生物可降解聚氨酯胶束表面交联构建可注射医用水凝胶及其组织工程应用研究

本项目针对医用水凝胶与待修复组织力学与形态顺应性差、功能设计与结构构建难协调、体内注射凝胶化难控制的问题，以多嵌段水性聚氨酯构建无毒、生物可降解、力学与形态适宜细胞粘附生长、易载药的可注射水凝胶。多嵌段聚氨酯通过模块化结构设计制备自组装水性乳液胶束。扩链剂的侧链含交联活性端基，并采用亲水性修饰使其暴露于胶束表面。注射成型时，活性基团发生自发交联键合，使胶束与胶束之间连接形成多孔结构的水凝胶。交联键合指离子键、席夫碱键、Diels-Alder反应等。该多嵌段聚氨酯中，聚乙二醇为其提供良好的亲水性，聚酯二醇控制其降解性与疏水性，改性的扩链剂实现水凝胶的功能构建和注射成型控制。该工作采用聚氨酯先乳化自组装成胶束后自发交联凝胶的思路构建新型可注射水凝胶，将其用于药物控释和脂肪、肌肉、脑等组织的修复探索，致力于建立具有普适性的可注射医用水凝胶的结构设计方案，促进水凝胶在生物组织工程中的应用。

To overcome the problems of medical hydrogels in low compliance with defective tissues on mechanics and morphology, difficulty in integrating functional design with structural construction, uncontrollable gelling kinetics by injecting in vivo, a series of injectable hydrogels based on multiblock waterborne polyurethanes are constructed. The hydrogels are non-toxic, biodegradable with appropriate mechanical properties and microstructure for cell adhesion/growth and drug delivery. The emulsion micelles were prepared by self-assembly of the well-designed multi-block polyurethanes. The side chain of chain extender contains cross-linkable end group and it is exposed to the surface of the micelle by hydrophilic modification. When injection molding, bonding interactions form spontaneously between paired end groups, which combine the micelles to construct porous hydrogel. The bonding interactions can be ionic bonds, Schiff base bonds, Diels-Alder reactions, etc. In the multiblock polyurethane, polyethylene glycol (PEG) shows good hydrophilicity, polyester diol (PE - diol) can control the degradability and hydrophobicity, and the functional modification of chain extender endows the hydrogel with expected function and injectable gelling. The work proposes a novel strategy to construct injectable hydrogels by constructing self-assembly polyurethane micelles before spontaneous gelation and explores their applications in drug delivery and tissue regenerations of adipose, muscle, brain. It is committed to establish a universal design scheme of injectable hydrogels and promote the applications of the hydrogels in biological tissue engineering.