贻贝仿生法构建抗菌及成骨双活性涂层的研究

Failures of orthopedic implants occur mainly due to implant-associated infection and deficient osseointegration. Biologic coating is a promising approach to confer implant materials with concomitant antibacterial activity and osteogenesis inducing ability. Compared with pristine chitosan, quaternized chitosan bears enhanced antibacterial ability that is pH independent. The underlying mechanism of mussel-inspired chemistry is that catechol compounds can form strong covalent and noncovalent interactions with surfaces of various materials. Inspired from the mussel adhesion mechanism, this project will conjugate dopamine onto the backbone of quaternized chitosan, resulting in a highly water-soluble chitosan derivative (q-CHI-c). During the gelation process of q-CHI-c solution, BMP-2 will be immobilized into the hydrogel, forming a dual functional hydrogel with concomitant antibacterial activity and osteogenesis promoting capability. Due to the presence of Catechol or Quinone groups, the hydrogel coating can bond strongly to the implant surface. We aim to develop a dual functional coating with universal applicability that is economic, maneuverable and stable.

导致硬组织植入材料失败的常见原因包括植入体相关感染和植入体/宿主硬组织界面骨整合不良。采用生物涂层的办法对植入材料进行抗菌和成骨双活性的改性是提高植入材料成功率的重要策略。季铵化壳聚糖(q-CHI)具有比壳聚糖(CHI)更强、且不受环境pH影响的抗菌性能。贻贝仿生化学的关键机制是含儿茶酚基的分子(如多巴胺)可通过儿茶酚基及其氧化产物醌基与不同基底表面发生共价或非共价键牢固结合。受贻贝仿生化学法启发，本项目拟对季铵化壳聚糖进行多巴胺修饰，形成高水溶性的q-CHI-c分子。在q-CHI-c水溶液胶化过程中，整合入BMP-2，以期合成抗菌和成骨双活性的水凝胶涂层。由于q-HCI-c水凝胶中儿茶酚基或醌基的存在，q-CHI-c水凝胶涂层可与植入材料表面牢固结合。本项目有望发展一种经济、操作简单、性质稳定的高效多功能涂层原料。

导致硬组织植入材料失败的常见原因包括植入体相关感染和植入体/宿主硬组织界面骨整合不良。采用生物涂层的办法对植入材料进行抗菌和成骨双活性的改性是提高植入.材料成功率的重要策略。本项目研究工作主要是通过对壳聚糖进行双重改性，即季铵化和接枝儿茶酚基团，以形成高水溶性的双修饰壳聚糖分子（q-CHI-c）。项目合成的q-CHI-c分子具有优异的细胞相容性和抗菌活性。q-CHI-c分子通过氧化聚合和金属配位反应机制牢固结合钛基材料表面，形成高稳定性的多功能涂层材料。在涂层有q-CHI-c的钛表面接种BM-MSC细胞，通过细胞增殖；OPN、 OCN 及ALP mRNA及蛋白表达水平进行验证了q-CHI-c涂层的促成骨能力。动物实验证明，钛植入材料经q-CHI-c涂层处理，可有效提高钛植入材料的骨整合。