Interconnected Porous Hydroxyapatite Scaffolds Functionalized by the Peptide DP7-C Incorporating miR-26a with Enhanced Osteogenic Activity for Critical Bone Defect Regeneration

The reconstruction of large critical bone defects remains a major challenge in clinical practice. The multifunctional scaffolds modified by miRNA with osteogenic induction have become an effective strategy for bone regeneration. Herein, an interconnected porous hydroxyapatite (HA) scaffold was prepared for bone regeneration. First, the porous PLGA microspheres were obtained by the double emulsification solvent evaporation method and loaded with the DP7-C/miR-26a complex. Then, the functionalized scaffold was prepared by a template-leaching technique and modified with the above microspheres. The scaffold possessed interconnected porous microstructures with a high porosity of 64%, efficient compressive strength of 10.54 kPa, and controlled release ability of 21 days. In vitro experiments suggested that the prepared scaffold showed good cytocompatibility and the potential to promote osteogenic differentiation of rat BMSCs. Moreover, in the cranial critical bone defect model, the scaffold was demonstrated to possess good in vivo biocompatibility and osteogenic efficacy. Overall, the functionalized scaffold prepared in this study will provide a potential therapeutic strategy for the treatment of critical bone defects.