Pore size of porous hydroxyapatite as the cell-substratum controls BMP-induced osteogenesis.
To elucidate the biochemical mechanism of osteogenesis, the effect of matrix geometry upon the osteogenesis 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 500-600 microns, was prepared. A block (approximately 5 x 5 x 1 mm, 40.0 mg) of each hydroxyapatite ceramics was combined with 4 micrograms of recombinant human BMP-2 and implanted subcutaneously into the back skin of rat. Osteoinductive ability of each implant was estimated by quantifying osteocalcin content and alkaline phosphatase activity in the implant up to 4 wk after implantation. In the ceramics of 106-212 microns, the highest alkaline phosphatase activity was found 2 wk after implantation, and the highest osteocalcin content 4 wk after implantation, consistent with the results observed with particulate porous hydroxyapatite [Kuboki, Y. et al. (1995) Connect. Tissue Res. 32: 219-226]. Comparison of the alkaline phosphatase activities at 2 wk and the osteocalcin contents at 4 wk after implantation revealed that the highest amount of bone was produced in the ceramics implants with pore size of 300-400 microns. In the ceramics with smaller or larger pore sizes, the amount of bone formation decreased as the pore size deviated from 300-400 microns. The results indicated that the optimal pore size for attachment, differentiation and growth of osteoblasts and vascularization is approximately 300-400 microns. This study using chemically identical but geometrically different cell substrata is the first demonstration that a matrix with a certain geometrical size is most favorable for cell differentiation.
Tsuruga
E
E
Department of Biochemistry, School of Dentistry, Hokkaido University, Sapporo.
Takita
H
H
Itoh
H
H
Wakisaka
Y
Y
Kuboki
Y
Y
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D018786:Bone Substitutes / Q000737:chemistry*; D001842:Bone and Bones / Q000166:cytology; D002448:Cell Adhesion; D017886:Durapatite / Q000737:chemistry*; D006801:Humans; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D016062:Porosity; D051381:Rats
D019485:Bone Morphogenetic Proteins; D018786:Bone Substitutes; D015675:Osteocalcin; D017886:Durapatite; D000469:Alkaline Phosphatase