Comprehensive Review of Hydrogel-Mediated Strategies for Diabetic Wound Healing.

Diabetic chronic wounds (particularly diabetic foot ulcers) are difficult to heal due to factors such as high glucose levels, infection, and inflammatory imbalance. In severe cases, they can lead to tissue necrosis and amputation. Hydrogel materials, as moist wound dressings, possess high water content, biocompatibility, and tunability, making them an important platform for promoting diabetic wound healing. In recent years, novel smart hydrogels have been developed to integrate multiple functions. They respond to abnormal stimuli in the wound microenvironment-such as acidic pH, high glucose levels, or excessive reactive oxygen species-to trigger the release of drugs, delivering on-demand antimicrobial, antioxidant, and anti-inflammatory effects. Simultaneously, they modulate immune responses (promoting macrophage polarization toward the M2 type) and stimulate angiogenesis, creating a microenvironment conducive to tissue regeneration. Some hydrogels incorporate antimicrobial agents, anti-biofilm components, or photothermal/photodynamic agents to effectively eliminate drug-resistant pathogens and control infections. Others serve as carriers for delivering stem cells and their exosomes, enhancing cell survival rates and releasing growth factors to accelerate wound healing. This review systematically summarizes recent advances in hydrogel strategies for diabetic wound treatment, focusing on stimulus-responsive hydrogels, antimicrobial and immune modulation mechanisms, pro-angiogenic and oxygen-supplying therapies, smart dressings and monitoring technologies, integration of stem cells and exosomes, as well as hydrogel injection, self-healing, and adhesion properties. Based on this, we analyze challenges and prospects for clinical translation of these strategies. Collectively, functionalized hydrogels hold promise as multifunctional therapeutic platforms for diabetic non-healing wounds. They offer a multi-pronged approach to disrupt the vicious cycle of "infection-inflammation-tissue destruction" thereby achieving more efficient wound healing.