Archives—January 2011

Tissue Engineered Models for Fundamental Study and Treatment of Heart Valve

Wednesday, January 19
211 Chemical Sciences & Engineering Building
2:00 pm

Presenter: Zannatul Ferdous, Ph.D., Parker H. Petit Institute of Bioengineering and Bioscience Georgia Institute of Technology

Abstract: My research uses unique model systems to study mechanisms and causes of cardiovascular diseases, particularly pathologies of heart valves. Valve diseases and defects are major causes of mortality in the elderly population and children in the US. Since altered expression of decorin has been observed in diseased heart valves, for my graduate research, the roles of proteoglycan decorin on extracellular matrix remodeling and tissue mechanics were investigated. Using tissueengineered collagen gels, we demonstrated that decorin-mediated matrix remodeling was heavily modulated by decorin-transforming growth factor beta (TGF-β) interaction. In addition, cyclic strain promoted compensatory behavior in collagen gels containing decorin-deficient cells, suggesting the influence of tissue mechanics on cellular function. We also showed the utility of a proper chemical and mechanical environment for studying  ex vivo tissue systems. For my postdoctoral research, the contributions of mechanical forces to the initiation and progression of vascular and valvular calcification are being studied using cells isolated from non-sclerotic human tissues. We have observed that expression of osteogenic and matrix remodeling markers are dependent on both cell source (vascular versus valvular) and mechanical strain. In addition, calcification is observed to be modulated by the magnitude of strain (physiological versus pathological) applied to either cell types. We anticipate that the tissue-engineered model would help determine biomarkers for early detection and prevention of valve calcification. Additionally, the roles of microRNAs (miRNAs) in valvular diseases are also being investigated using RNAs isolated from endothelial cells in freshly isolated porcine valves. We hope that this research would lead to the discovery of important miRNAs and their roles in aortic valve biology and diseases. Continued research would therefore improve our knowledge of the complex heart valve environment and help determine treatment options for the large population of elderly and children in need for valve replacement.

Recreate Biomimetic Microenvironment for Regenerative Medicine Tissue-engineering of Scaffold-free Small-diameter Blood Vessel

Tuesday, January 11
U113 M&M Building
2:00 pm

Presenter: Feng Zhao, Ph.D., Department of Biomedical Engineering, Duke University

Abstract: The recreation of a natural microenvironment is  of significant importance to realize the regeneration potential of cells for engineering functional tissues.  My research aims to replicate the in vivo cell-cell and cell-environment interactions by manipulating biomaterials, oxygen tension, and hydrodynamic culture conditions in a precisely controlled manner.  The current study focuses on tissue-engineering of scaffold-free small-diameter blood vessel using human mesenchymal stem cells (hMSCs) based on their unique antithrombogenic property, immunomodulatory ability, and pluripotency for differentiation into vascular phenotypes. The fulfillment of the therapeutic application of tissue-engineered blood vessel (TEBV) from hMSCs requires the cells to maintain high viability, organization, and stemness.  By culturing hMSCs under the combined stimulation of nanotopographical cue and low oxygen tension, an extensively aligned cell sheet was fabricated with well-preserved stemness and viability. The physiologically low O2 (2%) tension significantly improved the confluency and extracellular matrix proteins secretion of the cells, which facilitated the process of cell sheet harvesting.  The fabrication of a completely biological tubular structure was achieved by wrapping the aligned hMSC  sheets around a temporary supporting mandrel. Maturation of the cellular construct in the rotating wall bioreactor reinforced its mechanical stability and allowed its development into an implantable  small-diameter TEBV.  The preliminary animal study in a rat femoral artery model demonstrated the remodeling of the vascular graft as well as the infiltration of endothelial cells into the hMSC-based TEBV.