Mechanical Perspective on Increasing Brush Cytology Yield.

Brush cytology is a sampling technique extensively used for mucosal surfaces, particularly to identify malignancies. A sample is obtained by rubbing the brush bristles over the stricture or lesion several times until cells are trapped. Brush cytology detection rate varies, with malignancy confirmed in 15-65% of cases of adenocarcinoma-associated biliary strictures and 44-80% of cases of cholangiocarcinoma. Despite the widespread use of brush cytology, there is no consensus to date defining the optimal biliary brushing parameters for the collection of suspicious lesions, such as the number of passes, brushing rate, and force applied. The aim of this work is to increase the brush cytology diagnostic yield by elucidating the underlying mechanical phenomena. First, the mechanical interactions between the brush bristles and sampled tissue are analyzed. During brushing, mucus and detached cells are transferred to the space between the bristles through the capillary rise and flow eddies. These mass transfer mechanisms and their dependence on mucus rheology as a function of pH, brush displacement rate, and bristle geometry and configuration are examined. Lastly, results from ex vivo brushing experiments performed on porcine stomachs are presented. Clinical practitioners from a variety of disciplines can apply the findings of this study to outline clear procedures for cytological brushing to increase the sensitivity and specificity of the brushings.

Electrically Mediated Static Contact Angle and Hysteresis of Polyelectrolyte Solutions.

Manipulating a droplet by electrowetting-on-dielectric (EWOD) is vital in various fields ranging from industrial applications to life sciences. As of now, EWOD research has focused primarily on aqueous electrolytes and ionic liquids. This paper investigates the electrowetting behavior of weak polyelectrolyte solutions containing poly(acrylic acid) (PAA). The study reveals distinct wetting behavior of weakly and fully charged PAA droplets controlled by their solution pH. Under an applied electric field, strongly ionized PAA wets more effectively than weakly charged PAA. The electrowetting hysteresis of fully ionized PAA droplets was also higher than that of weakly charged droplets. The reason may be the suppression of retraction flow near the contact line. In this thin region, the electric field aligns the stretched polymer chains perpendicular to the dielectric surface, thus affecting the bulk rheological properties. The results reveal how charge-connectivity and polyelectrolyte conformation under an external electric field can control the electrowetting gain and the hysteresis. This previously unexplored electrowetting mechanism of polyelectrolyte solutions might help order and manipulate biological polyelectrolytes, such as deoxyribonucleic acid (DNA), polypeptides, and glycosaminoglycans.

Thermoregulation of Hydrogel Spatiotemporal Mechanics by Exploiting the Folding-Unfolding Characteristics of Globular Proteins.

The incorporation of proteins into hydrogel networks has the potential to enhance bioactivity and biocompatibility. In this work, we report on the fabrication of a polymer-protein hydrogel consisting of polymethacrylamide (PMAAm) and bovine serum albumin (BSA). The hydrogel was prepared by in situ polymerization of methacrylamide in the presence of BSA at elevated temperatures. Due to its specific interactions between corresponding functional groups, BSA acts as a cross-linker of polymer chains. Hydrogel with optimized composition and preparation conditions (BSA/methacrylamide ratio and synthesis temperature) demonstrated excellent mechanical properties. Due to the presence of side amide groups in PMAAm, the energy barrier required for heat-induced transformation of globular BSA structures into unfolded linear structures decreased, causing a significant shift in the transition temperature. This transition led to a steep and substantial strengthening of the two-component hydrogel. After compressive and shear deformation, the hydrogel restored damaged structure and demonstrated superior fatigue resistance. Compared to BSA that is globular, it was found that BSA in its unfolded state has a much greater impact on the mechanical properties of the hydrogel.

Injectable Hydrogels Based on Inter-Polyelectrolyte Interactions between Hyaluronic Acid, Gelatin, and Cationic Cellulose Nanocrystals.

