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 FDA-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 (pDNA) encoding PDGF was evaluated for promotion of periodontal wound repair in vivo. PEI-pPDGF-B polyplexes were tested in human periodontal ligament fibroblasts (hPLFs) and gingival fibroblasts (hGFs) 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 harvested at 21-days for histologic observation and histomorphometry. PEI-pPDGF-B polyplexes were biocompatible to cells tested and ELISA 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 non-viral gene therapy could have delayed bone healing. This non-viral gene delivery system in this model appeared to prolong inflammatory response, slowing alveolar bone regeneration in vivo.