Tibial segmental defect repair: chondrogenesis and biomechanical strength modulated by basic fibroblast growth factor

The effect of recombinant human basic fibroblast growth factor (bFGF) on cartilage development and bone biomechanical strength during healing of a tibial segmental defect was studied in the rat. Two reports on the effect of basic FGF administration during fracture healing and several reports on the effects of acidic FGF have documented different responses of callus cartilage to this important growth factor. This is the first report of the effect of bFGF on cartilage formation in the healing of a grafted segmental defect in the rat.

The tibiae of 80 male rats underwent segmental resection of the mid-diaphyseal region. One-half of this group consisted of controls that received insertion of an intramedullary wire with a coralline hydroxyapatite graft and Gelfoam without bFGF. The tibiae of the other half were treated identically but had the Gelfoam impregnated with 1 microgram bFGF. Animals were killed at 2, 4, and 8 weeks postoperatively. Histological sections were stained with toluidine blue to differentiate the cartilage. Areas of metachromatically stained extracellular matrix, cell areas, cell size, and cellularity were quantified by using image analysis. Unfixed treated and control tibiae were tested for bone failure strength by using four-point bending on an Instron machine.

Control bone failure strength was significantly greater than bFGF-treated bones at 2 weeks and energy-to-failure was significantly decreased in treated bones at 2 weeks. Although strength increased with time in all groups, treated groups at 4 and 8 weeks did not differ from controls. Basic FGF treatment promoted an increase in the development of normal hyaline cartilage and vasculogenesis at 2 weeks as compared with controls. Total cartilage declined over time in all groups. Average cell size and cell number did not change with either treatment or time. Bone formation and healing was equivalent in treated and control groups at 8 weeks.

The results indicate that bFGF released directly and initially but not continuously exerts a transient positive effect on hyaline cartilage formation at the expense of repair site strength and does not accelerate healing.