Local delivery of growth factors from coated titanium plates increases osteotomy healing in rats

Different methods for the stabilization of long bone fractures are used in clinic. Besides the development of further stabilization devices, the use of new materials, the modification of the surfaces, and the local application of stimulating factors for enhancement of healing are from great interest. Previous studies successfully used a biodegradable poly(d,l-lactide) coating as a local drug delivery system of growth factors from intramedullary (IM) implants to enhance fracture healing. In this study, we developed a new rat model (n = 60) for plate osteosynthesis and used a plate for stabilization and as a local drug delivery system for the growth factors IGF-I and TGF-beta1. A four-hole titanium plate was used for stabilization of a 0.6-mm osteotomy gap of the femur. The space between the inner holes was coated with 50 microg IGF-I and 10 microg TGF-beta1 incorporated in the poly(d,l-lactide) coating or with the coating alone. After 42 days, biomechanical tests and histomorphological analyses were performed to investigate osteotomy healing. Radiologically small differences were detectable between the groups. The biomechanical torsional testing revealed a significantly higher maximum load of the osteotomized femura after treatment with growth factors compared to the uncoated group. In the histomorphometric analyses measuring the callus composition, a significantly higher percentage of mineralized tissue in the osteotomy callus was assessed in the growth factor treated group compared to the uncoated. In conclusion, the local application of IGF-I and TGF-beta1 from a biodegradable coating enhances the osteotomy healing as shown in the biomechanical testing and the histomorphometry. Bioactive plates could be used in clinic for fracture stabilization and for local and controlled application of growth factors to stimulate bone healing.