Network physics of attractive colloidal gels: Resilience, rigidity, and phase diagram.

Colloidal gels exhibit solid-like behavior at vanishingly small fractions of solids, owing to ramified space-spanning networks that form due to particle-particle interactions. These networks give the gel its rigidity, and with stronger attractions the elasticity grows as well. The emergence of rigidity can be described through a mean field approach; nonetheless, fundamental understanding of how rigidity varies in gels of different attractions is lacking. Moreover, recovering an accurate gelation phase diagram based on the system's variables has been an extremely challenging task. Understanding the nature of colloidal clusters, and how rigidity emerges from their connections is key to controlling and designing gels with desirable properties. Here, we employ network analysis tools to interrogate and characterize the colloidal structures. We construct a particle-level network, having all the spatial coordinates of colloids with different attraction levels, and also identify polydisperse rigid fractal clusters using a Gaussian mixture model, to form a coarse-grained cluster network that distinctly shows main physical features of the colloidal gels. A simple mass-spring model then is used to recover quantitatively the elasticity of colloidal gels from these cluster networks. Interrogating the resilience of these gel networks shows that the elasticity of a gel (a dynamic property) is directly correlated to its cluster network's resilience (a static measure). Finally, we use the resilience investigations to devise [and experimentally validate] a fully resolved phase diagram for colloidal gelation, with a clear solid-liquid phase boundary using a single volume fraction of particles well beyond this phase boundary.

Harmonic resonance and entrainment of propagating chemical waves by external mechanical stimulation in BZ self-oscillating hydrogels.

Smart polymer materials that are nonliving yet exhibit complex "life-like" or biomimetic behaviors have been the focus of intensive research over the past decades, in the quest to broaden our understanding of how living systems function under nonequilibrium conditions. Identification of how chemical and mechanical coupling can generate resonance and entrainment with other cells or external environment is an important research question. We prepared Belousov-Zhabotinsky (BZ) self-oscillating hydrogels which convert chemical energy to mechanical oscillation. By cyclically applying external mechanical stimulation to the BZ hydrogels, we found that when the oscillation of a gel sample entered into harmonic resonance with the applied oscillation during stimulation, the system kept a "memory" of the resonant oscillation period and maintained it post stimulation, demonstrating an entrainment effect. More surprisingly, by systematically varying the cycle length of the external stimulation, we revealed the discrete nature of the stimulation-induced resonance and entrainment behaviors in chemical oscillations of BZ hydrogels, i.e., the hydrogels slow down their oscillation periods to the harmonics of the cycle length of the external mechanical stimulation. Our theoretical model calculations suggest the important roles of the delayed mechanical response caused by reactant diffusion and solvent migration in affecting the chemomechanical coupling in active hydrogels and consequently synchronizing their chemical oscillations with external mechanical oscillations.

Self-assembled active actomyosin gels spontaneously curve and wrinkle similar to biological cells and tissues.

Living systems adopt a diversity of curved and highly dynamic shapes. These diverse morphologies appear on many length scales, from cells to tissues and organismal scales. The common driving force for these dynamic shape changes are contractile stresses generated by myosin motors in the cell cytoskeleton, that converts chemical energy into mechanical work. A good understanding of how contractile stresses in the cytoskeleton arise into different three-dimensional (3D) shapes and what are the shape selection rules that determine their final configurations is still lacking. To obtain insight into the relevant physical mechanisms, we recreate the actomyosin cytoskeleton in vitro, with precisely controlled composition and initial geometry. A set of actomyosin gel discs, intrinsically identical but of variable initial geometry, dynamically self-organize into a family of 3D shapes, such as domes and wrinkled shapes, without the need for specific preprogramming or additional regulation. Shape deformation is driven by the spontaneous emergence of stress gradients driven by myosin and is encoded in the initial disc radius to thickness aspect ratio, which may indicate shaping scalability. Our results suggest that while the dynamical pathways may depend on the detailed interactions between the different microscopic components within the gel, the final selected shapes obey the general theory of elastic deformations of thin sheets. Altogether, our results emphasize the importance for the emergence of active stress gradients for buckling-driven shape deformations and provide insights on the mechanically induced spontaneous shape transitions in contractile active matter, revealing potential shared mechanisms with living systems across scales.

