Glucose oxidase-mineralized scaffolds with multiple bioactivities for accelerated diabetic bone regeneration

Diabetic bone defects pose a significant clinical challenge due to impaired healing under hyperglycemia. However, no effective therapy is available to treat diabetic bone defect in clinic. This study engineers a biomimetic 3D-printed scaffold for diabetic bone regeneration by integrating glucose oxidase-mineralized amorphous calcium phosphate (GOx@ACP) nanoparticles into a gelatin methacryloyl (GelMA) hydrogel. Biomineralization encapsulates GOx within ACP, enhancing enzymatic stability and enabling glucose-responsive degradation. The scaffold exerts dual therapeutic actions consuming glucose to alleviate hyperglycemia while generating trace H₂O₂ to promote angiogenesis, alongside releasing osteogenic ions (Ca²⁺/PO₄³⁻) upon ACP degradation. The scaffold's sustained degradation profile (with 61.02% mass retention after 28 days) ensures matched release kinetics of ions and enzymes, thereby synergistically promoting bone regeneration. In vitro, the scaffold significantly enhances bone marrow stromal cell proliferation, osteogenic differentiation with upregulated OPN/OCN/Runx2/Col-Ⅰ expression, and endothelial tubulogenesis. In diabetic rat cranial defects, the implantation significantly accelerated bone regeneration, with the bone volume (BV/TV) reaching approximately 52% by the 12th week. This enzyme-mineralized platform demonstrates promising potential for diabetic bone tissue engineering.