Heterogeneous Gel Research Articles

Emergent Synchronous Volumetric Oscillation in Hierarchically Structured Self-Oscillating Gel Clusters.

Emergent properties accompanying synchronization among oscillators are vital characteristics in biological systems. Belousov-Zhabotinsky (BZ) oscillators are an artificial model to study the emergence and synchronization in life. This research represents a self-oscillating gel system with clusterable properties to experimentally examine synchronous and emergent properties at a fundamental hierarchical level. Incorporating acrylic acid (AAc) moieties within the gel network facilitates cluster formation through hydrogen bonding in an acidic BZ substrate solution. Upon clustering, both homogeneous and heterogeneous gel assemblies─ranging from double to quadruple clusters─exhibit increased and synchronized periods and amplitudes during the BZ reaction. Notably, in heterogeneous clusters, gel units with initially short periods and small volumetric amplitudes display a significant increase, aligning with the lonfger periods and larger amplitudes of other elements within the cluster, an emergent property. This research can pave the way for a better understanding of synchronous and emergent properties in biological oscillators such as cardiomyocytes.

A New Algorithm for Detecting GPN Protein Expression and Overexpression of IDC and ILC Her2+ Subtypes on Polyacrylamide Gels Associated with Breast Cancer

Sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) is used to identify protein presence, absence, or overexpression and usually, their interpretation is visual. Some published methods can localize the position of proteins using image analysis on images of SDS-PAGE gels. However, they cannot automatically determine a particular protein band’s concentration or molecular weight. In this article, a new methodology to identify the number of samples present in an SDS-PAGE gel and the molecular weight of the recombinant protein is developed. SDS-PAGE images of different concentrations of pure GPN protein were created to produce homogeneous gels. Then, these images were analyzed using the developed methodology called Image Profile Based on Binarized Image Segmentation (IPBBIS). It is based on detecting the maximum intensity values of the analyzed bands and produces the segmentation of images filtered by a binary mask. The IPBBIS was developed to identify the number of samples in an SDS-PAGE gel and the molecular weight of the recombinant protein of interest, with a margin of error of 3.35%. An accuracy of 0.9850521 was achieved for homogeneous gels and 0.91736 for heterogeneous gels of low quality.

Multiscale homogenisation of diffusion in enzymatically-calcified hydrogels

Hydrogels are a promising class of material in biomedical and industrial applications, where both the mechanical and diffusion properties play an important role. The wide range of polymers that can be used and the different production methods allows these properties to be specifically tuned to a high degree for their application. Producing tough hydrogels with high stiffness has been a long-standing challenge that has recently been addressed by mineralisation methods. Those methods modify the hydrogel into one with a supporting mineral microstructure that is highly heterogeneous.This work investigates methods to determine the macroscopic diffusion behaviour of heterogeneous gels by a homogenisation method implemented in a finite element framework. This is applied to two recently developed materials by calcifying poly-dimethyl-acrylamide (PDMA) and polyacrylamide hydrogels (PAAm). The former has porous, spherical inclusions obstructing diffusion, while the latter has spherical pores enabling it. For both gels the unobstructed volume can be used as the primary parameter to tune the diffusivity. In PDMA the porosity of the obstructions is shown by multiscale analysis to give a strong, non-linear dependence of the diffusivity on the solute molecule radius. The framework is extended to other materials and comparisons are made to experimental works from the literature.

Study on the influence mechanism of micro-mechanical properties of heterogeneous geopolymer gels

