Gel-phase Materials Research Articles

3D Bioprinting of Cell-Laden Hydrogels for Improved Biological Functionality.

The encapsulation of cells within gel-phase materials to form bioinks offers distinct advantages for next-generation 3D bioprinting. 3D bioprinting has emerged as a promising tool for patterning cells, but the technology remains limited in its ability to produce biofunctional, tissue-like constructs due to a dearth of materials suitable for bioinks. While early demonstrations commonly used viscous polymers optimized for printability, these materials often lacked cell compatibility and biological functionality. In response, advanced materials that exist in the gel phase during the entire printing process are being developed, since hydrogels are uniquely positioned to both protect cells during extrusion and provide biological signals to embedded cells as the construct matures during culture. Here, an overview of the design considerations for gel-phase materials as bioinks is presented, with a focus on their mechanical, biochemical, and dynamic gel properties. Current challenges and opportunities that arise due to the fact that bioprinted constructs are active, living hydrogels composed of both acellular and cellular components are also evaluated. Engineering hydrogels with consideration of cells as an intrinsic component of the printed bioink will enable control over the evolution of the living construct after printing to achieve greater biofunctionality.

Noncovalent Aqua Materials Based on Perylene Diimides.

Most robust functional organic materials are currently based on polymers. These materials exhibit high stability, but once formed they are difficult to modify, adapt to their environment, and recycle. Materials based on small molecules that are held together by noncovalent interactions can offer an alternative to conventional polymer materials for applications that require adaptive and stimuli-responsive features. However, it is challenging to engineer macroscopic noncovalent materials that are sufficiently robust for practical applications. This Account summarizes progress made by our group towards the development of noncovalent "aqua materials" based on well-defined organic molecules. These materials are uniquely assembled in aqueous media, where they harness the strength of hydrophobic and π-π interactions between large aromatic groups to achieve robustness. Despite their high stability, these supramolecular systems can dynamically respond to external stimuli. We discuss design principles, fundamental properties, and applications of two classes of aqua materials: (1) supramolecular gels and (2) nanocrystalline arrays. The materials were characterized by a combination of steady-state and time-resolved spectroscopic techniques, electrical measurements, molecular modeling, and high-resolution microscopic imaging, in particular cryogenic transmission electron microscopy (cryo-TEM) and cryogenic scanning electron microscopy (cryo-SEM). All investigated aqua materials are based on one key building block, perylene diimide (PDI). PDI exhibits remarkably stable intermolecular bonds, together with useful chemical and optoelectronic properties. PDI-based amphiphiles carrying poly(ethylene glycol) (PEG) were designed to form linear supramolecular polymers in aqueous media. These one-dimensional arrays of noncovalently linked molecules can entangle and form three-dimensional supramolecular networks, leading to soft gel-like materials. Tuning the strength of interactions between fibers enables dynamic adjustment of viscoelastic properties and functional characteristics. Besides supramolecular gels, we show that simple PDI-based molecules can self-assemble in aqueous medium to form robust organic nanocrystals (ONCs). The mechanical and optoelectronic properties of ONCs are distinctly different from gel-phase materials. ONCs are excellent building blocks for macroscopic free-standing materials that can be used in dry state, unlike hydrogels. Being constructed from small molecules, ONC materials are easy to fabricate and recycle. High thermal robustness, good mechanical properties, and modular design render ONC materials versatile and suitable for a variety of applications. In the future, noncovalent aqua materials can become a sustainable alternative to conventional polymer materials. Examples from our research include stimuli-responsive and recyclable filtration membranes for preparative nanoparticle separation, water purification and catalysis, light-harvesting hydrogels for solar energy conversion, and nanocrystalline films for switchable surface coatings and electronic devices.

Supramolecular Fibers in Gels Can Be at Thermodynamic Equilibrium: A Simple Packing Model Reveals Preferential Fibril Formation versus Crystallization.

