基于羧甲基壳聚糖的载叶黄素多功能水凝胶敷料用于慢性伤口愈合

Lutein-loaded multifunctional hydrogel dressing based on carboxymethyl chitosan for chronic wound healing.

作者信息

Zhang Hongyan, Gao Xin, Dai Wen-Qing, Cui Na, Liu Jun-Qi, Wang Min-Ge, Zhou Yu-Feng, Fang Liang-Xing, Sun Jian, Jiang Gang-Biao, Liao Xiao-Ping

机构信息

National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.

College of Agriculture and Biology, Liaocheng University, Liaocheng, Shandong 252000, China.

出版信息

Int J Biol Macromol. 2025 Apr;300:140219. doi: 10.1016/j.ijbiomac.2025.140219. Epub 2025 Jan 22.

Abstract

Oxidative stress is a major contributor to the difficulties in chronic wound healing. Although antioxidant hydrogels have been developed, they are still insufficient for addressing the entire chronic wound healing process. In this study, a lutein-loaded multifunctional hydrogel dressing (Lutein/CMC/PVP/TA, Lutein/CPT) with synergistic antioxidation properties was developed by hydrogen bonding and electrostatic crosslinking of tannic acid (TA) with carboxymethyl chitosan (CMC) and polyvinylpyrrolidone (PVP). When loaded with 5 mg/mL of lutein, the 5Lutein/CPT hydrogel showed suitable swelling ratio, degradation rate, stability and biocompatibility. The hydrogel dressing demonstrates excellent self-healing behavior (≤20 s) and effectively extends the service life of the dressing. Importantly, this hydrogel displays pH-responsive drug release characteristics to meet the needs of the wound healing process. Specifically, under alkaline conditions (the initial stage of wound healing), TA and lutein are simultaneously released for synergistic antioxidant use in scavenging reactive oxygen species (ROS) and resolving inflammation. Under acidic conditions (late stage of wound healing), lutein is released to facilitate collagen formation. Additionally, the hydrogels demonstrated excellent antimicrobial (E. coli, S. aureus, and MRSA) activity and anti-biofilm ability. Animal experiments have shown that the 5Lutein/CPT hydrogel can promote wound closure, collagen fiber generation, angiogenesis and anti-inflammation. In conclusion, 5Lutein/CPT hydrogel dressings hold potential as candidate materials for promoting diabetic wound healing. Moreover, this study provides novel insights into the combined use of natural plant antioxidants in CMC-based hydrogel dressings to treat chronic wounds.

摘要

氧化应激是慢性伤口愈合困难的主要原因。尽管已经开发出抗氧化水凝胶,但它们仍不足以应对整个慢性伤口愈合过程。在本研究中,通过单宁酸(TA)与羧甲基壳聚糖(CMC)和聚乙烯吡咯烷酮(PVP)的氢键和静电交联,制备了具有协同抗氧化性能的负载叶黄素的多功能水凝胶敷料(叶黄素/CMC/PVP/TA,叶黄素/CPT)。当负载5mg/mL叶黄素时,5叶黄素/CPT水凝胶表现出合适的溶胀率、降解率、稳定性和生物相容性。该水凝胶敷料具有优异的自愈性能(≤20秒),并有效地延长了敷料的使用寿命。重要的是,这种水凝胶具有pH响应药物释放特性,以满足伤口愈合过程的需求。具体而言,在碱性条件下(伤口愈合初期),TA和叶黄素同时释放,用于协同抗氧化,以清除活性氧(ROS)和消除炎症。在酸性条件下(伤口愈合后期),叶黄素释放以促进胶原蛋白形成。此外,水凝胶表现出优异的抗菌(大肠杆菌、金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌)活性和抗生物膜能力。动物实验表明,5叶黄素/CPT水凝胶可促进伤口闭合、胶原纤维生成、血管生成和抗炎作用。总之,5叶黄素/CPT水凝胶敷料有望成为促进糖尿病伤口愈合的候选材料。此外,本研究为基于CMC的水凝胶敷料中天然植物抗氧化剂联合用于治疗慢性伤口提供了新的见解。

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