骨植入镁合金表面多尺度复合涂层的制备及其骨诱导抗菌耦合效应机理研究

Osteoinduction and antibacterial coupling effect is crucial for orthopedic implants that can inhibit bacterial growth at the initial stage of bone healing and simultaneously promote bone mineralization so as to reduce the bone healing period. As the traditional antibacterial agent, silver presents broad-spectrum antibacterial property, but the release rate of silver ion is highly uncontrollable and there is no effective technique to tailor the antibacterial efficacy without compromising the biocompatibility. This project proposes to build multifunctional composite coatings on biodegradable magnesium alloys with unique multiscale features, which consist of Ca-deficient hydroxyapatite layers with microscale features at the bottom and porous silk fibroin layers enhanced by silicon-substituted hydroxyapatite and silver-substituted hydroxyapatite nanoparticles. There are two types of factors (composition and porous structure characteristic) in this coating structure design that might affect coating performances. By adjusting the percentage of two types of hydroxyapatite nanoparticles in coatings as well as the porous structure characteristics, the influence of the above factors to coating degradation behaviors will be discussed; and the interacting mechanism of osteoinduction and antibacterial coupling effect will be investigated. Hence, the maximized antibacterial efficacy could be achieved with the optimized osteoinduction effect; in addition, the degradation behavior could be tailored with the optimized osteoinduction and antibacterial coupling effect. The concept of osteoinduction and antibacterial coupling effect is novel and has great significance in clinical practice; and the outcomes of this project shall shed the light in the design of functional coatings on magnesium implants.

理想的骨植入体表面，能够在骨折愈合初期抑制细菌感染；同时加速骨矿化，缩短骨折愈合时间。银作为一种传统抗菌剂，其抗菌效应具有广谱抗菌性的优点；但银离子释出不可控，缺乏调控抗菌效力与骨诱导效力的有效手段。本项目拟在骨植入镁合金表面引入多尺度复合涂层结构：微米级致密缺钙型羟基磷灰石作为基底层；装载有银代羟基磷灰石、硅代羟基磷灰石纳米颗粒的蚕丝蛋白纳米纤维层作为表面功能层。两种纳米颗粒作为成分因子、纤维膜作为结构因子，通过控制两种羟基磷灰石在涂层中的比例和纤维膜的结构特征，探讨成分和结构对其降解速率的影响，调控复合涂层的抗菌效力与骨诱导效力的主次关系，揭示涂层骨诱导抗菌耦合效应的作用机理；进而实现最大化抗菌效力下的骨诱导作用最优化和最优化骨诱导抗菌耦合效应下的涂层可控降解。本项目为骨植入镁合金表面抗菌涂层开发提供新思路，具有重要的指导意义。

理想的骨植入体表面，能够在骨折愈合初期抑制细菌感染；同时加速骨矿化，缩短骨折愈.合时间。本项目在骨植入镁合金表面引入多尺度复合涂层结构：利用电沉积工艺制备微米级致密缺钙型羟基磷灰石作为基底层；利用静电纺丝工艺制备装载有多种改性纳米羟基磷灰石颗粒的丝素蛋白纳米纤维层作为表面功能层。通过控制羟基磷灰石掺杂量与纤维膜制备工艺参数，深入探讨膜层成分和结构对其降解速率的影响规律，揭示涂层形成过程中纤维层二级结构与纳米颗粒掺杂量对膜层腐蚀行为的作用本质；通过体外血液相容性、细胞共培养（成骨细胞、骨髓间充质干细胞与巨噬细胞）和细菌共培养实验发现，该膜层具有较好的血液相容性，能够促进巨噬细胞M2表型转化、促进成骨分化，且具有一定的抗菌效力。结合膜层耐蚀性能研究发现，功能膜层的骨诱导效力和抗菌效力与其降解行为紧密相关，即通过调控膜层中的二级结构组成与羟基磷灰石掺杂量可实现膜层降解速率与生物学性能的有效调控，并由此建立“涂层制备工艺参数-膜层结构-降解性能-体外生物学性能“之间的构效关系。本项目为骨植入镁合金表面功能涂层开发提供新思路，具有重要的指导意义。.