Hypoxic Microenvironment Reconstruction with Synergistic Biofunctional Ions Promotes Diabetic Wound Healing

Chronic hypoxia and ischemia make diabetic wounds non-healing. Cellular functions of diabetic chronic wounds are inhibited under a pathological environment. Therefore, this work develops a composite hydrogel system to promote diabetic wound healing. The composite hydrogel system consists of epsilon-poly-lysine (EPL), calcium peroxide (CP), and borosilicate glass (BG). The hydrogel supplies continuous dissolved oxygen molecules to the wound that can penetrate the skin tissue to restore normal cellular function and promote vascular regeneration. Biofunctional ions released from BGs can recruit more macrophages through neovascularization and modulate macrophage phenotypic transformation. Combining oxygen-mediated vascular regeneration and ion-mediated inflammatory regulation significantly accelerated diabetic wound healing. These findings indicate that this composite hydrogel system holds promise as a novel tissue engineering material. A composite hydrogel (EPL@CP@BG) is developed for treatment of diabetic wounds. This oxygen and biofunctional ions delivery hydrogel effectively regulates the cell function for angiogenesis, inflammatory, and regeneration. Combining oxygen-mediated vascular regeneration and ion-mediated inflammatory regulation significantly accelerated diabetic wound healing.image