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Multicomponent supramolecular hydrogels are promising scaffolds for applications in biosensors and controlled drug release due to their designer stimulus responsiveness. To achieve rational construction of multicomponent supramolecular hydrogel systems, their in‐depth structural analysis is essential but still challenging. Confocal laser scanning microscopy (CLSM) has emerged as a powerful tool for structural analysis of multicomponent supramolecular hydrogels. CLSM imaging enables real‐time observation of the hydrogels without the need of drying and/or freezing to elucidate their static and dynamic properties. Through multiple, selective fluorescent staining of materials of interest, multiple domains formed in supramolecular hydrogels (e. g. inorganic materials and self‐sorting nanofibers) can also be visualized. CLSM and the related microscopic techniques will be indispensable to investigate complex life‐inspired supramolecular chemical systems., A powerful tool! Confocal laser scanning microscopy (CLSM) is powerful for structural analysis of supramolecular hydrogels. In situ imaging enables to evaluate not only static but dynamic properties of supramolecular nanofibers in real time. This minireview summarizes representative examples of CLSM imaging of multicomponent supramolecular hydrogel systems.

Supramolecular hydrogels can spontaneously undergo syneresis through fibre-fibre interactions and expel significant amounts of water upon aging. In this process, the hydrophobicity of fibres which regulates the 3D-rearrangement of the self-assembled structures during syneresis is important. Here, we show that we can control over the hydrophobic microenvironment of gels by incorporating organic salts into the gel fibre involving co-assembly enabling control of the macroscopic gel volume phase transition.

Supramolecular peptide hydrogel has shown promising potential in vaccine development largely because of its ability to function both as antigen depot and immune adjuvant. Nap‐GdFdFdY, a tetrapeptide hydrogel that has been previously reported to exhibit adjuvant effect, is inadvertently found to contain conserved peptide sequence for insulin, proinsulin, and glutamic acid decarboxylase, 3 major autoantigens for the autoimmune type 1 diabetes (T1D). At present, despite being managed clinically with insulin replacement therapy, T1D remains a major health threat with rapidly increasing incidences, especially in children and young adults, and antigen‐specific immune tolerance induction has been proposed as a feasible approach to prevent or delay T1D progression at an early stage. Here, it is reported that innoculation of Nap‐GdFdFdY leads to complete protection of nonobese diabetic (NOD) mice from T1D development till the age of 36 weeks. Better maintenance of pancreatic islet morphology with minimal immune cell infiltration is also observed from mice exposed to Nap‐GdFdFdY. This beneficial impact is mainly due to its facilitative role on enhancing peripheral T regulatory cell (Treg) population, shown as increased splenic Treg percentage, and function, demonstrated by maintenance of circulating TGF‐β1 level. Serum cytokine microarray data further implicate a “buffering” role of Nap‐GdFdFdY on systemic inflammatory tone in NOD mice. Thus, with its versatility, applicability, and excellent potency, Nap‐GdFdFdY is posited as a novel therapeutic intervention for T1D., A hydrogel of Nap‐GdFdFdY containing conserved sequence of autoantigens including insulin, proinsulin, and glutamic acid decarboxylase as a novel therapeutic intervention for the autoimmune type 1 diabetes. Better pancreatic islet morphology with minimal immune cell infiltration is observed from mice with hydrogel because of enhancing peripheral T regulatory cell population and maintenance of circulating TGF‐β1 level.

Here, transient supramolecular hydrogels that are formed through simple aging‐induced seeded self‐assembly of molecular gelators are reported. In the involved molecular self‐assembly system, multicomponent gelators are formed from a mixture of precursor molecules and, typically, can spontaneously self‐assemble into thermodynamically more stable hydrogels through a multilevel self‐sorting process. In the present work, it is surprisingly found that one of the precursor molecules is capable of self‐assembling into nano‐sized aggregates upon a gentle aging treatment. Importantly, these tiny aggregates can serve as seeds to force the self‐assembly of gelators along a kinetically controlled pathway, leading to transient hydrogels that eventually spontaneously convert into thermodynamically more stable hydrogels over time. Such an aging‐induced seeded self‐assembly process is not only a new route toward synthetic out‐of‐equilibrium supramolecular systems, but also suggests the necessity of reporting the age of self‐assembling building block solutions in other self‐assembly systems., A simple aging‐induced seeded self‐assembly resulting in transient supramolecular hydrogels is reported. The obtained transient hydrogels can convert into the thermodynamically more stable state over time. The findings demonstrate a new route toward out‐of‐equilibrium self‐assembly system, and suggest the necessity of stating the ages of self‐assembling building blocks in some other supramolecular systems.

