A biomimetic nanofiber composite hydrogel with tissue adhesion, self-healing and antibacterial ability for infected wound healing.

Abstract

Skin injuries represent a significant clinical challenge, as conventional dressings frequently induce secondary trauma and microbial infiltration due to suboptimal barrier properties, ultimately delaying tissue repair. Ideal wound dressings should not only replicate the structure of native skin tissue but also create an environment conducive to cell viability. In this study, an injectable nanofiber composite self-healing hydrogel was developed for treating infected wounds. The antimicrobial properties of the hydrogel were achieved through the adsorption of branched polyethyleneimine (PEI) on gelatin fibers, while its self-healing capabilities were enhanced via Schiff base reactions and its tissue adhesion was strengthened by the incorporation of dopamine. Results demonstrated that the hydrogel exhibited strong biocompatibility and antimicrobial activity, promoted macrophage polarization towards the M2 phenotype, effectively suppressed inflammation, and facilitated wound healing in an infected wound model. STATEMENT OF SIGNIFICANCE: Wound infections pose a significant clinical challenge, often impeding healing and, in severe cases, leading to ulceration or life-threatening complications. In this study, a gelatin nanofiber composite hydrogel (PGF@ALG/PLGA hydrogel) functionalized with branched polyethyleneimine (PEI) was developed to address infected wounds through a biomimetic structure and enhanced pro-healing properties. The gelatin nanofibers within the hydrogel matrix facilitated electrostatic immobilization of PEI, effectively mitigating its inherent cytotoxicity by restricting free cationic charge exposure while ensuring localized surface enrichment. The resulting hydrogel exhibited robust tissue adhesion and autonomous self-healing capability. In infected wound models, the PEI-modified nanofibers within PGF@ALG/PLGA hydrogels demonstrated obvious antibacterial efficacy and promoted macrophage polarization to the M2 phenotype, synergistically accelerating the transition from the inflammatory phase to tissue regeneration. These findings underscore the therapeutic potential of PGF@ALG/PLGA hydrogel as a multifunctional platform for managing chronic infected wounds.