基于壳聚糖的抗菌可注射自愈性水凝胶的制备及其生物相容性研究

Preparation and Biocompatibility of Antibacterial Injectable Chitosan-Based Hydrogel for Self-Healing Biomaterial

为了解决传统水凝胶作为敷料或支架在生物体内应用时所表现出的抑菌活性低、生物相溶性差和机械性能差等问题,本文以氧化普鲁兰多糖(OP)为交联剂,分别同硫醇化季铵盐壳聚糖(NAC-QCS)和己二酸二酰肼(ADH)发生动态化学反应,首次制备出一种可注射的自愈性抗菌的水凝胶——NQC-OP-ADH水凝胶,并对水凝胶的物理化学性质、抑菌活性和生物相容性进行研究。实验表明:NQC-OP-ADH对Escherichia coli和Staphlococcu aureus均表现出较高的抑菌活性,抑菌率分别为84%和99%;溶血率小于2%,具有良好的血液相容性;对培养24、48和72 h的L929细胞显示出较低的细胞毒性;在NQC-OP-ADH水凝胶表面和内部的培养至第5天的L929细胞仍具有良好的生长状态,特别是表面培养过程中有较多细胞迁移到NQC-OP-ADH水凝胶内部,表明NQC-OP-ADH水凝胶具有良好的细胞相容性。成胶后的NQC-OP-ADH可顺利通过注射器,无堵塞现象发生,且具有良好的自愈能力。

In order to solve the problems of low antibacterial activity and poor mechanical properties when traditional hydrogels are used as dressings or scaffolds in vivo.The antibacterial injectable self-healing hydrogel(NQC-OP-ADH)was prepared for the first time by dynamic chemical reactions between thiolated quaternary ammonium chitosan(NAC-QCS)and adipic acid dihydrazide(ADH)using oxidized pullulan(OP)as a crosslinker.The physicochemical properties,antibacterial properties,and biocompatibility of the hydrogel were studied.Experiments showed that NQC-OP-ADH exhibited high antibacterial activity against E.coli and S.aureus,with antibacterial rates of 84%and 99%,respectively;had good blood compatibility,with a hemolysis rate of less than 2%;and possessed low cytotoxicity to L929 cells cultured for 24,48 and 72 h.The hydrogel had good cytocompatibility,because L929 cells cultured on the surface and inside of the hydrogel for 5 days still had a good growth state,and lots of cells migrated inside the hydrogel in the process of surface culture.The gelatinized NQC-OP-ADH could pass through the syringe smoothly without clogging,and had good self-healing ability.