RESUMO
Multiple case reports using recombinant human bone morphogenetic protein-2 (rhBMP-2) have reported complications. However, the local adverse effects of rhBMP-2 application are not well documented. In this report we show that, in addition to promoting lumbar spinal fusion through potent osteogenic effects, rhBMP-2 augmentation promotes local cyst-like osteolytic formations in sheep trabecular bones that have undergone anterior lumbar interbody fusion. Three months after operation, conventional computed tomography showed that the trabecular bones of the rhBMP-2 application groups could fuse, whereas no fusion was observed in the control group. Micro-computed tomography analysis revealed that the core implant area's bone volume fraction and bone mineral density increased proportionately with rhBMP-2 dose. Multiple cyst-like bone voids were observed in peri-implant areas when using rhBMP-2 applications, and these sites showed significant bone mineral density decreases in relation to the unaffected regions. Biomechanically, these areas decreased in strength by 32% in comparison with noncystic areas. Histologically, rhBMP-2-affected void sites had an increased amount of fatty marrow, thinner trabecular bones, and significantly more adiponectin- and cathepsin K-positive cells. Despite promoting successful fusion, rhBMP-2 use in clinical applications may result in local adverse structural alterations and compromised biomechanical changes to the bone.
Assuntos
Proteína Morfogenética Óssea 2/administração & dosagem , Vértebras Lombares/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Fusão Vertebral/métodos , Fator de Crescimento Transformador beta/administração & dosagem , Animais , Densidade Óssea/efeitos dos fármacos , Proteína Morfogenética Óssea 2/efeitos adversos , Proteína Morfogenética Óssea 2/genética , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Modelos Animais , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/genética , Ovinos , Fusão Vertebral/efeitos adversos , Tomografia Computadorizada por Raios X , Fator de Crescimento Transformador beta/efeitos adversos , Fator de Crescimento Transformador beta/genéticaRESUMO
PURPOSE: The ovine model is often used to evaluate new spine fusion technologies prior to clinical testing. An important aspect of designing sheep surgery protocols is to select the appropriate postoperative time period for comparing fusion outcomes. Unfortunately, determining the ideal study endpoint is complicated by the fact that prior published studies have not used consistent timeframes. Thus, the primary aim of this study was to provide a reference for investigators as to the expected fusion outcomes of control groups at varying timepoints in sheep spine surgery models. METHODS: We identified published sheep fusion studies using autograft, interbody cages, and/or instrumentation. Fusion data were extracted, converted to a common scale, and analyzed across studied timepoints. RESULTS: Overall, 29 studies of 360 fusion levels were identified: 11 ALIF (158 levels), 3 PLIF/TLIF (28 levels), 8 PLF (90 levels), and 7 ACDF (84 levels). Studied timepoints ranged from 4 to 48 weeks postoperative. In general, fusion rates varied across techniques and instrumentation. The time to reach solid fusion differed by as many as 20 weeks between control groups. CONCLUSIONS: Recommended timeframes for future studies designed to show either superiority over controls or equivalent outcomes with controls were developed based on aggregate results. Designating ideal study endpoints for sheep fusion models has both ethical implications associated with responsible use of animals in research, and economic implications given the cost of animal research. The current results can guide the development of future research methods and help investigators choose appropriate study timelines for various control groups.
