On-chip construction of a fully structured scaffold-free vascularized renal tubule.

Renal tubule chips have emerged as a promising platform for drug nephrotoxicity testing. However, the reported renal tubule chips hardly replicate the unique structure of renal tubules with thick proximal and distal tubules and a thin loop of Henle. In this study, we developed a fully structured scaffold-free vascularized renal tubule on a microfluidic chip. On the chip, the renal epithelial cell-laden hollow calcium-polymerized alginate tube with thick segments at both ends and a thin middle segment was U-shaped embedded in collagen hydrogel, parallel to the endothelial cell-laden hollow calcium-polymerized alginate tube with uniform tube diameter. After the alginate tubes were on-chip degraded, the renal epithelial cells and endothelial cells automatically attached to the collagen hydrogel and proliferated to form the renal tubule with proximal tubule, loop of Henle and distal tubule as well as peritubular blood vessel. We evaluated the viability of cells on the hollow alginate tubes, characterized the distribution and morphology of cells before and after the degradation of the alginate tube, and confirmed the proliferation of cells and the metabolic function of cells in terms of ATP synthesis, fibronectin secretion and VEGFR2 expression on the chip. The enhanced metabolic functions of renal epithelial cells and endothelial cells were preliminarily demonstrated. This study provides new insights into designing a more biomimetic renal tubule on a microfluidic chip.

Alginate Core-Shell Capsules Production through Coextrusion Methods: Principles and Technologies.

This paper provides an overview of coextrusion methods for encapsulation. Encapsulation involves the coating or entrapment of a core material such as food ingredients, enzymes, cells, or bioactives. Encapsulation can help compounds add to other matrices, stabilize compounds during storage, or enable controlled delivery. This review explores the principal l coextrusion methods available that can be used to produce core-shell capsules through the use of coaxial nozzles. Four methods for encapsulation by coextrusion are examined in detail, including dripping, jet cutting, centrifugal, and electrohydrodynamic systems. The targeted capsule size determines the appropriate parameters for each method. Coextrusion technology is a promising encapsulation technique able to generate core-shell capsules in a controlled manner, which can be applied to cosmetic, food, pharmaceutical, agriculture, and textile industries. Coextrusion is an excellent way to preserve active molecules and present a significant economic interest.

Biosourced Multiphase Systems Based on Poly(Lactic Acid) and Polyamide 11 from Blends to Multi-Micro/Nanolayer Polymers Fabricated with Forced-Assembly Multilayer Coextrusion.

The objective of the present study was to investigate multiphase systems based on polylactic acid (PLA) and polyamide 11 (PA11) from blends to multilayers. Firstly, PLA/PA11 blends compatibilized with a multifunctionalized epoxide, Joncryl, were obtained through reactive extrusion, and the thermal, morphological, rheological, and mechanical behaviors of these materials were investigated. The role of Joncryl as a compatibilizer for the PLA/PA11 system was demonstrated by the significant decrease in particle size and interfacial tension as well as by the tensile properties exhibiting a ductile behavior. Based on these findings, we were able to further clarify the effects of interdiffusion and diffuse interphase formation on the structure, rheology, and mechanics of compatible multilayered systems fabricated with forced-assembly multilayer coextrusion. The results presented herein aim to provide a deeper understanding of the interfacial properties, including the rheological, mechanical, and morphological behaviors, towards the control of the interface and confinement in multilayer polymers resulting from coextrusion, and also to permit their use in advanced applications.

Durability of Flame-Retarded, Co-Extruded Profiles Based on High-Density Polyethylene and Wheat Straw Residues.

