Synthesis of active molecular chitosan with selective molecular weight and its potential to promote wound healing

Chitosan of various molecular weights are known to have biocompatibility, angiogenic, antimicrobial, and in vitro anti-inflammatory effects. However, the intricacies of wound healing using hydrogel formulations in vivo require further investigation. In this study, high-molecular-weight chitosan (HMWC) was sequentially treated with immobilized chitosanase to synthesize active molecular chitosan (AMC). The antimicrobial activity and wound-healing effect of AMC-based hydrogels were evaluated. Two types of AMC-based hydrogel, namely AMC-based hydrogel-h (AMC-h) from the hydrolysis of HMWC and AMC-based hydrogel-w (AMC-w) from water-soluble chitosan, were investigated for efficacy against methicillin-resistant Staphylococcus aureus (MRSA) and in vivo wound healing. Subsequently, 48 full-thickness wounds were created in the BALB/c nude mice. The wounds were treated with AMC-h, AMC-w, or phosphate-buffered saline as controls. Collagen synthesis and the production of VEGF and TGF-β were quantified using ELISA and immunohistochemistry. AMC-h treatment significantly reduced the unhealed wound areas and displayed potent antimicrobial activity. It also promoted higher collagen synthesis and more substantial wound contraction than AMC-w. Taken together, our results demonstrate that AMC-h has the potential to accelerate wound healing using hydrogel formulations by enhancing antimicrobial activity, collagen synthesis, and wound contraction.

Graphical abstract