Negatively charged beads and transforming growth factor-beta1 stimulate bone repair in rabbits

Previous studies have shown the osteogenic potential of negatively charged Sephadex beads when used to heal osseous defects in an animal model. The present study examined the effect of adding the growth factors transforming growth factor-beta1 and basic fibroblast growth factor to negatively charged Sephadex beads and neutral (non-osteogenic) Sephadex beads in a critical size calvarial defect in rabbits. New Zealand White rabbits were divided into six groups of five rabbits; 15 mm parietal defects were created and filled with either negatively charged Sephadex beads (three groups) or neutral Sephadex beads (three groups). Each group received either 2 microg of transforming growth factor-beta1, 1 microg of basic fibroblast growth factor, or buffer (control). Animals were killed at 5 weeks, and their calvaria were submitted to plain radiographic and histomorphometric analyses. Defects treated with negatively charged Sephadex beads produced significantly more new trabecular bone than neutral Sephadex beads (p < 0.01), whereas the neutral beads treated with transforming growth factor-beta1 formed significantly more bone than controls. The addition of transforming growth factor-beta1 to negatively charged beads resulted in near closure of the craniotomy defect. The application of transforming growth factor-beta1 to this model resulted in significantly more ectopic bone (p < 0.01) outside the defect on the dural and periosteal surfaces. Basic fibroblast growth factor, in the dose used, appeared to have an inhibitory effect on new bone formation fostered by negatively charged Sephadex beads. This study suggests that the addition of transforming growth factor-beta1 to the known osteoconductive matrix of negatively charged Sephadex beads may be therapeutically useful in nonhealing bony defects.