Hydration Mechanism in Blood-Compatible Polymers Undergoing Phase Separation.

Interactions involving intermediate water are crucial for the design of novel blood-compatible materials. Herein, we use a combination of atomic force microscopy, quartz crystal microbalance measurements, and soft X-ray emission spectroscopy to investigate the local hydrogen-bonded configuration of water on blood-compatible poly(2-methoxyethyl acrylate) and non-blood-compatible poly(n-butyl acrylate) grafted on a gold substrate. We find that the initially incorporated water induces polymer-dependent phase separation, facilitating further water uptake. For the blood-compatible polymer, tetrahedrally coordinated water coexists with water adsorbed on C═O groups in low-density regions of the grafted polymer surface, providing a scaffold for the formation of intermediate water. The amount of intermediate water is determined by the type of functional groups, local polymer configuration, and polymer morphology. Thus, blood compatibility is governed by the complex water/polymer interactions.

Effect of Branching Degree of Dendritic Polyglycerols on Plasma Protein Adsorption: Relationship between Hydration States and Surface Morphology.

This study focuses on dendritic glycerols and investigates the construction of biocompatible surfaces by understanding how differences in the branching of these molecules change the interactions with the biological components. The two molecules, polyglycerol dendrimer (PGD), which has a completely branched structure, and hyperbranched polyglycerol (HPG), which has an incompletely branched structure, are compared and the differences in branching are evaluated. It is shown that PGD has a little bit more intermediate water than HPG, which reflects the differences in the branching. The effect of surface state on the adsorption of the plasma proteins, human serum albumin (HSA), fibrinogen (Fib), and fibronectin (FN), is discussed by modifying a glass surface using these molecules with different hydration states. The adsorption of HSA decreases to several percent for HPG and 10% for PGD compared to unmodified substrate. Although the adsorption of Fib decreases to 5% for HPG, an increase to 150% is observed for PGD. Since this specific Fib adsorption observed only onto PGD is suppressed in the cases of a mixed solution of HSA and Fib or sequentially using HSA solution and then Fib solution, it is thought that the Vroman effect is suppressed on the PGD-modified surface. Furthermore, when AFM measurements are performed in PBS to understand the surface roughness, PGD is found to be more highly non-uniform. Because of this, the nanometer scale roughness that is significantly observed only on the PGD-modified surface is thought to have an effect on the characteristic adsorption properties of Fib. Thus, although both PGD and HPG with different branching have intermediate water, the proportion differs between PGD and HPG. Therefore, it is found that differences occur in the plasma protein adsorption mechanisms depending on the coordinates and density of hydroxyl groups within the molecules.

[A Case of Multiple Hepatic Metastases after Surgery for Low Differentiated Mucous Cancer of Sigmoid Colon with Notable Mesenteric Infiltration in Which Chemotherapy Was Effective].

Mucinous adenocarcinoma of the colon occasionally develops from the submucosa, depending on the pattern of onset; therefore, in many cases, it is already advanced at the time of diagnosis. This type of cancer is known to have a poor prognosis. We report the case of a 59-year-old woman who presented with abdominal pain on defecation for 1 month. A mass was palpable in the lower part of her abdomen. On computed tomography(CT), an extrinsic mass was seen in the sigmoid colon, and lower gastrointestinal endoscopy findings suggested an invasive tumor originating from another organ outside the intestinal wall. A high level of the tumor marker CEA(40.8 ng/mL)was observed. No findings suggestive of malignancy were present on biopsy examination, Colorectal cancer was suspected, for which a sigmoidectomy was performed. On histopathological examination, though there was little to indicate a primary colon tumor on HE staining, due to strong CDX2 positivity it was suspected to be an intestinal-type adenocarcinoma. The final clinical diagnosis was unclassifiable, poorly differentiated, mucinous adenocarcinoma of the colon. Multiple liver metastases appeared 4 months postoperatively, which were treated with XELOX plus BV and FOLFIRI plus BV. CT evaluation 24 months postoperatively showed a complete response radiographically. This case of mucinous adenocarcinoma of the colon, in which chemotherapy was successful and long-term survival of 5 years and 2 months was achieved postoperatively, is reported together with a discussion of the literature.

Effect of the Molecular Weight of Poly(2-methoxyethyl acrylate) on Interfacial Structure and Blood Compatibility.

