Colloidal Microgels Research Articles

Synergistic effect of Hypoxic Conditioning and Cell-Tethering Colloidal Gels enhanced Productivity of MSC Paracrine Factors and Accelerated Vessel Regeneration.

Microporous hydrogels have been widely used for delivering therapeutic cells. However, several critical issues, such as the lack of control over the harsh environment they are subjected to under pathological conditions and rapid egression of cells from the hydrogels, have produced limited therapeutic outcomes. To address these critical challenges, cell-tethering and hypoxic conditioning colloidal hydrogels containing mesenchymal stem cells (MSCs) are introduced to increase the productivity of paracrine factors locally and in a long-term manner. Cell-tethering colloidal hydrogels that are composed of tyramine-conjugated gelatin prevent cells from egressing through on-cell oxidative phenolic crosslinks while providing mechanical stimulation and interconnected microporous networks to allow for host-implant interactions. Oxygenating microparticlesencapsulated in tyramine-conjugated colloidal microgels continuously generated oxygen for 2 weeks with rapid diffusion, resulting in maintaining a mild hypoxic condition while MSCs consumed oxygen under severe hypoxia. Synergistically, local retention of MSCs within the mild hypoxic-conditioned and mechanically robust colloidal hydrogels significantly increased the secretion of various angiogenic cytokines and chemokines. The oxygenating colloidal hydrogels induced anti-inflammatory responses, reduced cellular apoptosis, and promoted numerous large blood vessels in vivo. Finally, mice injected with the MSC-tethered oxygenating colloidal hydrogels significantly improved blood flow restoration and muscle regeneration in a hindlimb ischemia (HLI) model.

Effect of particle stiffness on microgel self-assembly and suspension phase behavior over a broad temperature range

We synthesized thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) colloidal microgel particles of different stiffnesses by controlling the concentration of a polar crosslinker in a precipitation polymerization synthesis method. When suspended in an aqueous medium, the particles collapsed by expelling water as the temperature was raised toward the volume phase transition temperature (VPTT) of ≈ 34 °C. We noted that the sizes of the stiffer particles, synthesized with higher crosslinker concentration, collapsed less abruptly. Using Fourier transform infrared spectroscopy, we observed enhanced particle dehydration with increasing temperature and decreasing particle stiffness. Oscillatory rheology experiments on dense aqueous PNIPAM suspensions, prepared at a fixed particle effective volume fraction ϕeff = 1.5 at 25°C, revealed that suspensions constituted by the stiffest particles are the most elastic over a broad temperature range. Above the VPTT, suspensions of particles of intermediate stiffnesses exhibited two-step yielding, a typical signature of fragile gel formation. Zeta potential measurements showed that PNIPAM particles of lower stiffnesses are rendered electrostatically unstable in aqueous suspension. Combining cryogenic scanning electron microscopy and rheology, we noted a glass–glass transition when the temperature of a dense suspension of stiff PNIPAM particles was raised across the VPTT. In contrast, suspensions of particles of the lowest stiffnesses showed a gel-viscoelastic liquid–gel transition during an identical temperature ramp experiment. Our study reveals that temperature-induced phase transformations in dense PNIPAM suspensions depend sensitively on the stiffness of the constituent particles and can be explained by considering amphiphilicity-driven morphological changes in the suspension microstructures.

Electro-microgellation of CS/PL spheres in situ self-embedded with AgNPs as a losartan delivery system

