Molecularly engineered IR780SS-integrated hydrogel enables antibacterial phototherapy and regenerative repair of infected wounds

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds present a significant clinical challenge due to persistent inflammation and impaired tissue regeneration. Here, we developed an IR780SS-engineered hydrogel with a hydrogen-bond-regulated network for infected wound treatment. In this system, IR780SS serves not only as a NIR photosensitizer, but also as an active component that interacts with the hydrogel matrix through hydrogen bonding, hydrophobic interactions, and π-π stacking. These interactions improve the stability and dispersion of IR780SS within the hydrogel and help preserve its photoactivity. Under 808 nm NIR irradiation, the hydrogel generates mild local hyperthermia and abundant ROS, producing antibacterial effects through combined action of PTT and PDT mechanisms. This treatment disrupts bacterial membranes and induces severe oxidative damage inside bacterial cells, leading to the near-complete elimination of drug-resistant bacteria. In a MRSA-infected wound model, rapid bacterial clearance promoted the transition from the inflammatory phase to the proliferative phase and resulted in a wound closure rate of 85.6% on day 11. Histological and immunofluorescence analyses further confirmed improved tissue repair, including enhanced re-epithelialization, angiogenic responses, and collagen remodeling, as evidenced by increased cytokeratin 14 (CK14) and smooth muscle actin (α-SMA) expression, together with more organized collagen deposition. These results suggest that integrating IR780SS into a hydrogen-bonded hydrogel not only enables effective antibacterial phototherapy but also facilitates functional wound reconstruction, providing valuable insight into the clinical development of regenerative dressings for MRSA-infected wounds.