Geopolymers are inorganic, environmentally friendly cementing materials, and they exhibit broad application prospects in geotechnical engineering. These are formed by alkali activation and solidification with silicon- and aluminum-rich minerals or wastes as raw materials. Previous studies have revealed that the physical and mechanical properties of geopolymers from various raw materials differ significantly, which is closely aligned with those of geopolymer gels produced by alkali-activated hydration. However, no current systematic theory can explain these differences, so the design of mix proportions of raw materials and activators is particularly blind when preparing geopolymers. To solve this problem, this paper studies the composition and mechanical properties of the slag geopolymer by nano-indentation tests. On this basis, Raman mapping and SEM-EDS tests revealed the information of the polymerization degree and elemental composition of calcium silicoaluminate hydrate (CASH) in the heterogeneous gel phase. Finally, we carried out a verification test combined with ion implantation technology. The results revealed that the direct source of the difference in the mechanical properties of gel phases was the polymerization degree of CASH, and a secondary reason was the atomic ratio of active silicon to aluminum in CASH. Furthermore, the micro-mechanical properties of the gels could be improved by appropriately increasing the concentration of Al element. The results demonstrated the influence mechanism of mechanical properties of heterogeneous gel phases on the molecular scale, which helped evaluate the potential of raw materials to form specific gel phases and thus guided the scientific preparation of high-performance geopolymer materials.

Spatiotemporal Regulation of Injectable Heterogeneous Silk Gel Scaffolds for Accelerating Guided Vertebral Repair (Adv. Healthcare Mater. 7/2023)

Spatiotemporal Regulation of Injectable Heterogeneous Silk Gel Scaffolds for Accelerating Guided Vertebral Repair (Adv. Healthcare Mater. 7/2023)

Thiol-Ene Photo-Click Hydrogels with Tunable Mechanical Properties Resulting from the Exposure of Different -Ene Moieties through a Green Chemistry.

Temperature and light responsiveness are widely exploited stimuli to tune the physico-chemical properties of double network hydrogels. In this work, new amphiphilic poly(ether urethane)s bearing photo-sensitive moieties (i.e., thiol, acrylate and norbornene functionalities) were engineered by exploiting the versatility of poly(urethane) chemistry and carbodiimide-mediated green functionalization procedures. Polymers were synthesized according to optimized protocols maximizing photo-sensitive group grafting while preserving their functionality (approx. 1.0 × 1019, 2.6 × 1019 and 8.1 × 1017 thiol, acrylate and norbornene groups/gpolymer), and exploited to prepare thermo- and Vis-light-responsive thiol-ene photo-click hydrogels (18% w/v, 1:1 thiol:ene molar ratio). Green light-induced photo-curing allowed the achievement of a much more developed gel state with improved resistance to deformation (ca. 60% increase in critical deformation, γL). Triethanolamine addition as co-initiator to thiol-acrylate hydrogels improved the photo-click reaction (i.e., achievement of a better-developed gel state). Differently, L-tyrosine addition to thiol-norbornene solutions slightly hindered cross-linking, resulting in less developed gels with worse mechanical performances (~62% γL decrease). In their optimized composition, thiol-norbornene formulations resulted in prevalent elastic behavior at lower frequency compared to thiol-acrylate gels due to the formation of purely bio-orthogonal instead of heterogeneous gel networks. Our findings highlight that exploiting the same thiol-ene photo-click chemistry, a fine tuning of the gel properties is possible by reacting specific functional groups.

3D Printed Alginate Hydrogels with Stiffness-Gradient Structure in a Carbomer Supporting Bath by Controlled Ca2+ Diffusion

Manufacturing biocompatible materials with higher-order structure has great significance because they can mimic the extracellular medium of the human organism and are a novel strategy for tissue regeneration. In this study, a device with stiffness-gradient characteristics based on two biocompatible materials, alginate with presolidification and photocurable acrylamide-containing supporting bath, was designed and constructed by the 3D printing technique. The presolidification can avoid rapid diffusion of alginate in aqueous solutions, improve mechanical properties without the introduction of heterogeneous gel precursor, and endow gradient stiffness by the controlled diffusion of calcium ions. Besides, a photocurable supporting bath was combined to manufacture a device with a dual-gradient structure by a 4-step procedure, including 3D printing, removal of the inner hydrogel, solidification of alginate, and curing of the supporting bath. A cylinder-like container was manufactured as the template, and the wall of the resultant container with two types of gradient structures showed parabola-like stiffness changes (open upward), resulting from calcium ion diffusion-controlled gradient solidification and alginate diffusion-controlled gradient photocuring. Moreover, the resultant device exhibited lower cytotoxicity to both adherent and suspension cells than containers manufactured with alginate. Because of the high water uptake of the photocured supporting bath, the removal of toxic metabolic products together with cell culture medium from the container leads to better cell compatibility. This diffusion-controlled device is also applicable to other additive manufacturers with biomedical significance.

