Use of a polymeric device to deliver growth factors to a healing fracture.

Abstract

Fracture healing is a cascade of events regulated by systemic and local factors. Local growth factors are believed to play an integral role. The present study evaluates the effects of basic fibroblast growth factor (bFGF) and insulin-like growth factor-1 (IGF-1) using a controlled delivery system in a closed rodent femoral fracture model. Female Wistar rats (n = 144) were used in the present study. Animals were randomly allocated to six groups, with each group divided into three time-points of 2, 4 and 8 weeks. Two groups had growth factor administered. The others had no operation or sham operations. Growth factors were delivered to the fracture site using a specialised delivery system. This consisted of a Kirschner-wire coated with ethylene vinyl acetate co-polymer embedded with growth factors, inserted as an intramedullary nail. Fractures were effected with a three-point bending device. Femurs were tested in four-point bending and structural properties of peak load and stiffness were obtained from the load-displacement graphs. Specimens were prepared for qualitative analysis under a light microscope and using immunohistochemistry, specimens were analysed for expression of bFGF, IGF-1 and transforming growth factor beta (TGF-beta). The growth factor-treated groups exhibited larger calluses at 2 and 4 weeks. Four-point bending showed weaker structural properties (stiffness and peak load) at 4 weeks in both growth factor-treated groups. Administration of bFGF or IGF-1 increased the ratio of cartilaginous to mesenchymal tissues in the fracture callus compared with non-treated animals at 2 and 4 weeks. Immunostaining intensity and distribution of both growth factors in the treated groups was greater than the non-treated groups. Exogenous delivery of bFGF or IGF-1 alters the course of fracture healing.