Assuntos
Osseointegração , Fusão Vertebral/instrumentação , Fusão Vertebral/métodos , Animais , Modelos Animais , Ovinos , Fatores de TempoRESUMO
BACKGROUND: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a powerful osteoinductive morphogen capable of stimulating the migration of mesenchymal stem cells (MSCs) to the site of implantation and inducing the proliferation and differentiation of these MSCs into osteoblasts. Vertebral end-plate and vertebral body resorption has been reported after interbody fusion with high doses of rhBMP-2. In this study, we investigated the effects of 2 rhBMP-2 doses on peri-implant bone resorption and bone remodeling at 7 time points in an end-plate-sparing ovine interbody fusion model. METHODS: Twenty-one female sheep underwent an end-plate-sparing discectomy followed by interbody fusion at L2-L3 and L4-L5 using a custom polyetheretherketone (PEEK) interbody fusion device. The PEEK interbody device was filled with 1 of 2 different doses of rhBMP-2 on an absorbable collagen sponge (ACS): 0.13 mg (1×) or 0.90 mg (7×). Bone remodeling and interbody fusion were assessed via high-resolution radiography and histological analyses at 1, 2, 3, 4, 8, 12, and 20 weeks postoperatively. RESULTS: Peri-implant bone resorption peaked between 3 and 8 weeks in both the 1× and the 7× rhBMP-2/ACS-dose group. Osteoclastic activity and corresponding peri-implant bone resorption was dose-dependent, with moderate-to-marked resorption at the 7×-dose level and less resorption at the 1×-dose level. Both dose (p < 0.0007) and time (p < 0.0025) affected bone resorption significantly. Transient bone-resorption areas were fully healed by 12 weeks. Osseous bridging was seen at all but 1 spinal level at 12 and at 20 weeks. CONCLUSIONS: In the ovine end-plate-sparing interbody fusion model, rhBMP-2 dose-dependent osteoclastic resorption is a transient phenomenon that peaks at 4 weeks postoperatively. CLINICAL RELEVANCE: Using the U.S. Food and Drug Administration (FDA)-approved rhBMP-2 concentration and matching the volume of rhBMP-2/ACS with the volume of desired bone formation within the interbody construct may limit the occurrence of transient bone resorption.
Assuntos
Proteína Morfogenética Óssea 2/farmacologia , Remodelação Óssea/efeitos dos fármacos , Fusão Vertebral/métodos , Fator de Crescimento Transformador beta/farmacologia , Animais , Proteína Morfogenética Óssea 2/uso terapêutico , Discotomia , Relação Dose-Resposta a Droga , Feminino , Vértebras Lombares/cirurgia , Modelos Animais , Osteogênese/efeitos dos fármacos , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Ovinos , Fator de Crescimento Transformador beta/uso terapêutico , Resultado do TratamentoRESUMO
Bone quantity, or density, has insufficient power to discriminate fracture risk in individuals. Additional measures of bone quality, such as microarchitectural characteristics and bone tissue properties, including the presence of damage, may improve the diagnosis of fracture risk. Microdamage and microarchitecture are two aspects of trabecular bone quality that are interdependent, with several microarchitectural changes strongly correlated to damage risk after compensating for bone density. This study aimed to delineate the effects of microarchitecture and estrogen depletion on microdamage susceptibility in trabecular bone using an ovariectomized sheep model to mimic post-menopausal osteoporosis. The propensity for microdamage formation in trabecular bone of the distal femur was studied using a sequence of compressive and torsional overloads. Ovariectomy had only minor effects on the microarchitecture at this anatomic site. Microdamage was correlated to bone volume fraction and structure model index (SMI), and ovariectomy increased the sensitivity to these parameters. The latter may be due to either increased resorption cavities acting as stress concentrations or to altered bone tissue properties. Pre-existing damage was also correlated to new damage formation. However, sequential loading primarily generated new cracks as opposed to propagating existing cracks, suggesting that pre-existing microdamage contributes to further damage of bone by shifting load bearing to previously undamaged trabeculae, which are subsequently damaged. The transition from plate-like to rod-like trabeculae, indicated by SMI, dictates this shift, and may be a hallmark of bone that is already predisposed to accruing greater levels of damage through compromised microarchitecture.
