Tissue Equivalents
Tissue equivalents, or TEs, are formed by entrapping cells in a reconstituted
biopolymer matrix, typically type I collagen. TEs are used for two
distinct and important purposes:
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Because fibroblasts (in fact, most cells) generate a contractile stress
on the surrounding collagen matrix, a TE will compact over time.
This compaction was the basis of Bell's FPCL (Fibroblast-Populated Collagen
Lattice) assay, which is a simple, efficient way to assess the relative
contractility of cells under different circumstances. One constructs
TEs containing different cells (or under different conditions, such as
a change in media) and records how the TE size changes in each case.
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Within the past decade, researchers have recognized that TEs may be able
to serve as the basis for bioartificial tissues, particularly for the replacement
of skin, blood vessels, and cardiovascular valves.
Our theoretical work in this area hopes to improve and extend the Anisotropic
Biphasic Theory of Tissue-Equivalent Mechanics (ABT) developed by Barocas
and Tranquillo. The ABT provides a quantitative tool for modeling
and interpreting TE experiments, allowing cross-experiment comparisons
of cell behavior and preliminary design of bioartificial tissues.
Adaptive finite solution of the model equations has been effected in collaboration
with J. E. Flaherty of the Department of Computer Science at Rensselaer
Polytechnic Institute. Some movies of simulation results, as well
as the model equations, are available.
New experimental work, in collaboration with John Bischof of our department
and the Department of Mechanical Engineering, focuses on the development
of a tissue-equivalent model for cryoinjury. Our hypothesis is that
the presence of the extracellular matrix affects cellular resistance to
cryoinjury, which could partly explain why monolayer and suspension culture
cryoinjury models predict in vivo results poorly. Our basic
strategy is to fabricate a disk-shaped TE and then cryoinjure it and record
changes in cell behavior and in gross TE morphology.