The blood-compatible polymer poly(2-methoxyethyl acrylate) (PMEA) is composed of nanometer-scale interfacial structures because of the phase separation of the polymer and water at the PMEA/phosphate-buffered saline (PBS) interface. We synthesized PMEA with four different molecular weights (19, 30, 44, and 183 kg/mol) to investigate the effect of the molecular weight on the interfacial structures and blood compatibility. The amounts of intermediate water and fibrinogen adsorption were not affected by the molecular weight of PMEA. In contrast, the degree of denaturation of adsorbed fibrinogen molecules and platelet adhesion increased as the molecular weight increased. Atomic force microscopy observation revealed that the domain size of the microphase separation structures observed at the PMEA/PBS interfaces drastically (nearly 3 times in the mean area of a domain) changed with the molecular weight. PMEA with a lower molecular weight showed a smaller polymer-rich domain size, as expected on the basis of the microphase separation of polymer-rich and water-rich domains. The small domain size suppressed the aggregation and denaturation of adsorbed fibrinogen molecules because only a few fibrinogen molecules were adsorbed on a domain. Increasing the domain size enhanced the denaturation of adsorbed fibrinogen molecules. Controlling the interfacial structures is crucial for ensuring the blood compatibility of polymer interfaces.

Donor-Acceptor Core-Shell Nanoparticles and Their Application in Non-Volatile Transistor Memory Devices.

Donor-acceptor crosslinked poly[poly(ethylene glycol) methyl ether-methacrylate]-block-poly[1,1'-bis(2-ethylpentyl)-6-methyl-6'-(5-methyl-3-vinylthiophen-2-yl)-[3,3'-biindoline]-2,2'-dione] (poly(PEGMA)m -b-poly(VTIID)n ) nanoparticles with various vinylthiophene donor/isoindigo acceptor ratios are synthesized successfully. The prepared nanoparticles have uniform sizes and well-defined core-shell nanostructures. The intramolecular charge transfer is effectively enhanced due to the incorporation of acceptor groups after the crosslinking reaction. A transistor memory device is assembled using the synthesized polymer and has nonvolatile flash-type memory and amphiphilic trapping behavior. The optimized devices exhibit a significant memory window of approximately 38 V, a retention ability of over 104 s, and an endurance of at least 100 cycles. This study examines multiple applications of crosslinked core-shell nanoparticles, which demonstrates their promise as charge-storage dielectric materials for use in organic memory devices.

Wetting transition from the Cassie-Baxter state to the Wenzel state on textured polymer surfaces.

The wetting transition from the Cassie-Baxter state to the Wenzel state on textured surfaces was investigated. Nano- to microscale hexagonal pillared lattices were prepared by nanoimprint lithography on fluorinated cycloolefin polymer substrates. The transition was clearly observed for water and some ionic liquids through contact angle measurements and optical microscopy. A simple model clearly demonstrated that the energy barrier in the wetting transition from the Cassie-Baxter state to the Wenzel state was dominated by the competition between the energy barrier and external forces, particularly the Laplace pressure in the present case.

Spreading and structuring of water on superhydrophilic polyelectrolyte brush surfaces.

The wetting behavior of superhydrophilic polyelectrolyte brushes was investigated. Reflection interference contrast microscopy demonstrated that the contact angles of water on the polyelectrolyte brushes were extremely low but remained finite in the range of <3°. The presence of water molecules was evident, even outside the macroscopic water droplet. These water molecules were confined to the thin brush layers and contained a highly ordered hydrogen bond network, which was identified as structural water. The presence of the thin film and the structural water changed the surface energies, which prevented the complete wetting of the surface.

Measurement of the electrostatic interaction between polyelectrolyte brush surfaces by optical tweezers.

We demonstrated an optical tweezers method to measure the electrostatic interaction between the strong polyelectrolyte brushes, poly(2-(methacryloyloxy)ethyltrimethylammonium chloride) (PMTAC), grafted on silica particles in aqueous media. The weak electrostatic interaction was successfully detected with a resolution of less than 0.1 µN m(-1). The apparent Debye length, including the charge distribution in the polymer brush and the surface potential, decreased as the salt concentration in the medium increased. The experimentally obtained surface charge density was much smaller than that estimated from the amount of polyelectrolyte on the surface. Furthermore, the dissociation of ionic groups was enhanced by decreasing the grafting density of the polyelectrolyte brush. The results suggest that the majority of chloride counterions was immobilized in the dense polyelectrolyte brush layer to neutralize the high charge density.

Altering the bio-inert properties of surfaces by fluorinated copolymers of mPEGMA.