The co-existence of electrostatic attraction and repulsion between zwitterionic amphiphile and anionic polyoxometalate (POM) promotes the formation of aqueous inorganic-organic coassemblies. Injectable, luminescent supramolecular hydrogels have been fabricated by using this novel and versatile technique. Hydrogels with different characteristics can be flexibly manipulated by adjusting the molar ratios of compounds. Interestingly, a linear relationship between the luminescence intensity and temperature accompanying the sol-gel transition was observed. In addition, the emission properties of the hydrogels were sensitive to external acid and base gasses. Such multi-stimuli responsive luminescent hydrogels provide an attractive pathway to construct intelligent optical soft materials, especially for biological sensors for which stimuli responsiveness is necessary.

Photoresponsive smart materials transform light energy into sophisticated functions. They find increasing biomedical applications in light-induced drug-release and photopharmacology, because they can provide the desired therapeutic effect locally due to precise spatiotemporal dosage control. However, the majority of reported studies rely on cytotoxic UV light that penetrates tissues poorly. Here, we report the first drug-releasing system based on photochromic low molecular weight supramolecular hydrogels that is triggered with visible light. We demonstrated green-light-induced release of structurally unmodified antibiotic, anticancer, and anti-inflammatory drugs under physiological conditions. Using the antibiotic-loaded gel, we selectively inhibited bacterial growth with green light.

Dendrimer‐based supramolecular hydrogels have gained attention in biomedical fields. While biocompatible dendrimers were used to prepare hydrogels via physical and/or chemical crosslinking, smart functions such as pH and molecular control remain undeveloped. Here, we present polyglycerol dendrimer‐based supramolecular hydrogel formation induced by a specific interaction between the polyglycerol dendrimer and an amino group of glycol chitosan. Gelation was achieved by mixing the two aqueous solutions. Hydrogel formation was controlled by varying the polyglycerol dendrimer generation. The hydrogel showed pH‐dependent swelling; strongly acidic conditions induced degradation via dissociation of the specific interaction. It also showed unique l ‐arginine‐responsive degradation capability due to competitive exchange of the amino groups of glycol chitosan and l ‐arginine. These polyglycerol dendrimer‐based supramolecular characteristics allow multimodal application in smart biomaterials.

Many materials as immune adjuvant are researched to help raise immnogenicity of subunit vaccines. Among them, peptide-based hydrogels are gradually coming into notice because of their application in drugs delivery, cancer cell inhibition, vaccine adjuvants and detection of important analytes. In this work, we introduced a novel aromatic capping group based on indole to construct short peptide-based supramolecular hydrogelators Indol-GFFY and Indol-GDFDFDY and demonstrated their potential applications as vaccine adjuvants.

A two-component self-sorting hydrogel based on acylhydrazide and carboxylic acid derivatives of 1,3:2,4-dibenzylidene-d-sorbitol (DBS-CONHNH2 and DBS-COOH) is reported. A heating-cooling cycle induces the self-assembly of DBS-CONHNH2 , followed by the self-assembly of DBS-COOH induced by decreasing pH. Although the networks are formed sequentially, there is spectroscopic evidence of interactions between them, which impact on the mechanical properties and significantly enhance the ability of these low-molecular-weight gelators (LMWGs) to form gels when mixed. The DBS-COOH network can be switched "off" and "on" within the two-component gel through a pH change. By using a photo-acid generator, the two-component gel can be prepared combining the thermal trigger with photo-irradiation. Photo-patterned self-assembly of DBS-COOH within a pre-formed DBS-CONHNH2 gel under a mask yields spatially controlled multi-domain gels. Different gel domains can have different functions, for example, controlling the rate of release of heparin incorporated into the gel, or directing gold nanoparticle assembly. Such photo-patterned multi-component hydrogels have potential applications in regenerative medicine or bio-nano-electronics.

Novel reinforced cross-linked lysozyme crystals containing homogeneous dispersions of single-walled carbon nanotubes (SWCNTs) have been produced and characterized. The incorporation of SWCNTs inside lysozyme crystals gives rise to reinforced hybrid materials with tunable mechanical strength and electronic conductivity, while preserving the crystal-quality and morphology. These reinforced crystals show increase catalytic activity at higher temperature, being active even above the denaturation temperature. The electron transport through the crystals have been linked to the content and distribution of SWCNTs inside the crystals. The electron conduction through the crystals is isotropic and very efficient, presenting high conductivity values up to 600 nS at very low (0.05 wt%) SWCNTs concentration. To obtain these crystals a new protocol based on the in situ crystallization of lysozyme in hybrid SWCNTs-peptide hydrogels has been developed. These peptide hydrogels have been able to homogeneously dispersed hydrophobic SWCNTs allowing first, the crystallization of the enzyme lysozyme and secondly, transferring the new properties of the inorganic component to the crystals. Taken together, these hybrid crystals represent a notorious example of the versatility of proteins as biological substrates in the generation of novel functional materials, opening the door to use them in catalysis and bioelectronics at macroscale., Projects BIO2016-74875-P and FIS2017-85954-R (Ministerio de Economía, Industria y Competitividad, MINECO, and Agencia Estatal de Investigación, AEI, Spain, co-funded by Fondo Europeo de Desarrollo Regional, FEDER, European Union) and by Junta de Andalucía (Spain) projects P12-FQM-2721 and P12-FQM-790.

