A Pilot Study Evaluating Combinatorial and Simultaneous Delivery of Polyethylenimine-Plasmid DNA Complexes Encoding for VEGF and PDGF for Bone Regeneration in Calvarial Bone Defects.
Gene therapy is a promising strategy to deliver growth factors of interest locally in a sustained fashion and has the potential to overcome barriers to using recombinant protein therapy such as sustainability and cost. Recent studies demonstrate the safety and efficacy of non-viral delivery of plasmid DNA (pDNA) encoding a single growth factor to enhance bone healing. This pilot study is aimed at testing a non-viral gene delivery system that can deliver two different plasmids encoding two different growth factors. Polyethylenimine (PEI), a cationic polymer, was utilized as a gene delivery vector and collagen scaffold was used as a carrier to deliver the PEI-pDNA complexes encoding platelet derived growth factor B (PDGF-B) and/or vascular endothelial growth factor (VEGF). Calvarial defects in rats were implanted with scaffolds containing PEI-pPDGF-B complexes, PEI-pVEGF complexes or containing both PEIpPDGF- B and PEI-pVEGF complexes in a 1:1 ratio of plasmids. The results indicated that bone regeneration as measured using micro-CT and histological assessments was inferior in groups treated with PEI-(pPDGF-B + pVEGF) complexes, compared to defects treated with PEI-pPDGF-B complexes. This pilot study that explores the feasibility and efficacy of combinatorial non-viral gene delivery system for bone regeneration appears to provide a rationale for investigation of sequential delivery of growth factors at specific time points during the healing phases and this will be explored further in future studies.
Sheetal R
SR
D'Mello
801 Newton Road, S464, Department of Periodontics, University of Iowa College of Dentistry, Iowa City, Iowa-52242, USA. satheesh-elangovan@uiowa.edu.
Satheesh
S
Elangovan
Liu
L
Hong
Ryan D
RD
Ross
D Rick
DR
Sumner
Aliasger K
AK
Salem
D000818:Animals; D001861:Bone Regeneration / Q000235:genetics*; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000235:genetics*; D004247:DNA / Q000008:administration & dosage / Q000235:genetics; D018014:Gene Transfer Techniques; D010865:Pilot Projects; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics*; D011094:Polyethyleneimine / Q000008:administration & dosage; D051381:Rats; D012886:Skull / Q000473:pathology / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000235:genetics*
D019208:Brain-Derived Neurotrophic Factor; D042461:Vascular Endothelial Growth Factor A; C019277:brain-derived growth factor; C467498:vascular endothelial growth factor A, rat; D011094:Polyethyleneimine; D004247:DNA