PhD, Department of Bioengineering, Rice University, Houston, TX, USA
Jane Grande-Allen is the Isabel C. Cameron Professor and Chair of the Department of Bioengineering at Rice University. Her research group develops experimental and biomaterial platforms to investigate the biomechanics and mechanobiology of soft connective tissues under healthy and diseased conditions, focusing on the extracellular matrix. Dr. Grande-Allen received a BA in Mathematics and Biology from Transylvania University in 1991 and a PhD in Bioengineering from the University of Washington in 1998. Dr. Grande-Allen has been elected as Fellow of the American Institute of Biological and Medical Engineering, the Biomedical Engineering Society, the American Heart Association, the American Association for the Advancement of Science, and the Society for Experimental Mechanics. She has served on the Board of Directors of the Biomedical Engineering Society and the Society for Experimental Mechanics, and she is Deputy Editor-in-Chief of the Annals of Biomedical Engineering.
Statement of the Problem: The treatment of valve disease represents substantial health care costs, yet there are significant limitations in applying the currently available valve repair and replacement technologies to all patients needing treatment. Tissue engineered valves have the potential to improve the quality and range of treatment options for all patients. The essential function of valves is made possible by the arrangement of extracellular matrix (ECM) within the tissue, but these functional relationships have not been translated into the next generation of valve tissue engineering investigations. Aortic valves are notably anisotropic and their interconnected, layered structure provides valvular interstitial cells (VICs) with heterogeneous environments for substrate adhesion-driven signaling. Our research group is investigating these characteristics to incorporate them into hydrogel biomaterials. Methodology: Porcine aortic valves were characterized using immunohistochemistry, electron microscopy, and biochemical techniques to assess extracellular matrix composition across the valve microstructure. These characteristics were incorporated as patterns or layers within hydrogel scaffolds prepared from polyethylene glycol (PEG) or crosslinked hyaluronan. Findings: These in-depth investigations have provided new insights into of the layered structure of porcine aortic valves, which we are translating into hydrogel scaffold and combination hydrogel-electrospun mesh models of the valve. These laminate hydrogel scaffolds contain layers with different stiffness, much like the leaflet spongiosa, fibrosa, and ventricularis layers demonstrate unique material behavior. Conclusion & Significance: These investigations have demonstrated that the heterogeneous ECM composition of valves influences their mechanics and local valve cell behavior. This heterogeneity can be translated to scaffold materials for tissue engineered heart valves using patterning or other novel fabrication approaches. Laminate hydrogels can be fabricated with robust interfaces, integrating layers of different mechanical properties, as well as varied biofunctionalization, and thus forming the foundation for a multilaminate scaffold that more accurately represents native tissue.