Peptide Amphiphile Hydrogels Based on Homoternary Cucurbit[8]uril Host-Guest Complexes.

Supramolecular hydrogels based on peptide amphiphiles (PAs) are promising materials for tissue engineering and model extracellular matrixes for biological studies. While PA hydrogels are conventionally formed via electrostatic screening, new hydrogelation mechanisms might help to improve the design and functionality of these materials. Here, we present a host-guest-mediated PA hydrogelation method that relies on the formation of a host-guest homoternary complex with cucurbit[8]uril (CB[8]) and aromatic amino-acid-bearing PA nanofibers. As a result of the host-guest cross-linking between PA nanofibers, hierarchical morphologies and increased stiffness were found when host-guest-mediated PA hydrogels were compared to their ion-based equivalents. Additionally, both families of hydrogels exhibited similar biocompatibilities. These results demonstrate that CB[8]-mediated hydrogelation can be used as an alternative cross-linking method to upgrade the design of PA materials and extend their biomedical applications.

Host-Guest-Mediated Epitope Presentation on Self-Assembled Peptide Amphiphile Hydrogels.

A key feature in biomaterial design is the incorporation of bioactive signals into artificial constructs to stimulate tissue regeneration. Most currently used hydrogel cell culture systems depend on the covalent attachment of extracellular matrix (ECM)-derived peptides to either macromolecular units or smaller self-assembling building blocks, thereby restricting biosignal presentation and adaptability. However, new ways to rationally incorporate adhesion epitopes through noncovalent interactions would offer opportunities to better recreate the dynamic and reversible nature of the native ECM. Here, we report on a noncovalent epitope presentation approach mediated by host-guest interactions. Using peptide amphiphile hydrogels, we demonstrate that the adamantane/ß-cyclodextrin pair can be used to anchor RGDS cell adhesion signals onto self-assembled hydrogels via host-guest interactions. We evaluate hydrogel morphological and rheological properties as well as fibroblast attachment, organization, and spreading when cultured atop these scaffolds. This host-guest-mediated epitope display might lead to new self-assembling hydrogels for improved cell culture applications in fields such as tissue engineering and regenerative medicine.