In situ electrosynthesis of new hybrid colloidal microgel particles of chitosan (CS)-pullulan (PL) self-embedded with AgNPs and introduced as a drug carrier for losartan (LOS) as a drug model. The impact of using Platinum (Pt) and Silver (Ag) sheets as anode and the electrosynthesis time on the formation mechanism, morphology, compositional and structural properties have been examined. The prepared samples characterized using uv–visible spectroscopy (UV–vis), transmission electron microscope (TEM), zeta potential, Fourier transform infrared spectroscopy (FTIR), Inductively coupled plasma optical emission spectroscopy (ICP-OES), x-ray diffraction analysis (XRD), and stability test. In addition to the Assessment of the antibacterial activity of the prepared samples. Also, incorporation of LOS in situ during the preparation of the microgel was investigated. The results demonstrated that uniform AgNPs with an average size 5.4 nm successfully in situ self-embedded within CS/PL microgel particles of a dual size distribution 151.4 and 43.5 nm with surface charge +25 mV. Besides, the incorporation of AgNPs during the electrosynthesis process played a crucial role in the morphology transition from pearl-necklace to microsphere. additionally, stability examination of the microgel particles introduced a valuable result that the single sphere containing Ag+ ions underwent a slow reduction rate in consistency with nucleation favored overgrowth. Incorporation of AgNPs within CS/PL microgel has considerably enhanced the antimicrobial potential of the realized CS/PL against both gram-positive and gram-negative bacteria Investigation of the ability of the losartan incorporation explored a stable core/shell like structure with average size 95 nm and zeta potential + 39 mV promoting the spheres stability.

Development and characterization of colloidal pNIPAM-methylcellulose microgels with potential application for drug delivery in dentoalveolar tissue engineering strategies

Incorporation of growth factors, signaling molecules and drugs can be vital for the success of tissue engineering in complex structures such as the dentoalveolar region. This has led to the development of a variety of drug release systems. This study aimed to develop pNIPAM-methylcellulose microgels with different synthesis parameters based on a 23 full factorial design of experiments for this application. Microgel properties, including volume phase transition temperature (VPTT), hydrodynamic size, drug loading and release, and cytocompatibility were systematically evaluated. The results demonstrated successful copolymerization and development of the microgels, a hydrodynamic size ranging from ∼200 to ∼500 nm, and VPTT in the range of 34–39 °C. Furthermore, loading of genipin, capable of inducing odontoblastic differentiation, and its sustained release over a week was shown in all formulations. Together, this can serve as a solid basis for the development of tunable drug-delivering pNIPAM-methylcellulose microgels for specific tissue engineering applications.

Design of multi-responsive and actuating microgels toward on-demand drug release.

Multifunctional colloidal microgels that exhibit stimuli-responsive behaviour and excellent biocompatibility have attracted particular attention for developing functional compartmentalized networks. Herein, a series of stimuli-responsive microgels (M0, M1, and M2) were designed through the copolymerization of di(ethylene glycol) methyl ether methacrylate (DEGMA) and methacrylic acid (MAA) monomers using hydroxy ethyl methacrylate-coupled azobenzene (HEMA-Az) and ethylene glycol dimetharylate (EGDMA) as crosslinkers. The behaviour of the microgels in response to temperature, pH, and light was thoroughly investigated using spectroscopic, microscopic, and light-scattering techniques. Interestingly, the microgels deswelled with an increase in temperature, decrease in pH, and under the irradiation of UV light. Such a reversible swelling/deswelling behaviour was exploited for microgel M2, which showed better photoactuation at pH 5 with a higher fluid pumping velocity. The actuating microgel M2 was optimized for loading the drug ciprofloxacin (Cf) to study its release at different temperature, pH, and light conditions. Microgel M2 exhibited photoresponsive Cf release at pH 5 and 37 °C, demonstrating its potential for application in on-demand drug release.

Revisiting the density profile of the fuzzy sphere model for microgel colloids.

Common neutral polymer microgels exhibit an inhomogeneous density profile with a gradual decay that is commonly described using the fuzzy sphere model. The model is based on the idea of convolving the collapsed solid sphere profile with a Gaussian to describe inhomogeneous swelling of the microgel in a good solvent. Here we show that the corresponding density profile in real space used in several recent works - such as in super-resolution microscopy - is different from the fuzzy sphere model, and we explain how to correctly transition between reciprocal space modelling to real space. Our work aims to clarify the application of the model so that errors can be avoided in the future. Our discussion is also crucial when comparing alternative real-space models for the density profile with the established fuzzy sphere model.

