Bioinspired zwitterionic lysine glycopolymers: Enhancing wound repair through microenvironment modulation for bacterial elimination and optimal immunoregulation

Abstract

Bacterial infected wounds pose a significant threat to patient survival, necessitating prompt and effective therapeutic intervention. Biomaterials that are responsive to wound microenvironments, possess well-defined structures and are facile to fabricate are favored for fulfilling their mission of efficient wound repair. Drawing inspiration from the immunoregulatory properties of natural zwitterionic capsular polysaccharides (ZPS) and glucomannan (GM) as well as the biogenesis of nitric oxide (NO), this study introduces the zwitterionic lysine glycopolymers (ZLGs), which harmoniously integrate the antibacterial, anti-fouling and immunoregulatory functions into one entity, to effectively promote the healing of infected wounds without addition of any external cytokines or molecular drugs. The ZLGs, exhibiting excellent cytocompatibility, restore sustained NO biogenesis (∼7.1 μM) in wound environment and thus to clean bacteria fast and effectively (12 h clearance rate for S. aureus: 97 %; E. coli: 92 %). Notably, the cell-membrane affinitive ZLGs induce efficient aggregation of mannose receptors and polarize the macrophages to M2 phenotype via the PI3K-Akt/STAT3 pathway, resulting in a synergistic enhanced polarization efficiency increasement of 105 %, as compare to the cumulation of individual building modules. The bioinspired ZLGs accelerate the repair of S. aureus infected wounds in vivo, highlighting the significance of this multi-in-one construction strategy for chronic wound treatment.