Cardiothoracic and Vascular Program
Heart Valve Laboratory
This laboratory was originally established to study the mechanics of tissue based artificial heart valves (bioprostheses). The scope of the activities in the laboratory ranges from soft tissue mechanics, to image processing, to the study of valve calcification, to tissue engineering. The activities in the laboratory are primarily experimental in nature, although some projects involve mathematical modeling. The ultimate goal of this research program is to understand the structure and function of the cardiac valves, so that new, more durable bioprostheses can be developed. During this process, the knowledge learned about the structure and the proper function of cardiac valves can be applied to patient care at the Childrens Hospital Los Angeles.
The main approach of the Heart Valve Laboratory is to study the structure/function relationship of heart valve tissues so that we can determine the failure mechanisms and find ways to improve the design and fabrication of existing artificial heart valves. Our ultimate goal is to develop a bioprosthetic valve that completely mimics the function of the natural valve it must replace. As biomedical engineers, our research makes use of engineering approaches to study and understand the aortic and mitral valves. This involves materials testing, mathematical modeling, and microscopy and biochemical analysis.
Micro mechanical testing of the valve tissue is being done to determine the functional relationships between the fibrosa and the ventricularis, and the roles played by collagen and Elastin. This is done at very high speed to simulate physiological loading conditions. We are also using selective enzymatic degradation to remove certain valve tissue structural proteins (collagen, Elastin, Gag’s), and then measure the mechanics of the resulting material to determine how each constituent contributes to the mechanics of the whole tissue.
We use a video image processing technique to measure biaxial strains of the valve materials in their intact state. Such alternative materials testing techniques are needed to describe completely the material properties of such highly deformable and anisotropic fibrous materials.
We are using mathematical modeling to analyze the viscoelastic nature of the heart valve tissue, and to establish a closer link between testing and analysis. Through such a link, difficult-to-measure material parameters can be estimated, constitutive models verified, and difficult-to-perform tests simulated. Thus far, we have developed extensions to Fung's original Quasilinear Viscoelastic theory, that enable us to extract QLV parameters from conventional, medium speed materials tests, that are remarkably predictive of the long term cyclic loading behavior of the heart valve tissue. In collaboration with researchers at NASA, we are studying a fiber composite model in its ability to predict the mechanics of heart valves tissues.
Computerized video densitometry, polarized light microscopy, specific antibody staining, and 3-D reconstruction of serial sections all have been used to quantify the content and distribution of collagen, elastin and glycosaminoglycans throughout the aortic valve cusps.
The mechanical, microscopic and biochemical techniques developed on aortic valves, have recently been applied to the study of myxomatous mitral valve disease. This is a disease characterized by thickening of the valve tissues and stretching of the leaflets and chordae causing the valve to leak. Although it can be corrected surgically, the outcomes are not always satisfactory, and the disease itself is not at all understood. By understanding the cause of the disease, we can better treat the patient. To that end, we have been studying the specific biochemical and mechanical changes that occur in these tissues. Our results suggests that it is a disease more of the chordae, rather than the leaflets, as was previously thought. We are also beginning to explore the genetic determinants of the disease, to better understand its cause.
A long-term project is ongoing to engineer a viable tissue valve implant consisting of materials currently found in the natural tissues; the elastin, collagen and glycosaminoglycans. These molecul es can be synthesized by cells in culture or purified from tissues, and then manipulated to mimic the normal structural framework of the aortic valve. Living cells harvested from the intended recipient of this device can then be cultured on these materials to transform an essentially dead, inert material, to one that behaves biomechanically more like the native valve, and may be capable of repair and regeneration. This process is referred to as tissue engineering, and our approach is specifically focused on replacing connective tissues that are not capable of repair on their own.
This research is funded by grants from the NIH and the U.S. Army. We are actively seeking ways of augmenting our research funds by participating in technology transfer, through research contracts from Industry.