Effects of Intermittent and Incremental Cyclic Stretch on ERK Signaling and Collagen Production in Engineered Tissue

Jillian B. Schmidt, Kelley Chen, Robert T Tranquillo

Research output: Contribution to journalArticle

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Abstract

Intermittent cyclic stretching and incrementally increasing strain amplitude cyclic stretching were explored to overcome the reported adaptation of fibroblasts in response to constant amplitude cyclic stretching, with the goals of accelerating collagen production and understanding the underlying cell signaling. The effects of constant amplitude, intermittent, and incremental cyclic stretching regimens were investigated for dermal fibroblasts entrapped in a fibrin gel by monitoring the extracellular signal-regulated kinase (ERK1/2) and p38 pathways, collagen transcription, and finally the deposited collagen protein. Activation of ERK1/2, which has been shown to be necessary for stretch-induced collagen transcription, was maximal at 15 min and decayed by 1 h. ERK1/2 was reactivated by an additional onset of stretching or by an increment in the strain amplitude 6 h after the initial stimulus, which was approximately the lifetime of activated p38, a known ERK1/2 inhibitor. While both intermittent and incremental regimens reactivated ERK1/2, only incremental stretching increased collagen production compared to samples stretched with constant amplitude, resulting in a 37% increase in collagen per cell after 2 weeks. This suggests that a regimen with small, frequent increments in strain amplitude is optimal for this system and should be used in bioreactors for engineered tissues requiring high collagen content.

Original languageEnglish (US)
Pages (from-to)55-64
Number of pages10
JournalCellular and Molecular Bioengineering
Volume9
Issue number1
DOIs
StatePublished - Mar 1 2016

Fingerprint

Collagen
Stretch
Stretching
Tissue
Fibroblasts
Transcription
Increment
Cell signaling
Bioreactor
MAP Kinase Signaling System
Mitogen-Activated Protein Kinase 1
Extracellular Signal-Regulated MAP Kinases
Cell
Bioreactors
Fibrin
Inhibitor
Activation
Pathway
Lifetime
Gels

Keywords

  • Fibrin
  • Fibroblast
  • Mechanical conditioning
  • Mitogen activated protein kinase
  • p38

Cite this

Effects of Intermittent and Incremental Cyclic Stretch on ERK Signaling and Collagen Production in Engineered Tissue. / Schmidt, Jillian B.; Chen, Kelley; Tranquillo, Robert T.

In: Cellular and Molecular Bioengineering, Vol. 9, No. 1, 01.03.2016, p. 55-64.

Research output: Contribution to journalArticle

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