A hydrogen sulfide-releasing alginate dressing for effective wound healing

Abstract

For wounds with heavy exudate levels, a dressing that can help to absorb wound exudate and improve the wound healing process is highly desired. Hydrogen sulfide (H₂S) has been recognized as an important gasotransmitter that can improve angiogenesis which is crucial for wound healing. In this study, a functional sodium alginate (SA) dressing with H₂S-releasing property (SA/JK-1) was fabricated by incorporating JK-1 molecule, a pH-dependent H₂S donor, into SA sponge. The resultant SA/JK-1 sponge provided a moist and protective healing environment and was capable of releasing H₂S consistently under acidic pH condition by absorbing exudate at the wound interface. The H₂S release of JK-1 donor was prolonged by the SA sponge compared with JK-1 in solution. Cell study in vitro indicated that SA/JK-1 not only exhibited good cyto-compatibility, but also improved fibroblast proliferation and migration. In addition, the effects of the SA/JK-1 dressing on wound healing was evaluated using an in vivo full thickness dermal defect model, which revealed that SA/JK-1 can significantly improve wound healing process with enhanced granulation tissue formation, re-epithelialization, collagen deposition and angiogenesis, due to the H₂S released from JK-1. Taken together, our results showed that SA dressing doped with H₂S donor could potentially serves as an effective wound healing strategy. STATEMENT OF SIGNIFICANCE: The gasotransmitter H₂S has been proven to improve the wound healing process in nanofibrous dressing due to its biological functions on angiogenesis. However, for non-healing wounds with heavy exudates, a wound dressing that can absorb wound exudates and controlled gasotransmitter release to improve the wound healing process is still in urgent need. Here we fabricated a sodium alginate (SA) sponge incorporated with H₂S donor JK-1 (SA/JK-1), which showed strong water uptake capability, and released H₂S under acidic condition. The SA/JK-1 sponge exhibited biocompatibility to fibroblasts and promoted cell migration in vitro, and exhibited obviously positive influence on wound healing in vivo. This H₂S donor doped alginate wound dressing represents a promising strategy for treatment of non-healing wound.

Keywords: Hydrogen sulfide; Sodium alginate; Sponges; Wound healing; pH-dependent.