Cyclic strain increases fibroblast proliferation, matrix accumulation, and elastic modulus of fibroblast-seeded polyurethane constructs

J Biomech. 2006;39(6):1136-44. doi: 10.1016/j.jbiomech.2004.08.026. Epub 2005 Oct 26.


Rapid induction of matrix production and mechanical strengthening is essential to the development of bio-artificial constructs for repair and replacement of load-bearing connective tissues. Toward this end, we describe the development of a mechanical bioreactor and its application to investigate the influence of cyclic strain on fibroblast proliferation, matrix accumulation, and the mechanical properties of fibroblast-seeded polyurethane constructs (FSPC). Human fibroblasts were cultured in 10% serum-containing conditions within three-dimensional, porous elastomeric substrates under static conditions and a model regime of cyclic strain (10% strain, 0.25 Hz, 8 h/day), with and without ascorbic acid supplementation. After one week, the combination of cyclic strain and ascorbic acid resulted in significantly increased construct elastic modulus (>110%) relative to either condition alone. In contrast, cyclic strain alone was sufficient to stimulate significant increases in fibroblast proliferation. Mechanical strengthening of FSPCs was accompanied by increased type I collagen and fibronectin matrix accumulation and distribution, and significantly increased gene expression for type I collagen, TGFbeta-1, and CTGF. These results suggest that strain-induced conditioning in vitro leads to mechanical strengthening of fibroblast/material constructs, most likely resulting from increased collagen matrix deposition, secondary to strain-induced increases in cytokine production.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Ascorbic Acid / pharmacology
  • Bioreactors*
  • Cell Culture Techniques
  • Cell Proliferation / drug effects*
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / genetics
  • Fibroblasts / drug effects*
  • Humans
  • Ligaments
  • Molecular Sequence Data
  • Polyurethanes / pharmacology*
  • Stress, Mechanical
  • Tendons
  • Tissue Engineering / methods*
  • Transplantation, Autologous
  • Weight-Bearing / physiology


  • Polyurethanes
  • Ascorbic Acid