Apt‐19s‐Functionalized 3D‐Printed Mesoporous Bioactive Glass Scaffold Promotes BMSC Recruitment in Bone Regeneration via SDF‐1α/CXCR4 Axis and MAPK Signaling

Abstract Directional migration and differentiation of stem cells in situ are two essential processes for tissue regeneration. However, transplanted scaffold itself lacks sufficient ability to induce stem cell recruitment. As an artificial synthesized nucleic acid, aptamer 19s (Apt‐19s), with high cost‐effectiveness and bioactivity, demonstrates a robust capacity for specific binding and recruitment of mesenchymal stem cells. In this study, a mesoporous bioactive glass scaffold fabricated via a seamless route of self‐assembly and 3D printing (3D‐MBG), functionalized with Apt‐19s is successfully prepared via physical adsorption and lyophilization with optimized release kinetics and bone marrow‐derived mesenchymal stem cells (BMSCs) recruiting efficiency in vitro. This scaffold significantly enhanced migration and osteogenic differentiation of BMSCs in vitro and in vivo. The mechanism underlying Apt‐19s‐induced BMSCs recruitment is elucidated for the first time, that Apt‐19s promoted BMSCs migration by upregulating stromal cell‐derived factor‐1α (SDF‐1α) gene expression, facilitating SDF‐1α protein translation and secretion, and further activating the SDF‐1α/CXCR4 signaling axis and MAPK pathway. In summary, the Apt‐19s‐functionalized 3D‐MBG scaffold offers an economical and efficient solution for customized bone regeneration in situ, and the elucidation of Apt‐19s‐induced BMSCs recruitment at molecular biological level may shed light on its broader clinical applications.