At present, little information is available in the scientific literature related to the durability (weathering resistance) of fire-retarded wood and natural fiber-reinforced thermoplastics. In this work, thermoplastic profiles for façade applications based on high-density polyethylene, wheat straw particles, and fire-retardants were extruded and their reaction-to-fire performance before and after artificial weathering evaluated. Profile geometries were either solid or hollow-core profiles, and fire-retardants (FR) were added either in the co-extruded layer or in the bulk. Various FR for inclusion in the co-extruded layer were screened based on UL-94 tests. For profile extrusion, two types of FR were chosen: a coated intumescent combination based on ammonium polyphosphate (APP) and an APP coated with melamine and without formaldehyde. Before weathering, the peak heat release rate (pHRR) and the total heat release (THR), which were determined using cone calorimeter measurements, were reduced by up to 64% and 67% due to the FR. However, even before weathering, pHRR of the profiles was relatively high, with best (lowest) values between 230 and 250 kW/m2 under the test conditions. After 28 days of artificial weathering, changes in reaction-to-fire performance and color were evaluated. Use of the APP in the co-extruded layer worsened color change compared to the formulation without APP but the pHRR was not significantly changed. The influence of weathering on the fire behavior was small compared to the difference between fire-retarded and non-fire-retarded materials. Results from the cone calorimeter were analyzed with regard to ETAG 028, which provides requirements related to the durability of fire performance of building products. In many formulations, increase in THR was less than 20% compared to before weathering, which would place some of the profiles in class C or better (EN 13501-1). However, due to the high pHRR, at best, class D was obtained under the conditions of this study. In addition to cone calorimeter measurements, results from the single flame source test, limiting oxygen index determination and thermogravimetric analysis, are shown and discussed. Strength properties, water uptake and swelling of the profiles, thermal conductivity, and energy dispersive X-ray data are also presented.

Fixed Dose Combination Formulations: Multilayered Platforms Designed for the Management of Cardiovascular Disease.

Hyperlipidaemia is considered as one of the main risk factors associated with cardiovascular diseases (CVDs). Among different lipid-lowering agents used to manage hyperlipidaemia, statins are highly prescribed for management of hyperlipidaemia with simvastatin being one of the most common. Simvastatin is susceptible to extensive metabolism by CYP450 3A4 and 3A5, which are expressed both in the liver and the gastrointestinal tract. Nevertheless, the localization of these enzymes is site-dependent with lower concentration at the distal/proximal regions of the small intestine/colon. In addition to statins, medications such as antihypertensive agents and anticoagulants are introduced as adjuvants, for the treatment of cardiovascular disease. The aim of this study was to design a bilayer delivery system capable of delivering biphasic release of simvastatin and aspirin, within a fixed dose combination. A delayed release platform based on a combination of anionic polymers prepared using hot-melt extrusion was developed to delay the release of simvastatin. An optimized formulation tested for dissolution performance clearly demonstrated an ability to delay the release of simvastatin. In addition, an immediate release layer based on Kollidon VA64 was successfully developed to deliver aspirin. Both formulations were then manufactured as a bilayer drug delivery system (tablets and coextrudates), and the release performance was examined. On the basis of the obtained results, these formulations may be used as a platform for delivering a wide range of medications in a biphasic manner.

Polymer Nanosheet Containing Star-Like Copolymers: A Novel Scalable Controlled Release System.

Poly(ε-caprolactone) (PCL)-based nanomaterials, such as nanoparticles and liposomes, have exhibited great potential as controlled release systems, but the difficulties in large-scale fabrication limit their practical applications. Among the various methods being developed to fabricate polymer nanosheets (PNSs) for different applications, such as Langmuir-Blodgett technique and layer-by-layer assembly, are very effort consuming, and only a few PNSs can be obtained. In this paper, poly(ε-caprolactone)-based PNSs with adjustable thickness are obtained in large quantity by simple water exposure of multilayer polymer films, which are fabricated via a layer multiplying coextrusion method. The PNS is also demonstrated as a novel controlled guest release system, in which release kinetics are adjustable by the nanosheet thickness, pH values of the media, and the presence of protecting layers. Theoretical simulations, including Korsmeyer-Peppas model and Finite-element analysis, are also employed to discern the observed guest-release mechanisms.

Toxicity assessment of the extractables from multi-layer coextrusion poly ethylene bags exposed to pH=5 solution containing 4% benzyl alcohol and 0.1 M sodium acetate.

