Microgel Beads Research Articles

Dual-Responsive "Egg-Box" Shaped Microgel Beads Based on W1/O/W2 Double Emulsions for Colon-Targeted Delivery of Synbiotics.

In this study, for enhancing the resistance of probiotics to environmental factors, we designed a microgel beads delivery system loaded with synbiotics. Multiple droplets of W1/O/W2 emulsions stabilized with zein-apple pectin hybrid nanoparticles (ZAHPs) acted as the inner "egg," whereas a three-dimensional network of poly-L-lysine (PLL)-alginate-CaCl2 (Ca) crosslinked gel layers served as the outermost "box." ZAHPs with a mass ratio of 2:1 zein-to-apple pectin showed excellent wettability (three-phase contact angle = 89.88°). The results of the ζ-potentials and Fourier transform infrared spectroscopy demonstrate that electrostatic interaction forces and hydrogen bonding were the main forces involved in the formation of ZAHPs. On this basis, we prepared W1/O/W2 emulsions with other preparation parameters and observed their microstructures by optical microscopy and confocal laser scanning microscope. The multi-chambered structures of W1/O/W2 emulsions were successfully visualized. Finally, the W1/O/W2 emulsions were coated with PLL-alginate-Ca using the solution extrusion method. The results of the in vitro colonic digestion stage reveal that the survival rate of probiotics in the microgel beads was about 75.11%, which was significantly higher than that of the free. Moreover, probiotics encapsulated in microgel beads also showed positive storage stability. Apple pectin would serve as both an emulsifier and a prebiotic. Thus, the results indicate that the "egg-box" shaped microgel beads, designed on the basis of pH-sensitive and enzyme-triggered mechanisms, can enhance the efficiency of probiotics translocation in the digestive tract and mediate spatiotemporal controlled release.

Monodispersed biodegradable microparticles with wrinkled surface coated with silver nanoparticles for catalytic degradation of organic toxins

AbstractMicrofluidic fabrication of monodisperse microgels for biomedical, nanotechnological, environmental, and catalytic applications has become the subject of growing interest. In this work, monodisperse polyethylene glycol diacrylate [P(EGDA)] microgel particles were fabricated using a CNC-milled microfluidic device with a Lego-inspired interlocking mechanism. Silver nanoparticles (AgNPs) were synthesised and stabilised in situ on the wrinkled surface of the microgel particles using AgNO3 as a metal precursor and NaBH4 as a reductant. The loading of AgNPs (7.5 wt%) on microgel beads was confirmed by energy-dispersive X-ray spectroscopy, X-ray diffraction, and thermogravimetric analysis. Surface wrinkles were found to be a useful morphological feature acting as reservoirs for the accumulation of AgNPs. Ag–P(EGDA) hybrid polymer particles were shown to be an efficient catalyst for the reduction of 4-nitrophenol (4NP) into 4-aminophenol (4AP) by sodium borohydride at room temperature. After 40 min, 0.08 M 4NP was completely converted into 4AP using 2.1 mg/mL of Ag–P(EGDA) catalytic particles, and the reaction followed a pseudo-first-order kinetics. The apparent rate constant increased from 0.0142 to 0.117 min−1 when the loading of catalytic particles increased from 1.7 to 2.50 mg/mL indicating that the reduction is occurring on the catalyst surface according to the Langmuir–Hinshelwood model. Ag–P(EGDA) hybrid microgel was a potent and recyclable catalyst for room-temperature degradation of methylene blue (MeB) by NaBH4. At the Ag–P(EGDA) loading of 2.0 mg/mL, 25 µM of MeB was completely degraded in 6 min. Composite Ag–P(EGDA) microgel beads can be used as an eco-friendly and easily recoverable catalyst for the transformation of other organic pollutants into useful chemicals. Graphical abstract

High-throughput viscoelastic characterization of cells in hyperbolic microchannels.

