title: In vitro and in vivo evaluation of adenovirus combined silk fibroin scaffolds for bone morphogenetic protein-7 gene delivery.
abstract: OBJECTIVE
  For a scaffold material to be considered effective and efficient for tissue engineering, it should be biocompatible and bioinductive. Silk fiber is a natural biocompatible material suitable for scaffold fabrication; however, silk is tissue conductive and lacks tissue-inductive properties. One proposed method to make the scaffold tissue inductive is to introduce plasmids or viruses encoding a specific growth factor into the scaffold. In this study, we constructed adenoviruses encoding bone morphogenetic protein-7 (BMP-7) and incorporated these into silk scaffolds. The osteoinductive and new bone formation properties of these constructs were assessed in vivo in a critical-sized skull defect animal model.
  
  
  METHODS
  Silk fibroin scaffolds containing adenovirus particles coding BMP-7 were prepared. The release of the adenovirus particles from the scaffolds was quantified by tissue-culture infective dose (TCID50), and the bioactivity of the released viruses was evaluated on human bone marrow mesenchymal stromal cells (BMSCs). To demonstrate the in vivo bone forming ability of the virus-carrying silk fibroin scaffold, the scaffold constructs were implanted into calvarial defects in SCID mice.
  
  
  RESULTS
  In vitro studies demonstrated that the virus-carrying silk fibroin scaffold released virus particles over a 3-week period while preserving their bioactivity. In vivo test of the scaffold constructs in critical-sized skull defect areas revealed that silk scaffolds were capable of delivering the adenovirus encoding BMP-7, resulting in significantly enhanced new bone formation.
  
  
  CONCLUSIONS
  Silk scaffolds carrying BMP-7 encoding adenoviruses can effectively transfect cells and enhance both in vitro and in vivo osteogenesis. The findings of this study indicate that silk fibroin is a promising biomaterial for gene delivery to repair critical-sized bone defects.
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Fan
authors.forename: Luke
authors.initials: L
authors.lastname: Nothdurft
authors.forename: Chengtie
authors.initials: C
authors.lastname: Wu
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Ross
authors.initials: R
authors.lastname: Crawford
authors.forename: Yin
authors.initials: Y
authors.lastname: Xiao
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D001854:Bone Marrow Cells / Q000166:cytology; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics*; D004195:Disease Models, Animal; D005349:Fibroins / Q000494:pharmacology*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D021621:Imaging, Three-Dimensional; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D016513:Mice, SCID; D008855:Microscopy, Electron, Scanning / Q000379:methods; D016062:Porosity; D047011:Silk / Q000494:pharmacology*; D014057:Tomography, X-Ray Computed / Q000379:methods; D014162:Transfection; D055114:X-Ray Microtomography / Q000379:methods
chemical_list: D001672:Biocompatible Materials; D055419:Bone Morphogenetic Protein 7; D047011:Silk; D005349:Fibroins