A non-target analysis was developed for the analysis of extractables from multi-layer coextrusion bags exposed to 4% benzyl alcohol solution and 0.1 M sodium acetate at pH = 5 for defined periods (15 day, 45 day and 90 day) according to manufacturer instructions based on the ultra-performance liquid chromatography (UPLC) quadrupole-time of flight mass spectrometry (Q-TOF MS). In order to confirm the extractables, principal component analysis (PCA) was used to indicate the differences among samples of different periods. Then, the extractables were identified based on searching the self-built library or online searching. The total content of extractables of 90 day samples was 589.78 µg/L, and the content was in the range of acceptable levels for pharmaceutical manufacturers. The risk assessment of the extractables were evaluated by Toxtree and T.E.S.T. software to avoid the animals bioexperiment.

Establishment of a Molding Procedure to Facilitate Formulation Development for Co-extrudates.

Co-extrusion offers a number of advantages over conventional manufacturing techniques. However, the setup of a co-extrusion line is cost- and time-intense and formulation development is challenging. This work introduces a novel procedure to test the applicability of a co-extruded reservoir-type system at an early product development stage. We propose vacuum compression molding (VCM), a fast procedure that requires only small material amounts, for the manufacturing of cylindrical reservoir-type system. To this end, the commercially available co-extruded product NuvaRing® and variations thereof were used as test systems. All VCM systems showed a homogeneous skin thickness that adhered well to the core, thereby providing a precise core/skin interface. As drug release is a key criterion for pharmaceutical products, a modified in vitro dissolution method was set up to test the VCM systems. The drug release from the VCM systems was in the same order of magnitude as the corresponding co-extruded strands and followed the same release kinetics. Moreover, the VCM systems were capable of indicating the relative effect of formulation-related modifications on drug release. Overall, this shows that this system is a powerful tool that facilitates formulation tailoring and co-extrusion process setup at the earliest stage.

Evaluation of morphological representative sample sizes for nanolayered polymer blends.

The size of representative microstructural samples obtained from atomic force microscopy is addressed in this paper. The case of an archetypal one-dimensional nanolayered polymer blend is considered. Image analysis is performed on micrographs obtained through atomic force microscopy, yielding statistical data concerning morphological properties of the material. The variability in terms of microstructural morphology is due to the thermomechanical processing route. The statistical data is used in order to estimate sample size representativity, based on an asymptotic relationship relating the inherent point variance of the indicator function of one material phase to the statistical, size-dependent, ensemble variance of the same function. From the study of nanolayered material systems, the statistical approach was found to be an effective mean for discriminating and characterizing multiple scales of heterogeneity.

A Facile Method to Prepare Double-Layer Isoporous Hollow Fiber Membrane by In Situ Hydrogen Bond Formation in the Spinning Line.

A double-layer hollow fiber is fabricated where an isoporous surface of polystyrene-block-poly(4-vinylpyridine) is fixed on a support layer by co-extrusion. Due to the sulfonation of the support layer material, delamination of the two layers is suppressed without increasing the number of subsequent processing steps for isoporous composite membrane formation. Electron microscope-energy-dispersive X-ray spectroscopy images unveil the existence of a high sulfur concentration in the interfacial region by which in-process H-bond formation between the layers is evidenced. For the very first time, our study reports a facile method to fabricate a sturdy isoporous double-layer hollow fiber.

Development of Fused Deposition Modeling of Multiple Materials (FD3M) Through Dynamic Coaxial Extrusion.

Multimaterial additive manufacturing is expanding the design space realizable with 3D printing, yet is largely constrained to sequential deposition of each individual material. The ability to coextrude two materials and change the ratio of materials while printing would enable custom-tailored polymer composites. Here, the evolution of a dynamic material coextrusion process for additive manufacturing capable of printing any ratio between and including two neat input materials is described across 3 hot-end generations and 14 implemented design iterations. The designs evolved with increased understanding of manufacturing constraints associated with the additive manufacturing of metal components with internal flow bore diameters on the order of 2 mm and typical bore length around 50 mm. The second generation overcame this issue by partitioning the design into two pieces to locate the flow channel geometry at the interface between the components so that the details could be easily printed on the components' external surfaces. The third concept generation then focused on minimizing flow channel volume to reduce the average length when transitioning between materials by 92%. The third-generation design was also used to investigate the improvements in dimensional stability during annealing of acrylonitrile butadiene styrene (ABS) made possible by coextruding ABS with a polycarbonate (PC) core. The standard deviation of part shrinkage after annealing was 7.08% for the neat ABS but reduced to 0.24% for the coextruded ABS/PC components.

