高分子骨科材料表面含氮功能基团构建及其抗细菌感染/BMSCs成骨分化机理研究

In this proposal, nitrogen plasma modification of polymeric orthopedic materials will be employed to achieve the fine nitrogen containing chemistry, endowing their surface with functions of up-regulating bone mesenchymal stem cells (BMSCs) osteogenic differentiation and inhibiting bacterial growth. Inert gas plasma will be implanted into polymeric surface to obtain the carbonized surface with low concentration of hydrogen, oxygen or nitrogen. Then, nitrogen containing plasma implantation will be implemented to the resultant surface by controlling plasma composition and implantation parameters, in order to precisely construct various nitrogen containing chemistry (PolyS-N), composed of C-NH2、C-NH-C、C-N=C or C-N（C）-C, etc. Influences of these nitrogen containing groups on BMSCs and bacterial biological behaviors will be investigated for screening out bifunctional PolyS-N, inducing BMSCs to differentiate down osteogenic pathways and suppressing bacterial growth, and their mechanisms will also be disclosed by key siginal pathways. It is believed that our research results will offer one feasible approach to enhancing osseo-integration between polymer and bone tissue by way of surface chemical groups, and promote polymeric materials' application in the orthopedic medicine.

高分子骨科材料表面细菌感染及骨髓间充质干细胞（BMSCs）成骨能力低，阻碍了材料与骨组织间的整合。本项目利用等离子体注入技术在高分子骨科材料表面原位构建含氮功能基团，抑制细菌感染进而诱导BMSCs骨向分化，从而改善骨科材料与组织间的适配性。采用惰性气体等离子体轰击材料表面，实现分子链结构的归一性；通过氮等离子体原位修饰归一化分子链结构，赋予高分子骨科材料表面含氮功能基团。揭示功能基团的化学组成和结构对材料表面抑制细菌生长的作用规律，阐明含氮化学结构对细菌外基质和信号传递的相互关系；探讨不同含氮功能基团对BMSCs在材料表面的粘附、增殖的影响，上调BMSCs骨特征基因的表达，促进BMSCs在高分子骨科材料表面骨向分化。在此基础上进一步分析抑菌、诱骨的含氮功能基团内在结构特征及其作用机制。该研究对于开发基于高分子骨科材料，推动植入器械的发展具有重要意义。

高分子骨科材料表面易于细菌感染和较低骨诱导活性，阻碍了与骨组织间的整合。本项目采用氩等离子体轰击高分子材料表面生成碳化结构，实现了表面结构归一化，并通过注入含氮等离子体实现可控构建含氮基团表面。研究发现含氮基团表面能够阻止金黄色葡萄球菌生长，而且有着优异的生物相容性，上调BMSCs骨特征基因表达、诱导新骨生成。其中叔氮基团表面有着较高的表面电势，表现出最强的抗菌与骨诱导活性，主要源于该表面高电势抑制了群体感应相关基因、生物膜形成相关基因和毒力相关基因表达实现抑菌作用，通过电荷/iNOS通路调控BMSCs骨特征基因表达水平从而诱导新骨生成。通过化学法构建阳离子表面也证实了高电势表面同时具备“抗菌与生物活性”，并提出“阳离子界面抗菌理论”，为解决材料“抗菌与生物活性”兼容性提供了理论基础，有助于推动抗菌医疗器械发展。