Enhancing\nBone Regeneration\nand Osteogenic Quality\nby <i>n</i>‑HA Internalized Osteoblasts Synergized\nwith ON Protein: Mechanistic Insights

Bone scaffolds offer hope for oral\njawbone repair, yet\nimproving\ntheir osteogenic performance remains a clinical challenge. This study\ninvestigates a novel approach to enhance early bone formation and\nosteogenic quality by coloading hydroxyapatite (HA)internalized\nosteoblasts (OHA) and osteonectin (ON) onto various scaffolds. Our\nfindings demonstrated that the OHA could effectively facilitate the\nearly bone regeneration by providing rapid calcium and phosphorus\nion release via lysosome-mediated HA degradation, while the ON protein\nhelps in ion deposition, cell proliferation, and matrix mineralization.\nWhen the PHA (PCL+HA) scaffold was incorporated with both the OHA\nand ON, the scaffold exhibited superior pro-osteogenic performance,\ndriven by synergistic effects of rapid ion release from the OHA, slow\nion release from the PHA, and upregulation of osteogenesis-related\ngenes. The analyses of mechanisms revealed that the OHA activated\nMAPK and PI3K–Akt pathways, while ON stimulated calcium and\nWnt signaling, collectively promoting the osteogenic potential. The\nstrategy presented in this study paves a promising way for the development\nof advanced bone scaffolds to improve the bone regeneration quality.