Optimizing non-Newtonian fluids for impact protection of laminates.

Non-Newtonian fluids can be used for the protection of flexible laminates. Understanding the coupling between the flow of the protecting fluid and the deformation of the protected solids is necessary in order to optimize this functionality. We present a scaling analysis of the problem based on a single coupling variable, the effective width of a squeeze flow between flat rigid plates, and predict that impact protection for laminates is optimized by using shear-thinning, and not shear-thickening, fluids. The prediction is verified experimentally by measuring the velocity and pressure in impact experiments. Our scaling analysis should be generically applicable for non-Newtonian fluid-solid interactions in diverse applications.

Thinning by cluster breaking: Active matter and shear flows share thinning mechanisms.

Among many unexpected phenomena of active matter is the recently observed superfluid-like thinning (viscosity drop) behavior of bacteria suspensions. Understanding this peculiar self-propelled thinning by active matter is of theoretical and practical importance. Here, we find that, although distinct in driving mechanisms, active matter and shear flows exhibit similar thinning behaviors upon the increase of self-propulsion and shear forces, respectively. Our structural characterizations reveal that they actually share the same cluster-breaking mechanism of thinning. How fast and how shattered the cluster is broken determines the (dis)continuity of the thinning. This explains why adding active particles to Newtonian fluids can cause thinning, in which rotation of active particles play a key role in breaking clusters. Our work proposes a mechanism of self-propelled thinning and further establishes the underlying connections between active matter and shear flows.

Hybrid Shear-thinning Hydrogel Integrating Hyaluronic Acid with ROS-Responsive Nanoparticles.

Nanoparticle (NP) supra-assembly offers unique opportunities to tune macroscopic hydrogels' mechanical strength, material degradation, and drug delivery properties. Here, synthetic, reactive oxygen species (ROS)-responsive NPs are physically crosslinked with hyaluronic acid (HA) through guest-host chemistry to create shear-thinning NP/HA hydrogels. A library of triblock copolymers composed of poly(propylene sulfide)-bl-poly(N,N-dimethylacrylamide)-bl-poly(N,N-dimethylacrylamide-co-N-(1-adamantyl)acrylamide) are synthesized with varied triblock architectures and adamantane grafting densities and then self-assembled into NPs displaying adamantane on their corona. Self-assembled NPs are mixed with ß-cyclodextrin grafted HA to yield eighteen NP/HA hydrogel formulations. The NP/HA hydrogel platform demonstrates superior mechanical strength to HA-only hydrogels, susceptibility to oxidative/enzymatic degradation, and inherent cell-protective, antioxidant function. The performance of NP/HA hydrogels is shown to be affected by triblock architecture, guest/host grafting densities, and HA composition. In particular, the length of the hydrophilic second block and adamantane grafting density of self-assembled NPs significantly impacts hydrogel mechanical properties and shear-thinning behavior, while ROS-reactivity of poly(propylene sulfide) protects cells from cytotoxic ROS and reduces oxidative degradation of HA compared to HA-only hydrogels. This work provides insight into polymer structure-function considerations for designing hybrid NP/HA hydrogels and identifies antioxidant, shear-thinning hydrogels as promising injectable delivery platforms for small molecule drugs and therapeutic cells.

Injectable Shear-Thinning Hydrogels with Sclerosing and Matrix Metalloproteinase Modulatory Properties for the Treatment of Vascular Malformations.

