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Persistent periprosthetic infection following total knee arthroplasty is one of the most dreaded complications of orthopaedic surgery. Treatment strategies include arthrodesis of the knee joint, stable fistula, long-lasting antibiotic therapy, or above-knee amputation. The advantage of amputation in comparison to other treatment options is the possible cure of infection, because the source of infection is removed and no foreign material left in situ. The aim of the study is to examine whether a septic amputation of the femur in case of persistent periprosthetic infection at the knee joint leads to the healing of the patient. Moreover, the physical and mental state should be evaluated. All patients with above-knee amputation because of periprosthetic joint infection after primary total knee arthroplasty between 2016 and 2018 were included in this retrospective study. A questionnaire with the clinical scores visual analog scale, modified Lysholm, Western Ontario and McMaster Universities Osteoarthritis Index and 36-Item Short Form Survey has been designed. In addition, all characteristics and perioperative data were documented. Eleven patients were included in the study. One patient died after above-knee amputation; all other patients live with a marked impairment of quality of life but with absence of the infection of the leg. Two out of ten are able to walk regularly with an exoprosthesis with forearm crutches, 50% are in a wheelchair, while 30% are bedridden. Patients with above-knee amputation after persistent periprosthetic infections were free of infection and without signs of inflammation. However, this is associated with worse mobility and high mortality rate.
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Artroplastia do Joelho , Prótese do Joelho , Infecções Relacionadas à Prótese , Amputação Cirúrgica/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Humanos , Prótese do Joelho/efeitos adversos , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/cirurgia , Qualidade de Vida , Reoperação , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Posttraumatic maltorsion and implant failure after closed reduction of proximal femoral fractures remain a cause of concern. Although the reproducibility of torsion measuring techniques on CT for femoral shaft fractures has been thoroughly analyzed, little is known about the trochanteric fractures. Apart from the well-known CT limitations, posttraumatic alteration of bony landmarks makes torsional assessment even more challenging. Main goal of this study was to examine the reliability of different CT techniques on trochanteric femoral fractures after closed nail fixation. Secondary goal was to see whether the measurements within the examined population were influenced by the fracture type and patient age or BMI. METHODS: 20 cases (AO.31-A1 or -A2) were retrospectively examined. Six established CT techniques for torsional assessment were performed from three different investigators twice at different time points. The intraclass correlation coefficient (ICC for 95% CI) was used to analyze the interobserver and intraobserver reliability. RESULTS: The Hernandez method (0.986) followed by the Jend method (0.982) by a mean difference of <1° showed the highest reliability. Although increasing fracture complexity from A1 to A2 led to an overall worsening of the measurement precision, the Hernandez and Jend techniques revealed a very good consistency. Within the examined population, age and BMI had no impact on the precision of the measurements. CONCLUSIONS: The Hernandez and Jend methods represent reliable alternatives for torsional assessment of trochanteric femur fractures treated with closed nail fixation when compared to the other measurement techniques here involved. Documentation of the torsion measuring method used in each case constitutes an essential element of the radiological reports.
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Fraturas do Fêmur , Fraturas do Quadril , Pinos Ortopédicos , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/cirurgia , Fraturas do Quadril/diagnóstico por imagem , Fraturas do Quadril/cirurgia , Humanos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
(1) Background: In polytrauma patients, femur fractures are usually stabilised by external fixation for damage control, later being treated with definitive plate or nail osteosynthesis. Screw/rod systems established in spinal surgery might be inserted for internal fixation, providing sufficient fracture stability that subsequent intervention is unnecessary. This was to be investigated biomechanically. (2) Methods: The unilaterally applied spinal internal fixator (IF) was subjected to load and deformation analysis on artificial femurs with 32-A3 fracture according to AO classification. Distance of screws to fracture and rod to cortical bone were analysed as parameters influenced surgically as stiffness and deformation of the treated fracture. In addition, the stability of another construct with a second screw/rod system was determined. The axial load in stance phase during walking was simulated. The results were compared against an established fixed-angle plate osteosynthesis (IP). (3) Results: There were no implant failures in the form of fractures, avulsions or deformations. All unilateral IF combinations were inferior to IP in terms of stability and stiffness. The bilateral construct with two screw/rod systems achieved biomechanical properties comparable to IP. 4) Conclusion: Biomechanically, a biplanar screw/rod system is suitable for definitive fracture stabilisation of the femur, despite a damage control approach.
