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Infections caused by biofouling have become a serious concern in the health care sector. Multifunctional coatings with antifouling and antibacterial properties are widely used to combat these biofouling related infections. However, in practice macro or micro scratches or damages can happen to the coating, which can act as an active site for microbial deposition and destroy the antifouling or antibacterial functionality of the coating. Considering this fact, we have developed an excellent biocompatible and multifunctional coating with antifouling, antibacterial and self-healing properties. In this study, prebiotic chemistry inspired self-polymerization of aminomalononitrile (AMN) was used as a primary coating layer, which acted as a primer to graft vitamin B5 analogous methacrylamide polymer poly(B5AMA) and zwitterionic compound 2-methacryloyloxyethyl phosphorylcholine (MPC) containing polymer poly (MPC

Double-hydrophilic diblock copolymers, PMPC

Epithelial barriers that seal cell gaps by forming tight junctions to prevent the free permeation of nutrients, electrolytes, and drugs, are essential for maintaining homeostasis in multicellular organisms. The development of nanocarriers that can permeate epithelial tissues without compromising barrier function is key for establishing a safe and efficient drug delivery system (DDS). Previously, we have demonstrated that a water-soluble phospholipid-mimicking random copolymer, poly(2-methacryloyloxyethyl phosphorylcholine30-random-n-butyl methacrylate70) (PMB30W), enters the cytoplasm of live cells by passive diffusion mechanisms, without damaging the cell membranes. The internalization mechanism was confirmed to be amphiphilicity-induced membrane fusion. In the present study, we demonstrated nonendocytic permeation of PMB30W through the model epithelial barriers of Madin-Darby canine kidney (MDCK) cell monolayers in vitro. The polymer penetrated epithelial MDCK monolayers via transcellular pathways without breaching the barrier functions. This was confirmed by our unique assay that can monitor the leakage of the proton as the smallest indicator across the epithelial barriers. Moreover, nonendocytic transepithelial permeation was achieved when insulin was chemically conjugated with the phospholipid-mimicking nanocarrier. The bioactivity of insulin as a growth factor was found to be maintained even after translocation. These fundamental findings may aid the establishment of transepithelial DDS with advanced drug efficiency and safety.

Alternative liposome surface coatings for PEGylation to evade the immune system, particularly the complement system, have garnered significant interest. We previously reported poly(2-methacryloyloxyethyl phosphorylcholine) (MPC)-based lipids (PMPC-lipids) and investigated the surface modification of liposomes. In this study, we synthesize PMPC-lipids with polymerization degrees of 10 (MPC10-lipid), 20 (MPC20-lipid), 50 (MPC50-lipid), and 100 (MPC100-lipid), and coated liposomes with 1, 5, or 10 mol% PMPC-lipids (PMPC-liposomes). Non-modified and PEGylated liposomes are used as controls. We investigate the liposome size, surface charge, polydispersity index, and adsorption of plasma proteins to the liposomes post incubation in human plasma containing N,N,N',N'-ethylenediamine tetraacetic acid (EDTA) or lepirudin by some methods such as sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), western blotting, and automated capillary western blot, with emphasis on the binding of complement protein C3. It is shown that the coating of liposome PMPC-lipids can suppress protein adsorption more effectively with an increase in the molecular weight and molar ratio (1-10 mol%). Apolipoprotein A-I is detected on PMPC-liposomes with a higher molecular weight and higher molar ratio of PMPC-lipids, whereas α2-macroglobulin is detected on non-modified, PEGylated, and PMPC-liposomes with a shorter polymer chain. In addition, a correlation is shown among the PMPC molecular weight, molar ratio, and C3 binding. The MPC10-lipid cannot inhibit C3 binding efficiently, whereas surface modifications with 10 mol% MPC20-lipid and 5 mol% and 10 mol% MPC50-lipid suppress both total protein and C3 binding. Hence, liposome modification with PMPC-lipids can be a possible strategy for avoiding complement activation.

