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Patient‐derived cancer organoids (PDOs) hold considerable promise for personalizing therapy selection and improving patient outcomes. However, it is challenging to generate PDOs in sufficient numbers to test therapies in standard culture platforms. This challenge is particularly acute for pancreatic ductal adenocarcinoma (PDAC) where most patients are diagnosed at an advanced stage with non‐resectable tumors and where patient tissue is in the form of needle biopsies. Here the development and characterization of microfluidic devices for testing therapies using a limited amount of tissue or PDOs available from PDAC biopsies is described. It is demonstrated that microfluidic PDOs are phenotypically and genotypically similar to the gold‐standard Matrigel organoids with the advantages of 1) spheroid uniformity, 2) minimal cell number requirement, and 3) not relying on Matrigel. The utility of microfluidic PDOs is proven by testing PDO responses to several chemotherapies, including an inhibitor of glycogen synthase kinase (GSKI). In addition, microfluidic organoid cultures are used to test effectiveness of immunotherapy comprised of NK cells in combination with a novel biologic. In summary, our microfluidic device offers considerable benefits for personalizing oncology based on cancer biopsies and may, in the future, be developed into a companion diagnostic for chemotherapy or immunotherapy treatments. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic cancer is predicted to be the second-highest cause of cancer mortality in the US by 2040. It is driven by various mutations including KRAS, TP53, SMAD4, and CDKN2A. Roughly 1 in 10 patients with pancreatic cancer have wildtype KRAS (KRASWT). We studied 27 patients with KRASWT to better understand their molecular characteristics and potential for precision medicine. Our findings revealed that KRASWT PDAC is enriched with potentially treatable genetic alterations, including those affecting the MAPK pathway, DNA repair pathway, and kinase fusion genes. One of our KRASWT PDAC patients was found to have a specific, targetable TFG-MET mutation and they responded well to treatment with a cMET inhibitor. This suggests that KRASWT PDAC has unique genetic characteristics that could be targeted with specific treatments tailored to each patient, highlighting the importance of comprehensive genetic profiling in KRASWT PDAC. Purpose: To investigate the molecular characteristics of and potential for precision medicine in KRAS wildtype pancreatic ductal adenocarcinoma (PDAC). Patients and Methods: We investigated 27 patients with KRASWT PDAC at our institution. Clinical data were obtained via chart review. Tumor specimens for each subject were interrogated for somatic single nucleotide variants, insertion and deletions, and copy number variants by DNA sequencing. Gene fusions were detected from RNA-seq. A patient-derived organoid (PDO) was developed from a patient with a MET translocation and expanded ex vivo to predict therapeutic sensitivity prior to enrollment in a phase 2 clinical trial. Results: Transcriptomic analysis showed our cohort may be stratified by the relative gene expression of the KRAS signaling cascade. The PDO derived from our patient harboring a TFG-MET rearrangement was found to have in vitro sensitivity to the multi-tyrosine kinase inhibitor crizotinib. The patient was enrolled in the phase 2 SPARTA clinical trial and received monotherapy with vebrelitinib, a c-MET inhibitor, and achieved a partial and durable response. Conclusions: KRASWT PDAC is molecularly distinct from KRASMUT and enriched with potentially actionable genetic variants. In our study, transcriptomic profiling revealed that the KRAS signaling cascade may play a key role in KRASWT PDAC. Our report of a KRASWT PDAC patient with TFG-MET rearrangement who responded to a cMET inhibitor further supports the pursuit of precision oncology in this sub-population. Identification of targetable mutations, perhaps through approaches like RNA-seq, can help enable precision-driven approaches to select optimal treatment based on tumor characteristics. [ABSTRACT FROM AUTHOR]

Environmental pollution arising from plastic waste is a major global concern. Plastic macroparticles, microparticles, and nanoparticles have the potential to affect marine ecosystems and human health. It is generally accepted that microplastic particles are not harmful or at best minimal to human health. However direct contact with microplastic particles may have possible adverse effect in cellular level. Primary polystyrene (PS) particles were the focus of this study, and we investigated the potential impacts of these microplastics on human health at the cellular level. We determined that PS particles were potential immune stimulants that induced cytokine and chemokine production in a size-dependent and concentration-dependent manner. [ABSTRACT FROM AUTHOR]