Low molecular weight gelators are able to form nanostructures, typically fibers, which entangle to form gel-phase materials. These materials have wide-ranging applications in biomedicine and nanotechnology. While it is known that supramolecular gels often represent metastable structures due to the restricted molecular dynamics in the gel state, the thermodynamic nature of the nanofibrous structure is not well understood. Clearly, 3D extended structures will be able to form more interactions than 1D structures. However, self-assembling molecules are typically amphiphilic, thus giving rise to a combination of solvophobic and solvophilic moieties where a level of solvent exposure at the nanostructure surface is favorable. In this study, we introduce a simple packing model, based on prisms with faces of different nature (solvophobic and solvophilic) and variable interaction parameters, to represent amphiphile self-assembly. This model demonstrates that by tuning shape and "self" or "solvent" interaction parameters either the 1D fiber or 3D crystal may represent the thermodynamic minimum. The model depends on parameters that relate to features of experimentally known systems: the number of faces exposed to the solvent or buried in the fiber; the overall shape of the prism; and the free energy penalties associated with the interactions can be adjusted to match their chemical nature. The model is applied to describe the pH-dependent gelation/precipitation of well-known gelator Fmoc-FF. We conclude that, despite the fact that most experimentally produced gels probably represent metastable states, one-dimensional fibers can represent thermodynamic equilibrium. This conclusion has critical implications for the theoretical treatment of gels.

MICROWAVE PYROLYSIS ASSISTED WITH CARBON BASED ABSORBENT: AN OVERVIEW

Over recent years, there has been an explosive growth of interest in the development of novel gel-phase materials based on small molecules. It has been recognised that an effective gelator should possess functional groups that interact with each other via temporal associative forces. This process leads to the formation of supramolecular polymer-like structures, which then aggregated further hence, gelating the solvent. Supramolecular interactions between building blocks that enable gel formation include hydrogen bonds, interactions, solvatophobic effects and van der Waals forces.

ChemInform Abstract: Supramolecular Organogels Based on Dendrons and Dendrimers

AbstractReview: [93 refs.

PULSE LASER ABLATION IN LIQUID INDUCE GOLD NANOPARTICLE PRODUCTION

Over recent years, there has been an explosive growth of interest in the development of novel gel-phase materials based on small molecules. It has been recognized that an effective gelator should possess functional groups that interact with each other via temporal associative forces. This process leads to the formation of supramolecular polymer-like structures, which then aggregate further, hence gelating the solvent. Supramolecular interactions between building blocks that enable gel formation include hydrogen bonds, interactions, solvatophobic effects and van der Waals forces.

Tailor-made design of J- or H-aggregated naphthalenediimide-based gels and remarkable fluorescence turn on/off behaviour depending on solvents.

A naphthalenediimide (NDI)-based new gelator molecule has been discovered, the molecule forms interesting J/H-aggregated species depending on solvents (aliphatic/aromatic) and remarkably, the fluorescence of the gel phase materials is nicely tuned according to the electron donating capacity of the aromatic solvent.

Using EPR spectroscopy as a unique probe of molecular-scale reorganization and solvation in self-assembled gel-phase materials.

We describe the synthesis of spin-labeled bis-ureas which coassemble with bis-urea gelators and report on self-assembly as detected using electron paramagnetic resonance spectroscopy (EPR). Specifically, EPR detects the gel-sol transition and allows us to quantify how much spin-label is immobilized within the gel fibers and how much is present in mobile solvent pools-as controlled by temperature, gelator structure, and thermal history. EPR is also able to report on the initial self-assembly processes below the gelation threshold which are not macroscopically visible and appears to be more sensitive than NMR to intermediate-sized nongelating oligomeric species. By studying dilute solutions of gelator molecules and using either single or double spin-labels, EPR allows quantification of the initial steps of the hierarchical self-assembly process in terms of cooperativity and association constant. Finally, EPR enables us to estimate the degree of gel-fiber solvation by probing the distances between spin-labels. Comparison of experimental data against the predicted distances assuming the nanofibers are only composed of gelator molecules indicates a significant difference, which can be assigned to the presence of a quantifiable number of explicit solvent molecules. In summary, EPR provides unique data and yields powerful insight into how molecular-scale mobility and solvation impact on assembly of supramolecular gels.

Differential self-assembly and tunable emission of aromatic peptide bola-amphiphiles containing perylene bisimide in polar solvents including water.

We demonstrate the self-assembly of bola-amphiphile-type conjugates of dipeptides and perylene bisimide (PBI) in water and other polar solvents. Depending on the nature of the peptide used (glycine-tyrosine, GY, or glycine-aspartic acid, GD), the balance between H-bonding and aromatic stacking can be tailored. In aqueous buffer, PBI-[GY]2 forms chiral nanofibers, resulting in the formation of a hydrogel, while for PBI-[GD]2 achiral spherical aggregates are formed, demonstrating that the peptide sequence has a profound effect on the structure formed. In water and a range of other polar solvents, self-assembly of these two PBI-peptides conjugates results in different nanostructures with highly tunable fluorescence performance depending on the peptide sequence employed, e.g., fluorescent emission and quantum yield. Organogels are formed for the PBI-[GD]2 derivative in DMF and DMSO while PBI-[GY]2 gels in DMF. To the best of our knowledge, this is the first successful strategy for using short peptides, specifically, their sequence/structure relationships, to manipulate the PBI nanostructure and consequent optical properties. The combination of controlled self-assembly, varied optical properties, and formation of aqueous and organic gel-phase materials may facilitate the design of devices for various applications related to light harvesting and sensing.