Spatiotemporal Regulation of Injectable Heterogeneous Silk Gel Scaffolds for Accelerating Guided Vertebral Repair.

Osteoporotic vertebral fracture is jeopardizing the health of the aged population around the world, while the hypoxia microenvironment and oxidative damage of bone defect make it difficult to perform effective tissue regeneration. The balance of oxidative stress and the coupling of vessel and bone ingrowth are critical for bone regeneration. In this study, an injectable heterogeneous silk gel scaffold which can spatiotemporally and sustainedly release bone mesenchymal stem cell-derived small extracellular vesicles, HIF-1α pathway activator, and inhibitor is developed for bone repair and vertebral reinforcement. The initial enhancement of HIF-1α upregulates the expression of VEGF to promote angiogenesis, and the balance of reactive oxygen species level is regulated to effectively eliminate oxidative damage and abnormal microenvironment. The subsequent inhibition of HIF-1α avoids the overexpression of VEGF and vascular overgrowth. Meanwhile, complex macroporous structures and suitable mechanical support can be obtained within the silk gel scaffolds, which will promote in situ bone regeneration. These findings provide a new clinical translation strategy for osteoporotic vertebral augmentation on basis of hypoxia microenvironment improvement.

Лечение огнестрельных ран конечностей с использованием физических и ортобиологических методов

Currently, despite the wide possibilities in the treatment of wounds, patients with gunshot wounds of the extremities present a complex surgical task. The study included 60 patients with gunshot wounds of the extremities who underwent inpatient examination and treatment at the Center of Traumatology and Orthopedics of the Main Military Clinical Hospital named after academician N.N. Burdenko of Ministry of Defence of the Russian Federation. The patients were divided into groups. In group I, physical methods of treatment were used, such as vacuum therapy (35 people), of which 19 patients underwent combined vacuum therapy with laser irradiation of the wound (group IA), 16 patients underwent vacuum therapy in combination with high-intensity pulsed optical irradiation (group IB). Group II included patients in whom orthobiological techniques were used in the complex treatment of wounds (25 patients), including platelet-enriched fibrin glue — in 13 patients (group IIA) and a composition of heterogeneous implantable gel SpheroGEL® in the LONG version (hereinafter SpheroGEL®) — in 12 patients (group IIB). Results. Comparison of the results of the treatment revealed a significant improvement in the regenerative process according to the histological method in group IA: the maturation of mature granulation tissue was observed on the 9th day after the application of local treatment methods. Positive adhesive and wound healing effects were observed in group IIA. According to the "AnalyRan" program, there was a significant reduction in the time of wound healing in all groups under study. According to the results of the study, all techniques showed positive dynamics of wound healing and reduction of the inflammatory process.

Fabrication of Ionic Cellulose Nanofiber Composites by Electrospinning Cellulose Microfibril-Gel-Dispersions in Poly(vinyl Alcohol) Solution

ABSTRACT In this study, we propose a fabrication method to obtain composites of poly(vinyl alcohol) (PVA)/ionic cellulose nanofibers, in which a fiber structure is manipulated through a reconstruction of 2,2,6,6-tetramethyl-piperidinyl-1-oxyl radical (TEMPO)-oxidized cellulose nanofiber (TCNF) or the carboxymethyl cellulose nanofiber (CMCNF) heterogeneous microfibril gels using electrospinning method. The key concept is to assemble nanofibers from thin few-nanometer-scale width cellulose nanofibers (microfibrils) to thicker several-hundred-nanometer-scale width cellulose nanofibers by electrospinning insoluble microfibril-gel-dispersion in PVA solution. In the case of CMCNF, nanofibers with less-fused structures were successfully reconstructed via electrospinning. Energy-dispersive X-ray spectroscopy revealed that sodium ions exist in the fibers, where they function as counter ions of carboxylate groups of polyelectrolyte moiety of CMCNF. Thus, the obtained composites do contain both ionic cellulose nanofibers and PVA. The proposed fabrication route can be used to fabricate composites as nonwoven fabrics of polyelectrolyte nanofibers. These natural polymer based ionic fabrics will be widely useful to propose low-environmental-impact polymer actuators and active sensing elements involving the ion transport phenomena.

