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儿茶酚功能化壳聚糖/活性肽微球水凝胶用于皮肤伤口愈合。

Catechol functionalized chitosan/active peptide microsphere hydrogel for skin wound healing.

机构信息

Faculty of Chemistry and Environmental Science, Guangdong Ocean University, Zhanjiang 524088, China; Southern Marine Science and Engineering Guangdong Laboratory (Zhanjiang), Zhanjiang 524000, China.

Guangdong Key Laboratory for Research and Development of Natural Drugs, Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, China.

出版信息

Int J Biol Macromol. 2021 Mar 15;173:591-606. doi: 10.1016/j.ijbiomac.2021.01.157. Epub 2021 Jan 26.

Abstract

Chitosan-based thermosensitive hydrogels have been widely used in drug delivery and tissue engineering, but their poor bioactivity has limited their further applications. Integral active oyster peptide microspheres (OPM) with an average particle diameter of 3.9 μm were prepared with high encapsulation efficiency (72.8%) and loading capacity (11.9%), exhibiting desirable sustained release effects. Using catechol functionalized chitosan (CS-C) as the polymeric matrix, OPM as the filler, and β-sodium glycerophosphate (β-GP) as a thermal sensitizer, the thermosensitive hydrogel CS-C/OPM/β-GP was prepared. Besides, the application of the hydrogel on wound healing was studied, and its biosafety was evaluated. The results of cell migration in vitro showed that the cell migration rate of CS-C/OPM/β-GP reached 97.47 ± 5.41% within 48 h, indicating that the hydrogel accelerated the migration of L929 cells. As demonstrated in the mouse skin wound experiment, CS-C/OPM/β-GP hydrogel not only inhibited the aggregation of diversified inflammatory cells and accelerated the generation of collagen fibers and new blood vessels of the wound, but also enhanced the synthesis of total protein (TP) in granulation tissue, and up-regulated the expression of Ki-67 and VEGF in the injury, thereby achieving fast wound healing. Safety evaluation results showed that CS-C/OPM/β-GP hydrogel was not cytotoxic to L929 cells, and the hemolysis ratio was less than 5% within 1 mg/mL. In conclusion, CS-C/OPM/β-GP hydrogel is expected as a promising medical dressing for wound healing.

摘要

基于壳聚糖的温敏水凝胶已广泛应用于药物输送和组织工程,但由于其生物活性较差,限制了其进一步的应用。本研究采用平均粒径为 3.9μm 的 integral active oyster peptide microspheres (OPM),具有较高的包封率(72.8%)和载药量(11.9%),展现出良好的持续释放效果。以儿茶酚功能化壳聚糖(CS-C)为聚合物基质,OPM 为填充剂,β-甘油磷酸钠(β-GP)为热敏剂,制备了温敏水凝胶 CS-C/OPM/β-GP。此外,还研究了水凝胶在伤口愈合中的应用,并对其生物安全性进行了评估。体外细胞迁移实验结果表明,CS-C/OPM/β-GP 水凝胶在 48 h 内的细胞迁移率达到 97.47±5.41%,表明水凝胶能加速 L929 细胞的迁移。在小鼠皮肤伤口实验中,CS-C/OPM/β-GP 水凝胶不仅能抑制多种炎症细胞的聚集,促进伤口胶原纤维和新生血管的生成,还能增加肉芽组织中总蛋白(TP)的合成,上调损伤组织中 Ki-67 和 VEGF 的表达,从而实现快速伤口愈合。安全性评价结果表明,CS-C/OPM/β-GP 水凝胶对 L929 细胞无细胞毒性,在 1mg/mL 内的溶血率小于 5%。综上所述,CS-C/OPM/β-GP 水凝胶有望成为一种有前途的用于伤口愈合的医用敷料。

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