智能自愈合多功能水凝胶涂层对促进生物材料安全长效使用的研究

Functional polymer coatings have been extensively employed in the surface modification of biomaterials, especially in imparting the anticoagulant and antibacterial properties to the biomaterials. However, the occurrence of microcracks in polymer coatings is inevitable in the long-term interaction between coatings and human body. If the microcracks are not repaired or healed in time, they will greatly reduce the stability of polymer coatings, leading to the dysfunction of the coating and biomaterials, as well as harm to patients. To solve this problem, intelligent self-healing multifunctional hydrogel coatings will be developed in this project. The self-healing functionality will be incorporated into the anticoagulant and antibacterial polymer coatings, to improve their stabilities and long-term usage of corresponding biomaterials. More specifically, the functional monomers and cross-linker containing disulfide bond will be copolymerized on metal biomaterials in situ via thiol-initiated photopolymerization. On one hand, based on the thiol/disulfide dynamic exchange, the resultant multifunctional polymer coatings are capable of multiple self-healing under room temperature repeatedly; on the other hand, the functionalities of polymer coatings, such as anticoagulant and antibacterial properties, can be tuned by selection of functional monomers. To conclude, the multifunctional polymer coatings, with both anticoagulant and antibacterial properties and intelligent self-healing property, have great potential in improving the safe and long-term usage of biomaterials.

功能高分子在生物材料的表面修饰领域应用广泛，可有效引入抗凝血、抗菌等多种功能。然而，在与人体环境的长期相互作用中，这些功能涂层的微损伤不可避免，如不进行及时有效的修复，将显著降低涂层的稳定性，导致涂层功能的退化、生物材料的失效甚至有害于人体健康。为了解决这一关键问题，本项目拟合成智能自愈合多功能水凝胶涂层，增加抗凝血和抗菌水凝胶涂层的微损伤智能自愈合性质，有效提高涂层的稳定性，促进生物材料的安全长效使用。具体实验方案为：采用功能性单体和含双硫键的交联剂，通过高效的巯基引发光聚合反应，原位制备智能自愈合-多功能水凝胶涂层；利用硫醇/双硫键氧化还原可逆反应的智能响应，实现微损伤的常温修复及多次修复；同时，通过功能性单体的选择，赋予水凝胶涂层抗凝血和抗菌功能。本项目可实现涂层生物应用功能与智能自愈合性能的统一，对促进生物材料的安全长效应用具有重要意义。

自愈合材料因其对外界环境因素变化能自动做出响应，并具有自我诊断、自我调节和自我修复的功能而成为智能高分子材料前沿研究热点。本项目从生物材料安全长效应用的实际需求出发，基于“外植型”和“本征型”自愈合机制，构建了多种新型自愈合水凝胶材料，探究了多功能自愈合涂层在生物材料表面改性中的应用，提高了生物材料的稳定性和使用安全性。首先，基于“本征型”自愈合机制，利用功能性单体和含双硫键的交联剂通过光引发自由基聚合反应制备得到同时具有防污染、抗菌及自愈合性能的多功能水凝胶涂层。该水凝胶涂层具有良好的抗蛋白吸附（吸附率可减小至6%），抗细菌粘附（表面粘附率减小至5%）及杀菌的性能。水凝胶涂层中的双硫键可通过双硫键动态可逆交换反应实现了不同厚度涂层对应不同裂纹深度、宽度的自愈合，提高了生物材料表面功能涂层的损伤修复能力。该水凝胶涂层制备方法具有普适性，可采用不同的功能性单体来实现涂层不同的生物功能，更好的应用于生物材料及生物医用器件表面性质的调控，提高了生物材料表面防污染、抗菌涂层的稳定性。其次，在基于双硫键动态交换反应的“本征型”自愈合机制的基础上，进一步引入“外植型”自愈合机制，结合两种机制的优势构建自愈合水凝胶涂层。制备了分散性良好、较大比表面积和负载孔容的介孔二氧化硅纳米颗粒。该二氧化硅纳米容器可有效负载愈合剂，结合抗菌功能性单体，通过光引发聚合制备水凝胶涂层，探索了潜在的自愈合/抗菌应用。最后，针对“本征型”水凝胶材料，采用简单、高效的迈克尔加成反应和巯基-炔基点击反应，设计构建了具有不同刺激响应的“本征型”自愈合水凝胶，实现了快速、高效的双重刺激响应愈合修复性能，并具有良好的生物相容性。