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Research Summary
My overall research focus is characterization and modeling of the structure-function-biomechanics of native and engineered soft tissues, and linking these studies to cell-tissue mechanobiological interactions. In particular, my laboratory has focused on the mechanical behavior and function of the native aortic and mitral heart valves, including the development of the first constitutive (stress-strain) models for these tissues using a structural approach. To acquire the necessary critical experimental data, my laboratory has developed several novel methods to quantify tissue structure and multi-axial mechanical testing techniques. By integrating the resulting experimental data obtained from both techniques, we have developed structural constitutive (stress-strain) models that directly integrate information on tissue composition and structure. These models avoid ambiguities in material characterization, offering insight into the function, structure, and mechanics of tissue components. Recent work includes multi-scale studies of cell/tissue/organ mechanical interactions in natie and engineered heart valves. I am particularly interested in determining the local stress environment for heart valve interstitial cells. This work aims to utilize an integrated experimental/multi-scale finite element approach to determine how hemodynamic loading on the valve translates to altered stress states on the valve interstitial cell function and, in-turn, changes in local extra-cellular structure/composition and valve function. My laboratory is also very active in the biomechanics of engineered tissues, and in particular understanding the in-vitro and in-vivo remodeling processes from a functional biomechanical perspective. Our long-term research goal is to develop a rigorous quantitative understanding of the morphological and functional events that occur during both in-vitro development and in-vivo remodeling, and to use this knowledge to improve replacement heart valves for the pediatric population. Specifically, a question fundamental to the successful development of a clinically feasible tissue engineered pulmonary valve (TEPV) is how well does the TEPV functionally match the native pulmonary valve tissue, and what mechanical, structural, and biological factors guide the remodeling process and final outcome. Once these factors are sufficiently well understood, it should then be possible in subsequent studies to optimize cell sourcing, fabrication techniques, and in-vitro conditioning procedures to produce a functioning TEPV designed for long-term in-vivo function. The goal of the current research program is to thus quantify and simulate tissue remodeling events that occur post-implantation, and to understand what primary factors influence the remodeling rate and final tissue state. Specific applications include: Curriculum Vita |
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