pH/glucose dual-responsive drug release hydrogel loaded with tannic acid and gallium ions enhances diabetic wound healing upon bacterial infection

Chronic infected diabetic wounds pose a significant global health challenge. This study explores a novel therapeutic approach using a [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SBMA), 3-(acrylamidophenyl)boronic acid (AAPBA) and tannic acid (TA) based pH/glucose dual-responsive drug release hydrogel loaded with gallium ions (Ga3+) (named “STAG hydrogel”) to enhance the treatment of Staphylococcus aureus (S. aureus) -infected diabetic wounds. The hydrogel was designed to respond to the acidic and hyperglycemic microenvironment typical of chronic diabetic wounds, ensuring controlled release of its antimicrobial components. In vitro, the hydrogel demonstrated significant antibacterial activity against S. aureus and Escherichia coli (E. coli), reducing bacterial viability and inhibiting biofilm formation. Furthermore, the hydrogel exhibited excellent biocompatibility, promoting fibroblast viability and migration, crucial for wound healing. In vivo studies using a diabetic mouse model confirmed the hydrogel’s efficacy in accelerating wound closure, reducing bacterial load, and enhancing collagen deposition and CD31 and VEGF levels. The dual-responsive drug release hydrogel also modulated the inflammatory response, promoting M2 macrophage polarization, which is essential for tissue repair and regeneration. These findings highlight the potential of the STAG hydrogel as an effective therapeutic strategy for managing chronic infected diabetic wounds.