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Journal of Clinical Periodontology

Effect of rhBMP-2 dose on bone formation/maturation in a rat critical-size calvarial defect model

Authors

  • Manuel Pelaez,

    1. Laboratory for Applied Periodontal & Craniofacial Regeneration (LAPCR), Georgia Regents University College of Dental Medicine, Augusta, GA, USA
    2. US Army Dental Activity, Fort Bragg, NC, USA
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  • Cristiano Susin,

    1. Laboratory for Applied Periodontal & Craniofacial Regeneration (LAPCR), Georgia Regents University College of Dental Medicine, Augusta, GA, USA
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  • Jaebum Lee,

    1. Laboratory for Applied Periodontal & Craniofacial Regeneration (LAPCR), Georgia Regents University College of Dental Medicine, Augusta, GA, USA
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  • Tiago Fiorini,

    1. Laboratory for Applied Periodontal & Craniofacial Regeneration (LAPCR), Georgia Regents University College of Dental Medicine, Augusta, GA, USA
    2. Section of Periodontology, School of Dentistry, Federal University, Porto Alegre, Rio Grande do Sul, Brazil
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  • Frederick C. Bisch,

    1. US Army Advanced Education Program in Periodontics, Fort Gordon, GA, USA
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  • Douglas R. Dixon,

    1. US Army Dental Activity, West Point, NY, USA
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  • James C. McPherson III,

    1. US Army, Department of Clinical Investigations, Ft. Gordon, GA, USA
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  • Amanda N. Buxton,

    1. Medtronic Spine & Biologics, Memphis, TN, USA
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  • Ulf M.E. Wikesjö

    Corresponding author
    1. Laboratory for Applied Periodontal & Craniofacial Regeneration (LAPCR), Georgia Regents University College of Dental Medicine, Augusta, GA, USA
    • Address:

      Ulf M.E. Wikesjö

      Laboratory for Applied Periodontal & Craniofacial Regeneration (LAPCR)

      Georgia Regents University College of Dental Medicine

      1120 Fifteenth Street, # GC 4265

      Augusta, GA 30912, USA

      E-mail: uwikesjo@gru.edu

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  • Conflict of interest and source of funding statement

    This study was supported in part by a grant from Medtronic Spine & Biologics, Memphis, TN, USA. Drs. Cristiano Susin, Jaebum Lee and Ulf M.E. Wikesjö are supported by a grant from Nobel Biocare AG. Dr. Amanda N. Buxton is an employee of Medtronic Spine & Biologics. All other authors claim no conflict of interest. The opinions expressed in this article do not represent the views of the US Department of Defense, the Department of the Army or the US Army Dental Corps. Use of any commercial products in this project does not imply endorsement by the US Government.

Abstract

Background

Application of recombinant human bone morphogenetic protein-2 (rhBMP-2) has been associated with significant adverse events in craniofacial settings, including swelling and seroma formation. Recent work has demonstrated an inverse relationship between bone formation/maturation and rhBMP-2 dose, frequency/severity of adverse events increasing with rising dose.

Objective

The objective of this study was to determine the most effective dose for rhBMP-2 soak-loaded onto an absorbable collagen sponge (ACS) carrier for bone formation/maturation using an established defect model.

Methods

One hundred sixty-eight outbred male Sprague-Dawley rats, age 11–13 weeks, weight 325–375 g randomized into seven groups of 24 subdivided into groups of eight, were used to provide radiographic and light microscopy observations of bone formation/maturation and aberrant healing events at 2, 4 and 8 weeks following application of rhBMP-2/ACS into critical-size, ø8-mm, through-through, calvarial osteotomy defects for a dose of 1.25, 2.5, 5.0, 10.0 and 20.0 μg rhBMP-2/defect, or serve as ACS or sham-surgery controls.

Results

rhBMP-2 dosages ≥2.5 μg/defect showed histological defect closure >90% within 2 weeks, and complete resolution within 4 weeks. Adverse healing events including swelling, excessive bone formation or seroma formation could not be determined with certainty in this defect model. Notably ACS control sites showed complete defect closure at the 8-week healing interval.

Conclusions

rhBMP-2/ACS accelerates local bone formation in the rat critical-size through-through calvarial defect model once reaching an osteoinductive dose threshold. This threshold may already be reached at a 1.25-/2.5-μg dose in this model. No further enhancement to bone formation/maturation may be observed adding rhBMP-2 above the 2.5-μg dose. The 1.25–20.0 μg dose range did not invoke appreciable aberrant healing events.

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