Structurally colored silica foams using colloidal templating

We produce solid silica dry foam structures that exhibit structural color. For this purpose, we use densely packed colloidal microgels decorated with silica nanoparticles that are much smaller than the microgels. By concentrating and overpacking the microgel particles, we can control their morphology so that the silica nanoparticles spontaneously form honeycomb-like structures or networks. We obtain pure silica dry foam structures by burning the organic polymer, leaving behind silica networks. The resulting foams exhibit vivid structural colors. We can control the color by changing the microgel particles’ size and degree of compression. Furthermore, thanks to the softness of the particles, compression can also lead to the appearance of facets. This faceting behavior distinguishes microgels from hard spherical particles. We present details about the synthesis and fabrication strategies and report on a comprehensive characterization of optical and structural properties. Our study provides insight into the fabrication of innovative self-assembled materials with structural colors by colloidal templating.

Physicochemical investigations on the interaction of an anionic surfactant with cellulose based polymer microgel

Abstract This work focuses on the interaction of cellulose-based colloidal microgel dispersions with the anionic surfactant sodium dodecyl sulfate (SDS) at different concentrations. First, a Cellulose-P(NIPAAm-MAA)-based responsive microgel sample was prepared by a radical polymerization method using a one-pot process. The samples thus obtained were purified, characterized and used to study microgel-surfactant interactions. To this end, SDS solutions with different concentrations were prepared and the interactions of SDS in the premicellar and micelle regions with polymer microgel were investigated using different physicochemical techniques. Experiments were also performed at different temperatures to obtain the degree of binding of SDS to microgel in gel surfactant mixtures. Due to the temperature-sensitive properties of microgel, we observed significant changes in various properties of microgel-surfactant mixtures when the solution temperature changed. The overall results showed that various experimental variables, such as the polymer gel/surfactant ratio and temperature, affect the gel–surfactant interaction quantitatively and qualitatively. With increasing surfactant concentration, conductance, viscosity and absorbance values ​​increased, but a decrease in surface tension was observed. This is due to the adsorption of SDS at the air-water interface. The micellar activity of surfactants is enhanced by the addition of microgels. It was found that the strength and nature of the interaction depended not only on the gel/surfactant ratio, solvent type and test temperature, but also on the chemical structure of the surfactant used. Furthermore, the visual stability of the colloidal particles in the mixture of microgel and SDS was also noticeable over time.

Soluble protein particles produced directly from mung bean flour by simple coacervation

Poor solubility is a common characteristic of many plant protein ingredients which often hampers product formulation. We exploit simple coacervation, or liquid-liquid phase separation, of plant proteins in flours, to formulate plant proteins as powders consisting of submicron colloids with good solubility and dispersibility. We consider the specific case of mung bean flour, but the approach is more general. First, we study the influence of pH on the formation of submicron protein droplets (“coacervates”) after alkaline protein extraction from mung bean flour. Next, the proteins in droplets were heat-set into colloidal protein microgels, and the morphology of the colloids was assessed by scanning electron microscopy. The mung bean protein colloids have an intrinsic viscosity much lower than typical food thickeners, indicating the dense nature of the particles. After spray-drying, they maintain a good dispersibility even close to the isoelectric point. Heat-induced gelation of redispersed protein particles resulted in gels with moduli much less than those of commercial mung bean protein concentrates at equivalent protein concentration. Hence, the main impact of the pretreatment is on dispersibility and heat stability, with relevance to formulations such as plant-protein based beverages.

Controlling Kinetic Pathways in Demixing Microgel-Micelle Mixtures.

