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PDGF-B gene therapy accelerates bone engineering and oral implant osseointegration

Gene Therapy volume 17, pages 95–104 (2010)Cite this article

Abstract

Platelet-derived growth factor-BB (PDGF-BB) stimulates repair of healing-impaired chronic wounds such as diabetic ulcers and periodontal lesions. However, limitations in predictability of tissue regeneration occur due, in part, to transient growth factor bioavailability in vivo. Here, we report that gene delivery of PDGF-B stimulates repair of oral implant extraction socket defects. Alveolar ridge defects were created in rats and were treated at the time of titanium implant installation with a collagen matrix containing an adenoviral (Ad) vector encoding PDGF-B (5.5 × 108 or 5.5 × 109 pfu ml−1), Ad encoding luciferase (Ad-Luc; 5.5 × 109 pfu ml−1; control) or recombinant human PDGF-BB protein (rhPDGF-BB, 0.3 mg ml−1). Bone repair and osseointegration were measured through backscattered scanning electron microscopy, histomorphometry, micro-computed tomography and biomechanical assessments. Furthermore, a panel of local and systemic safety assessments was performed. Results indicated that bone repair was accelerated by Ad-PDGF-B and rhPDGF-BB delivery compared with Ad-Luc, with the high dose of Ad-PDGF-B more effective than the low dose. No significant dissemination of the vector construct or alteration of systemic parameters was noted. In summary, gene delivery of Ad-PDGF-B shows regenerative and safety capabilities for bone tissue engineering and osseointegration in alveolar bone defects comparable with rhPDGF-BB protein delivery in vivo.

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Acknowledgements

We thank Valeria Pontelli Navarro Tedeschi for assistance with animal surgeries, Dennis Kayner for assisting removal of the implants, Dr. Noboru Kikuchi for establishing finite element models and Anna Colvig for performing hematological and clinical chemical examinations. This study was supported in part by the grants from the National Institutes of Health (NIH)/National Institute of Dental and Craniofacial Research (NIDCR) (R01-DE13397) and the AO Foundation Research Advisory Council (Davos, Switzerland) to WVG.

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Author notes

  1. P-C Chang and Y-J Seol: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, USA

    P-C Chang, Y-J Seol, J A Cirelli, G Pellegrini, Q Jin, L M Franco & W V Giannobile

  2. Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, MI, USA

    P-C Chang, S A Goldstein & W V Giannobile

  3. Department of Periodontology, School of Dentistry, Seoul National University, Seoul, Korea

    Y-J Seol

  4. Department of Periodontology, School of Dentistry at Araraquara, State University of São Paulo, Araraquara, São Paulo, Brazil

    J A Cirelli

  5. Department of Periodontology, Clinics Hospital Mangiagalli, University of Milan, Milan, Italy

    G Pellegrini

  6. Department of Orthopaedic Surgery, School of Medicine, University of Michigan, Ann Arbor, MI, USA

    S A Goldstein

  7. Tissue Repair Company, San Diego, CA, USA

    L A Chandler & B Sosnowski

Authors
  1. P-C Chang
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  2. Y-J Seol
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  8. L A Chandler
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  10. W V Giannobile
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Corresponding author

Correspondence to W V Giannobile.

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Supplementary Information accompanies the paper on Gene Therapy website (http://www.nature.com/gt)

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Chang, PC., Seol, YJ., Cirelli, J. et al. PDGF-B gene therapy accelerates bone engineering and oral implant osseointegration. Gene Ther 17, 95–104 (2010). https://doi.org/10.1038/gt.2009.117

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