In situ heart valve tissue engineering: simple devices, smart materials, complex knowledge

Evolution of heart valve tissue engineering Since the implantation of the first artificial aortic heart valve by Hufnagel et al., the design and construction of heart valve prostheses has undergone continuous and drastic changes to improve the survival and quality of life of approximately 300,000 patients with end-stage valvular disease per year [1]. These include the development of bioprostheses consisting of animal or human tissue [2,3], and the more recent introduction of valve designs for transcatheter valve replacement [4]. The most revolutionary change, however, has been the introduction of living valves, obtained via the process of tissue engineering [5]. These valves can grow and adapt to physiological demand changes and offer the potential of true regeneration. As such, they can circumvent many existing prosthesis-related complications and last a lifetime, which is of particular relevance for the relatively young patient group with congenital heart disease currently receiving a mechanical prosthesis [6]. Classical in vitro heart valve tissue engineering (HVTE) strategies involve the harvest and expansion of autologous cells, cell seeding onto preshaped biodegradable carriers or scaffolds, and prolonged tissue culture outside the human body prior to implantation. Despite optimistic outlooks based on breakthrough results in sheep over a decade ago [7,8], in vitro HVTE has not yet been introduced in the clinic. This is mainly owing to the complexity of the procedure and suboptimal long-term in vivo performance – the biggest issue being valve leaflet retraction and consequent regurgitation [9,10]. Another aspect is significant inter-patient variability, preventing early prediction of HVTE and intervention outcome [11]. In the mean time, numerous modifications to the HVTE scheme have been explored to optimize valve performance and to simplify the procedure to accelerate clinical introduction. Important steps taken are the use of on-the-f ly harvest able cells to avoid cell and tissue culture (the so-called ‘one-step procedure’) [12], and percutaneous implantation of in vitro engineered valves [9].