Role of geometrical factors of cell-substratum in BMP-induced osteogensis, topology of bone formation

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The effect of matrix geometry upon the osteogenis induced by bone morphogenetic protein (BMP) was studied. A series of five porous hydroxyapatites with different pore sizes, 106-212,212-300,300-400,400-500, and 500-600mum, was prepared. A block (approximately 5x5x1mm, 40.0mg) of each hydroxyapatite ceramics was combined with 4mug of recombinant human BMP-2 and implanted subcutaneously into the back of rat. Osteoinductive ability of each implant was estimated by quantifying osteocalcin content (OC) and alkaline phosphatase activity (ALP) in the implant up to 4 weeks after implantation. Comparison of the ALP at 2 week and the OC at 4 weeks after implantation revealed that the highest amount of bone was produced in the implants with pore size of 300-400mum. In the ceramcs with smaller of larger pore sizes, the amount of formation decreased as the pore size deviated from 300-400mum. The results indicated that the optimal pore size of attachment, differentiation and growth of osteoblasts and vascularization is approximately 300-400mum. This study using chemical identical but geometrically different cell substrata is the first demonstration that a matrix with a certain geometrical size is most favorable for cell differentiation.