蛋白质纳米纤维的取向组装机理及其对磷灰石仿生矿化结构的调控

The hierarchically staggered nanostructures of bone, which are formed by orientated protein nanofibrils arrays and hydroxyapatite (HA) nanosheets, is of great significance to their mechanical property and biological activity (e.g., cell behavior regulation property). The present proposal focuses on the self-assembled protein nanofibrils, studies the methods and mechanisms of the orientated assembly of protein nanofibrils, and controls the mineralization of HA through modulating the orientated structure. The mechanical properties, physical/chemical stability, and bioactivity of the composites are optimized and guided through the rearrangement of protein nanofibrils alignments, the structure-activity relationship between the orientation structure and bone repairing activity is revealed, and a new "bottom up" way to synthesize oriented protein nanofibrils/HA composites with bone-like microstructures is built. The current work hopes to extend the applications of oriented protein nanofibrils as bone repair materials, help understanding the mechanisms of protein regulation and mineralization in organisms, and provide further leads in the design and synthesis of novel nanostructures with highly-ordered orientation structures and specified biological functions.

天然骨骼中蛋白质纳米纤维与磷灰石形成的多级取向结构对其力学性能、生物活性（如精细调控细胞行为等）等有重要意义。本项目拟以蛋白质超分子组装而成的纳米纤维为研究对象，系统研究蛋白质纳米纤维的取向组装方法和机理，分析取向结构对磷灰石矿化形貌和结构的控制；进而通过调控复合材料的微观取向结构，优化其各向异性的力学性能、物理/化学稳定性及其对细胞行为的调控，揭示有序取向结构与生物活性间的构效关系，发展一种“自下而上”可控制备具有仿骨有序取向结构的蛋白质纳米纤维/羟基磷灰石复合物的新方法，并探索在骨骼修复领域的应用。期望通过本项目的成功实施，不仅为理解生物体内蛋白质调控矿化的分子机制开拓新途径，而且成为设计与合成具有高度有序取向结构及特定功能的新型纳米材料的重要来源。

本项目以牛血清白蛋白（BSA）超分子组装而成的纳米纤维为研究对象，发展出一种将BSA纳米纤维取向组装成有序结构的新方法，并系统研究了其取向组装机理；进而，分析了BSA取向结构对磷灰石矿化和细胞生长的调控，为设计与合成具有高度有序取向结构及特定功能的新型纳米材料提供了新思路。.另一方面，本项目发展出一种将BSA纳米纤维自交联成膜的反透析新方法。所获得的BSA自交联膜厚度可调、透明度高、韧性强、稳定性高，进一步负载抗菌成分（例如：银纳米粒子）或抗炎药物（例如：山奈酚）后的复合膜材料仍具有优秀的生物相容性（无细胞毒性、无溶血、无刺激性），并具备明显的抗菌、抗炎效果，作为创伤敷料的应用前景明朗。例如，BSA纳米纤维/银纳米粒子/甘油复合膜可通过为伤口提供物理保护、保持伤口的湿润性、降低炎症反应、促进上皮细胞增殖和迁移、促进皮肤附属器的再生等加速皮肤创面的愈合；BSA纳米纤维/山奈酚复合膜可通过延长山奈酚药物与创面的接触时间而减少给药频率，提高山奈酚的生物利用度，加快创面愈合。