Extrusion and Co-extrusion: A Technology in Probiotic Encapsulation with Alternative Materials.

Encapsulation, in particular extrusion and co-extrusion, is a common practice to protect probiotics from the harsh conditions of the digestive tract as well as processing. Hydrocolloids, including proteins and carbohydrates, natural or modified, are a group of ingredients used as the wall material in extrusion. Hydrocolloids, due to their specific properties, can significantly improve the probiotic survivability of the final powder during the microencapsulation process and storage. The present article will discuss the different kinds of hydrocolloids used for microencapsulation of probiotics by extrusion and co-extrusion, along with new sources of novel gums and their potential as wall material.

Scalable Microwires through Thermal Drawing of Co-Extruded Liquid Metal and Thermoplastic Elastomer.

This article demonstrates scalable production of liquid metal (LM)-based microwires through the thermal drawing of extrudates. These extrudates were first co-extruded using a eutectic alloy of gallium and indium (EGaIn) as a core element and a thermoplastic elastomer, styrene-ethylene/butylene-styrene (SEBS), as a shell material. By varying the feed speed of the co-extruded materials and the drawing speed of the extrudate, it was possible to control the dimensions of the microwires, such as core diameter and shell thickness. How the extrusion temperature affects the dimensions of the microwire was also analyzed. The smallest microwire (core diameter: 52 ± 14 µm and shell thickness: 46 ± 10 µm) was produced from a drawing speed of 300.1 mm s-1 (the maximum attainable speed of the apparatus used), SEBS extrusion speed of 1.50 mm3 s-1, and LM injection rate of 5 × 105 µL s-1 at 190 °C extrusion temperature. The same extrusion condition without thermal drawing generated significantly large extrudates with a core diameter of 278 ± 26 µm and shell thickness of 430 ± 51 µm. The electrical properties of the microwires were also characterized under different degrees of stretching and wire kinking deformation which proved that these LM-based microwires change electrical resistance as they are deformed and fully self-heal once the load is removed. Finally, the sewability of these microwires was qualitatively tested by using a manual sewing machine to pattern microwires on a traditional cotton fabric.

Montmorillonite Exfoliation in LLDPE and Factors Affecting Its Orientation: From Monolayer to Multi-Nano-Layer Polymer Films.

The motivations of the present work are to investigate the exfoliation of montmorillonite within a linear low-density polyethylene matrix and to control its orientation during the cast extrusion process. The first part is focused on the exfoliation of the montmorillonite through the melt extrusion process. The accuracy and relevance of each method used to determine the exfoliation state of montmorillonite have been examined, thanks to X-ray diffraction, transmission electronic microscopy, and rheology. All these methods have presented limitations, but the combination of all leads to a better estimation of the exfoliation state. Finally, the orientation of the montmorillonite is quantified systematically by X-ray texture analysis and correlated with process parameters to discern which one is affecting their orientation. The results have demonstrated an enhancement of the "in-plane" orientation of the montmorillonite with the exfoliation, especially at high concentration and when combined with cast extrusion. Finally, in the multi-nano-layer polymer film configuration, the reduction of the individual layers 29 nm thickness leads to some orientation improvements. However, these improvements are almost at the same level as the concentration effect in a monolayer system. This work gives an overview of all the parameters needed to achieve a significant organo-modified montmorillonite "in-plane" orientation.

Confinement Effect in Multilayer Films Made from Semicrystalline and Bio-Based Polyamide and Polylactic Acid.

