title: Cyclic strain increases fibroblast proliferation, matrix accumulation, and elastic modulus of fibroblast-seeded polyurethane constructs.
abstract: 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.
authors.affiliation: Department of Bioengineering, The Keck Center for Tissue Engineering, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Ken
authors.initials: K
authors.lastname: Webb
authors.forename: Robert W
authors.initials: RW
authors.lastname: Hitchcock
authors.forename: Roy M
authors.initials: RM
authors.lastname: Smeal
authors.forename: Wenhua
authors.initials: W
authors.lastname: Li
authors.forename: Steven D
authors.initials: SD
authors.lastname: Gray
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Tresco
mesh_terms: D001205:Ascorbic Acid / Q000494:pharmacology; D019149:Bioreactors; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects*; D005109:Extracellular Matrix / Q000187:drug effects / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D008022:Ligaments; D008969:Molecular Sequence Data; D011140:Polyurethanes / Q000494:pharmacology*; D013314:Stress, Mechanical; D013710:Tendons; D023822:Tissue Engineering / Q000379:methods*; D014182:Transplantation, Autologous; D016474:Weight-Bearing / Q000502:physiology
chemical_list: D011140:Polyurethanes; D001205:Ascorbic Acid