The present invention provides methods for manipulating the intrinsic
strain of cells by treating tissue engineered constructs or native tissue
with compounds which affect the intrinsic strain setpoint of the cells in
order to modulate matrix synthesis, secretion, organization and/or
remodeling so that the tissues withstand in vivo mechanical forces and
have the structural characteristics of host tissue which has been
permanently altered by injury, atrophy or disease. The compounds include
binding site peptides, ATP, UTP and related analogues, IL-1&bgr;
TGF-&agr; cytochalasin D, hyaluronic acid, nocodazole and others. Also
provided are methods for applying a mechanical external strain to the
tissues, as well as methods for modulating the expression of cytoskeletal
genes that transcribe cytoskeletal proteins which regulate a cell's
intrinsic strain setpoint.