Abstract:
Chitosan (CS)-based photo-cross-linkable hydrogels have gained increasing attention in biomedical applications. In this study, we grafted CS with gallic acid (GA) by carbodiimide chemistry to prepare the GA-CS conjugate, which was subsequently modified with methacrylic anhydride (MA) modification to obtain the methacrylated GA-CS conjugate (GA-CS-MA). Our results demonstrated that the GA-CS-MA hydrogel not only exhibited improved physicochemical properties but also showed antibacterial, antioxidative, and anti-inflammatory capacity. It showed moderate antibacterial activity and especially showed a more powerful inhibitory effect against Gram-positive bacteria. It modulated macrophage polarization, downregulated pro-inflammatory gene expression, upregulated anti-inflammatory gene expression, and significantly reduced reactive oxygen species (ROS) and nitric oxide (NO) production under lipopolysaccharide (LPS) stimulation. Subcutaneously implanted GA-CS-MA hydrogels induced significantly lower inflammatory responses, as evidenced by less inflammatory cell infiltration, thinner fibrous capsule, and predominately promoted M2 polarization. This study provides a feasible strategy to prepare CS-based photo-cross-linkable hydrogels with improved physicochemical properties for biomedical applications.
摘要:
基于壳聚糖(CS)的光交联水凝胶在生物医学应用中得到了越来越多的关注。在这项研究中,我们通过碳二亚胺化学接枝CS与没食子酸(GA)制备GA-CS共轭物,其随后用甲基丙烯酸酐(MA)改性以获得甲基丙烯酸酯化的GA-CS缀合物(GA-CS-MA)。我们的结果表明,GA-CS-MA水凝胶不仅表现出改善的理化性质,而且还表现出抗菌,抗氧化,和抗炎能力。它显示出中等的抗菌活性,尤其是对革兰氏阳性细菌显示出更强的抑制作用。它调节巨噬细胞极化,下调促炎基因表达,上调抗炎基因表达,并且在脂多糖(LPS)刺激下显着降低了活性氧(ROS)和一氧化氮(NO)的产生。皮下植入的GA-CS-MA水凝胶可显著降低炎症反应,炎症细胞浸润减少,较薄的纤维胶囊,并主要促进M2极化。本研究为制备用于生物医学应用的具有改善的物理化学性质的基于CS的光交联水凝胶提供了可行的策略。