FRESH Bioprinting of Dynamic Hydrazone-Cross-Linked Synthetic Hydrogels.

Dynamic covalent chemistry is an attractive cross-linking strategy for hydrogel bioinks due to its ability to mimic the dynamic interactions that are natively present in the extracellular matrix. However, the inherent challenges in mixing the reactive precursor polymers during printing and the tendency of the soft printed hydrogels to collapse during free-form printing have limited the use of such chemistry in 3D bioprinting cell scaffolds. Herein, we demonstrate 3D printing of hydrazone-cross-linked poly(oligoethylene glycol methacrylate) (POEGMA) hydrogels using the freeform reversible embedding of suspended hydrogels (FRESH) technique coupled with a customized low-cost extrusion bioprinter. The dynamic nature and reversibility of hydrazone cross-links enables reconfiguration of the initially more heterogeneous gel structure to form a more homogeneous internal gel structure, even for more highly cross-linked hydrogels, over a relatively short time (<3 days) while preserving the degradability of the scaffold over longer time frames. POEGMA hydrogels can successfully print NIH/3T3 fibroblasts and human umbilical vein endothelial cells while maintaining high cell viability (>80%) and supporting F-actin-mediated adhesion to the scaffold over a 14-day in vitro incubation period, demonstrating their potential use in practical tissue engineering applications.

Первый опыт применения имплантируемого объемообразующего материала «Сферо®ГЕЛЬ» при стрессовом недержании мочи у женщин.

Introduction. Among minimally invasive technologies for the treatment of stress urinary incontinence (SUI) in women, a special place is occupied by the method of paraurethral administration of bulking agents (BA). Recently, great attention has been paid to the new generation of natural biopolymers with a set of unique qualities that allow using the body's own resources to restore damaged tissues. Heterogeneous implantable gel (JSC «BIOMIR service», Russia) belongs to such BA. Objective: to evaluate the efficacy and safety of transurethral administration of BA «Sphero®GEL» LONG (SGL) in women with SUI. Materials and methods. The open prospective study included 20 women with mild or moderate SUI, aged 41-76 years, who underwent one/two transurethral implantation of SGL into the submucosal and muscular layers after clinical and urodynamic examination. Results. According to the preliminary survey, mild SUI was detected in 13 (65%) women, and moderate SUI – in 7 (35%). Initial data: visual analog scale (VAS) – 7.7 ± 2.0; quality of life (QOL) – 3.3 ± 1.2; maximum urine flow rate (Qmax) – 20.5 ± 5.3 ml/s; post-void residual urine volume (PVR) – 7.0 ± 2.1 ml; voided volume (VV) – 297.2 ± 65.6 ml; maximal cystometric capacity (MCC) – 312.1 ± 83.3 ml; maximum urethral closure pressure (MUCP) – 48.4 ±11.9 cm H2O; functional urethral length (FUL) – 20.3 ± 8.2 mm; one-hour PadTest 8.2 ± 1.9 g. Two weeks after the introduction of SGL, the satisfactory effect was detected in 17 women (85%) 6 of them (30%) were completely dry. The need for SGL additional administration occurred in 11 women (55%), which was fulfilled. There was an improvement in key parameters compared to the initial data 3 and 6 months after treatment: VAS index significant decrease by 70.1 and 63.6%; increase of MUCP by 8.9 and 7.9%; increase of FUL by 14.3 and 18.2%; statistically significant decrease of PadTest weight by 61.0 and 53.7%; improvement of QOL by 60.6 and 48.5%, respectively. There was a slight decrease in Qmax – by 11.2 – 8.3%. Changes in other indicators did not exceed normal values. When evaluating the results after 6 months in 17 patients (85%), the effect of treatment and the quality of life were assessed as satisfactory: according to PadTest results urine loss was less than 5 g. Moreover, in 11 cases (55%) urinary incontinence disappeared, so the full effect was achieved. There was no satisfactory effect in 3 women (15%), they were offered surgical treatment of SUI. Long–term results up to 12 months were followed in a group of 9 women with a good effect of SGL implantation. The dynamics of the main indicators a year after implantation was: 52.8% decrease according to VAS; 41.1% decrease according to PadTest; 48.3% of QOL improvement. SUI was also absent after a year of observation. Request for SGL re-administration was received from 3 of 8 women with unsatisfactory result, although their urine loss did not exceed 5 g per hour. No complications were observed during the SGL implantations. After the procedure urinary retention and the need for catheterization were not observed in any of patients. Allergic reactions, pain, severe hematuria, infection, tissue erosion at the injection site of SGL, as well as bladder overactivity «de novo» were not observed. Conclusion. The first experience of using the implantable heterogeneous volume-forming material SGL in women with mild and moderate SUI has confirmed the high efficiency of the technology, no worse than other samples of BA, with a high safety profile exceeding many of them. It is necessary to continue clinical research in this direction in order to implement the method into wide practice, also as part of import replacement activities.

