We investigate the functional structure and cell/matrix biology, and tissue engineering of heart valves. The objectives of these studies are to understand the mechanisms of normal valve functional dynamics and how these are disrupted in valve disease, and the limitations to the success of currently available prosthetic devices. Our studies provide input to the development of improved management strategies for native and prosthetic valve disease and potentially new medical devices.
Specifically, we study healthy and diseased native heart valves and heart valve prostheses retrieved at reoperation or post-mortem examination. Ongoing investigations of native valves explore the mechanisms of regulation of valvular interstitial cell phenotypes and collagenous matrix under various conditions of altered mechanical environment and patient age throughout life and approaches to the creation of a living valve replacement through in-vitro and in-vivo tissue engineering approaches based on an understanding of valve developmental biology, valvular cell and matrix biology and valve responses to injury. Studies of valve substitutes are designed to establish failure modes, pathologic correlations of clinical function and other details of patient/prosthesis interactions. In preclinical studies, we analyze new valve configurations with modified and potentially improved materials or designs implanted in animals as actual valve replacements in order to evaluate the long-term efficacy and safety of these designs, to predict complications, and to develop new materials and configurations. We also study the mechanisms of particular failure modes associated with degeneration of bioprostheses in experimental animal model systems. For example, our experimental studies of calcification, the major cause of failure of contemporary bioprosthetic valves, have provided the correlation of observations on human material with experimental data and hypotheses, delineating clinicopathologic correlates of failure, the role in calcification of key physiological variables and structural determinants. We are also participating in the development of innovative heart valve replacements, including devices that can be implanted percutaneously through a catheter, and engineered tissue heart valves.
Rabkin-Aikawa E, Aikawa M, Farber, M, Kratz, JR, Garcia-Cardena G, Kouchoukos NT, Mitchell MB, Jonas RA, Schoen FJ: Clinical pulmonary autograft valves: Pathological evidence of adaptive remodeling in the aortic site. J Thorac Cardiovasc Surg. 2004; 128:552-562.
Sutherland FWH, Perry TE, Yu Y, Sherwood MC, Rabkin E, Masuda Y, Garcia GA, McLellan DL, Engelmayr GC, Sacks MS, Schoen FJ, Mayer JE. From stem cells to viable autologous semilunar heart valve. Circulation 2005; 111:2783-2791.
Schoen FJ, Levy RJ. Calcification of tissue heart valve substitutes: progress toward understanding and prevention. Ann Thorac Surg 2005; 79:1072-1080.
Mendelson KM, Schoen FJ: Heart valve tissue engineering: Concepts, approaches, progress, and challenges. Ann Biomed Engin 2006; 34:1799-1819.
Paruchuri S, Yang JH, Aikawa E, Melero-Martin JM, Khan ZA, Loukogeorgakis S, Schoen FJ, Bischoff J: Human pulmonary valve progenitor cells exhibit endothelial/mesenchymal plasticity in response to VEGF-A and TGFβ2. Circ Res 2006; 99:861-869.
Aikawa E, Whittaker P, Farber M, Mendelson K, Padera RF, Aikawa M, Schoen FJ: Human semilunar cardiac valve remodeling by activated cells from fetus to adult: Implications for postnatal adaptation, pathology and tissue engineering. Circulation 2006; 113:1344-1352.
Mikos A, Herring SW, Elisseeff J, Lu HH, Kandel R, Schoen FJ, Toner M, Mooney D, Atala A, Kaplan DL, Vunjak-Novakovic G: Engineering complex tissues. Tissue Eng, 2006, 12:3307-3339.
Schoen FJ. Evolving concepts of cardiac valve dynamics. The continuum of development, functional structure, pathobiology and tissue engineering. Circulation (submitted)
Biomaterials-tissue interactions, medical devices and tissue engineering: cardiovascular pathology; CIMIT Site Miner at BWH