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Autosomal dominant polycystic kidney disease (ADPKD) is one of the best-known genetic diseases. Almost half of the patients with ADPKD will develop end-stage renal disease, and the majority of patients are treated with renal transplantation. The current study presents a case that developed papillary renal cell carcinoma (PRCC) in the native right kidney 10 years after renal transplantation. PRCC is a not common malignant tumour entity (18.5% of all cases of renal cell carcinoma) compared with common clear cell renal carcinoma (65-70% of all cases of RCC).
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Oil-based calcium phosphate cement (Paste-CPC) shows not only prolonged shelf life and injection times, but also improved cohesion and reproducibility during application, while retaining the advantages of fast setting, mechanical strength, and biocompatibility. In addition, poly(L-lactide-co-glycolide) (PLGA) fiber reinforcement may decrease the risk for local extrusion. Bone defects (diameter 5 mm; depth 15 mm) generated ex vivo in lumbar (L) spines of female Merino sheep (2-4 years) were augmented using: (i) water-based CPC with 10% PLGA fiber reinforcement (L3); (ii) Paste-CPC (L4); or (iii) clinically established polymethylmethacrylate (PMMA) bone cement (L5). Untouched (L1) and empty vertebrae (L2) served as controls. Cement performance was analyzed using micro-computed tomography, histology, and biomechanical testing. Extrusion was comparable for Paste-CPC(-PLGA) and PMMA, but significantly lower for CPC + PLGA. Compressive strength and Young's modulus were similar for Paste-CPC and PMMA, but significantly higher compared to those for empty defects and/or CPC + PLGA. Expectedly, all experimental groups showed significantly or numerically lower compressive strength and Young's modulus than those of untouched controls. Ready-to-use Paste-CPC demonstrates a performance similar to that of PMMA, but improved biomechanics compared to those of water-based CPC + PLGA, expanding the therapeutic arsenal for bone defects. O, significantly lower extrusion of CPC + PLGA fibers into adjacent lumbar spongiosa may help to reduce the risk of local extrusion in spinal surgery.
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BACKGROUND: Whilst traumatology around elderly population becomes more and more popular nowadays, the knowledge of local bone quality prior to osteosynthesis is of paramount importance. Assessment of the local bone mechanical properties provides essential information related to implant stability and can support treatment strategies in a timely manner. In the acute setting, dual-energy X-ray absorptiometry and quantitative computer tomography cannot be used routinely, and up till now no known intraoperative methods have been established. METHODS: A novel technique was developed to determine the local bone strength. A feasibility and sensitivity analysis were performed on synthetic cancellous bone models of various densities [including osteoporotic ranges (0.12 - 0.48g/cm3)] by testing the permeability of different rod probe designs. RESULTS: The Intraoperative Osseomechanical Strength Measurement (IOSM) method revealed high sensitivity for the evaluation of local density on synthetic bone material. Among the indenter designs tested, the one with 40° sharp apex and 5 mm diameter reflected accurately the density changes of the synthetic bones. It was also associated with less invasiveness posing no risk for the primary implant stability of the osteosynthesis that may follow. CONCLUSION: The IOSM method using the indicated indenter design on synthetic cancellous models appears to be a minimal invasive technique with high accuracy in identifying different bone densities . Further studies on human bone material are now focused on the evaluation of the IOSM sensitivity compared to the gold standards (Dual-energy X-ray absorptiometry and quantitative computer tomography).
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BACKGROUND: Cut-out of gamma nail often results from poor primary bone stability, suboptimal reduction (varus) and excentric placement of the head element which may lead to "instability" and frequently requires revision. Various studies have shown that augmentation with polymethylmethacrylate cement increases the primary stability of osteosynthesis. However, it has not yet been widely used in fracture treatment due to certain disadvantages, e.g., the lack of osteointegration, the formation of an interface membrane or the presence of toxic monomers. Few studies show that biodegradable bone cements increase the stability of osteosynthesis in different anatomical regions and therefore could be an alternative to polymethylmethacrylate cement in the treatment of pertrochanteric fractures. METHODS: Two biomechanical situations were simulated using 24 Sawbones (simple and multifragmentary pertrochanteric fractures; AO-classification 31-A1 and 31-A2. Both groups were stabilized using the Gamma3® nailing system with and without biodegradable bone cement. Sawbones underwent the same cyclic loading test, simulating 10.000 gait cycles loading the bones with three times body weight. Migration was determined by comparing computed tomography scans recorded before and after the mechanical testing. The three-dimensional migration of the lag screw was calculated, and the rotation of the head around the longitudinal axis was determined. FINDINGS: Biodegradable cement reduced migration by approximately 35% in 31-A1 fractures (25.4% in 31-A2 fractures) and the rotation of the head around the lag screw by approximately 37% in 31-A1 fractures (17.8%, 31-A2). INTERPRETATION: Use of biodegradable bone cement improved the primary stability of gamma nail osteosynthesis in the biomechanical model.
