Clinical Orthopaedics and Related Research®

, Volume 470, Issue 9, pp 2478–2487 | Cite as

Quantifying Massive Allograft Healing of the Canine Femur In Vivo and Ex Vivo: A Pilot Study

  • Brandon G. Santoni
  • Nicole Ehrhart
  • Ricardo Betancourt-Benitez
  • Christopher A. Beck
  • Edward M. Schwarz
Symposium: Allograft Research and Transplantation

Abstract

Background

Allograft integration in segmental osseous defects is unpredictable. Imaging techniques have not been applied to investigate angiogenesis and bone formation during allograft healing in a large-animal model.

Questions/purposes

We used dynamic contrast-enhanced (DCE)-MRI and cone beam (CB)-CT to quantify vascularity and bone volume in a canine femoral allograft model and determined their relationship with biomechanical testing and histomorphometry.

Methods

Femoral ostectomy was performed in three dogs and reconstructed with a 5-cm allograft and compression plate. At 0.5, 3, and 6 months, we performed DCE-MRI to quantify vascular permeability (Ktrans) and perfused fraction and CB-CT to quantify bone volume. We also performed posteuthanasia torsional testing and dynamic histomorphometry of the grafted and nonoperated femurs.

Results

DCE-MRI confirmed the avascular nature of allograft healing (perfused fraction, 2.08%–3.25%). CB-CT demonstrated new bone formation at 3 months (26.2, 3.7, and 2.2 cm3) at the graft-host junctions, which remodeled down at 6 months (14.0, 2.2, and 2.0 cm3). The increased bone volume in one subject was confirmed with elevated Ktrans (0.22) at 3 months. CB-CT-identified remodeled bone at 6 months was corroborated by histomorphometry. Allografted femurs recovered only 40% of their strength at 6 months.

Conclusions

CB-CT and DCE-MRI can discriminate differences in angiogenesis and bone formation in the canine allograft model, which has potential to detect a small (32%) drug or device effect on biomechanical healing with only five animals per group.

Clinical Relevance

These radiographic tools may have the potential to assess adjuvant effects on vascular invasion and new bone formation after segmental allograft transplantation.

Notes

Acknowledgments

We thank our collaborative authors from the University of Rochester, Masahiko Takahata, MD, and Chao Xie, MD, for their assistance in the daily observations of the canine subjects and care for the animals during DCE-MRI and CB-CT; David Conover, MS, for his help running the CB-CT scanner; and Hani A. Awad, PhD, for help with the experimental design and data analyses. We also thank Synthes Inc for providing surgical equipment and implants.

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Copyright information

© The Association of Bone and Joint Surgeons® 2012

Authors and Affiliations

  • Brandon G. Santoni
    • 1
  • Nicole Ehrhart
    • 2
  • Ricardo Betancourt-Benitez
    • 3
  • Christopher A. Beck
    • 4
  • Edward M. Schwarz
    • 5
    • 6
  1. 1.Phillip Spiegel Orthopaedic Research LaboratoryFoundation for Orthopaedic Research and EducationTampaUSA
  2. 2.Department of Clinical SciencesColorado State UniversityFort CollinsUSA
  3. 3.Department of Imaging SciencesUniversity of RochesterRochesterUSA
  4. 4.Department of Biostatistics & Computational BiologyUniversity of RochesterRochesterUSA
  5. 5.Department of Biomedical EngineeringUniversity of Rochester RochesterUSA
  6. 6.The Center for Musculoskeletal ResearchUniversity of Rochester Medical CenterRochesterUSA

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