title: Bone morphogenetic protein-2 plasmid DNA as a substitute for bone morphogenetic protein-2 protein in bone tissue engineering.
abstract: Bone regeneration is one of the focus points in the field of regenerative medicine. A well-known stimulus of bone formation is bone morphogenetic protein-2 (BMP-2), which has already been extensively used in clinical applications. However, due to a short half-life, supraphysiological doses are applied resulting in severe side effects such as ectopic bone formation or even loss of bone. We compared the effectivity of transient BMP-2 gene delivery with the BMP-2 protein at clinical (high) and physiological (low) doses by subcutaneous implantation of alginate-based constructs in mice. After 6 weeks of implantation, both the protein laden constructs and BMP-2 plasmid DNA-based constructs showed similar early bone onset and elevated bone formation compared to controls without any BMP-2 added. We found no differences in efficiency by using BMP-2 plasmid DNA or any of the BMP-2 protein dosages. Therefore, we conclude that BMP-2 plasmid DNA-based gene therapy in alginate is a promising new strategy for BMP-2 administration for bone (re)generation.
authors.affiliation: 1 Department of Orthopaedics, University Medical Center Utrecht , Utrecht, The Netherlands .
authors.forename: Fiona
authors.initials: F
authors.lastname: Wegman
authors.forename: Yvonne
authors.initials: Y
authors.lastname: van der Helm
authors.forename: F Cumhur
authors.initials: FC
authors.lastname: Öner
authors.forename: Wouter J A
authors.initials: WJ
authors.lastname: Dhert
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Alblas
mesh_terms: D000464:Alginates / Q000494:pharmacology*; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000096:biosynthesis* / Q000235:genetics; D001861:Bone Regeneration; D001842:Bone and Bones / Q000378:metabolism*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D020723:Glucuronic Acid / Q000494:pharmacology; D006041:Goats; D006603:Hexuronic Acids / Q000494:pharmacology; D006801:Humans; D051379:Mice; D010957:Plasmids / Q000494:pharmacology*; D023822:Tissue Engineering
chemical_list: D000464:Alginates; C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D006603:Hexuronic Acids; D020723:Glucuronic Acid