Assuntos
Osso Esponjoso/lesões , Osso Esponjoso/metabolismo , Estrogênios/deficiência , Animais , Densidade Óssea , Osso Esponjoso/citologia , Osso Esponjoso/fisiologia , Feminino , Fêmur/citologia , Fêmur/lesões , Fêmur/metabolismo , Fêmur/fisiologia , Fraturas Ósseas/metabolismo , Fraturas Ósseas/fisiopatologia , Ovariectomia , Pressão , Risco , Ovinos , Estresse Mecânico , Suporte de CargaRESUMO
BACKGROUND: Vertebral compression fractures related to osteoporosis greatly afflict the aging population. One of the most commonly used therapy today is balloon kyphoplasty. However, this treatment is far from ideal and is associated with significant side effects. NELL-1, an osteoinductive factor that possesses both pro-osteogenic and anti-osteoclastic properties, is a promising candidate for an alternative to current treatment modalities. This study utilizes the pro-osteogenic properties of recombinant human NELL-1 (rhNELL-1) in lumbar spine vertebral defect model in osteoporotic sheep. METHODS: Osteoporosis was induced through ovariectomy, dietary depletion of calcium and vitamin D, and steroid administration. After osteoporotic induction, lumbar vertebral body defect creation was performed. Sheep were randomly implanted with the control vehicle, comprised of hyaluronic acid (HA) with hydroxyapatite-coated ß-tricalcium phosphate (ß-TCP), or the treatment material of rhNELL-1 protein lyophilized onto ß-TCP mixed with HA. Analysis of lumbar spine defect healing was performed by radiographic, histologic, and computer-simulated biomechanical testing. RESULTS: rhNELL-1 treatment significantly increased lumbar spine bone formation, as determined by bone mineral density, % bone volume, and mean cortical width as assessed by micro-computed tomography. Histological analysis revealed a significant increase in bone area and osteoblast number and decrease in osteoclast number around the implant site. Computer-simulated biomechanical analysis of trabecular bone demonstrated that rhNELL-1-treatment resulted in a significantly more stress-resistant composition. CONCLUSION: Our findings suggest rhNELL-1-based vertebral implantation successfully improved cortical and cancellous bone regeneration in the lumbar spine of osteoporotic sheep. rhNELL-1-based bone graft substitutes represent a potential new local therapy.
Assuntos
Implantes Experimentais , Vértebras Lombares/patologia , Proteínas do Tecido Nervoso/farmacologia , Osteogênese/efeitos dos fármacos , Osteoporose/patologia , Absorciometria de Fóton , Animais , Fenômenos Biomecânicos , Densidade Óssea/efeitos dos fármacos , Proteínas de Ligação ao Cálcio , Contagem de Células , Modelos Animais de Doenças , Análise de Elementos Finitos , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/fisiopatologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/patologia , Osteoclastos/efeitos dos fármacos , Osteoclastos/patologia , Osteoporose/diagnóstico por imagem , Osteoporose/fisiopatologia , Osteoporose/terapia , Ovinos , Microtomografia por Raio-XRESUMO
NELL-1 is a secreted, osteoinductive protein whose expression rheostatically controls skeletal ossification. Overexpression of NELL-1 results in craniosynostosis in humans and mice, whereas lack of Nell-1 expression is associated with skeletal undermineralization. Here we show that Nell-1-haploinsufficient mice have normal skeletal development but undergo age-related osteoporosis, characterized by a reduction in osteoblast:osteoclast (OB:OC) ratio and increased bone fragility. Recombinant NELL-1 binds to integrin ß1 and consequently induces Wnt/ß-catenin signalling, associated with increased OB differentiation and inhibition of OC-directed bone resorption. Systemic delivery of NELL-1 to mice with gonadectomy-induced osteoporosis results in improved bone mineral density. When extended to a large animal model, local delivery of NELL-1 to osteoporotic sheep spine leads to significant increase in bone formation. Altogether, these findings suggest that NELL-1 deficiency plays a role in osteoporosis and demonstrate the potential utility of NELL-1 as a combination anabolic/antiosteoclastic therapeutic for bone loss.
Assuntos
Osso e Ossos/patologia , Proteínas do Tecido Nervoso/administração & dosagem , Proteínas do Tecido Nervoso/deficiência , Osteoporose/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Proteínas de Ligação ao Cálcio , Células Cultivadas , Avaliação Pré-Clínica de Medicamentos , Feminino , Haploinsuficiência , Humanos , Cadeias beta de Integrinas/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Osteoporose/etiologia , Osteoporose/metabolismo , Osteoporose/patologia , Fenótipo , Ovinos , Proteínas Wnt/metabolismo , Adulto Jovem , beta Catenina/metabolismoRESUMO
Osteoporosis is a bone disease resulting in increased fracture risk as a result of alterations in both quantity and quality of bone. Bone quality is a combination of metabolic and microarchitectural properties of bone that can help to explain the increased susceptibility to fracture. Translational animal models are essential to understanding the pathology and for evaluating potential treatments of this disease. Large animals, such as the ovariectomized sheep, have been used as models for post-menopausal osteoporosis. However, long-term studies have not been carried out to observe the effects of ovariectomy after more than one year. This study employed micro-computed tomography to quantify changes in microarchitectural and mechanical parameters in femoral condyles and vertebral bodies of sheep that were sacrificed one or two years following ovariectomy. In the vertebral body, microarchitectural characteristics were significantly degraded following one year of ovariectomy in comparison to controls. The mechanical anisotropy, determined from micro-scale finite element models, was also greater in the ovariectomized groups, although the fabric tensor anisotropy was similar. There was no greater architectural degradation following two years of ovariectomy compared to one. Ovariectomy had minimal effects on the trabecular architecture of the distal femur even after two years. These results indicate that the vertebral body is the preferred anatomic site for studying bone from the ovariectomized sheep model, and that architectural changes stabilize after the first year.
