钛种植体表面电学微环境构建及其调控成骨/破骨细胞间耦联作用机制研究

The dental implant success is largely dependent on the regulation of coupling mechanisms between bone formation of osteoblasts and bone resorption of osteoclasts in the alveolar bone tissue. Previous studies have confirmed that electrical microenvironment is a key factor in osteoblastic bone formation and osteoclast bone resorption. It is one of the key issues to be solved urgently for enhancing implant osseointegration to providing an ideal electrical microenvironment for osteoblast and osteoclast by constructing a film layer with similar hard tissue piezoelectric function on the surface of implant. In this project, the inorganic-organic piezoelectric functional film composed of potassium niobate potassium piezoelectric ceramics and collagen was constructed on the surface of titanium implant by photochemical grafting and immobilization technology, and its composition was controlled. The osteoblast and osteoclast co-culture system was established. The cell adhesion, proliferation, differentiation and other cytological behavior of osteoblasts or osteoclasts and co-cultured osteoblasts and osteoclasts were studied on the surface of the piezoelectric film under external stress loading. The effects of electrical microenvironment constructed on the surface of implant on the biochemical coupling, signal transduction and intercellular response of co-cultured osteogenesis and osteoclasts was studied in depth. The role of electrical microenvironment in osteogenesis and osteoclasts and its mechanism of coupling were revealed. A theoretical basis for the clinical construction of new implant materials to promote bone bonding will be provided.

种植体材料对牙槽骨组织中成骨细胞的骨形成反应与破骨细胞的骨吸收反应这对耦联作用的调控，直接影响种植体的临床近远期效果。研究发现电学微环境是介导成骨细胞骨形成与破骨细胞骨吸收的关键因素，在种植体表面构建具有类似天然牙体硬组织压电功能的膜层，为成骨/破骨细胞提供理想的电学微环境，是促进种植体骨结合亟待解决的关键问题之一。本项目拟采用光化学接枝固定技术，在钛种植体表面构建由铌酸钠钾压电陶瓷和胶原组成的无机-有机压电功能膜层，并调控其组成结构；建立成骨/破骨细胞共培养体系，对比研究在外加应力载荷作用下，压电膜层表面单独培养成骨或破骨细胞和共培养成骨/破骨细胞的粘附、增殖、分化等细胞学行为规律；深入探讨种植体表面构建的电学微环境对共培养成骨/破骨细胞的生化耦联、信号传递和细胞间响应等作用机理，揭示其对成骨/破骨细胞间的作用与耦联调控机制，为临床构建出促进骨结合的新型种植体材料提供理论依据。

骨植入材料是目前临床应用量最大的生物医用材料之一。目前研究大量集中在提高传统骨植入材料的生物活性及其与组织的骨性结合，少有模拟生物组织的电学特性及骨内电生理微环境促进骨组织生长的研究。研究发现电信号刺激有利于骨形成，与骨组织的生长、重建密切相关。骨组织具有压电特性，能够响应机械应力产生电信号刺激，从而调控骨的再生与重建。因此，具有电信号刺激功能的植入材料有望调控骨的再生与重建。利用聚吡咯的导电性和聚偏氟乙烯的压电性，通过电化学聚合法构建纳米结构聚吡咯复合聚偏氟乙烯材料，使其具有电信号刺激功能。该材料因聚偏氟乙烯的压电性可以响应机械刺激从而产生电信号，并通过导电的聚吡咯纳米结构传导电信号刺激至细胞，引起细胞行为上的响应。通过对比分析了在动、静态培养状态下该材料对其表面骨髓间充质干细胞成骨分化的影响，结果表明动态培养下产生电信号刺激及纳米结构对细胞成骨分化具有协同作用。本研究为通过导电、压电活性材料复合构建具有电信号刺激功能的材料构建出促进骨整合的新型种植体材料将具有较长远的参考价值。