仿皮肤Janus凝胶膜片的构建及作为伤口敷料的研究

Human skin can effectively prevent the hydrogel-like body it covers from dehydration and invasion of bacteria. Inspired by the skin, this proposal will construct a novel Janus gel film with distinct sides: one side is a biocompatible hydrogel and the other side is an amphiphilic barrier that can prevent rapid dehydration of hydrogel and invasion of bacteria. The prepared Janus gel film will be used as wound dressing to eliminate the cell and tissue damage caused by the antibacterial agents loaded in hydrogel and achieve the nontoxic wound healing. In this project, polycondensation will be conducted to synthesize polyester with multi-thiol, controlled radical polymerization will be used to synthesize quaternized amphiphilic polymer with multi-epoxy. Hydrogel film will be prepared by radical polymerization and subsequently be used as substrate to construct heterogeneous polymer gel by layer-by-layer thiol-epoxy click assembly. Research will be systemically conducted to study the dehydration, oxygen permeation, cytotoxicity, hemolysis and antibacterial property. The Janus gel film will be utilized as wound dressing to test its wound healing property and tissue compatibility. This project will achieve good wound healing without side effects and provide a new idea of polymer gel for biomedical application.

人体皮肤具有防止机体失水和免受病原微生物侵入等功能。受此启发，本项目拟仿生设计构建一类两面性质不同的Janus凝胶膜片：一面为生物相容性良好的水凝胶，一面为抵抗细菌入侵和防止水凝胶快速失水的两亲屏障。将制备的Janus凝胶膜片用作伤口敷料，消除抗菌剂对机体细胞和组织造成的损伤，实现无毒副作用的伤口愈合。本项目将采用缩合聚合制备多巯基聚酯，采用可控自由基聚合制备季铵化多环氧两亲性聚合物，通过自由基聚合制备环氧官能化水凝胶膜片并以此为基体，基于巯-环氧层层点击组装，构建非均质高分子凝胶膜片。研究Janus凝胶膜片的失水性和氧渗透性；通过体外细胞毒性和溶血测试以及抗菌测试，检测凝胶膜片的生物相容性和对细菌的抵抗性能；以大鼠为动物模型，研究其作为伤口敷料的功能，测试其组织相容性，以期实现无毒副作用的伤口愈合，为高分子凝胶的生物医学应用提供新思路。

抗菌水凝胶是通过（1）抗菌剂有效避免了可能的伤口细菌感染和（2）提供良好的创伤生理环境达到促进伤口愈合的目标。然而，已报道的抗菌水凝胶存在两大问题：（1）抗菌剂无选择性地杀伤细菌和人体细胞；（2）水凝胶伤口敷料在使用过程中存在水分挥发。本项目构建了一类仿皮肤的 Janus 凝胶膜片并将其用作伤口敷料， 在保留水凝胶促进伤口愈合的功能基础上， 防止水凝胶快速失水和消除抗菌剂引起的毒副作用， 保持良好的氧渗透性，实现了无毒副作用的伤口愈合。本研究首先合成了凝胶前体：自由基聚合合成水溶性聚醛，缩合反应合成聚乙二醇二氰乙酸酯，自由基聚合合成季铵化水溶性聚醛；基于醛与活泼亚甲基的Knoevenagel缩合反应制备了双层凝胶——Janus凝胶。通过流变学实验测定所得水凝胶具有较好的力学性能，与组织强度匹配；SEM观察到凝胶具有多孔结构；含有季铵盐的凝胶能够高效的杀死大肠杆菌和金黄色葡萄球菌；体外溶血实验表明水凝胶基本无溶血现象发生，而季铵盐凝胶会有较严重的溶血现象；体外细胞毒性实验表明水凝胶生物相容性良好，季铵盐凝胶会对细胞有较大的杀伤作用。最终通过体内实验发现，本研究所制备的Janus凝胶膜片能够有效地促进伤口愈合，减少细菌感染。因此本研究在保留水凝胶促进伤口愈合的功能基础上，消除了抗菌剂引起的毒副作用，实现了无毒副作用的伤口愈合，为凝胶抗菌敷料的商品化和临床应用提供了重要的科学依据。