The Halogen Bond in the Design of Functional Supramolecular Materials: Recent Advances

Halogen bonding is an emerging noncovalent interaction for constructing supramolecular assemblies. Though similar to the more familiar hydrogen bonding, four primary differences between these two interactions make halogen bonding a unique tool for molecular recognition and the design of functional materials. First, halogen bonds tend to be much more directional than (single) hydrogen bonds. Second, the interaction strength scales with the polarizability of the bond-donor atom, a feature that researchers can tune through single-atom mutation. In addition, halogen bonds are hydrophobic whereas hydrogen bonds are hydrophilic. Lastly, the size of the bond-donor atom (halogen) is significantly larger than hydrogen. As a result, halogen bonding provides supramolecular chemists with design tools that cannot be easily met with other types of noncovalent interactions and opens up unprecedented possibilities in the design of smart functional materials.This Account highlights the recent advances in the design of halogen-bond-based functional materials. Each of the unique features of halogen bonding, directionality, tunable interaction strength, hydrophobicity, and large donor atom size, makes a difference. Taking advantage of the hydrophobicity, researchers have designed small-size ion transporters. The large halogen atom size provided a platform for constructing all-organic light-emitting crystals that efficiently generate triplet electrons and have a high phosphorescence quantum yield. The tunable interaction strengths provide tools for understanding light-induced macroscopic motions in photoresponsive azobenzene-containing polymers, and the directionality renders halogen bonding useful in the design on functional supramolecular liquid crystals and gel-phase materials. Although halogen bond based functional materials design is still in its infancy, we foresee a bright future for this field. We expect that materials designed based on halogen bonding could lead to applications in biomimetics, optics/photonics, functional surfaces, and photoswitchable supramolecules.

Aqueous Self-Sorting in Extended Supramolecular Aggregates

Self-organization and self-sorting processes are responsible for the regulation and control of the vast majority of biological processes that eventually sustain life on our planet. Attempts to unveil the complexity of these systems have been devoted to the investigation of the binding processes between artificial molecules, complexes or aggregates within multicomponent mixtures, which has facilitated the emergence of the field of self-sorting in the last decade. Since, artificial systems involving discrete supramolecular structures, extended supramolecular aggregates or gel-phase materials in organic solvents or—to a lesser extent—in water have been investigated. In this review, we have collected diverse strategies employed in recent years to construct extended supramolecular aggregates in water upon self-sorting of small synthetic molecules. We have made particular emphasis on co-assembly processes in binary mixtures leading to supramolecular structures of remarkable complexity and the influence of different external variables such as solvent and concentration to direct recognition or discrimination processes between these species. The comprehension of such recognition phenomena will be crucial for the organization and evolution of complex matter.

Formation of Hybrid Hydrogels Consisting of Tripeptide and Different Silver Nanoparticle-Capped Ligands: Modulation of the Mechanical Strength of Gel Phase Materials

An N-terminally Boc (tert-butyloxycarbonyl) group-protected synthetic tripeptide (Boc-Phe-Phe-Ala-OH) has been found to form a translucent hydrogel in basic aqueous medium. This hydrogel material has been characterized using field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), Fourier transformed infrared spectroscopy, differential scanning calorimetric, X-ray diffraction (XRD), and rheological studies. FE-SEM and TEM studies have revealed the formation of a nanofibrillar network structure upon gelation. Thiol (-SH) containing ligands (amino acid/peptide) have been used to stabilize small silver nanoparticles (AgNPs), and these thiol-capped silver nanoparticles have been incorporated into this hydrogel to prepare hybrid hydrogels. Morphological study of silver nanoparticles containing a hybrid hydrogel (using TEM experiments) has indicated the nice fabrication of AgNPs along the gel nanofibers. Fabrication of nanoparticles upon the gel nanofibers is due to noncovalent interactions between the capping ligands of the nanoparticles and the peptide-based hydrogel nanofibers. Rheological investigations of these hybrid hydrogels have shown the weakening of the mechanical strength of the hydrogel after incorporation of AgNPs within the native hydrogel system. Our studies have vividly shown the dependence of the elastic modulus (G') and yield stress (σ(y)) on three factors: (a) the nature of the stabilizing ligands used for AgNPs, (b) the size of the AgNPs, and (c) the amount of AgNPs used for the preparation of hybrid hydrogel systems. Modulation of the mechanical strength of the hybrid hydrogel can be successfully achieved by varying these above-mentioned factors. This modulation of the mechanical properties keeps a future promise to make tunable soft materials with interesting properties.

