Novel Therapy for Bone Regeneration in Large Segmental Defects

Abstract

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.

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Document Details

Document Type
Technical Report
Publication Date
Dec 01, 2017
Accession Number
AD1049893

Entities

People

  • Melissa A. Kacena
  • Tien-min Chu
  • Todd O McKinley

Organizations

  • Indiana University

Tags

DTIC Thesaurus Topics

  • Bone And Bones
  • Bone Fractures
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Health Services
  • Joints (Anatomy)
  • Medical Personnel
  • Orthopedics
  • Osteogenesis
  • Peptide Growth Factors
  • Stem Cells

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