Herein, we report the synthesis of simple TPE/single amino acid conjugates, TPE-Ser and TPE-Asp with side-chains featuring functional groups that may provide an additional hydrogen bonding network for hydrogelation in aqueous medium. TPE-Ser, which has the lowest molecular weight, containing hydroxyl groups undergoes self-assembly into supramolecular hydrogels under physiological pH conditions. TPE-Asp with a carboxylic group side chain undergoes the self-assembly and hydrogelation processes under slightly acidic conditions (pH = 6.0). UV-vis, IR, PL and rheological studies clearly indicate the formation, stability and fluorescence properties of TPE-amino acid hydrogels. TEM micrographs of the hydrogels indicate that the compounds are self-assembled into a nanosheet morphology with random size and shape. Further, in vitro analysis of TPE-Ser and TPE-Asp with 3A6 cells shows that the compounds exhibit unique fluorescence signals in microcellular environments thus making them suitable candidates for bioimaging applications. Overall, these findings highlight the importance of the structure-hydrogelation relationship and provide new insights into the design of single amino-acid-based supramolecular hydrogels.

The importance of side chains of amino acids for NDI–Py co-assembled hydrogelation is described.

Hydrogels are a class of biomaterials used in the field of tissue engineering and drug delivery. Many tissue engineering applications depend on the material properties of hydrogel scaffolds, such as mechanical stiffness, pore size, and interconnectivity. In this work, we describe the synthesis of peptide/polymer hybrid double-network (DN) hydrogels composed of supramolecular and covalent polymers. The DN hydrogels were prepared by combining the self-assembled pentafluorobenzyl diphenylalanyl aspartic acid (PFB-FFD) tripeptide for the first network and the polymeric PNIPAM-PEGDA copolymer for the second network. During this process, self-assembled peptide nanostructures are cross-linked to the polyacrylamide group in the polymer network through non-covalent interactions. The PNIPAM-PEGDA:PFB-FFD hydrogel exhibited higher mechanical stiffness (G′ ∼2 kPa) than the PNIPAM-PEGDA copolymer. Moreover, PNIPAM-PEGDA:PFB-FFD hydrogel shows a decrease in pore size (∼1.2 μm) compared to the original copolymer (∼5.2 μm), with the structural framework of highly interconnected fibrous peptide network. The mechanical stiffness of hydrogels was systematically investigated by rheological analysis in response to various variables, including UV exposure time, concentration of peptides, and amino acid functionalization. Modulating the time of UV irradiation resulted in PNIPAM-PEGDA:PFB-FFD hydrogels with a four-fold increase in stiffness. The influence of amino acid side chains and terminal charge of peptides on the strength of DN hydrogels was also investigated using pentafluorobenzyl diphenylalanyl lysine (PFB-FFK). Interestingly, PFB-FFK, which has an amine group on the side chain, does not exhibit the DN structures. The mechanical properties and pore sizes of PNIPAM-PEGDA:PFB-FFK hydrogel were very similar to those of the PNIPAM-PEGDA copolymer due to poor cross-linking. The biocompatibility of the hydrogel materials was tested with the hMSC cell line using the MTT method, and the results indicate that the materials are non-toxic and potentially useful for biological applications.

Mg²⁺ induced peptide hydrogels exhibit tunable stiffness, nanostructures and self-assembly of hMSC into multicellular spheroids.

A series of FFK tripeptides capped with phenylacetic acid of various fluoro-substitutions at the N-terminus has been synthesized and examined for self-assembly under aqueous conditions. The material properties of the FFK tripeptides dramatically changed from precipitate to hydrogel phase upon increasing the number of fluorine atoms. Peptides linked with benzyl (B-FFK) or monofluoro-benzyl (MFB-FFK) groups rapidly form solid precipitates under physiological pH conditions. The trifluoro-decorated compound (TFB-FFK) self-assembled into a metastable hydrogel which slowly transformed into a solid precipitate upon standing. A stable hydrogel formation was noticed in the case of the pentafluorobenzyl-diphenylalanyllysine (PFB-FFK) compound. TEM analysis indicates that the PFB-FFK peptide assembled into twisted nanofibril structures, which are predominantly stabilized by strong quadrupole π-stacking interactions and electrostatic interactions of amino acid side chains. Furthermore, the combination of PFB-FFK and PFB-FFD peptides was also investigated for hydrogelation and the self-assembly of such systems resulted in the formation of untwisted 1D nanofibril structures. Supramolecular coassembled hydrogels of variable stiffness have also been achieved by modulating the concentration of the peptide components, which was evident from the rheological analysis. Such low molecular weight (LMW) peptide materials with tuneable mechanical properties might be a potential material for a wide range of applications in nanotechnology and biotechnology.

Hydrogels’ exceptional mechanical strength and skin-adhesion characteristics offer significant advantages for various applications, particularly in the fields of tissue adhesion and wearable sensors. Herein, we incorporated a combination of metal-coordination and hydrogen-bonding forces in the design of stretchable and adhesive hydrogels. We synthesized four hydrogels, namely PAID-0, PAID-1, PAID-2, and PAID-3, consisting of acrylamide (AAM), N,N′-methylene-bis-acrylamide (MBA), and methacrylic-modified dopamine (DA). The impact of different ratios of iron (III) ions to DA on each hydrogel’s performance was investigated. Our results demonstrate that the incorporation of iron–dopamine complexes significantly enhances the mechanical strength of the hydrogel. Interestingly, as the DA content increased, we observed a continuous and substantial improvement in both the stretchability and skin adhesiveness of the hydrogel. Among the hydrogels tested, PAID-3, which exhibited optimal mechanical properties, was selected for adhesion testing on various materials. Impressively, PAID-3 demonstrated excellent adhesion to diverse materials and, combined with the low cytotoxicity of PAID hydrogel, holds great promise as an innovative option for biomedical engineering applications.