Caffeic acid-mediated photodynamic multifunctional hyaluronic acid-gallic acid hydrogels with instant and enduring bactericidal potency accelerate bacterial infected wound healing

The emergence of drug-resistant bacteria poses significant challenges in wound treatment. Antimicrobial photodynamic therapy has emerged as an effective approach to eliminating bacteria by inducing oxidative stress without causing drug resistance. Here, we developed a natural hyaluronic acid (HA)-gallic acid (GA) conjugation-based hydrogel combined with herbal photosensitizer-caffeic acid (CA), which exhibits self-healing ability, shape adaptability, biodegradability, and robust tissue adhesion. Under exposure to 400 nm light, caffeic acid acts as a photosensitizer, generating reactive oxygen species and oxidative damage to bacterial cell membranes. Furthermore, the presence of GA and CA displayed a continuous inhibitory effect on bacterial growth, along with antioxidant properties that promote wound healing even after the cessation of light exposure. The antibacterial mechanism of the HA-GA/CA hydrogel against MRSA, S. aureus, and E. coli was investigated through various assays measuring ATP levels, Zeta potential, hydroxyl radicals (·OH) generated by light irradiation, and biofilm clearance rate. Additionally, hydrogel's application in treating MRSA-infected wounds in mice under light irradiation demonstrated rapid wound-healing effects and biocompatibility. Overall, HA-GA/CA hydrogel provides a sustainable, antibiotic-free alternative for treating MRSA-infected wounds.