Hydrophilic materials display "bio-inert properties", meaning that they are less recognized as foreign substances by proteins and cells. Such materials are often water soluble; therefore, one general approach to enable the use of these materials in various applications deals with copolymerizing hydrophilic monomers with hydrophobic ones to facilitate such resulting copolymers water insoluble. However, reducing the hydrophilic monomer amount may reduce the bio-inert properties of the material. The decrease in bio-inert properties can be avoided when small amounts of fluorine are used in copolymers with hydrophilic monomers, as presented in this article. Even in small quantities (7.9 wt%), the fluorinated monomer, 1,1,1,3,3,3-hexafluoropropan-2-yl 2-fluoroacrylate (FAHFiP), contributed to the improved hydrophobicity of the polymers of the long side-chain poly(ethylene glycol) methyl ether methacrylate (mPEGMA) bearing nine ethylene glycol units turning them water insoluble. As evidenced by the AFM deformation image, a phase separation between the FAHFiP and mPEGMA domains was observed. The copolymer with the highest amount of the fluorinated monomer (66.2 wt%) displayed also high (82 %) FAHFiP amount at the polymer-water interface. In contrast, the hydrated sample with the lowest FAHFiP/highest mPEGMA amount was enriched of three times more hydrophilic domains at the polymer-water interface compared to that of the sample with the highest FAHFiP content. Thus, by adding a small FAHFiP amount to mPEGMA copolymers, water insoluble in the bulk too, could be turned highly hydrophilic at the water interface. The high content of intermediate water contributed to their excellent bio-inert properties. Platelet adhesion and fibrinogen adsorption on their surfaces were even more decreased as compared to those on poly(2-methoxyethyl acrylate), which is typically used in medical devices.

X-ray photon correlation spectroscopy using a fast pixel array detector with a grid mask resolution enhancer.

The performance of a fast pixel array detector with a grid mask resolution enhancer has been demonstrated for X-ray photon correlation spectroscopy (XPCS) measurements to investigate fast dynamics on a microscopic scale. A detecting system, in which each pixel of a single-photon-counting pixel array detector, PILATUS, is covered by grid mask apertures, was constructed for XPCS measurements of silica nanoparticles in polymer melts. The experimental results are confirmed to be consistent by comparison with other independent experiments. By applying this method, XPCS measurements can be carried out by customizing the hole size of the grid mask to suit the experimental conditions, such as beam size, detector size and sample-to-detector distance.

Wettability and antifouling behavior on the surfaces of superhydrophilic polymer brushes.

The surface wettabilities of polymer brushes with hydrophobic and hydrophilic functional groups were discussed on the basis of conventional static and dynamic contact angle measurements of water and hexadecane in air and captive bubble measurements in water. Various types of high-density polymer brushes with nonionic and ionic functional groups were prepared on a silicon wafer by surface-initiated atom-transfer radical polymerization. The surface free energies of the brushes were estimated by Owens-Wendt equation using the contact angles of various probe liquids with different polarities. The decrease in the water contact angle corresponded to the polarity of fluoroalkyl, hydroxy, ethylene oxide, amino, carboxylic acid, ammonium salt, sulfonate, carboxybetaine, sulfobetaine, and phosphobetaine functional groups. The poly(2-perfluorooctylethyl acrylate) brush had a low surface free energy of approximately 8.7 mN/m, but the polyelectrolyte brushes revealed much higher surface free energies of 70-74 mN/m, close to the value for water. Polyelectrolyte brushes repelled both air bubbles and hexadecane in water. Even when the silicone oil was spread on the polyelectrolyte brush surfaces in air, once they were immersed in water, the oil quickly rolled up and detached from the brush surface. The oil detachment behavior observed on the superhydrophilic polyelectrolyte brush in water was explained by the low adhesion force between the brush and the oil, which could contribute to its excellent antifouling and self-cleaning properties.

Observing the repulsion layers on blood-compatible polymer-grafted interfaces by frequency modulation atomic force microscopy.

Blood-compatible materials that do not promote reactions in contact with human blood are required to support emerging medical technologies. The interfaces of poly(2-methoxyethyl acrylate) (PMEA), a blood-compatible polymer, and its analogues were investigated by frequency modulation atomic force microscopy (FM-AFM). The grafted polymers exhibited phase separation into polymer-rich and water-rich domains. Thin repulsive layers of hydrated polymer chains were observed in the water-rich domains of the blood-compatible polymers; on the other hand, such layers were not observed for the non-blood-compatible polymers. We report for the first time that FM-AFM enables characteristic repulsive layers composed of hydrated polymer chains in water-rich domains to be observed, which is a significant design factor for blood-compatible polymers.

