Diphasic CeO2 Nanocrystal/Bioactive Glass Nanosphere-Based Composite Hydrogel for Diabetic Wound Healing by Reactive Oxygen Species Scavenging and Inflammation Regulation.

Background: Antioxidant therapy aimed at reducing excessive local oxidative stress is one of the most important strategies for promoting diabetic wound repair. The reversible transformation of Ce³⁺/Ce⁴⁺ in ceria (CeO₂) can reduce excessive local oxidative stress. However, inducing angiogenesis, local anti-inflammatory effects, and other positive effects are challenging. Therefore, ideal dressings for chronic diabetic wound management must concurrently reduce excessive oxidative stress, promote angiogenesis, and have anti-inflammatory effects. Methods: In this study, Ce-doped borosilicate bioactive glasses (BGs) were prepared using the sol-gel method, and CeO₂ nanocrystals (CeO₂-NCs) were precipitated on the glass surface by heat treatment to obtain BG-xCe composite glass nanospheres. Subsequently, nanospheres were modified by amino group and combined with dopamine and acrylamide to obtain BG-xCe/polydopamine/polyacrylamide (PDA/PAM) composite hydrogel. Then, the morphology and properties of composite hydrogels were detected, and the properties to treat the diabetic wounds were also evaluated. Results: The results demonstrated that the BG-10Ce/PDA/PAM composite hydrogel possessed excellent tensile and adhesive properties. In vitro, the migration and angiogenesis of human umbilical vein endothelial cells (HUVECs) and fibroblasts (L929) were enhanced by reducing reactive oxygen species (ROS) levels in the conditioned medium. Animal experiments have shown that CeO₂-NCs in hydrogels effectively scavenge ROS in diabetic wounds, and Sr dissolved from the glassy phase can modulate macrophage polarization to the M2 phenotype. Conclusions: The synergistic effect of both amorphous materials and nanocrystals provides the BG-10Ce/PDA/PAM composite hydrogel with great potential for diabetic wound healing.