Nanoparticle-Reinforced Hydrogel with a Well-Defined Pore Structure for Sustainable Drug Release and Effective Wound Healing.

Impaired chronic wounds are a common complication of diabetes. Inhibited angiogenesis and dysfunctional inflammation render diabetic wound healing a critical challenge. Herein, a sustainable therapeutic composite hydrogel is presented for diabetic wound healing, consisting of a cocktail formulation of anti-inflammatory and local anesthetic nanoparticles incorporated into a composite hydrogel. The surface-modified drug nanoparticles are loaded into the biocompatible hydrogels and cross-linked with a gel precursor to enhance the structure. The sustainable delivery system achieves more than 90% drug release, with a total therapy duration tunable from 4 to 72 h. Through the long-lasting anti-inflammatory and analgesic effects of the composite hydrogel, diabetic wounds are swiftly transitioned into the proliferation phase, augmenting the survival and migration of keratinocytes and facilitating neovascularization and collagen alignment in diabetic wounds. These effects significantly improve the wound healing rate and skin regeneration process, achieving a healing rate that is 17 times that of untreated wounds. This study demonstrates that the hydrogel platform loaded with cocktail drug nanoparticles is promising for the rapid healing of diabetic wounds.