The effects of differentiated cells on stem cell differentiation were analyzed by co-culture using a cell-encapsulated double-layered hydrogel system. As a polymer hydrogel matrix, a water-soluble zwitterionic polymer having both 2-methacryloyloxyethyl phosphorylcholine unit and p-phenylboronic acid unit (PMBV), was complexed spontaneously with poly(vinyl alcohol) (PVA) under mild cell culture conditions. The elastic modulus of the hydrogel was controlled by changing the composition of the polymer in the solution. Mouse mesenchymal stem cells (MSCs), C3H10T1/2 cells, were encapsulated into PMBV/PVA hydrogels and cultured. In the PMBV/PVA hydrogel with a lower creep modulus (0.40 kPa), proliferation of C3H10T1/2 cells occurred, and the formation of cell aggregates was observed. On the other hand, a higher creep modulus (1.7 kPa) of the hydrogel matrix prevented cell proliferation. Culturing C3H10T1/2 cells encapsulated in PMBV/PVA hydrogel in the presence of bone morphogenetic protein-2 increased the activity of intracellular alkaline phosphatase (ALP). This indicated that C3H10T1/2 cells differentiated into mature osteoblasts. When the C3H10T1/2 cells encapsulated in the PMBV/PVA hydrogel were cultured in combination with the mature osteoblasts in the hydrogel by a closed contacting double-layered hydrogel structure, higher ALP activity was observed compared with the cells cultured separately. It was considered that the differentiation of C3H10T1/2 cells in the hydrogel layer was induced by cytokines diffused from mature osteoblasts encapsulated in another hydrogel layer. It could be concluded that the PMBV/PVA hydrogel system provides a good way to observe the effects of surrounding cells on cell function in three-dimensional culture.

Fabrication of devices that accurately recognize, detect, and separate target molecules from mixtures is a crucial aspect of biotechnology for applications in medical, pharmaceutical, and food sciences. This technology has also been recently applied in solving environmental and energy-related problems. In molecular recognition, biomolecules are typically complexed with a substrate, and specific molecules from a mixture are recognized, captured, and reacted. To increase sensitivity and efficiency, the activity of the biomolecules used for capture should be maintained, and non-specific reactions on the surface should be prevented. This review summarizes polymeric materials that are used for constructing biointerfaces. Precise molecular recognition occurring at the surface of cell membranes is fundamental to sustaining life; therefore, materials that mimic the structure and properties of this particular surface are emphasized in this article. The requirements for biointerfaces to eliminate nonspecific interactions of biomolecules are described. In particular, the major issue of protein adsorption on biointerfaces is discussed by focusing on the structure of water near the interface from a thermodynamic viewpoint; moreover, the structure of polymer molecules that control the water structure is considered. Methodologies enabling stable formation of these interfaces on material surfaces are also presented.

A triblock copolymer (PEG-b-PUEM-b-PMPC; EUM) comprising poly(ethylene glycol) (PEG), thermo-responsive poly(2-ureidoethyl methacrylate) (PUEM), and poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC) blocks was synthesized via controlled radical polymerization. PEG and PMPC blocks exhibit hydrophilicity and biocompatibility. The PUEM block exhibits an upper critical solution temperature (UCST). PMPC can dissolve hydrophobic fullerenes in water to form a complex by grinding PMPC and fullerene powders. Fullerene-C70 (C70) and EUM were ground in a mortar and phosphate-buffered saline (PBS) was added to synthesize a water-soluble complex (C70/EUM). C70/EUM has a core-shell-corona structure, whose core is a complex of C70 and PMPC, the shell is PUEM, and corona is PEG. The maximum C70 concentration dissolved in PBS was 0.313 g L-1 at an EUM concentration of 2 g L-1. The C70/EUM hydrodynamic radius (Rh) was 34 nm in PBS at 10 °C, which increased due to the PUEM block's UCST phase transition with increasing temperature, and Rh attained a constant value of 38 nm above 36 °C. An anticancer drug, doxorubicin, was encapsulated in the PUEM shell by hydrophobic interactions in C70/EUM at room temperature, which can be released by heating. The generation of singlet oxygen (1O2) from C70/EUM upon visible-light irradiation was confirmed using the singlet oxygen sensor green indicator. Water-soluble C70/EUM may be used as a carrier that releases encapsulated drugs when heated and as a photosensitizer for photodynamic therapy.

