LOCAL APPLICATION OF BASIC FIBROBLAST-GROWTH-FACTOR MINIPELLET INDUCES THE HEALING OF SEGMENTAL BONY DEFECTS IN RABBITS

Fibroblast growth factor (FGF) has been reported to increase the volum e of callus in a fracture model of rats. There are, however, no report s of successful repair of segmental bony defects by application of an FGF solution. In this study, the effects of basic FGF on the repair of segmental bony defects in the rabbit femur were examined. Minipellet, a new drug delivery system using atelocollagen, was employed to ensur e effective delivery of FGF. Segmental bony defects (10 mm in length) were created in the right femurs of 19 rabbits. In pilot studies, no d efects of this size healed spontaneously within 6 weeks. Bones were st abilized with miniexternal fixators. Minipellets containing basic FGF were implanted between fragments so as to bridge the two fragments. Th e healing processes were monitored radiographically and studied histol ogically. In rabbits in which FGF was added to the defect site at dose s of 1.4 mu g or higher, approximately 90% of the defects were filled with new bone and cartilage within 6 weeks after minipellet implantati on. In rabbits receiving placebo minipellets, however, approximately 1 5% of the defects were filled by callus within 6 weeks. Furthermore, t his callus did not change into mature bone. An injection of 2 mu g of FGF solution to bony defects had no effect on the repair of segmental bony defects. These findings suggest that FGF plays a role in the prod uction of adequate volumes of callus particularly in the initial stage s of fracture healing and that sustained local release enables FGF to be effective at a low dose. In summary, large segmental bony defects h ealed after insertion of low-dose FGF minipellets. An adequate dose of FGF and an appropriate delivery system are required for successful he aling of large bony defects. These findings imply the potential value of FGF minipellets in clinical practice.