Cohesion-adhesion balanced microsphere-reinforced hydrogel promotes bacterial-infected wound healing by modulating the inflammatory microenvironment

Chronic infected wounds experience delayed healing due to persistent bacterial colonization, excessive accumulation of reactive oxygen species (ROS), and prolonged inflammation. Although adhesive hydrogels are promising as wound dressings, challenges in achieving strong tissue adhesion coupled with adequate internal cohesion have hindered their clinical application. Here, we developed a multifunctional adhesive hydrogel designed around a cohesion–adhesion balance strategy for infected wound treatment. Specifically, we synthesized a gelatin microsphere-reinforced adhesive hydrogel (Gel-GM) by embedding gelatin microspheres (GMs) and the antimicrobial peptide LL-37 into a dopamine-grafted alginate network. Incorporation of GMs strengthened the hydrogel network through increased intermolecular interactions, enhancing cohesive strength while preserving sufficient exposed catechol groups to ensure interfacial adhesion. In vitro studies demonstrated that Gel-GM significantly improves ROS scavenging, promotes anti-inflammatory M2 macrophage polarization, and enhances fibroblast proliferation and migration. Additionally, LL-37 confers potent antibacterial activity by disrupting bacterial membranes via electrostatic interactions. In vivo evaluations revealed that Gel-GM possesses robust antibacterial and anti-inflammatory properties, effectively accelerating infected wound healing. Collectively, this study emphasizes the potential of employing a cohesion–adhesion balance approach to engineer multifunctional adhesive hydrogels for managing infected wounds.