Engineered polypeptides for tissue engineering

Engineered polypeptides have emerged as attractive materials to construct artificial extracellular matrices (ECMs) in tissue engineering. These materials offer advantages over conventional synthetic materials in recapitulating essential characteristics of complex and dynamic native ECMs, which is one of the key requirements for successful tissue engineering, because proteins are major players in providing structural support, cell adhesion, and signal regulation in native ECMs. The structures and functions of these proteins and their domains, as well as those of de novo designed polypeptide domains having self-assembly and molecular recognition abilities, can be combined in engineered polypeptides in a modular manner to yield multifunctional, bioactive materials to mimic native ECMs and optimize tissue engineering outcomes. Engineered polypeptides can be synthesized both chemically and biosynthetically. In recent years, the biosynthetic methodology has received increasing attention because the advances in molecular biology and protein engineering have expanded its capacity. Biosynthetic preparation allows polypeptide materials to be genetically engineered in a modular manner and the resulting polymers have absolutely uniform sequence, composition, molecular weight, and consequently higher order structures and functions. These properties not only allow us to engineer novel multifunctional materials to elicit desired cell responses toward functional tissue regeneration, but also offer the opportunity to create well-controlled and tunable systems for systematic studies to enhance our understanding of the relationships among extracellular microenvironments, cell behavior and fate selection, and tissue assembly. Such understanding will provide valuable guidelines for design of future generations of artificial ECMs. In this chapter, engineered polypeptides that have been used or have the potential to be used in tissue engineering will be discussed with an emphasis placed on their molecular design as well as examples of their use in tissue engineering studies.