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Fraturas do Fêmur , Fixação Intramedular de Fraturas , Fenômenos Biomecânicos , Cimentos Ósseos/uso terapêutico , Fixação Interna de Fraturas , HumanosRESUMO
INTRODUCTION: Existing osteoporosis models in sheep exhibit some disadvantages, e.g., challenging surgical procedures, serious ethical concerns, failure of reliable induction of substantial bone loss, or lack of comparability to the human condition. This study aimed to compare bone morphological and mechanical properties of old and young sheep, and to evaluate the suitability of the old sheep as a model for senile osteopenia. MATERIALS AND METHODS: The lumbar vertebral body L3 of female merino sheep with two age ranges, i.e., old animals (6-10 years; n = 41) and young animals (2-4 years; n = 40), was analyzed concerning its morphological and mechanical properties by bone densitometry, quantitative histomorphometry, and biomechanical testing of the corticalis and/or central spongious region. RESULTS: In comparison with young sheep, old animals showed only marginally diminished bone mineral density of the vertebral bodies, but significantly decreased structural (bone volume, - 15.1%; ventral cortical thickness, - 11.8%; lateral cortical thickness, - 12.2%) and bone formation parameters (osteoid volume, osteoid surface, osteoid thickness, osteoblast surface, all - 100.0%), as well as significantly increased bone erosion (eroded surface, osteoclast surface). This resulted in numerically decreased biomechanical properties (compressive strength; - 6.4%). CONCLUSION: Old sheep may represent a suitable model of senile osteopenia with markedly diminished bone structure and formation, and substantially augmented bone erosion. The underlying physiological aging concept reduces challenging surgical procedures and ethical concerns and, due to complex alteration of different facets of bone turnover, may be well representative of the human condition.
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Doenças Ósseas Metabólicas/patologia , Modelos Animais de Doenças , Ovinos/fisiologia , Animais , Fenômenos Biomecânicos , Densidade Óssea , Doenças Ósseas Metabólicas/fisiopatologia , Osso Esponjoso/patologia , Osso Esponjoso/fisiopatologia , Força Compressiva , Módulo de Elasticidade , Feminino , Vértebras Lombares/patologia , Vértebras Lombares/fisiopatologia , OsteogêneseRESUMO
INTRODUCTION: The increasing number of geriatric traumatology cases has intensified the need to reliably and objectively evaluate local bone quality, the latter poses a decisive factor for the choice of an optimal approach to treat osteoporotic fractures. Osteodensitometry imaging techniques are not routinely available in acute operative settings, nor do they provide objective information on local bone properties specifically needed for the prognosis of implant stability. MATERIALS AND METHODS: This study sought to verify ex vivo the feasibility and sensitivity of a novel method for the determination of local bone strength in the acute operative setting (intraoperative osseomechanical strength measurement; IOSM) that is based on the principle of material displacement resistance against the force of a rotary indenter. Samples consisted of human femoral heads obtained after total hip replacement. Comparisons were made with results obtained via conventional dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (qCT). RESULTS: Regression analyses of the results showed a highly significant correlation between the IOSM and the control methods (r = 0.61 and r = 0.56; p < 0.01), indicating that this new approach qualifies as a reliable tool for the intraoperative evaluation of the intrinsic local bone strength. CONCLUSIONS: The intraoperative integration of this method may support surgeon on taking proper decisions in terms of optimal surgical approaches and prevention of complications inherent to osteoporotic bone.