3D Traction Force Microscopy in Biological Gels: From Single Cells to Multicellular Spheroids.

Cell traction force plays a critical role in directing cellular functions, such as proliferation, migration, and differentiation. Current understanding of cell traction force is largely derived from 2D measurements where cells are plated on 2D substrates. However, 2D measurements do not recapitulate a vital aspect of living systems; that is, cells actively remodel their surrounding extracellular matrix (ECM), and the remodeled ECM, in return, can have a profound impact on cell phenotype and traction force generation. This reciprocal adaptivity of living systems is encoded in the material properties of biological gels. In this review, we summarize recent progress in measuring cell traction force for cells embedded within 3D biological gels, with an emphasis on cell-ECM cross talk. We also provide perspectives on tools and techniques that could be adapted to measure cell traction force in complex biochemical and biophysical environments.

Real-Space Visualization of Charged Polymer Network of Hydrogel by Double Network Strategy and Mineral Staining.

Hydrogels consist of three-dimensional (3D) and complicated polymer networks that determine their physical properties. Among the methods for structural analyses of hydrogels, the real-space imaging of a polymer network of hydrogels on a nanometer scale is one of the optimal methods; however, it is highly challenging. In this study, we propose a direct observation method for cationic polymer networks using transmission electron microscopy (TEM). By combining the double network strategy and the mineral staining technique, we overcame the challenges of polymer aggregation and the low electron density of the polymer. An objective cationic network was incorporated into a neutral skeleton network to suppress shrinkage during subsequent staining. Titania mineralization along the cationic polymer strands provided sufficient electron density for the objective polymer network for TEM observation. This observation method enables the visualization of local structures in real space and plays a complementary role to scattering methods for soft matter structure analysis.

Counter-intuitive discovery in the formulation of poorly water-soluble drugs: Amorphous small-molecule gels.

Amorphous strategies have been extensively used in improving the dissolution of insoluble drugs for decades due to their high free energy. However, the formation of amorphous small-molecule gels (ASMGs) presents a counter-intuitive discovery that significantly limits their practical application. Recently, ASMGs have garnered attention because of their noncovalent structures, excellent biodegradability, and significant potential in various drug delivery systems in the pharmaceutical field. Hence, a comprehensive review is necessary to contribute to a better understanding of recent advances in ASMGs. This review aimed to introduce the main formation mechanisms, summarize possible influencing factors, generalize unique properties, outline elimination strategies, and discuss clinical application potential with preclinical cases of ASMGs. Moreover, few ASMGs are advanced to clinical stages. Intensive clinical research is needed for further development. We hope that this review can provide more efficient and rational guidance for exploring further clinical applications of ASMGs.

Ferula latisecta gels for synthesis of zinc/silver binary nanoparticles: antibacterial effects against gram-negative and gram-positive bacteria and physicochemical characteristics.

This study explores the potential antibacterial applications of zinc oxide nanoparticles (ZnO NPs) enhanced with silver (Ag) using plant gel (ZnO-AgO NPs). The problem addressed is the increasing prevalence of pathogenic bacteria and the need for new, effective antimicrobial agents. ZnO NPs possess distinctive physicochemical properties that enable them to selectively target bacterial cells. Their small size and high surface area-to-volume ratio allow efficient cellular uptake and interaction with bacterial cells. In this study, the average size of the synthesized ZnO-Ag nanoparticles was 77.1 nm, with a significant standard deviation of 33.7 nm, indicating a wide size distribution. The nanoparticles demonstrated remarkable antibacterial efficacy against gram-negative and gram-positive bacteria, with inhibition zones of 14.33 mm for E. coli and 15.66 mm for B. subtilis at a concentration of 300 µg/ml. Minimum inhibitory concentrations (MIC) were determined to be 100 µg/ml for E. coli and 75 µg/ml for S. saprophyticus. Additionally, ZnO-Ag NPs exhibited excellent biocompatibility, making them appropriate for various pharmacological uses. This study utilizes Ferula latisecta gels, offering a sustainable and eco-friendly approach to nanoparticle synthesis. Incorporating of Ag into ZnO NPs significantly enhances their antimicrobial properties, with the combined results showing great inhibition effects on pathogenic microbes. The findings suggest that ZnO-Ag NPs could be a promising candidate for addressing the challenges posed by drug-resistant bacterial infections and enhancing antimicrobial treatments.