Bio-based multilayer films were prepared by using the innovative nanolayer coextrusion process to produce films with a number of alternating layers varying from 3 to 2049. For the first time, a semicrystalline polymer was confined by another semicrystalline polymer by nanolayering in order to develop high barrier polyamide (PA11)/polylactic acid (PLA) films without compromising thermal stability and mechanical behavior. This process allows the preparation of nanostratified films with thin layers (down to nanometric thicknesses) in which a confinement effect can be induced. The stratified structure has been investigated, and the layer thicknesses have been measured. Barrier properties were successfully correlated to the microstructure, as well as the thermal behavior, and mechanical properties. The layer continuity was fully achieved for most of the films, but some layer breakups have been observed on the film with the thinnest PLA layer (2049-layers film). Coextruding PLA with PA11 has induced an increase in PLA crystallinity (from 4 to 16%) along with an increase in thermal stability of the multilayer films without impacting PA11 properties. Gas barrier properties were driven by the PLA confined layers due to the microstructural rearrangement by increasing crystallinity, whereas water barrier properties were governed by the PA11 confining layers due to its lower water affinity. As a consequence, a decrease of water permeability (up to 11 times less permeable for the 6M film) but an increase of gas barrier properties (barrier improvement factor (BIF) of 66% for the 0M film for N2 and BIF of 36% for the 6M film for CO2 for instance) were evidenced as the layer number was increased. This study paves the way for the development of ecofriendly materials with outstanding barrier performances and highlights the importance of nonmiscible polymers adhesion at melt state and additives presence.

Producing mixed-soy protein adsorption layers on alginate microgels to controlled-release ß-carotene.

In this study, the effects of soy protein isolate (SPI) on the morphology, encapsulation efficiency, storage stability, swelling behavior, and in vitro digestion behavior of calcium alginate (CA) microgels were investigated. CA and calcium alginate-SPI (CAS) microgels with encapsulated ß-carotene were prepared by extruding a mixture of alginate and SPI using a co-extrusion technique, followed by cross-linking with Ca2+. All microgels exhibited homogeneous sizes and spherical shapes, and CAS microgels showed high levels of protein loading efficiency. The encapsulation efficiency and storage stability of ß-carotene within CAS microgels were higher than those within CA microgels. The introduction of SPI into CAS microgels resulted in a higher degree of gel size shrinkage in gastric fluid and a lower degree of swelling in intestinal fluid compared to CA microgels. In vitro digestion was conducted to investigate the effects of the addition of SPI on the release behavior of CA and CAS microgels. Results obtained showed that CAS microgels were more resistant to simulated gastric fluid than CA microgels. Cryo-scanning electron microscopy (cryo-SEM) and confocal laser scanning microscopy (CLSM) observations indicated that the release behavior was dependent on the porosity of the CA and CAS microgels, and the porosity was influenced by the concentration of SPI. This study showed that the introduction of SPI to CA microgels can lead to the development of an effective controlled release delivery system.

Improved Optimization of a Coextrusion Die with a Complex Geometry Using the Coupling Inverse Design Method.

The main challenge in a polymer coextrusion process is to have a good die design prior to the process, which can minimize the geometric errors that are caused by extrusion swell and interface motion. For this purpose, a coupling method of optimization and inverse design for a coextrusion die was studied for a medical striped catheter. In the study, the main material was thermoplastic polyurethane (TPU), and the auxiliary material was TPU filled with 30 wt% barium sulfate. An overall optimization design method was used to optimize the geometry of the extrusion die channel for the striped catheter, which had a complex geometry. In the global optimization process, the local inverse design method was used to design the inlet of the auxiliary material. The non-linear programming by quadratic Lagrangian (NLPQL) algorithm was used to obtain the optimal geometric solution of the coextrusion die runner. The experimental verification results showed that the coupling method for coextrusion die design improved the design efficiency of the coextrusion die remarkably. The value of the objective function, which was used to measure the geometric error of the product, was reduced by 72.3% compared with the initial die design.

Modeling Materials Coextrusion in Polymers Additive Manufacturing.

