title: Evaluation of adenoviral vascular endothelial growth factor-activated chitosan/hydroxyapatite scaffold for engineering vascularized bone tissue using human osteoblasts: In vitro and in vivo studies.
abstract: Bone tissue is dependent on an efficient blood supply to ensure delivery of nutrients and oxygen. One method to acquire a vascular-engineered bone tissue could be the use of an angiogenic gene-activated scaffold. In the current study, porous chitosan/hydroxyapatite (C/HA) scaffolds were fabricated via freeze-drying with desired pore size, and then combined with the adenoviral vector encoding vascular endothelial growth factor and green fluorescence protein (Ad-VEGF). Human osteoblasts were cultured and seeded on characterized scaffolds. The attachment, proliferation, and differentiation of cells on gene-activated and unactivated C/HA scaffolds were evaluated in vitro and in vivo by histo- and immunohistochemistry. Findings confirmed that human osteoblasts cultured on gene-activated C/HA scaffold secreted vascular endothelial growth factor, besides maintaining its characteristic phenotype with specific extracellular matrix production. In vivo experiments indicated that scaffolds were tissue biocompatible, and that gene-activated scaffold provided a suitable environment for neovessel formation by recruiting host endothelial cells into the newly forming ectopic bone-like tissue. This study revealed that the Ad-VEGF-activated C/HA composite scaffold has potential for vascular bone regeneration applications.
authors: Tissue Engineering, Biomaterials and Nanobiotechnology Laboratory, Ankara University Faculty of Science and Ankara University Stem Cell Institute, Ankara, Turkey.
authors: Aysel
authors: A
authors: Koç
authors: Department of Plastic and Hand Surgery, University of Freiburg Medical Center, Freiburg, Germany.
authors: Günter
authors: G
authors: Finkenzeller
authors: Tissue Engineering, Biomaterials and Nanobiotechnology Laboratory, Ankara University Faculty of Science and Ankara University Stem Cell Institute, Ankara, Turkey.
authors: A Eser
authors: AE
authors: Elçin
authors: Department of Plastic and Hand Surgery, University of Freiburg Medical Center, Freiburg, Germany.
authors: G Björn
authors: GB
authors: Stark
authors: Tissue Engineering, Biomaterials and Nanobiotechnology Laboratory, Ankara University Faculty of Science and Ankara University Stem Cell Institute, Ankara, Turkey elcinmurat@gmail.com.
authors: Y Murat
authors: YM
authors: Elçin
mesh_terms: D000256:Adenoviridae; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D001842:Bone and Bones / Q000473:pathology; D049109:Cell Proliferation; D048271:Chitosan / Q000737:chemistry*; D017886:Durapatite / Q000737:chemistry*; D005612:Freeze Drying; D006801:Humans; D066298:In Vitro Techniques; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D009389:Neovascularization, Pathologic; D010006:Osteoblasts / Q000166:cytology*; D010012:Osteogenesis; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: D001672:Biocompatible Materials; D042461:Vascular Endothelial Growth Factor A; D048271:Chitosan; D017886:Durapatite
keywords: Bone tissue engineering; adenoviral vector; angiogenesis; chitosan; gene therapy; human osteoblasts; hydroxyapatite; rat; scaffold; vascular endothelial growth factor