Osteogenic Nanozymes for Diabetic Bone Regeneration via Synergistic Antioxidant and Osteoinductive Functions

Bone regeneration under diabetic conditions remains a formidable challenge, predominantly due to persistent oxidative stress, chronic inflammation, and impaired osteogenic potential of stem cells. Nanozymes have been widely employed to modulate oxidative stress and inflammation, and are considered promising candidates for diabetic bone regeneration. However, they have a limited osteogenic capacity, which substantially hinders their direct application in bone repair. Here, a series of osteogenic ion-doped Prussian blue (PB) nanozymes was designed to endow classical antioxidant PB with osteoinductive capacity, among which copper-doped PB (CuPB) exhibits optimal performance. The screened CuPB nanozyme effectively scavenges various types of excessive reactive oxygen species, suppresses inflammation, and simultaneously promotes osteogenic differentiation via activation of the phosphoinositide 3-kinase/protein kinase B (PI3K-Akt) pathway. In type II diabetic rats, both the CuPB nanoparticulate formulation and the CuPB-functionalized three-dimensional scaffold pronouncedly enhance bone regeneration in models of periodontitis-associated alveolar bone loss and cranial defects, respectively. This study establishes an integrated "osteogenic nanozyme" platform that synergistically couples antioxidant and osteoinductive functions.