Smart Hydrogel\nDressing Enhances the Healing of Chronic\nInfectious Diabetic Wounds through Dual-Barrier Drug Delivery Action

Chronic diabetic wounds struggle to heal due to drug-resistant\nbacterial infections, oxidative stress microenvironment, and immune\ndysfunction. At present, the disease has become a huge clinical challenge.\nMultifunctional hydrogels with antibacterial, antioxidant, and anti-inflammatory\nproperties are becoming an emerging trend in the treatment of chronic\nwounds. However, matching different bioactive functions with the wound\nhealing process to sequentially exert antibacterial, antioxidant,\nanti-inflammatory, and immunomodulatory functions remains a significant\nchallenge. In this research, a hydrogel dressing with bactericidal\nand anti-inflammatory properties was synthesized by crafting a pH/ROS-responsive\nscaffold from phenylboronic acid-grafted hyaluronic acid (HA-PBA)\nand 4-arm-PEG-dopamine (4A-PEG-Dopa), employing dynamic borate ester\nbonds. This structure was then infused with the antimicrobial peptide\n(AMP) and ROS-sensitive micelle mPEG-TK-PLGA loaded with quercetin\n(QC). This dressing embodied a dual-barrier drug delivery mechanism,\nengineered for the prolonged and consistent liberation of QC. In the\nexperiment, the hydrogel dissociated within the acidic microenvironment\nof diabetic wounds, thereby liberating the encapsulated micelles and\nAMP. Upon further dissociation, the micelles release QC due to the\nROS-abundant microenvironment, which could relieve oxidative stress\nand encourage M2 polarization of macrophage via the Akt/STAT6 signaling\npathway. Therefore, this smart delivery system, developed through\nour innovative approach, holds promise for treating chronic infectious\ndiabetic wounds.