Engineering osteoinductive hydroxyapatite via zinc and strontium co-substitution

concentrations for bone tissue engineering applications. Accordingly, Zn-substituted, Sr-substituted, and Zn/Sr co-substituted hydroxyapatite nanoparticles (Zn-HAp, Sr-HAp, and ZnSr-HAp) were synthesised and systematically characterised. Physicochemical analysis revealed that, in comparison with single-ion substitution, Zn/Sr co-substitution significantly altered crystal nucleation and growth behaviour while preserving phase purity. Biological evaluation using bone-derived cells demonstrated that ZnSr-HAp nanoparticles were highly biocompatible and significantly enhanced cell attachment, proliferation, and matrix mineralisation compared to pristine and single ion-substituted HAp. Furthermore, ZnSr-HAp treatment markedly upregulated the expression of collagen type I (COL I) and osteocalcin (OCN), indicating the promotion of both early extracellular matrix formation and late-stage osteogenic maturation. Collectively, these findings demonstrate a synergistic effect of Zn and Sr co-substitution in enhancing the osteoinductive and osteoconductive properties of HAp. Overall, Zn/Sr co-substituted hydroxyapatite nanoparticles represent a promising bioactive platform for advanced bone regeneration applications.