The present work dealt with the development of physically cross-linked injectable hydrogels with potential applications in tissue engineering. The hydrogels were composed of a ternary mixture of a polyanion and a polyampholyte, hyaluronic acid (HA) and gelatin, respectively, bridged by cationic cellulose nanocrystals (cCNCs). A 3D network is formed by employing attractive electrostatic interactions and hydrogen bonding between these components under physiological conditions. The hydrogels demonstrated low viscosity at high stresses, enabling easy injection, structural stability at low stresses (<15 Pa), and nearly complete structure recovery within several minutes. Increasing the cCNC content (>3%) reduced hydrogel swelling and decelerated the degradation in phosphate-buffered saline as compared to that in pure HA and HA-gelatin samples. Biological evaluation of the hydrogel elutions showed excellent cell viability. The proliferation of fibroblasts exposed to elutions of hydrogels with 5% cCNCs reached ∼200% compared to that in the positive control after 11 days. Considering these results, the prepared hydrogels hold great potential in biomedical applications, such as injectable dermal fillers, 3D bioprintable inks, or 3D scaffolds to support and promote soft tissue regeneration.

Bioinspired Cationic-Aromatic Copolymer for Strong and Reversible Underwater Adhesion.

Developing new underwater glue adhesives with robust and repeatable adhesion to various surfaces is promising and useful in marine life and medical treatments. In this work, we developed a novel glue based on a copolymer with a cation-co-aromatic sequence where the cationic units contain both catechol and positively charged sites. The glue consists of a crosslinked copolymer of poly(2-hydroxy-3-phenoxypropyl acrylate-co-3-(5-(3,4 dihydroxyphenyl)-4-oxo-3 N-pentyl)imidazolium) bromide in dimethyl sulfoxide. Solidification of the glue, triggered by contact with water, undergoes a coacervation stage and causes a drastic growth of its mechanical properties over time. The glue demonstrates fast-developing, strong, and repeatable underwater adhesion to different materials and can maintain its strength for a long time. The adhesion strength tends to increase with the surface energy of the substrate material, to a maximum value of 160 kPa found in plywood. Experiments conducted in aqueous media with different pH and ionic strengths, including physiological conditions and seawater, showed an even stronger adhesion than that evolved in deionized water. Thus, the developed glue is a promising candidate for use in marine life, tissue adhesives, and other freshwater and saline water applications.

Phase Change Material with Gelation Imparting Shape Stability.

Blending two gelators with different chemistries (12-hydroxystearic acid and a bis-urea derivative, Millithix MT-800) was used to impart shape stability to CrodaTherm 29, a bio-based phase change material (PCM), melting/crystallizing at near-ambient temperature. The gelators immobilized the PCM by forming an interpenetrating fibrillar network. 15 wt % concentration of the gelators was found to be effective in preventing liquid PCM leakage. In order to improve the mechanical properties and thermal conductivity (TC) of the PCM, gelation of suspensions of multiwalled carbon nanotubes (MWCNTs) and graphene nanoplatelets (GnPs) in a molten material was done at concentrations exceeding their percolation thresholds. Compared to pristine PCM, the gelled PCM containing 3.0 wt % of GnPs demonstrated a shorter crystallization time, ∼1.5-fold increase in strength, improved stability, and ∼65% increase in TC. At the same time, PCM filled with up to 0.6 wt % of MWCNTs had diminished strength and increased leakage with a slight TC improvement. Gelation of PCM did not significantly alter its thermal behavior, but it did change its crystalline morphology. The developed shape-stable PCMs may have a wide range of applications in ambient temperature solar-thermal installations, for example, temperature-controlled greenhouses, net zero-energy buildings, and water heaters.

Electrostatically crosslinked cellulose nanocrystal and polyelectrolyte complex sponges with pH responsiveness.

