Preparation and Characterization of Trimethyl Chitosan /Hyaluronic Acid Composite Encapsulated with LL37 to Promote Wound Healing in an Animal Model

Abstract

Wound treatment is one of the most prevalent concerns and economic burden in healthcare system. Because of antibacterial and re-epithelialization properties, trimethyl chitosan (TMC) has the potential to be used in wound healing dressing. Hyaluronic acid (HA), the main component of the extracellular matrix is capable to activate specific cell signals involved in fibroblast proliferation and new vessel formation, improving the quality of the scars. LL37 peptide promotes wound healing, angiogenesis and also has potential antimicrobial properties. Hence, we aimed to fabricate LL37 encapsulated in TMC-HA composite as a novel topical wound dressing and evaluated its efficacy to accelerate wound closure in an animal model. Composites were optimized based on physical properties such as, porosity, swelling, biodegradation, and mechanical properties. The release of LL37 from the optimized composite (3:3 v/v) was completed during 8 h using bicinchoninic acid assay (BCA) protein quantification kit. LL37-loaded TMC-HA composites displayed antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa. Animal experiments demonstrated the complete wound healing in the group that received LL37-loaded TMC-HA following 16 days of treatment. Based on histological studies, the formation of advanced granulation tissue with significantly higher collagen deposition and re-epithelialized tissues were observed in LL37-loaded TMC-HA-treated wounds. In conclusion, we successfully developed a biodegradable wound healing dressing that promoted healing processes in mice wound model contributed to simultaneous positive effects of the polymers and LL37.