Glycosaminoglycan-Based Hydrogel Delivery System Regulates the Wound Microenvironment to Rescue Chronic Wound Healing

Chronic wounds cannot proceed through the normal, orderly, and timely sequence of repair. The adverse cycle between excess reactive oxide species (ROS) and a persistent inflammatory response is an important mechanism of impaired wound healing. Herein, by combining the intrinsic bioactivities of natural polysaccharides and natural drugs, a glycosaminoglycan-based hydrogel delivery system is proposed to regulate the wound microenvironment. Dynamic supramolecular cross-linking enables the hydrogel to easily encapsulate the drug and fully fill the wound area. As the backbone of the hydrogel, heparin captures inflammatory chemokines at the wound site, while hyaluronic acid mimics the function of ECM. The hydrophobic drug curcumin has been ingeniously encapsulated in the hydrogel through micellization, thereby exerting good ROS scavenging ability and anti-inflammatory activity. Evaluations in diabetic mice showed that this antioxidant and anti-inflammatory hydrogel was effective in reducing the influx of immune cells at the wound site and in down-regulating the inflammatory response. Accelerated wound healing was also observed, as evidenced by faster re-epithelialization and better ECM remodeling. The proposed hydrogel can regulate the microenvironment of wounds from multiple aspects and thereby achieve regression of wound repair, which may provide a new therapeutic strategy for chronic wounds.