This work focuses on the development of a responsive sponge made of an anionic cellulose nanocrystal (CNC) skeleton that is electrostatically crosslinked by a pH-responsive poly(allylamine hydrochloride) (PAH) and poly(acrylic acid) (PAA) polyelectrolyte complex (PEC). The results prove the formation of a global percolated network comprised of disordered CNC rods crosslinked by PEC clusters. The bulk density of the freeze-dried CNC-PEC sponges increases from 35 to 93 mg/cm3 with PEC concentration, while the compression modulus of dry specimens increases from 7 up to 62 kPa. At the lowest PEC concentration of 1 wt%, at pH 2.0, the compression modulus decreases to 0.9 kPa, whereas at pH 5.5, it increases to 42 kPa. The intensive complexation between sponge constituents is also reflected in a reduced ability to bind charged dyes at neutral pH values. Decreasing the pH results in an increased adsorption efficiency for anionic dyes, while raising the pH improves the cationic dye adsorption.

Synergistic Effect of Two Organogelators for the Creation of Bio-Based, Shape-Stable Phase-Change Materials.

Two organogelators of different chemistry (a fatty acid derivative and a bis-urea derivative), as well as their blends, were used to impart shape stability to a bio-based phase-change material (PCM) bearing a near-ambient phase-transition temperature. Characterization of the individual gelators and their blends revealed their ability to immobilize the PCM by forming a continuous fibrillar network. The fibrils formed by the fatty acid derivative were helical, while the bis-urea derivative formed smooth fibrils. Also, the bis-urea derivative formed a continuous network at a lower critical concentration than the fatty acid derivative. At each fixed concentration, the bis-urea derivative yielded gels with higher thermal stability than the fatty acid derivative. The two gelators blended in certain ratios demonstrated a strong synergistic effect, providing gels with a significantly higher modulus (∼20-fold) and yield stress (∼1.5-fold) than each gelator individually. PCM gelation did not significantly affect its thermal behavior, however, affected its crystalline morphology. The gelled PCM displayed stacked structures, consisting of alternating pure PCM layers separated by layers formed by gelator fibrils. The phase diagram of the triple system comprising both gelators and PCM demonstrated either single or double gelation behavior depending on the composition. These findings may provide guidelines for the development of novel, shape-stable PCMs, which could be of potential use in various thermal energy storage applications.

The Role of Electrical Polarity in Electrospinning and on the Mechanical and Structural Properties of As-Spun Fibers.

Electric field strength and polarity in electrospinning processes and their effect on process dynamics and the physical properties of as-spun fibers is studied. Using a solution of the neutral polymer such as poly(methyl methacrylate) (PMMA) we explored the electrospun jet motion issued from a Taylor cone. We focused on the straight jet section up to the incipient stage of the bending instability and on the radius of the disk of the fibers deposited on the collecting electrode. A new correlation formula using dimensionless parameters was found, characterizing the effect of the electric field on the length of the straight jet, L˜E~E˜0.55. This correlation was found to be valid when the spinneret was either negatively or positively charged and the electrode grounded. The fiber deposition radius was found to be independent of the electric field strength and polarity. When the spinneret was negatively charged, L˜E was longer, the as-spun fibers were wider. The positively charged setup resulted in fibers with enhanced mechanical properties and higher crystallinity. This work demonstrates that often-overlooked electrical polarity and field strength parameters influence the dynamics of fiber electrospinning, which is crucial for designing polymer fiber properties and optimizing their collection.

Enhanced Electrospinning of Active Organic Fibers by Plasma Treatment on Conjugated Polymer Solutions.

Realizing active, light-emitting fibers made of conjugated polymers by the electrospinning method is generally challenging. Electrospinning of plasma-treated conjugated polymer solutions is here developed for the production of light-emitting microfibers and nanofibers. Active fibers from conjugated polymer solutions rapidly processed by a cold atmospheric argon plasma are electrospun in an effective way, and they show a smoother surface and bead-less morphology, as well as preserved optical properties in terms of absorption, emission, and photoluminescence quantum yield. In addition, the polarization of emitted light and more notably photon waveguiding along the length of individual fibers are remarkably enhanced by electrospinning plasma-treated solutions. These properties come from a synergetic combination of favorable intermolecular coupling in the solutions, increased order of macromolecules on the nanoscale, and resulting fiber morphology. Such findings make the coupling of the electrospinning method and cold atmospheric plasma processing on conjugated polymer solutions a highly promising and possibly general route to generate light-emitting and conductive micro- and nanostructures for organic photonics and electronics.