Assuntos
Densidade Óssea , Fêmur/diagnóstico por imagem , Osteoporose/diagnóstico por imagem , Coluna Vertebral/diagnóstico por imagem , Animais , Anisotropia , Feminino , Fraturas Ósseas/diagnóstico por imagem , Estudos Longitudinais , Modelos Animais , Ovariectomia , Ovinos , Carneiro Doméstico , Estresse Mecânico , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND CONTEXT: Osteoconductive porous ceramic bone graft materials supplemented with mesenchymal precursor cells (MPC) derived from autologous bone marrow aspirates have been shown to stimulate successful interbody and posterolateral spine fusion in preclinical models. Recent advances in immunomagnetic cell sorting have enabled purification and isolation of pluripotent stem cells from marrow aspirates and have expanded stem cell technology to allogeneic cell sources. Allogeneic MPC technology combined with appropriate synthetic biomaterial carriers could provide both the osteogenic and osteoconductive components needed for successful posterolateral spine fusion without the need for autologous bone harvest or expensive recombinant protein technology. PURPOSE: To determine the safety and efficacy of a hydroxyapatite:tricalcium phosphate graft material supplemented with allogeneic mesenchymal precursor cells in posterolateral lumbar spine fusion using an ovine model. STUDY DESIGN: Skeletally mature ewes underwent single-level instrumented posterolateral lumbar spine fusion using either autograft (AG), hydroxyapatite:tricalcium phosphate carrier (CP), or CP supplemented with allogeneic mesenchymal progenitor cells (MPCs). Three doses of MPCs were evaluated: 25 × 106 cells (low dose, LD), 75 × 106 cells (mid dose, MD), and 225 × 106 cell (high dose, HD). Animals survived for either 4 or 9 months. METHODS: Plain radiographs were acquired and scored for bridging bone at regular intervals during healing to monitor fusion development. Hematology, coagulation, and serum chemistry were monitored at regular intervals throughout the study to monitor animal health. After necropsy, computed tomography, high-resolution radiography, biomechanical testing, organ pathology, bone histopathology, and bone histomorphometry were conducted to monitor the safety and ascertain the efficacy of MPC treatment. RESULTS: MPC treatment in this spine fusion model resulted in no observed adverse systemic or local tissue responses. Radiographically, fusion scores for MPC-treated animals were uniformly higher compared with those treated with carrier alone (CP) after 3 months and continued the same trend throughout 9 month of healing. Quantitative computed tomography confirmed better connectivity of the fusion for MPC treatment groups compared with CP. Biomechanical analyses were not able to differentiate between treatment groups. Histomorphometry results confirmed radiographic and quantitative computed tomography results; cell-supplemented treatment groups and autograft had equivalent amounts of bone within the fusion mass and less bony fusion tissue was found within the fusion mass in specimens from the CP treatment group. No conclusive effects of cell dose of fusion efficacy were noted. CONCLUSIONS: Adult allogeneic mesenchymal precursor cells delivered via a hydroxyapatite:tricalcium phosphate carrier were both safe and efficacious in this ovine spine fusion model. Results from this preclinical study support that allogeneic mesenchymal precursor cells produced fusion efficacy similar to that achieved using iliac crest autograft, thereby providing a safe and viable option to achieve successful posterolateral spine fusion.