Sac embolization of abdominal aortic aneurysms (AAAs) remains clinically limited by endoleak recurrences. These recurrences are correlated with recanalization due to the presence of endothelial lining and matrix metalloproteinases (MMPs)-mediated aneurysm progression. This study incorporated doxycycline (DOX), a well-known sclerosant and MMPs inhibitor, into a shear-thinning biomaterial (STB)-based vascular embolizing hydrogel. The addition of DOX was expected to improve embolizing efficacy while preventing endoleaks by inhibiting MMP activity and promoting endothelial removal. The results showed that STBs containing 4.5% w/w silicate nanoplatelet and 0.3% w/v of DOX were injectable and had a 2-fold increase in storage modulus compared to those without DOX. STB-DOX hydrogels also reduced clotting time by 33% compared to untreated blood. The burst release of DOX from the hydrogels showed sclerosing effects after 6 h in an ex vivo pig aorta model. Sustained release of DOX from hydrogels on endothelial cells showed MMP inhibition (ca. an order of magnitude larger than control groups) after 7 days. The hydrogels successfully occluded a patient-derived abdominal aneurysm model at physiological blood pressures and flow rates. The sclerosing and MMP inhibition characteristics in the engineered multifunctional STB-DOX hydrogels may provide promising opportunities for the efficient embolization of aneurysms in blood vessels.

Rheology as a Tool for Fine-Tuning the Properties of Printable Bioinspired Gels.

Over the last decade, efforts have been oriented toward the development of suitable gels for 3D printing, with controlled morphology and shear-thinning behavior in well-defined conditions. As a multidisciplinary approach to the fabrication of complex biomaterials, 3D bioprinting combines cells and biocompatible materials, which are subsequently printed in specific shapes to generate 3D structures for regenerative medicine or tissue engineering. A major interest is devoted to the printing of biomimetic materials with structural fidelity after their fabrication. Among some requirements imposed for bioinks, such as biocompatibility, nontoxicity, and the possibility to be sterilized, the nondamaging processability represents a critical issue for the stability and functioning of the 3D constructs. The major challenges in the field of printable gels are to mimic at different length scales the structures existing in nature and to reproduce the functions of the biological systems. Thus, a careful investigation of the rheological characteristics allows a fine-tuning of the material properties that are manufactured for targeted applications. The fluid-like or solid-like behavior of materials in conditions similar to those encountered in additive manufacturing can be monitored through the viscoelastic parameters determined in different shear conditions. The network strength, shear-thinning, yield point, and thixotropy govern bioprintability. An assessment of these rheological features provides significant insights for the design and characterization of printable gels. This review focuses on the rheological properties of printable bioinspired gels as a survey of cutting-edge research toward developing printed materials for additive manufacturing.

Fluid rheological effects on streaming dielectrophoresis in a post-array microchannel.

Recent studies have demonstrated the strong influences of fluid rheological properties on insulator-based dielectrophoresis (iDEP) in single-constriction microchannels. However, it is yet to be understood how iDEP in non-Newtonian fluids depends on the geometry of insulating structures. We report in this work an experimental study of fluid rheological effects on streaming DEP in a post-array microchannel that presents multiple contractions and expansions. The iDEP focusing and trapping of particles in a viscoelastic polyethylene oxide solution are comparable to those in a Newtonian buffer, which is consistent with the observations in a single-constriction microchannel. Similarly, the insignificant iDEP effects in a shear-thinning xanthan gum solution also agree with those in the single-constriction channel except that gel-like structures are observed to only form in the post-array microchannel under large DC electric fields. In contrast, the iDEP effects in both viscoelastic and shear-thinning polyacrylamide solution are significantly weaker than in the single-constriction channel. Moreover, instabilities occur in the electroosmotic flow and appear to be only dependent on the DC electric field. These phenomena may be associated with the dynamics of polymers as they are electrokinetically advected around and through the posts.

Ink Rheology Regulates Stability of Bioprinted Strands.

Three-dimensional (3D) extrusion bioprinting typically requires an ad hoc trial-and-error optimization of the ink composition toward enhanced resolution. The ink solutions are solidified after leaving cone-shaped or cylindrical nozzles. The presence of ink instability not only hampers the extrusion resolution but also affects the behavior of embedded cellular components. This is a key factor in selecting (bio)inks and bioprinting design parameters for well-established desktop and handheld bioprinters. In this work, we developed an analytical solution for the process of ink deposition and compared its predictions against numerical simulations of the deposition. We estimated the onset of ink instability as a function of ink rheological properties and nozzle geometry. Our analytical results suggest that enhancing the shear-thinning behavior of the ink shortens the toe region of the deposition. Such an extrusion process is often desired, as it leads to faster depositions. However, we demonstrated that such conditions increase the possibility of lateral buckling of the strand once touching the substrate defined as instability in this study. The present study serves as a benchmark for detailed simulations of the extrusion process for optimal bioprinting.