Numerical study of gelation and flow restart in a waxy crude oil riser

Precipitation of paraffin wax during crude oil transportation in low ambient temperature presents many technological challenges in petroleum industries. During a complete shutdown, the precipitation intensifies to form a gel-like structure which usually demands high restart pressure during flow restart operation. Numerical simulations are performed to investigate the gelation process in the shutdown pipeline and subsequent non-isothermal flow start-up operation in a heterogeneously gelled pipeline. A Finite volume method is used to solve the mass, momentum and energy conservation-based governing equations over an orthogonal static grid setup. The gelation model utilizes a modified Eyring-based viscosity model to account for temperature-dependent changes in gel strength. On the other hand, the flow restart process follows the deformation and temperature-dependent shear-thinning based rheological model. The pipeline under consideration in the present work is vertical, replicating flow in risers. Our gelation model considers natural convection-driven flow inside the pipeline, which incites the hot oil in the core to mix with cooler fluid at the wall. The gelation is achieved through cooling the static crude oil in the pipeline for different timespans varying from 3 h to 15 h. The gelation stage ends up producing spatial heterogeneity in gel strength. Such heterogeneity leads to weaker gel structure in the core causing early flow restart due to cohesive failure of the gel medium at some interior radial location. Hence, it can be concluded that depending on the cooling stage, the heterogeneous gel with a weaker gel in the pipe core can restart faster than when the pipeline is filled with the gel having an equivalent average temperature. The findings provide realistic insights into the mechanism of gel failure in the pipeline, and the knowledge can be utilized to develop a better flow assurance strategy.

Anomalous rheological aging of a model thermoreversible colloidal gel following a thermal quench.

We investigate the aging behavior in a well-studied model system comprised of a colloidal suspension of thermoreversible adhesive hard spheres (AHS) but thermally quenched below the gel transition to much larger depths than previously studied. The aging behavior in the model AHS system is monitored by small amplitude oscillatory shear rheology measurements conducted while rapidly quenching from the liquid state at 40 °C to a temperature below the gel temperature, and new, anomalous aging behaviors are observed. Shallow quenches lead to monotonic development of the elastic modulus with time, consistent with prior reports for the development of a homogeneous gel [Gordon et al., J. Rheol. 61, 23-34 (2017)]. However, for deeper quenches, a unique and new phenomenon is reported, namely, after an initial rise in the modulus, a reproducible drop in the modulus is observed, followed by a plateau in the modulus value. This drop can be gradual or sudden and the extent of the drop depends on the quench depth. After this drop in the modulus, AHS gel evolves toward a quench-path independent state over the experimental timescale. These effects of the extent of quenching on aging behavior are hypothesized to be a consequence of quenching into different underlying thermodynamic states of colloidal gels and the possible influence of the adhesive glass dynamical arrest for the deepest quenches. The research connects homogeneous gelation with heterogeneous gel formation due to phase separation and shows that the extent of quench can be used as an independent parameter to govern the rheological response of the arrested gel.

