Glucose-responsive hyaluronic acid/carboxymethyl chitosan-based hydrogel with on-demand berberine release for...

Chronic diabetic wound healing is hindered by bacterial colonization, dysregulated inflammation, and oxidative stress. Conventional wound dressings fail to adapt to the dynamic wound microenvironment, limiting their therapeutic efficacy. An innovative glucose-responsive and self-healing hydrogel (OAC-10BH) was developed, integrating oxidized hyaluronic acid modified with 3-aminophenylboronic acid (OHA-3-APBA), carboxymethyl chitosan (CMCS), and berberine hydrochloride (BH), to address these challenges. The hydrogel network was constructed via reversible Schiff base linkages and borate ester bonds, exhibiting glucose-triggered drug release behavior. Specifically, the elevated glucose levels within the wound permeate the hydrogel matrix, selectively binding to phenylboronic acid groups. This interaction cleaves the borate ester bonds, reducing the hydrogel's crosslinking density and enabling the controlled release of BH. OAC-10BH exhibits broad-spectrum antimicrobial efficacy, achieving >96 % inhibition against E. coli, S. aureus, and MRSA within 24 h and disrupting established biofilms. In addition, its therapeutic mechanism reduces oxidative stress and promotes a balanced inflammatory response by clearing ROS (reactive oxygen species), leveraging inherent anti-inflammatory effects. In the diabetes mouse model, OAC-10BH achieved 99.7 % wound closure within 14 days via bacterial eradication, inflammation modulation, angiogenesis, and extracellular matrix (ECM) remodeling. This glucose-sensing platform offers a closed-loop strategy for intelligent diabetic wound management.