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具有剪切变稀可注射性和自愈合特性的氧化透明质酸/ε-聚赖氨酸/季铵化壳聚糖水凝胶用于全天候和多功能伤口愈合

Oxidized hyaluronic acid/ε-polylysine/quaternized chitosan hydrogel with shear thinning injectability and self-healing properties for full-time and multipurpose wound healing.

作者信息

Zheng Huiyuan, Zhang Xiaofeng, Wang Weijiang, Xin Huan, Yu Bin, Wang Lichen, Xie Huiqian, Zhang Yage, Song Yang, Ma Qingming

机构信息

School of Pharmacy, Qingdao University, Qingdao 266071, China.

Shandong Qingdao Hospital of Integrated Traditional and Western Medicine, Qingdao 266002, China.

出版信息

Int J Biol Macromol. 2025 Mar;293:139347. doi: 10.1016/j.ijbiomac.2024.139347. Epub 2025 Jan 2.

DOI:10.1016/j.ijbiomac.2024.139347
PMID:39755307
Abstract

Complex wound closure scenarios necessitate the development of advanced wound dressings that can effectively address the challenges of filling irregularly shaped wounds and managing fatigue failures encountered in daily patient activities. To tackle these issues, we develop a multifunctional hydrogel from natural polysaccharides and polypeptides with injectability and self-healing properties for promoting full-time and multipurpose wound healing. Synthesized through dynamic Schiff base linkages between oxidized hyaluronic acid (OHA), ε-polylysine (ε-PL), and quaternized chitosan (QCS), the OHA/ε-PL/QCS hydrogel can gel rapidly within 50 s. It exhibits notable strong shear-thinning and self-healing behavior, allowing easy injection to fit various wound shapes while maintaining integrity. In rat models of liver and femoral artery injuries, the hydrogel shows significantly reduced bleeding and accelerated hemostasis. The hydrogel can enhance cell proliferation through cell migration and tube formation, stimulate angiogenesis, support collagen deposition, and reduce inflammation. Its superior biocompatibility also supports the safe encapsulation of epidermal growth factor (EGF). In infected full-thickness skin wound models, the OHA/ε-PL/QCS/EGF hydrogel achieves nearly complete wound closure within 10 days. Overall, this study highlights the outstanding therapeutic potentials of the injectable and self-healing OHA/ε-PL/QCS hydrogel as a promising solution for fulfilling the multi-purpose, sophisticated needs in complicated wound closure scenarios.

摘要

复杂的伤口闭合情况需要开发先进的伤口敷料,以有效应对填充不规则形状伤口以及处理日常患者活动中遇到的疲劳失效等挑战。为解决这些问题,我们利用具有可注射性和自愈特性的天然多糖和多肽开发了一种多功能水凝胶,以促进全天候和多用途的伤口愈合。通过氧化透明质酸(OHA)、ε-聚赖氨酸(ε-PL)和季铵化壳聚糖(QCS)之间的动态席夫碱连接合成的OHA/ε-PL/QCS水凝胶可在50秒内迅速凝胶化。它表现出显著的强剪切变稀和自愈行为,便于注射以适应各种伤口形状,同时保持完整性。在肝损伤和股动脉损伤的大鼠模型中,该水凝胶显示出血明显减少且止血加速。该水凝胶可通过细胞迁移和管形成增强细胞增殖,刺激血管生成,支持胶原蛋白沉积,并减轻炎症。其优异的生物相容性还支持对表皮生长因子(EGF)的安全封装。在感染的全层皮肤伤口模型中,OHA/ε-PL/QCS/EGF水凝胶在10天内实现了近乎完全的伤口闭合。总体而言,本研究突出了可注射且自愈的OHA/ε-PL/QCS水凝胶作为满足复杂伤口闭合场景中多用途、复杂需求的有前景解决方案的卓越治疗潜力。

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