Assuntos
Transplante Ósseo/métodos , Cerâmica , Vértebras Lombares/cirurgia , Transplante de Células-Tronco Mesenquimais/métodos , Fusão Vertebral/métodos , Animais , Fenômenos Biomecânicos , Fosfatos de Cálcio , Durapatita , Feminino , Vértebras Lombares/diagnóstico por imagem , Masculino , Modelos Animais , Radiografia , Ovinos , Transplante AutólogoRESUMO
Fibrillar collagens in connective tissues are organized into complex and diverse hierarchical networks. In dermis, bone, and tendon, one common phenomenon at the micrometer scale is the organization of fibrils into bundles. Previously, we have reported that collagen fibrils in these tissues exhibit a 10 nm width distribution of D-spacing values. This study expands the observation to a higher hierarchical level by examining fibril D-spacing distribution in relation to the bundle organization. We used atomic force microscopy imaging and two-dimensional fast Fourier transform analysis to investigate dermis, tendon, and bone tissues. We found that, in each tissue type, collagen fibril D-spacings within a single bundle were nearly identical and frequently differ by less than 1 nm. The full 10 nm range in D-spacing values arises from different values found in different bundles. The similarity in D-spacing was observed to persist for up to 40 µm in bundle length and width. A nested mixed model analysis of variance examining 107 bundles and 1710 fibrils from dermis, tendon, and bone indicated that fibril D-spacing differences arise primarily at the bundle level (â¼76%), independent of species or tissue types.
Assuntos
Osso e Ossos/ultraestrutura , Colágeno Tipo I/ultraestrutura , Nanoestruturas/ultraestrutura , Pele/ultraestrutura , Tendões/ultraestrutura , Animais , Humanos , Especificidade de Órgãos , Ovinos , Especificidade da EspécieRESUMO
Tissue cryo-sectioning combined with atomic force microscopy imaging reveals that the nanoscale morphology of dermal collagen fibrils, quantified using the metric of D-periodic spacing, changes under the condition of estrogen depletion. Specifically, a new subpopulation of fibrils with D-spacings in the region between 56 and 59 nm is present 2 years following ovariectomy in ovine dermal samples. In addition, the overall width of the distribution, both values above and below the mean, was found to be increased. The change in width due to an increase in lower values of D-spacings was previously reported for ovine bone; however, this report demonstrates that the effect is also present in non-mineralized collagen fibrils. A nonparametric Kolmogorov-Smirnov test of the cumulative density function indicates a statistical difference in the sham and OVX D-spacing distributions (P<0.01).
Assuntos
Colágeno/ultraestrutura , Derme/química , Derme/ultraestrutura , Estrogênios/fisiologia , Animais , Osso e Ossos/química , Osso e Ossos/ultraestrutura , Colágeno/análise , Feminino , Microscopia de Força Atômica , Ovariectomia , OvinosRESUMO
STUDY DESIGN: This study was designed to determine whether Augment Bone Graft (Augment, Biomimetic Therapeutics, Inc., Franklin, TN) and Augment Injectable Bone Graft (Augment Injectable, Biomimetic Therapeutics, Inc., Franklin, TN), 2 combination devices comprising recombinant human platelet-derived growth factor-BB and ß-tricalcium phosphate-containing matrices, promote bone bridging in an ovine model of lumbar spine fusion. Autologous bone graft (autograft) was used as a positive control. OBJECTIVE: The purpose of this study was to determine the ability of Augment products to promote fusion of the L2-L3 and L4-L5 vertebral bodies in an ovine model. SUMMARY OF BACKGROUND DATA: In interbody spine fusion, the intervertebral disc is removed and a spacer is inserted for support and to facilitate bone growth. The fusion is commonly enhanced with grafts. Autograft is the "gold standard" but it has limitations including availability and donor-site morbidity. Synthetic graft substitutes eliminate these complications. Augment products are combination devices including recombinant human platelet-derived growth factor-BB, a well-characterized chemotactic, mitogenic, and proangiogenic protein essential in wound and bone healing. METHODS: Twenty-two sheep received an uninstrumented, double-level, interbody lumbar spinal fusion procedure using a polyetheretherketone spacer, which was either empty or packed with iliac crest autograft, Augment or Augment Injectable. The same treatment was used at both levels. Animals were 24 weeks after surgery, and fusion was assessed by micro-computed tomography (micro-CT) and histology. RESULTS: Micro-CT and histologic assessment of fusion revealed that empty controls had significantly lower fusion rates. No differences were detected among autografts, Augment, and Augment Injectable-treated specimens. Residual ß-tricalcium phosphate particles embedded in the newly formed bone were visible in Augment- and Augment Injectable-treated specimens. CONCLUSION: Augment-treated specimens had the highest fusion scores. Treatment with either of the Augment products significantly promoted interbody spine fusion compared with empty spacers and was equivalent to autograft-induced fusion. No adverse events were noted.