Nanoscopic analyses of cell-adhesive protein adsorption on poly(2-methoxyethyl acrylate) surfaces.

Regulation of protein adsorption on the surface of biomaterials is important for modulating cell adhesion. Two important proteins in this regard are fibrinogen and fibronectin. Poly(2-methoxyethyl acrylate) (PMEA) and its derivatives have been developed as promising coating materials for biomaterial surfaces. Previous studies have highlighted that PMEA-coated substrates suppress thrombogenicity but promote cell adhesiveness. However, it was unclear what was responsible for these differences in adhesion. In this study, we focused on the correlation between protein adsorption and the nanometer-scale structures on the surfaces of the PMEA substrates. An atomic force microscope using protein- or antibody-conjugated cantilevers was used to perform nanoscopic analyses of the adsorption forces and conformational changes in fibrinogen and fibronectin adsorbed on the nanometer-scale PMEA structures. The adsorption force of fibronectin in the polymer-poor region was higher than that of fibrinogen, whereas the polymer-rich region showed a negligible difference in adsorption force between the two proteins. Interestingly, a greater conformational change in the adsorbed fibronectin was induced in the polymer-poor region than that in fibronectin in the polymer-rich region or fibrinogen in either regions, resulting in the induction of cell adhesion. Nanoscopic analyses of protein adsorption on biomaterial surfaces provide promising insights into the design of novel biomaterials that control protein adsorption and cell adhesion.

Effect of Osmolytes on Water Mobility Correlates with Their Stabilizing Effect on Proteins.

There is a long, ongoing debate on how small molecules (osmolytes) affect the stability of proteins. The present study found that change in collective rotational dynamics of water in osmolyte solutions likely has a dominant effect on protein denaturation. According to THz spectroscopy analysis, osmolytes that stabilize proteins are accompanied by bound hydration water with slow dynamics, while the collective rotational dynamics of water is accelerated in the case of denaturant osmolytes. Among 15 osmolytes studied here, there is a good correlation between the change in mobility in terms of water rotational dynamics and the denaturation temperature of ribonuclease A. The changes in water dynamics due to osmolytes can be regarded as a pseudo-temperature-change, which agrees well with the change in protein denaturation temperature. These results indicate that the molecular dynamics of water around the protein is a key factor for protein denaturation.

Experimental Evidence of Slow Mode Water in the Vicinity of Poly(ethylene oxide) at Physiological Temperature.

In some synthetic polymers used for medical applications, hydration water in the vicinity of the polymer chains is known to play an important role in biocompatibility and is referred to as intermediate water. The crystallization of water below 0 °C observed during thermal analysis has been considered as evidence of the presence of intermediate water. However, the origin and physicochemical properties of intermediate water have not yet been elucidated. In this study, as a typical biocompatible polymer, poly(ethylene oxide) and its hydration water were investigated with the use of terahertz time-domain spectroscopy and quasi-elastic neutron scattering. The obtained results prove the existence of a significant amount of mobile water that interacts with the polymer chains even when the water content is low at physiological temperatures.

Infrared Spectra and Hydrogen-Bond Configurations of Water Molecules at the Interface of Water-Insoluble Polymers under Humidified Conditions.

Elucidating the state of interfacial water, especially the hydrogen-bond configurations, is considered to be key for a better understanding of the functions of polymers that are exhibited in the presence of water. Here, an analysis in this direction is conducted for two water-insoluble biocompatible polymers, poly(2-methoxyethyl acrylate) and cyclic(poly(2-methoxyethyl acrylate)), and a non-biocompatible polymer, poly(n-butyl acrylate), by measuring their IR spectra under humidified conditions and by carrying out theoretical calculations on model complex systems. It is found that the OH stretching bands of water are decomposed into four components, and while the higher-frequency components (with peaks at ∼3610 and ∼3540 cm-1) behave in parallel with the C═O and C-O-C stretching and CH deformation bands of the polymers, the lower-frequency components (with peaks at ∼3430 and ∼3260 cm-1) become pronounced to a greater extent with increasing humidity. From the theoretical calculations, it is shown that the OH stretching frequency that is distributed from ∼3650 to ∼3200 cm-1 is correlated to the hydrogen-bond configurations and is mainly controlled by the electric field that is sensed by the vibrating H atom. By combining these observed and calculated results, the configurations of water at the interface of the polymers are discussed.

Pulmonary lymphoepithelial cyst with no prior HIV infection: A case report.

