脂肪酸-硫代NHS酯疏水改性鱼胶原及其静电纺纳米纤维结构与性能调控机理研究

The electrospinning of collagen-based nanofibers to prepare scaffolds for tissue engineering is a hot and difficult issue of research in the field of biomaterials. There remains a problem of contradiction concerning the structural stability of collagen and its electrospinnability. Additionally, the correlation between the aggregation behavior of collagen in the electrospinning solution and the structure-property of electrospun nanofibers has not been clarified. Based on the fact that hydrophobically associating interactions are resistant to temperature and shear force and are beneficial to the electrospinning of collagen, this project proposes a novel idea about "Modification first and then electrospinning" and aims to synchronously strengthen the structural stability of collagen and its electrospinnability, achieving the regulation of the structure-property of electrospun collagen fibers. The project is to prepare novel fatty acidic N-Hydroxysulfosuccinimide esters to hydrophobically modify fish collagen and the mechanism of the synchronous enhancement of the structural stability and the electrospinnability of the modified collagen will be disclosed using several techniques including thermal kinetics, two-dimensional correlation analysis, rheology and so on. Moreover, the internal relations between the aggregation behavior of the hydrophobically modified fish collagen in the electrospinning solution and the structure-property of electrospun nanofibers will be clarified. Finally, the mechanism of the regulation of the structure-property of electrospun collagen nanofibers through the hydrophobic modification of fish collagen by fatty acidic N-Hydroxysulfosuccinimide esters will be mastered. The project has important theoretical significances and application values for reducing the cooperative denaturation effects on collagen of electrospinning solvents, temperature and shear force, and for developing water-based solvent for collagen electrospinning. And the project will provide theoretical basis for the promotion of the modification and application of fish collagen, as well as the high-value utilization of fish offal resources.

静电纺胶原基纳米纤维仿生制备组织工程支架是生物材料领域的研究热点和难点。相关研究仍存在胶原结构稳定性与静电可纺性的矛盾问题，且未明确纺丝液中胶原聚集行为与电纺纤维性质的关系。本项目基于疏水缔合作用耐温、耐剪切及其利于胶原电纺的优势，提出“先改性，再纺丝”创新思路，旨在通过疏水改性同步增强胶原结构稳定性与静电可纺性，实现对电纺胶原纤维性质的调控。拟制备新型脂肪酸-硫代NHS酯对鱼胶原进行疏水改性，采用热动力学、二维相关分析、流变等技术阐明改性鱼胶原稳定性与静电可纺性的同步增强机制；揭示电纺液中改性鱼胶原聚集行为与电纺纤维性质的内在关联；掌握脂肪酸-硫代NHS酯疏水改性对电纺鱼胶原纳米纤维构效关系的调控机理。本项目对减轻电纺溶剂、温度和剪切力对胶原的协同变性作用及发展胶原电纺用水性溶剂体系，都有重要理论意义和应用价值，也为促进鱼胶原的改性与应用以及推动鱼下脚料资源高值转化利用进程提供理论依据。

静电纺胶原纳米纤维因其具有模仿天然细胞外基质中胶原纤维的形貌结构，是当前胶原基生物材料制备领域的研究热点。然而，胶原在静电纺丝溶剂及电纺过程中的变性现象制约了胶原电纺纤维的相关研究及应用。本项目旨在设计合成能够用于同步增强胶原结构稳定性与静电可纺性的化学改性剂（脂肪酸-硫代NHS酯），通过“先改性，再纺丝”实现电纺胶原纤维的可控制备。项目执行期间主要围绕以下几个方面开展了研究：1）合成制备了不同碳链长度的脂肪酸硫代NHS酯并进行了较系统的结构表征；2）研究优化了高品质、高得率胶原的原料预处理和胶原提取工艺；3）考察了脂肪酸硫代NHS酯对胶原的疏水改性效果，并总结了需要克服的技术问题；4）分析比较了胶原在不同水性溶剂体系的热变性动力学等溶液聚集行为；5）研究了胶原电纺稳定性的影响因素，并分析了解决胶原电纺困难的可行途径；6）基于最新电纺文献启示，研究了开环易位聚合（ROMP）大分子交联剂对蛋白材料的交联特性及其在胶原电纺中的应用探索。本项目研究成果为胶原的结构强化提出了新的化学改性策略（脂肪酸-硫代NHS酯疏水改性与嵌段共聚物大分子交联改性），为静电纺胶原基纳米纤维的可控制备提供了一定的理论参考，同时也为推动鱼胶原在生物材料领域的高值转化利用具有指导意义。近三年，在本项目的资助下共发表学术期刊论文10篇，其中包括Polymer、Process Biochemistry、Polymer Reviews等SCI论文7篇；申请国家发明专利2项；多次参加国内外学术会议并宣讲项目相关研究成果。