Bioglass (R) 45S5 stimulates osteoblast turnover and enhances bone formation in vitro: Implications and applications for bone tissue engineering

We investigated the concept of using bioactive substrates as templates for in vitro synthesis of bone tissue for transplantation by assessing the oste ogenic potential of a melt-derived bioactive glass ceramic (Bioglass(R) 45S 5) ill vitro. Bioactive glass ceramic and bioinert (plastic) substrates wer e seeded with human primary osteoblasts and evaluated after 2, 6, and 12 da ys. Flow cytometric analysis of the cell cycle suggested that the bioactive glass-ceramic substrate induced osteoblast proliferation, as indicated by increased cell populations in both S (DNA synthesis) and G2/M (mitosis) pha ses of the cell cycle. Biochemical analysis of the osteoblast differentiati on markers alkaline phosphatase (ALP) and osteocalcin indicated that the bi oactive glass-ceramic substrate augmented osteoblast commitment and selecti on of a mature osteoblastic phenotype. Scanning electron microscopic observ ations of discrete bone nodules over the surface of the bioactive material, from day 6 onward, further supported this notion. A combination of fluores cence, confocal, transmission electron microscopy, and X-ray microprobe (SE M-EDAX) examinations revealed that the nodules were made of cell aggregates which produced mineralized collagenous matrix. Control substrates did not exhibit mineralized nodule formation at any point studied up to 12 days. In conclusion, this study shows that Bioglass 45S5 has the ability to stimula te the growth and osteogenic differentiation of human primary osteoblasts. These findings have potential applications for tissue engineering where thi s bioactive glass substrate could be used as a template for the formation o f bioengineered bone tissue.