Application of LL-37-loaded hydrogel for deep tissue injury healing in mouse models

Background: Deep tissue injury is a unique type of pressure injury, the consequences of which, result in the impairment of angiogenesis. There is a present and unmet need for clinically effective therapeutic options. The human antimicrobial peptide, LL-37, has been shown to enhance wound healing in chronic wounds. However, its low stability within the wound environment limits its overall efficacy. Methods: An injectable, biocompatible and thermosensitive chitosan hydrogel embedded with LL-37 (LL-37/CS hydrogel) was developed and the efficacy of these hydrogels on deep tissue injury in mouse models was investigated. Results: The cytotoxicity assay demonstrated that the LL-37/CS hydrogel did not affect Mouse embryonic fibroblast cells (NIH3T3) viability. Moreover, it displayed antimicrobial activity on Staphylococcus Aureus and it also effectively inhibited the expression of TNF-α in vitro inflammatory models induced by LPS. Consistently, levels of mRNA and protein expression of key angiogenesis growth factors were up-regulated (p < 0.05) in the LL-37 hydrogeltreated wounds, compared with untreated wounds in vivo. Moreover, levels of the mRNA expression of inflammation factors were significantly increased (p < 0.05).