All tissues in the human body continuously grow, remodel, and adapt to changes in their physiological environment, in order to maintain homeostasis or to retain it in case of pathologies. The growth and remodeling (GR) process results in changes in structure and composition. To elucidate how observed changes in tissue components are related to altered tissue level mechanical behavior, structural constitutive models are required with physiologically relevant model parameters. Specifically what is required is a finite deformation constitutive model describing the tissue mechanical behavior, in combination with the appropriate kinematics for the multiple tissue components, and experimental data of a relevant tissue application. An excellent example is the urinary bladder wall (UBW), which undergoes profound remodeling in response to different pathologies, such as spinal cord injury (SCI). The overall objective of this dissertation was to develop a morphologically-driven, multi-phase constitutive model that would allow for separate investigation of the contribution of individual tissue components to the tissue-level remodeling process. As a first step, a constitutive model was developed of UBW extracellular matrix (ECM). Removing the smooth muscle cells from UBW tissue via decellularization allowed for the separate mechanical and structural investigation of UBW ECM. It was shown that the presence of de novo produced elastin in the UBW ECM post-SCI induced, indirectly, a distinct mechanical behavior with higher compliance, allowing for a higher overall extensibility of the post-SCI UBW and increased bladder storage capacity. The ECM constitutive model was extended and modified to be able to apply it to a multi-component tissue with individual model components existing in different reference states. Parameters were determined from biaxial mechanical data of decellularized and intact UBW tissue using a step-wise fitting approach implemented in MATLAB. As an initial step towards a theoretical GR framework, a parametric analysis was performed to investigate if observed mechanical changes in post-SCI UBW were due to changes in morphology or intrinsic constituent properties. The developed model has the potential to explain underlying remodeling mechanisms of individual constituents in muscular tissues in several pathologies (e.g. UBW post-SCI), and predict remodeling events in a tissue engineering setting of muscular tissues.
|Publication status||Published - 1 Sept 2010|