Past Event: Babuška Forum

A triphasic constrained mixture model of engineered tissue formation under in vitro dynamic mechanical conditioning

Michael Sacks, Professor, ICES, UT Austin

Abstract

While it has become axiomatic that mechanical signals promote in vitro engineered tissue formation, the underlying mechanisms remain largely unknown.Moreover, efforts to date to determine parameters for optimal extracellular matrix (ECM) development have been largely empirical. In the present work, we propose a two-pronged approach involving novel theoretical developments coupled with key experimental data to develop better mechanistic understanding of growth and development of dense connective tissue under mechanical stimuli. To describe cellular proliferation and ECM synthesis that occur at rates of days to weeks, we employ mixture theory to model the construct constituents as a nutrient-cell-ECM triphasic system, their transport, and their biochemical reactions. Dynamic conditioning protocols with frequencies around 1Hz are described with multi-scale methods to couple the dissimilar time scales.Enhancement of nutrient transport due to pore fluid advection is upscaled into the growth model, and the spatially dependent ECM distribution describes the evolving poroelastic characteristics of the scaffold-engineered tissue construct. Simulation results compared favorably to the existing experimental data, and most importantly, distinguish between static and dynamic conditioning regimes. The theoretical framework for mechanically conditioned tissue engineering (TE) permits not only the formulation of novel and better-informed mechanistic hypothesis describing the phenomena underlying TE growth and development, but also the exploration/optimization of conditioning protocols in a rational manner. Bio: Dr. Sacks is professor of biomedical engineering and holder of the W. A. "Tex" Moncrief, Jr. Endowment in Simulation-Based Engineering and Sciences Chair No. 1. He is also director of the ICES Center for Cardiovascular Simulation-based Engineering. Dr. Sacks formerly held the John A. Swanson Chair in the Department of Bioengineering at the University of Pittsburgh. He earned his B.S. and M.S. in engineering mechanics from Michigan State University, and his Ph.D. in biomedical engineering (biomechanics) from The University of Texas Southwestern Medical Center at Dallas. His recent research has included developing novel constitutive models of right ventricular myocardium that allow for the individual contributions of the myocyte and connective tissue networks.