Most lymphoepithelial cysts (LECs) occur in the salivary glands and are considered one of the autoimmune syndromes caused by the human immunodeficiency virus (HIV). In this report, we present a case of pulmonary LEC without prior HIV infection, paying special attention to radiographic features. A chest radiograph revealed an oval mass with a smooth surface, localized in the left lower lung field, which was in direct contact with the diaphragm. Computed tomography showed an oval homogenous mass with a smooth surface in the lower left lobe. Further, magnetic resonance imaging demonstrated that the mass was a homogeneous internal structure with a smooth surface and a slightly high signal in T2-weighted images and a slightly low signal in T1-weighted images. Surgical resection was performed, and pathological examination confirmed the diagnosis of a pulmonary LEC. To the best of our knowledge, no cases of pulmonary LECs without prior HIV infection have been reported in the literature to date, therefore, the case presented here is considered very rare and informative.

Effect of interfacial structure based on grafting density of poly(2-methoxyethyl acrylate) on blood compatibility.

An excellent blood-compatible polymer, poly(2-methoxyethyl acrylate) (PMEA), exhibits nanometer-scale phase-separated structures at the interface with water or phosphate-buffered saline (PBS), and fibrinogen adsorption is suppressed, especially on the water-rich region. To understand the correlation between the interfacial structure based on the grafting density of PMEA and blood compatibility, grafted PMEA (gPMEA) surfaces with controlled density were prepared by immobilizing thiol-terminated PMEA on a gold substrate. The amount of adsorbed fibrinogen and the number of adhered platelets on gPMEAs decreased first with the increasing grafting density (σ), but increased after showed minimum at σ of approximately 0.11 chains/nm2. The interfacial structures of the gPMEA/PBS interface changed with grafting density, and the maximum area of water-rich region was obtained at σ = 0.11. The water contact angle at σ = 0.11 is smaller than that at the other grafting density. These results revealed that hydration to the polymer is very effective to suppress the platelet adhesion and water-rich region shows excellent blood compatibility on gPMEA surfaces. This work clearly indicated that the density of PMEA affects the interfacial structure and plays an important role in the blood compatibility of the material.

Local Dynamics of the Hydration Water and Poly(Methyl Methacrylate) Chains in PMMA Networks.

The dynamic behavior of water molecules and polymer chains in a hydrated poly(methyl methacrylate) (PMMA) matrix containing a small amount of water molecules was investigated. Water molecules have been widely recognized as plasticizers for activating the segmental motion of polymer chains owing to their ability to reduce the glass transition temperature. In this study, combined with judicious hydrogen/deuterium labeling, we conducted quasi-elastic neutron scattering (QENS) experiments on PMMA for its dry and hydrated states. Our results clearly indicate that the dynamics of hydrated polymer chains are accelerated, and that individual water molecules are slower than bulk water. It is therefore suggested that the hydration water affects the local motion of PMMA and activates the local relaxation process known as restricted rotation, which is widely accepted to be generally insensitive to changes in the microenvironment.

Protein- and Cell-Resistance of Zwitterionic Peptide-Based Self-Assembled Monolayers: Anti-Biofouling Tests and Surface Force Analysis.

Peptide-based self-assembled monolayers (peptide-SAMs) with specific zwitterionic amino acid sequences express an anti-biofouling property. In this work, we performed protein adsorption and cell adhesion tests using peptide-SAMs with repeating units of various zwitterionic pairs of amino acids (EK, DK, ER, and DR). The SAMs with the repeating units of EK and DK (EK and DK SAMs) manifested excellent bioinertness, whereas the SAMs with the repeating units of ER and DR (ER and DR SAMs) adhered proteins and cells. We also performed surface force measurements using atomic force microscopy to elucidate the mechanism underlying the difference in the anti-biofouling property. Our measurements revealed that water-induced repulsion with a range of about 8 nm acts between EK SAMs (immobilized on both probe and substrate) and DK SAMs, whereas such repulsion was not observed for ER and DR SAMs. The strength of the repulsion exhibited a clear correlation with the protein- and cell-resistance of the SAMs, indicating that the interfacial water in the vicinity of EK and DK SAMs is considered as a physical barrier to deter protein and cells from their adsorption or adhesion. The range of the repulsion observed for EK and DK SAMs is longer than 8 nm, indicating that the hydrogen bonding state of the interfacial water with a thickness of 4 nm is modified by EK and DK SAMs, resulting in the expression of the anti-biofouling property.