Dynamic hydrogel with environment-adaptive autonomous wound-compressing ability enables rapid hemostasis and inflammation amelioration for hemorrhagic wound healing

Abstract

Severe trauma wound management remains a crucial challenge in the clinics owing to the uncontrollable bleeding and acute inflammatory responses. To achieve rapid hemostasis and reduce local inflammation of large hemorrhagic wounds, we proposed a composite hydrogel dressing through the free radical polymerization of methacrylate gelatin (GelMA), bisphosphonic acid (BP) and cyclodextrin (CD)-modified hyaluronic acid (HA) and loaded with anti-inflammatory drug resveratrol (RES) through supramolecular inclusion. After implantation into bleeding wounds, the hydrogel could electrostatically enrich blood cells and platelets around the wound area to accelerate thrombosis and also increase its own weight to compress local blood vessels for reducing blood loss. Moreover, the cross-linking degree of the HG-CB-based hydrogels could be enhanced in a self-evolving manner through coordination between BP and blood-derived iron ions, leading to increasing biomechanical performance to avoid hydrogel rupture and secondary bleeding. In addition, the hydrogel continuously released RES to increase secretion of anti-inflammation factors, which may stimulate fibroblast migration and accelerate collagen deposition at the wound site. Overall, the HG-CB-based composite hydrogels exhibited excellent rapid hemostatic properties for treating large bleeding wounds and accelerated wound repair via RES-mediated inflammation amelioration, which may provide an approach for managing severe traumatic wounds in the clinics.