Extensive research has demonstrated the potential of cell viscoelastic properties as intrinsic indicators of cell state, functionality, and disease. For this, several microfluidic techniques have been developed to measure cell viscoelasticity with high-throughput. However, current microchannel designs introduce complex stress distributions on cells, leading to inaccuracies in determining the stress-strain relationship and, consequently, the viscoelastic properties. Here, we introduce a novel approach using hyperbolic microchannels that enable precise measurements under a constant extensional stress and offer a straightforward stress-strain relationship, while operating at a measurement rate of up to 100 cells per second. We quantified the stresses acting in the channels using mechanical calibration particles made from polyacrylamide (PAAm) and found that the measurement buffer, a solution of methyl cellulose and phosphate buffered saline, shows strain-thickening following a power law up to 200 s-1. By measuring oil droplets with varying viscosities, we successfully detected changes in the relaxation times of the droplets and our approach could be used to get the interfacial tension and viscosity of liquid-liquid droplet systems from the same measurement. We further applied this methodology to PAAm microgel beads, demonstrating the accurate recovery of Young's moduli and the near-ideal elastic behavior of the beads. To explore the influence of altered cell viscoelasticity, we treated HL60 human leukemia cells with latrunculin B and nocodazole, resulting in clear changes in cell stiffness while relaxation times were only minimally affected. In conclusion, our approach offers a streamlined and time-efficient solution for assessing the viscoelastic properties of large cell populations and other microscale soft particles.

Microfluidic Fabrication of Monodisperse and Recyclable TiO2-Poly(ethylene glycol) Diacrylate Hybrid Microgels for Removal of Methylene Blue from Aqueous Medium.

Nearly monodisperse titanium oxide-polyethylene glycol diacrylate [TiO2-P(EGDA)] hybrid microbeads containing 0.5 wt % TiO2 nanoparticles entrapped within a P(EGDA) cross-linked polymeric network were synthesized using a modular Lego-inspired glass capillary microfluidic device. TiO2-P(EGDA) hybrid microgels were characterized by optical microscopy, scanning electron microscopy, X-ray diffraction, energy dispersive X-ray spectroscopy, and thermogravimetric analysis. The fabricated TiO2-P(EGDA) hybrid microgel system showed 100% removal efficiency of methylene blue (MB) from its 1-3 ppm aqueous solutions after 4 h of UV light irradiation at 0.2 mW/cm2 at the loading of 25 g/L photocatalyst beads in the reaction mixture, corresponding to the loading of naked TiO2 of just 0.025 g/L. No decrease in photocatalytic efficiency was observed in 10 repeated runs with recycled photocatalyst using a fresh 1 ppm MB solution in each cycle. The rate of photocatalytic degradation was controlled by the UV light irradiance, catalyst loading, and the initial dye concentration. Physical adsorption of MB onto the surface of composite microgel was also observed. The adsorption data was best fitted with the Langmuir adsorption isotherm and the Elovich kinetic model. TiO2-P(EGDA) microgel beads are biocompatible, can be prepared with a tunable size in the microfluidic device, and can easily be separated from the reaction mixture by gravity settling. The TiO2-P(EGDA) system can be used for the removal of other toxic dyes and micropollutants from industrial wastewater.

Synthesis of sodium-alginate capped silver nanocomposite microgel beads via bio-reduction featuring multifunctional antibacterial and apoptotic properties in human prostate cancer

Synthesis of sodium-alginate capped silver nanocomposite microgel beads via bio-reduction featuring multifunctional antibacterial and apoptotic properties in human prostate cancer

Bioprinting of hair follicle germs for hair regenerative medicine.

