Hydroxyapatite as a Driver of Osteogenic Differentiation in Mesenchymal Stem Cells: A Review of Molecular Mechanisms, Biomaterial Design, and Translational ProspectsA Review

Abstract

Hydroxyapatite (HA), the calcium phosphate mineral that constitutes the inorganic phase of bone, is among the most widely used bioceramics for guiding mesenchymal stem cell (MSC) commitment toward the osteoblastic lineage. This review synthesizes current understanding of how HA drives osteogenic differentiation, covering the biomolecular mechanisms, ionic dissolution and calcium/phosphate signaling, integrin-mediated focal adhesion, and activation of the Wnt/β-catenin, BMP/Smad, and MAPK (ERK1/2, p38) pathways, alongside the biomaterial design strategies that exploit these mechanisms, including porous and three-dimensionally printed scaffolds, polymer–HA composites, ion-substituted HA (strontium, magnesium, zinc), and HA coatings for metallic implants. Clinical and translational applications in orthopedics, craniofacial reconstruction, and dental implantology are discussed alongside persisting barriers, including scaffold degradation kinetics, vascularization of large defects, and the gap between preclinical efficacy and regulatory approval. The review concludes that continued integration of nanostructural control, ion doping, and additive manufacturing represents the most promising route toward clinically translatable, osteoinductive HA based bone graft substitutes.