Structural Arrest and Phase Transition in Glassy Nanocellulose Colloids.

From drying blood to oil paint, the developing of a glassy phase from colloids is observed on a daily basis. Colloidal glass is solid soft matter that consists of two intertwined phases: a random packed particle network and a fluid solvent. By dispersing charged rod-like cellulose nanoparticles into a water-ethylene glycol cosolvent, here we demonstrate a new kind of colloidal glass with a high liquid crystalline order, namely, two general superstructures with nematic and cholesteric packing states are preserved and jammed inside the glass matrix. During the glass formation process, structural arrest and phase transition occur simultaneously at high particle concentrations, yielding solid-like behavior as well as a frozen liquid crystal texture that is because of caging of the charged colloids through neighboring long-ranged repulsive interactions.

Modulating the Structural Orientation of Nanocellulose Composites through Mechano-Stimuli.

It is of great interest to dynamically manipulate the optical property by controlling nanostructures under external stimuli. In this work, chiral photonic cellulose nanocrystal (CNC) and elastic polyurethane (PU) composite films demonstrate reversible optical tunability arising from structural transition between the chiral nematic and layered pseudonematic order. The composite films exhibit impressive water resistance and mechanical adaptability. Reversible modulation of the optical property of the composite CNC/PU film is enabled during mechanical stretching and water absorption. Film stretching is accompanied by CNC transition from a chiral nematic to layered pseudonematic structure. After fixation, shape recovery takes place when exposed to water, and the CNC structure reverts to the initial chiral nematic order. These reversibly switchable shape and optical properties further advance the study and design of smart optical and mechanical sensors.

Flow induced stability of pluronic hydrogels: Injectable and unencapsulated nucleus pulposus replacement.

Poloxamers, or pluronics, have been proposed as biomimetic substitutes for physiological gels. Concern regarding their ability to resist swelling under fluid flows has impeded their implementation. Using a combination of techniques including cryo-TEM and rapid X-ray imaging, we found that rapid flow rates stabilized the gels against dissolution. Energy balance calculations confirmed that disentanglement of individual micelles was not possible at time scales faster than the reptation time when the system response was that of a solid which dissipated the hydrodynamic force field via cooperative deformation. In-vivo tests were performed where the hydrogel was injected as a substitute for the nucleus pulposus following discectomy in dogs. The results indicated that the gel was still present after 3 months, and radiographs indicated that compression of the disc space was prevented despite the gel being exposed to constant perfusion. STATEMENT OF SIGNIFICANCE: This paper demonstrates a highly unexpected result and counter intuitive result, namely the inverse dependence of the dissociation rate of a physical hydrogel on the flow velocity of the liquid medium. Using cryo-electron microscopy we demonstrate that the gel responds like deformable solid in high flow rates, with minimal dissociation. Since these gels are thermoreversible, they were injected into dogs, where we show that they were a viable alternative to the nucleus pulposus, without dissolution in physiological fluid flows for at least three months.

Structure and Rheology of Polyelectrolyte Complexes in the Presence of a Hydrogen-Bonded Co-Solvent.