Hair regenerative medicine is a promising approach to treat hair loss. The replication of in vivo tissue configurations and microenvironments, such as hair follicle germs, has been studied to prepare tissue grafts for hair regenerative medicine. However, such approaches should be scalable, because a single patient with alopecia requires thousands of tissue grafts. In this paper, we propose an approach for the scalable and automated preparation of highly hair-inductive tissue grafts using a bioprinter. Two collagen droplets (2µL each) containing mesenchymal and epithelial cells were placed adjacent to each other to fabricate hair-follicle-germ-like grafts. During three days of culture, the pairs of microgel beads were spontaneously contracted by cell traction forces, whereas the two cell types remained separated, where the densities of the cells and collagen were enriched more than 10 times. This approach allowed us to fabricate submillimeter objects printed with millimeter-order accuracy, facilitating scalable and automated tissue graft preparation. Because of mesenchymal-epithelial interactions, hair microgels (HMGs, i.e., collagen- and cell-enriched microgels) efficiently regenerate hair follicles and shafts when transplanted into the back skin of mice. However, the generated hair shafts mostly remain under the skin. Therefore, we printed microgel beads onto surgical suture guides arrayed on a stage. The microgel beads were contracted along with the suture guides in culture prior to transplantation. The guide-inserted HMGs significantly improved hair-shaft sprouting through the skin, owing to the control of the orientation of the HMGs transplanted into the skin. This approach is a promising strategy to advance hair regenerative medicine. STATEMENT OF SIGNIFICANCE: This study proposes an approach for the scalable and automated preparation of highly hair-inductive grafts using a bioprinter. Two collagen droplets containing mesenchymal and epithelial cells were placed adjacently. Cell traction forces caused the pairs of microgel beads to spontaneously contract in culture. Because of mesenchymal-epithelial interactions, hair microgels (HMGs) efficiently regenerated hair follicles on the back skin of mice. However, the generated hair shafts remained mostly beneath the skin. Therefore, we printed microgel beads onto surgical suture guides arrayed on a stage. The guide-inserted HMGs significantly improved hair-shaft sprouting through the skin owing to the control of the orientation of the HMGs in the skin. This approach represents a promising strategy for advancing hair regenerative medicine.

Bone beads enveloped with vascular endothelial cells for bone regenerative medicine.

The transplantation of pre-vascularized bone grafts is a promising strategy to improve the efficacy of engraftment and bone regeneration. We propose a hydrogel microbead-based approach for preparing vascularized and high-density tissue grafts. Mesenchymal stem cell-encapsulated collagen microgels (2µL), termed bone beads, were prepared through spontaneous constriction, which improved the density of the mesenchymal stem cells and collagen molecules by more than 15-fold from the initial day of culture. Constriction was attributed to cell-attractive forces and involved better osteogenic differentiation of mesenchymal stem cells than that of spheroids. This approach was scalable, and ∼2000 bone beads were prepared semi-automatically using a liquid dispenser and spinner flask. The mechanical stimuli in the spinner flask further improved the osteogenic differentiation of the mesenchymal stem cells in the bone beads compared with that in static culture. Vascular endothelial cells readily attach to and cover the surface of bone beads. The in vitro assembly of the endothelial cell-enveloped bone beads resulted in microchannel formation in the interspaces between the bone beads. Significant effects of endothelialization on in vivo bone regeneration were shown in rats with cranial bone defects. The use of endothelialized bone beads may be a scalable and robust approach for treating large bone defects. STATEMENT OF SIGNIFICANCE: A unique aspect of this study is that the hMSC-encapsulated collagen microgels were prepared through spontaneous constriction, leading to the enrichment of collagen and cell density. This constriction resulted in favorable microenvironments for the osteogenic differentiation of hMSCs, which is superior to conventional spheroid culture. The microgel beads were then enveloped with vascular endothelial cells and assembled to fabricate a tissue graft with vasculature in the interspaces among the beads. The significant effects of endothelialization on in vivo bone regeneration were clearly demonstrated in rats with cranial bone defects. We believe that microgel beads covered with vascular endothelial cells provide a promising approach for engineering better tissue grafts for bone-regenerative medicine.

Mesoporous Ca-alginate/melamine-rich covalent organic polymer/cupric oxide-based microgel beads as heterogeneous catalyst for efficient catalytic reduction of hazardous water pollutants

Present work focused on employing the advantages of novel porous melamine-rich covalent organic polymer (MCOP)-nano cupric oxide (CuO)–based heterogeneous catalysts for catalytic reduction of diverse pollutants including aromatic nitro compounds (p-nitrophenol, o-nitrophenol), toxic dyes (rhodamine B, methylene blue, congo red, methyl orange), and heavy metal ions (chromium(VI)). First, nano-CuO was prepared in a green process, and MCOP was fabricated by a solvothermal method. Subsequently, MCOP@CuO hybrids were developed. To improve the recyclability and stability of the MCOP@CuO hybrids and prevent secondary contamination by the powdery form of hybrids in the water, microgel beads based on alginate substrate were developed. First, the fabricated catalysts were employed for p-nitrophenol reduction, and the effect of catalyst loading and NaBH4 concentration were optimized. In optimum conditions, the catalytic reduction of other pollutants was tested and kinetic studies were examined. Furthermore, the proposed mechanisms for catalytic reductions were presented. Ca-alginate/MCOP@CuO microgel beads efficiently and successfully reduced toxic contaminants in a short time. All pollutants were removed in the time range of 14–55 min. Conversion percentages in removing pollutants were obtained at 90–98% for Ca-alginate/MCOP@CuO Ex-situ microgel beads. These microgel beads were greatly stable and effortlessly recycled without loss of their performance (for 5 consecutive cycles). The kinetics data were fit to the pseudo-first-order model with good correlation coefficients (R2 > 98). Such microgel-based catalysts will expose an innovative frontier in design materials for different potential requests such as treating toxic pollutants.

