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.