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Fenômenos Biomecânicos/fisiologia , Fêmur , Período Intraoperatório , Procedimentos Ortopédicos/métodos , Absorciometria de Fóton , Estudos de Viabilidade , Fêmur/fisiopatologia , Fêmur/cirurgia , Humanos , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Easy revisability is gaining increasingly in importance. The removal of well-fixed cemented stems is very demanding and is often associated with increased operative morbidity. Implant design may be here a decisive impact factor, and the best way to ascertain it is experimentally. Aim of this study is to assess different cemented stems of established knee revision implants in regard to their removal capability. METHODS: Based on their sagittal profile, five stem extensions from known manufacturers were divided in conical, conical-cylindrical and cylindrical designs. The pedicles were also characterized in respect to their cross section, diameter and surface roughness. The cemented stems were dismounted six times each in a reproducible biomechanical setup. The explantation energy required was determined and statistical analyzed. RESULTS: The conical shaft needed significantly the slightest explantation energy with 19.2 joules (p = 0.004). There was a strong negative linear correlation between conicity proportion and explantation energy of the cemented stems (R2 = 0.983). The removal of the three purely cylindrical shafts-regardless of their differences in diameter, cross-sectional design and surface- was the most demanding (98.3, 105, and 116.7 joules) with only secondary differences between them. CONCLUSION: The longitudinal stem profile may have a primary impact on the explantability of well-fixed cemented shafts with conical designs showing superiority. Cross-sectional profile and surface roughness had here a less decisive influence on the explantability. Surgeons can choose proper implants and removal techniques depending on potential implant-associated revision risks and re-revisions to be expected.
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Artroplastia do Joelho , Remoção de Dispositivo/métodos , Articulação do Joelho , Prótese do Joelho , Desenho de Prótese , Reoperação/métodos , Artroplastia do Joelho/efeitos adversos , Artroplastia do Joelho/instrumentação , Artroplastia do Joelho/métodos , Fenômenos Biomecânicos , Estudos Transversais , Análise de Falha de Equipamento , Humanos , Articulação do Joelho/fisiopatologia , Articulação do Joelho/cirurgia , Prótese do Joelho/efeitos adversos , Prótese do Joelho/classificação , Teste de Materiais , Desenho de Prótese/efeitos adversos , Desenho de Prótese/métodosRESUMO
OBJECTIVE: Limitations of matrix-assisted autologous chondrocyte implantation to regenerate functional hyaline cartilage demand a better understanding of the underlying cellular/molecular processes. Thus, the regenerative capacity of a clinically approved hydrogel collagen type I implant was tested in a standardized bovine cartilage punch model. METHODS: Cartilage rings (outer diameter 6 mm; inner defect diameter 2 mm) were prepared from the bovine trochlear groove. Collagen implants (± bovine chondrocytes) were placed inside the cartilage rings and cultured up to 12 weeks. Cartilage-implant constructs were analyzed by histology (hematoxylin/eosin; safranin O), immunohistology (aggrecan, collagens 1 and 2), and for protein content, RNA expression, and implant push-out force. RESULTS: Cartilage-implant constructs revealed vital morphology, preserved matrix integrity throughout culture, progressive, but slight proteoglycan loss from the "host" cartilage or its surface and decreasing proteoglycan release into the culture supernatant. In contrast, collagen 2 and 1 content of cartilage and cartilage-implant interface was approximately constant over time. Cell-free and cell-loaded implants showed (1) cell migration onto/into the implant, (2) progressive deposition of aggrecan and constant levels of collagens 1 and 2, (3) progressively increased mRNA levels for aggrecan and collagen 2, and (4) significantly augmented push-out forces over time. Cell-loaded implants displayed a significantly earlier and more long-lasting deposition of aggrecan, as well as tendentially higher push-out forces. CONCLUSION: Preserved tissue integrity and progressively increasing cartilage differentiation and push-out forces for up to 12 weeks of cultivation suggest initial cartilage regeneration and lateral bonding of the implant in this in vitro model for cartilage replacement materials.