Self-Assembling Graphene Layers for Electrochemical Sensors Printed in a Single Screen-Printing Process.

This article reports findings on screen-printed electrodes employed in microfluidic diagnostic devices. The research described includes developing a series of graphene- and other carbon form-based printing pastes compared to their rheological parameters, such as viscosity in static and shear-thinning conditions, yield stress, and shear rate required for thinning. In addition, the morphology, electrical conductivity, and electrochemical properties of the electrodes, printed with the examined pastes, were investigated. Correlation analysis was performed between all measured parameters for six electrode materials, yielding highly significant (p-value between 0.002 and 0.017) correlations between electron transfer resistance (Ret), redox peak separation, and static viscosity and thinning shear-rate threshold. The observed more electrochemically accessible surface was explained according to the fluid mechanics of heterophase suspensions. Under changing shear stress, the agglomeration enhanced by the graphene nanoplatelets' interparticle affinity led to phase separation. Less viscous pastes were thinned to a lesser degree, allowing non-permanent clusters to de-agglomerate. Thus, the breaking of temporary agglomerates yielded an unblocked electrode surface. Since the mechanism of phase ordering through agglomeration and de-agglomeration is affected by the pastes' rheology and stress during the printing process and requires no further treatment, it can be appropriately labeled as a self-assembling electrode material.

Numerical Assessment of the Hydrodynamic Behavior of a Volute Centrifugal Pump Handling Emulsion.

Although emulsion pumping is a subject of growing interest, a detailed analysis of the fluid dynamic phenomena occurring inside these machines is still lacking. Several computational investigations have been conducted to study centrifugal pumps carrying emulsion by analyzing their overall performance, but no studies involved the rheological behavior of such fluids. The purpose of this study is to perform a computational analysis of the performance and flow characteristics of a centrifugal pump with volute handling emulsions and oil-water mixtures at different water cuts modeled as a shear-thinning non-Newtonian fluid. The studied pump consists of a five-bladed backward curved impeller and a volute and has a specific speed of 32 (metric units). The rheological properties of the mixtures studied were measured experimentally under a shear rate ranging from 1 s-1 to 3000 s-1 and were fitted to conventional Cross and Carreau effective viscosity models. Numerical results showed the flow topology in the pump is directly related to the viscosity plateau of the pseudoplastic behavior of emulsions. The viscosity plateau governs pump performance by influencing the loss mechanisms that occur within the pump. The larger the ν∞, the less recirculation loss the fluid experiences, and conversely, the smaller the value of ν0, the less friction loss the fluid experiences.

A Thermodynamically Consistent, Microscopically-Based, Model of the Rheology of Aggregating Particles Suspensions.

In this work, we outline the development of a thermodynamically consistent microscopic model for a suspension of aggregating particles under arbitrary, inertia-less deformation. As a proof-of-concept, we show how the combination of a simplified population-balance-based description of the aggregating particle microstructure along with the use of the single-generator bracket description of nonequilibrium thermodynamics, which leads naturally to the formulation of the model equations. Notable elements of the model are a lognormal distribution for the aggregate size population, a population balance-based model of the aggregation and breakup processes and a conformation tensor-based viscoelastic description of the elastic network of the particle aggregates. The resulting example model is evaluated in steady and transient shear forces and elongational flows and shown to offer predictions that are consistent with observed rheological behavior of typical systems of aggregating particles. Additionally, an expression for the total entropy production is also provided that allows one to judge the thermodynamic consistency and to evaluate the importance of the various dissipative phenomena involved in given flow processes.

