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Tissue-engineered cartilage with inducible and tunable immunomodulatory properties.

Publication ,  Journal Article
Glass, KA; Link, JM; Brunger, JM; Moutos, FT; Gersbach, CA; Guilak, F
Published in: Biomaterials
July 2014

The pathogenesis of osteoarthritis is mediated in part by inflammatory cytokines including interleukin-1 (IL-1), which promote degradation of articular cartilage and prevent human mesenchymal stem cell (MSC) chondrogenesis. In this study, we combined gene therapy and functional tissue engineering to develop engineered cartilage with immunomodulatory properties that allow chondrogenesis in the presence of pathologic levels of IL-1 by inducing overexpression of IL-1 receptor antagonist (IL-1Ra) in MSCs via scaffold-mediated lentiviral gene delivery. A doxycycline-inducible vector was used to transduce MSCs in monolayer or within 3D woven PCL scaffolds to enable tunable IL-1Ra production. In the presence of IL-1, IL-1Ra-expressing engineered cartilage produced cartilage-specific extracellular matrix, while resisting IL-1-induced upregulation of matrix metalloproteinases and maintaining mechanical properties similar to native articular cartilage. The ability of functional engineered cartilage to deliver tunable anti-inflammatory cytokines to the joint may enhance the long-term success of therapies for cartilage injuries or osteoarthritis.

Duke Scholars

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Published In

Biomaterials

DOI

EISSN

1878-5905

ISSN

0142-9612

Publication Date

July 2014

Volume

35

Issue

22

Start / End Page

5921 / 5931

Related Subject Headings

  • Up-Regulation
  • Tissue Scaffolds
  • Tissue Engineering
  • Osteoarthritis
  • Mesenchymal Stem Cells
  • Interleukin-1
  • Interleukin 1 Receptor Antagonist Protein
  • Humans
  • Genetic Therapy
  • Chondrogenesis
 

Citation

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Glass, K. A., Link, J. M., Brunger, J. M., Moutos, F. T., Gersbach, C. A., & Guilak, F. (2014). Tissue-engineered cartilage with inducible and tunable immunomodulatory properties. Biomaterials, 35(22), 5921–5931. https://doi.org/10.1016/j.biomaterials.2014.03.073
Glass, Katherine A., Jarrett M. Link, Jonathan M. Brunger, Franklin T. Moutos, Charles A. Gersbach, and Farshid Guilak. “Tissue-engineered cartilage with inducible and tunable immunomodulatory properties.Biomaterials 35, no. 22 (July 2014): 5921–31. https://doi.org/10.1016/j.biomaterials.2014.03.073.
Glass KA, Link JM, Brunger JM, Moutos FT, Gersbach CA, Guilak F. Tissue-engineered cartilage with inducible and tunable immunomodulatory properties. Biomaterials. 2014 Jul;35(22):5921–31.
Glass, Katherine A., et al. “Tissue-engineered cartilage with inducible and tunable immunomodulatory properties.Biomaterials, vol. 35, no. 22, July 2014, pp. 5921–31. Epmc, doi:10.1016/j.biomaterials.2014.03.073.
Glass KA, Link JM, Brunger JM, Moutos FT, Gersbach CA, Guilak F. Tissue-engineered cartilage with inducible and tunable immunomodulatory properties. Biomaterials. 2014 Jul;35(22):5921–5931.
Journal cover image

Published In

Biomaterials

DOI

EISSN

1878-5905

ISSN

0142-9612

Publication Date

July 2014

Volume

35

Issue

22

Start / End Page

5921 / 5931

Related Subject Headings

  • Up-Regulation
  • Tissue Scaffolds
  • Tissue Engineering
  • Osteoarthritis
  • Mesenchymal Stem Cells
  • Interleukin-1
  • Interleukin 1 Receptor Antagonist Protein
  • Humans
  • Genetic Therapy
  • Chondrogenesis