Elastic fiber production in cardiovascular tissue-equivalents

Jennifer L. Long, Robert T. Tranquillo

Research output: Contribution to journalArticlepeer-review

216 Scopus citations

Abstract

Elastic fiber incorporation is critical to the success of tissue-engineered arteries and heart valves. Elastic fibers have not yet been observed in tissue-engineered replacements fabricated in vitro with smooth muscle cells. Here, rat smooth muscle cells (SMC) or human dermal fibroblasts (HDF) remodeled collagen or fibrin gels for 4 weeks as the basis for a completely biological cardiovascular tissue replacement. Immunolabeling, alkaline extraction and amino acid analysis identified and quantified elastin. Organized elastic fibers formed when neonatal SMC were cultured in fibrin gel. Fibrillin-1 deposition occurred but elastin was detected in regions without fibrillin-1, indicating that a microfibril template is not required for elastic fiber formation within fibrin. Collagen did not support substantial elastogenesis by SMC. The quantity of crosslinked elastic fibers was enhanced by treatment with TGF-β1 and insulin, concomitant with increased collagen production. These additives overcame ascorbate's inhibition of elastogenesis in fibrin. The elastic fibers that formed in fibrin treated with TGF-β1 and insulin contained crosslinks, as evidenced by the presence of desmosine and an altered elastin labeling pattern when β-aminopropionitrile (BAPN) was added. These findings indicate that in vitro elastogenesis can be achieved in tissue engineering applications, and they suggest a physiologically relevant model system for the study of three-dimensional elastic structures.

Original languageEnglish (US)
Pages (from-to)339-350
Number of pages12
JournalMatrix Biology
Volume22
Issue number4
DOIs
StatePublished - Jun 2003

Bibliographical note

Funding Information:
We gratefully acknowledge Dr Barry Starcher for performing the desmosine RIA. This work has been supported by NHLBI 1R01 HL60495 (R.T.T.), a Whitaker Foundation Graduate Fellowship (J.L.L.), and a Bakken/McKnight M.D./Ph.D. Endowment (J.L.L.).

Keywords

  • Elastin
  • Fibrillin
  • Fibrin
  • Smooth muscle cell
  • Tissue engineering

Fingerprint

Dive into the research topics of 'Elastic fiber production in cardiovascular tissue-equivalents'. Together they form a unique fingerprint.

Cite this