Chitosan hydrogel encapsulated with LL-37 peptide promotes deep tissue injury healing in a mouse model

作者：Xu Yang, Jinglin Guo, Jing Han, Ruijuan Si, Panpan Liu, Zi-Rui Zhang, Aimin Wang, Ju Zhang · 发表于：Military Medical Research · 年份：2020 · DOI：10.1186/s40779-020-00249-5 · 被引用次数：79 · 研究领域：Antimicrobial Peptides and Activities、Wound Healing and Treatments、Advancements in Transdermal Drug Delivery

BACKGROUND: LL-37 peptide is a member of the human cathelicidin family, and has been shown to promote the healing of pressure ulcers. However, the low stability of this peptide within the wound environment limits its clinical use. Chitosan (CS) hydrogel is commonly used as a base material for wound dressing material. METHODS: CS hydrogel (2.5% w/v) was encapsulated with LL-37. Cytotoxicity of the product was examined in cultured NIH3T3 fibroblasts. Effects on immune response was examined by measuring tumor necrosis factor-α (TNF-α) release from RAW 264.7 macrophages upon exposure to lipopolysaccharides. Antibacterial activity was assessed using Staphylococcus aureus. Potential effect on pressure ulcers was examined using a mouse model. Briefly, adult male C57BL/6 mice were subjected to skin pressure using magnets under a 12/12 h schedule for 21 days. Mice were randomized to receive naked LL-37 (20 μg), chitosan gel containing 20-μg LL-37 (LL-37/CS hydrogel) or hydrogel alone under the ulcer bed (n = 6). A group of mice receiving no intervention was also included as a control. RESULTS: LL-37/CS hydrogel did not affect NIH3T3 cell viability. At a concentration of 1-5 μg/ml, LL-37/CS inhibited TNF-α release from macrophage. At 5 μg/ml, LL-37/CS inhibited the growth of Staphylococcus aureus. The area of the pressure ulcers was significantly lower in mice receiving LL-37/CS hydrogel in comparison to all other 3 groups on days 11 (84.24% ± 0.25%), 13 (56.22% ± 3.91%) and 15 (48.12%...