Research Summary
Our overall research focus is the characterization and modeling of the structure-function-biomechanics of native and engineered cardiovascular soft tissues, and linking these studies to the underlying cellular mechanobiological responses. In particular, our laboratory has focused on the mechanical behavior and function of the native heart valve tissues, including the development of the first constitutive (stress-strain) models for these tissues using a structural approach. To acquire the necessary critical experimental data, our laboratory has developed several novel methods to quantify tissue structure and 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. We are particularly interested in determining the local stress environment of heart valve interstitial cells. This work aims to utilize and 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.
We also interested in pediatric applications which seek to correct congenital anomalies of the pulmonary valve, wherein accommodation of somatic growth is essential to eliminate multiple reoperations. Tissue engineered pulmonary valves (TEPV) are one such approach that have the potential to develop into a permanent replacement. A fundamental aspect of the development a TEPV capable of physiologic function at the time of implant is knowledge of the biological and mechanical stimulatory requirements to form mechanically robust, biomimetic valvular tissues in-vitro. While it has become axiomatic that in vitro mechanical conditioning promotes engineered tissue formation in-vitro, the underlying mechanisms remain largely unknown, as well as a means to systematically translate these phenomena to the organ level. This lack of knowledge remains a major limiting factor in the rational development engineered heart valve tissues, especially when considering that valve leaflets are subjected to complex, time varying loading environments. Thus, many questions remain regarding the exact nature and timeframe of in-vitro conditioning necessary for optimal tissue formation. This optimization process must also take into consideration multiple factors, such as leaflet shape and scaffold material properties that will provide the construct with sufficient in vivo functionality. At a minimum, sufficient tissue formation, with the appropriate physical qualities, needs to occur prior to implantation so that the TEPV construct can functionally sustain the in vivo hemodynamic environment. We are currently developing novel experimental and computational approaches to address these issues.