Assuntos
Transplante Ósseo/métodos , Vértebras Lombares/cirurgia , Fusão Vertebral/métodos , Animais , Becaplermina , Discotomia , Ílio/transplante , Disco Intervertebral/diagnóstico por imagem , Disco Intervertebral/cirurgia , Vértebras Lombares/diagnóstico por imagem , Proteínas Proto-Oncogênicas c-sis/uso terapêutico , Radiografia , Ovinos , Transplante AutólogoRESUMO
BACKGROUND: Rotator cuff tears are a common source of shoulder pain. High rates (20%-94%) of structural failure of the repair have been attributed to multiple factors, including poor repair tissue quality and tendon-to-bone integration. Biologic augmentation using growth factors has potential to promote tendon-to-bone integration, improving the function and long-term success of the repair. One such growth factor is platelet-derived growth factor-BB (PDGF-BB), which has been shown to improve healing in tendon and bone repair models. HYPOTHESIS: Recombinant human PDGF-BB (rhPDGF-BB) combined with a highly porous type I bovine collagen matrix will improve the biomechanical function and morphologic appearance of the repair in a dose-dependent manner, relative to a suture-only control, after 12 weeks in an acute ovine model of rotator cuff repair. STUDY DESIGN: Controlled laboratory study. METHODS: An interpositional graft consisting of rhPDGF-BB and a type I collagen matrix was implanted in an ovine model of rotator cuff repair. Biomechanical and histologic analyses were performed to determine the functional and anatomic characteristics of the repair after 12 weeks. RESULTS: A significant increase in the ultimate load to failure was observed in repairs treated with 75 µg (1490.5 ± 224.5 N, P = .029) or 150 µg (1486.6 ± 229.0 N, P = .029) of rhPDGF-BB, relative to suture-only controls (910.4 ± 156.1 N) and the 500-µg rhPDGF-BB group (677.8 ± 105.9 N). The 75-µg and 150-µg rhPDGF-BB groups also exhibited increased tendon-to-bone interdigitation histologically. No differences in inflammation or cellularity were observed among treatments. CONCLUSION: This study demonstrated that an interpositional graft consisting of rhPDGF-BB (75 or 150 µg) and a type I collagen matrix was able to improve the biomechanical strength and anatomic appearance in an ovine model of rotator cuff repair compared to a suture-only control and the 500-µg rhPDGF-BB group. CLINICAL RELEVANCE: Recombinant human PDGF-BB combined with a type I collagen matrix has potential to be used to augment surgical repair of rotator cuff tears, thereby improving clinical success.
Assuntos
Indutores da Angiogênese/administração & dosagem , Fator de Crescimento Derivado de Plaquetas/administração & dosagem , Manguito Rotador/cirurgia , Traumatismos dos Tendões/terapia , Cicatrização/efeitos dos fármacos , Animais , Becaplermina , Fenômenos Biomecânicos , Bovinos , Colágeno Tipo I/uso terapêutico , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Humanos , Proteínas Proto-Oncogênicas c-sis , Proteínas Recombinantes/administração & dosagem , Manguito Rotador/efeitos dos fármacos , Manguito Rotador/patologia , Ovinos , Traumatismos dos Tendões/patologiaRESUMO
The authors evaluated the effects of locally anesthetizing the sciatic and femoral nerves in sheep undergoing stifle (femorotibial) surgery (16 sheep received nerve blocks; 16 sheep underwent a nerve localization procedure but received no nerve blocks). Heart rate, mean arterial blood pressure and end-tidal isoflurane were recorded every 5 min while sheep were anesthetized. At some of the observed time points, the mean heart rate in the sheep that had received no nerve blocks was significantly higher than in the sheep that had received the nerve blocks. Postoperatively, each sheep was assigned scores for comfort and attitude, movement, flock behavior, feeding behavior and appetite and respiratory rate (based on predefined descriptions). Though the authors found no undesirable effects of this local anesthesia, beneficial effects of the nerve blocks were minimal or not readily apparent under the conditions of this study.