Intermolecular interactions as well as macromolecular conformation affect the rheological and microstructural properties of polyelectrolyte complexes (PECs) solutions. The properties of semi-dilute solutions of weakly charged PECs can be controlled by the degree of ionization and solvent composition. In this work, we examined the effect of ethanol as a co-solvent on PECs composed of poly(allylamine hydrochloride) (PAH) and poly(acrylic acid) (PAA) at low pH. The aqueous PECs solution was turbid, indicating formation of large aggregates, whereas PECs solution in water/ethanol (60:40 w/w) was transparent, implying no aggregation, and demonstrated higher relative viscosity than the aqueous solution, implying pronounced network formation. Imaging PECs solution by transmission electron microscopy (TEM) demonstrated aggregation, whereas the solution prepared with the mixed solvent revealed almost no phase contrast. Small-angle X-ray scattering (SAXS) of PECs in the aqueous solution indicated the presence of aggregates, while PECs in mixed solvent demonstrated a swelled macromolecular conformation with diminished aggregation. PECs with no ionic interactions in the mixed solvent assumes a homogenous network structure, which enables PECs solution processing by electrospinning.

Hybrid Nanocomposites for 3D Optics: Using Interpolymer Complexes with Cellulose Nanocrystals.

Manipulation of optical paths by three-dimensional (3D) integrated optics with customized stacked building blocks has gained considerable attention. Herein, we present functional thin films with assembly ability for 3D integrated optics based on nanocomposites made of cellulose nanocrystals (CNCs) embedded in hydrogen-bonded (H-bonded) interpolymer complexes (IPCs). We selected H-bonded IPC poly(ethylene oxide) and neutralized poly(acrylic acid) to render films assembly ability without undesired interplay with charge distribution in CNCs. The CNCs can form a stable chiral nematic liquid crystalline phase with long-range orientational order and helical organization. The resulting nanocomposites are characterized with a high elastic modulus of 8.8 GPa and an adhesion strength of 1.35 MPa through reversible intermolecular interactions at the contact interface upon exposure to acidic vapor. Instead, simply stacked into 3D optics, these functional thin films serve as a facile material for providing a conceptually simple approach to assemble 3D integrated optics with different liquid crystalline orderings to manipulate the light polarization state.

Exclusion and Trapping of Carbon Nanostructures in Nonisotropic Suspensions of Cellulose Nanostructures.

Incorporation of carbon nanotubes (CNTs) into liquid crystalline phases of cellulose nanocrystals (CNCs) may be used for preparation of hybrids with novel optical, electrical, and mechanical properties. Here, we investigated the effect of nanoparticle diameter, geometry, aspect ratio, and flexibility on the exclusion of dispersed carbon nanostructures (CNs) from the chiral nematic phase (N*) of the CNCs. Although the CNs are nicely dispersed in isotropic suspensions of CNCs, we observe that fullerenes, carbon black, and CNTs are depleted from the N* phase. This observation is surprising as theoretical predictions and previous observations of nanoparticles indicate that nanometric inclusions would be incorporated within the N* phase. Cryogenic transmission electron microscopy imaging reveals that the dispersed CNs induce misorientation of the CNCs, irrespective of their geometry and size. Rheological measurements suggest that about 10% of the CNCs are affected by the CNs. The multiparticle nature of the interaction may be the origin of the nonsize selective exclusion of the CNs. Re-entrant behavior is observed at high CNC concentrations (about 13 wt %), where a (nematic) gel-like phase kinetically traps the CNs. These phases exhibit non-Newtonian flow behavior and birefringence, offering a pathway for preparation of nonisotropic CNCs-CNT composites and thin films via liquid processing.

3D Structure and Processing Methods Direct the Biological Attributes of ECM-Based Cardiac Scaffolds.

High hopes are held for cardiac regenerative therapy, driving a vast research effort towards the development of various cardiac scaffolds using diverse technologies and materials. Nevertheless, the role of factors such as fabrication process and structure in determining scaffold's characteristics is yet to be discovered. In the present study, the effects of 3D structure and processing method on cardiac scaffolds are addressed using three distinct scaffolds made through different production technologies from the same biomaterial: decellularized porcine cardiac extracellular matrix (pcECM). pcECM patch, injectable pcECM hydrogel, and electrospun pcECM scaffolds were all proven as viable prospective therapies for MI, thus generally preserving pcECM beneficial properties. Yet, as we demonstrate, minor differences in scaffolds composition and micro-morphology as well as substantial differences in their mechanical properties, which arise from their production process, highly affect the interactions of the scaffold with both proliferating cells and functional cells. Hence, the rates of cell attachment, survival, and proliferation significantly vary between the different scaffolds. Moreover, major differences in cell morphology and alignment as well as in matrix remodeling are obtained. Overall, the effects revealed herein can guide a more rational scaffold design for the improved cellular or acellular treatment of different cardiac disease scenarios.

