A Dual-Enzyme Hydrogen Peroxide Generation Machinery in Hydrogels Supports Antimicrobial Wound Treatment

The aging population and accompanying diseases like diabetes resulted in an increased occurrence of chronic wounds. Topical wound treatment with antimicrobial agents to inhibit bacterial invasion and promote wound healing is often associated with difficulties. Here, we investigated the potential of succinyl chitosan (SC)-carboxymethyl cellulose (CMC) hydrogels which constantly release clinically relevant levels of hydrogen peroxide (H₂O₂). CMC hydrogel matrix was in situ converted by limited hydrolysis by a cellulase into substrates accepted by cellobiose dehydrogenase (CDH) for continuous production of H₂O₂ (30 μM over 24 h). This dual-enzyme catalyzed in situ H₂O₂ generation system proved its antimicrobial activity in a zone of inhibition (ZOI) assay best simulating the application as wound dressing and was found to be biocompatible toward mouse fibroblasts (95% viability). The hydrogels were thoroughly characterized regarding their rheological properties indicating fast gel formation (<3 min) and moderate cross-linking (1.5% strain, G' = 10 Pa). Cooling (fridge conditions) was found to be the simple on/off switch of the enzymatic machinery which is of great importance regarding storage and applicability of the bioactive hydrogel. This robust and bioactive antimicrobial hydrogel system overcomes dosing issues of common topical wound treatments and constitutes a promising wound healing approach for the future.