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Research Article

Substantial expression of mature elastin in arterial constructs

Kee-Won Lee, Donna B. Stolz, and Yadong Wang
PNAS first published January 31, 2011; https://doi.org/10.1073/pnas.1017834108
Kee-Won Lee
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Donna B. Stolz
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Yadong Wang
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  • For correspondence: yaw20@pitt.edu
  1. Edited by Robert Langer, Massachusetts Institute of Technology, Cambridge, MA, and approved December 30, 2010 (received for review December 2, 2010)

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Abstract

Mature elastin synthesis is a key challenge in arterial tissue engineering. Most engineered vessels lack elastic fibers in the medial layer and those present are poorly organized. The objective of this study is to increase mature elastin synthesis in small-diameter arterial constructs. Adult primary baboon smooth muscle cells (SMCs) were seeded in the lumen of porous tubular scaffolds fabricated from a biodegradable elastomer, poly(glycerol sebacate) (PGS) and cultured in a pulsatile flow bioreactor for 3 wk. We tested the effect of pore sizes on construct properties by histological, biochemical, and mechanical evaluations. Histological analysis revealed circumferentially organized extracellular matrix proteins including elastin and the presence of multilayered SMCs expressing calponin and α-smooth muscle actin. Biochemical analysis demonstrated that the constructs contained mature elastin equivalent to 19% of the native arteries. Mechanical tests indicated that the constructs could withstand up to 200 mmHg burst pressure and exhibited compliance comparable to native arteries. These results show that nontransfected cells in PGS scaffolds in unsupplemented medium produced a substantial amount of mature elastin within 3 wk and the elastic fibers had similar orientation as those in native arteries. The 25–32 μm pore size supported cell organization and elastin synthesis more than larger pore sizes. To our knowledge, there was no prior report of the synthesis of mature and organized elastin in arterial constructs without exogenous factors or viral transduction.

  • blood vessel
  • regenerative medicine

Footnotes

  • 1To whom correspondence may be addressed at: Department of Bioengineering and the McGowan Institute for Regenerative Medicine, University of Pittsburgh, 300 Technology Drive, Pittsburgh, PA 15219. E-mail: yaw20{at}pitt.edu.
  • Author contributions: Y.W. designed research; K.-W.L. performed research; K.-W.L., D.B.S., and Y.W. analyzed data; and K.-W.L. and Y.W. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1017834108/-/DCSupplemental.

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Substantial expression of mature elastin in arterial constructs
Kee-Won Lee, Donna B. Stolz, Yadong Wang
Proceedings of the National Academy of Sciences Feb 2011, DOI: 10.1073/pnas.1017834108

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Substantial expression of mature elastin in arterial constructs
Kee-Won Lee, Donna B. Stolz, Yadong Wang
Proceedings of the National Academy of Sciences Feb 2011, DOI: 10.1073/pnas.1017834108
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