Cationic magnetic hydrogel microparticles with high retention on cell surfaces were prepared using a two-step procedure. Using these magnetic hydrogel microparticles, cells were clustered with each other, and cell aggregates were prepared effectively. Cross-linked poly(vinyl alcohol) (PVA) hydrogel microparticles containing iron oxide nanoparticles were prepared. The diameter of the microparticles was in the range of 200-500 nm. Water-soluble cationic polymers containing both trimethyl ammonium (TMA) groups and phenylboronic acid (PBA) groups were synthesized for the surface modification of the microparticles. To regulate the composition, electrically neutral phosphorylcholine groups were introduced into the polymer. Covalent bonds were formed between the hydroxy groups of PVA microparticles and PBA groups in the polymer. The surface zeta potential of the microparticles reflected the composition of the TMA groups. The particles responded to an external magnetic field and clustered rapidly. Microparticles were adsorbed on the floating cell surface and induced cell aggregation quickly when a magnetic field was applied. Under the most effective conditions, the diameter of the cell aggregates increased to approximately 1 mm after 30 min. Denser cell aggregates were formed by the synergistic effects of the magnetic field and the properties of the microparticles. The formed cell aggregates continued to grow for more than 4 days under an applied magnetic field, indicating that the ability of the cells in the aggregate to proliferate was well maintained.

BACKGROUND: One crucial factor in skin tissue engineering is to understand the hydration and barrier property of skin. We investigated the skin hydration and stabilization strategy of inter-lamellar structure of stratum corneum (SC) using poly (2-methacryloyloxyethyl phosphorylcholine) (PMPC). METHODS: The unique hydration and stabilization potency of PMPC on the barrier function of the SC examined using freshly excised hairless mouse skin as a model membrane and the relationship between the stabilization of the lipid lamellar bilayer (LLB) and its enhanced water holding capacity was established. RESULTS: Differential scanning calorimeter based on the phase-transition temperature of lipid domain of SC demonstrated that PMPC stabilized the LLB. The ratio of the heat of lipid phase transition (△H) of SC exposed to water and PMPC for 24 h was 1.51. X-ray crystallography showed the presence of well- organized lipids in intercellular membranes exhibiting short and long periodicity of lamellar phases. The peak at 4.4 nm attributed to the long periodicity phase (LPP) was missing in water-treated SC, where, the presence of 4.2- 4.4 nm peak in PMPC treated SC indicated that PMPC stabilized LPP. Transmission electron microscopy study demonstrated that the LLB structure became more rigid and orderly in PMPC treated SC. CONCLUSION: The unique ion paired structure of PMPC enhances the barrier function of the SC by stabilizing LLB structure and hydration by inducing weakly bound water. The unique hydration state and stabilization effect from extended water exposure could provide a valuable information to prepare reliable artificial skin matrix and skin tissue. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13770-021-00379-4.

The use of amphiphilic molecules such as poly(ethylene glycol)-conjugated phospholipid (PEG-lipid) enables incorporation into liposome surfaces by exogenous addition as a result of the self-assembly with lipids. This technique can be applicable for manipulation of both liposomes and cells. In this study, we aimed to characterize Tat peptide (YGRKKRRQRRR)-conjugated PEG-lipids when used to exogenously surface modify liposomes (size: ca. 100 nm). We earlier reported that cells, which were surface modified with Tat peptides conjugated to PEG-lipids could attach spontaneously to material surfaces without any chemical modification. Here, we synthesized different types of Tat-PEG-lipids by combining PEG of different molecular weights (5 and 40 kDa) with different lipids with three acyl chains (myristoyl, palmitoyl, and stearoyl, respectively) and then studied the spontaneous adsorption of modified liposomes onto a substrate surface induced by the different Tat-PEG-lipids. The amount of adsorbed liposomes strongly depended on the number of incorporated Tat-PEG-lipid moieties: a decrease in both the PEG and the acyl chain lengths led to adsorption of higher amounts of liposomes. Furthermore, when a collagenase-cleavable amino acid sequence was inserted between the Tat sequence and the PEG segment, adsorbed liposomes could be harvested from the substrate by collagenase treatment with no difference in desorption efficiency between the different Tat-PEG-lipids. Thus, Tat-PEG-lipid can be a suitable tool for the manipulation of liposomes and cells.