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Cartilagem Articular/metabolismo , Colágeno Tipo I/metabolismo , Proteoglicanas/metabolismo , Regeneração/fisiologia , Extratos de Tecidos/metabolismo , Agrecanas/metabolismo , Animais , Autoenxertos , Bovinos , Movimento Celular/fisiologia , Condrócitos/metabolismo , Condrócitos/transplante , Colágeno/metabolismo , Hidrogéis , RNA Mensageiro/metabolismoRESUMO
BACKGROUND: According to literature, more than 30% of revised knee arthroplasties will require at least one re-revision. Practical experience has shown that there are considerable product-specific differences in the explantability of cemented long-stem prostheses. In the registers of successful implants, stem geometry varies considerably between the manufacturers. However, comparative data on explantability of the respective stems are missing. Objective of the present study was to identify a correlation between the geometry of a smooth cemented long stem and the necessary explantation energy required until failure of the implant-cement interface occurs. METHODS: Eight cemented stems with different conical profile angles (0°-3°) were explanted in a reproducible biomechanical setup each six times to evaluate the correlation between the stem design and the required explantation energy. RESULTS: The average explantation energy was highest in the case of the cylindrical stem, at 18.1 ± 3.6 J. At a cone angle of 0.25°, it was just 12.1 ± 2.1 J (p < 0.001) and dropped beyond 0.5° to an average of 5.7 ± 1.8 J (p < 0.001). Between 0.5° and 3°, no significant difference in the required extraction energy was observed. CONCLUSIONS: Whereas smooth conical stems can mostly be removed easily, an early decision in favour of osteotomy or fenestration can be taken in the case of cylindrical cemented stems.
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Artroplastia do Joelho/instrumentação , Cimentos Ósseos/efeitos adversos , Prótese do Joelho/efeitos adversos , Desenho de Prótese/métodos , Falha de Prótese/etiologia , Artroplastia do Joelho/efeitos adversos , Artroplastia do Joelho/métodos , Humanos , Desenho de Prótese/efeitos adversos , ReoperaçãoRESUMO
Traumatic knee dislocation is a rare but potentially limb-threatening injury. Thus proper initial diagnosis and treatment up to final ligament reconstruction are extremely important and a precondition to successful outcomes. Reports suggest that evidence-based systematic approaches lead to better results. Because of the complexity of this injury and the inhomogeneity of related literature, there are still various controversies and knowledge gaps regarding decision-making and step-sequencing in the treatment of acute multi-ligament knee injuries and knee dislocations. The use of ankle-brachial index, routine or selective angiography, braces, joint-spanning or dynamic external fixation, and the necessity of initial ligament re-fixation during acute surgery constitutes current topics of a scholarly debate. The aim of this article was to provide a comprehensive literature review bringing light into some important aspects about the initial treatment of knee dislocation (vascular injury, neural injury, immobilization techniques) and finally develop an accurate data-based universal algorithm, enabling attending physicians to become more acquainted with the management of acute knee dislocation.
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Luxação do Joelho/diagnóstico , Luxação do Joelho/terapia , Ligamentos Articulares/cirurgia , Algoritmos , Humanos , Imobilização/métodos , Luxação do Joelho/complicações , Luxação do Joelho/cirurgia , Articulação do Joelho/irrigação sanguínea , Articulação do Joelho/inervação , Articulação do Joelho/cirurgia , Ligamentos Articulares/lesões , Traumatismos dos Nervos Periféricos/etiologia , Traumatismos dos Nervos Periféricos/terapia , Procedimentos de Cirurgia Plástica/métodos , Lesões do Sistema Vascular/etiologia , Lesões do Sistema Vascular/terapiaRESUMO
