Abstract
Over 1 million fractures occur each year in the UK. Approximately 5-10% of these fractures have problems with healing. The treatments used for these patients often have a poor outcome and are associated with increased morbidity and disability. Application of synthetic peptides such as thrombin degradation peptide (TP508) has been shown to accelerate fracture repair in a closed rat femoral fracture model. Controlled release of TP508 using microspheres has been shown to enhance repair of articular cartilage defects and stimulate bone formation in segmental defects in rabbits. The aim of this study was to determine whether TP508 could bring about healing in an established fracture non-union model.
A validated rat model of fracture non-union was used. The model was created and left for 8 weeks in order to represent a clinically equivalent model of a non union of a fracture. Rats were randomised into two treatment groups receiving 10microg and 1microg doses of TP508 diluted in 50microL of microspheres and delivered directly to the non union site using percutaneous injection 8 weeks after surgery. The control group received no treatment. At 16 weeks post-surgery, osseous bridging was assessed both radiographically and histologically.
Radiographically there was no difference between the control and two treatment groups. However, histomor-phometric analysis demonstrated that bone formation increased by 43.9% in animals that received high dose of TP508 compared to the control animals. The analysis also indicated that administration of the low dose of TP508 increased the amount of bone formation compared to the control by 9.9 %.
Administration of TP508 has been shown to enhance healing of segmental defects in both critically and noncritically sized defects. However, in our model which is an established fracture non-union model, TP508 did not manage to achieve full osseous union. It has been suggested that the action of this peptide is concentration and environment dependent possibly indicating that TP508 might be less effective when administered in a chronic situation such as that associated with the established non-union fracture. However, even in this sub-optimal situation an increased amount of bone formation was observed.
Correspondence should be addressed to Mr Carlos Wigderowitz, Senior Lecturer, University Department of Orthopaedic and Trauma Surgery, Ninewells Hospital and Medical School, Dundee DD1 9SY.
