关键词: aseptic loosening fibrotic tissue in vivo mice osseointegration

来  源:   DOI:10.1002/jor.25915

Abstract:
An in vivo animal model of a weight-bearing intra-articular implant is crucial to the study of implant osseointegration and aseptic loosening caused by osseointegration failure. Osseointegration, defined as a direct structural and functional attachment between living bone tissue and the surface of a load-carrying implant, is essential for implant stability and considered a prerequisite for the long-term clinical success of implants in total joint arthroplasty. Compared to large animal models, murine models offer extensive genetic tools for tracing cell differentiation and proliferation. The 18- to 22-week-old C57BL/6J background mice underwent either press-fitted or loose implantation of a titanium implant, achieving osseointegration or fibrous integration. A protocol was developed for both versions of the procedure, including a description of the relevant anatomy. Samples were subjected to microcomputed tomography and underwent biomechanical testing to access osseointegration. Lastly, samples were fixed and embedded for histological evaluation. The absence of mineralized tissue and weakened maximum pull-out force in loose implantation samples indicated that these implants were less mechanically stable compared to the control at 4 weeks postoperation. Histological analysis demonstrated extensive fibrotic tissue in the peri-implant area of loose implantation samples and excellent implant osseointegration in press-fitted samples at 4 weeks. Both mechanically stable and unstable hemiarthroplasty models with either osseous ingrowth or a robust periprosthetic fibrosis were achieved in mice. We hope that this model can help address current limitations for in vivo study of aseptic loosening and lead to necessary translational benefits.
摘要:
负重关节内植入物的体内动物模型对于研究由骨整合失败引起的植入物骨整合和无菌性松动至关重要。骨整合,定义为活骨组织和承载植入物表面之间的直接结构和功能附着,对于植入物的稳定性至关重要,并且被认为是全关节置换术中植入物长期临床成功的先决条件。与大型动物模型相比,小鼠模型为追踪细胞分化和增殖提供了广泛的遗传工具。18至22周龄的C57BL/6J背景小鼠接受了钛植入物的压配合或宽松植入,实现骨整合或纤维整合。为该程序的两个版本都开发了协议,包括相关解剖结构的描述。对样品进行显微计算机断层扫描,并进行生物力学测试以获得骨整合。最后,将样品固定并包埋以进行组织学评估。在松散的植入样品中没有矿化组织和减弱的最大拉出力表明,与术后4周的对照相比,这些植入物的机械稳定性较差。组织学分析表明,在4周时,松散植入样品的植入物周围区域存在广泛的纤维化组织,并且在压装样品中具有出色的植入物骨整合。在小鼠中实现了具有骨向内生长或稳健的假体周围纤维化的机械稳定和不稳定的半关节成形术模型。我们希望该模型可以帮助解决无菌性松动体内研究的当前局限性,并带来必要的转化益处。
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