Journal article
Effect of sustained PDGF nonviral gene delivery on repair of tooth-supporting bone defects
Gene therapy, Vol.24(1), pp.31-39
01/2017
DOI: 10.1038/gt.2016.73
PMCID: PMC5269540
PMID: 27824330
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.
Details
- Title: Subtitle
- Effect of sustained PDGF nonviral gene delivery on repair of tooth-supporting bone defects
- Creators
- A B Plonka - Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry. Ann Arbor, MI, USAB Khorsand - Division of Pharmaceutics and Translational Therapeutics, The University of Iowa College of Pharmacy, Iowa City, IA, USAN Yu - Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry. Ann Arbor, MI, USAJ V Sugai - Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry. Ann Arbor, MI, USAA K Salem - Department of Periodontics, The University of Iowa College of Dentistry and Dental Clinics, Iowa City, IA, USAW V Giannobile - Department of Biomedical Engineering, University of Michigan College of Engineering, Ann Arbor, MI, USAS Elangovan - Department of Periodontics, The University of Iowa College of Dentistry and Dental Clinics, Iowa City, IA, USA
- Resource Type
- Journal article
- Publication Details
- Gene therapy, Vol.24(1), pp.31-39
- DOI
- 10.1038/gt.2016.73
- PMID
- 27824330
- PMCID
- PMC5269540
- NLM abbreviation
- Gene Ther
- ISSN
- 0969-7128
- eISSN
- 1476-5462
- Publisher
- England
- Grant note
- R21 DE024206 / NIDCR NIH HHS R01 DE013397 / NIDCR NIH HHS
- Language
- English
- Date published
- 01/2017
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering; Periodontics
- Record Identifier
- 9983985849702771
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