We investigate the temperature-dependent phase behavior of mixtures of poly(N-isopropylacrylamide) (pNIPAM) microgel colloids and a triblock copolymer (PEO-PPO-PEO) surfactant. Usually, gelation in these systems results from an increase in temperature. Here we investigate the role of the heating rate, and surprisingly, we find that this causes the mechanism of aggregation to change from one which is driven by depletion of the microgels by the micelles at low temperatures to the association of the two species at high temperatures. We thus reveal two competing mechanisms for attractions between the microgel particles which can be controlled by changing the heating rate. We use this heating-rate-dependent response of the system to access multiple structures for the same system composition. Samples were found to demix into phases rich and poor in microgel particles at temperatures below 33 °C, under conditions where the microgels particles are partially swollen. Under rapid heating full demixing is bypassed, and gel networks are formed instead. The temperature history of the sample, therefore, allows for kinetic selection between different final structures, which may be metastable.

Responsive Polyphenol‐Crosslinked Supramacromolecular Microgels with pH‐Triggered Disassembly in Aqueous Solution

AbstractThis work focuses on the pH‐triggered disassembly of supramacromolecular microgels, which are composed of the temperature‐responsive poly(N‐vinylcaprolactam) (PVCL) and the natural polyphenol tannic acid (TA). A systematic investigation of the microgel formation demonstrates that a retarded addition of tannic acid during semi‐batch precipitation polymerization influences the yield, chemical composition, and properties of the microgels to a great extent. Microgel properties, such as size, deformability, and chemical stability, can be easily tuned by varying the ratio between both building blocks PVCL and TA. Finally, the pH‐triggered disassembly of supramacromolecular microgels at different pH and temperatures demonstrates that their chemical structure can precisely control the degradation profile. Temperatures lower than the volume phase transition temperature (VPTT) of PVCL (T < 32 °C) and a pH > 10 result in a complete disassembly of the microgels into PVCL chains and TA due to the destruction of the hydrogen bonds responsible for the formation of a colloidal microgel. Interestingly, at temperatures above VPTT, the microgels keep their integrity due to enhanced hydrophobic interactions between the polymer chains of the microgel and are no longer affected by pH changes.

Pd Nanoparticle-Loaded Smart Microgel-Based Membranes as Reusable Catalysts.

In this work, palladium-loaded smart membranes made by UV cross-linking of thermoresponsive microgels are prepared to obtain a reusable, catalytically active material which can, for example, be implemented in chemical reactors. The membranes are examined with respect to their coverage of a supporting mesh via atomic force microscopy measurements. Force indentation mapping was performed in the dried, collapsed state and in the swollen state in water to determine the Young modulus. Furthermore, we compare the catalytic activity of the membrane with the corresponding suspended colloidal nanoparticle microgel hybrids. For this purpose, the reduction of 4-nitrophenol is an established model reaction to quantify the catalytic activity by UV-vis spectroscopy. The membrane is embedded inside a continuous stirred tank reactor equipped for continuous monitoring of the reaction progress. Although catalysis with membranes shows lower catalytic activity than freely dispersed particles, membranes allow straightforward separation and recycling of the catalyst. The fabricated membranes in this work show no decrease in catalytic activity between several cycles, unlike free particles. The feasible and durable deposition of catalytically active inter-cross-linked microgel particles on commercial nylon meshes as supporting scaffolds, as demonstrated in this work, is promising for up-scaling of continuous industrial processes.

Elastic Deformations of Spherical Core-Shell Systems Under an Equatorial Load

Macroscopic elastic core-shell systems can be generated as toy models to be deformed and haptically studied by hand. On the mesoscale, colloidal core-shell particles and microgels are fabricated and investigated by different types of microscopy. We analyse, using linear elasticity theory, the response of spherical core-shell systems under the influence of a line density of force that is oriented radially and acts along the equator of the outer surface. Interestingly, deformational coupling of the shell to the core can determine the resulting overall appearance in response to the forces. We address various combinations of radii, stiffness, and Poisson ratio of core and shell and illustrate the resulting deformations. Macroscopically, the situation could be realized by wrapping a cord around the equator of a macroscopic model system and pulling it tight. On the mesoscale, colloidal microgel particles symmetrically confined to the interface between two immiscible fluids are pulled radially outward by surface tension.

Macroporous Silica Foams Fabricated via Soft Colloid Templating.

