面向具有原位成骨活性植入材料制备的表面引发蛋白印迹聚合研究

鉴于目前骨科植入物如人工关节、椎间融合器可能因固定松动导致假体失效，新一代植入材料需表面能诱导成骨，以增强骨组织与假体界面骨性结合。在材料表面固定骨形态发生蛋白-2（BMP-2）是可行方案，但受限于外源性BMP-2易失活和副作用多。近期发现，高效的内源性BMP-2可在骨缺损部位被相应抗体识别并富集，促进骨修复。同时，我们已证实分子印迹聚合物对模板蛋白分子具有特异性识别能力，能可逆捕获与释放该蛋白。据此，本项目以提高材料成骨活性为目标，通过结合表面引发的活性聚合与分子印迹技术，在钛合金表面可控固定含BMP-2识别位点的印迹聚合物薄层，通过体内外试验考察其捕获BMP-2的效率。最终可望发展一类可在体内"原位"选择性富集内源性BMP-2、从而获得稳定成骨活性的新型骨科植入材料。这一基于分子印迹技术的材料表面功能化新理念的成功实施，将为开发具有持续生物活性的植入材料提供理论基础和实践依据。

Currently, implantation of orthopedic prostheses such as artificial joints and interbody cages may be associated with many complications including loosening and dislocation, which eventually lead to failure of prostheses. Therefore, the next generation of orthopaedic implants should possess excellent osteogenic activity in order to enhance the integration of implant and host bone tissue. Immobilizing the bone morphogenetic protein 2 (BMP-2) at the surface of implants appears to be an effective approach toward this goal. However, its application is largely limited as a result of the rapid activity loss and complications of recombinant BMP-2. Recently, we and other groups have found that endogenous BMP-2 can be immobilized at the bone defect area by BMP-2 antibody to promote bone repair. Our previous studies have also shown that protein imprinted polymers possess excellent affinity and specific recognition ability toward template protein molecules, and can therefore be used for identifying and capturing that protein. Therefore, the proposed study aims to improve the osteogenic activity of orthopedic implants through the combined use of surface-initiated living polymerization and molecular imprinting technologies. A layer of imprinted polymers containing specific recongnition sites toward BMP-2 will be immobilized on the surface of titanium alloy in a controllable fashion. Then the imprinted titanium will be tested both in vitro and in vivo to evaluate its efficacy of capturing BMP-2. Ultimately, a novel type of orthopaedic implants is expected to be developed, which will be capable of capturing and enriching highly effective endogenous BMP-2 in-situ, thereby promoting new bone formation consistently. Upon successful completion, this study will bring in an innovative approach toward bioactive surface functionalization of materials. It will also provide a solid foundation for further development of smart implants with stable and continuous biological functionalities.