具有自主修复功能的高强度可注射水凝胶的构建及其作为组织植入材料的研究

The effective therapeutic strategy for various diseases caused by soft tissue defects and deficiencies is implanting biomaterials. Injectable hydrogel provides an effective way to solve the problems of trauma and further infection caused by implanting biomaterials surgically. However, injectable hydrogel is prone to damage under a variety of environmentally and therapeutically relevant stressors, such as impressed forces and body fluids after injection, which may affect the integrity of hydrogels’ structures and their mechanical strength. In this project, an injectable hydrogel with enhanced mechanical strength and self-healing properties is developed. The dual supramolecular interactions are introduced in the hydrogel, such as the host-guest interactions based on polyethylene glycol and α-cyclodextrins and the multiple hydrogen-bonding between 2-ureido-4-pyrimidone (UPy). The hydrogel is cross-linked with α-cyclodextrins bridged with disulfide bonds. RAFT and click chemical reaction are employed to obtain hydrogel with well-defined structures and well-controlled properties, with the ultimate aim of synthesizing an injectable hydeogel with enhanced mechanical strength and self-healing properties for tissue implant application. Based on these foreseeable advances, the injectable hydrogel in this project, could not only expand the application area of injectable hydrogels, but also provide a novel approach for studying the effect of dual supramolecular interactions on hydrogel formation. It is able to yield vast scientific contribution and potential applications which will lead to the significant development of novel hydrogels based on dual supramolecular interactions.

植入填充材料是目前治疗局部软组织结构松弛所造成的疾病普遍采用的有效方法。可注射水凝胶为解决手术植入造成的创伤及并发炎症提供了有效手段。然而，可注射水凝胶在注入体内后会由于外力作用或体液侵蚀而受损，进而影响凝胶结构的完整性和力学性能。本项目旨在通过分子设计，发展一种具有自主修复功能的高强度可注射水凝胶体系。该体系的构建基于聚乙二醇和环糊精的主客体相互作用及2-脲-4[1H]-嘧啶酮(UPy)的多重氢键的双重超分子作用，以双硫桥联环糊精为拓扑交联剂，通过RAFT及点击化学反应，实现水凝胶结构和性能的调控，从而达到构建具有自主修复功能和高强度的可注射水凝胶的目的，考察其作为组织植入材料的可行性。本项目的实施，不仅为可注射水凝胶在生物医学领域的应用提供新的方向，而且为解决双重超分子作用在水凝胶的构建中如何协同作用这一关键科学问题提供思路，为研制出基于双重超分子作用的新型水凝胶奠定理论和技术基础。

近年来，以可注射水凝胶作为组织工程支架用于组织修复已成为组织再生医学研究的热点。然而，可注射水凝胶在注入体内后会由于外力作用或体液侵蚀而受损，进而影响凝胶结构的完整性和力学性能。本项目通过分子设计，基于氢键、主客体相互作用或动态共价键制备了一系列可注射自修复水凝胶，考察了水凝胶的凝胶化时间、降解性能、机械强度和自修复性能等，研究了非共价键和动态共价键对水凝胶性能的影响，探讨了水凝胶在组织修复及颅骨缺损修复中的作用。研究表明，非共价键和动态共价键协同作用于水凝胶，提高了水凝胶的机械强度，改善了其降解性能。水凝胶可通过注射的方式注入缺损部位，促进缺损组织的愈合。本项目的实施为可注射水凝胶在生物医学领域的应用提供了新的思路和方向。