title: The ability of a collagen/calcium phosphate scaffold to act as its own vector for gene delivery and to promote bone formation via transfection with VEGF(165).
abstract: Collagen/calcium phosphate scaffolds have been used for bone reconstruction due to their inherent similarities to the bone extracellular matrix. Calcium phosphate alone has also been used as a non-viral vector for gene delivery. The aim of this study was to determine the capability of a collagen/calcium phosphate scaffold to deliver naked plasmid DNA and mediate transfection in vivo. The second goal of the study was to deliver a plasmid encoding vascular endothelial growth factor(165) (pVEGF(165)) to promote angiogenesis, and hence bone formation, in a mouse intra-femoral model. The delivery of naked plasmid DNA resulted in a 7.6-fold increase in mRNA levels of beta-Galactosidase compared to the delivery of plasmid DNA complexed with a partially degraded PAMAM dendrimer (dPAMAM) in a subcutaneous murine model. When implanted in a muirne intra-femoral model, the delivery of pVEGF(165) resulted in a 2-fold increase in bone volume at the defect site relative to control scaffolds without pVEGF(165). It was concluded that a collagen/calcium phosphate scaffold can mediate transfection without the use of additional transfection vectors and can promote bone formation in a mouse model via the delivery of pVEGF(165).
authors.affiliation: Network of Excellence for Functional Biomaterials, National University of Ireland Galway, NFB Building, IDA Business Park, Newcastle Road, Dangan, Ireland.
authors.forename: Michael
authors.initials: M
authors.lastname: Keeney
authors.forename: Jeroen J J P
authors.initials: JJ
authors.lastname: van den Beucken
authors.forename: Peter M
authors.initials: PM
authors.lastname: van der Kraan
authors.forename: John A
authors.initials: JA
authors.lastname: Jansen
authors.forename: Abhay
authors.initials: A
authors.lastname: Pandit
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology; D002130:Calcium Phosphates / Q000494:pharmacology*; D003094:Collagen / Q000494:pharmacology*; D005269:Femur / Q000187:drug effects / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D017930:Genes, Reporter; D020007:Implants, Experimental; D007249:Inflammation / Q000150:complications / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000150:complications; D010012:Osteogenesis / Q000187:drug effects*; D040521:Subcutaneous Tissue / Q000187:drug effects; D054457:Tissue Scaffolds / Q000737:chemistry*; D014162:Transfection / Q000379:methods*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D002130:Calcium Phosphates; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D003094:Collagen; C020243:calcium phosphate