Macroporous materials with controlled pore sizes are of high scientific and technological interest, due to their low specific weight, as well as unique acoustic, thermal, or optical properties. Solid foams made of titania, silica, or silicon, as representative materials, have been previously obtained with several hundred nanometer pore sizes, by using sacrificial templates such as spherical emulsion droplets or colloidal particles. Macroporous structures in particular are excellent candidates as photonic materials with applications in structural coloration and photonic bandgap devices. However, whereas using spherical building blocks as templates may provide tight control over pore shape and size, it results in materials with an often unfavorable local topology. Templating dry-foam or compressed-emulsion structures appear as attractive alternatives, but have not been demonstrated so far for submicron pore sizes. Herein, the use of soft, flexible microgel colloids decorated with silica nanoparticles as templates of macroporous foams is reported. These purposely synthesized core-shell colloids are assembled at ultra-high effective volume fractions by centrifuging and thermal swelling, thereby resulting in uniform disordered materials with facetted pores, mimicking dry foams. After removal of the polymer component via calcination, lightweight pure silica structures are obtained with a well-defined cellular or networktopology.

Cell-derived Extracellular Matrix Proteins in Colloidal Microgel as a Self-Assembly Hydrogel for Regenerative Endodontics

IntroductionThis study investigated a colloidal microgel for angiogenic and odontogenic differentiation of cells in the presence of cell-derived extracellular matrix (ECM) proteins using a 3-dimensional culture model. MethodsViscoelastic properties of human dental pulp were determined to understand the native ECM environment. ECM proteins were extracted from dental pulp stem cell (DPSC) cultures, and MaxGel (Millipore Sigma, Burlington, MA) was used as a commercially available ECM protein. DPSCs were incubated in colloidal microgels in the presence of ECM proteins or gelatin methacryloyl (GelMA) as a bulk hydrogel (n = 9/group). The viability and odontogenic differentiation of DPSCs within hydrogels was determined using viability assays, mineralization staining, calcium and alkaline phosphatase assays, and quantitative polymerase chain reaction for odontogenic gene expression. Angiogenic properties of endothelial cells were determined using tubule formation assays and quantitative polymerase chain reaction to detect angiogenic gene expression. ResultsDental pulp had a higher elastic modulus than the viscous modulus, showing a solidlike response similar to hydrogels. DPSC-derived ECM showed higher collagen and GAG than MaxGel (P < .05). The viability of DPSCs was similar in colloidal microgels, whereas higher cell viability, calcium deposition, and alkaline phosphatase activity were observed in GelMA (P < .05). Colloidal microgels allowed tubule-like structures by endothelial cells, whereas no tubular formation was observed in GelMA. DPSC-derived ECM in colloidal microgel up-regulated odontogenic gene expression, whereas MaxGel up-regulated angiogenic gene expression (P < .05). ConclusionsColloidal microgels allowed cellular organization that can improve penetration and nutritional supply in a full-length root canal system. The bioactivity of cell-derived ECM proteins can be modified depending on the external stimulus.

2H NMR Study of Polymer Segmental Dynamics at Varying Cross-Linking in Poly(N-isopropylacrylamide) Microgels.

A microscopic understanding of the internal structure and dynamics of poly(N-isopropylacrylamide) (PNIPAM) chains, in microgel colloids, is developed using deuterium NMR (2H NMR) to study deuterated PNIPAM suspensions as functions of temperature and pressure for four cross-linker molar fractions (f). The PNIPAM polymers were labeled with deuterons at the backbone (d3-PNIPAM) or on side chains (d7-PNIPAM). 2H NMR spectra of the d3-PNIPAM suspensions for all cross-linker molar fractions indicated freely moving chains at low temperature and a nearly immobilized fraction above ∼35 °C. Polymer segments in the collapsed phase of the d3-PNIPAM suspension were more mobile than those in the dry powder. This is direct microscopic evidence that the polymer remains significantly hydrated in the collapsed phase, consistent with strong, indirect evidence from recent light scattering and rheology measurements from our laboratory. However, the observation of a small fraction of immobilized segments in the swollen phase for higher cross-linker molar fraction suggests that, particularly for high levels of cross-linking, some polymer is nonhydrated even in the swollen phase. Finally, variable-pressure NMR (up to 90 MPa) showed a slight increase in transition temperature with pressure for lower cross-linker molar fractions and a larger increase in transition temperature with pressure for higher cross-linker molar fractions. This is consistent with a previously reported dependence of collapse transition enthalpy on cross-linker molar fraction.