A non-isothermal approach to evaluate the impact of the cooling stage on the startup flow of waxy crude oils

Waxy crude oils submitted to low temperatures at quiescent conditions turn into a gel with a corresponding yield stress. Thus, a higher pressure drop is needed to restart, leading to a flow assurance issue. Generally, this problem is tackled by considering the material at rest, with a given state and an imposed pressure drop. In the present work, we investigate how the cooling process after a shutdown impacts the problem. We emulate a stoppage of short duration so that the cooling after the shutdown stage does not lead to a condition of uniform temperature. The temperature-dependent rheology of the material is such that the crude oil shows viscoplastic behavior only below the gelation temperature. The early stages of the process, before and during the shutdown, resulting in a heterogeneous gel, which serves as an initial condition for the restart stage. We perform 2D non-isothermal simulations in a pipe considering three stages, namely (i) normal operation conditions; (ii) cooling stage at rest after stoppage; (iii) restart by an imposed pressure drop. Particular emphasis is given to the role of the plastic number ( P l ) and the duration of the cooling after the shutdown stage. A comparison with the corresponding homogeneous condition is also made. The results show that higher values of P l and higher waiting times in the cooling after the shutdown stage lead to conditions less prone to restart. Only cooling times of short duration lead to restart in the same conditions as the normal operation ones. The pressure drop necessary for a restart is an increasing function of the cooling time. • We examine the restart problem of a waxy crude oil modeled as a viscoplastic material. • The rheological properties are dependent on the temperature. • The previous stages like normal flow and cooling after shutdown are considered. • Heterogeneous initial conditions at the restart are obtained for different cooling times. • Comparisons between heterogeneous and homogeneous conditions show the importance of previous stages.

Gradient Printing Alginate Herero Gel Microspheres for Three-Dimensional Cell Culture.

Hydrogel microspheres are widely used in tissue engineering, such as 3D cell culture and injection therapy, and among which, heterogeneous microspheres are drawing much attention as a promising tool to carry multiple cell types in separated phases. However, it is still a big challenge to fabricate heterogeneous gel microspheres with excellent resolution and different material components in limited sizes. Here, we developed a multi-channel dynamic micromixer, which can use active mechanical mixing to achieve rapid mixing with multi-component materials and extrude the homogenized material. By changing the flow rate ratio of the solutions of the two components and by rapidly mixing in the micromixer, real-time concentration change of the mixed material at the outlet could be monitored in a process so-called “gradient printing”. By studying the mixing efficiency of the micromixer, its size and process parameters were optimized. Using the novel dynamic gradient printing method, the composition of the hydrogel microspheres can be distributed in any proportion and alginate heterogeneous gel microspheres with adjustable cell concentration were fabricated. The effects of cell concentration on cell viability and proliferation ability under three-dimensional culture conditions were also studied. The results showed that cells have very low death rate and can exchange substances within the microspheres. Due to the micromixing ability of the micromixers, the demand for biological reagents and materials such as cells, proteins, cytokines and other materials could be greatly reduced, which helps reduce the experimental cost and improve the feasibility of the method in practical use. The heterogeneous gel microsphere can be greatly valuable for research in various fields such as analytical chemistry, microarray, drug screening, and tissue culture.

Study on the Formation Mechanism of Heterogeneous Gels Based on Slag Geopolymer

Study on the Formation Mechanism of Heterogeneous Gels Based on Slag Geopolymer

Fabrication and characterization methods for investigating cell-matrix interactions in environments possessing spatial orientation heterogeneity

