Sustained Oxygenation Accelerates Diabetic Wound Healing by Simultaneously Promoting Epithelialization and Angiogenesis, and Decreasing Tissue Inflammation

Abstract

Non-healing diabetic wound is one of the most common complications for diabetic patients. Chronic hypoxia is among the prominent factors that delay the wound healing process. Therefore, sustained oxygenation to alleviate hypoxia is hypothesized to promote diabetic wound healing. Yet it cannot be achieved by current clinical approaches including hyperbaric oxygen therapy. Herein, we developed a sustained oxygenation system consisting of oxygen-release microspheres and a reactive oxygen species (ROS)-scavenging hydrogel. The hydrogel was used to capture the ROS that is elevated in the diabetic wounds, and that may be generated due to oxygen release. The sustainedly released oxygen augmented survival and migration of keratinocytes and dermal fibroblasts; promoted angiogenic growth factor expression, and angiogenesis in the diabetic wounds; and decreased M1 macrophage density. These effects led to a significant increase of wound closure rate. These findings reveal that sustained oxygenation alone without using drugs is capable of healing diabetic wounds.