The future of heart valve replacement: recent developments and translational challenges for heart valve tissue engineering.

Heart valve replacement is often the only solution for patients suffering from valvular heart disease. However, currently available valve replacements require either life-long anticoagulation or are associated with valve degeneration and calcification. Moreover, they are suboptimal for young patients, because they do not adapt to the somatic growth. Tissue-engineering has been proposed as a promising approach to fulfil the urgent need for heart valve replacements with regenerative and growth capacity. This review will start with an overview on the currently available valve substitutes and the techniques for heart valve replacement. The main focus will be on the evolution of and different approaches for heart valve tissue engineering, namely the in vitro, in vivo and in situ approaches. More specifically, several heart valve tissue-engineering studies will be discussed with regard to their shortcomings or successes and their possible suitability for novel minimally invasive implantation techniques. As in situ heart valve tissue engineering based on cell-free functionalized starter materials is considered to be a promising approach for clinical translation, this review will also analyse the techniques used to tune the inflammatory response and cell recruitment upon implantation in order to stir a favourable outcome: controlling the blood-material interface, regulating the cytokine release, and influencing cell adhesion and differentiation. In the last section, the authors provide their opinion about the future developments and the challenges towards clinical translation and adaptation of heart valve tissue engineering for valve replacement.