P103 ASSESMENT OF A NOVEL ANGIOGENIC FACTOR IN A SMALL ANIMAL MODEL OF ATROPHIC NONUNION

Abstract

Introduction: Atrophic nonunion is a well recognised complication of long bone fractures. Clinical trials show that BMP-2 accelerates healing and reduces nonunion in open tibial fractures. We are interested in a natural small molecule that has been previously demonstrated to stimulate angiogenesis in vivo. Our aim is to assess the two treatments in the prevention of nonunion. The small animal model we used is a non-critical size defect of the tibia deprived it of its blood supply by surgical stripping of the periosteum and curetting of the local endosteum thus closely reflecting the clinical situation. The outcomes were measured by radiographic assessment and histology. Methods: Wistar rats were treated with either the angiogenic molecule (0.1% or 0.003%), BMP-2 or vehicle alone (PBS) soaked in a type I collagen sponge. All animals underwent a 2mm osteotomy, stripping of the periosteum and endosteum proximally and distally for the length of the diameter of the tibia. Fluorescent markers were injected at 2 weekly intervals. The rats were sacrificed at 8 weeks. Both tibiae were disarticulated; fixator and soft tissues were removed and AP and lateral X-rays were taken. Subjective assessment of the healing on X-ray was carried out in two ways; using a radiographic scoring system and by grey scale analysis. The samples were embedded, sectioned and stained for new bone formation. Results: Bridging or potential to bridge was seen in a number of animals on x-ray. Bridging or potential to bridge was judged to be present in 72.22% of the BMP-2 group and 66.67% of the high dose group compared to 22.22% of the control group. Histological analysis is being performed to confirm these findings. Discussion: Atrophic nonunion is a serious clinical complication, unfortunately BMP-2 is a highly costly treatment option and therefore alternative molecular therapies are much sought after. We describe here an angiogenic molecule has some potential in preventing formation of nonunion.

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