Rheological Analysis of Bio-ink for 3D Bio-printing Processes.

3D bio-printing is an emerging technology to fabricate tissue scaffold in-vitro through the controlled allocation of biomaterial and cells, which can mimic the in-vivo counterpart of living tissue. Live cells are often encapsulated into the biomaterials (i.e., bio-ink) and extruded by controlling the printing parameters. The functionality of the bioink depends upon three factors: (a) printability, (b) shape fidelity, and (c) bio-compatibility. Increasing viscosity will improve the printability and the shape fidelity but require higher applied extrusion pressure, which is detrimental to the living cell dwelling in the bio-ink, which is often ignored in the bio-ink optimization process. This paper demonstrates a roadmap to develop and optimize bio-inks, ensuring printability, shape fidelity, and cell survivability. The pressure exerted on the bio-ink during extrusion processes is measured analytically, and the information is incorporated in the bio-ink's rheology design. Cell-laden filaments are fabricated with multiple cell lines, i.e., Human Embryonic Kidney (HEK 293), BxPC3, and prostate cancer cells which are analyzed for cell viability. The cross-sectional live-dead assay of the extruded filament demonstrates a spatial pattern for HEK 293 cell viability, which correlates with our analytical finding of the shear stress at the nozzle tip. All three cell lines were able to sustain a transient shear stress of 3.7 kPa and demonstrate 90% viability with our designed bio-ink after 15 days of incubation. Simultaneously, the shape fidelity and printability matrices show its suitability for 3D bio-printing process.

Insulator-based dielectrophoretic focusing and trapping of particles in non-Newtonian fluids.

Insulator-based dielectrophoretic (iDEP) microdevices have been limited to work with Newtonian fluids. We report an experimental study of the fluid rheological effects on iDEP focusing and trapping of polystyrene particles in polyethylene oxide, xanthan gum, and polyacrylamide solutions through a constricted microchannel. Particle focusing and trapping in the mildly viscoelastic polyethylene oxide solution are slightly weaker than in the Newtonian buffer. They are, however, significantly improved in the strongly viscoelastic and shear thinning polyacrylamide solution. These observed particle focusing behaviors exhibit a similar trend with respect to electric field, consistent with a revised theoretical analysis for iDEP focusing in non-Newtonian fluids. No apparent focusing of particles is achieved in the xanthan gum solution, though the iDEP trapping can take place under a much larger electric field than the other fluids. This is attributed to the strong shear thinning-induced influences on both the electroosmotic flow and electrokinetic/dielectrophoretic motions.

Static Retention of Dynamic Chiral Arrangements for Achiral Shear Thinning Metal-Organic Colloids.

Chiral compounds are known to be important not only because they are the fundamental components of living organisms, but also for their unique chiroptical properties. In recent years, scientists have fabricated several chiral organic supramolecular aggregates by using chiral physical fields, such as vortex flow. Herein, the relationship between dynamic chiroptical properties and rheological nature is discussed, suggesting the shear thinning properties of non-Newtonian fluids might help colloidal particles adopt a chiral arrangement in vortices. Furthermore, the storage modulus of colloids could be increased by adding a linking agent, which successfully kept the dynamic chiroptical properties in the static state. Moreover, the salt effect on the host-guest interaction involved in the colloids was studied, the results suggested a significant enhancement of the transferred dynamic circular dichroism for the achiral guest molecule.

Cluster Percolation Causes Shear Thinning Behavior in Concentrated Solutions of Monoclonal Antibodies.