Microfluidic tapered aspirators for mechanical characterization of microgel beads.

In this study, we report a microfluidic approach for the measurement of mechanical properties of spherical microgel beads. This technique is analogous to tapered micropipette aspiration, while harnessing the benefits of microfluidics. We fabricate alginate-based microbeads and determine their mechanical properties using the microfluidic tapered aspirators. Individual microgel beads are aspirated and trapped in tapered channels, the deformed equilibrium shape is measured, and a stress balance is used to determine the Young's modulus. We investigate the effect of surface coating, taper angle, and bead diameter and find that the measured modulus is largely insensitive to these parameters. We show that the bead modulus increases with alginate concentration and follows a trend similar to that of the modulus measured using standard uniaxial compression. The critical pressure to squeeze out the beads from the tapered aspirators was found to depend on both the modulus and the bead diameter. Finally, we demonstrate how temporal changes in bead moduli due to enzymatic degradation of the hydrogel could be quantitatively determined. The results from this study highlight that the microfluidic tapered aspirators are a useful tool to measure hydrogel bead mechanics and have the potential to characterize dynamic changes in mechanical properties.

Removal of cationic and anionic dyes using Ca-alginate and Zn-Al layered double hydroxide/metal-organic framework

In this study, a novel effective bio adsorbent was produced and employed to remove congo red and methylene blue dyes from water matrices. First, Zn-Al layered double hydroxide (Zn-Al LDH) was manufactured in a hydrothermal process. Next, through in-situ nucleation and growing of crystalline NH2-modified Ti metal-organic framework (NH2-MIL-125(Ti) on Zn-Al sheets by solvothermal method, Zn-Al LDH@NH2-MIL-125(Ti) hybrid was produced. The prepared hybrid showed good adsorption capacity (qmax values: 294 mg/g and 158 mg/g) for congo red and methylene blue dyes in optimum condition (adsorbent amount = 5–7 mg, dye concentration = 100–150 mg/L, V = 10 mL, pH = no adjustment, and contact time = 2–5 h). Based on the isotherm and kinetic models, the Langmuir isotherm, as well as the pseudo-second-order model, were fit to the equilibrium data. In the next attempt, to improve the reusability of the powder and particle form of Zn-Al LDH@NH2-MIL-125(Ti) hybrid, as well as prevent of formation of secondary contamination in water, Na-alginate, as a cheap and effective substrate, was used. Novel architectures of robust, reusable, and efficient Ca-alginate/Zn-Al LDH@NH2-MIL-125(Ti) microgel beads were prepared and the performances of the microbeads were compared with pure LDH@NH2-MIL-125(Ti) hybrid.

Characterization of hydrophilic and hydrophobic core-shell microcapsules prepared using a range of antisolvent approaches

This study describes three straightforward approaches to leveraging gel network-restricted antisolvent precipitation techniques as a means of preparing hydrophilic hydrophobic core-shell microparticles. Briefly, hydrophilic polysaccharides (sodium alginate (ALG), κ-carrageenan (CAR), and agar (AG)) were utilized to prepare microgel beads that were then immersed in zein solutions (70% ethanol aqueous solution, 70% urea aqueous solution, and zein in 70% acetic acid, respectively), thereby facilitating the controlled, slow antisolvent precipitation of the protein layer on the microbead surfaces and inducing hydrophilic hydrophobic core-shell structure formation. This technique can be readily applied to a range of gelling systems and can be tailored to target particle sizes and shell thicknesses. The resultant core-shell particles offer great promise for controlled delivery of fragrances, drugs, or other bioactive compounds in an application-specific fashion, and can be individually tailored based upon the selected input concentrations and preparation methods. Importantly, this technique is generalizable and can be extended to prepare diverse particles with a range of core-shell structures produced from a wide assortment of hydrophobic materials. • Core-shell microcapsules were prepared using a range of antisolvent approaches. • Size and shell thickness of microcapsules can be regulated. • Core-shell particles offer great promise for controlled delivery in an application-specific fashion.