Dramatic Specific‐Ion Effect in Supramolecular Hydrogels

We report on a pronounced specific-ion effect on the intermolecular and chiral organization, supramolecular structure formation, and resulting materials properties for a series of low molecular weight peptide-based hydrogelators, observed in the presence of simple inorganic salts. This effect was demonstrated using aromatic short peptide amphiphiles, based on fluorenylmethoxycarbonyl (Fmoc). Gel-phase materials were formed due to molecular self-assembly, driven by a combination of hydrogen bonding and π-stacking interactions. Pronounced morphological changes were observed by atomic force microscopy (AFM) for Fmoc-YL peptide, ranging from dense fibrous networks to spherical aggregates, depending on the type of anions present. The gels formed had variable mechanical properties, with G' values between 0.8 kPa and 2.4 kPa as determined by rheometry. Spectroscopic analysis provided insights into the differential mode of self-assembly, which was found to be dictated by the hydrophobic interactions of the fluorenyl component, with comparable H-bonding patterns observed in each case. The efficiency of the anions in promoting the hydrophobic interactions and thereby self-assembly was found to be consistent with the Hofmeister anion sequence. Similar effects were observed with other hydrophobic peptides, Fmoc-VL and Fmoc-LL. The effect was found to be less pronounced for a less hydrophobic peptide, Fmoc-AA. To get more insights into the molecular mechanism, the effect of anions on sol-gel equilibrium was investigated, which indicates the observed changes result from the specific-ion effects on gels structure, rather than on the sol-gel equilibrium. Thus, we demonstrate that, by simply changing the ionic environment, structurally diverse materials can be accessed providing an important design consideration in nanofabrication via molecular self-assembly.

Mechanosensitive peptidegelation: mode of agitation controls mechanical properties and nano-scale morphology

In this study we demonstrate the sensitivity of fibrillar self-assembly and gelation of aromatic peptide amphiphiles to different modes of mechanical agitation. In particular, we show how different homogenization techniques (vortex vs. manual or orbital agitation) during the gelation process can dramatically influence the mechanical properties and the nano-scale organization of self-assembled materials. The pH-induced self-assembly of mixtures of fluorenylmethoxycarbonyl-diphenylalanine (Fmoc-FF) and Fmoc-diglycine (Fmoc-GG) to gel phase materials was performed under different agitation conditions (vortex vs. manual or orbital agitation). We demonstrate that mechanically induced differences of up to one order of magnitude in shear modulus could be obtained for chemically identical samples as measured using oscillatory rheology and in creep and recovery experiments. AFM imaging and nanoindentation were then employed to highlight morphological, mechanical and physico-chemical differences in the fibrillar elements (ribbons). Furthermore, we have demonstrated that although Fmoc-diglycine alone does not undergo fibrillar aggregation, nor is capable of gelation at neutral pH, its presence influences the properties of gels at both fibrillar and macroscopic level; in particular, a Fmoc-diglycine/Fmoc-diphenylalanine 1 : 1 molar ratio appeared to provide the highest moduli and the most regular fibers, suggesting a specific mode of intercalation of Fmoc-diglycine in Fmoc-diphenylalanine fibrils.

