Abstract
Background: Wound healing impaired by multidrug-resistant bacteria (MDRB) remains a significant clinical challenge, primarily due to persistent bacterial infection, excessive inflammation, overproduction of reactive oxygen species (ROS), and compromised vascularization. Importantly, the cellular metabolic state plays a vital role in regulating cellular behavior, and strategies aimed at enhancing cellular energy metabolism hold great promise for promoting tissue regeneration. Methods: Herein, we present a multifunctional and bioactive silk fibroin-poly(citrate-curcumin)-metal-based biomimetic matrix (SFPC) designed to treat methicillin-resistant staphylococcus aureus (MRSA)-infected wounds by promoting bioenergy-induced angiogenesis. Results: SFPC exhibited robust broad-spectrum antimicrobial, anti-inflammatory, intracellular ROS-scavenging, and pro-angiogenic properties. Notably, SFPC effectively enhanced mitochondrial membrane potential and promoted adenosine triphosphate (ATP) production in HUVECs, thereby accelerating angiogenesis through the controlled release of citrate. Conclusions: This study suggests that SFPC is a promising alternative for the treatment of MRSA infected wounds and provides a facile approach for the development of a multifunctional hydrogel that promotes the healing of MRSA infected wounds at the level of cellular energy biology.