The synergistic effects of strontium/magnesium-doped calcium silicate cement accelerates early angiogenesis and bone regeneration through double bioactive ion stimulation

Periodontitis-induced alveolar bone defects necessitate the use of bone grafts for optimal therapeutic outcomes. Therefore, synthetic bone grafts exhibiting consistent properties, sufficient amounts, and multiple application forms have been extensively studied. Our previously designed Ca–Si–Mg cement has demonstrated benefits regarding cell proliferation, osteogenesis, and angiogenesis. Similarly, Sr exhibits osteogenic, anti-osteoclastogenic, and angiogenic properties by influencing several intracellular signaling pathways. In this study, we modified the previously established Ca–Si–Mg cement by incorporating Sr, which resulted in the formation of Mg–Sr-calcium silicate (CS) cement. Furthermore, we evaluated its biocompatibility and efficacy in promoting osteogenesis and angiogenesis. The results revealed that the setting time of the cement was extended with the individual incorporation of either Mg or Sr; notably, the setting time of M5S5 (integrating both Sr and Mg in equal proportions) was 2.7 min shorter than that of M5S0 (integrating only Mg). In addition, the presence of Sr enhanced the mechanical strength to an ultimate strength of 1.89 MPa and reduced the biodegradation rate of the Mg-doped CS cement from a weight loss of 13.9 %–11.5 %. Sr and Mg also demonstrated a synergistic effect on cell proliferation, with no observed cytotoxicity in human periodontal ligament cells (hPDLs). Osteogenic markers such as alkaline phosphate, bone sialoprotein, and osteocalcin were significantly expressed in hPDLs under the combined influence of Mg and Sr on osteogenic activity. Similarly, the angiogenesis-related proteins, vascular endothelial growth factor and angiopoietin-1 exhibited considerable enhancement, indicating the angiogenic capability of M5S5. In summary, our in vitro experiments confirmed that M5S5 is a potential candidate for osteogenic substitutes and alveolar bone regeneration, suggesting its potential applicability in clinical practice.