BACKGROUND CONTEXT: Targeted delivery of osteoinductive bone morphogenetic proteins (eg, GDF5) in bioresorbable calcium phosphate cement (CPC), potentially suitable for vertebroplasty and kyphoplasty of osteoporotic vertebral fractures, may be required to counteract augmented local bone catabolism and to support complete bone regeneration. The biologically optimized GDF5 mutant BB-1 may represent an attractive drug candidate for this purpose. PURPOSE: The aim of the current study was to test an injectable, poly(l-lactide-co-glycolide) acid (PLGA) fiber-reinforced, brushite-forming CPC containing low-dose BB-1 in a sheep lumbar osteopenia model. STUDY DESIGN/ SETTING: This is a prospective experimental animal study. METHODS: Bone defects (diameter 5 mm) were generated in aged, osteopenic female sheep and were filled with fiber-reinforced CPC alone (L4; CPC+fibers) or with CPC containing different dosages of BB-1 (L5; CPC+fibers+BB-1; 5, 100, and 500 µg BB-1; n=6 each). The results were compared with those of untouched controls (L1). Three and 9 months after the operation, structural and functional effects of the CPC (±BB-1) were analyzed ex vivo by measuring (1) bone mineral density (BMD); (2) bone structure, that is, bone volume/total volume (BV/TV) (assessed by micro-CT and histomorphometry), trabecular thickness (Tb.Th), and trabecular number (Tb.N); (3) bone formation, that is, osteoid volume/bone volume (OV/BV), osteoid surface/bone surface (OS/BS), osteoid thickness, mineralizing surface/bone surface (MS/BS), mineral apposition rate, and bone formation rate/bone surface; (4) bone resorption, that is, eroded surface/bone surface; and (5) compressive strength. RESULTS: Compared with untouched controls (L1), CPC+fibers (L4) and/or CPC+fibers+BB-1 (L5) significantly improved all parameters of bone formation, bone resorption, and bone structure. These effects were observed at 3 and 9 months, but were less pronounced for some parameters at 9 months. Compared with CPC without BB-1, additional significant effects of BB-1 were demonstrated for BMD, bone structure (BV/TV, Tb.Th, and Tb.N), and bone formation (OS/BS and MS/BS). The BB-1 effects on bone formation at 3 and 9 months were dose dependent, with 100 µg as the potentially optimal dosage. CONCLUSIONS: BB-1 significantly enhanced the bone formation induced by a PLGA fiber-reinforced CPC in sheep lumbar osteopenia. A single local dose as low as 100 µg BB-1 was sufficient to augment middle- to long-term bone formation. A CPC containing the novel GDF5 mutant BB-1 may thus represent an alternative to the bioinert, supraphysiologically stiff polymethylmethacrylate cement presently used to treat osteoporotic vertebral fractures by vertebroplasty and kyphoplasty.
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Cimentos Ósseos/uso terapêutico , Doenças Ósseas Metabólicas/tratamento farmacológico , Regeneração Óssea/efeitos dos fármacos , Fator 5 de Diferenciação de Crescimento/uso terapêutico , Ácido Láctico/uso terapêutico , Osteogênese/efeitos dos fármacos , Ácido Poliglicólico/uso terapêutico , Vertebroplastia/métodos , Animais , Densidade Óssea/efeitos dos fármacos , Força Compressiva , Modelos Animais de Doenças , Feminino , Fator 5 de Diferenciação de Crescimento/administração & dosagem , Ácido Láctico/administração & dosagem , Região Lombossacral , Ácido Poliglicólico/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Polimetil Metacrilato/administração & dosagem , Polimetil Metacrilato/uso terapêutico , Estudos Prospectivos , OvinosRESUMO
[This corrects the article on p. 5 in vol. 6, PMID: 27299113.].
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Antibacterianos/uso terapêutico , Prótese Articular , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/terapia , Biofilmes , Terapia Combinada , Humanos , Comunicação Interdisciplinar , Colaboração Intersetorial , Falha de Prótese , Infecções Relacionadas à Prótese/microbiologia , ReoperaçãoRESUMO
Presently, no intra-operative method for a direct assessment of bone vitality exists. Therefore, we set out to test the applicability of tetrazolium-based staining on bone samples. The explanted femoral heads of 37 patients were used to obtain either cancellous bone fragments or bone slices. Samples were stained with 2,3,5-triphenyl-2H-tetrazolium chloride (TTC) or 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (thiazolyl blue, MTT) at different times (one to twelve hours) after explantation. Staining was quantified either spectrophotometrically after extraction of the dyes or by densitometric image analysis. TTC-staining of cancellous bone fragments and bone slices, respectively, indicated the detectability of vital cells in both types of samples in a window of up to six hours after explantation. Staining intensity at later time-points was indistinguishable from the staining of untreated samples or sodium azide treated samples, which represent dead cells. In contrast, MTT-staining of bone slices revealed intense unspecific staining, which obscured the evaluation of the vitality of the samples. The lack of a detectable increase of colour intensity in TTC-stained bone samples, which were treated more than six hours after explantation, corresponds to reduced fracture healing. The described simple procedure could provide a basis for an intraoperative decision by the orthopaedic surgeon.
