Peptide Stereocomplexation Orchestrates Supramolecular Assembly of Hydrogel Biomaterials.

Stereocomplexation, or specific interactions among complementary stereoregular macromolecules, is burgeoning as an increasingly impactful design tool, exerting exquisite control of material structure and properties. Since stereocomplexation of polymers produces remarkable transformations in mechanics, morphology, and degradation, we sought to leverage stereocomplexation to tune these properties in peptide-based biomaterials. We found that blending the pentapeptides l- and d-KYFIL triggers dual mechanical and morphological transformations from stiff fibrous hydrogels into less stiff networks of plates, starkly contrasting prior reports that blending l- and d-peptides produces stiffer fibrous hydrogels than the individual constituents. The morphological transformation of KYFIL in phosphate-buffered saline from fibers that entangle into hydrogels to plates that cannot entangle explains the accompanying mechanical transformation. Moreover, the blends shield l-KYFIL from proteolytic degradation, producing materials with comparable proteolytic stability to d-KYFIL but with distinct 2D plate morphologies that in biomaterials may promote unique therapeutic release profiles and cell behavior. To confirm that these morphological, mechanical, and stability changes arise from differences in molecular packing as in polymer stereocomplexation, we acquired X-ray diffraction patterns, which showed l- and d-KYFIL to be amorphous and their blends to be crystalline. Stereocomplexation is particularly apparent in pure water, where l- and d-KYFIL are soluble random coils, and their blends form ß-sheets and gel within minutes. Our results highlight the role of molecular details, such as peptide sequence, in determining the material properties resulting from stereocomplexation. Looking forward, the ability of stereocomplexation to orchestrate supramolecular assembly and tune application-critical properties champions stereochemistry as a compelling design consideration.

Biomaterials via peptide assembly: Design, characterization, and application in tissue engineering.

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 ß-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: Engineering peptide-based biomaterials that mimic the topological and mechanical properties of natural extracellular matrices provide excellent opportunities to direct cell behavior for regenerative medicine and tissue engineering. Here we review the molecular-scale features of assembling peptides that result in biomaterials that exhibit a variety of relevant extracellular matrix-mimetic properties and promote beneficial cell-biomaterial interactions. Aiming to inspire and guide researchers approaching this challenge from both the peptide biomaterial design and tissue engineering perspectives, we also 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.