Environmental pollution caused by plastic waste is a growing global problem. Discarded plastic products and debris (microplastic particles) in the oceans detrimentally affect marine ecosystems and may impact human. Humans are exposed to plastic debris via the consumption of seafood and drinking water, contact with food packaging, or inhalation of particles. The accumulation of microplastic particles in humans has potential health risks such as cytotoxicity, hypersensitivity, unwanted immune response, and acute response like hemolysis. We investigated the cellular responses of secondary polypropylene microplastics (PP particles) of approximately ~20 μm and 25–200 μm in different condition and size to normal cells, immune cells, blood cells, and murine immune cells by cytokine analysis, ROS assay, polarization assay and proliferation assay. We found that PP particles showed low cytotoxicity effect in size and concentration manner, however, a high concentration, small sized, DMSO method of PP particles stimulated the immune system and enhanced potential hypersensitivity to PP particles via an increase in the levels of cytokines and histamines in PBMCs, Raw 264.7 and HMC-1 cells. Unlabelled Image • PP particles are able to induce pro-inflammatory cytokines such as IL-6, TNF alpha and histamine that cause local immune response. • PP particles induce pro-inflammatory cytokines in size-dependent and concentration manner. [ABSTRACT FROM AUTHOR]

We demonstrate a simple method for fabricating multilayer thin films containing ferrite (Co0.5Zn0.5Fe2O4) nanoparticles, using layer-by-layer (LbL) self-assembly. These films have microwave absorbing properties for possible radar absorbing and stealth applications. To demonstrate incorporation of inorganic ferrite nanoparticles into an electrostatic-interaction-based LbL self-assembly, we fabricated two types of films: (1) a blended three-component LbL film consisting of a sequential poly(acrylic acid)/oleic acid-ferrite blend layer and a poly(allylamine hydrochloride) layer and (2) a tetralayer LbL film consisting of sequential poly(diallyldimethylammonium chloride), poly(sodium-4-sulfonate), bPEI-ferrite, and poly(sodium-4-sulfonate) layers. We compared surface morphologies, thicknesses, and packing density of the two types of ferrite multilayer film. Ferrite nanoparticles (Co0.5Zn0.5Fe2O4) were prepared via a coprecipitation method from an aqueous precursor solution. The structure and composition of the ferrite nanoparticles were characterized by X-ray diffraction, energy dispersive X-ray spectroscopy, transmission electron microscopy, and scanning electron microscopy. X-ray diffraction patterns of ferrite nanoparticles indicated a cubic spinel structure, and energy dispersive X-ray spectroscopy revealed their composition. Thickness growth and surface morphology were measured using a profilometer, atomic force microscope, and scanning electron microscope. [ABSTRACT FROM AUTHOR]

Insulin nanoparticles (NPs) were prepared by pH-shift precipitation and a newly developed disassembly method at room temperature. Then, an electrostatic interaction-based, layer-by-layer (LbL) multilayer film incorporating insulin NPs was fabricated with poly(acrylic acid) (PAA) and poly(allylamine hydrochloride) (PAH), which is described herein as Si/(PAH/PAA) 5 (PAH/PAA-insulin NPs) n . The positively charged insulin NPs were introduced into the LbL film in the form of biocompatible PAA-insulin NP aggregates at a pH of 4.5 and were released in phosphate-buffered saline (pH 7.4), triggered by changes in the charges of the insulin molecules. In addition, the insulin-incorporated multilayer was swollen because of the different ionic environment, leading also to insulin release. Eighty percent of the insulin was released from the LBL film in the first stage of 3 h, and sustained release could be maintained in the second stage for up to 7 days in vitro , which is very critical for specific diabetic patients. These striking findings could offer novel directions to researchers in establishing insulin delivery systems for diabetic therapy and fabricating other protein nanoparticles applied to various biomedical platforms. [ABSTRACT FROM AUTHOR]