Self-Assembled Molecular Fibers Aligned by Compression in Water.

Molecular self-assembly has attracted much attention as a potential approach for fabricating nanostructured functional materials. To date, energy-efficient fabrication of nano-objects such as nanofibers, nanorings, and nanotubes is achieved using well-designed self-assembling molecules. However, the application of molecular self-assembly to industrial manufacturing processes remains challenging because regulating the positions and directions of self-assembled products is difficult. Non-covalent molecular assemblies are also too fragile to allow mechanical handling. The present work demonstrates the macroscopic alignment of self-assembled molecular fibers using compression. Specifically, the macroscopic bundling of self-assembled nanofibers is achieved following dispersion in water. These fiber bundles can also be chemically crosslinked without drastic changes in morphology via trialkoxysilyl groups. Subsequently, vertically oriented porous membranes can be produced rapidly by slicing the bundles. This technique is expected to be applicable to various functional self-assembled fibers and can lead to the development of innovative methods of producing anisotropic nanostructured materials.

Hybrid Hydrogen Bonding Strategy to Construct Instantaneous Self-Healing Highly Elastic Ionohydrogel for Multi-Functional Electronics.

Gels show great promise for applications in wearable electronics, biomedical devices, and energy storage systems due to their exceptional stretchability and adjustable electrical conductivity. However, the challenge lies in integrating multiple functions like elasticity, instantaneous self-healing, and a wide operating temperature range into a single gel. To address this issue, a hybrid hydrogen bonding strategy to construct gel with these desirable properties is proposed. The intricate network of hybrid strong weak hydrogen bonds within the polymer matrix enables these ionohydrogel to exhibit remarkable instantaneous self-healing, stretching up to five times their original length within seconds. Leveraging these properties, the incorporation of ionic liquids, water, and zinc salts into hybrid hydrogen bond crosslinked network enables conductivity and redox reaction, making it a versatile ionic skin for real-time monitoring of human movements and respiratory. Moreover, the ionohydrogel can be used as electrolyte in the assembly of a zinc-ion battery, ensuring a reliable power supply for wearable electronics, even in extreme conditions (-20 °C and extreme deformations). This ionohydrogel electrolyte simplifies the diverse structural requirements of gels to meet the needs of various electronic applications, offering a new approach for multi-functional electronics.

Impact of a carrageenan gel on viral load of genital human papillomavirus infections in sexually active women: Findings from the Carrageenan-gel Against Transmission of Cervical Human papillomavirus (CATCH) trial.

Previous research has shown that women's use of a carrageenan gel reduces the risk of acquiring genital human papillomavirus (HPV) infections but does not help to clear existing ones. Although gel use may not result in complete clearance, it may decrease the viral load of HPV infections. We tested this hypothesis in the Carrageenan-gel Against Transmission of Cervical Human papillomavirus (CATCH) randomized controlled trial. Participants of the CATCH study were selected for viral load testing if they had completed the first four study visits and tested positive for HPV42 or HPV51 in at least one of these visits. HPV42 and HPV51 were chosen as they were among the most abundant low- and high-risk types, respectively, in the study sample. We measured viral load with a type-specific real-time polymerase chain reaction. Results were displayed using summary statistics. Of 461 enrolled participants, 39 were included in the HPV42 analysis set and 56 in the HPV51 analysis set. The median time between visits 1 and 4 was 3.7 months. The viral load (copies/cell) of HPV42 ranged from <0.001 to 13 434.1, and that of HPV51 from <0.001 to 967.1. The net median change in HPV42 viral load over all four visits was -1.04 copies/cell in the carrageenan and -147 copies/cell in the placebo arm (Wilcoxon rank sum test, p = 0.26). There was no net median change in HPV51 viral load over all four visits in either arm (p = 0.45). The use of a carrageenan-based gel is unlikely to reduce the viral load of HPVs 42 or 51.

