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Effect of sustained PDGF nonviral gene delivery on repair of tooth-supporting bone defects

Gene Therapy volume 24, pages 31–39 (2017)Cite this article

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Abstract

Recombinant human platelet-derived growth factor-BB (rhPDGF-BB) promotes soft tissue and bone healing, and is Food and Drug Administration-approved for treatment of diabetic ulcers and periodontal defects. The short half-life of topical rhPDGF-BB protein application necessitates bolus, high-dose delivery. Gene therapy enables sustained local growth factor production. A novel gene activated matrix delivering polyplexes of polyethylenimine (PEI)-plasmid DNA encoding PDGF was evaluated for promotion of periodontal wound repair in vivo. PEI-pPDGF-B polyplexes were tested in human periodontal ligament fibroblasts and human gingival fibroblasts for cell viability and transfection efficiency. Collagen scaffolds containing PEI-pPDGF-B polyplexes at two doses, rhPDGF-BB, PEI vector or collagen alone were randomly delivered to experimentally induced tooth-supporting periodontal defects in a rodent model. Mandibulae were collected at 21 days for histologic observation and histomorphometry. PEI-pPDGF-B polyplexes were biocompatible to cells tested and enzyme-linked immunosorbent assay confirmed the functionality of transfection. Significantly greater osteogenesis was observed for collagen alone and rhPDGF-BB versus the PEI-containing groups. Defects treated with sustained PDGF gene delivery demonstrated delayed healing coupled with sustained inflammatory cell infiltrates lateral to the osseous defects. Continuous PDGF-BB production by nonviral gene therapy could have delayed bone healing. This nonviral gene delivery system in this model appeared to prolong inflammatory response, slowing alveolar bone regeneration in vivo.

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Acknowledgements

This study was supported by NIH/NIDCR DE 13397 (WVG), NIH/NIDCR DE024206 (SE and AKS) and the Lyle and Sharon Bighley Professorship (AKS). We thank Mr Anh-Vu Do (University of Iowa College of Pharmacy, Iowa City) for his assistance in plasmids expansion.

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Authors and Affiliations

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

    A B Plonka, N Yu, J V Sugai & W V Giannobile

  2. Division of Pharmaceutics and Translational Therapeutics, The University of Iowa College of Pharmacy, Iowa City, IA, USA

    B Khorsand & A K Salem

  3. Department of Periodontics, The University of Iowa College of Dentistry and Dental Clinics, Iowa City, IA, USA

    A K Salem & S Elangovan

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

    W V Giannobile

Authors
  1. A B Plonka
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  2. B Khorsand
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Correspondence to S Elangovan.

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Plonka, A., Khorsand, B., Yu, N. et al. Effect of sustained PDGF nonviral gene delivery on repair of tooth-supporting bone defects. Gene Ther 24, 31–39 (2017). https://doi.org/10.1038/gt.2016.73

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  • DOI: https://doi.org/10.1038/gt.2016.73

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