For the polymeric carriers of solid dispersions, it is important that carriers themselves dissolve quickly and maintain the supersaturated state of amorphous drugs during their dissolution period to improve bioavailability. Amphipathic 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers can be dissolved in water, owing to the extremely high hydrophilicity of the MPC units, and are used as an ideal feeder for drug molecules to form aggregates in aqueous conditions. We synthesized amphipathic MPC copolymers with different hydrophobic side chains and molar ratios of MPC units, and evaluated the effect of the polymers on dissolution rate and supersaturation maintenance of solid dispersions of indomethacin. In most of the water-soluble amphipathic MPC copolymers, “spring-parachute”-like dissolution behavior was observed, where the drug initially became supersaturated followed by slow precipitation. In particular, MPC copolymers with aromatic rings in their side chains or polymers with a high percentage of hydrophobic units remained in a supersaturated state for a longer period. In contrast, urethane groups, which form hydrogen bonds with drug molecules, could also interact with water and were not conducive to maintaining supersaturation. In addition, water solubility of the polymer is important for rapid dissolution.

Redox-active molecules are promising anticancer compounds because cancer cells are vulnerable to oxidative stress. Anticancer drugs are often incorporated into synthetic polymers to improve water solubility, stability, and retention in the body. Most conventional redox-active polymers are regarded as stimuli-responsive polymers, which induce the release of anticancer drugs in response to the surrounding redox environment. Here, we prepared redox phospholipid polymers composed of 2-methacryloyloxyethyl phosphorylcholine units and ferrocene or quinone units as anticancer redox polymers. Redox phospholipid polymers can disturb the intracellular redox state owing to their redox activity and cell membrane permeability. We observed that the redox potential of the polymers affected the reactivity with intracellular redox species and O

Measurements of wear resistance and metal ion release are important for designing bearing couples or interfaces in total hip arthroplasty (THA). In this study, we investigated wear resistance and metal ion release of surface-modified metal-free all-polymer hip bearings, such as poly(ether-ether-ketone), (PEEK) on cross-linked polyethylene (PEEK-on-CLPE), with a hydrated gel-like surface layer, to propose an improved alternative to the conventional materials used to design THA bearings. The PEEK surface resulted in less metal ion release than the cobalt-chromium-molybdenum (Co-Cr-Mo) alloy surface owing to the lack of metal. The PEEK-on-CLPE bearing (6.33 mg/106 cycles) had lower wear (rate) than the bearing with Co-Cr-Mo alloy-on-CLPE (10.47 mg/106 cycles) under controlled laboratory conditions; the wear performance of the all-polymer hip bearings was further improved with hemi- or both-surface modified with a hydrated poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) layer (3.74 and 3.06 mg/106 cycles, respectively). The PMPC-grafted interface of PEEK-on-CLPE will be especially suitable for THA candidates. This study is of key importance for the design of lifelong THA and a better understanding of the limitations resulting from using PEEK. Further studies are necessary to evaluate the possibility of using this material in artificial hips.

In the present study, water-soluble molecular complexes between carboxylic acid-functionalized multiwalled carbon nanotubes (MWCNTs) and biocompatible poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) were prepared by hand grinding. MWCNTs could be solubilized in phosphate-buffered saline using this simple method. The suspended concentration of MWCNTs was found to increase with increasing polymer concentration and pH of the solution. Heat generation from the complexes was studied upon irradiation with near-infrared (NIR) radiation at a wavelength of 808 nm. The results demonstrated that MWCNTs absorbed light and generated heat when the molecular complex was irradiated by NIR. The solution temperature increased with increasing MWCNT concentration and irradiation time. This study presents a facile method for preparation of water-soluble molecular complexes between carboxylic acid-functionalized multiwalled carbon nanotube and poly(2-methacryloyloxyethyl phosphorylcholine) (MWCNTs/PMPC) by hand grinding. MWCNTs could be solubilized in aqueous environment with higher suspended concentrations when increasing polymer concentration and pH of the solution. MWCNTs/PMPC adsorbed light and induced heat generation to reach the temperature required for photothermal therapy (PTT) when the complexes were irradiated by near-infrared (NIR) at a wavelength of 808 nm. The water-soluble MWCNT complex covered by biocompatible PMPC is a promising candidate for PTT application.

