组织整合和抗感染水凝胶的仿生构建及原位诱导皮肤再生研究

Hydrogels in situ inducing regeneration has been an effective way to solve skin defect and function lost. However, the weak binding to the target tissue and wound infection severely hamper the effectiveness in wound care management. In this project, based on the “catechol-lysine synergistic adhesion” of mussel protein, antibacterial polymer epsilon-polylysine (ε-PL) molecules will be employed to construct mussel- inspired polymer molecules with biomimetic structure distribution. Additionally, in view of the present poor mechanical properties of mussels inspired hydrogels, UV crosslinking is used to improve the mechanical strength of hydrogel scaffold materials whilst possessing organization integration and ability to resist infection. We will firstly study the effect of the functional groups proportion on the molecular backbone and the gelation condition on the mechanical properties and microstructure of hydrogels, which will determine the optimum parameters of the gelation for follow-up study. At the same time, the properties and mechanism of tissue integration and in vitro antibacterial performance will be evaluated. Finally, the hydrogel scaffold will be transplanted into rat skin damage model to determine the capabilities of tissue integration and anti-infection hydrogel for inducing skin regeneration.This study aims to establish a safe and effective new method to induce in situ skin regeneration, which will lay theoretical basis for the construction of tissue integration and anti-infection hydrogels for induction of skin regeneration.

水凝胶原位诱导再生是解决皮肤缺损及功能丧失的有效途径。但组织整合性差及感染问题已成为制约其走上临床应用的瓶颈。本项目借鉴贻贝蛋白中“邻苯二酚-赖氨酸协同作用”（“CLSA”）增强基质整合效应的思路，以ε-聚赖氨酸（ε-PL）为主体材料，设计制备仿贻贝蛋白结构分布的聚合物分子单元，并利用紫外光交联手段实现ε-PL端链自由基聚合，原位构建高仿贻贝水凝胶材料。首先系统研究ε-PL分子骨架中功能基团和成胶功能单元的比例对水凝胶组织整合性能的影响，考察基于“CLSA”机制增强水凝胶组织整合的构效关系；同时对水凝胶的抗感染能力进行评价，并对其机理进行解析，优选最佳成胶参数。最后将水凝胶支架移植到大鼠皮肤损伤模型上，确定组织整合和抗感染水凝胶诱导皮肤再生的科学性和可行性。本研究旨在建立一种安全、有效的原位诱导皮肤再生的方法，为基于贻贝仿生概念构建组织整合型水凝胶及水凝胶诱导皮肤再生的研究奠定理论基础。

皮肤创面修复过程容易导致感染和延迟愈合，严重威胁人类健康和生活质量。新型功能敷料的开发具有很大挑战。本研究面向该实际应用需求现状，模仿贻贝蛋白湿性粘附效应，构建聚氨基酸基贻贝蛋白仿生水凝胶材料，建立一种安全、有效的原位诱导皮肤再生的方法。分别利用酶催化、热聚合和分子自组装技术构建系列粘附抗菌水凝胶敷料。从聚合物浓度、交联系数等层面调控水凝胶的力学性能、抗菌和粘附功能。重点考察了水凝胶材料组织整合和抗感染功效，并对其界面自排水粘附分子机制进行了解析；此外，对水凝胶促进皮肤创面修复进行评价，结果显示，聚氨基酸基贻贝仿生粘附抗菌水凝胶具有优异促进创面修复功能，同时具有很好的生物安全性。我们的科研工作为新型聚氨基酸仿生贻贝蛋白水凝胶的设计和制备提供新的思路和策略，为皮肤难愈合创面水凝胶新材料的商业化应用提供了理论依据。项目执行期间申请了中国发明专利4项，授权3项，一共发表了标注该基金项目的SCI收录论文4篇，其中包括影响因子大于10的文章2篇，影响因子大于8的文章2篇；培养了生物医用水凝胶研究方面的多名优秀人才，包括1名博士研究生（赴中科院温州生物材料研究院工作）和3名硕士生。