硬段交联型酶敏感可降解形状记忆聚氨酯的研究

In this project, to obtain controllable degradation shape memory polyurethane materials, which could meet the rapidly degradable requirements in physiological environment of non vascular cavities, one kind of controllable degradation multifunctional shape memory polyurethane will be designed and prepared. Thus, peptide compounds that could be degraded by specific enzymes (such as trypsin), will be first synthesized. And then, these peptides will be used as starting agents for synthesis of polyester oligomer diols (poly (caprolactone and glycolide) glycol copolymer), subsequently, linear biodegradable polyurethanes will be synthesize using the obtained oligomer diols, aliphatic diisocyanate, and chain extenders containing double bond in side chain. Finally, Enzyme-induced biodegradable cross-linked shape memory polyurethanes will be prepared through crosslinking of hard segments. Herein, the structures and ratios between soft and hard segments, effects of cross-linked structures and hydrogen bonding on shape memory properties of these polyurethanes will be investigated, and their biocompatibility will also be evaluated through cell experiments in vitro and animal experiments. Simultaneously, the influence of these specific structures on degradation rate of these polyurethanes through studies of degradation in vitro and in vivo will be explored, which will be applied to guide the design of biodegradable shape memory materials. These obtained results will provide novel biodegradable shape memory polyurethane materials and a new approach to the design and preparation of stent materials of non vascular cavities in minimally invasive treatment.

针对现有形状记忆材料难于满足生理环境降解的要求，本课题提出制备一类降解性能易于调控的多功能形状记忆聚氨酯。设计合成对特定酶（如胰蛋白酶）高度选择性的多肽化合物，以此为起始剂合成无定形的聚（己内酯和乙交酯）共聚物二醇，以其为基础合成可降解聚氨酯，并通过硬段的后交联获得一类酶敏感的、易水解的交联型形状记忆聚氨酯新材料。研究软硬段结构和比例、交联结构和氢键结构在材料形状记忆和回复中的作用；并通过体外细胞实验和动物体内植入实验评价材料的生物相容性。通过体内外的降解研究，揭示各种结构因素对降解的影响规律，这将为微创治疗使用的非血管腔道支架材料的结构设计提供理论基础和科学依据。

本课题针对非血管腔道支架材料的生物降解性、形状记忆性能、力学性能等方面进行研究。首先通过结构设计在聚氨酯结构中引入对糜蛋白酶敏感的拟肽结构（PHP），以聚己内酯（PCL）2000、3000和4000为软段，合成了糜蛋白酶敏感的形状记忆聚氨酯，调节PHP在扩链剂中的占比得到一系列酶敏感同时可以水解的聚氨酯，酶敏感基团的加入会提高形状记忆材料的降解速度，且聚氨酯中引入两个脲基，增加了硬段之间的氢键作用，增强了形状记忆的效果；并且材料在生理环境下仍能保持较好的力学性能。通过硬段的后交联可提高材料的形状记忆性能，并通过引入近红外响应的纳米金，得到了获得一类酶敏感的、形状记忆响应快、力学性能优异的形状记忆聚氨酯材料。.另外根据人体内管腔支架使用过程中要求力学模量高的需求，设计了一种新型的主链上全部是硬段，软段PEG在侧链的聚氨酯，这类形状记忆聚氨酯材料能在水环境中发生形状回复，但回复后材料的模量升高，使得其在植入时较软，易于通过弯曲的管腔和导管，植入后吸水导致模量升高，从而获得更高的径向抗力，起到更好的支撑效果。.这些研究成果对可降解的形状记忆材料的设计起到指导性作用，为微创治疗使用的非血管类腔道支架材料的结构设计提供思路。