Extremely Stable Supramolecular Hydrogels Assembled from Nonionic Peptide Amphiphiles

Abstract

Peptide hydrogels with high stability in different media are of great interest in biomedical applications. In this paper, we report an easy, fast, and scalable method for preparing a family of nonionic peptide amphiphiles (PAs) obtained by direct aminolysis of alkyl-oilgo(γ-benzyl-l-glutamate) samples, which were synthesized via the alkyl amine-initiated sequence ring-opening reaction of α-amino acid N-carboxyanhydrides. One great advantage of this method is that vast chemical diversity and large-scale yields can be achieved easily using commercially available hydramines. These PA samples can readily form a clear hydrogel without any external aid and show exceptionally enhanced gelation properties with a critical gelation concentration as low as 0.05 wt %. The hydrogels are highly stable against extreme pH values of 1 and 14 and a high salt concentration of 200 mM NaCl. These properties combined with the shear-thinning properties make these PA hydrogels ideal candidates for the new generation of injectable scaffolds.

Effects of molecular flexibility and head group repulsion on aramid amphiphile self-assembly

“…As a result, rational design of self-assembling nanoarchitectures of amphiphiles with strong hydrogen bonding requires advanced computational molecular dynamics simulations. 17 In fact, the introduction of hydrogen bonding and π-π stacking can produce exotic and unpredictable geometries like helices, [18][19][20] twisted nanoribbons, 19,21 and 3D cages. 22 An outstanding objective is to better understand the relationships between molecular design and ultimate morphological outcomes.…”

Unusual confinement properties of a water insoluble small peptide hydrogel

“…14 Although the stability of such hydrogels in buffers and cell culture medium is reported in the literature, it is not clear whether they can full the above-mentioned criteria since no quantitative analysis is available. [19][20][21] An attractive alternative could be a water insoluble and highly stable supramolecular hydrogel which may get dissolved slowly by a biomolecule (stimuli to break the gel) present in the bio-uid and thus result in sustained and prolonged application. A supramolecular hydrogel made of small molecules has not been reported so far, where the gel does not get dissolved in bulk solvent systems and exchange of solutes as well as solvents with an external bulk medium is highly restricted.…”

Fine tuning the assembly and gel behaviors of PEGylated polypeptide conjugates by the copolymerization of l‐alanine and γ‐benzyl‐l‐glutamate N‐carboxyanhydrides

“…Self‐assembled peptides or their derivatives are of tremendous interest for targeted drug delivery, vaccine engineering and tissue regeneration . In response to changes in their assembly environment, such as temperature, pH or ionic strength, peptide molecules can intelligently self‐assemble into specific supramolecular nano/macroscale architectures by rational design, including nanomicelles, nanofibers, nanotubes, nanoribbons, and macroscale hydrogels . Depending on their assembly, the obtained architectures have a various range of physicochemical and mechanical properties associated with their applications.…”

“…[1][2][3][4][5][6][7][8] In response to changes in their assembly environment, such as temperature, pH or ionic strength, peptide molecules can intelligently selfassemble into specific supramolecular nano/macroscale architectures by rational design, including nanomicelles, 9 nanofibers, [10][11][12] nanotubes, [13][14][15] nanoribbons, 16 and macroscale hydrogels. [17][18][19][20][21][22] Depending on their assembly, the obtained architectures have a various range of physicochemical and mechanical properties associated with their applications. Generally speaking, self-assembled peptide structures are of their own advantages in encapsulation of hydrophobic drugs, sustained drug release, biocompatibility, stability, culture environment for cells, and/or immunoadjuvant properties.…”