Batch versus microfluidic emulsification processes to produce whey protein microgel beads from thermal or acidic gelation

Producing food-grade soft particles with controlled structure is of interest to elucidate the structure-properties relationship in soft-particles suspensions. The aim of this work is to evaluate the ability of two elaboration processes to produce homogenous and spherical whey protein microgels with adjustable diameters in the range 40–100 μm. Microgels are formed in two steps: (1) emulsification of a whey protein aqueous solution in oil and (2) gelation of the protein solution droplets. We compare a continuous emulsification in a home-made microfluidic setup, designed on purpose, with a more simple emulsification by mixing. In addition, two gelation processes are studied: a thermal gelation at 80 °C and an acid gelation. Results show that emulsification controls the size polydispersity (pdI<0.1 for microfluidics) while gelation controls the microgels structure and assembly. Acid gelation in the microfluidic setup results in spherical, homogeneous microgels which properties are controlled by the process parameters.

Nanoscale Mechanical Properties of Core–Shell-like Poly-NIPAm Microgel Particles: Effect of Temperature and Cross-Linking Density

Poly-NIPAm microgel particles with two different cross-linking densities were prepared with the classical batch polymerization process. These particles were adsorbed onto modified silica surfaces, and their nanomechanical properties were measured by means of atomic force microscopy. It was found that these particles have a hard core-soft shell structure both below and above the volume transition temperature. The core-shell-like structure appears due to a higher reaction rate of the cross-linker compared to that of the monomer, leading to depletion of cross-linker in the shell region. The microgel beads with lower average cross-linking density were found to be less stiff below the volume transition temperature than the microgel with higher cross-linking density. Increasing the temperature further to just above the volume transition temperature led to lower stiffness of the more highly cross-linked microgel compared to its less cross-linked counterpart. This effect is explained with the more gradual deswelling with temperature for the more cross-linked microgel particles. This phenomenon was confirmed by dynamic light scattering measurements in the bulk phase, which showed that the larger cross-linking density microgel showed a more gradual collapse in aqueous solution as the temperature was increased.

Evaluation of anti-tumor effects of crocin on a novel 3D tissue-engineered tumor model based on sodium alginate/gelatin microbead

Crocin, as one of the biologically active components of saffron, has anti-inflammatory, anti-oxidant, anti-depressant and auxiliary anti-tumor effects. Studies have shown that crocin could promote breast cancer cell apoptosis. However, conventional methods are mainly based on two-dimensional (2D) cell culture models, which are difficult to reproduce the tumor environment in vivo due to space constraints. In this study, we prepared a three-dimensional (3D) cell model in vitro based on sodium alginate/gelatin to evaluate the inhibitory effect of crocin on MCF-7 cells, which could bridge the gap in crocin drug evaluation between 2D and 3D cell model in vitro. Different from the 2D culture, the cells were found to aggregate in a spherical shape in the 3D microgel beads. And the CCK-8 assay showed that the growth of MCF-7 cells exposed to crocin was inhibited in a time-related and concentration-related manner. Compared with 2D culture (IC50 that MCF-7 cells treated with crocin at 24 h, 48 h, 72 h: 3.68, 2.55 and 1.53 mg/mL, respectively), the IC50 value of 3D culture (IC50 that MCF-7 cells treated with crocin at 24 h, 48 h, 72 h: 10.12, 6.89 and 6.64 mg/mL, respectively) was significantly increased by 2.77, 2.70, 4.34 times, respectively. Besides, live/dead staining and scanning electron microscope (SEM) revealed that the 2D cultured cells shrank and ruptured after crocin treatment, and the number of living cells was considerably reduced; the size of the cell colonies in the 3D microgel beads decreased.

Mechanical properties of cell- and microgel bead-laden oxidized alginate-gelatin hydrogels.