Assuntos
Nervo Femoral/efeitos dos fármacos , Bloqueio Nervoso/veterinária , Procedimentos Ortopédicos/veterinária , Nervo Isquiático/efeitos dos fármacos , Carneiro Doméstico/cirurgia , Joelho de Quadrúpedes/cirurgia , Anestesia Local/veterinária , Anestésicos Gerais/farmacologia , Anestésicos Locais/metabolismo , Animais , Comportamento Animal , Bupivacaína/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Isoflurano/farmacologia , Bloqueio Nervoso/métodos , Procedimentos Ortopédicos/métodos , Período Pós-OperatórioRESUMO
Surgical mesh composed of extracellular matrix promotes healing of difficult soft tissue and orthopedic repairs in preclinical and clinical trials. In this study, a novel extracellular matrix prepared from porcine hydrated dermis was evaluated in an in vivo fascial defect model in sheep. Fascial defects were created, and then acutely repaired with surgical mesh. Healed surgical sites were evaluated grossly, histologically, and biomechanically at 6 and 12 weeks. Porcine hydrated dermis extracellular matrix performed favorably compared to negative control empty defects and native fascia, with minimal gross adhesion, low histologic inflammatory scores, and significantly greater tensile strength of the healing surgical site when compared with native fascia.
Assuntos
Derme , Matriz Extracelular , Face/anormalidades , Face/cirurgia , Telas Cirúrgicas , Animais , Modelos Animais de Doenças , Humanos , Ovinos , Suínos , Fatores de Tempo , CicatrizaçãoRESUMO
Gamma radiation is established as a procedure for inactivating bacteria, fungal spores and viruses. Sterilization of soft tissue allografts with high dose (60)Co gamma radiation has been shown to have adverse effects on allograft biomechanical properties. In the current study, bone-patellar tendon-bone (BPTB) allografts from 32 mature sheep were divided into two treatment groups: low-dose radiation at 15 kGy (n = 16) and high-dose radiation at 25 kGy (n = 16) with the contralateral limb serving as a 0 kGy (n = 32) non-irradiated control. Half of the tendons from all treatment groups were biomechanically tested to determine bulk BPTB mechanical properties, cancellous bone compressive properties, and interference screw pull-out strength. The remaining tissues were prepared, implanted, and mechanically tested in an acute in vitro anterior crucial ligament (ACL) reconstruction. Low-dose radiation did not adversely affect mechanical properties of the tendon allograft, bone, or ACL reconstruction compared to internal non-irradiated control. However, high-dose radiation compromised bulk tendon load at failure and ultimate strength by 26.9 and 28.9%, respectively (P < 0.05), but demonstrated no negative effect on the cancellous bone compressive properties or interference screw pull-out strength. Our findings suggest that low dose radiation (15 kGy) does not compromise the mechanical integrity of the allograft tissue, yet high dose radiation (25 kGy) significantly alters the biomechanical integrity of the soft tissue constituent.
Assuntos
Transplante Ósseo , Osso e Ossos/efeitos da radiação , Ligamento Patelar/efeitos da radiação , Ligamento Patelar/transplante , Ovinos/cirurgia , Esterilização/métodos , Animais , Fenômenos Biomecânicos/efeitos da radiação , Raios gamaRESUMO
Bone morphogenetic proteins (BMPs) are widely used as bone graft substitutes in spinal fusion, but are associated with numerous adverse effects. The growth factor Nel-like molecule-1 (Nell-1) is mechanistically distinct from BMPs and can minimize complications associated with BMP therapies. This study evaluates the efficacy of Nell-1 combined with demineralized bone matrix (DBM) as a novel bone graft material for interbody spine fusion using sheep, a phylogenetically advanced animal with biomechanical similarities to human spine. Nell-1+sheep DBM or Nell-1+heat-inactivated DBM (inDBM) (to determine the osteogenic effect of residual growth factors in DBM) were implanted in surgical sites as follows: (1) DBM only (control) (n=8); (2) DBM+0.3 mg/mL Nell-1 (n=8); (3) DBM+0.6 mg/mL Nell-1 (n=8); (4) inDBM only (control) (n=4); (5) inDBM+0.3 mg/mL Nell-1 (n=4); (6) inDBM+0.6 mg/mL Nell-1 (n=4). Fusion was assessed by computed tomography, microcomputed tomography, and histology. One hundred percent fusion was achieved by 3 months in the DBM+0.6 mg/mL Nell-1 group and by 4 months in the inDBM+0.6 mg/mL Nell-1 group; bone volume and mineral density were increased by 58% and 47%, respectively. These fusion rates are comparable to published reports on BMP-2 or autograft bone efficacy in sheep. Nell-1 is an independently potent osteogenic molecule that is efficacious and easily applied when combined with DBM.
