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

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.

• Authors: A B Plonka, B Khorsand, N Yu, J V Sugai, A K Salem, W V Giannobile, S Elangovan
• Journal: Gene therapy (Gene Ther) Vol. 24 Issue 1 Pg. 31-39 (01 2017) ISSN: 1476-5462 [Electronic] England
• PMID: 27824330 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biocompatible Materials
• Platelet-Derived Growth Factor
• Recombinant Proteins
• Polyethyleneimine

Topics

• Animals
• Biocompatible Materials (adverse effects)
• Bone Regeneration
• Fibroblasts (drug effects, metabolism, physiology)
• Gene Transfer Techniques (adverse effects)
• Humans
• Osteogenesis
• Periodontal Diseases (therapy)
• Platelet-Derived Growth Factor (genetics, metabolism)
• Polyethyleneimine (adverse effects)
• Rats
• Rats, Sprague-Dawley
• Recombinant Proteins (genetics, metabolism)