High-concentration (>100 g/L) solutions of monoclonal antibodies (mAbs) are typically characterized by anomalously large solution viscosity and shear thinning behavior for strain rates ≥103 s-1. Here, the link between protein-protein interactions (PPIs) and the rheology of concentrated solutions of COE-03 and COE-19 mAbs is studied by means of static and dynamic light scattering and microfluidic rheometry. By comparing the experimental data with predictions based on the Baxter sticky hard-sphere model, we surprisingly find a connection between the observed shear thinning and the predicted percolation threshold. The longest shear relaxation time of mAbs was much larger than that of model sticky hard spheres within the same region of the phase diagram, which is attributed to the anisotropy of the mAb PPIs. Our results suggest that not only the strength but also the patchiness of short-range attractive PPIs should be explicitly accounted for by theoretical approaches aimed at predicting the shear rate-dependent viscosity of dense mAb solutions.

Structural predictor for nonlinear sheared dynamics in simple glass-forming liquids.

Glass-forming liquids subjected to sufficiently strong shear universally exhibit striking nonlinear behavior; for example, a power-law decrease of the viscosity with increasing shear rate. This phenomenon has attracted considerable attention over the years from both fundamental and applicational viewpoints. However, the out-of-equilibrium and nonlinear nature of sheared fluids have made theoretical understanding of this phenomenon very challenging and thus slower to progress. We find here that the structural relaxation time as a function of the two-body excess entropy, calculated for the extensional axis of the shear flow, collapses onto the corresponding equilibrium curve for a wide range of pair potentials ranging from harsh repulsive to soft and finite. This two-body excess entropy collapse provides a powerful approach to predicting the dynamics of nonequilibrium liquids from their equilibrium counterparts. Furthermore, the two-body excess entropy scaling suggests that sheared dynamics is controlled purely by the liquid structure captured in the form of the two-body excess entropy along the extensional direction, shedding light on the perplexing mechanism behind shear thinning.

Glass and Jamming Rheology in Soft Particles Made of PNIPAM and Polyacrylic Acid.

The phase behaviour of soft colloids has attracted great attention due to the large variety of new phenomenologies emerging from their ability to pack at very high volume fractions. Here we report rheological measurements on interpenetrated polymer network microgels composed of poly(N-isopropylacrylamide) (PNIPAM) and polyacrylic acid (PAAc) at fixed PAAc content as a function of weight concentration. We found three different rheological regimes characteristic of three different states: a Newtonian shear-thinning fluid, an attractive glass characterized by a yield stress, and a jamming state. We discuss the possible molecular mechanisms driving the formation of these states.

Therapeutic Efficacy of Cryopreserved, Allogeneic Extracellular Vesicles for Treatment of Acute Myocardial Infarction.

Extracellular vesicles (EV) that are derived from endothelial progenitor cells (EPC) have been determined to be a novel therapy for acute myocardial infarction, with a promise for immediate "off-the-shelf" delivery. Early experience suggests delivery of EVs from allogeneic sources is safe. Yet, clinical translation of this therapy requires assurances of both EV stability following cryopreservation and absence of an adverse immunologic response to EVs from allogeneic donors. Thus, more bioactivity studies on allogeneic EVs after cold storage are necessary to establish quality standards for its widespread clinical use. Thus, in this study, we aimed to demonstrate the safety and efficacy in delivering cryopreserved EVs in allogeneic recipients as a therapy for acute myocardial infarction.In this present study, we have analyzed the cardioprotective effects of allogeneic EPC-derived EVs after storage at -80°C for 2 months, using a shear-thinning gel (STG) as an in vivo delivery vehicle. EV size, proteome, and nucleic acid cargo were observed to remain steady through extended cryopreservation via nanoparticle tracking analysis, mass spectrometry, and nanodrop analysis, respectively. Fresh and previously frozen EVs in STG were delivered intramyocardially in a rat model of myocardial infarction (MI), with both showing improvements in contractility, angiogenesis, and scar thickness in comparison to phosphate-buffered saline (PBS) and STG controls at 4 weeks post-MI. Pathologic analyses and flow cytometry revealed minimal inflammatory and immune upregulation upon exposure of tissue to EVs pooled from allogeneic donor cells.Allogeneic EPC-EVs have been known to elicit minimal immune activity and retain therapeutic efficacy after at least 2 months of cryopreservation in a post-MI model.

