Energetic metabolism-regulatory glycopeptide hydrogel accelerates pressure ulcer wound repair

Pressure ulcers are a serious health-threatening condition, with wounds that are difficult to heal due to metabolic disorders, insufficient energy supply, and impaired tissue regeneration. Although current clinical treatments for chronic wounds show some reparative effects, ideal healing outcomes remain unattainable. Inspired by the chemical composition of the natural extracellular matrix (ECM), this study developed a multifunctional glycopeptide hydrogel (GMI^gel) via dynamic chemical crosslinking of glucomannan and bioactive peptides. GMI^gel integrates antibacterial activity with mitochondrial metabolism modulation, offering a promising strategy for the treatment of pressure ulcers. This hydrogel not only rapidly eradicates bacterial infection, providing a sterile microenvironment for chronic wounds, but also significantly restores mitochondrial morphology and function, including inhibiting glycolysis and enhancing tricarboxylic acid (TCA) cycle activity, thereby promoting macrophage metabolic reprogramming and inducing their polarization toward the reparative M2 phenotype. In vivo experiments demonstrated that GMI^gel effectively cleared methicillin-resistant Staphylococcus aureus from the wounds and significantly alleviated local inflammatory responses. More importantly, GMI^gel markedly induced macrophage polarization toward the reparative M2 phenotype, with higher than those in the control and chitosan (CS) groups. Concurrently, this treatment also significantly promoted angiogenesis, with CD31⁺ vessel density reaching 4.6 times and 1.9 times that of the control and CS groups. These combined effects accelerated the healing of infected pressure ulcers by approximately 20% (P < 0.01). This study confirms that GMI^gel, through targeted cellular metabolic regulation, can synergistically exert antibacterial, anti-inflammatory, and pro-repair effects, offering a novel strategy for the treatment of Methicillin-resistant Staphylococcus aureus (MRSA)-infected pressure ulcer wounds.