Engineering multifunctional intracellular energy metabolism enhanced polycitrate-based hydrogel for MRSA infected wound therapy

Multidrug resistant-bacteria (MDRB) impaired wound repair and regeneration is still a challenge, due to the refractory infection, excessive inflammation and deficient vascularization. Herein, an anti-inflammatory, antibacterial, vascularized and bioenergetic-active hydrogel (PCDO-Co) for treating MDRB infection and accelerating wound healing is reported. The PCDO-Co hydrogel was formed by cross-linking of enamine and hydrogen bonding between oxidized hyaluronic acid (OHA) and citric acid-based polymers (PCDA) with chelating Co²⁺. The PCDO-Co possesses self-healing, hemostatic, anti-bacterial, anti-inflammatory, and reactive oxygen species (ROS) scavenging activities. PCDO-Co effectively induces the upregulation of HIF-1α and significantly promotes expression of VEGF, cell migration, tube formation, angiogenesis. PCDO-Co can accelerate injured skin tissue repair and regeneration by participating in the cellular tricarboxylic acid cycle (TCA) cycle, enhancing mitochondrial membrane potential, and boosting energy metabolism. The in vivo studies demonstrated that PCDO-Co could effectively promote methicillin-resistant staphylococcus aureus (MRSA) infected wound healing and skin regeneration. This work implies that the cellular energy reinforcing and antibacterial functions design on bioactive materials is a promising alternative for the treatment of MDRB infected tissue repair.