Quantitative Characterization of RCA-based DNA Hydrogels - Towards Rational Design.

DNA hydrogels hold significant promise for biomedical applications and can be synthesized through enzymatic Rolling Circle Amplification (RCA). Due to the exploratory nature of this emerging field, standardized RCA protocols specifying the impact of reaction parameters are currently lacking. This study varied template sequences and reagent concentrations, evaluating RCA synthesis efficiency and hydrogel mechanical properties through quantitative PCR (qPCR) and indentation measurements, respectively. Primer concentration and stabilizing additives showed minimal impact on RCA efficiency, while changes in polymerase and nucleotide concentrations had a stronger effect. Concentration of the circular template exerted the greatest influence on RCA productivity. An exponential correlation between hydrogel viscosity and DNA amplicon concentration was observed, with nucleobase sequence significantly affecting both amplification efficiency and material properties, particularly through secondary structures. This study suggests that combining high-throughput experimental methods with structural folding prediction offers a viable approach for systematically establishing structure-property relationships, aiding the rational design of DNA hydrogel material systems.

Luminescent Supramolecular Metallogels: Drug Loading and Eu(III) as Structural Probe.

Supramolecular metallogels combine the rheological properties of gels with the color, magnetism, and other properties of metal ions. Lanthanide ions such as Eu(III) can be valuable components of metallogels due to their fascinating luminescence. In this work, we combine Eu(III) and iminodiacetic acid (IDA) into luminescent hydrogels. We investigate the tailoring of the rheological properties of these gels by changes in their metal:ligand ratio. Further, we use the highly sensitive Eu(III) luminescence to obtain information about the chemical structure of the materials. In special, we take advantage of computational calculations to employ an indirect method for structural elucidation, in which the simulated luminescent properties of candidate structures are matched to the experimental data. With this strategy, we can propose molecular structures for different EuIDA gels. We also explore the usage of these gels for the loading of bioactive molecules such as OXA, observing that its aldose reductase activity remains present in the gel. We envision that the findings from this work could inspire the development of luminescent hydrogels with tunable rheology for applications such as 3D printing and imaging-guided drug delivery platforms. Finally, Eu(III) emission-based structural elucidation could be a powerful tool in the characterization of advanced materials.

Tailoring the Properties of Gel Polymer Electrolytes for Sodium-Ion Batteries Using Ionic Liquids: A Review.

Ionic liquids are an extraordinary group of compounds, fully ionic in structure like inorganic salts but with low melting points, that resemble organic molecular solvents. Their chemical, electrochemical, and thermal stability is what draws the attention and enables their use in many applications, including electrochemical power sources. Even though they are no longer considered eco-friendly because of nonnegligible toxicity and long bioaccumulation, they can still be efficiently recovered, purified, and reused. These attributes can be harvested to enhance the properties of gel polymer electrolytes for the emerging sodium-ion batteries. The variety of anions and cations for ILs and their influence on the final properties of the compound opens the road to tuning the properties of gel polymer electrolytes. Ionic liquids as plasticizers constitute a major part of gel polymer electrolytes (average of 70 wt%) and hence, they affect the fundamental properties of gel electrolytes like ionic conductivity and electrochemical window. They also improve the safety features of sodium-ion batteries, which is relevant for their anticipated applications in stationary energy storage and electric vehicles. The presented review paper aims to explain the relationship between the cation and anion in ionic liquid and the properties of gel electrolytes for sodium-ion batteries.

Low-molecular-weight gels from amino acid and peptide derivatives for controlled release and delivery.