Solvent–gelator interactions—using empirical solvent parameters to better understand the self-assembly of gel-phase materials

By studying a family of L-lysine bis-urea gelators with variable peripheral groups in different solvents, a more detailed understanding of the way in which gelator fibres interact with the surrounding solvent environment is obtained. In all cases, these gelators establish the same hydrogen bonding molecular recognition pathways—however, this process is mediated by the nature of the solvent. In terms of Kamlet–Taft parameters, the α parameter of the solvent (hydrogen bond donor ability) has primary importance in controlling whether the gelator can establish a hydrogen bond network; the β parameter (hydrogen bond acceptor ability) plays a secondary role in tuning the thermal stability of the gel, and the π* parameter (polarisability) controls the solvation of the peripheral groups on the gelator by the solvent, and hence tunes the gel stability and the ability of the gelator to establish fibre–fibre interactions, as evidenced by scanning electron microscopy imaging. Considering solvent parameters allows us to gain a unique insight into hierarchical assembly processes at different length scales, i.e., molecular scale gelator–gelator interactions, and nanoscale fibre–fibre and fibre–solvent interactions. These processes are at the heart of developing effective models for the dynamic assembly of gel-phase soft materials.

ChemInform Abstract: Anion‐Tuned Supramolecular Gels: A Natural Evolution from Urea Supramolecular Chemistry

AbstractReview: 70 refs.

A potent triphenylbenzene-based H-bonding donor to assist formation of two-component organogels with stilbazoles

Abstract Two-component organogelators based on a discotic H-bonding donor of 1,3,5-tris(4-amidobutanoic acid)phenyl benzene ( 2 ), and acceptors of 4-(4-alkoxybenzoyloxy)-4′-stilbazole derivatives were reported. These complexes showed good gelation ability for alcohols, which are known to be unfavorable for H-bonding formation. SEM study revealed that sheet-like network, nanotapes, and nanorods were gained from the self-assembling of the complexes with small difference of the carbon chain length. Based on XRD, IR, temperature-dependent 1 H NMR, and UV–vis absorption investigations, the gel-phase materials were generated from 1D columnar-type packing of complexes facilitated by cooperative H-bonding, π-stacking, and van der Walls interactions.

Anion-tuned supramolecular gels: a natural evolution from urea supramolecular chemistry

This tutorial review looks at the formation of low molecular weight gels from molecular principles using the well-explored supramolecular chemistry of ureas as an example. Synthesising lessons learned from classical urea inclusion chemistry, ureas in crystal engineering, ureas in self-assembly, urea functional groups in anion binding and sensing, and ureas as organocatalysts lead to the development and understanding of a new class of anion-tunable, urea-based soft materials. This review concludes with a look at emerging application areas for tunable gel-phase materials as controlled crystal growth media, both in templating metallic nanoparticles and in the growth and isolation of high quality crystals of molecular organic compounds, including polymorphic pharmaceuticals.

Metathesis within Self-Assembled Gels: Transcribing Nanostructured Soft Materials into a More Robust Form

This article reports the covalent capture of self-assembled gel-phase materials using alkene metathesis. Gels assembled from a gelator functionalized with peripheral alkene groups were reacted with Grubbs' second generation catalyst, added as a solution to the top of the gel and allowed to diffuse into the material for 24 h. Using this approach, the fibrillar self-assembled network was covalently captured, yielding a large amount of insoluble material that was robust, thermally stable, and highly swellable in solvents compatible with the gelator. Scanning electron microscopy demonstrated that the insoluble metathesized material contained nanoscale fibers, which were aligned into rigid fiber bundles on drying. When the gelator was assembled in the presence of a second non-cross-linkable gelator, self-sorting took place, giving rise to two independent gelator networks. Metathesis then generated an insoluble material in which the individual gel fibers of the cross-linkable gelator were captured, whereas the nonreactive gelator could be washed away. Intriguingly, using this approach appeared to hinder the alignment of gel fibers into rigid fiber bundles. Instead, individual, well-defined, robust gelator nanofibers were visualized in the dried materials. In addition, the material synthesized this way appeared to be even more highly porous and swellable on the addition of solvent. In summary, this article demonstrates that metathesis is an effective way to capture nanostructured gel-phase materials covalently, with the judicious choice of additives helping to control the morphology and behavior of the materials generated. This approach to nanofabrication could ultimately give rise to nanostructured polymeric materials with a wide range of applications.

Lost in translation? Chirality effects in the self-assembly of nanostructured gel-phase materials

Gel-phase materials are generated when molecular building blocks assemble into nanoscale architectures, usually 'one-dimensional' fibrils, which hierarchically assemble into bundles and subsequently form an entangled sample spanning network, capable of preventing the flow of bulk solvent. This tutorial review explores the vital role of chirality in gel formation. In particular, we focus on how fundamental self-assembly processes can translate molecular scale chiral information into nanoscale architectures, and then into the macroscopic behaviour of the gel. Chiral molecular gels have potential applications in nanofabrication and as addressable functional nanomaterials.