Gelatin/hyaluronic acid-based in situ forming hydrogel promotes wound regeneration by the synergy of ROS-scavenging and pro-healing activity.

Abstract

The development of advanced hydrogel dressings that integrate biocompatibility, antioxidant activity and dynamic adaptability remains critical for addressing the complex demands of modern wound management. In this study, we designed a multinetwork hydrogel (GHrCT) through synergistic strategies: A robust covalent network is constructed through photocrosslinked gelatin methacryloyl, while a secondary dynamic network formed via hydrogen bonds and electrostatic interactions is established among dopamine-modified hyaluronic acid (HD), tannic acid (TA) and recombinant collagen type III (rhCol III). Through a series of experiments, we systematically characterized key properties of the hydrogel, including its microscopic morphology, swelling behavior, rheological characteristics and mechanical strength. Biocompatibility was assessed through in vitro assays, while the wound healing efficacy was validated in vivo. In vitro experiments demonstrated that GHrCT hydrogel has interconnected porosity, excellent hemocompatibility and good cytocompatibility. Its strong antioxidant capacity (DPPH scavenging rate of 88.63%) can cope with the excessive accumulation of ROS in the wound microenvironment and reduce the damage caused by oxidative stress. Further, in vivo experiments showed that it could improve wound healing therapy by accelerating epithelial re-formation, angiogenesis and collagen deposition at full-thickness skin defects in SD rats. This study presents a strategy for functionalizing natural polymer hydrogels to enhance wound repair through the synergistic effect of scavenging ROS and promoting repair.