Biomimetic Calcium-Silicate Cements Support Differentiation of Human Orofacial Mesenchymal Stem Cells

IntroductionHuman orofacial bone mesenchymal stem cells (OFMSCs) from maxilla and mandible have robust osteogenic regenerative properties on the basis of our previous reports that demonstrate phenotypic and functional differences between jaw and axial bone mesenchymal stem cells in same individuals. Furthermore, a combination of OFMSCs with bioactive calcium-releasing cements can potentially improve OFMSC multilineage differentiation capacity, but biocompatibility of calcium-silicate cements with OFMSCs is still unclear. We tested the hypothesis that material extracts of calcium-releasing calcium-silicate cements support biomimetic microenvironment for survival and differentiation of human OFMSCs.MethodsTwo experimental calcium-silicate cements, (1) calcium-silicate mineral powder (wTC) containing dicalcium and tricalcium-silicate, calcium sulfate, and calcium chloride and (2) wTC doped with alpha-tricalcium phosphate (wTC-αTCP), were designed and prepared. Cement setting times were assessed by Gilmore needles, ability to release calcium and hydroxyl ions was assessed by potentiometric methods, and OFMSC attachment to calcium-silicate discs was assessed. Calcium-silicate material extracts were tested for ability to support OFMSC survival and in vitro/in vivo differentiation.ResultsFewer OFMSCs attached to calcium-silicate discs relative to tissue culture plastic (P = .001). Extracts of calcium-silicate cements sustained OFMSC survival, maintained steady state levels of vascular cell adhesion molecule-1, alkaline phosphatase, and bone sialoprotein while up-regulating their respective gene transcripts. Adipogenic and in vivo bone regenerative capacities of OFMSCs were also unaffected by calcium-silicate extracts.ConclusionsIon-releasing calcium-silicate cements support a biomimetic microenvironment conducive to survival and differentiation of OFMSCs. Combination of OFMSCs and calcium-silicate cement can potentially promote tissue regeneration in periapical bone defects.