Biointerphases最新文献

Interactions between molecules in the synovial fluid and the cartilage surface may play a vital role in the formation of adsorbed films that contribute to the low friction of cartilage boundary lubrication. Osteoarthritis (OA) is the most common degenerative joint disease. Previous studies have shown that in OA-diseased joints, hyaluronan (HA) not only breaks down resulting in a much lower molecular weight (MW), but also its concentration is reduced ten times. Here, we have investigated the structural changes of lipid-HA complexes as a function of HA concentration and MW to simulate the physiologically relevant conditions that exist in healthy and diseased joints. Small angle neutron scattering and dynamic light scattering were used to determine the structure of HA-lipid vesicles in bulk solution, while a combination of atomic force microscopy and quartz crystal microbalance was applied to study their assembly on a gold surface. We infer a significant influence of both MW and HA concentrations on the structure of HA-lipid complexes in bulk and assembled on a gold surface. Our results suggest that low MW HA cannot form an amorphous layer on the gold surface, which is expected to negatively impact the mechanical integrity and longevity of the boundary layer and could contribute to the increased wear of the cartilage that has been reported in joints diseased with OA.

Fibril curvature is bioinstructive to attached cells. Similar to natural healthy tissues, an engineered extracellular matrix can be designed to stimulate cells to adopt desired phenotypes. To take full advantage of the curvature control in biomaterial fabrication methodologies, an understanding of the response to fibril subcellular curvature is required. In this work, we examined morphology, signaling, and function of human cells attached to electrospun nanofibers. We controlled curvature across an order of magnitude using nondegradable poly(methyl methacrylate) (PMMA) attached to a stiff substrate with flat PMMA as a control. Focal adhesion length and the distance of maximum intensity from the geographic center of the vinculin positive focal adhesion both peaked at a fiber curvature of 2.5 μm^-1 (both ∼2× the flat surface control). Vinculin experienced slightly less tension when attached to nanofiber substrates. Vinculin expression was also more affected by a subcellular curvature than structural proteins α-tubulin or α-actinin. Among the phosphorylation sites we examined (FAK397, 576/577, 925, and Src416), FAK925 exhibited the most dependance on the nanofiber curvature. A RhoA/ROCK dependance of migration velocity across curvatures combined with an observation of cell membrane wrapping around nanofibers suggested a hybrid of migration modes for cells attached to fibers as has been observed in 3D matrices. Careful selection of nanofiber curvature for regenerative engineering scaffolds and substrates used to study cell biology is required to maximize the potential of these techniques for scientific exploration and ultimately improvement of human health.

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is used widely throughout industrial and academic research due to the high information content of the chemically specific data it produces. Modern ToF-SIMS instruments can generate high mass resolution data that can be displayed as spectra and images (2D and 3D). This enables determining the distribution of molecules across and into a surface and provides access to information not obtainable from other methods. With this detailed chemical information comes a steep learning curve in how to properly acquire and interpret the data. This Tutorial is aimed at helping ToF-SIMS users to plan for and collect ToF-SIMS data. The second Tutorial in this series will cover how to process, display, and interpret ToF-SIMS data.

Gastrointestinal tract (GIT) malignancies are an important public health problem considering the increased incidence in recent years and the high morbidity and mortality associated with it. GIT malignancies constitute 26% of the global cancer incidence burden and 35% of all cancer-related deaths. Gastrointestinal cancers are complex and heterogenous diseases caused by the interplay of genetic and environmental factors. The tumor microenvironment (TME) of gastrointestinal tract carcinomas is dynamic and complex; it cannot be recapitulated in the basic two-dimensional cell culture systems. In contrast, three-dimensional (3D) in vitro models can mimic the TME more closely, enabling an improved understanding of the microenvironmental cues involved in the various stages of cancer initiation, progression, and metastasis. However, the heterogeneity of the TME is incompletely reproduced in these 3D culture models, as they fail to regulate the orientation and interaction of various cell types in a complex architecture. To emulate the TME, 3D bioprinting has emerged as a useful technique to engineer cancer tissue models. Bioprinted cancer tissue models can potentially recapitulate cancer pathology and increase drug resistance in an organ-mimicking 3D environment. In this review, we describe the 3D bioprinting methods, bioinks, characterization of 3D bioprinted constructs, and their application in developing gastrointestinal tumor models that integrate their microenvironment with different cell types and substrates, as well as bioprinting modalities and their application in therapy and drug screening. We review prominent studies on the 3D bioprinted esophageal, hepatobiliary, and colorectal cancer models. In addition, this review provides a comprehensive understanding of the cancer microenvironment in printed tumor models, highlights current challenges with respect to their clinical translation, and summarizes future perspectives.

