Tissue engineering of heart valves: decellularized valve scaffolds.

In 1956, Gordon Murray first reported the human clinical surgical use of fresh aortic valve homografts (cadaveric) transplanted into the descending thoracic aorta for clinical amelioration of the consequences of native aortic valve insufficiency.1 His initial operation preceded by 5 years the availability of mechanical aortic valve prostheses. Although the operation was only partly successful hemodynamically, these “homograft valves” had remarkable durability and performance. Some patients had no calcification or transvalvular gradients for up to 20 years, whereas others ultimately failed as a consequence of progressive fibrosis and calcification.2,3 In 1962, the initial use of aortic valve homografts in the orthotopic position were reported independently by Sir Donald Ross of England and Sir Brian Barrett-Boyes of New Zealand.4–6 As manufactured prosthetic valves gradually evolved in design and range of choices, homograft use began to decline because of issues of acquisitional logistics, banking, transport, sizing, infectious disease transmission, and others. With the development of organized organ and tissue donation for transplantation in the 1980s and 1990s, cardiovascular allograft tissues became increasingly available primarily as cryopreserved valves with variably retained native cell viability. Importantly, the terrific surgical and specific performance advantages of allograft semilunar cardiac valves have been recognized by reconstructive surgeons worldwide.7 These valve “transplants” have by and large crossed histocompatibility and ABO constraints, however. Although they perform well in the shortto mid-term, they have been associated with ultimate fibrosis and failure in a significant proportion of cases, especially in patients for whom the desirability of a living transplant would be the greatest: neonates, infants, and young children (ie, for whom retained growth and repair functions would be ideal). Thus, there have been many attempts to modify homograft valve transplants at either the donor or recipient level to achieve relative or actual immune tolerance with the thought that this would retain the outstanding engineering design of the native semilunar valve while avoiding the inevitable foreign body reaction seen when antigenic or proinflammatory materials are transplanted. No truly satisfactory solution has been achieved; even with these durability constraints, for many indications the allograft valve remains the best option for reconstructing certain cardiac lesions in patients such as destroyed ventricular outflow tracts resulting from bacterial endocarditis and complex reconstructions for congenital structural heart disease.8