HPLA-Alg core-shell microspheres enable dual-level BMP-2 delivery on porous Ti6Al4V scaffolds for sustained pro-osteogenic activity

Efficient bone regeneration requires scaffolds that combine mechanical strength with controlled osteoinductive factor delivery. Here, we present a porous Ti6Al4V scaffold (PXTC4) functionalized with polydopamine and integrated with dual-level BMP2–PLA–Alg core–shell microspheres (BMP2-HPLA-Alg) for sustained BMP2 release. The PXTC4 scaffold exhibited high porosity (∼75%) and an elastic modulus (∼6.5 GPa) compatible with cortical bone, while the microspheres ensured heparin-mediated BMP2 adsorption, tunable degradation, and reduced initial burst release by 53.5% compared to the single-level BMP2-Alg microspheres. In vitro studies demonstrated enhanced MC3T3-E1 adhesion, proliferation, cytoskeletal organization, early osteogenic differentiation, and late-stage matrix mineralization. These results indicate that BMP2 synergizes with scaffold topography to create a favorable osteogenic microenvironment. This BMP2-HPLA-Alg microsphere-functionalized porous Ti6Al4V scaffold provides a robust platform with mechanical stability and sustained pro-osteogenic activity, offering a promising strategy for bone regeneration that warrants further in vivo investigation.