânicos , Placas Ósseas , Feminino , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/fisiopatologia , Análise de Elementos Finitos , Fixação Interna de Fraturas/instrumentação , Fixação Interna de Fraturas/métodos , Humanos , Modelos Lineares , Masculino , Mecanotransdução Celular , Pessoa de Meia-Idade , Modelos Biológicos , Análise Multivariada , Radiografia , Resultado do Tratamento
20.
Acta Cir Bras ; 30(11): 727-35, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26647791

RESUMO

PURPOSE: To investigate the effect of vibration therapy on the bone callus of fractured femurs and the bone quality of intact femurs in ovariectomized rats. METHODS: Fifty-six rats aged seven weeks were divided into four groups: control with femoral fracture (CON, n=14), ovariectomized with femoral fracture (OVX, n=14), control with femoral fracture plus vibration therapy (CON+VT, n=14), and ovariectomized with femoral fracture plus vibration therapy (OVX+VT, n=14). Three months after ovariectomy or sham surgery, a complete fracture was produced at the femoral mid-diaphysis and stabilized with a 1-mm-diameter intramedullary Kirschner wire. X-rays confirmed the fracture alignment and fixation. Three days later, the VT groups underwent vibration therapy (1 mm, 60 Hz for 20 minutes, three times per week for 14 or 28 days). The bone and callus quality were assessed by densitometry, three-dimensional microstructure, and mechanical test. RESULTS: Ovariectomized rats exhibited a substantial loss of bone mass and severe impairment in bone microarchitecture, both in the non-fractured femur and the bone callus. Whole-body vibration therapy exerted an important role in ameliorating the bone and fracture callus parameters in the osteoporotic bone. CONCLUSION: Vibration therapy improved bone quality and the quality of the fracture bone callus in ovariectomized rats.


Assuntos
Calo Ósseo/fisiologia , Fraturas do Fêmur/terapia , Consolidação da Fratura/fisiologia , Osteoporose/fisiopatologia , Ovariectomia/efeitos adversos , Vibração/uso terapêutico , Absorciometria de Fóton , Animais , Densidade Óssea/fisiologia , Feminino , Fraturas do Fêmur/etiologia , Fraturas do Fêmur/fisiopatologia , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/fisiopatologia , Fraturas por Osteoporose/terapia , Distribuição Aleatória , Ratos Wistar , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento
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