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INTRODUCTION

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Tissue engineering is a developing science, comprising elements of engineering and biology, whose aim is to build replacement tissues de novo, from individual cellular and structural components. The impetus for our work on tissue-engineered cardiovascular structures arises from the need to replace cardiovascular tissues that failed to develop normally during embryogenesis or have become dysfunctional as a consequence of disease. In pediatric patients, the cardiovascular structures most often afflicted by congenital anomalies involve the cardiac valves and great vessels, and the theoretical advantages of a tissue-engineered structure containing live cells are the ability to grow, remodel, and repair. Although growth potential is not a consideration for the adult population, durability of valve structures remains an important issue for bioprosthetic valves, and a tissue engineering approach offers the potential to improve durability by providing the repair and remodeling capability.

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Diseases of the heart valves and large “conduit” arteries account for approximately 60,000 cardiac surgical procedures each year in the United States, and all of the currently available replacement devices have significant limitations.1,2 Ideally, any valve or artery substitute would function like a normal valve or artery. For valves, this function includes allowing pulsatile blood flow without a transvalvar gradient or valvar regurgitation. The theoretical advantage of engineered tissue replacements is that they could also display other desirable characteristics, such as (1) durability, (2) growth (for infants and children), (3) compatibility with blood components and the absence of thrombosis or destructive inflammation, and (4) resistance to infection. None of the currently available devices, constructed from either synthetic or biologic materials, meet these criteria. Mechanical heart valves are very durable, but they require anticoagulation to reduce the risk of thrombosis and thromboembolism.1,2 Therapeutic anticoagulation carries associated morbidity, and even among patients who receive therapeutic anticoagulation, the incidence of thromboembolic complications of mechanical heart valve replacement is not zero.1,2 Biologic valves, whether of allograft or heterograft origin, remain subject to structural deterioration after implantation.2-4 Neither mechanical nor biologic valves have any growth potential, and this limitation represents a major source of morbidity for pediatric patients who must undergo multiple reoperations to replace valves and/or valved conduits during the period of maximum somatic growth.

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Tissue engineering is an approach based upon the hypothesis that when properly designed and fabricated, these “living” devices will simulate the biology of normal cardiovascular structures, thereby overcoming the shortcomings of currently available heart valve replacements. Of particular relevance to pediatric heart surgery is the long-term function of the engineered valve over time and the potential capacity to grow, self-repair, and remodel. This chapter summarizes some of the progress that has been made in tissue engineering research as it relates to cardiac valves and conduit arteries, and then outlines the areas where additional efforts must be focused in order to direct cardiovascular tissue engineering toward clinical utility.

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NORMAL HEART VALVE BIOLOGY

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