Facile Double-Injection Strategy for the Engineering of Versatile Multiresponsive Hydrogels Encapsulating Drug-Loaded Micelles for Promoting Diabetic Wound Healing

Diabetic wound usually accompanied by adverse factors such as hyperglycemia, oxidative stress damage, and inflammatory response is a typical refractory chronic wound. An insufficient regulation of the wound microenvironment is the limiting factor of diabetic wound healing. A drug-loaded micelle is a potential material for the treatment of diabetic wounds. Herein, an injectable, self-healable, and multiresponsive hydrogel (hydrogel@MIC&bFGF) was developed for the integrated diabetic wound therapy by a facile double-injection strategy. Meanwhile, the anti-inflammatory acetyl-11-keto-beta-boswellic acid (AKBA) from a medicinal plant loaded in the hyaluronic acid-based micelles (MIC@AKBA) was encapsulated in the hydrogel along with basic fibroblast growth factor (bFGF). Hydrogel@MIC&bFGF had integrated rheology properties, antioxidant properties, and multiresponse abilities that realized the sustained release of AKBA and bFGF to treat inflammation and promote wound healing in response to glucose, reactive oxygen species, and an acidic environment. In vitro and in vivo experiments substantiated that hydrogel@MIC&bFGF showed the desired therapeutic effects for the treatment of full-thickness skin defects in diabetic rats, which promoted wound healing by reducing inflammation and oxidative stress while accelerating angiogenesis. This study provides a potential strategy for drug-loaded hydrogels for diabetic wound treatment.