Polyethersulfone (PES) membranes are widely used in medical devices, especially intravascular devices such as intravascular bioartificial pancreases. In the current work, the pure PES and PES-pyrolytic carbon (PyC) composite membranes were synthesized and permeability studies were conducted. In addition, the cytocompatibility and hemocompatibility of the pure PES and PES-PyC membranes were investigated. These materials were characterized using peripheral blood mononuclear cell (PBMC) activation, platelet activation, platelet adhesion, ß-cell viability and proliferation, and ß-cell response to hyperglycemia. The results showed that platelet activation decreased from 87.3% to 27.8%. Any alteration in the morphology of sticking platelets was prevented, and the number of attached platelets decreased by modification with PyC. The 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay corroborated that PBMC activation was encouraged by the PyC-modified PES membrane surface. It can be concluded that PES-modified membranes show higher hemocompatibility than pure PES membranes. ß-cells cultured on all the three membranes displayed a lower rate of proliferation although the cells on the PES-PyC (0.1 wt. %) membrane indicated a slightly higher viability and proliferation than those on the pure PES and PES-PyC (0.05 wt. %) membranes. It shows that the PES-PyC (0.1 wt. %) membrane possesses superior cytocompatibility over the other membranes.

Tumor invasion is likely driven by the product of intrinsic and extrinsic stresses, reduced intercellular adhesion, and reciprocal interactions between the cancer cells and the extracellular matrix (ECM). The ECM is a dynamic material system that is continuously evolving with the tumor microenvironment. Although it is widely reported that cancer cells degrade the ECM to create paths for migration using membrane-bound and soluble enzymes, other nonenzymatic mechanisms of invasion are less studied and not clearly understood. To explore tumor invasion that is independent of enzymatic degradation, we have created an open three-dimensional (3D) microchannel network using a novel bioconjugated liquid-like solid (LLS) medium to mimic both the tortuosity and the permeability of a loose capillary-like network. The LLS is made from an ensemble of soft granular microgels, which provides an accessible platform to investigate the 3D invasion of glioblastoma (GBM) tumor spheroids using in situ scanning confocal microscopy. The surface conjugation of the LLS microgels with type 1 collagen (COL1-LLS) enables cell adhesion and migration. In this model, invasive fronts of the GBM microtumor protruded into the proximal interstitial space and may have locally reorganized the surrounding COL1-LLS. Characterization of the invasive paths revealed a super-diffusive behavior of these fronts. Numerical simulations suggest that the interstitial space guided tumor invasion by restricting available paths, and this physical restriction is responsible for the super-diffusive behavior. This study also presents evidence that cancer cells utilize anchorage-dependent migration to explore their surroundings, and geometrical cues guide 3D tumor invasion along the accessible paths independent of proteolytic ability.

Pathogenic bacteria represent a severe threat to global public health, particularly with the growing rate of antibiotic resistance, and, therefore, indicate a critical need for developing efficient sensing platforms. Liposome-based sensors are collocating interest due to their intrinsic fusogenic ability to fuse with the outer membrane of bacteria. However, the lack of a conducting property limits their applicability for developing biosensing platforms. In this study, we report conjugation of liposomes with reduced graphene oxide (rGO) for fabricating a rapid and sensitive biosensor for electrochemical detection of Escherichia coli (E. coli). The large surface area of rGO facilitated binding of liposomes with their surface, and the intrinsic electrical and biocompatible properties assisted electrochemical sensing of bacteria. The electrochemical response of the liposome and the rGO-liposome coated electrode shows nonconducting and conducting characteristics, respectively. A significant change in the peak current of differential pulse voltammetry with the gradual variation of bacterial density in the electrolyte was observed for the glassy carbon electrode rGO-liposome (GCE-L-rGO) surface only. The detection sensitivity of GCE-L-rGO sensors was ∼26 μA/106 cells per ml of electrolyte for varying cell densities from 3 × 103 to 3 × 104 cells/ml. The proposed sensing technique can serve as an alternative to conventional methodologies for rapid and in situ detection of bacterial load in different samples, laying the foundation for new applications in clinical diagnostics.

