OICC Press Journal of Nanostructure in Chemistry 2193-8865 15 3 2025 06 29 Synthesis, Surface Chemical Characterization, and Enhanced Osteoblast Response of Strontium-Substituted Hydroxyapatite Nanoparticles for Alveolar Bone Regeneration 10.57647/jnsc.2025.1503.12 EN Jing Qiao First Clinical Division, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, 100034, China Guanghao Wu School of Medical Technology, Beijing Institute of Technology, Beijing, 100081, China Sicong Jiang Division of Thoracic and Endocrine Surgery, University Hospitals and University of Geneva, Geneva 4,1211, Switzerland Zhang Yong First Clinical Division, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, 100034, China Feifei Ma First Clinical Division, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, 100034, China https://orcid.org/0000-0003-3319-9880 Jian Jiao First Clinical Division, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, 100034, China Journal Article 2025 06 29 Strontium-substituted hydroxyapatite (Sr-HA) nanoparticles hold significant potential for alveolar bone regeneration due to their dual capacity to modulate bone remodeling. In this study, we synthesized Sr-HA nanoparticles with varying Sr/(Ca+Sr) molar ratios (0%, 25%, 50%, 75%, 100%) via wet chemical precipitation and systematically characterized their structural, surface, and biological properties. X-ray diffraction, FTIR, and solid-state NMR analyses confirmed a progressive anisotropic lattice expansion and reduction in carbonate and water incorporation with increasing strontium content. Surface analyses using XPS and ToF-SIMS revealed modest Sr²⁺ enrichment at the nanoparticle periphery, correlating with changes in ion release kinetics. In vitro assays using primary rat calvarial osteoblasts demonstrated enhanced proliferation, alkaline phosphatase activity, mineral deposition, and osteogenic gene expression in response to Sr50, which also showed a favorable burst-plus-sustain Sr²⁺ release profile. These results support a mechanistic model in which moderate Sr incorporation promotes osteogenesis through combined surface-enrichment effects and ionic signaling. Collectively, the findings identify Sr50 as an optimized composition for promoting osteoblastic activity and highlight compositional tuning as a viable strategy for developing next-generation graft materials for alveolar ridge preservation.