Fibrillar collagen is a ubiquitous structural protein that plays a significant role in determining the mechanical properties of various tissues. The constituent collagen architecture can give direct insight into the respective functional role of the tissue due to the strong structure-function relationship that is exhibited. In such tissues, matrix structure can vary across local subregions contributing to mechanical heterogeneity which can be implicated in tissue function or failure. The post-myocardial infarction scar environment is an example of note where mechanically insufficient collagen can result in impaired cardiac function and possibly tissue rupture due to post-MI cellular response and matrix interactions. In order to further develop the understanding of cell-matrix interactions within heterogeneous environments, we developed a method of heterogeneous collagen gel fabrication which produces a region of randomly oriented fibers directly adjacent to an interconnected region of anisotropic alignment. To fully capture and evaluate the degree of alignment and spatial orientation heterogeneity, several image processing and automated analysis methods were employed. Our analysis revealed the successful fabrication of an interconnected spatially heterogeneous collagen gel possessing distinct regions of random or preferential alignment. Additionally, embedded cell populations were observed to recognize and reorient with their underlying and surrounding architectures through our cell-centric analysis techniques. Statement of significanceFibrillar collagen is a structural protein that contributes to the architecture-function relationship exhibited by various tissues where mechanically insufficient collagen architecture can lead to tissue failure. One environment where this can occur is the post-myocardial infarction scar environment where too much or too little collagen accumulation coupled with spatial fiber orientation heterogeneity can lead to environments incapable of normal mechanical functionality. While there are methodologies capable of generating aligned constructs, they do so with varying degrees of control and complexity with many producing uniform construct alignment. The presented platform is simple and produces continuous constructs possessing inherent spatial orientation heterogeneity. Coupling this with image processing and automated analysis methods enables the probing of fundamental cell-matrix interactions within heterogeneous environments.

Cell Migration Regulated by Spatially Controlled Stiffness inside Composition‐Tunable Three‐Dimensional Dextran Hydrogels

AbstractStiffness of the extracellular matrix plays an important role in regulating cell migration. In this paper, two types of 3D dextran hydrogel, with the stiffness distributed homogeneously and heterogeneously in subcellular scales, have been designed and fabricated to serve as macromolecule scaffolds in which C2C12 cells, an immortalized mouse myoblast cell line, can migrate in a rationally controllable manner. The experimental results indicate that heterogeneous gels can support higher migration velocities, and effective supporting time‐stage for enhancing migration depended on the bulk stiffness that can be rationally and elaborately tuned. Moreover, migration velocity for both types of gels, in most cases, tends to decrease first and then increase from day 0 to day 6. These results show advantages for regulation of cell migration using this easy‐to‐implement heterogeneous cross‐linking approach. Further, associated principles regarding the relationship among cell migration, gel stiffness distribution, and expression of F‐actin and myosin II are also discussed. These studies support rational control of cell migration velocity in heterogeneously cross‐linked hydrogels that are widely applicable in biomaterial field.

Smoothing temperature and ratio of casein to whey protein: Two tools to improve nonfat stirred yogurt properties

Consumers are not always ready to compromise on the loss of texture and increased syneresis that nonfat stirred yogurts display compared with yogurts that contain fat. In this study, we investigated milk protein composition and smoothing temperature as a means to control nonfat yogurt microstructure, textural properties, and syneresis. Yogurts were prepared with different ratios of casein to whey protein (R1.5, R2.8, and R3.9). Yogurts were pumped through a smoothing pilot system comprising a plate heat exchanger set at 15, 20, or 25°C and then stored at 4°C until analysis (d 1, 9, and 23). Yogurt particle size and firmness were measured. Yogurt syneresis and water mobility were determined, respectively, by centrifugation and time domain low-frequency proton nuclear magnetic resonance (1H-LF-NMR). Increasing the smoothing temperature increased gel firmness and microgel (dense protein aggregates) sizes independently of the whey protein content. Also, yogurt microgel sizes changed with storage time, but the evolution pattern depended on protein ratio. Yogurt R1.5 showed the largest particles, and their sizes increased with storage, whereas R2.8 and R3.9 had smaller microgels, and R3.9 did not show any increase in microgel size during storage. Micrographs showed a heterogeneous gel with the empty area occupied by serum for R1.5, whereas R2.8 and R3.9 showed fewer serum zones and a more disrupted gel embedding microgels. Induced syneresis reduced with greater whey protein content and time of storage. This is in agreement with 1H-LF-NMR showing less bulk water mobility with increasing whey protein content during storage. However, 1H-LF-RMN revealed higher values of spontaneous serum separation during storage for R1.5 and R3.9 yogurts, whereas these were lower and stable for R2.8 yogurt. Microgels play an important structural role in yogurt textural attributes, and their characteristics are modulated by whey protein content and smoothing temperature. Optimization of these parameters may help improve nonfat stirred dairy gel.