Determination of cellular and matrix mechanics in engineered tissues during cyclic mechanical stretch

Bioartificial tissues are being developed as replacements for damaged or diseased tissues and as model systems for in vitro studies. In both cases, it is desirable to understand the mechanics of the individual cell and matrix components of the tissue. This is particularly important when studying or engineering load-bearing (e.g. cardiovascular) tissues.;This dissertation investigates the cellular and matrix mechanics of ring-shaped bioartificial tissues fabricated using chick embryonic cardiac fibroblasts and collagen.;The short-term response was studied in rings undergoing uniaxial cyclic stretch over a range of amplitudes and frequencies after incubation times of 2 to 8 days. Tissue and matrix forces were monitored continuously for 12 hours. Cell forces were estimated by subtracting matrix force from tissue force. Both cell and matrix mechanics were influenced more by cyclic stretch amplitude than frequency. Peak cell force was similar for different stretch amplitudes, resulting in decreasing cell stiffness with increasing amplitude. The matrix response was highly non-linear with a continuous decrease in peak force over 12 hours.;The response to long-term cyclic stretch was studied in rings undergoing continuous cyclic stretch for 6 days at three frequencies and two amplitudes. Long-term cyclic stretch at 0.25 Hz had little effect on cell or matrix mechanics, but stretching at 1.47 Hz resulted in increased cell and matrix force and stiffness while stretching at 3.50 Hz reduced the per cell force. These results suggest that cardiac fibroblasts may have a response tuned to physiologic stretching frequencies.;A previous model (Wagenseil and Okamoto 2006) was used to provide insight into the structural basis for observed changes in cell and matrix mechanics. Model parameters were modified to be functions of cyclic stretch amplitude, frequency, and number of cycles. These parameters were fit to data from the short-term studies and the model predicted values closely matching experimental data.;The studies presented in this dissertation provide insight into changes in tissue, matrix, and cell mechanics during short-term and long-term cyclic stretching. Data for the matrix and cell components can be used to modify existing models or as a basis for developing new models for cardiovascular tissues.