Development of a hydrogel-based drug delivery system for wound infection management with enhanced recombinant Reg3A bioactivity.

Reg3A, a member of the regenerating islet-derived protein family, possesses both antibacterial and trophic effects, offering substantial benefits in the treatment of bacteria-induced wound infections. To overcome the challenges of protein drug inactivation and degradation in the hostile microenvironment of severely infected wounds, a multifunctional hydrogel dressing composed of polyvinyl alcohol (PVA), the bifunctional crosslinker TSPBA (TPA), and recombinant Reg3A protein (rReg3A) has been developed. The TPA-PVA/rReg3A hydrogel responds to infection-induced reactive oxygen species (ROS) through dynamic boronate ester bonds. Meanwhile, it releases the active rReg3A protein in a sustained manner, thereby delivering prolonged robust antibacterial and wound-healing properties. It was demonstrated that TPA-PVA/rReg3A hydrogel exhibited significant bactericidal activity against both Staphylococcus aureus (S. aureus) and methicillin-resistant Staphylococcus aureus (MRSA). In the MRSA-induced severe wound infection murine model, TPA-PVA/rReg3A hydrogel effectively promoted wound healing by clearing pathogenic bacteria, enhancing re-epithelialization, and stimulating hair follicle formation. As expected, the therapeutic effect of the TPA-PVA/rReg3A hydrogel was obviously better than that of the active rReg3A alone. In conclusion, our study provides a promising therapeutic strategy for managing severe wound infections by enhancing the bioactivity of antimicrobial proteins.