Initial fiber alignment pattern alters extracellular matrix synthesis in fibroblast-populated fibrin gel cruciforms and correlates with predicted tension

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Abstract

Human dermal fibroblasts entrapped in fibrin gels cast in cross-shaped (cruciform) geometries with 1:1 and 1:0.5 ratios of arm widths were studied to assess whether tension and alignment of the cells and fibrils affected ECM deposition. The cruciforms of contrasting geometry (symmetric vs. asymmetric), which developed different fiber alignment patterns, were harvested at 2, 5, and 10 weeks of culture. Cruciforms were subjected to planar biaxial testing, polarimetric imaging, DNA and biochemical analyses, histological staining, and SEM imaging. As the cruciforms compacted and developed fiber alignment, fibrin was degraded, and elastin and collagen were produced in a geometry-dependent manner. Using a continuum mechanical model that accounts for direction-dependent stress due to cell traction forces and cell contact guidance with aligned fibers that occurs in the cruciforms, the mechanical stress environment was concluded to influence collagen deposition, with deposition being the greatest in the narrow arms of the asymmetric cruciform where stress was predicted to be the largest.

Original languageEnglish (US)
Pages (from-to)714-729
Number of pages16
JournalAnnals of Biomedical Engineering
Volume39
Issue number2
DOIs
StatePublished - Feb 2011

Bibliographical note

Funding Information:
Support for this study was provided by the National Institutes of Health (R01 EB005813 and F32 EB007433). Parts of this study were carried out in the University of Minnesota I.T. Characterization Facility, which receives partial support from the National Science Foundation through the NNIN program. The authors thank Carry Valley, Naomi Fergusen, Sandy Johnson, Mike Evans, Chris Frethem, and Nat Dyment for their technical assistance during the study.

Keywords

  • Collagen
  • Fibrin
  • Mechanical properties
  • Remodeling
  • Tension

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