Biodegradable and biomimetic elastomeric scaffolds for tissue-engineered heart valves.

Valvular heart diseases are the third leading cause of cardiovascular disease, resulting in more than 25,000 deaths annually in the United States. Heart valve tissue engineering (HVTE) has emerged as a putative treatment strategy such that the designed construct would ideally withstand native dynamic mechanical environment, guide regeneration of the diseased tissue and more importantly, have the ability to grow with the patient. These desired functions could be achieved by biomimetic design of tissue-engineered constructs that recapitulate in vivo heart valve microenvironment with biomimetic architecture, optimal mechanical properties and possess suitable biodegradability and biocompatibility. Synthetic biodegradable elastomers have gained interest in HVTE due to their excellent mechanical compliance, controllable chemical structure and tunable degradability. This review focuses on the state-of-art strategies to engineer biomimetic elastomeric scaffolds for HVTE. We first discuss the various types of biodegradable synthetic elastomers and their key properties. We then highlight tissue engineering approaches to recreate some of the features in the heart valve microenvironment such as anisotropic and hierarchical tri-layered architecture, mechanical anisotropy and biocompatibility. STATEMENT OF SIGNIFICANCE: Heart valve tissue engineering (HVTE) is of special significance to overcome the drawbacks of current valve replacements. Although biodegradable synthetic elastomers have emerged as promising materials for HVTE, a mature HVTE construct made from synthetic elastomers for clinical use remains to be developed. Hence, this review summarized various types of biodegradable synthetic elastomers and their key properties. The major focus that distinguishes this review from the current literature is the thorough discussion on the key features of native valve microenvironments and various up-and-coming approaches to engineer synthetic elastomers to recreate these features such as anisotropic tri-layered architecture, mechanical anisotropy, biodegradability and biocompatibility. This review is envisioned to inspire and instruct the design of functional HVTE constructs and facilitate their clinical translation.