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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/β-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.

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