医用高分子生物活性表界面与干细胞的相互作用

针对骨关节炎关节置换缺乏初期稳定性的临床挑战，受髓间充质干细胞（MSCs）微环境启发，本项目旨在针对性地优化医用高分子设计与合成、表面改性钛合金，构筑生物活性表界面，介导与细胞相互作用。拟结合贯通沟槽和表面固载细胞外基质类似物（改性壳聚糖/明胶/透明质酸/硫酸软骨素等）的水凝胶层，搭建探究复杂微环境单/多因素（基材硬度、生化因子/剂量、流体传质等）在静态/动态条件下对MSCs生理功能影响的定量/半定量基础研究平台，明确最优理化参数，进而拓展至层层组装多层结构。以系列体外生物学实验揭示医用高分子改性钛合金表界面对MSCs募集/迁移、老化功能激活、成骨分化、特定蛋白/基因表达的影响规律及分子机制。最后，以骨关节炎动物模型在体研究钛合金植入体表界面对体内骨形成的影响规律。本研究将阐明钛基材微环境对宿主细胞功能/组织再生的影响规律及分子机制，并为研发自主知识产权人工关节植入体提供理论基础及新技术。

Towards the clinical challenge of the lack of early stage stability of osteoarthritis resulting joint arthroplasty, inspired by the microenvironment of mesenchymal stem cells (MSCs), the project aims at correspondingly optimizing the design and of synthesis of biomedical polymers and surface modifying titanium alloy, so as to construct bioactive surface/interface, which regulating the interactions with cells. By employing the combination of inter-connecting groove structure and hydrogel layer of extracellular matrix analogues (modified chitosan, gelatin, hyaluronic acid, chondroitin sulfate etc.), we intend to construct quantitative/semi-quantitative platform for basic research toward the investigations of the influences of single/multi- factors (matrix stiffness, biochemical factors/dosage, fluid transport, etc.) deriving from complex microenvironment on the biological functions of MSCs, to determine the optimal physical and chemical parameters, in turn extending to layer by layer structures. By using a series of in vitro tests, we would clarify the influences of surface/interface of biomedical polymers surface modified titanium alloy on the MSCs’ recruitment/ migration, activation of aged functions, osteogenic differentiation and expressions of specific proteins and genes, as well as the potential molecular mechanism. Finally, we will employ osteoarthritis animal model to investigate the effects of surface/interface of titanium alloy implant on the bone formation in vivo. The project would clarify the influences of titanium materials’ microenvironments on a host’s cellular functions/tissue regeneration and potential molecular mechanisms, and provide theory basis and new technologies for the developments of artificial joint implants with independent intellectual property rights.