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Osso e Ossos/metabolismo , Coloração e Rotulagem , Sais de Tetrazólio , Sobrevivência de Tecidos , Idoso , Osso e Ossos/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Osteonecrose/diagnóstico , Osteonecrose/metabolismo , Curva ROC , Coloração e Rotulagem/métodosRESUMO
BACKGROUND CONTEXT: Bioresorbable calcium phosphate cement (CPC) may be suitable for vertebroplasty/kyphoplasty of osteoporotic vertebral fractures. However, additional targeted delivery of osteoinductive bone morphogenetic proteins (BMPs) in the CPC may be required to counteract the augmented local bone catabolism and support complete bone regeneration. PURPOSE: This study aimed at testing an injectable, poly (l-lactide-co-glycolide) acid (PLGA) fiber-reinforced, brushite-forming cement (CPC) containing low-dose bone morphogenetic protein BMP-2 in a sheep lumbar osteopenia model. STUDY DESIGN/ SETTING: This is a prospective experimental animal study. METHODS: Bone defects (diameter 5 mm) were generated in aged, osteopenic female sheep and filled with fiber-reinforced CPC alone (L4; CPC+fibers) or with CPC containing different dosages of BMP-2 (L5; CPC+fibers+BMP-2; 1, 5, 100, and 500 µg BMP-2; n=5 or 6 each). The results were compared with those of untouched controls (L1). Three and 9 months after the operation, structural and functional effects of the CPC (±BMP-2) were analyzed ex vivo by measuring (1) bone mineral density (BMD); (2) bone structure, that is, bone volume/total volume (assessed by micro-computed tomography [micro-CT] and histomorphometry), trabecular thickness, and trabecular number; (3) bone formation, that is, osteoid volume/bone volume, osteoid surface/bone surface, osteoid thickness, mineralizing surface/bone surface, mineral apposition rate, and bone formation rate/bone surface; (4) bone resorption, that is, eroded surface/bone surface; and (5) compressive strength. RESULTS: Compared with untouched controls (L1), CPC+fibers (L4) and/or CPC+fibers+BMP-2 (L5) significantly improved all parameters of bone formation, bone resorption, and bone structure. These effects were observed at 3 and 9 months, but were less pronounced for some parameters at 9 months. Compared with CPC without BMP-2, additional significant effects of BMP-2 were demonstrated for bone structure (bone volume/total volume, trabecular thickness, trabecular number) and formation (osteoid surface/bone surface and mineralizing surface/bone surface), as well as for the compressive strength. The BMP-2 effects on bone formation at 3 and 9 months were dose-dependent, with 5-100 µg as the optimal dosage. CONCLUSIONS: BMP-2 significantly enhanced the bone formation induced by a PLGA fiber-reinforced CPC in sheep lumbar osteopenia. A single local dose as low as ≤100 µg BMP-2 was sufficient to augment middle to long-term bone formation. The novel CPC+BMP-2 may thus represent an alternative to the bioinert, supraphysiologically stiff polymethylmethacrylate cement presently used to treat osteoporotic vertebral fractures by vertebroplasty/kyphoplasty.
Assuntos
Cimentos Ósseos/química , Doenças Ósseas Metabólicas/tratamento farmacológico , Proteína Morfogenética Óssea 2/uso terapêutico , Regeneração Óssea/efeitos dos fármacos , Região Lombossacral/patologia , Animais , Cimentos Ósseos/uso terapêutico , Densidade Óssea , Proteína Morfogenética Óssea 2/administração & dosagem , Proteína Morfogenética Óssea 2/farmacologia , Fosfatos de Cálcio/química , Força Compressiva , Feminino , Polimetil Metacrilato/química , OvinosRESUMO
BACKGROUND CONTEXT: Biodegradable calcium phosphate cement (CPC) represents a promising option for the surgical treatment of osteoporotic vertebral fractures. Because of augmented local bone catabolism, however, additional targeted delivery of bone morphogenetic proteins with the CPC may be needed to promote rapid and complete bone regeneration. PURPOSE: In the present study, an injectable, poly(l-lactide-co-glycolide) acid (PLGA) fiber-reinforced, brushite-forming cement (CPC) containing the bone morphogenetic protein GDF5 was tested in a sheep lumbar osteopenia model. STUDY DESIGN/SETTING: This is a prospective experimental animal study. METHODS: Defined bone defects (diameter 5 