Sequential Dual‐Biofactor Release from the Scaffold of Mesoporous HA Microspheres and PLGA Matrix for Boosting Endogenous Bone Regeneration

Abstract The combined design of scaffold structure and multi‐biological factors is a prominent strategy to promote bone regeneration. Herein, a composite scaffold of mesoporous hydroxyapatite (HA) microspheres loaded with the bone morphogenetic protein‐2 (BMP‐2) and a poly(DL‐lactic‐co‐glycolic acid) (PLGA) matrix is constructed by 3D printing. Furthermore, the chemokine stromal cell‐derived factor‐1 α (SDF‐1 α ) is adsorbed on a scaffold surface to achieve the sequential release of the dual‐biofactors. The results indicate that the rapid release of SDF‐1 α chemokine on the scaffold surface effectively recruits bone marrow‐derived mesenchymal stem cells (BMSCs) to the target defect area, whereas the long‐term sustained release of BMP‐2 from the HA microspheres in the degradable PLGA matrix successfully triggers the osteogenic differentiation in the recruited BMSCs, significantly promoting bone regeneration and reconstruction. In addition, these structures/biofactors specially combining scaffold exhibit significantly better biological performance than that of other combined scaffolds, including the bare HA/PLGA scaffold, the scaffold loaded with SDF‐1 α or BMP‐2 biofactor alone, and the scaffold with surface SDF‐1 α and BMP‐2 dual‐biofactors. The utilization of mesoporous HA, the assembly method, and sequential release of the two biofactors in the 3D printed composite scaffold present a new method for future design of high‐performance bone repairing scaffolds.