Assuntos
Proteínas do Tecido Nervoso/metabolismo , Osteogênese/fisiologia , Fusão Vertebral/métodos , Animais , Feminino , Análise de Elementos Finitos , Radiografia , Ovinos , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/cirurgiaRESUMO
A prospective, randomized study was performed in an ovine model to compare the efficacy of an anorganic bovine-derived hydroxyapatite matrix combined with a synthetic 15 amino acid residue (ABM/P-15) in facilitating lumbar interbody fusion when compared with autogenous bone harvested from the iliac crest. P-15 is a biomimetic to the cell-binding site of Type-I collagen for bone-forming cells. When combined with ABM, it creates the necessary scaffold to initiate cell invasion, binding, and subsequent osteogenesis. In this study, six adult ewes underwent anterior-lateral interbody fusion at L3/L4 and L4/L5 using PEEK interbody rings filled with autogenous bone at one level and ABM/P-15 at the other level and no additional instrumentation. Clinical CT scans were obtained at 3 and 6 months; micro-CT scans and histomorphometry analyses were performed after euthanization at 6 months. Clinical CT scan analysis showed that all autograft and ABM/P-15 treated levels had radiographically fused outside of the rings at the 3-month study time point. Although the clinical CT scans of the autograft treatment group showed significantly better fusion within the PEEK rings than ABM/P-15 at 3 months, micro-CT scans, clinical CT scans, and histomorphometric analyses showed there were no statistical differences between the two treatment groups at 6 months. Thus, ABM/P-15 was as successful as autogenous bone graft in producing lumbar spinal fusion in an ovine model, and it should be further evaluated in clinical studies.
Assuntos
Substitutos Ósseos/uso terapêutico , Transplante Ósseo/métodos , Colágeno/uso terapêutico , Vértebras Lombares/cirurgia , Fragmentos de Peptídeos/uso terapêutico , Fusão Vertebral/métodos , Animais , Vértebras Lombares/diagnóstico por imagem , Estudos Prospectivos , Radiografia , Distribuição Aleatória , Ovinos , Transplante Autólogo/métodosRESUMO
BACKGROUND: Rotator cuff repair is a commonly performed procedure, but many of these repairs fail in the postoperative term. Despite advances in surgical methods to optimize the repair, failure rates still persist clinically, thereby suggesting the need for novel mechanical or biological augmentation strategies. Nonresorbable implants provide an appealing approach because patch materials may confer acute mechanical stability and act as a conductive scaffold for tissue ingrowth at the site of the tendon insertion. HYPOTHESIS: The polyurethane scaffold mesh will confer greater biomechanical function relative to a nonaugmented repair after 12 weeks in vivo using a chronic ovine model of rotator cuff repair. STUDY DESIGN: Controlled laboratory study. METHODS: After development of the chronic rupture model, the tensile failure properties of the nonresorbable mesh-augmented repair (n, 9) were compared with those of a surgical control in an ovine model (n, 8). RESULTS: Rotator cuff repair with the scaffold mesh in the chronic model resulted in a significant 74.2% increase in force at failure relative to the nonaugmented surgical control (P = .021). Apparent increases in stiffness (55.4%) and global displacement at failure (21.4%) in the mesh-augmented group relative to nonaugmented controls were not significant (P = .126 and P = .123, respectively). At the study endpoint, the augmented shoulders recovered 37.8% and 40.7% of the force at failure and stiffness, respectively, of intact, nonoperated controls. CONCLUSION: Using the previously described chronic rupture model, this study demonstrated that repair of a chronic tendon tear with the polyurethane scaffold mesh provides greater mechanical strength in the critical healing period than that of traditional suture anchor repair. CLINICAL RELEVANCE: This device could be used to enhance the surgical repair of the rotator cuff and consequently improve long-term clinical outcome.