Hydrogel actuators that can undergo structural change upon external stimuli are highly demanded due to their potential applications in diverse fields. However, the actuators based on physically cross-linked supramolecular hydrogels are largely unexplored. This study reports the engineering of an electrically controllable supramolecular hydrogel as an actuator from a self-assembling short peptide, in which a catechol moiety is introduced as the stimuli-responsive motif. This kind of electrochemically responsive hydrogel is mechanically stable and can switch its physical properties dramatically upon the applied electric field. The mechanism and reversibility of the change are studied in detail. As a proof of principle, devices are designed to perform the unidirectional expansion and rotational motion under electrical stimulations. The applications of the actuators for controllable drug release and actuation of microfluidic devices are also illustrated. It is expected that these kind of supramolecular hydrogel actuators can find broad applications as novel biosensors, artificial robots, and smart soft materials.

Attempts to rationally tune the macroscopic mechanical performance of supramolecular hydrogel networks through noncovalent molecular interactions have led to a wide variety of supramolecular materials with desirable functions. While the viscoelastic properties are dominated by temporal hierarchy (crosslinking kinetics), direct mechanistic studies on spatiotemporal control of supramolecular hydrogel networks, based on host-guest chemistry, have not yet been established. Here, supramolecular hydrogel networks assembled from highly branched cucurbit[8]uril-threaded polyrotaxanes (HBP-CB[8] ) and naphthyl-functionalized hydroxyethyl cellulose (HECNp) are reported, exploiting the CB[8] host-guest complexation. Mechanically locking CB[8] host molecules onto a highly branched hydrophilic polymer backbone, through selective binary complexation with viologen derivatives, dramatically increases the solubility of CB[8]. Additionally, the branched architecture enables tuning of material dynamics of the supramolecular hydrogel networks via both topological (spatial hierarchy) and kinetic (temporal hierarchy) control. Relationship between macroscopic properties (time- and temperature-dependent rheological properties, thermal stability, and reversibility), spatiotemporal hierarchy, and chain dynamics of the highly branched polyrotaxane hydrogel networks is investigated in detail. Such kind of tuning of material mechanics through spatiotemporal hierarchy improves our understanding of the challenging relationship between design of supramolecular polymeric materials and their complex viscoelasticity, and also highlights a facile strategy to engineer dynamic supramolecular materials., Ministry of Education of Malaysia and Universiti Teknologi MARA, Marie Curie Fellowship. Grant Number: 658360

We have synthesised a neutral, water-soluble, Pt(II) complex able to aggregate more efficiently in aqueous solutions than in organic solvents. The aggregates are luminescent and are not quenched by molecular oxygen. Further, we have prepared phosphorescent hydrogels utilising host-guest interactions between cyclodextrins and the tetraethylene glycol tails of the Pt(II) complex. The soft assemblies feature host-dependent emission properties.

As a consequence of the self-assembly of small organic molecules in water, supramolecular hydrogels are evolving from serendipitous events during organic synthesis to become a new type of materials that hold promise for applications in biomedicine. In this Focus Review, we describe recent advances in the use of basic biological building blocks for creating molecules that act as hydrogelators and the potential applications of the corresponding hydrogels. After introducing the concept of supramolecular hydrogels and defining the scope of this review, we briefly describe the methods for making and characterizing supramolecular hydrogels. We then discuss representative hydrogelators according to the categories of their building blocks, such as amino acids, nucleobases, and saccharides, and highlight the applications of the hydrogels when necessary. Finally, we offer our perspective and outlook on this fast-growing field at the interface of organic chemistry, materials, biology, and medicine. By providing a snapshot for chemists, engineers, and medical scientists, we hope that this Focus Review will contribute to the development of multidisciplinary research on supramolecular hydrogels for a wide range of applications in different fields.

Hydrogels based on natural polymers have bright application prospects in biomedical fields due to their outstanding biocompatibility and biodegradability. However, the poor mechanical performances of pure natural polymer-based hydrogels greatly limit their application prospects. Recently, a variety of strategies has been applied to prepare natural polymer-based hydrogels with enhanced mechanical properties, which generally exhibit stiffening, strengthening, and stretchable behaviors. This article summarizes the recent progress of natural polymer-based hydrogels with enhanced mechanical properties. From a structure point of view, four kinds of hydrogel are reviewed; double network hydrogels, nanocomposite hydrogels, click chemistry-based hydrogels, and supramolecular hydrogels. For each typical hydrogel, its preparation, structure, and mechanical performance are introduced in detail. At the end of this article, the current challenges and future prospects of hydrogels based on natural polymers are discussed and it is pointed out that 3D printing may offer a new platform for the development of natural polymer-based hydrogels.