Low-molecular-weight (LMW) gelators are a versatile class of compounds able to self-assemble and to form supramolecular materials, such as gels. The use of LMW peptides to produce these gels shows many advantages, because of their wide structure tunability, the low-cost and effective synthesis, and the in vivo biocompatibility and biodegradability, which makes them optimal candidates for release and delivery applications. In addition, in these materials, the binding of the hosts may occur through a variety of noncovalent interactions, which are also the main factors responsible for the self-assembly of the gelators, and through specific interactions with the fibers or the pores of the gel matrix. This review aims to report LMW gels based on amino acid and peptide derivatives used for the release of many different species (drugs, fragrances, dyes, proteins, and cells) with a focus on the possible strategies to incorporate the cargo in these materials, and to demonstrate how versatile these self-assembled materials are in several applications.

Self-assembly of heterochiral, aliphatic dipeptides with Leu.

This work describes the self-assembly behavior of heterochiral, aliphatic dipeptides, l-Leu-d-Xaa (Xaa = Ala, Val, Ile, Leu), in green solvents such as acetonitrile (MeCN) and buffered water at neutral pH. Interestingly, water plays a structuring role because at 1% v/v, it enables dipeptide self-assembly in MeCN to yield organogels, which then undergo transition towards crystals. Other organic solvents and oils were tested for gelation, and metastable gels were formed in tetrahydrofuran, although at high peptide concentration (80 mM). Single-crystal X-ray diffraction revealed the dipeptides' supramolecular packing modes in amphipathic layers, as opposed to water channels reported for the homochiral Leu-Leu, or hydrophobic columns reported for homochiral Leu-Val and Leu-Ile.

Reversible Solubility Switching of a Polymer Triggered by Visible-Light Responsive Azobenzene Photochromism with Negligible Thermal Relaxation.

This study reports the reversible solubility switching of a polymer triggered by non-phototoxic visible light. A photochromic polymerizable azobenzene monomer with four methoxy groups at the ortho-position (mAzoA) was synthesized, exhibiting reversible photoisomerization between trans- and cis-states using green (546 nm) and blue light (436 nm). Free radical copolymerization of hydrophilic dimethylacrylamide (DMAAm) with mAzoA produced a light-responsive random copolymer (P(mAzoA-r-DMAAm)) that shows a reversible photochromic reaction to visible light. Optimizing mAzoA content resulted in P(mAzoA10.7-r-DMAAm)3.0 kDa exhibiting LCST-type phase separation in PBS (pH 7.4) with trans- and cis-states at 39.2 °C and 32.9 °C, respectively. The bistable temperature range of 6.3 °C covers 37 °C, suitable for mammalian cell culture. Reversible solubility changes were demonstrated under alternating green and blue light at 37 °C. 1H NMR indicated significant retardation of thermal relaxation from cis- to trans-states, preventing undesired thermal mechanical degradation. Madin Darby Canine Kidney (MDCK) cells adhered to the P(mAzoA-r-DMAAm) hydrogel, confirming its non-cytotoxicity and potential for biocompatible interfaces. This principle is useful for developing hydrogels that can reversibly stimulate cells mechanically or chemically in response to visible light.

Temperature-Adaptative Self-Oscillating Gels: Toward Autonomous Biomimetic Soft Actuators with Broad Operating Temperature Region.

Self-oscillating gel systems exhibiting an expanded operating temperature and accompanying functional adaptability are showcased. The developed system contains nonthermoresponsive main-monomers, such as N,N-dimethylacrylamide (DMAAm) or 2-acrylamido-2-methylpropane sulfonic acid (AMPS) or acrylamide (AAm) or 3-(methacryloylamino)propyl trimethylammonium chloride (MAPTAC). The gels volumetrically self-oscillate within the range of the conventional (20.0 °C) and extended (27.0 and 36.5 °C) temperatures. Moreover, the gels successfully adapt to the environmental changes; they beat faster and smaller as the temperature increases. The period and amplitude are also controlled by tuning the amount of main-monomers and N-(3-aminopropyl) acrylamide. Furthermore, the record amplitude in the bulk gel system consisting of polymer strand and cross-linker at 36.5 °C is achieved (≈10.8%). The study shows new self-oscillation systems composed of unprecedented combinations of materials, giving the community a robust material-based insight for developing more life-like autonomous biomimetic soft robots with various operating temperatures and beyond.

On the Swelling of Polymer Network Strands.

