Research Progress on Advanced Responsive Hydrogels for Diabetic Wound Healing

Diabetic wounds are difficult to heal due to their complex pathological microenvironment (e.g., hyperglycemia, abnormal pH fluctuations, reactive oxygen species overload, and overexpression of matrix metalloproteinases).Conventional dressings, which rely on a single drug release mode, are inadequate for achieving precision therapy.Hydrogels, as an emerging class of wound dressings, offer unique advantages in treating irregular wounds.In recent years, smart responsive hydrogels have demonstrated significant advantages in diabetic wound therapy by dynamically modulating drug release mechanisms.Currently, the responsiveness of hydrogels is primarily achieved through two forms: endogenous environmental responses and exogenous stimuli.Endogenously responsive drug-controlled release hydrogels can sense environmental changes in diabetic wounds to achieve on-demand drug release: glucose-responsive hydrogels, pH-sensitive hydrogels, reactive oxygen species-responsive hydrogels, and matrix metalloproteinase-responsive hydrogels perceive the microenvironmental changes in diabetic wounds and dynamically release anti-inflammatory and antibacterial agents to promote the wound to enter a normal healing process.In addition, exogenous physical stimuli (e.g., electric field and ultrasound) enhance drug penetration and controlled release capability by modulating gel swelling, electrophoretic migration, or structural disintegration.These multimodal drug delivery systems, by spatiotemporally matching the dynamic changes of the wound microenvironment, synergistically regulate key processes including inflammation, antibacterial activity, angiogenesis, and tissue remodeling, significantly improving drug bioavailability and circumventing the risk of drug resistance, and are expected to promote the clinical translation of smart dressings.