Amphiphilic diblock copolymers (M98En) composed of hydrophilic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC, M) and hydrophobic poly(2-methoxyethyl acrylate) (PMEA, E) were prepared via controlled radical polymerization. The degree of polymerization (DP) of the PMPC block was 98, and the DP values of the PMEA block (=n) were 95 and 314. In water, M98En formed micelles with hydrophobic PMEA cores and hydrophilic PMPC shells. The size, density, and aggregation number of M98E314 were larger than those of M98E95 because the hydrophobic interactions became stronger with increasing PMEA block length. A hydrophobic anticancer agent, i.e., doxorubicin, was encapsulated into the core of the polymer micelles to assess the potential of these micelles as carriers in a drug delivery system. Micelles formed from M98En did not interact with proteins in the aqueous solution because the micelle surfaces were covered with biocompatible PMPC shells. Amphiphilic diblock copolymers (M98En) composed of hydrophilic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) and hydrophobic poly(2-methoxyethyl acrylate) were synthesized via controlled radical polymerization. M98En formed micelles in water, which can encapsulate hydrophobic guest molecules into the core. The micelles did not interact with proteins in an aqueous solution due to the PMPC shells.

When multilayer heterogeneous proteins are adsorbed on substrate surfaces, the effects of the adsorption state of the initially adsorbed proteins may affect subsequent adsorption. In this study, the relationships between the adsorption state of the initially adsorbed proteins and the amount of secondary adsorbed proteins were examined. A carboxylate-terminated self-assembled monolayer was applied to bovine serum albumin (BSA) solutions of different concentrations for 180 min and subsequently applied to phosphate-buffered saline (PBS) for an additional 180 min to remove weakly adsorbed proteins. The amount of adsorbed proteins was measured using a quartz crystal microbalance with dissipation. The obtained BSA adsorption layer was then applied to mucin solution for 60 min. When a 1.7 mg/mL BSA solution was applied to the surface, the amount of adsorbed BSA after 10 min of adsorption and after washing with PBS for 167 min was >5 × 102 ng/cm2, representing the saturation amount of monolayer-adsorbed BSA in a side-on orientation. In contrast, the amount of adsorbed BSA after 10 min adsorption was

Inspired by the cell membrane surface as well as the ocular tissue, a novel and clinically applicable antifouling silicone hydrogel contact lens material was developed. The unique chemical and biological features on the surface on a silicone hydrogel base substrate were achieved by a cross-linked polymer layer composed of 2-methacryloyloxyethyl phosphorylcholine (MPC), which was considered important for optimal on-eye performance. The effects of the polymer layer on adsorption of biomolecules, such as lipid and proteins, and adhesion of cells and bacteria were evaluated and compared with several conventional silicone hydrogel contact lens materials. The MPC polymer layer provided significant resistance to lipid deposition as visually demonstrated by the three-dimensional confocal images of whole contact lenses. Also, fibroblast cell adhesion was decreased to a 1% level compared with that on the conventional silicone hydrogel contact lenses. The movement of the cells on the surface of the MPC polymer-modified lens material was greater compared with other silicone hydrogel contact lenses indicating that lubrication of the contact lenses on ocular tissue might be improved. The superior hydrophilic nature of the MPC polymer layer provides improved surface properties compared to the underlying silicone hydrogel base substrate.

Boronic ester, one typical example of dynamic covalent bonds, has presented great potential to prepare self-healing hydrogels. However, most of currently reported hydrogels based on boronic esters are formed at pH > 8, which impeded their further use in physiological conditions. In this study, we designed two kinds of zwitterionic copolymers with benzoxaborole and catechol pendant groups, respectively. Owing to the lower pKa value of benzoxaborole (7.2), gelation can happen easily at pH 7.4 PBS after mixing these two copolymers due to efficient formation of benzoxaborole-catechol complexations. The resulting hydrogels exhibited excellent self-healing property as well as dual pH/sugar responsiveness due to the dynamic nature of boronic ester. Moreover, benefiting from the cell membrane bioinspired 2-methacryloyloxyethyl phosphorylcholine (MPC)-based polymeric matrix, the hydrogel was further investigated for 3D cell encapsulation. The combination of biocompatible zwitterionic polymers with dynamic benzoxab...

