The enhancement of bone regeneration by gene activated matrix encoding for platelet derived growth factor

Satheesh Elangovan; Sheetal R D'Mello; Liu Hong; Ryan D Ross; Chantal Allamargot; Deborah V Dawson; Clark M Stanford; Georgia K Johnson; D. Rick Sumner; Aliasger K Salem

doi:10.1016/j.biomaterials.2013.10.021

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The enhancement of bone regeneration by gene activated matrix encoding for platelet derived growth factor

Journal article

Peer reviewed

The enhancement of bone regeneration by gene activated matrix encoding for platelet derived growth factor

Satheesh Elangovan, Sheetal R D'Mello, Liu Hong, Ryan D Ross, Chantal Allamargot, Deborah V Dawson, Clark M Stanford, Georgia K Johnson, D. Rick Sumner and Aliasger K Salem

Biomaterials, Vol.35(2), pp.737-747

01/2014

DOI: 10.1016/j.biomaterials.2013.10.021

PMCID: PMC3855224

PMID: 24161167

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Abstract

Gene therapy using non-viral vectors that are safe and efficient in transfecting target cells is an effective approach to overcome the shortcomings of protein delivery of growth factors. The objective of this study was to develop and test a non-viral gene delivery system for bone regeneration utilizing a collagen scaffold to deliver polyethylenimine (PEI)-plasmid DNA (pDNA) [encoding platelet derived growth factor-B (PDGF-B)] complexes. The PEI-pPDGF-B complexes were fabricated at amine (N) to phosphate (P) ratio of 10 and characterized for size, surface charge, and in vitro cytotoxicity and transfection efficacy in human bone marrow stromal cells (BMSCs). The influence of the complex-loaded collagen scaffold on cellular attachment and recruitment was evaluated in vitro using microscopy techniques. The in vivo regenerative capacity of the gene delivery system was assessed in 5 mm diameter critical-sized calvarial defects in Fisher 344 rats. The complexes were ∼100 nm in size with a positive surface charge. Complexes prepared at an N/P ratio of 10 displayed low cytotoxicity as assessed by a cell viability assay. Confocal microscopy revealed significant proliferation of BMSCs on complex-loaded collagen scaffolds compared to empty scaffolds. In vivo studies showed significantly higher new bone volume/total volume (BV/TV) % in calvarial defects treated with the complex-activated scaffolds following 4 weeks of implantation (14- and 44-fold higher) when compared to empty defects or empty scaffolds, respectively. Together, these findings suggest that non-viral PDGF-B gene-activated scaffolds are effective for bone regeneration and are an attractive gene delivery system with significant potential for clinical translation.

Gene delivery

Polyethylenimine

Scaffold

Plasmid DNA

Bone regeneration

Platelet derived growth factor

Details

Title: Subtitle: The enhancement of bone regeneration by gene activated matrix encoding for platelet derived growth factor
Creators: Satheesh Elangovan - Department of Periodontics, University of Iowa College of Dentistry, Iowa City, IA, USA
Sheetal R D'Mello - Division of Pharmaceutics and Translational Therapeutics, University of Iowa College of Pharmacy, Iowa City, IA, USA
Liu Hong - Department of Prosthodontics, University of Iowa College of Dentistry, Iowa City, IA, USA
Ryan D Ross - Department of Anatomy and Cell Biology, Rush Medical College, Chicago, IL, USA
Chantal Allamargot - Central Microscopy Research Facility, University of Iowa, Iowa City, IA, USA
Deborah V Dawson - Division of Biostatistics and Research Design, College of Dentistry, Depts. of Pediatric Dentistry & Biostatistics and the Interdisciplinary Programs in Genetics and in Informatics, University of Iowa, Iowa City, IA, USA
Clark M Stanford - Department of Prosthodontics, University of Iowa College of Dentistry, Iowa City, IA, USA
Georgia K Johnson - Department of Periodontics, University of Iowa College of Dentistry, Iowa City, IA, USA
D. Rick Sumner - Department of Anatomy and Cell Biology, Rush Medical College, Chicago, IL, USA
Aliasger K Salem - Division of Pharmaceutics and Translational Therapeutics, University of Iowa College of Pharmacy, Iowa City, IA, USA
Resource Type: Journal article
Publication Details: Biomaterials, Vol.35(2), pp.737-747
DOI: 10.1016/j.biomaterials.2013.10.021
PMID: 24161167
PMCID: PMC3855224
NLM abbreviation: Biomaterials
ISSN: 0142-9612
eISSN: 1878-5905
Publisher: Elsevier Ltd
Grant note: name: University of Iowa Start-up Grant; name: International Team for Implantology Grant, award: 855-2012; DOI: 10.13039/100000048, name: American Cancer Society, award: RSG-09-015-01-CDD; name: National Cancer Institute at the National Institutes of Health
Language: English
Date published: 01/2014
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Core Research Facilities; Pharmaceutical Sciences and Experimental Therapeutics; Biostatistics; Prosthodontics; Orthopedics and Rehabilitation; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering; Periodontics
Record Identifier: 9983985718202771

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