Automated tangential-flow diafiltration device

Tangential flow filtration (TFF) is a chemical unit operation used to purify and concentrate liquid suspensions of colloids, proteins, or cells. The solution flows tangentially across a membrane, such that a selective part of the fluid permeates the membrane while the filtrated matter is retained, increasing its concentration. TFF is a mild mechanical purification method that does not interact chemically with the filtrate. It is applied in sensitive separation tasks in protein chemistry, microbiology, or immunology. It is a fast alternative for dialysis applications, also applicable in the field of colloid purification. However, the costs of automated lab-scale devices (30,000 €) and the consumable membrane modules (100–600 €) make TFF currently hardly accessible for lab-scale polymer researchers. Therefore, we built a low-cost TFF system (2400 €) partly automated by an Arduino microcontroller and optimized for diafiltration buffer exchange and concentration processes in soft matter colloid research. We use medical hemodialysis membrane modules that only cost a share (20–50 €) of alternative TFF modules, and we demonstrate the functionality of the system for an exemplary colloidal microgel purification process.

Dual-Responsive Microgels for Structural Repair and Recovery of Nonwoven Membranes for Liquid Filtration

This study presents dual-responsive colloidal microgels to repair nonwoven fiber mats (NWFs) and recover their native morphological and functional properties. The formulation comprises poly(N-isopr...

Colloidal and polymeric contributions to the yielding of dense microgel suspensions

HypothesisSoft microgel colloids can be densely packed since particle networks can compress and interpenetrate. This evolution of the particle’s internal structure associated with packing is expected to determine the linear viscoelastic properties and the yielding behavior of dense suspensions of microgel colloids. ExperimentsWe investigated the volume fraction-dependent linear and non-linear rheological response of suspensions of soft core-shell particles formed by a poly(N-isopropylacrylamide) (PNIPAM) microgel core and a thin poly(ethylene glycol) (PEG) shell. FindingsThe linear viscoelasticity of suspensions reveals a transition from a fluid to a jammed glass state. Increasing volume fraction within the jammed state, the linear storage modulus and the yield stress show distinct regimes associated with the evolution of particle contacts, which involve progressive compression and interpenetration of the shell and core. The yielding of jammed suspensions occurs in two-steps: At small strains jammed cages are rearranged, while full disentanglement of interpenetrating networks only occurs at large deformations and results in fluidization. Yield strains and stresses increase with increasing shear rate or frequency, suggesting a progressive dominance of the timescale associated with shear over that associated with the internal dynamics of the system.

Smart conducting PNIPAM-co-AAc microgels with controllable phase transition and stimuli responsibility

The accurate detection of external stimuli is critical to achieve the functions of responsive photonic crystals. Electrical signals capable of detecting external stimuli lead to more advanced applications. Here we report a smart PNIPAM-co-AAc microgel colloids with conductive property which could detect external stimuli by outputting electrical signals. The conductivity of PNIPAM-co-AAc microgels is derived from doping with PEDOT:PSS. The resulting doped microgels do not exhibit a separate phase because of the hydrophilicity of the dopant and the host. By decreasing the temperature from 52.4 °C to 20.1 °C, the resistance of the smart microgels would increase from 40 kΩ to 180 kΩ and the color of the microgels change from light blue to dark blue. Moreover, due to the responsibility of PNIPAM-co-AAc to external stimuli such as temperature and pH, the new conductive photonic crystal microgels could transform these stimuli to electric signals which makes it hold great potential applications in smart filler of artificial skins and muscles.