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

Abstract

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 (HO). CMC hydrogel matrix was in situ converted by limited hydrolysis by a cellulase into substrates accepted by cellobiose dehydrogenase (CDH) for continuous production of HO (30 μM over 24 h). This dual-enzyme catalyzed in situ HO 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.

Biomimetic recyclable microgels for on-demand generation of hydrogen peroxide and antipathogenic application

“…Although this hydrogel system exhibited strong antimicrobial property against gram-positive bacteria, H 2 O 2 was not generated in situ . A carboxymethyl cellulose (CMC)–based hydrogels that contained cellobiose dehydrogenase, an enzyme that catalyze CMC while generating H 2 O 2 as a byporduct, demonstrated in situ release of 0.03 mM of H 2 O 2 for 24 h [65]. This hydrogel inhibited the growth of both E. coli and Staphylococcus aureus .…”

Flexible electrical stimulation device with Chitosan-Vaseline® dressing accelerates wound healing in diabetes

“…Diabetic foot ulcers require long courses of treatment and remain highly susceptible to infections; these wounds have become a major cause of lower limb amputations not directly associated with external trauma [ 2 ]. The increased morbidity associated with diabetic wounds and the costs associated with long-term care of affected individuals have a significant negative economic impact on the healthcare economy in China [ 3 ]. Conventional treatments of diabetic wounds include debridement and frequent dressing changes; these modalities often do not result in a reliable or satisfactory outcome in terms of rapid wound closure [ [4] , [5] , [6] , [7] ].…”

Stabilization and Controlled Release of Microencasulated Hydrogen Peroxide for Wound Treatment Applications

“…; Huber et al . ). These approaches may incorporate the enzyme substrate into the hydrogel or may rely on the presence of the substrate in wound exudate.…”

“…Another approach to utilizing hydrogels and H 2 O 2 in topical wound treatment includes the incorporation of enzymes such as cellobiose dehydrogenase or glucose oxidase into a hydrogel, resulting in generation of H 2 O 2 in situ (Sakai et al 2013;Huber et al 2017). These approaches may incorporate the enzyme substrate into the hydrogel or may rely on the presence of the substrate in wound exudate.…”