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Scaffold-mediated lentiviral transduction for functional tissue engineering of cartilage.

Publication ,  Journal Article
Brunger, JM; Huynh, NPT; Guenther, CM; Perez-Pinera, P; Moutos, FT; Sanchez-Adams, J; Gersbach, CA; Guilak, F
Published in: Proceedings of the National Academy of Sciences of the United States of America
March 2014

The ability to develop tissue constructs with matrix composition and biomechanical properties that promote rapid tissue repair or regeneration remains an enduring challenge in musculoskeletal engineering. Current approaches require extensive cell manipulation ex vivo, using exogenous growth factors to drive tissue-specific differentiation, matrix accumulation, and mechanical properties, thus limiting their potential clinical utility. The ability to induce and maintain differentiation of stem cells in situ could bypass these steps and enhance the success of engineering approaches for tissue regeneration. The goal of this study was to generate a self-contained bioactive scaffold capable of mediating stem cell differentiation and formation of a cartilaginous extracellular matrix (ECM) using a lentivirus-based method. We first showed that poly-L-lysine could immobilize lentivirus to poly(ε-caprolactone) films and facilitate human mesenchymal stem cell (hMSC) transduction. We then demonstrated that scaffold-mediated gene delivery of transforming growth factor β3 (TGF-β3), using a 3D woven poly(ε-caprolactone) scaffold, induced robust cartilaginous ECM formation by hMSCs. Chondrogenesis induced by scaffold-mediated gene delivery was as effective as traditional differentiation protocols involving medium supplementation with TGF-β3, as assessed by gene expression, biochemical, and biomechanical analyses. Using lentiviral vectors immobilized on a biomechanically functional scaffold, we have developed a system to achieve sustained transgene expression and ECM formation by hMSCs. This method opens new avenues in the development of bioactive implants that circumvent the need for ex vivo tissue generation by enabling the long-term goal of in situ tissue engineering.

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Published In

Proceedings of the National Academy of Sciences of the United States of America

DOI

EISSN

1091-6490

ISSN

0027-8424

Publication Date

March 2014

Volume

111

Issue

9

Start / End Page

E798 / E806

Related Subject Headings

  • Transforming Growth Factor beta3
  • Transduction, Genetic
  • Tissue Scaffolds
  • Tissue Engineering
  • Regenerative Medicine
  • Polylysine
  • Polyesters
  • Microscopy, Fluorescence
  • Microscopy, Electron, Scanning
  • Mesenchymal Stem Cells
 

Citation

APA
Chicago
ICMJE
MLA
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Brunger, J. M., Huynh, N. P. T., Guenther, C. M., Perez-Pinera, P., Moutos, F. T., Sanchez-Adams, J., … Guilak, F. (2014). Scaffold-mediated lentiviral transduction for functional tissue engineering of cartilage. Proceedings of the National Academy of Sciences of the United States of America, 111(9), E798–E806. https://doi.org/10.1073/pnas.1321744111
Brunger, Jonathan M., Nguyen P. T. Huynh, Caitlin M. Guenther, Pablo Perez-Pinera, Franklin T. Moutos, Johannah Sanchez-Adams, Charles A. Gersbach, and Farshid Guilak. “Scaffold-mediated lentiviral transduction for functional tissue engineering of cartilage.Proceedings of the National Academy of Sciences of the United States of America 111, no. 9 (March 2014): E798–806. https://doi.org/10.1073/pnas.1321744111.
Brunger JM, Huynh NPT, Guenther CM, Perez-Pinera P, Moutos FT, Sanchez-Adams J, et al. Scaffold-mediated lentiviral transduction for functional tissue engineering of cartilage. Proceedings of the National Academy of Sciences of the United States of America. 2014 Mar;111(9):E798–806.
Brunger, Jonathan M., et al. “Scaffold-mediated lentiviral transduction for functional tissue engineering of cartilage.Proceedings of the National Academy of Sciences of the United States of America, vol. 111, no. 9, Mar. 2014, pp. E798–806. Epmc, doi:10.1073/pnas.1321744111.
Brunger JM, Huynh NPT, Guenther CM, Perez-Pinera P, Moutos FT, Sanchez-Adams J, Gersbach CA, Guilak F. Scaffold-mediated lentiviral transduction for functional tissue engineering of cartilage. Proceedings of the National Academy of Sciences of the United States of America. 2014 Mar;111(9):E798–E806.
Journal cover image

Published In

Proceedings of the National Academy of Sciences of the United States of America

DOI

EISSN

1091-6490

ISSN

0027-8424

Publication Date

March 2014

Volume

111

Issue

9

Start / End Page

E798 / E806

Related Subject Headings

  • Transforming Growth Factor beta3
  • Transduction, Genetic
  • Tissue Scaffolds
  • Tissue Engineering
  • Regenerative Medicine
  • Polylysine
  • Polyesters
  • Microscopy, Fluorescence
  • Microscopy, Electron, Scanning
  • Mesenchymal Stem Cells