[Display omitted] • Laponite-based film on fabric can be applied for facial masks or air ventilation. • Laponite filters can strongly filter proteinaceous pathogen, S-protein. • Laponite filters have an antibacterial effect due to adsorption of copper ions. • Laponite filters can be reusable under several protein adsorption cycles. Infectious pollutants bioaerosols can threaten human public health. In particular, the indoor environment provides a unique exposure situation to induce infection through airborne transmission like SARS-CoV-2. To prevent the infection from spreading, personal protective equipment or indoor air purification is necessary. However, it has been discovered that the conventional filter can become contaminated by pathogen-containing aerosols, meaning that advanced filtering and self-sterilization systems are required. Here, we fabricate a multilayered nanocoating around the fabric using laponite (LAP) with Cu2+ ions (LAP-Cu2+ nanocoating) two contradictory functions in one system: trapping proteinaceous pathogens and antibacterial effect. Due to the strong LAP-protein interaction, albumin and spike protein (S-protein) are trapped into the fabric when proteins are sprayed using a nebulizer. The protein-blocking performance of the nanocoated fabric is 9.55-fold higher than bare fabric. These trapping capacities are retained after rinsing and repeated adsorption cycles, showing reproducibility for air filtration. Even though the protein-binding occurred, the LAP-Cu2+ fabric indicates antibacterial effect. LAP-Cu2+ fabric has an equivalent air and water transmittance rate to that of bare fabric with a stability under physiological environment. Therefore, given its excellent "Spear-and-shield" functions, the proposed LAP-Cu2+ fabric shows great potential for use in filter and masks during the viral pandemic. [ABSTRACT FROM AUTHOR]

Microplastics which are gradually and randomly decompose into small fragment by exposure of physical and biological external stress are emerging as a significant threat to the all the environments. Here, we have demonstrated the in vitro toxicity of microplastics of two different shapes. To minimize the chemical effect, polyethylene (PE), was used. PE microplastics with two different shapes were prepared, high-density PE microbeads and irregularly ground low-density PE from bulk pellets. It is hypothesized that morphological characteristics and concentration of PE microplastics could affect cellular viability, immunity, and lysis. To quantify the randomness of the microplastic shape, the edge patterns of the generated PE microplastics were converted into numerical values and analyzed using a statistical method. A 10-fold difference in curvature value was observed between microbeads and ground microfragments. To correlate shape differences to toxicology, cells were exposed to PE microplastics on the demand of toxicology studies. We found that the higher concentration and rough structure were associated with the toxicity of plastics toward cells, pro-inflammatory cytokine release, and hemolysis, even though PE is buoyant onto medium. The PE microbeads did not exhibit severe cytotoxicity at any of the tested concentrations, but induced immune and hemolysis responses at high concentrations. When comparing the toxicity of different shapes of PE microplastics, we confirmed by statistical analysis that irregular-shape plastics with sharp edges and higher curvature differences may adversely affect cells, further having possibility to human toxicity in real environment. Unlabelled Image • Investigation of in vitro toxicity on polyethylene microplastics • Statistical quantification of 1st and 2nd microplastic shape differences • Confirmation of increased immune response on 1st microplastic • Confirmation of roughness and concentration-dependent toxicity on 2nd microplastic [ABSTRACT FROM AUTHOR]

Functionalized scaffolds hold promise for stem cell therapy by controlling stem cell fate and differentiation potential. Here, we have examined the potential of a 2-dimensional (2D) scaffold to stimulate bone regeneration. Solubilized extracellular matrix (ECM) from human bone tissue contains native extracellular cues for human skeletal cells that facilitate osteogenic differentiation. However, human bone ECM displays limited mechanical strength and degradation stability under physiological conditions, necessitating modification of the physical properties of ECM before it can be considered for tissue engineering applications. To increase the mechanical stability of ECM, we explored the potential of synthetic Laponite® (LAP) clay as a counter material to prepare a 2D scaffold using Layer-by-Layer (LbL) self-assembly. The LAP and ECM multilayer nanofilms (ECM/LAP film) were successfully generated through electrostatic and protein–clay interactions. Furthermore, to enhance the mechanical properties of the ECM/LAP film, application of a NaCl solution wash step, instead of deionized water following LAP deposition resulted in the generation of stable, multi-stacked LAP layers which displayed enhanced mechanical properties able to sustain human skeletal progenitor cell growth. The ECM/LAP films were not cytotoxic and, critically, showed enhanced osteogenic differentiation potential as a consequence of the synergistic effects of ECM and LAP. In summary, we demonstrate the fabrication of a novel ECM/LAP nanofilm layer material with potential application in hard tissue engineering. Unlabelled Image • ECM/Laponite® multilayer nanofilm was successfully generated via electrostatic interaction. • Washing method affected the orientation of Laponite® particles. • Depositing more Laponite® particles within ECM/Laponite® nanofilm improved mechanical properties. • ECM/Laponite® nanofilm was able to uptake more BMP-2 molecules than single material drop-cased films. • Re-structured nanofilm by salt washing facilitated osteogenic differentiation potential of human skeletal progenitor cells. [ABSTRACT FROM AUTHOR]