3D-printing technologies, such as biofabrication, capitalize on the homogeneous distribution and growth of cells inside biomaterial hydrogels, ultimately aiming to allow for cell differentiation, matrix remodeling, and functional tissue analogues. However, commonly, only the mechanical properties of the bioinks or matrix materials are assessed, while the detailed influence of cells on the resulting mechanical properties of hydrogels remains insufficiently understood. Here, we investigate the properties of hydrogels containing cells and spherical PAAm microgel beads through multi-modal complex mechanical analyses in the small- and large-strain regimes. We evaluate the individual contributions of different filler concentrations and a non-fibrous oxidized alginate-gelatin hydrogel matrix on the overall mechanical behavior in compression, tension, and shear. Through material modeling, we quantify parameters that describe the highly nonlinear mechanical response of soft composite materials. Our results show that the stiffness significantly drops for cell- and bead concentrations exceeding four million per milliliter hydrogel. In addition, hydrogels with high cell concentrations (≥6 mio ml-1) show more pronounced material nonlinearity for larger strains and faster stress relaxation. Our findings highlight cell concentration as a crucial parameter influencing the final hydrogel mechanics, with implications for microgel bead drug carrier-laden hydrogels, biofabrication, and tissue engineering.

Fabrication of monodisperse alginate microgel beads by microfluidic picoinjection: a chelate free approach.

Micron-sized alginate hydrogel beads are extensively employed as an encapsulation medium for biochemical and biomedical applications. Here we report on the microfluidic assisted fabrication of calcium alginate (Ca-alginate) beads by on-chip picoinjection of aqueous calcium chloride (CaCl2) in emulsified aqueous sodium alginate (Na-alginate) droplets or by picoinjection of Na-alginate solution in emulsified aqueous CaCl2 droplets. There is no added chelator to reduce the Ca activity in either of the two strategies. The two fabrication strategies are implemented using a flow-focusing and picoinjection modules in a single PDMS chip. Aqueous alginate solution was emulsified and infused with CaCl2 solution as the squeezed droplet pass the picoinjection channel; consequently, monodisperse, spherical, and structurally homogeneous Ca-alginate beads were obtained. Monodisperse alginate microgel populations with a mean diameter in the range of 8 to 28 μm and standard deviation less than 1 μm were successfully generated using microfluidic channels with various dimensions and controlling the flow parameters. Monodisperse but also non-spherical particles with diameters 6 to 15 μm were also fabricated when picoinjecting Na-alginate solution in emulsified aqueous CaCl2 droplets. The Ca-alginate microbeads fabricated with tailormade size in the range from sub-cellular and upwards were in both strategies realized without any use of chelators or change in pH conditions, which is considered a significant advantage for further exploitation as encapsulation process for improved enzymatic activity and cell viability.

Self-assembled low-molecular-weight gelator injectable microgel beads for delivery of bioactive agents.

We report the preparation of hybrid self-assembled microgel beads by combining the low molecular weight gelator (LMWG) DBS-CONHNH2 and the natural polysaccharide calcium alginate polymer gelator (PG). Microgel formulations based on LMWGs are extremely rare due to the fragility of the self-assembled networks and the difficulty of retaining any imposed shape. Our hybrid beads contain interpenetrated LMWG and PG networks, and are obtained by an emulsion method, allowing the preparation of spherical gel particles of controllable sizes with diameters in the mm or μm range. Microgels based on LMWG/alginate can be easily prepared with reproducible diameters <1 μm (ca. 800 nm). They are stable in water at room temperature for many months, and survive injection through a syringe. The rapid assembly of the LMWG on cooling plays an active role in helping control the diameter of the microgel beads. These LMWG microbeads retained the ability of the parent gel to deliver the bioactive molecule heparin, and in cell culture medium this enhanced the growth of human mesenchymal stem cells. Such microgels may therefore have future applications in tissue repair. This approach to fabricating LMWG microgels is a platform technology, which could potentially be applied to a variety of different functional LMWGs, and hence has wide-ranging potential.

