Abstract
Bacterial infections and chronic inflammation disrupt wound immune homeostasis and impair healing progression. Herein, we report a novel nanofibrous dressings that exhibits a synergistic antibacterial-anti-inflammatory effect through the integration of the physical barrier properties of electrospun nanofibers, the antimicrobial activity of biomacromolecule polylysine (PLys), and the anti-inflammatory and antioxidant effects of natural macromolecule tannic acid (TA). Using poly(L-lactide-co-ε-caprolactone) (PLCL) as the base biomaterial, sequential surface modification with TA and PLys enhanced wettability and introduced a positive surface charge, yielding a dressing with exceptional cytocompatibility and potent antimicrobial activity against Staphylococcus aureus. In vitro studies revealed that the PLys-grafted, mussel-inspired nanofibers (PLys@TA@PLCL) modulated the wound microenvironment by suppressing fibroblast-to-myofibroblast differentiation, mitigating pro-inflammatory responses, and accelerating extracellular matrix (ECM) deposition and remodeling. In vivo evaluations demonstrated that PLys@TA@PLCL nanofibers effectively reduced bacterial burden and prevented yellow scab formation, while accelerating healing of infected wounds. Notably, these dressings exhibited robust anti-inflammatory activity during early stages of repair and promoted near-complete wound closure by 2 weeks, accompanied by enhanced collagen synthesis, skin regeneration, and hair follicle neogenesis. Collectively, these findings highlight the therapeutic potential of PLys@TA-modified nanofibrous dressings for managing chronic, full-thickness wounds.