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In vitro and in vivo evaluation of adenovirus combined silk fibroin scaffolds for BMP-7 gene delivery

Zhang , Yufeng, Fan, Wei, Nothdurft, Luke, Wu , Chengtie, Zhou, Yinghong, Crawford, Ross, & Xiao, Yin (2011) In vitro and in vivo evaluation of adenovirus combined silk fibroin scaffolds for BMP-7 gene delivery. Tissue Engineering Part C: Methods, 17(8), pp. 789-797.

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Abstract

Introduction and aims: For a scaffold material to be considered effective and efficient for tissue engineering it must be biocompatible as well as 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 osteo-inductive and new bone formation properties of these constructs were assessed in vivo in a critical-sized skull defect animal model. Materials and 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 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 silk fibroin is a promising biomaterial for gene delivery to repair critical-sized bone defects.

Impact and interest:

11 citations in Scopus
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ID Code: 41454
Item Type: Journal Article
Keywords: Tissue regeneration, scaffold, silk fibroin, BMP-7, adenovirus, gene delivery
DOI: 10.1089/ten.TEA.2010.0453
ISSN: 1937-3384
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100)
Australian and New Zealand Standard Research Classification > ENGINEERING (090000) > BIOMEDICAL ENGINEERING (090300)
Divisions: Past > Schools > Biogeoscience
Past > QUT Faculties & Divisions > Faculty of Built Environment and Engineering
Current > Institutes > Institute of Health and Biomedical Innovation
Past > Schools > School of Engineering Systems
Copyright Owner: Copyright 2011 Please consult the authors.
Deposited On: 28 Apr 2011 12:37
Last Modified: 27 Oct 2011 08:51

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