Biomaterials via Peptide Assembly: Design, Characterization, and Application in Tissue Engineering

Abstract

A core challenge in biomaterials, with both fundamental significance and technological relevance, concerns the rational design of bioactive microenvironments. Designed properly, peptides can undergo supramolecular assembly into dynamic, physical hydrogels that mimic the mechanical, topological, and biochemical features of native tissue microenvironments. The relatively facile, inexpensive, and automatable preparation of peptides coupled with low batch-to-batch variability motivates the expanded use of assembling peptide hydrogels for biomedical applications. Integral to realizing dynamic peptide assemblies as functional biomaterials for tissue engineering is an understanding of the molecular and macroscopic features that govern assembly, morphology, and biological interactions. In this review, we first discuss the design of assembling peptides, including primary structure (sequence), secondary structure (e.g., α-helix and β-sheets), and molecular interactions that facilitate assembly into multiscale materials with desired properties. Next, we describe characterization tools for elucidating molecular structure and interactions, morphology, bulk properties, and biological functionality. Understanding of these characterization methods enables researchers to access a variety of approaches in this ever-expanding field. Finally, we discuss the biological properties and applications of peptide-based biomaterials for engineering several important tissues. By connecting molecular features and mechanisms of assembling peptides to the material and biological properties, we aim to guide the design and characterization of peptide-based biomaterials for tissue engineering and regenerative medicine. STATEMENT OF SIGNIFICANCE: Well-defined topological and mechanical properties of assembled peptides can be used to direct biological responses. Engineering peptide-based extracellular matrices offers immense opportunity for regenerative medicine and tissue engineering. Here we review the molecular-scale features of assembling peptides that result in useful extracellular matrix properties and desired cell interactions. Aiming to inspire researchers approaching this challenge from both the peptide biomaterial design and tissue engineering perspectives, we present characterization tools for understanding the connection between peptide structure and properties and highlight the use of peptide-based biomaterials in neural, orthopedic, cardiac, muscular, and immune engineering applications.