| Bio-artificial tissue constructs serve as a realistic environment in which to test the biophysics of living cells, and as potential replacements for diseased or injured tissues. Continuum constitutive laws are needed to ensure that bio-artificial tissue constructs replicate the mechanical response of the tissues they replace, and to understand how the constituents of these constructs contribute to their overall mechanical response. The complexity and small size of the tissue constituents complicates measurement of their mechanical properties. Therefore, these constitutive laws are useful for deriving microscopic mechanical properties from macroscopic mechanical measurements. In this dissertation, an elastic constitutive framework is developed, and used to characterize several aspects of cell and extracellular matrix mechanics in bio-artificial tissue constructs. The constitutive framework reduces to Eshelby's exact solution (Eshelby, 1957) for special cases of sparse cell distributions and to the Zahalak model (Zahalak et al., 2000) for dense cell distributions. Limitations are discussed and quantified, and corrections are provided for special cases in which they are needed. The beginnings of an extension of this work to viscoelasticity are presented in the form of a rheological model for tissue constructs based on simple viscoelastic elements. The constitutive framework is applied in this dissertation to experimentally identify how cell concentration affects the mechanics cells and of remodeled collagen in a bio-artificial tissue construct via experiments. Several experimental tools are developed, including an automated scheme to measure cell orientation distributions, a very important determinant of the mechanical properties of these constructs. The results obtained are useful to establish which variables that govern cell and matrix mechanical properties, and also to predict tissue mechanical response as a function of these variables. |