Supramolecular hydrogels (SMHs) are three-dimensional networks filled with a large amount of water. The crosslinking force in the 3D network is always constructed by relatively weak and dynamic non-covalent interactions, and thus SMHs usually possess extremely high susceptibility to external environment and can show extraordinary stimuli-responsive, self-healing or other attractive properties. However, the overall crosslinking force in hydrogel networks is difficult to flexibly modulate, and this leads to limited functions of the SMHs. In this regard, hierarchical hydrogen bonds, that is, the mixture of relatively strong and relatively weak hydrogen bonds, are used herein as crosslinking force for the hydrogel preparation. The ratio of strong and weak hydrogen bonds can be finely tuned to tailor the properties of resultant gels. Thus, by delicate manipulation of the overall crosslinking force in the system, a hydrogel with multiple (thermal, pH and NIR light) responsiveness, autonomous self-healing property and interesting temperature dependent, reversible adhesion behavior is obtained. This kind of hierarchical hydrogen bond manipulation is proved to be a general method for multiple-functionality hydrogel preparation, and the resultant material shows potential for a range of applications.

This paper highlights recent developments in the design and construction of functional materials such as supramolecular hydrogels and ion channels using a guanine motif as a self-assembling building block.

A thermoregulated catalytic process has been elaborated using a ruthenium-nanoparticle catalyst embedded into a supramolecular cyclodextrin-based hydrogel matrix. Upon heating, the gel phase turned into a sol phase in which alkenes could be efficiently hydrogenated. Upon cooling, the reaction products and the metallic catalyst could be easily separated. The reusability of the system was clearly demonstrated.

Self-healing supramolecular hydrogels have emerged as a novel class of biomaterials that combines hydrogels with supramolecular chemistry to develop highly functional biomaterials with advantages including native tissue mimicry, biocompatibility, and injectability. These properties are endowed by the reversibly cross-linked polymer network of the hydrogel. These hydrogels have great potential for realizing yet to be clinically translated tissue engineering therapies. This review presents methods of self-healing supramolecular hydrogel formation and their uses in tissue engineering as well as future perspectives.

Supramolecular hydrogels that are assembled through dynamic host-guest interactions have presented apparent potential in the construction of materials with promising performance. Herein, a photoregulated hydrogel cross-linked by host-guest interactions with multifunctions of high stretchability, strong toughness, and rapid self-healing property is reported. The hydrogel exhibits unique light-responsive property due to the introduction of two photoisomerized groups. For example, the stress-strain curve of the original hydrogel indicates 1020% rupture strain with the maximum tensile strain value of 214 kPa. Upon 365 nm light irradiation for an hour, its tensile strain increases to 15 times with lower tensile stress indicating a better stretchability. Moreover, the hydrogel is photochromic and surface patternable, where it can reversibly switch color between luminous yellow and brown while exposed to 365 and 440 nm light irradiation. It holds great promise for applying in self-recovering optically controlled and labeled elastic mechanical materials.

In this paper, four gelators (defined as G1–G4) were prepared from 3,3′,4,4′-benzophenonetetracarboxylic acid (BPTA) and para-hydroxylpyridine or meta-hydroxylpyridine at molar ratios 1:2 and 1:4 respectively, and characterized by 1H NMR, IR, UV-Vis spectra and elemental analysis. Due to the amphiphilic features, all the gelators were able to gel water via cooling their aqueous solution under different stimulations. The structure of the assembling fibers and the macroscopic properties of the gels were investigated by multiple techniques. The results indicated that the minimum gelator concentration (MGC) increased by the order of G1, G2, G3 and G4, while the gel-to-sol dissociation temperature (Tgel) decreased by the same order, which were explained from the assembling structures of the gels.

The self assembly of peptide hydrogelators that carry aromatic substituents can be modeled by a novel nanocylindrical architecture. The proposed model suggests that the nanocylinders are formed by anti-parallel β-sheets interlocked by the π-stacking interactions of fluorenyl groups and phenyl rings. This explanation is consistent with the structures observed in TEM and the data obtained by a variety of spectroscopic techniques.

Over the past years, the gelation of aqueous solutions by low molecular weight (LMW) compounds has become an area of increasing interest, owing to developments in the field of LMW organogelators. Until recently, LMW hydrogelators were found only by serendipity, nowadays rational design as well as application of LMW hydrogelators has become feasible. As a consequence, an increasing number of responsive and functional LMW hydrogels are reported, offering great prospects for diverse applications including drug delivery and smart materials. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005).