title: Dose effect of dual delivery of vascular endothelial growth factor and bone morphogenetic protein-2 on bone regeneration in a rat critical-size defect model.
abstract: The dose effect of dual delivery of vascular endothelial growth factor (VEGF) and bone morphogenetic protein-2 (BMP-2) on bone regeneration was investigated in a rat cranial critical-size defect (CSD). It was hypothesized that decreasing amounts of BMP-2 would result in a dose-dependent decrease in bone formation, and that this reduction in bone formation could be reversed by adding increasing amounts of VEGF. In vitro release kinetics of VEGF or BMP-2 were examined over 28 days. Next, scaffolds were implanted within a rat cranial CSD containing different combinations of both BMP-2 and VEGF. At 12 weeks, samples were analyzed using microcomputed tomography and histology. In vitro, VEGF and BMP-2 exhibited burst release in the first 24 h followed by a significant decrease in release rate over 27 days. Overall, BMP-2 had a more sustained release versus VEGF. An in vivo dose-dependent decrease in percentage of bone fill (PBF) was observed for BMP-2. The addition of VEGF was unable to reverse this decrease in PBF, although improvements in the number of bridged defects did occur in some groups. This suggests that for this particular model simultaneous release of BMP-2 and VEGF does not increase bone formation over BMP-2 alone at 12 weeks.
authors.affiliation: Department of Bioengineering, Rice University, Houston, Texas 77251-1892, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Young
authors.forename: Zarana S
authors.initials: ZS
authors.lastname: Patel
authors.forename: James D
authors.initials: JD
authors.lastname: Kretlow
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Murphy
authors.forename: Paschalia M
authors.initials: PM
authors.lastname: Mountziaris
authors.forename: L Scott
authors.initials: LS
authors.lastname: Baggett
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ueda
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.forename: John A
authors.initials: JA
authors.lastname: Jansen
authors.forename: Mark
authors.initials: M
authors.lastname: Wong
authors.forename: Antonios G
authors.initials: AG
authors.lastname: Mikos
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D002021:Buffers; D017364:Collagenases / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D005650:Fumarates / Q000494:pharmacology; D007700:Kinetics; D010012:Osteogenesis / Q000187:drug effects; D011126:Polypropylenes / Q000494:pharmacology; D016062:Porosity / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D012886:Skull / Q000187:drug effects / Q000473:pathology*; D054457:Tissue Scaffolds; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000494:pharmacology*; D055114:X-Ray Microtomography
chemical_list: D055396:Bone Morphogenetic Protein 2; D002021:Buffers; D005650:Fumarates; D011126:Polypropylenes; D042461:Vascular Endothelial Growth Factor A; C097850:poly(propylene fumarate); D017364:Collagenases