In vivo evaluation of a novel porous hydroxyapatite to sustain osteogenesis of transplanted bone marrow-derived osteoblastic cells

Biosynthetic bone grafts are considered to contain one or more of three cri tical components: osteoprogenitor cells, an osteoconductive matrix, and ost eoinductive growth factors. The basic requirements of the scaffold material are biocompatibility, mechanical integrity, and osteoconductivity. A major design problem is satisfying these requirements with a single composite. I n this study, we hypothesize that one composite that combines bone marrow-d erived osteoblasts and a novel mechanical reinforced porous hydroxyapatite with good biocompatibility and osteoconductivity (HA/BMO) can reach these r equirements. A novel sintered porous hydroxyapatite (HA) was prepared by th e following procedures. The HA slurry was foamed by adding polyoxyethylenel aurylether (PET) and mixing. The pores were fixed by crosslinking PEI with diepoxy compounds and the HA porous body was sintered at 1200 degreesC for 3 h. The HA sintered porous body had a high porosity (77%), and was complet ely interconnected. Average pore diameter was 500 mum and the interconnecti ng path 200 mum in diameter. The compressive (17 MPa) and three-point bendi ng (7 MPa) strengths were high. For in vivo testing, the 2-week subcultured HA/BMO (+) composites were implanted into subcutaneous sites of syngeneic rats until 8 weeks after implantation. These implants were harvested at dif ferent time points and prepared for the biochemical analysis of alkaline ph osphatase activity (ALP) and bone osteocalcin content (OCN), and histologic al analysis. ALP and OCN in the HA/BMO group were much higher than those in the HA without BMOs control group 1 week after implantation (p < 0.001). L ight microscopy revealed mature bone formation in the HA/BMO composite 4 we eks after implantation. In the SEM study, mineralized collagenous extracell ular matrix was noted in HA/BMO composite 2 weeks after implantation with n umbers of active osteoblasts. We conclude that the composite of the novel H A and cultured BMOs has osteogenic ability in vivo. These results provide a basis for further studies on the use of this composite as an implant in or thopaedic surgery. (C) 2001 John Wiley & Sons, Inc.