Strontium/Silicon/Calcium‐Releasing Hierarchically Structured 3D‐Printed Scaffolds Accelerate Osteochondral Defect Repair

Abstract Articular cartilage defects are a global challenge, causing substantial disability. Repairing large defects is problematic, often exceeding cartilage's self‐healing capacity and damaging bone structures. To tackle this problem, a scaffold‐mediated therapeutic ion delivery system is developed. These scaffolds are constructed from poly(ε‐caprolactone) and strontium (Sr)‐doped bioactive nanoglasses (SrBGn), creating a unique hierarchical structure featuring macropores from 3D printing, micropores, and nanotopologies due to SrBGn integration. The SrBGn‐embedded scaffolds (SrBGn‐µCh) release Sr, silicon (Si), and calcium (Ca) ions, which improve chondrocyte activation, adhesion, proliferation, and maturation‐related gene expression. This multiple ion delivery significantly affects metabolic activity and maturation of chondrocytes. Importantly, Sr ions may play a role in chondrocyte regulation through the Notch signaling pathway. Notably, the scaffold's structure and topological cues expedite the recruitment, adhesion, spreading, and proliferation of chondrocytes and bone marrow‐derived mesenchymal stem cells. Si and Ca ions accelerate osteogenic differentiation and blood vessel formation, while Sr ions enhance the polarization of M2 macrophages. The findings show that SrBGn‐µCh scaffolds accelerate osteochondral defect repair by delivering multiple ions and providing structural/topological cues, ultimately supporting host cell functions and defect healing. This scaffold holds great promise for osteochondral repair applications.