Poly(ethylene glycol) (PEG) is frequently used for liposomal surface modification. However, as PEGylated liposomes are cleared rapidly from circulation upon repeated injections, substitutes of PEG are being sought. We focused on a water-soluble polymer composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) units, and synthesized poly(MPC) (PMPC)-conjugated lipid (PMPC-lipid) with degrees of MPC polymerization ranging from 10 to 100 (calculated molecular weight: 3 to 30 kDa). In addition, lipids with three different alkyl chains, myristoyl, palmitoyl, and stearoyl, were applied for liposomal surface coating. We studied the interactions of PMPC-lipids with plasma albumin, human complement protein C3 and fibrinogen using a quartz crystal microbalance with energy dissipation, and found that adsorption of albumin, C3 and fibrinogen could be suppressed by coating with PMPC-lipids. In particular, the effect was more pronounced for PMPC chains with higher molecular weight. We evaluated the size, polydispersity index, surface charge, and membrane fluidity of the PMPC-lipid-modified liposomes. We found that the effect of the coating on the dispersion stability was maintained over a long period (98 days). Furthermore, we also demonstrated that the anti-PEG antibody did not interact with PMPC-lipids. Thus, our findings suggest that PMPC-lipids can be used for liposomal coating.

The generation of singlet oxygen (1O2) by sonicating a water-soluble complex of fullerene/poly(2-methacryloyloxyethyl phosphorylcholine) (C60/PMPC) was investigated for sonodynamic therapy (SDT). The effect of sonication time and the solubilized concentration of water-soluble fullerene C60 on the amount of generated 1O2 was studied. Singlet oxygen sensor green was used to confirm the generation of 1O2. 1O2 was generated from C60/PMPC under ultrasonic irradiation, and the amount of 1O2 increased with increasing solubilized C60 concentration and irradiation time. In cell viability tests, after 3 h of incubation, the cell viabilities were 10 and 84% in the presence of C60/PMPC with and without sonication, respectively. This result suggests that C60/PMPC shows a sonodynamic effect, which demonstrates its potential application in SDT. The generation of singlet oxygen (1O2) by sonicating a water-soluble complex of fullerene/poly(2-methacryloyloxyethyl phosphorylcholine) (C60/PMPC) was investigated for sonodynamic therapy (SDT). 1O2 was generated from C60/PMPC under ultrasonic irradiation, and the amount of 1O2 increased with increasing solubilized C60 concentration and irradiation time. In cell viability tests, after 3 h of incubation, the cell viabilities were 10% and 84% in the presence of C60/PMPC with and without sonication, respectively. This result suggests that C60/PMPC shows a sonodynamic effect, which demonstrates its potential application in SDT.

The aim of this study was to design a material surface for use in the analysis of the behavior of biomolecules at the interface of direct cell contact. A superhydrophilic surface was prepared with poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), which was grafted onto a substrate with controlled polymer chain density. An arginine-glycine-aspartic acid (RGD) peptide was immobilized at the surface of the polymer graft surface (PMPC-RGD surface). Initial adhesion of the cells to this substrate was observed. The PMPC-RGD surface could enable cell adhesion only through RGD peptide-integrin interactions. The density and movability of the RGD peptide at the terminal of the graft PMPC chain and the orientation of the RGD peptide affected the density of adherent cells. Thus, the PMPC graft surface may be a good candidate for a new platform with the ability to immobilize biomolecules to a defined position and enable accurate analysis of their effects on cells.