• In vitro toxicology PS microfragments to mimic 2nd microplastics was investigated. • PS microfragments increased acute inflammation, cell death by chemical toxicity. • PS microfragments induced cell membrane damage caused by physical toxicity. • Roughness of PS microfragments were quantitatively analyzed to correlate toxicity. With the increase in plastic production, a variety of toxicological studies on microplastics have been conducted as microplastics can be accumulated in the human body and cause unknown disease. However, previous studies have mainly assessed the toxicity of sphere-type microbeads, which may differ from randomly-shaped microplastics in a real environment. Here, we conducted in vitro toxicology analysis for randomly-shaped microplastics based on the hypotheses that (1) physical cytotoxicity is affected by nano-/micro-size roughness in polystyrene (PS) microfragments and (2) chemical toxicity is caused by chemical reagents from microplastics. We confirmed that the PS microfragments increased the acute inflammation of immune cells 20 times than control, the production of reactive oxygen species, and cell death of fibroblasts and cancer cells by releasing chemical reagents. In addition, when the PS microfragments were in direct contact with fibroblasts and red blood cells, the physical stress caused by them resulted in lactose dehydrogenase and hemoglobin release, respectively, due to cell membrane damage and hemolysis. This phenomenon was amplified when the concentration and roughness of the microfragments increased. Moreover, we quantitatively analyzed roughness differences between microplastics, which revealed a strong relationship between the physical damage of cells and the roughness of microplastics. [ABSTRACT FROM AUTHOR]

This study demonstrates the possibility of developing a rapidly degradable chitosan-based multilayer film for controlled drug release. The chitosan (CHI)-based multilayer nanofilms were prepared with three different types of anions, hyaluronic acid (HA), alginic acid (ALG) and tannic acid (TA). Taking advantage of the Layer-by-Layer (LBL) assembly, each multilayer film has different morphology, porosity and thickness depending on their ionic density, molecular structure and the polymer functionality of the building blocks. We loaded drug models such as doxorubicin hydrochloride (DOX), fluorescein isothiocyanate (FITC) and ovalbumin (Ova) into multilayer films and analyzed the drug loading and release profiles in phosphate-buffered saline (PBS) buffer with the same osmolarity and temperature as the human body. Despite the rapid degradation of the multilayer film in a high pH and salt solution, the drug release profile can be controlled by increasing the functional group density, which results in interaction with the drug. In particular, the abundant carboxylate groups in the CHI/HA film increased the loading amount of DOX and decreased rapid drug release. The TA interaction with DOX via electrostatic interaction, hydrogen bonding and hydrophobic interaction showed a sustained drug release profile. These results serve as principles for fabricating a tailored multilayer film for drug delivery application. [ABSTRACT FROM AUTHOR]

Surface modification involves developing a versatile thin film by combining the physical, chemical, or biological characteristics of the functional materials and can facilitate controlling material for desirable aims. Layer-by-layer (LbL) assembly can be used to create materials with controlled thicknesses and morphologies, diverse functionalities, and unique structures on any surface. However, despite the advantages of the LbL fabrication technique, there are limits to its application because it is a time-consuming process and has difficulty controlling the shape of nanofilms. In addition, controlling the lateral organization is difficult because the preparation methods are based on one-pot self-assembly. In this study, a multilayered fabrication system is developed for the high-throughput LbL assembly of nanofilms through inkjet printing. With various types of materials from synthetic polymer to graphene oxide to natural polymer and protein, the approach can tune the preparation of nanoscale multilayers with desired structures and shapes for specific applications on various substrates, including a silicon wafer, quartz glass, and cellulose-based paper. [ABSTRACT FROM AUTHOR]

