自愈性甲壳素基涂层的构建及其构效关系研究

Biofouling caused by damage of coatings on implantable medical devices by accidental scratching and rough handling in practical usage results significant morbidity and mortality worldwide. The self-healing coating can repair the damaged area itself which can prevent biofouling from forming on the surface of medical devices. The research of coating for implantable medical devices mainly focuses on the properties related with antiadhesion of microorganisms and proteins. So it is urgent to develop the self-healing property of the coating. This project utilizes the formation of Schiff base between amino on chitin/chitosan derivatives and aldehyde on oxidized polysaccharides to fabricate self-healing coating with antibiofouling property through layer-by-layer assembly. The key scientific problems we are trying to figure out are the relationships between structure adjustments and functions of the multilayered polysaccharides based coating. This study tries to figure out the key role of molecular parameters, pH, and ionic strength of solution in the structure regulation of coating. This study also tries to illustrate relationship and mechanism between structure regulation and self-healing, antibiofouling of the coating and to reveal the function of self-healing property in preventing the biofouling formation. The project integrates the merits of chitin/chitosan and self-healing of the coating. The multilayered biopolymer based coating with self-healing and antibiofouling properties will play an important role in the field of medical packaging materials.

体内植入医疗器械涂层在使用过程中容易受损，引起生物污染，致使人体发病和死亡。自愈合涂层能在体内自我修复伤口，阻止微生物及蛋白质从受损处入侵。目前对医疗器械涂层的研究主要集中于抗细菌、蛋白粘附性及相容性上，因此迫切需要研究涂层的自愈合性。本项目利用甲壳素/壳聚糖衍生物的氨基和氧化天然多糖的醛基形成席夫碱为驱动力，以层层自组装的方式构建自愈合抗生物污染涂层。项目拟解决的关键科学问题是席夫碱驱动下的天然多糖和氧化天然多糖自组装涂层的结构调控与功能之间关系问题。弄清多糖分子参数、溶液pH值、离子强度等在涂层结构调控中的关键作用，阐明涂层结构与自愈合和抗生物污染之间的相互关系，揭示自愈合在抗生物污染中的微观机制。本项目整合甲壳素/壳聚糖和自愈合涂层的优点，制备的自愈合抗生物污染涂层将在医用包装材料领域发挥重要作用。

本项目针对体内植入医疗器械涂层在使用过程中容易受损，引起生物污染，致使人体发病和死亡的问题，拟利用壳聚糖、甲壳素中的氨基和氧化天然多糖中的醛基发生席夫碱反应，构建具有自愈合性能的多糖基涂层。首先，在碱/尿素体系中通过一步法均相地制备了丙烯酰胺壳聚糖。通过调节丙烯酰胺和壳聚糖的摩尔比及反应时间，制备了取代度在0.49到0.93之间的丙烯酰胺壳聚糖。通过红外光谱、核磁共振、X射线衍射对产物进行了表征。利用同样的体系，还可以制备丙烯酰胺甲壳素、羧甲基壳聚糖等衍生物。随后，利用丙烯酰胺壳聚糖中的氨基和氧化海藻酸的醛基发生席夫碱反应，构建了凝胶材料。席夫碱键是一类动态共价键，存在动态平衡，赋予凝胶自愈合性。pH值对凝胶的自愈合能力有影响，席夫碱在酸性环境中不稳定，凝胶变成溶液，凝胶在碱性环境中变弱，但可以完好地保留自愈合性。材料的比例影响凝胶自愈合，氧化海藻酸的用量越大，凝胶的自愈合越弱。交联时间越久，凝胶的自愈合能力越弱。凝胶的自愈合性能及力学性能可以通过调节pH值进行恢复。此类自愈合凝胶的制备方法简单，可以扩展到其他多糖基自愈合凝胶。最后，利用丙烯酰胺改性壳聚糖和氧化海藻酸的交联反应，通过层层自组装（LBL）制备了透明的自修复涂层。傅立叶变换红外光谱和X射线光电子能谱表征表明涂层中存在席夫碱键。紫外可见光谱和场发射扫描电子显微镜表征表明，涂层在LBL过程中表现出线性生长特性。涂层具有重复自修复性能，并且涂层的厚度和重复修复损伤的次数的能力成正比关系。除了优异的自修复性能外，涂层还具有抗细胞黏附的性能。此多功能涂层在生物医药及包装领域具有应用前景。