Material extrusion additive manufacturing enables us to combine more materials in the same nozzle during the deposition process. This technology, called material coextrusion, generates an expanded range of material properties, which can gradually change in the design domain, ensuring blending or higher bonding/interlocking among the different materials. To exploit the opportunities offered by these technologies, it is necessary to know the behavior of the combined materials according to the materials fractions. In this work, two compatible pairs of materials, namely Polylactic Acid (PLA)-Thermoplastic Polyurethane (TPU) and Acrylonitrile Styrene Acrylate (ASA)-TPU, were investigated by changing the material fractions in the coextrusion process. An original model describing the distribution of the materials is proposed. Based on this, the mechanical properties were investigated by analytical and numerical approaches. The analytical model was developed on the simplified assumption that the coextruded materials are a set of rods, whereas the more realistic numerical model is based on homogenization theory, adopting the finite element analysis of a representative volume element. To verify the deposition model, a specific experimental test was developed, and the modeled material deposition was superimposed and qualitatively compared with the actual microscope images regarding the different deposition directions and material fractions. The analytical and numerical models show similar trends, and it can be assumed that the finite element model has a more realistic behavior due to the higher accuracy of the model description. The elastic moduli obtained by the models was verified in experimental tensile tests. The tensile tests show Young's moduli of 3425 MPa for PLA, 1812 MPa for ASA, and 162 MPa for TPU. At the intermediate material fraction, the Young's modulus shows an almost linear trend between PLA and TPU and between ASA and TPU. The ultimate tensile strength values are 63.9 MPa for PLA, 35.7 MPa for ASA, and 63.5 MPa for TPU, whereas at the intermediate material fraction, they assume lower values. In this initial work, the results show a good agreement between models and experiments, providing useful tools for designers and contributing to a new branch in additive manufacturing research.

Viscoelastic Numerical Simulation Study on the Co-Extrusion Process of Tri-Composite Tire Tread.

The co-extrusion process is widely used to produce composite tire treads with better performance. This study investigated the rubber co-extrusion flow process and quality influencing factors of tri-composite tire tread through numerical simulation and experimental methods. Here, RPA 2000 rubber processing analyzer was used to carry out rheological tests on the three rubber materials, the PTT viscoelastic constitutive model was fitted, and the fitting curves were in good agreement with the test data. Then, a three-dimensional viscoelastic numerical simulation model of the tri-composite tread co-extrusion process was established using Ansys Polyflow software. The parameter evolution technique is adopted in the model establishment to improve the calculation convergence. In addition, a global remeshing function is used to avoid excessive mesh deformation. A co-extrusion experiment is conducted to verify the model's accuracy using a tri-screw extruder. The extruded tread size error rate between the experiment and simulation is less than 6%. The variation of the velocity field, pressure field and shear rate field during extrusion is analyzed, and the formation mechanism of die swell is explained simultaneously. Finally, the influence of process parameters (inflow rate and traction speed) and die structure (convergence angle and thickness) on the extruded tire tread shape and quality was investigated, which can provide theoretical guidance for improving tread quality and production efficiency. Furthermore, the numerical simulation method can assist the design of the die plate in enhancing the efficiency of the die plate design.

Investigation of the Polymer Coextrusion Process: A Review.

A review of the different coextrusion processes and the related processing problems is presented. A one-dimensional bilayer coextrusion Poiseuille flow model is first developed with Newtonian and shear-thinning rheological behaviors. A transitory computation at the convergence between the two independent polymer layers shows that stationary interface position and velocity profile are established after a short distance of the order of the die gap which justifies the validity of the 1D stationary model. This model is then applied to multilayer temperature dependent coextrusion flows which correspond to realistic industrial coextrusion conditions. Marked interface instabilities may be observed depending on the rheology of the coextruded polymers and of their flow rate ratios. Experiments point clearly out that these instabilities may be amplified along the die land. Convective stability analysis as well as direct numerical computation discriminate flow situations which amplify or damp down instabilities. These 1D models are unable to account for the complex feedblock coat-hanger die geometries. A thin layer coextrusion model is then developed, based on the Hele-Shaw lubrication approximations already used for single layer extrusion problems. It allows to predict the location of the interfaces between the different layers in the whole die, and especially at die exit. This represents a major issue in feedblock die coextrusion. These thin layer approaches are unable to address the encapsulation of one polymer by the other in these complex die geometries with important gap thicknesses. Experiments conducted in dies of square section allow identifying the dynamics of encapsulation. 3D models are required to account for this phenomenon but the management of the sticking contact at the die wall poses difficult numerical problems.