The ternary system amylose-amylopectin-formic acid as precursor for electrospun fibers with tunable mechanical properties.

Electrospun starch fibers are promising materials, with potential utility in many fields, including food packaging and tissue engineering. In the present work, we used formylated derivatives of starch constituents, amylose and amylopectin. Various blends of amylose and amylopectin were used to characterize the behavior of starch in formic acid. This approach allowed us to focus on the effect of the polysaccharides ratio on phase behavior, rheological properties and spinnability of solutions and eliminate the effect of molecular characteristics of the polymers. All the tested solutions including pure amylopectin solution proved electrospinnable. All the fibers were largely amorphous and exhibited much higher elongation at break when compared to cast films of the same composition. Amylose-rich fibers demonstrated higher strength, stiffness and ductility, while amylopectin-rich fibers were weak and brittle. This difference in mechanical properties marks possible fields of application of these two types of materials. Fibers with high amylose content may have potential application in food packaging or tissue engineering while fibers with high amylopectin concentration are in favor for control drug release.

The role of polymer-solvent interactions in polyvinyl-alcohol dispersions of multi-wall carbon nanotubes: from coagulant to dispersant.

Dispersion of carbon nanotubes in solutions of polyvinyl-alcohol is required for solution casting of composite materials with improved interfacial adhesion where chains adsorbed on the nanotubes serve in the dual role of dispersant and compatible "connector" to the polyvinyl-alcohol matrix. Yet polyvinyl-alcohol is known to induce coagulation of nanotubes in aqueous solutions and thus far, it has not been used for dispersing pristine nanotubes. Here, we report that non-fully hydrolyzed (80-90%) polyvinyl-alcohol can be used for the preparation of stable, surfactant-free, dispersions of multi-wall carbon nanotubes in ethanol-water mixtures (of at least 50 vol% ethanol). Cryo-TEM imaging and rheological measurements of stable, long-lived dispersions reveal the formation of random networks of suspended tubes, with an averaged mesh size of ∼500 nm, indicating that the individual tubes do not aggregate or coagulate. We hypothesize that the polyvinyl-acetate sequences found in non-fully hydrolyzed polymers swell in the presence of ethanol, leading to the formation of a long-ranged steric (entropic) repulsion among polymer-decorated nanotubes. The unexpected role of the polyvinyl-acetate sequences along with a detailed dispersion mechanism are described.

Controlled Assembly of Nanocellulose-Stabilized Emulsions with Periodic Liquid Crystal-in-Liquid Crystal Organization.

Colloidal particles combined with a polymer can be used to stabilize an oil-water interface forming stable emulsions. Here, we described a novel liquid crystal (LC)-in-LC emulsion composed of a nematic oil phase and a cholesteric or nematic aqueous cellulose nanocrystal (CNC) continuous phase. The guest oil droplets were stabilized and suspended in liquid-crystalline CNCs, inducing distortions and topological defects inside the host LC phase. These emulsions exhibited anisotropic interactions between the two LCs that depended on the diameter-to-pitch ratio of suspended guest droplets and the host CNC cholesteric phase. When the ratio was high, oil droplets were embedded into a cholesteric shell with a concentric packing of CNC layers and took on a radial orientation of the helical axis. Otherwise, discrete surface-trapped LC droplet assemblies with long-range ordering were obtained, mimicking the fingerprint configuration of the cholesteric phase. Thus, the LC-in-LC emulsions presented here define a new class of ordered soft matter in which both nematic and cholesteric LC ordering can be well-manipulated.