Double Network Hydrogel for Rapid Repair of Chronic Diabetic Wounds via Spatiotemporal Drug Release

Diabetic wound repair is severely impeded by a multifaceted environment containing bacterial infection, persistent inflammation, and impaired angiogenesis, resulting in a disrupted physiological repair process. Restoring an orderly repair process in diabetic wounds remains a critical unmet need. To address this, a double-network hydrogel system is developed with distinctive release kinetics tailored for staged therapeutic effects. The first network, GAG, provides an initial release to exert an anti-inflammatory effect. The second network, Zn/PCA/TAU, ensures sustained release to improve cell migration and collagen deposition. Due to the disrupted self-assembly of GA and the feature of the imine bond, by incorporating those two hydrogels, the double-network hydrogel is capable of modulating its degradation rate with a reduced nanoscale aggregate size, enabling the spatiotemporal controlled release of GAG and Zn/PCA/TAU. An in vivo result confirmed that the DN hydrogel can accelerate wound repair by reducing inflammation, promoting epithelialization, and facilitating collagen deposition. This DN hydrogel with spatiotemporal controlled release property exhibits broad applicability and significant promise for advancing diabetic wound healing.