Strontium-baicalein coated β-tricalcium phosphate scaffold enhances diabetic bone regeneration via synergistic ROS scavenging and osteogenic activation

Abstract Conventional bone repair materials, such as β-tricalcium phosphate (β-TCP) scaffolds, are widely used in orthopaedic applications due to their excellent biocompatibility and osteoconductivity. However, their regenerative efficacy is markedly compromised under diabetic microenvironments, as they lack the ability to counteract persistent oxidative stress and hyperglycemia-induced impairment of osteogenic activity. To address this limitation, we developed a strontium-baicalein (SrB) coated β-TCP scaffold (β-TCP@SrB) with integrated antioxidative and osteoinductive functions. In this system, baicalein provides robust cytoprotective and reactive oxygen species (ROS) scavenging effects under high-glucose (HG) conditions. Meanwhile, its polyphenolic structure enables strong interfacial adhesion to β-TCP and coordination-driven assembly with Sr2+ ions, which serve as potent osteogenic cues. In vitro studies demonstrated that β-TCP@SrB scaffolds effectively reduced excessive ROS accumulation and significantly enhanced osteogenic differentiation of HG-injured bone marrow mesenchymal stem cells, accompanied by activation of the Wnt signaling pathway. Furthermore, in a type 2 diabetic rat calvarial defect model, β-TCP@SrB scaffolds markedly promoted new bone formation compared with unmodified β-TCP scaffolds. Collectively, these results demonstrate a rational and clinically relevant surface-engineering strategy that integrates antioxidation and osteogenesis within a single bioactive interface, providing a promising approach for restoring bone regeneration in diabetes and potentially other metabolically compromised conditions.