Engineered Microalgae Promoting Angiogenesis for Diabetic Bone Regeneration.

Diabetic bone defects, characterized by hyperglycemia-induced accumulation of advanced glycation end products (AGEs), oxidative stress, and an inflammatory microenvironment, face impaired angiogenesis, and compromised bone regeneration. This study demonstrates that palladium (Pd)-engineered 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-inflammatory M1 macrophages toward the anti-inflammatory M2 phenotype, and promotes the proliferation, migration, and tube formation of HUVECs under hyperglycemic conditions. Moreover, SPP treatment upregulates the HIF-1α/VEGF signaling axis. To further validate its therapeutic potential, SPP was incorporated into a 3D-bioprinted hydrogel scaffold (SPP@Gel), which accelerated the repair of critical-sized cranial defects in diabetic rats by reducing AGEs accumulation and inflammatory marker expression in the defect area, promoting local angiogenesis. Overall, this study establishes the feasibility of using Pd nanoparticle engineering to potentiate the bioactivity of natural microalgae, offering an exploratory strategy for diabetic bone regeneration.