The novel cathelicidin-DM antimicrobial peptide conjugated carbomer and thermosensitive chitosan hydrogel speeds up wound-healing in both non-infected and S. aureus-infected wounds.

Abstract

The emergence of chronic wound infections and bacterial resistance presents substantial clinical challenges that impact millions worldwide. Antimicrobial peptides (AMPs), recognized for their potent antimicrobial properties, are considered promising alternatives to conventional antibiotics in light of escalating drug resistance. In previous research, we isolated an AMP named cathelicidin-DM from Duttaphrynus melanostictus, which exhibited broad-spectrum efficacy against multidrug-resistant bacteria and demonstrated wound-healing capabilities. This peptide represents a novel therapeutic option for treating infected chronic wounds. However, AMPs are susceptible to degradation when applied in the treatment of wound infections, which may compromise their effectiveness. To further advance the application of cathelicidin-DM in wound healing, we developed cathelicidin-DM-carbomer and thermosensitive cathelicidin-DM-chitosan hydrogels. Our results indicated that cathelicidin-DM interacted with both carbomer and chitosan at the molecular level, adhering to the surface of the hydrogels, which exhibit a three-dimensional network structure and favorable rheological properties. Animal experiments demonstrated that these cathelicidin-DM hydrogels exhibited hemostatic capabilities and significantly enhance the healing of both infected and non-infected full-thickness skin wounds in mice when applied as wound dressings. In summary, cathelicidin-DM carbomer and cathelicidin-DM chitosan hydrogels represent a dual-functional materials with both antimicrobial and wound-healing properties, thereby demonstrating considerable potential for clinical application.