Hyperbaric oxygen-generating hydrogels.

Oxygen plays a critical role as a substrate for metabolism and as a signaling molecule regulating cellular activities. In particular, hyperbaric oxygen has been demonstrated to facilitate wound healing processes, including cell proliferative activity, tissue growth, and vascular recruitment, via transient oxidative stress in surrounding tissues. In this study, we report hyperbaric oxygen-generating (HOG) hydrogels comprising thiolated gelatin (GtnSH) that can form hydrogel networks in situ via a calcium peroxide-mediated oxidative cross-linking reaction with oxygen generation. We demonstrate that the HOG hydrogels rapidly generate molecular oxygen up to hyperoxic levels and maintain hyperoxic levels for up to 12 days in vitro and 4 h in vivo. The HOG hydrogel enhances cell proliferative activities of human dermal fibroblasts and endothelial cells, which are closely related to wound healing and angiogenesis. Moreover, the HOG hydrogel promotes wound healing with enhanced tissue infiltration and vascular recruitment in vivo. The HOG hydrogels is a new type of oxygen-generating biomaterials that have great potential as advanced hydrogel materials for tissue regenerative medicine applications, including the treatment of wound and vascular disorders.