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Oxidative stress-responsive hydrogen sulfide-releasing composite hydrogel for refractory diabetic wounds repair

Jingyue Wang,Yilei Ding,Jianan Liu,Yian Chen,Yuanfeng Wang,Ansha Zhao

While revascularization is acknowledged as a critical process in wound healing, the scenario becomes more complex when considering diabetic wounds. In such cases, oxidative stress introduces two primary challenges that impede the healing process: ensuring the directional movement of functional cells to the wound site and combating the heightened risk of infection. These challenges underscore the need for innovative therapeutic strategies that can effectively address these restrictions in the context of diabetic wound healing. Hydrogen sulfide (H 2 S) acts as a signaling gas and shows significant therapeutic potential in biomedical research. In this study, we encapsulate Allicin, a natural H 2 S donor, in selenium micelles that specifically respond to oxidative stress. To create the GMA (Allicin@Micelle-GelMA) Composite hydrogel system, we utilize Methacrylic anhydride gelatin (GelMA) hydrogel as a matrix and form it through in-situ light curing. This composite system effectively addresses the problem of healing deep, narrow, and lengthy wounds that pose a challenge, as well as preventing nonspecific sudden release of H 2 S. Additionally, the composite hydrogel system promotes angiogenesis, anti-inflammatory, antibacterial, and antioxidant properties. It also facilitates the directional movement of stem cells and macrophages, as demonstrated through the chicken embryo chorioallantoic membrane vascular test and the establishment of a diabetes wound model that is difficult to heal. Consequently, we conclude that the GMA composite hydrogel has the potential to serve as a versatile skin wound dressing that can effectively respond to oxidative stress.