Dynamic defect-engineered ceria nanozyme-embedded electron-donor hydrogel for diabetic bone defect repair

Diabetic bone defect repair remains a formidable challenge owing to hyperglycemia-induced oxidative stress, chronic inflammation, and vascular dysfunction within the pathological microenvironment. Although conventional hydrogels exhibit favorable biocompatibility, their static and single-functional characteristics are insufficient to address the dynamic and multifactorial nature of diabetic bone regeneration. Herein, we developed an electron-donating hydrogel system based on GG, CMCS, DMOG, and CeO₂ nanozymes for the treatment of diabetic bone defects. Within this platform, the GG/CMCS network served as an electron donor, while DMOG functioned as a "bioelectronic shuttle" bridging the interface between the GG/CMCS matrix and CeO₂ nanozymes. This synergistic interaction continuously drove the Ce^3 +/Ce⁴⁺ redox cycling of CeO₂ nanozymes, enabling in situ regeneration of oxygen vacancies and efficient scavenging of ROS, thereby facilitating bone regeneration. The engineered hydrogel exhibited an interconnected porous architecture, excellent swelling behavior, controllable degradability, robust mechanical support, and sustained drug-release capability. Furthermore, in vivo diabetic bone defect models confirmed its superior capacity to accelerate bone matrix deposition and mineralization. Collectively, this work not only presents a highly promising therapeutic strategy for diabetic bone defect repair, but also provides new insights into the rational design of dynamic regenerative biomaterials for complex pathological microenvironments.