[Display omitted] • hiPSCs were utilized to study human developmental toxicity of nanoplastics. • Excessive amounts of nanoplastics were internalized in hiPSCs within 48 h. • Nanoplastics reduced viable cells and their self-renewal capacity in a short time. • No serious toxicity was caused by nanoplastics in long-term differentiation tests. The threat to humans from nanoplastics (NPs) is increasing invisibly. Nowadays, many people are concerned about human safety and health, but few are reported about the effects of NP on humans. To overcome the limitations in human studies, human induced pluripotent stem cells (hiPSCs) were used as an optimal platform to investigate toxicity and subtle changes in differentiation caused by intracellular NPs accumulation for a long-term. Negatively charged polystyrene nanoplastics (PS NPs) were used to exclude acute toxic issues of surface charge and investigate the impact of the NP's size and nature during bioaccumulation. Intracellular observations revealed that excessive amounts of NPs were internalized into single cells and colonies within 48 h. Substantial growth inhibition and a slight reduction in self renewal capacity of hiPSCs occurred with respect to internalized NPs. Unexpectedly, the accumulated NPs in hiPSC did not exhibit chronic toxicity or adversely affect differentiation for 14 days. [ABSTRACT FROM AUTHOR]

Carbon capture and storage (CCS) is the process of capturing carbon dioxide (CO 2) produced from the combustion of fossil fuels. CO 2 is a major contributor to global warming and should be removed after combustion. The objective of this research is to design a CO 2 capture membrane consisting of tertiary-amine-stabilized gold nanoparticles (Au NPs), graphene oxide (GO), and polyelectrolytes. A high CO 2 capture ability is most important for designing a CO 2 capture membrane that can maintain a high gas permeance. Multilayer films were fabricated using an automatic spray-assisted layer-by-layer (LbL) machine. The polar affinity of polyelectrolytes assisted the CO 2 capture of tertiary amines. The randomly oriented and loosely stacked GO layers not only helped align the Au NPs in the polyelectrolyte matrix, but also helped maintain the permeance of N 2. Thus, we successfully fabricated a CO 2 adsorptive multilayer nanocoating with a maximum CO 2 /N 2 selectivity of 48.48 while maintaining the N 2 permeance at 1204.25 GPU. Image 1 • Spray-assisted LbL multilayer films were fabricated by electrostatic interactions. • The polar affinity of the polyelectrolytes aided in the CO 2 capture of DMAP-Au NPs. • The GO layers helped align the DMAP-Au NPs in the polyelectrolyte matrix. • The randomly oriented and loosely packed GOs helped maintain the permeance of N 2. • The maximum N 2 /CO 2 selectivity of 48.48 was achieved. [ABSTRACT FROM AUTHOR]

Cell surface modification has been extensively studied to enhance the efficacy of cell therapy. Still, general accessibility and versatility are remaining challenges to meet the increasing demand for cell-based therapy. Herein, we present a facile and universal cell surface modification method that involves mild reduction of disulfide bonds in cell membrane protein to thiol groups. The reduced cells are successfully coated with biomolecules, polymers, and nanoparticles for an assortment of applications, including rapid cell assembly, in vivo cell monitoring, and localized cell-based drug delivery. No adverse effect on cellular morphology, viability, proliferation, and metabolism is observed. Furthermore, simultaneous coating with polyethylene glycol and dexametha-sone-loaded nanoparticles facilitates enhanced cellular activities in mice, overcoming immune rejection. [ABSTRACT FROM AUTHOR]

