Date of Award

Fall 2014

Degree Type


Degree Name

Doctor of Philosophy (PhD)


Mechanical Engineering

First Advisor

Bumsoo Han

Committee Chair

Bumsoo Han

Committee Member 1

Yoon Yeo

Committee Member 2

Steve Wereley

Committee Member 3

Sherry Voytik-Harbin

Committee Member 4

Xianfan Xu


Tissue engineering is a promising technology that enables scientists to create artificial organs or replace damaged tissues using animal cells and other components. For successful tissue regeneration, many factors should be taken into account, however, three components are most crucial: cell, scaffold, and soluble factor(s). In order to check the functionality after regeneration of desired tissues, various approaches have been attempted, depending on the physical, biological, and chemical properties of the tissues. Recently, the importance of the extracellular matrix (ECM) microstructure is being considered to be important in this regard. The ECM is closely associated with various functional properties of the tissues including mechanical properties, diffusivity, and hydraulic conductivity or permeability. Besides providing structural support and determining the physical and functional properties, the ECM plays various roles in tissue physiology by regulating cell morphology, growth and intercellular signaling. The ECM can also be reconfigured by cells during tissue remodeling and wound healing. In this thesis, in order to investigate the structure-functionality relationship of engineered tissues (ETs), computational modeling and experimental studies were performed based on the following three topics: (1) the effect of different ECM structures on the tissue transport property, (2) the effect of the different ECM structures on the cell functionality and subsequent tissue mechanical property, and (3) the evaluation of functionality of new vessel networks formed by modulation of ECM structures. ^ The first study developed computational models (i.e., parameter- and image-based models) using experimental data to predict transport properties (i.e.,permeability and diffusivity) of two different microstructural matrices (i.e., monomer and oligomer) for tissue functionality. The developed computational models underestimated the permeability result compared to what was obtained experimentally. The image- and parameter-based models developed in the present study were able to predict values closest to the experiment data, when compared with previously reported models of permeability. For diffusivity, the computational results showed a similar trend and magnitude to the experimental ones. ^ During cryopreservation of tissues, freezing-induced structural deformation of the tissues and cells occurs due to formation of ice within the intracellular and extracellular spaces. Several studies focused on developing optimal combinations of cryoprotective agent (CPA) and freeze/thaw (F/T) protocols for functional tissue and cell preservation. In the second study, a hypothesis was tested that the modulation of the cytoskeletal structure can mitigate the freezing-induced changes of the functionality, therefore, may reduce the amount of CPA necessary to preserve the tissue's functionality during cryopreservation. In order to test the above hypothesis, the engineered tissues (ETs) were exposed to various F/T conditions with or without CPAs, and the freezing-induced cell-fluid-matrix interactions and subsequent functional properties of the ETs were assessed. Our result showed that, the use of only a small concentration of CPA was very successful in completely preserving the elastic modulus and the viscous friction to the state of the unfrozen 3D stressed structure (STR). This result underscores the importance of CPA in preserving the cytoskeleton structure and how that impacts functional properties of the tissue after freeze-thaw cycles. ^ The third study performed the parametric study to estimate endothelium hydraulic conductivity for vessel functionality. Currently, it is known that formation of vasculatures within the tissues is the most difficult aspect of tissue engineering. Moreover, a method to evaluate new vessel functionality has not been well-established to date. Therefore, a new method with the osmotic pressure-driven vessel deformation and the poroelastic theory was developed using new vessel networks formed by vasculogenesis for hydraulic conductivity estimation. Results showed that the hydraulic conductivity was more sensitive to the elastic modulus compared to other parameters. When the elastic modulus with 10 - 100 Pa and Possions's ratio with 0.3 were applied, the hydraulic conductivity was well-matched with the previously reported hydraulic conductivity.