Mechanical stress and cellular metabolism in living soft tissue composites.

A soft tissue substitute composed of a three-dimensional collagen lattice infiltrated with living fibroblasts was modelled as a two-phase composite material. The phases consisted of an extracellular matrix containing fibres and fluid and cellular inclusions. A mathematical model that had been previously derived for calculating the elastic stress and energy distribution around spherical inclusions and voids in a three-dimensional elastic medium was applied to a biological composite containing cells in an elastic medium. The model predicted an increase in stress inside the cells in the direction of applied load and a decrease in the direction perpendicular to the applied load. The model also predicted increased interfacial stress at the cell-matrix boundary in the direction of applied load with maximum and minimum values at different points on the cell periphery. It was hypothesized that the interfacial stress around the cell inclusions might play a function in signal transduction. To test this hypothesis, an average unidirectional stress was applied to the boundary of a 1 cm X 2 cm X 3 mm lattice containing fibroblasts. When cells were cultured for 7 d and placed under stress of 15 g, cell growth was increased 1.7 fold, protein synthesis decreased 48% and intracellular cAMP was increased 3.7 fold in 24 h. The changes were a function of externally applied stress. Cells cultured for 14 d and placed under stress displayed similar results. The results supported the concept that soft tissue extracellular matrix depicted as an elastic medium can affect cell growth and development.(ABSTRACT TRUNCATED AT 250 WORDS)