Fungal-derived chitosan-based hydrogels with antimicrobial properties for infectious wound healing

Persistent bacterial infections hinder wound healing by disrupting tissue repair and perpetuating inflammatory states. However, conventional therapies adopting antibiotics and passive dressings could only suppress pathogens temporarily and ignore antibiotic resistance or actively promote regenerative microenvironments. Herein, based on fungal-derived chitosan, guanidinium-functionalized chitosan (GCS) and aldehyde-modified chitosan (ACS) were synthesized, then chitosan hydrogels (SCgel) with self-healing capacity were prepared via the Schiff base reaction between GCS and ACS. Through a simple local injection through a dual-barrel syringe, a protective SCgel hydrogel barrier can be rapidly established on the wound. This hydrogel not only quickly eliminates bacteria in infected wounds but also reduces the level of wound inflammation, thereby promoting wound healing. In infected full-thickness rat wounds, SCgel achieved a 94.5 ± 1.1 % wound closure rate within 14 days, significantly superior to commercial silver-coated Aquacel™ Ag⁺. By integrating potent antimicrobial activity with inflammation control, this design reduces the reliance on systemic antibiotics and addresses the unmet need for microenvironment-responsive wound dressings.