钛材表面pH响应性抗菌涂层的构筑及生物学评价

In order to solve the currently existed postoperative infection, it is great significance to make titanium and its alloys with antibacterial function via surface modification. This project is aimed at developing a pH-responsive antibacterial coating on the surface of titanium substrate, concerning the weakly acidic environment in case of bacterial infection. The fabrication approach combines the techniques of layer-by-layer (LBL) self-assembly and electrochemical anodization with sustained release of drugs. Titania nanotube arrays as reservoirs for antibacterial drug are constructed on titanium substrate via electrochemical anodization method. pH-responsive polyelectrolyte multilayer films are fabricated on the surface of titania nanotube for sealing antibacterial drug via LBL self-assembly. The lightly acidic environment occurring in case of bacterial infection leads to a disassembly of multilayer film, which consequently induces controlled release of antibacterial drug from nanotube. Thus, a pH-responsive antibacterial coating is gradually constructed on the surface of titanium substrate. The effectiveness of pH-responsive polyelectrolyte multilayer films via LBL self-assembly is systematically investigated. The release mechanism of antibacterial drug is explored. Antibacterial property and biocompatibility of this system in vitro are evaluated. This project presented here will provide novel strategies for designing antibacterial coating on titanium-based implants and accelerate the application of them in tissue repair and regeneration.

通过表面修饰赋予钛及钛合金材料抗菌性能，对于解决其临床术后感染问题具有重要意义。本项目旨在结合层层自组装、电化学阳极氧化和药物释放技术，针对细菌感染的弱酸性环境，展开钛材表面新型pH响应性抗菌涂层的研究。通过电化学阳极氧化在钛材表面制备二氧化钛纳米管阵列，作为抗菌药物的存储器；进而利用层层自组装技术在二氧化钛纳米管表面构筑pH响应性聚电解质多层膜，作为抗菌药物的封堵层；在细菌感染的弱酸性环境下，多层膜发生解组装，实现纳米管中药物的可控释放；从而在钛材表面逐步建立起一个能够对pH刺激进行智能响应的抗菌涂层。系统研究层层自组装制备pH响应性多层膜的有效性，探寻抗菌药物的释放机制，评价该功能涂层的体外抗菌性和细胞相容性。本课题将为钛基植入材料表面抗菌设计提供新思路，促进其在组织修复与再生领域的应用。

钛及其合金材料由于具有良好的生物相容性和机械性能，现已广泛用于骨科、牙植入体及整形外科等领域。尽管钛基植入材料具有优良的性能，但其存在的细菌感染问题，往往会导致临床植入手术失败。本项目旨在结合层层自组装、电化学阳极氧化和药物释放技术，针对细菌感染的弱酸性环境，展开钛材表面新型pH响应性抗菌涂层的研究。研究中，尝试通过表面改性方法，减少细菌粘附，同时促进成骨细胞在钛材上的生长。利用层层自组装（layer-by-layer, LBL）技术在钛材表面制备了负载锌离子（Zn2+）的壳聚糖（chitosan, Chi）/明胶（gelatin, Gel）的多层膜涂层。利用壳聚糖、明胶对Zn2+的络合作用，将锌离子装载进多层膜内。该涂层能够实现Zn2+的pH响应性释放。实验结果表明：含锌的（壳聚糖/明胶）多层膜涂层在一定程度上能够抑制细菌生长，体现出抗菌能力。含适量锌离子的多层膜涂层提高了成骨细胞活力和碱性磷酸酶活性，促进了细胞在材料表面的粘附。进一步，将层层自组装技术与电化学阳极氧化技术相结合，在钛材表面制备了负载抗菌药物的功能涂层。利用电化学阳极氧化的方法，在钛材表面制备了二氧化钛纳米管（TiO2 nanotubes, TNT）阵列。进一步，以TNT为储存器，实现了庆大霉素/纳米银的装载。利用LBL技术，在TNT阵列修饰的钛材表面构筑了壳聚糖和双醛海藻酸钠的多层膜结构，实现对抗菌药物的封装。利用壳聚糖和双醛海藻酸钠之间形成的席夫碱，构筑pH 响应性聚电解质多层膜，实现抗菌药物的可控释放。载药涂层能够抑制细菌的生长，提高钛材的抗菌能力，同时具有良好的细胞相容性。通过表面修饰赋予钛及钛合金材料抗菌性，对于解决其临床骨术后感染问题具有重要意义。本研究将为钛基植入材料表面改性提供新思路，促进其在组织修复与再生领域的应用。