In this study, WE43 magnesium alloy was produced by the powder metallurgy method. Microstructural analyses of the produced samples were carried out using the scanning electron microscopy method. X-ray fluorescence, energy dispersive x-ray (EDS) analysis, and hardness tests were also implemented to investigate the physical and chemical properties of the alloys. The volumetric hardness was measured to be approximately 53 HV. The microstructural analysis and EDS results indicated the presence of Mg24Y5 and Mg41Nd5 phases in the alloys. Reciprocating-type experiments were carried out in dry and corrosive environments to evaluate the wear resistance. Hanks's solution containing 2% g/l glucose was used as the corrosive environment. Gluconic acid resulting from the oxidation of glucose in the Hanks's solution formed a new thin layer on the alloy surface, which was observed in the worn surface images. The formation of the thin film on the alloy surface resulted in an increase in wear resistance by 37%. The results unraveled the potential of the WE43 alloys as implant materials in areas in contact with glucose.

Oily wastewater discharged by industrial development is an important factor causing water pollution. Membrane separation technology has the advantages of low cost, simple operation, and high efficiency in the treatment of oily wastewater. However, membrane materials are easily eroded by microorganisms during long-term storage or use, thereby resulting in reduced separation efficiency. Herein, a zeolite imidazole skeleton-8@silver nanocluster composite polyacrylonitrile (ZIF-8@AgNCs/PAN) nanofibrous membrane was fabricated by electrospinning and in situ growth technology. The surface chemistry, morphology, and wettability of the composite membranes were characterized. The carboxyl groups on the surface of hydrolyzed PAN nanofibers, which can be complexed with zinc ions (Zn2+), are utilized as growth sites for porous metal organic frameworks (ZIF-8). Meanwhile, AgNCs are loaded into ZIF-8 to achieve stable hybridization of ZIF-8@AgNCs and nanofibers. The loading quantity of ZIF-8@AgNCs, which can dominantly affect the surface roughness and the porosity of the membranes, is regulated by the feeding amount of AgNCs. The ZIF-8@AgNCs/PAN membrane achieves effective oil-water separation with high separation efficiency toward petroleum ether-in-water emulsion (98.6%) and permeability (62 456 ± 1343 Lm-2 h-1 bar-1). Furthermore, the ZIF-8@AgNCs/PAN membrane possesses high antibacterial activity against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus), which is beneficial for the long-term storage and use of the membrane.

In beam-based ionization methods, the substrate plays an important role on the desorption mechanism of molecules from surfaces. Both the specific orientation that a molecule adopts at a surface and the strength of the molecule-surface interaction can greatly influence desorption processes, which in turn will affect the ion yield and the degree of in-source fragmentation of a molecule. In the beam-based method of secondary ion mass spectrometry (SIMS), in-source fragmentation can be significant and molecule specific due to the hard ionization method of using a primary ion beam for molecule desorption. To investigate the role of the substrate on orientation and in-source fragmentation, we have used atomistic simulations-molecular dynamics in combination with density functional theory calculations-to explore the desorption of a sphingolipid (palmitoylsphingomyelin) from a model surface (gold). We then compare SIMS data from this model system to our modeling findings. Using this approach, we found that the combined adsorption and binding energy of certain bonds associated with the headgroup fragments (C₃H₈N⁺, C₅H₁₂N⁺, C₅H₁₄NO⁺, and C₅H₁₅PNO₄ ⁺) was a good predictor for fragment intensities (as indicated by relative ion yields). This is the first example where atomistic simulations have been applied in beam-based ionization of lipids, and it presents a new approach to study biointerfacial lipid ordering effects on SIMS imaging.