Antimicrobial Peptide-Decorated Wound Scaffold Fights Infection and Flips Macrophages to Healing Mode

Cathelicidin-BF-decorated hyaluronan scaffold (HAG-g-C) provided dual antibacterial and anti-inflammatory function, killing S. aureus and E. coli while driving M1-to-M2 macrophage polarization and accelerating infected wound healing in mice.

Designed HAG-g-C scaffold by cross-linking hyaluronan with gallic acid-modified gelatin and decorating with cathelicidin-BF antimicrobial peptide. Tested antibacterial activity against S. aureus and E. coli in vitro. Assessed macrophage polarization (M1→M2). Evaluated wound healing in S. aureus-infected full-thickness skin defect mouse model over 12 days.

Infected wounds are a major clinical challenge, especially with rising antibiotic resistance. A wound dressing that simultaneously kills bacteria AND shifts the immune response from inflammation to healing addresses both problems at once — potentially reducing healing time and antibiotic use for infected wounds.

This study exemplifies the trend toward 'smart' wound dressings that do more than passively cover wounds. By combining an antimicrobial peptide with an immune-modulating scaffold, it addresses the two sequential challenges of infected wound healing: first clear the infection, then promote tissue repair. The use of a natural AMP (cathelicidin-BF) rather than a conventional antibiotic reduces resistance concerns.

Mouse model — wound healing differs between mice and humans. Only tested against two bacterial species. Long-term degradation profile of the scaffold not fully characterized. Manufacturing complexity and cost vs. conventional wound dressings not assessed. Single antimicrobial peptide — synergy with additional antimicrobials not explored.