Magnesium (Mg2 +), Strontium (Sr2 +), and Zinc (Zn2 +) Co-substituted Bone Cements Based on Nano-hydroxyapatite/Monetite for Bone Regeneration

New bone cement type that combines Sr2 + /Mg2 + or Sr2 + /Zn2 + co-substituted nano-hydroxyapatite (n-HAs) with calcium phosphate dibasic and chitosan/gelatin polymers was developed to increase adhesion and cellular response. The cements were physicochemically described and tested in vitro using cell cultures. All cements exhibited quite hydrophilic and had high washout resistance. Cement releases Ca2 + , Mg2 + , Sr2 + , and Zn2 + in concentrations that are suitable for osteoblast proliferation and development. All of the cements stimulated cell proliferation in fibroblasts, endothelial cells, and osteoblasts, were non-cytotoxic, and produced apatite. Cements containing co-substituted n-HAs had excellent cytocompatibility, which improved osteoblast adhesion and cell proliferation. These cements had osteoinductive potential, stimulating extracellular matrix (ECM) mineralization and differentiation of MC3T3-E1 cells by increasing ALP and NO production. The ions Ca2 + , Mg2 + , Zn2 + , and Sr2 + appear to cooperate in promoting osteoblast function. The C3 cement (HA-SrMg5%), which was made up of n-HA co-substituted with 5 mol% Sr and 5 mol% Mg, showed exceptional osteoinductive capacity in terms of bone regeneration, indicating that this new bone cement could be a promising material for bone replacement.