Growth and differentiation of human bone marrow osteoprogenitors on novel calcium phosphate cements

Materials that augment bone cell proliferation and osteogenic activity have important therapeutic implications for bone regeneration and for use in skeletal reconstruction and joint replacement. We have studied the growth and interactions of human bone marrow cells on a variety of new cement composites in vitro. These cement materials are composed of calcium-deficient hydroxyapatites, carbonated apatite and amorphous calcium phosphate. Cell proliferation was significantly reduced and cell differentiation increased in the presence of these cements compared with cells cultured on tissue culture plastic. Alkaline phosphatase, one of the markers of the osteoblast phenotype, was dramatically stimulated by 3 of the 4 cements examined between day 4 and day 10, above levels observed following culture of human osteoblasts on plastic alone. Photomicroscopic examination demonstrated growth and close integration of bone marrow cells and 3 of the composites. Longer term marrow cultures (15 day) on the cements confirmed the stimulation of cell differentiation over proliferation. From these studies, enhanced osteoblastic differentiation was observed on a 70% carbonated apatite, which has a composition similar to bone mineral, whereas, cell toxicity was observed on cells grown on amorphous calcium phosphate. This in vitro culture system demonstrates the use of human bone marrow cells for the potential evaluation of new biomaterials and the development of a novel carbonated apatite that may be of potential use in orthopaedic implant

Effects of novel calcium phosphate cements on human bone marrow fibroblastic cells

The identification and characterization of biocompatible materials that augment bone cell proliferation and osteogenic activity have important therapeutic implications in skeletal reconstruction and joint replacement. In the present study, we have examined the effects of three biocements, biocement H, calcium-deficient apatite; biocement F, apatite + CaHPO(4); biocement D, carbonated apatite + CaHPO(4) + CaCO(3) and an amorphous calcium phosphate (ACP) proposed as implant fixing materials, on the growth, differentiation, and cell surface interaction of human bone marrow fibroblastic cells. These cells are known to be progenitors of osteoblasts, chondroblasts, adipocytes, myoblasts, and reticulocytes. Alkaline phosphatase enzyme activity, a marker of the osteoblast phenotype, was increased by a factor of two- to sixfold on carbonated apatite, one- to sixfold on apatite and three- to 10-fold on calcium-deficient apatite, over levels observed on plastic. Cell proliferation was significantly reduced. Photomicroscopic examination indicated high biocompatibility with close adhesion of the bone marrow fibroblastic cells to composites D, F, and H. Longer term marrow cultures (15 days) confirmed the stimulation of cell differentiation, as assessed by collagen production, over cell proliferation, of cells grown on carbonated apatite. Enhanced osteoblastic differentiation was observed on a 70% carbonated apatite, which has a composition similar to bone mineral, whereas cell toxicity was observed on cells grown on amorphous calcium phosphate. This in vitro human bone marrow fibroblast culture system provides a simple and effective method for the evaluation of new biomaterials. The development of these novel cements may be of potential use in orthopedic implant