Viscoelasticity and Solution Stability of Cyanoethylcellulose with Different Molecular Weights in Aqueous Solution.

Water-soluble cellulose ethers are widely used as stabilizers, thickeners, and viscosity modifiers in many industries. Understanding rheological behavior of the polymers is of great significance to the effective control of their applications. In this work, a series of cyanoethylcellulose (CEC) samples with different molecular weights were prepared with cellulose and acrylonitrile in NaOH/urea aqueous solution under the homogeneous reaction. The rheological properties of water-soluble CECs as a function of concentration and molecular weight were investigated using shear viscosity and dynamic rheological measurements. Viscoelastic behaviors have been successfully described by the Carreau model, the Ostwald-de-Waele equation, and the Cox-Merz rule. The entanglement concentrations were determined to be 0.6, 0.85, and 1.5 wt% for CEC-11, CEC-7, and CEC-3, respectively. All of the solutions exhibited viscous behavior rather than a clear sol-gel transition in all tested concentrations. The heterogeneous nature of CEC in an aqueous solution was determined from the Cox-Merz rule due to the coexistence of single chain complexes and aggregates. In addition, the CEC aqueous solutions showed good thermal and time stability, and the transition with temperature was reversible.

Elastic instabilities in the electroosmotic flow of non-Newtonian fluids through T-shaped microchannels.

Electroosmotic flow (EOF) has been widely used to transport fluids and samples in micro- and nanofluidic channels for lab-on-a-chip applications. This essentially surface-driven plug-like flow is, however, sensitive to both the fluid and wall properties, of which any inhomogeneity may draw disturbances to the flow and even instabilities. Existing studies on EOF instabilities have been focused primarily upon Newtonian fluids though many of the chemical and biological solutions are actually non-Newtonian. We carry out a systematic experimental investigation of the fluid rheological effects on the elastic instability in the EOF of phosphate buffer-based polymer solutions through T-shaped microchannels. We find that electro-elastic instabilities can be induced in shear thinning polyacrylamide (PAA) and xanthan gum (XG) solutions if the applied direct current voltage is above a threshold value. However, no instabilities are observed in Newtonian or weakly shear thinning viscoelastic fluids including polyethylene oxide (PEO), polyvinylpyrrolidone (PVP), and hyaluronic acid (HA) solutions. We also perform a quantitative analysis of the wave parameters for the observed elasto-elastic instabilities.

Multi-phase catheter-injectable hydrogel enables dual-stage protein-engineered cytokine release to mitigate adverse left ventricular remodeling following myocardial infarction in a small animal model and a large animal model.

Although ischemic heart disease is the leading cause of death worldwide, mainstay treatments ultimately fail because they do not adequately address disease pathophysiology. Restoring the microvascular perfusion deficit remains a significant unmet need and may be addressed via delivery of pro-angiogenic cytokines. The therapeutic effect of cytokines can be enhanced by encapsulation within hydrogels, but current hydrogels do not offer sufficient clinical translatability due to unfavorable viscoelastic mechanical behavior which directly impacts the ability for minimally-invasive catheter delivery. In this report, we examine the therapeutic implications of dual-stage cytokine release from a novel, highly shear-thinning biocompatible catheter-deliverable hydrogel. We chose to encapsulate two protein-engineered cytokines, namely dimeric fragment of hepatocyte growth factor (HGFdf) and engineered stromal cell-derived factor 1α (ESA), which target distinct disease pathways. The controlled release of HGFdf and ESA from separate phases of the hyaluronic acid-based hydrogel allows extended and pronounced beneficial effects due to the precise timing of release. We evaluated the therapeutic efficacy of this treatment strategy in a small animal model of myocardial ischemia and observed a significant benefit in biological and functional parameters. Given the encouraging results from the small animal experiment, we translated this treatment to a large animal preclinical model and observed a reduction in scar size, indicating this strategy could serve as a potential adjunct therapy for the millions of people suffering from ischemic heart disease.