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This study demonstrates that palladium (Pd)\u2010engineered Spirulina platensis (SPP) effectively modulates the pathological diabetic bone microenvironment. Compared with native SP, SPP exhibits significantly enhanced capabilities: it reduces intracellular reactive oxygen species (ROS) and AGEs accumulation in endothelial cells, promotes pro\u2010inflammatory M1 macrophages toward the anti\u2010inflammatory M2 phenotype, and promotes the proliferation, migration, and tube formation of HUVECs under hyperglycemic conditions. Moreover, SPP treatment upregulates the HIF\u20101\u03b1\/VEGF signaling axis. To further validate its therapeutic potential, SPP was incorporated into a 3D\u2010bioprinted hydrogel scaffold (SPP@Gel), which accelerated the repair of critical\u2010sized cranial defects in diabetic rats by reducing AGEs accumulation and inflammatory marker expression in the defect area, promoting local angiogenesis. 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