This study investigated whether hydroxyapatite nanoparticles modified with 3-aminopropyltriethoxysilane (HA-NPs-APTES) and carrying microRNA-302a-3p (miR) within a 3D-printed tricalcium phosphate/hydroxyapatite (TCP/HA) scaffold could enhance bone regeneration in a critical-sized mouse calvarial defect. Two modification methods (M1, M2) were compared. M2, involving surface application of HA-NPs-APTES-miR, showed superior miR delivery, downregulating COUP-TFII and upregulating RUNX2 mRNA. In vivo, M2 scaffolds significantly increased BV/TV and reduced unfilled spaces compared to controls. Histomorphometry showed earlier new bone formation in the M2 group. The modified TCP/HA scaffold facilitated miR delivery and enhanced bone regeneration.