Large scale computer simulations are employed to analyze the conformations of network strands in polymer networks at preparation conditions (characterized by a polymer volume fraction of ϕ0) and when swollen to equilibrium (characterized by a polymer volume fraction ϕ < ϕ0). Network strands in end-linked model networks are weakly stretched and partially swollen at preparation conditions as compared to linear polymers in the same solvent at ϕ0. Equilibrium swelling causes non-ideal chain conformations characterized by an effective scaling exponent approaching 7/10 on intermediate length scales for increasing overlap of the chains. The chain size in a network consists of a fluctuating and a time average "elastic" contribution. The elastic contribution swells essentially affinely ∝(ϕ0/ϕ)2/3, whereas the swelling of the fluctuating part lies between the expected swelling of the entanglement constraints and the swelling of non-cross-linked chains in a comparable semi-dilute solution. The total swelling of chain size results from the changes of both fluctuating and non-fluctuating contributions.

Predictable Synthesis of 3D Polymer Networks Using Crystal Component-Linking.

Controlled synthesis of 3D polymer networks presents a significant challenge because of the complexity of the polymerization reaction in solution. In this study, a polymerization system that facilitates the prediction of a polymer network structure via percolation simulations is realized. The most significant difference between general percolation simulations and experimental polymerization systems is the mobility of the molecules during the reaction. A crystal component-linking method that connects the precisely arranged monomer as a supramolecular crystalline state to imitate the simple percolation theory is adopted. The percolation simulation based on the crystal structure of the arranged monomers is used to accurately calculate the gelation point, gel fraction, degree of swelling, and atomic formula, which correspond with the experimental results. This suggests that the network structures polymerized via the crystal component-linking method can be predicted precisely by a simple percolation simulation. Further, the percolation simulation predicts the structures of the loop, branched polymer, and crosslinking point, which are difficult to measure experimentally. The polymerization of precisely-arranged immobilized monomers in supramolecular structures is promising in synthesizing precisely controlled polymer networks.

Calcium hydroxide-loaded nanoparticles dispersed in thermosensitive gel as a novel intracanal medicament.

AIM: Design, produce and assess the viability of a novel nanotechnological antibacterial thermo-sensible intracanal medicament This involves encapsulating calcium hydroxide (Ca(OH)2) within polylactic-co-glycolic acid (PLGA) nanoparticles (NPs) and dispersing them in a thermosensitive gel (Ca(OH)2-NPs-gel). In addition, perform in vitro and ex vivo assessments to evaluate tissue irritation and penetration capacity into dentinal tubules in comparison to free Ca(OH)2. METHODOLOGY: Reproducibility of Ca(OH)2-NPs was confirmed by obtaining the average size of the NPs, their polydispersity index, zeta potential and entrapment efficiency. Moreover, rheological studies of Ca(OH)2-NPs-gel were carried out with a rheometer, studying the oscillatory stress sweep, the mean viscosity value, frequency and temperature sweeps. Tolerance was assessed using the membrane of an embryonated chicken egg. In vitro Ca(OH)2 release was studied by direct dialysis in an aqueous media monitoring the amount of Ca(OH)2 released. Six extracted human teeth were used to study the depth of penetration of fluorescently labelled Ca(OH)2-NPs-gel into the dentinal tubules and significant differences against free Ca(OH)2 were calculated using one-way anova. RESULTS: Ca(OH)2-NPs-gel demonstrated to be highly reproducible with an average size below 200 nm, a homogeneous NPs population, negative surface charge and high entrapment efficiency. The analysis of the thermosensitive gel allowed us to determine its rheological characteristics, showing that at 10°C gels owned a fluid-like behaviour meanwhile at 37°C they owned an elastic-like behaviour. Ca(OH)2-NPs-gel showed a prolonged drug release and the depth of penetration inside the dentinal tubules increased in the most apical areas. In addition, it was found that this drug did not produce irritation when applied to tissues such as eggs' chorialantoidonic membrane. CONCLUSION: Calcium hydroxide-loaded PLGA NPs dispersed in a thermosensitive gel may constitute a suitable alternative as an intracanal antibacterial medicament.