Methods for creating unique superhydrophilic interfaces by means of layer-by-layer (LbL) assembly have been demonstrated, and such interfaces have been used extensively in a variety of practical applications. Further, fabricating multifunctional superhydrophilic coatings using low-cost, nontoxic, environment-friendly, and plentiful materials from biological resources is highly desirable. Herein, superhydrophilic coatings with a highly jagged surface morphology were synthesized based on the electrostatic-interaction- or hydrogen-bonding-based LbL assembly of the biotic materials chitosan (CHI) and rice husk ash (RHA) nanosilica, which are abundantly available in nature. The synthesized multilayered (CHI/RHA nanosilica) n films were highly transparent and resisted fogging, frosting, and biofouling. Specifically, given the water-absorbing capability of the films, they showed excellent antifogging and antifrosting properties even under aggressive fogging and frosting conditions. Further, the as-prepared superhydrophilic multilayered films, which had a rough surface structure at the micro- and nanoscale, showed potential in reducing the attachment of proteins and various microorganisms, significantly preventing the phenomenon of biofouling in stagnant liquids. Hence, this work provides a new route for assembling superwetting coatings from cost-effective natural materials for use in industrial applications. [ABSTRACT FROM AUTHOR]

The potential health hazards of particulates, such as micro/nano-sized plastics and carbon materials have recently received extensive attention. However, their toxicological properties in association with stem cell differentiation is still relatively unexplored. In this study, we elucidated the cytotoxic effects of 2D graphene oxide (GO), in relation to differentiation of human induced pluripotent stem cells (hiPSCs). Supplementation of GO to hiPSCs demonstrated uptake of GO through the plasma membrane and intracellular accumulation was observed. Increasing the concentration of GO led to reduced viability and increased likelihood of hiPSC colony detachment. Moreover, treatment of GO resulted in significant loss in pluripotency markers, OCT-4 and NANOG. In particular, when hiPSCs were cultured with GO in cardiomyocyte induction medium, upregulation of cardiomyocyte marker, NKX2.5 , along with observation of early triggering of differentiation were observed. Taken together, our results highlight the risk in the uptake and accumulation of GO on the stem cell development by unwanted loss in pluripotency and accelerated initiation of differentiation. [Display omitted] • GO attaches on plasma membrane and accumulates in cytoplasm of hiPSCs. • Short term exposure to GO reduced cell viability and detachment of hiPSC colony. • GO leads to loss in pluripotency and unwanted differentiation of hiPSC. • GO initiates early triggering of differentiation. [ABSTRACT FROM AUTHOR]

• Polysilsesquioxanes with siloxane network and antibacterial chains are synthesized. • The polysilsesquioxanes have a ladder-like structure suitable for durable coating. • The polysilsesquioxanes are easily coated on dental materials via self-assembly. • The coated dental materials show strong antibacterial effect for various bacteria. • Coatings with nanoscale thickness improve the mechanical strength of the materials. Significant progress has been made in endowing biomedical materials with antibacterial properties. However, the commercialization of these systems still poses various practical challenges. In this study, we report a facile technique for the preparation of practical and efficient antibacterial coatings based on well-defined polysilsesquioxane (PSQ) structures containing quaternary ammonium cation and long alkyl chains. PSQ is a hybrid material containing organic groups within a flexible and robust siloxane network, and can be endowed with different functions according to the synthetic conditions employed in the sol-gel process. However, depending on the synthetic precursors, a non-uniform PSQ structure can be formed, which limits the functions and stability of the resulting material. Accordingly, we synthesized PSQs with homogeneously distributed quaternary ammonium cation and long alkyl chains, using optimized synthetic conditions. The PSQs were coated on devices via self-assembly, and the thickness of the coating could be controlled from the nano- to the microscale depending on the deposition time. All coated substrates exhibited more than 60% bacterial reduction rate for three types of bacteria compared to the control groups. The coating inhibited the activity of the membrane adhesins, which prevented the strong adhesion of bacteria to the surfaces. Furthermore, the coated substrates also showed an increased mechanical strength in bulk strength tests. The nanoscale coatings notably increased the hardness of the dental substrates more than twofold compared to that of the control. The easy preparation and efficacy of the PSQs highlight their applicability as antibacterial coatings in various medical devices requiring high durability. [ABSTRACT FROM AUTHOR]