Novel Therapy for Bone Regeneration in Large Segmental Defects
Technical Report,30 Sep 2013,29 Sep 2017
Trustee of Indiana University Indianapolis United States
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The purpose of this study is to test the efficacy of thrombopoietin TPO to heal a segmental bone defect SBD in a large animal model, the minipig. The scope of the research comprises the following specific aims i to determine the union rate of tibial midshaft defects in minipigs treated with BMP-2, TPO, or saline control and ii to evaluate the safety and side effects of treating tibial midshaft defects in minipigs treated with BMP-2, TPO, or saline control. Over the course of our study we completed surgeries on 51 minipigs. Three minipigs were used to develop our model. Of the others, 24 had a 25mm defect and were fixed with an IM nail, 12 had a 25mm defect and were fixed with a compression plate, and 12 had a 40mm defect and were also fixed with a compression plate. Perhaps the two most significant findings are 1 we discovered that fixation type IM nail vs. compression plates impacts the size requirement for a critical size defect, and2 although the dose and timing may not yet be optimized, TPO can heal bone defects in pigs and is able to more rapidly allow for bone healing than observed in saline treated controls. Further, no toxic effects were observed, and although additional analyses remain to be completed, TPO and BMP-2 appear to work by different mechanisms to elicit bone healing.
- Anatomy and Physiology