Effect of sustained PDGF nonviral gene delivery on repair of tooth-supporting bone defects.
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.
Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry. Ann Arbor, MI, USA.
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Plonka
Division of Pharmaceutics and Translational Therapeutics, The University of Iowa College of Pharmacy, Iowa City, IA, USA.
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Khorsand
Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry. Ann Arbor, MI, USA.
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Yu
Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry. Ann Arbor, MI, USA.
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Sugai
Division of Pharmaceutics and Translational Therapeutics, The University of Iowa College of Pharmacy, Iowa City, IA, USA.|Department of Periodontics, The University of Iowa College of Dentistry and Dental Clinics, Iowa City, IA, USA.
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Salem
Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry. Ann Arbor, MI, USA.|Department of Biomedical Engineering, University of Michigan College of Engineering, Ann Arbor, MI, USA.
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Giannobile
Department of Periodontics, The University of Iowa College of Dentistry and Dental Clinics, Iowa City, IA, USA.
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Elangovan
D000818:Animals; D001672:Biocompatible Materials / Q000009:adverse effects*; D001861:Bone Regeneration; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D018014:Gene Transfer Techniques / Q000009:adverse effects*; D006801:Humans; D010012:Osteogenesis; D010510:Periodontal Diseases / Q000628:therapy*; D010982:Platelet-Derived Growth Factor / Q000235:genetics* / Q000378:metabolism; D011094:Polyethyleneimine / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
D001672:Biocompatible Materials; D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; D011094:Polyethyleneimine