mm) were placed in aged, osteopenic female sheep. Defects were treated with fiber-reinforced CPC alone (L4; CPC+fibers) or with CPC containing different dosages of GDF5 (L5; CPC+fibers+GDF5; 1, 5, 100, and 500 µg GDF5; n=5 or 6 each). The results were compared with those of untouched controls (L1). Three and 9 months postoperation, structural and functional effects of the CPC (±GDF5) were assessed ex vivo by measuring (1) bone mineral density (BMD); (2) bone structure, that is, bone volume/total volume (assessed by micro-computed tomography and histomorphometry), trabecular thickness, and trabecular number; (3) bone formation, that is, osteoid volume/bone volume, osteoid surface/bone surface, osteoid thickness, mineralized surface/bone surface, mineral apposition rate, and bone formation rate/bone surface; (4) bone resorption, that is, eroded surface/bone surface; and (5) compressive strength. RESULTS: Compared with untouched controls (L1), both CPC+fibers (L4) and CPC+fibers+GDF5 (L5) numerically or significantly improved all parameters of bone formation, bone resorption, and bone structure. These significant effects were observed both at 3 and 9 months, but for some parameters they were less pronounced at 9 months. Compared with CPC without GDF5, additional significant effects of CPC with GDF5 were demonstrated for BMD and parameters of bone formation and structure (bone volume/total volume, trabecular thickness, and trabecular number, as well as mineralized surface/bone surface). The GDF5 effects were dose-dependent (predominantly in the 5-100 µg range) at 3 and 9 months. CONCLUSIONS: GDF5 significantly enhanced the bone formation induced by a PLGA fiber-reinforced CPC in sheep lumbar osteopenia. The results indicated that a local dose as low as ≤100 µg GDF5 may be sufficient to augment middle to long-term bone formation. The novel CPC+GDF5 combination may thus qualify as an alternative to the bioinert, supraphysiologically stiff poly(methyl methacrylate) cement currently applied for vertebroplasty/kyphoplasty of osteoporotic vertebral fractures.
Assuntos
Cimentos Ósseos/química , Doenças Ósseas Metabólicas/tratamento farmacológico , Regeneração Óssea , Fator 5 de Diferenciação de Crescimento/uso terapêutico , Animais , Cimentos Ósseos/uso terapêutico , Densidade Óssea , Fosfatos de Cálcio/química , Força Compressiva , Feminino , Fator 5 de Diferenciação de Crescimento/administração & dosagem , Região Lombossacral/patologia , Polimetil Metacrilato/química , OvinosRESUMO
BACKGROUND CONTEXT: Injectable, brushite-forming calcium phosphate cements (CPC) show potential for bone replacement, but they exhibit low mechanical strength. This study tested a CPC reinforced with poly(l-lactide-co-glycolide) acid (PLGA) fibers in a minimally invasive, sheep lumbar vertebroplasty model. PURPOSE: The study aimed to test the in vivo biocompatibility and osteogenic potential of a PLGA fiber-reinforced, brushite-forming CPC in a sheep large animal model. STUDY DESIGN/SETTING: This is a prospective experimental animal study. METHODS: Bone defects (diameter: 5 mm) were placed in aged, osteopenic female sheep, and left empty (L2) or injected with pure CPC (L3) or PLGA fiber-reinforced CPC (L4; fiber diameter: 25 µm; length: 1 mm; 10% [wt/wt]). Three and 9 months postoperation (n=20 each), the structural and functional CPC effects on bone regeneration were documented ex vivo by osteodensitometry, histomorphometry, micro-computed tomography (micro-CT), and biomechanical testing. RESULTS: Addition of PLGA fibers enhanced CPC osteoconductivity and augmented bone formation. This was demonstrated by (1) significantly enhanced structural (bone volume/total volume, shown by micro-CT and histomorphometry; 3 or 9 months) and bone formation parameters (osteoid volume and osteoid surface; 9 months); (2) numerically enhanced bone mineral density (3 and 9 months) and biomechanical compression strength (9 months); and (3) numerically decreased bone erosion (eroded surface; 3 and 9 months). CONCLUSIONS: The PLGA fiber-reinforced CPC is highly biocompatible and its PLGA fiber component enhanced bone formation. Also, PLGA fibers improve the mechanical properties of brittle CPC, with potential applicability in load-bearing areas.