In Situ Microfluidic Preparation and Solidification of Alginate Microgels

Biomimetic fabrication of alginate beads has promising applications in the field of synthetic bioarchitecture. Combining microfluidic technology with in situ gelation enables the creation of alginate microgels with precisely tunable size, as well as allowing control of the crosslinking process. Owing to the wide range of applications of alginate microgel beads, this study aimed to develop various microfluidic models for the generation of such beads by investigating the influence of several parameters on their morphologies and dispersity. Four types of glass microfluidic chips with flow focusing or co-flowing droplet generators were used to continuously form alginate droplets, with the possibility of either internal or external alginate gelation by a cross-linking agent supplied by a microfluidic channel. In all four models, alginate was used at a fixed concentration, Span 80 was used as a surfactant to improve the long-term stability of the beads, either mineral oil or oleic acid was used as a continuous phase, and either calcium carbonate (CaCO3) or calcium chloride (CaCl2) was used as a crosslinking agent. The generated beads exhibited various architectures, including individual monodisperse or polydisperse beads, small clusters, and multicompartment systems. The results of the study revealed the importance of microfluidic design and gelation strategy for the generation of stable polymeric architectures. The current study proposes a simple user’s guide to create alginate microgels in various architectures. The fabricated biomimetic models in the form of polymeric-based vesicles can be further exploited in several applications, including cell-like structures, tissue engineering, and cell and drug encapsulation. Additional investigations will be needed, however, to improve these models so that they more closely resemble the natural structures of cells and tissues.

DryMass: handling and analyzing quantitative phase microscopy images of spherical, cell-sized objects

BackgroundQuantitative phase imaging (QPI) is an established tool for the marker-free classification and quantitative characterization of biological samples. For spherical objects, such as cells in suspension, microgel beads, or liquid droplets, a single QPI image is sufficient to extract the radius and the average refractive index. This technique is invaluable, as it allows the characterization of large sample populations at high measurement rates. However, until now, no universal software existed that could perform this type of analysis. Besides the choice of imaging modality and the variety in imaging software, the main difficulty has been to automate the entire analysis pipeline from raw data to ensemble statistics.ResultsWe present DryMass, a powerful tool for QPI that covers all relevant steps from loading experimental data (multiple file formats supported), computing the phase data (built-in, automated hologram analysis), performing phase background corrections (offset, tilt, second order polynomial) to fitting scattering models (light projection, Rytov approximation, Mie simulations) to spherical phase objects for the extraction of dry mass, radius, and average refractive index. The major contribution of DryMass is a user-convenient, reliable, reproducible, and automated analysis pipeline for an arbitrary number of QPI datasets of arbitrary sizes.ConclusionDryMass is a leap forward for data analysis in QPI, as it not only makes it easier to visualize raw QPI data and reproduce previous results in the field, but it also opens up QPI analysis to users without a background in programming or phase imaging.

All-Natural Food-Grade Hydrophilic-Hydrophobic Core-Shell Microparticles: Facile Fabrication Based on Gel-Network-Restricted Antisolvent Method.

Hydrophilic-hydrophobic core-shell microparticles are highly appealing for a variety of industrial applications (foods, pharmaceutics, cosmetics, biomedicines, etc.) owing to their unique properties of moisture resistance and controlled release. However, the fabrication of such structured microparticles proves to be nontrivial due to the difficulty in assembling two materials of distinctly different hydrophilicities and hydrophobicities. This paper reports a facile method to fabricate hydrophilic-hydrophobic core-shell microparticles using all-natural food-grade polysaccharides and proteins, based on a novel principle of gel-network-restricted antisolvent precipitation. Immersion of microgel beads prepared from hydrophilic polysaccharides (i.e., alginates, κ-carrageenan, agarose) into a hydrophobic protein solution (i.e., zein in 70% aqueous ethanol) enables slow and controllable antisolvent precipitation of a protein layer around the microbead surface, leading to the formation of a hydrophilic-hydrophobic core-shell structure. The method applies to various gelling systems and can easily tailor the particle size and shell thickness. The resulting freeze-dried microparticles demonstrate restricted swelling in water, improved moisture resistance, and sustained release of encapsulants, with great potential in applications such as protection of unstable and/or hygroscopic compounds and delivery and controlled release of drugs, bioactives, flavors, etc. The method is rather universal and can be extended to prepare more versatile core-shell structures using a large variety of hydrophilic and hydrophobic materials.