医用可降解强韧性天然高分子/聚氨酯复合水凝胶材料的制备与应用研究

To overcome the disadvantages of current biomedical hydrogels including low mechanical strength and toughness, poor biological compliance and non-degradability, a series of novel natural polymer/polyurethane hydrogels will be fabricated using natural polymer and waterborne polyurethane. The toughing mechanism is based on “sacrificial bonds” mechanism in double network hydrogel. The clinical available natural polymers such as gelatin, agar，combine with structural tailorable, biodegradable, biocompatible and tough waterborne polyurethane to form a novel biomedical double network hydrogel. Natural polymers based on the coil–helix structural transition will be used to construct the first stiff network framework. Meanwhile, the multifunctional prepolymer of polyurethane will be imported and then polymerized to from the second soft network. Multiblock polyurethane will be designed by tune the components of hard segments and soft segments to prepare multifunctional hydrogels with various functions, such as biodegradable, drug delivery and stimulating response. The structural characters, mechanical properties, biodegradable feature and biocompatibility of the hydrogels will be investigated in detail to ascertain the structure-property relationship and design strategy. This work will greatly promote the applications of such biomedical hydrogels in soft tissues regeneration and repair, medical devices, such as artificial skin, the membrane for preventing postsurgical adhesion, and wound dressing.

本项目针对当前生物医用水凝胶材料力学性能差、生物顺应性低、不可降解等关键科学问题，运用双网络水凝胶“牺牲键”增韧理论，以天然高分子和水性聚氨酯为基体研究新一代降解型强韧性复合水凝胶医用材料。采用临床应用的天然高分子如明胶、琼脂等与结构可裁剪、力学性能优良、生物相容性好并具可降解性的水性聚氨酯复合，形成双网络结构水凝胶。利用天然高分子的分子构象变换形成第一层刚性网络骨架。将水性聚氨酯预聚体引入其网络进行聚合形成第二层柔性网络结构。通过对水性聚氨酯的软段和硬段进行多嵌段结构设计赋予材料多功能性，如降解性、环境响应性等。通过对材料结构分析、力学性能测试、生物降解与相容性等表征工作,研究该水凝胶材料的结构性能关系，获得制备综合性能优良的复合水凝胶医用材料的控制工艺与方法。该双网络结构水凝胶材料将有望应用于人体软组织修复、医疗器件等领域,如人工皮肤、术后防粘连膜、创伤敷料等。

本项目针对生物医用水凝胶材料力学性能差、生物顺应性低、不可降解等关键科学问题，运用双网络水凝胶杂化复合理论，以天然高分子（透明质酸、姜黄素、壳聚糖、海藻酸钠等）和水性聚氨酯为基体研究新一代降解型强韧性复合水凝胶医用材料。通过对水性聚氨酯的软段和硬段进行多嵌段结构设计赋予材料多功能性，并实现其与天然高分子的良好复合，获得了一系列性能优良的复合结构水凝胶。如，透明质酸/聚氨酯复合水凝胶具有良好的可降解性和生物相容性，复合水凝胶还具有温敏可注射性和自修复性，引入含季铵盐阳离子拟肽结构可实现良好的抗菌作用。聚氨酯/姜黄素复合水凝胶具有良好的力学强韧性（强度大于3MPa,断裂伸长率大于700%）和抗氧化、抗菌等性能。壳聚糖/四臂聚乙二醇水凝胶可以包载抗癌药物，实现凝胶原位注射控制释药，对抑制肿瘤生长表现出良好的效果。海藻酸钠/聚氨酯水凝胶具有优良的促组织修复特性。本研究通过对材料结构分析、力学性能测试、生物降解与相容性等表征工作, 研究了该系列水凝胶材料的结构性能关系，获得了制备综合性能优良的复合水凝胶医用材料的控制工艺与方法。该系列水凝胶材料将有望应用于人体软组织修复、医疗器件等医学领域, 如组织工程支架、隔膜、创伤敷料等。