TI-6AL-4V ION SOLUTION INHIBITION OF OSTEOGENIC CELL PHENOTYPE AS A FUNCTION OF DIFFERENTIATION TIMECOURSE IN-VITRO

Metal ions released from the implant surface are suspected of playing some contributing role in loosening of hip and knee prostheses. Previo us work in this laboratory demonstrated that sublethal doses of the io nic constituents of Ti-6Al-4V alloy suppressed expression of the osteo blastic phenotype and deposition of a mineralized matrix. The purpose of this work was to further explore this suppression as a function of the normal time-course of phenotype expression. Bone marrow stromal ce lls were harvested from juvenile rats and exposed to time-staggered do ses of a solution of ions representing Ti-6Al-4V alloy. Cells were cul tured for four weeks and assayed for total protein, alkaline phosphata se, intra- and extracellular osteocalcin, and calcium. TI-6Al-4V solut ions were found to produce little difference from control solutions fo r total protein or alkaline phosphatase levels, but strongly inhibited osteocalcin synthesis. Calcium levels were reduced when ions were add ed before a critical point of osteoblastic differentiation (between 2 and 3 weeks after seeding). These results indicate that ions associate d with Ti-6Al-4V alloy inhibited the normal differentiation of bone ma rrow stromal cells to mature osteoblasts in vitro, suggesting that ion s released from implants in vivo may contribute to implant failure by impairing normal bone deposition. (C) 1996 Elsevier Science Limited.