Abstract
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.
Highlights
Progress in supramolecular chemistry has led to growing control over molecular self-assembly and provided robust approaches to design biomaterials with increasing biomimicry, structural complexity, and functionality.[1,2] Remarkable examples of functional self-assembling systems based on polymers,[3] sugars,[4] nucleic acids,[5] proteins,[6] and their combination[7] have been reported.Research on synthetic constructs for tissue engineering and regenerative medicine applications has evidenced the importance of mimicking morphological,[8] mechanical,[9] and biochemical[10] aspects of the extracellular matrix (ECM).[11]
Though the use of light[40] or enzymes[41] has proved effective on the modulation of bioactivity in polymer-based systems, we have demonstrated that host-guest interactions[42,43] may offer an effective approach to aid in this effort
In this study, we have introduced and demonstrated the efficacy of a new high-density epitope presentation strategy on self-assembled Peptide amphiphiles (PAs) scaffolds mediated by non-covalent interactions
Summary
Progress in supramolecular chemistry has led to growing control over molecular self-assembly and provided robust approaches to design biomaterials with increasing biomimicry, structural complexity, and functionality.[1,2] Remarkable examples of functional self-assembling systems based on polymers,[3] sugars,[4] nucleic acids,[5] proteins,[6] and their combination[7] have been reported.Research on synthetic constructs for tissue engineering and regenerative medicine applications has evidenced the importance of mimicking morphological,[8] mechanical,[9] and biochemical[10] aspects of the extracellular matrix (ECM).[11]. Non-covalent epitope presentation and cell adhesion response As rheological studies revealed that E3G3Ada-PA was a suitable candidate to co-assemble with E3PA without compromising the resulting mechanical properties of the gel, we investigated the formation of host-guest complexes involving these components.
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