Supramolecular hydrogels assembled from amino acids and peptide-derived hydrogelators have shown great potential as biomimetic three-dimensional (3D) extracellular matrices because of their merits over conventional polymeric hydrogels, such as non-covalent or physical interactions, controllable self-assembly, and biocompatibility. These merits enable hydrogels to be made not only by using external stimuli, but also under physiological conditions by rationally designing gelator structures, as well as in situ encapsulation of cells into hydrogels for 3D culture. This review will assess current progress in the preparation of amino acids and peptide-based hydrogels under various kinds of external stimuli, and in situ encapsulation of cells into the hydrogels, with a focus on understanding the associations between their structures, properties, and functions during cell culture, and the remaining challenges in this field. The amino acids and peptide-based hydrogelators with rationally designed structures have promising applications in the fields of regenerative medicine, tissue engineering, and pre-clinical evaluation.

To circumvent the influence from varied topographies, the systematic study of wettability regulated Gram-positive bacteria adhesion is carried out on bioinspired hierarchical structures duplicated from rose petal structures. With the process of tuning the interfacial chemical composition of the self-assembled films from supramolecular gelators, the varied wettable surfaces from superhydrophilicity to superhydrophobicity can be obtained. The investigation of Gram-positive bacteria adhesion on the hierarchical surfaces reveals that Gram-positive bacteria adhesion is crucially mediated by peptidoglycan due to its different interaction mechanisms with wettable surfaces. The study makes it possible to systematically study the influence mechanism of wettability regulated bacteria adhesion and provides a sight to make the bioinspired topographies in order to investigate wettability regulated bioadhesion.

Metrics & MoreArticle Recommendations CONSPECTUS: Chirality exits from molecular-level, supramolecular, and nanoscaled helical structures to the macroscopic level in biological life. Among these various levels, as the central structural motifs in living systems (e.g., double helix in DNA, α-helix, β-sheet in proteins), supramolecular helical systems arising from the asymmetrical spatial stacking of molecular units play a crucial role in a wide diversity of biochemical reactions (e.g., gene replication, molecular recognition, ion transport, enzyme catalysis, and so on). However, the importance of supramolecular chirality and its potential biofunctions has not yet been fully explored. Thus, generating chiral assembly to transfer nature's chiral code to artificial biomaterials is expected to be utilized for developing novel functional biomaterials. As one of the most commonly used biomaterials, supramolecular hydrogels have attracted considerable research interest due to their resemblance to the structure and function of the native extracellular matrix (ECM). Therefore, the performance and manipulation of chiral assembled nanoarchitectures in supramolecular hydrogels may provide useful insights into understanding the role of supramolecular chirality in biology.In this Account, recent progress on chiral supramolecular hydrogels is presented, including how to construct and regulate assembled chiral nanostructures in hydrogels with controllable handedness and then use them to develop chiral hydrogels that could be applied in biology, biochemistry, and medicine. First, a brief introduction is provided to present the basic concept related to supramolecular chirality and the importance of supramolecular chirality in living systems. The chiral assemblies in supramolecular hydrogels are strongly driven by noncovalent interactions between molecular building blocks (such as hydrogen bonding, π−π stacking, hydrophobic, and van der Waals interactions). Consequently, the handedness of these chiral assemblies can be regulated by many extra stimuli including solvents, temperature, pH, metal ions, enzymes, and photoirradiation, which is presented in the second section. This manipulation of the chirality of nanoarchitectures in supramolecular hydrogels can result in the development of potential biofunctions. For example, specific supramolecular chirality-induced biological phenomena (such as controlled cell adhesion, proliferation, differentiation, apoptosis, protein adsorption, drug delivery, and antibacterial adhesion) are presented in detail in the third section. Finally, the outlook of open challenges and future developments of this rapidly evolving field is provided. This account that highlights the diverse chirality-dependent biological phenomena not only helps us to understand the importance of chirality in life but also provides new ideas for designing and preparing chiral materials for more bioapplications.

