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基于双功能化透明质酸的自交联组织粘附水凝胶对活性氧的清除及角膜上皮伤口愈合作用

ROS scavenging and corneal epithelial wound healing by a self-crosslinked tissue-adhesive hydrogel based-on dual-functionalized hyaluronic acid.

作者信息

Pan Xin-Yang, Wang Zi-Han, Wu Xiao-Qing, Guo Chang-Rong, Yang Lin-Xing, Liu Hui-Ru, Wang Yuan-Hao, Chen Wen-Juan, Wang Jing-Jie, Nan Kai-Hui, Li Ling-Li

机构信息

National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China.

Tianjin Stomatological Hospital, School of Medicine, Nankai University, Tianjin 300041, China.

出版信息

Int J Biol Macromol. 2025 Mar;293:139200. doi: 10.1016/j.ijbiomac.2024.139200. Epub 2024 Dec 25.

DOI:10.1016/j.ijbiomac.2024.139200
PMID:39730051
Abstract

Reactive oxygen species (ROS) scavenging is a viable approach to promote corneal epithelium wound healing. This study created a single-component hydrogel (HA Gel) with a novel dual-functionalized hyaluronic acid derivative (HA-GA-PBA) containing gallol and phenylboronic acid (PBA) moieties. Both of these moieties were dual-functional. Specifically, they not only functioned as structural building blocks for hydrogel formation, but also served as bioactive ingredients for therapeutic purpose. Dynamic covalent complexation between gallol and PBA moieties led to the self-crosslinked HA Gel, which was antioxidative and tissue-adhesive. It was demonstrated that the hydrogel enhanced the proliferation rate of human corneal epithelial cells by over 2.5 folds. When treating the mouse corneal alkali burn model with HA Gel, the corneal epithelial healing percentages reached 69.19 ± 9.41 % and 84.12 ± 6.09 % on day 3 and 5, respectively, which were significantly higher than the placebo group (51.14 ± 9.63 % and 67.32 ± 10.54 % on day 3 and 5, respectively). Meanwhile, reduced scar formation and inflammation was observed. These findings indicated HA Gel could find applications in various of ocular diseases for improved corneal epithelial wound healing.

摘要

活性氧(ROS)清除是促进角膜上皮伤口愈合的一种可行方法。本研究制备了一种单组分水凝胶(HA凝胶),其含有一种新型的双功能化透明质酸衍生物(HA-GA-PBA),该衍生物含有没食子醇和苯硼酸(PBA)基团。这两个基团都具有双重功能。具体而言,它们不仅作为水凝胶形成的结构构建单元,还作为治疗用途的生物活性成分。没食子醇和PBA基团之间的动态共价络合导致了自交联的HA凝胶,该凝胶具有抗氧化和组织粘附性。结果表明,该水凝胶使人类角膜上皮细胞的增殖速率提高了2.5倍以上。在用HA凝胶治疗小鼠角膜碱烧伤模型时,在第3天和第5天角膜上皮愈合率分别达到69.19±9.41%和84.12±6.09%,显著高于安慰剂组(第3天和第5天分别为51.14±9.63%和67.32±10.54%)。同时,观察到瘢痕形成和炎症减轻。这些发现表明,HA凝胶可用于多种眼部疾病,以改善角膜上皮伤口愈合。

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