Natural Polymers in Heart Valve Tissue Engineering: Strategies, Advances and Challenges.

In the history of biomedicine and biomedical devices, heart valve manufacturing techniques have undergone a spectacular evolution. However, important limitations in the development and use of these devices are known and heart valve tissue engineering has proven to be the solution to the problems faced by mechanical and prosthetic valves. The new generation of heart valves developed by tissue engineering has the ability to repair, reshape and regenerate cardiac tissue. Achieving a sustainable and functional tissue-engineered heart valve (TEHV) requires deep understanding of the complex interactions that occur among valve cells, the extracellular matrix (ECM) and the mechanical environment. Starting from this idea, the review presents a comprehensive overview related not only to the structural components of the heart valve, such as cells sources, potential materials and scaffolds fabrication, but also to the advances in the development of heart valve replacements. The focus of the review is on the recent achievements concerning the utilization of natural polymers (polysaccharides and proteins) in TEHV; thus, their extensive presentation is provided. In addition, the technological progresses in heart valve tissue engineering (HVTE) are shown, with several inherent challenges and limitations. The available strategies to design, validate and remodel heart valves are discussed in depth by a comparative analysis of in vitro, in vivo (pre-clinical models) and in situ (clinical translation) tissue engineering studies.