The development of novel bioinspired surfaces with hierarchical micro- and nanoscale topographic structures for efficient capture and release of circulating tumor cells (CTCs) is reported. The capture of CTCs, facilitated by surface-immobilized epithelial cell adhesion molecule antibodies (anti-EpCAM), was shown to be significantly enhanced in novel three-dimensional hierarchically structured surfaces that were fabricated by replicating the natural micro- and nanostructures of rose petals. Under static conditions, these hierarchical capture substrates exhibited up to 6 times higher cell capture ability at concentrations of 100 cells mL in contrast to flat anti-EpCAM-functionalized polydimethylsiloxane (PDMS) surfaces. As indicated by scanning electron microscopy (SEM) and immunofluorescent images, this enhancement can be in large part attributed to the topographical interaction between nanoscale cell surface components and nanostructures on the substrate. Similarly, the increased surface area affords a higher nominal coverage of anti-EpCAM, which increases the number of available binding sites for cell capture. By treating the substrates with the biocompatible reductant glutathione (GSH), up to 85% of the captured cells were released, which displayed over 98% cell viability after culturing on tissue culture polystyrene (TCP) for 24 h. Therefore, these bioinspired hierarchically structured and functionalized substrates can be successfully applied to capture CTCs, as well as release CTCs for subsequent analysis. These findings provide new prospects for designing cell-material interfaces for advanced cell-based biomedical studies in the future.

With the development of industry, organic dyes used in printing, textile, plastic, foods, and cosmetics have brought health and environmental issues. A C 2 -symmetric benzene-based hydrogel with unique layered structure mimicking activated carbon was developed and found capable of the controllable adsorption of 97-99% of certain organic dyes (methylene blue and methyl violet 2B) within two minutes. The adsorption equilibrium of the dyes is in good agreement with the Langmuir adsorption isotherm model. The controllable adsorption of the dyes was confirmed by varying the pH of the medium. The hydrogel's rapid, highly effective, reusable, and controllable adsorption of organic dyes makes it possible to not only adsorb toxic dyes from wastewater, but also be used as potential delivery vehicles for small drug molecules in the field of drug delivery.

Many low molecular weight (LMWG) hydrogels have been widely used as scaffolds and substrates due to their particular structures and properties. However, LMWG hydrogels generally show a weak mechanical performance which confines their applications in the field of tissue engineering. Here, we report a new kind of hydrogel derived from the combination of a C 2 -phenyl-derived gelator and a polysaccharide (alginate). Rheology testing showed that the elastic modulus of C 2 -phenyl-derived hydrogels could be increased by nearly one order of magnitude by interpenetrating them with an alginate-calcium network. Increasing the concentrations of the gelator and calcium ions or decreasing the concentration of alginate will lead to an increase of the elastic modulus of the hybrid hydrogels. Imaging and spectroscopic analysis confirmed that the surface roughness and morphology of the hybrid hydrogels were almost the same with that of a pure C 2 hydrogel. Significant improvements in cell adhesion and spreading were observed on the reinforced hydrogels. The new hybrid hydrogels have great potential for tissue engineering applications in vivo.

Supramolecular fluorescent hydrogelators (SFH) have emerged as a promising system for bio-imaging applications, such as detecting molecules/signals and sensing markers of diseases with the highest specificity, mapping molecular events, in vivo tracking and understanding cell behavior, in the past few years.

The influence of chirality on cell behavior is closely related with relevant biological events; however, many recent studies only focus on the apparent chiral influence of supramolecular nanofibers and ignore the respective effects of molecular chirality and supramolecular chirality in biological processes. Herein, the inherent molecular and supramolecular chiral effects on cell spreading and differentiation are studied. Left-handed nanofibers (referring to supramolecular chirality) assembled from L-amino acid derivatives can enhance cell spreading and proliferation compared to flat L-surfaces (referring to molecular chirality). However, compared to the D-surfaces (referring to molecular chirality), right-handed nanofibers (referring to supramolecular chirality) derived from D-amino acid suppress cell spreading and proliferation, overturning the conventional view that a fibrous morphology generally enhances cell adhesion. The results directly suggest that the amplification of chirality from chiral molecules to chiral assemblies significantly enhances the effect on regulated cell behavior by supramolecular helical handedness. Moreover, cell differentiation is found to be chirality dependent. It suggests that both the L-amino acid derivatives and the left-handed fibers facilitate osteogenic differentiation. This study provides useful insight into understanding the origin of chiral expression from the molecular to the macroscopic level in nature.