“主动响应”型表面结构制备及生物学效应

"Active response" is a property that provides a material with capability to "recognize" biological signals, take specific actions and "reply to" the biological systems. Based on the structural and metabolic differeces in bacterial and mammalian cells, this project proposes to introduce,via plasma-based surface modification techniques,silver nano particles or/and some soluble calcium,strontium and magnesium into titanium-based materials(including pure titanium and titanium oxide),and obtain surface structures with "active response" to those "proton-coupled electron transfer" related processes in bacterial and mammalian cells, leading to biological properties that inhibit the adhesion of bacteria but promote that of mammalian cells. The formation kinetics and thermodynamics of those nano surface structures will be characterized and optimized to obtain a technique that can fabricate "responsive" surfaces with controllable and steady property.The adhesion, replication, differentiation as well as the related protein, gene expression behaviors of both bacterial and bone cells cultured on the structures will be studied at the molecular level to reveal the interacting mechanism between these cells and the fabricated surface structures. Animal experiments will be carried out to test the in vivo performances of these structures, and finally confirm the design idea on "Fabrication of surface structures with active response". On the basis of the"proton-coupled electron transfer" theory, a common phenomenon in both materials and biology, this project proposes to endow titanium based materials with "controlled biological response" and "active repairing" properties with nano surface structures of both short and long range activities to biological systems. The results obtained in the present study may become important references in fabrication of implantable devices with both excellent antibacterial and osteogenic properties.

材料"识别"生物信号并采取特异性行动"应答"生物系统的过程谓之"主动响应"。基于细菌和细胞在结构及代谢方面的差异，本项目拟采用等离子体技术将纳米银及可溶的钙、锶、镁等组分引入钛材料(含纯钛和氧化钛)表面，利用相关协同效应"主动响应"细菌和细胞"质子耦合电子转移"过程，探讨其"抑制细菌而促进细胞"的生物学效应。了解纳米表面结构形成的热力学及动力学机制，完善"响应"型表面结构制备工艺；从分子生物学层面研究细菌及成骨相关细胞的粘附、分化和增殖，检测蛋白和基因表达，阐述影响细菌和细胞行为的规律，并设计动物模型研究其体内生物学表现，验证"主动响应"型表面结构设计思想。本项目以贯通"材料"和"生物"领域的普遍现象──"质子耦合电子转移"过程为基础，提出从材料与生物系统相互作用的"近程"和"远程"途径出发，赋予钛材料"可控生物响应" 和"主动修复"功能，为兼具抗菌和成骨植入体制备储备解决方案及基础数据。

项目基于“肖特基接触”效应和“微电池”效应，提出“安全抗菌”和“成骨兼抗菌”的钛表面设计思路，制备氧化钛/纳米银、氧化钛/纳米铁、纳米银/镁、纳米银/锌、纳米银/钙等复合功能涂层。发现其 “安全抗菌”和“成骨兼抗菌”功能与材料表面的“收集电子”或“消耗质子”特征和生物系统的“质子耦合电子转移”生理过程之间的相互作用相关。第三方对镶嵌式纳米银的钛表面进行生物安全检测，均呈正面结论。对相关技术进行医学转化，发展具有抗菌功能的钛牙种植体，其6周骨整合率(BIC, 犬模型)达79.3%。在 Biomateirals、The Journal of Physical Chemistry Letters、ACS Applied Materials & Interfaces等杂志发表标注项目资助号的SCI论文24篇，编著英文专著1部，申请发明专利2项，在国内外会议作邀请报告3次。培养研究生5名。项目负责人曹辉亮入选上海市青年科技启明星计划(A)和中国科学院青年创新促进会。