关节假体界面的力学与生物学耦合行为、机理及调控研究

The prosthetic arthroplasty is the most successful clinical treatment of the osteoarthritis and femur head fracture, etc. However, the aseptic loosening remains a major reason, which causes the long-term prosthetic failure and brings the patients both the economic and social burdens. The aseptic loosening is caused by the degradation in the interfacial bonding, which was mediated by the bone growth and remodeling according to the mechanical and biological environment at the implant-bone interface. The objectives of this project are to experimentally study the mechanical and biological mechanisms underlying the bone ingrowth and remodeling processes, to establish their mathematical descriptions and subsequently integrate these mathematical descriptions into mechano-bioregulatory and multi-scale simulation model in order to solve the problem of clinical aseptic loosening. First, the animal models of bone ingrowth and remodeling will be established while the mechanical and biological environments are controlled and varied, and the concentrations, distributions, and morphologies of the related cytokines, cells, and tissues will be observed. Secondly, based on these experimental results, mathematical descriptions will be abstracted and mathematical model will be deduced to represent the cellular activities in both the bone ingrowth and remodeling processes, respectively. And then combined with the consideration of the micro-structures of the prosthetic surface and the bioactive coating, the mathematical model will be used to discover the coupling mechanism of mechanics and biology in both the bone ingrowth and remodeling processes, and to analyze and optimize the micro-structure and fabrication of the porous coating and the compositions of the bioactive coating. Finally, the micro-scale simulation model will be converted to the macro and multi-scale simulation model, and will be used to investigate the surgical procedure of the prosthetic arthroplasty and post-operation rehabilitation, additionally considering the physiological loadings and the individual differences in patients in order to achieve earlier load bearing ability and improve the long-term retention of the prostheses.

关节假体置换是治疗骨性关节炎、股骨颈骨折等疾病的最有效手段，无菌松动仍是目前假体置换远期失效的主要问题，给患者带来了精神和经济上的双重负担。无菌松动的原因是假体-骨界面上的力学、生物学环境介导的骨生长与重构造成的界面结合性能的退化。本项目提出从界面骨长入与重构的实验研究入手，建立其关键过程的数学描述，形成力学-生物学耦合、微宏观跨尺度机理模型，解决临床无菌松动难题。首先建立控制力学和生物学环境的骨长入与重构动物模型，观测细胞因子、细胞和组织信息。其次对实验现象进行数学抽象，分别提出基于细胞行为描述的骨长入与重构数学模型。然后结合假体植入表面的微观结构与生物活性涂层研究骨长入与重构特性，揭示力学与生物学耦合作用机理，优化假体表面微观结构和涂层。最后通过数学手段将微观仿真模型转化为宏观跨尺度模型，考虑生理载荷、患者个体差异，对关节假体的手术置换、术后康复进行研究，以提高假体远期留存率。

骨折和关节置换是目前骨科临床中的两类重要问题。虽然各种骨科固定器械以及关节假体植入物已经在临床中得到了广泛的应用并获得了巨大的成功，但对于这些产品的设计仿真手段还局限于传统的材料制备、加工工艺、材料力学以及结构力学领域，人工材料、结构对于骨折愈合或植入物骨长入的影响尚缺乏计算方法和优化手段。研究和建立针对该过程的数学模型和仿真手段，可提高相关产品设计开发阶段的设计效率、缩短设计周期和降低设计成本。.骨愈合和生长是治疗骨折和生物型假体置换术中的基础性问题。针对骨愈合与生长，基于力学介导分化模型和生物学介导模型，建立了力学-生物学耦合的骨愈合生长模型。发展出基于内皮成血管因子介导作用的跨尺度成血管数学模型和氧分布模型，实现了骨愈合与血管生长过程的双向耦合计算。将骨重构模型整合到骨愈合模型中，使仿真的时间跨度由短期扩展至长期。.采用大鼠骨折实验研究了不同力学载荷下骨折愈合的不同形式和组织分布特点。将仿真计算结果与实验观测结果进行了比对，验证了仿真模型对骨愈合过程预测的正确性和准确性。.采用骨愈合模型对临床中骨折愈合问题进行了仿真分析，包括对不同骨折固定器械疗效的对比、提出确定最优固定刚度的算法、对固定器械在使用中装配条件的研究以及对采用可降解材料制作固定器械的可行性研究。.提出并建立了用于描述多孔界面之间骨生长过程的多场接触算法。通过该算法可以实现对松质骨骨折愈合以及植入物多孔涂层表面骨长入问题的仿真分析。采用该算法对股骨颈骨折问题和全髋关节假体多孔涂层表面骨长入问题进行了仿真分析，检验了算法的可行性，并讨论了固定器械和假体置换的治疗效果