The effects of Runx2 immobilization on poly (ε-caprolactone) on osteoblast differentiation of bone marrow stromal cells in vitro

Ying Zhang, Xiaopei Deng, Erica L. Scheller, Tae Geon Kwon, Joerg Lahann, Renny T. Franceschi, Paul H. Krebsbach

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

In vivo regenerative gene therapy is a promising approach for bone regeneration and can help to address cell-source limitations through surgical implantation of osteoinductive materials and subsequent recruitment of host-derived cells. Localized viral delivery may reduce the risk of virus dispersion, enhance transduction efficiency, and reduce administration/injection dosing, which subsequently increases patient safety. In this manuscript, we present a custom-tailored strategy to immobilize adenovirus expressing runt-related transcription factor 2 (AdRunx2) by using reactive polymer coatings to enhance in vitro osteoblast differentiation of bone marrow stromal cells (BMSCs). A thin polymer film of poly[p-xylylene carboxylic acid pentafluorophenol ester-co-p-xylylene] equipped with amine-reactive active ester groups was deposited on the surface of poly (ε-caprolactone) (PCL) using the chemical vapor deposition (CVD) polymerization technique and then anti-adenovirus antibody was conjugated on the material with an amide chemical bond. Following antibody conjugation, AdRunx2 was conjugated to the PCL surface through antibody-antigen interaction. Osteoblast differentiation of BMSCs was induced by incubation in osteogenic medium. Alkaline phosphatase (ALP) activity, calcium deposition, and matrix mineralization were confirmed as markers of osteoblast formation. Incubation of the BMSCs in the presence of AdRunx2 modified PCL resulted in a 6.5-fold increase in ALP activity and significant increases in matrix mineralization when compared to controls. These results demonstrate that adenovirus vectors driving the expression of transcription factors can be delivered directly from biomaterials to direct cell differentiation.

Original languageEnglish
Pages (from-to)3231-3236
Number of pages6
JournalBiomaterials
Volume31
Issue number12
DOIs
StatePublished - Apr 1 2010
Externally publishedYes

Keywords

  • Biomaterials
  • Bone marrow stromal cells
  • Local immobilization
  • Osteogenesis
  • Reactive coatings
  • Regenerative gene therapy

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