Hyaluronic acid-based hydrogel loaded with berberine hydrochloride promotes MRSA-infected wound healing

Antibacterial hydrogels are highly recommended biomaterials for managing chronic wounds. In this study, a berberine hydrochloride-loaded hyaluronic acid/collagen (BH-HA/Col) hydrogel was prepared through an optimization approach. The optimization was performed using HA/Col and EDC/NHS ratios as independent variables while swelling (%) and gel fraction (%) were considered as response parameters. The optimized formulation, which demonstrated optimum swelling (%) and gel fraction (%), was evaluated for its physicochemical properties (FTIR, TGA, SEM) and anti-biofilm effects on Methicillin resistant Staphylococcus aureus (MRSA). The cell viability and migration assays were determined via MTT and wound closure. Histocompatibility was evaluated by H&E and trichrome staining. Finally, in vivo wound healing assays wereconducted in a mouse model of MRSA-infected wounds. FTIR results of the optimized formulation showed that BH was successfully loaded into the hydrogel without changing its structure. Thermal analyses confirmed that the optimized BH-HA/Col hydrogel had higher stability and better crosslinking. SEM images showed smaller pores and a tighter network. This hydrogel-based system exhibited excellent anti-MRSA biofilm effect (59.7 % biofilm eradication in the optimized formulation in the concentration of 156 μg/mL of BH). Furthermore, this formulation showed less cytotoxicity than free BH in the L929 cell line and significantly enhanced wound closure at the later time points. The optimized BH-HA/Col hydrogel promoted angiogenesis and collagen deposition without an inflammatory response.This hydrogel significantly accelerated the healing and re-epithelialization of MRSA-infected wounds. Therefore, this loaded hydrogel could be a promising wound dressing for the treatment of cutaneous infected wounds.