# Enzyme responsive antimicrobial hyaluronan-nanocellulose hybrid wound dressings for the treatment of infected wounds

## TL;DR

This paper introduces a smart wound dressing that releases antimicrobial peptides only in infected wounds, reducing bacteria and improving healing.

## Contribution

A novel enzyme-responsive hybrid hydrogel wound dressing with localized antimicrobial peptide delivery is developed.

## Key findings

- SOAP-loaded dressings showed potent activity against clinical wound pathogens in vitro.
- The dressings significantly reduced bacterial load and accelerated wound healing in a porcine model.
- Infection-associated enzymes triggered AMP release and hydrogel breakdown.

## Abstract

Wound infections pose a substantial clinical challenge and an escalating healthcare burden, further complicated by the rapid increase in multidrug-resistant bacteria. Antimicrobial peptides (AMPs) offer an alternative to conventional antibiotics, but their rapid degradation, hemolytic activity, and potential cytotoxicity complicate systemic delivery and can have negative impact on wound healing. Here we show a bacterial nanocellulose hyaluronan (BC-HA) hybrid hydrogel wound dressing functionalized with mesoporous silica nanoparticles (MSNs) for localized, enzyme responsive delivery of a sequence optimized antimicrobial peptide (SOAP) for treatment of infected wounds. The dressings provide moisture retention and excellent skin conformability while enabling infection-triggered AMP release by bacterial and host proteases. In vitro, SOAP-loaded dressings showed potent activity against clinical wound pathogens while remaining compatible with human primary dermal fibroblasts and keratinocytes. In a contaminated porcine wound model, the dressings significantly reduced bacterial load while accelerating wound re-epithelialization and epithelial maturation compared to the controls. By integrating a dual-function hydrogel that promotes healing and provides on-demand antimicrobial activity, critical limitations in the use of AMPs in wound care can be addressed, providing new possibilities to treat infected wounds.

Image 1

•Bacterial nanocellulose is grafted with an enzyme-responsive hyaluronic acid hydrogel.•Hyaluronic acid network degrades selectively in infected wounds environments.•Antimicrobial peptides are loaded into mesoporous silica carriers inside the hydrogel.•Infection-associated enzymes accelerate peptide release and hydrogel breakdown.•Dressings lower bacterial burden and enhance re-epithelialization in infected wounds.

Bacterial nanocellulose is grafted with an enzyme-responsive hyaluronic acid hydrogel.

Hyaluronic acid network degrades selectively in infected wounds environments.

Antimicrobial peptides are loaded into mesoporous silica carriers inside the hydrogel.

Infection-associated enzymes accelerate peptide release and hydrogel breakdown.

Dressings lower bacterial burden and enhance re-epithelialization in infected wounds.