Metallic materials are used for clinical medical devices such as vascular stents and coils to treat both ischemic and hemorrhagic vascular diseases. An antiplatelet drug is required to avoid thromboembolic complication until metallic surface is covered with a neo-endothelial cell layer. It is important to identify endothelial cell coverage on the metallic surface. However, it is difficult since there are no selective ligands. Here, we used the phage display method to identify peptide ligands that had high affinity for the metallic surface of Ni-Ti stents, Pt-W coils, and Co-Cr stents. The binding assay using fluorescence labeling revealed that several synthetic peptides could bind onto those surfaces. We also chose some oligopeptides for the conjugation onto superparamagnetic iron oxide (SPIO) nanoparticles and liposome-encapsulating SPIO nanoparticles and studied their ability to bind to the stent and coils. By SEM and fluorophotometry, we found that those modified SPIOs and liposomes were selectively bound onto those surfaces. In addition, both treated stents and coils could be detected by magnetic resonance imaging due to the magnetic artifact through the SPIOs and liposomes that were immobilized onto the surface. Thus, we identified metal-binding peptides which may enable to stop antiplatelet therapy after vascular stenting or coiling.

Hydrophilic poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC) shows biocompatibility because the pendant phosphorylcholine group has the same chemical structure as the hydrophilic part of phospholipids that form cell membranes. Hollow particles can be used in various fields, such as a carrier in drug delivery systems because they can encapsulate hydrophilic drugs. In this study, vinyl group-decorated silica particles with a radius of 150 nm were covered with cross-linked PMPC based on the graft-through method. The radius of PMPC-coated silica particles increased compared to that of the original silica particles. The PMPC-coated silica particles were immersed in a hydrogen fluoride aqueous solution to remove template silica particles to prepare the hollow particles. The PMPC hollow particles were characterized by dynamic light scattering, infrared spectroscopy, thermogravimetric analysis, and transmission electron microscopy observations. The thickness of the hollow particle shell can be controlled by the polymerization solvent quality. When a poor solvent for PMPC was used for the polymerization, PMPC hollow particles with thick shells can be obtained. The PMPC hollow particles can encapsulate hydrophilic guest molecules by immersing the hollow particles in a high-concentration guest molecule solution. The biocompatible PMPC hollow particles can be used in a drug carrier.

G. Julius Vancso, Jian Ji, Kazuhiko Ishihara, M. Cristina L. Martins and Shaoyi Jiang introduce the Journal of Materials Chemistry B themed collection on bioinspired surfaces engineering for biomaterials.

Poly(ether ether ketone) (PEEK) has seen increasing use in biomedical fields as a replacement for metal implants. Accordingly, the surface functionalities of PEEK are important for the development of medical devices. We have focused on the application of photoinduced reactions in PEEK to immobilize a functional polymer

The self-assembly of pH-responsive random and block copolymers composed of 2-(N,N-diisopropylamino)ethyl methacrylate and 2-methacryloyloxyethyl phosphorylcholine was investigated in aqueous media. Their pH-responsive behaviors were investigated in aqueous media by dynamic light scattering (DLS) and fluorescence measurements using a pyrene hydrophobic fluorescence probe. In an acidic environment, these copolymers existed as single polymer chains that did not interact with each other. In contrast, upon increasing the pH of the solution above the critical value of ~8, separated micelles were formed in the mixture, which was indicated by bimodal distribution in DLS results with radius of 4.5 and 10.4 nm, corresponding to the random and block copolymer micelles, respectively. Fluorescence resonance energy transfer efficiencies were near to zero in the mixture of the donor labeled block and acceptor labeled random copolymers under both acidic and basic pH. These results demonstrated the coexistence of two distinct micelles.

There is considerable interest in the cryopreservation in 3D cell culture, as structurally preserving intact cells and tissues is critical in utilizing these systems to promote cell differentiation and tissue organization. Temperature-responsive physical gels and zwitterionic polymers are useful materials as 3D scaffolds for cell culture which may also provide cryoprotection to the composite cells. Nevertheless, there has been a lack of relevant data for polymer systems that have both of these properties. In this study, highly biocompatible triblock copolymers were examined for their effectiveness both as gelators and as cryo-protectants. The triblock copolymers were synthesized with 2-methacryloyloxyethyl phosphorylcholine (MPC) and di(ethylene glycol) methyl ether methacrylate (DEGMA) via atom transfer radical polymerization (PDEGMA113-b-PMPC243-b-PDEGMA113). ABA triblock copolymers composed of hydrophilic “B” block and temperature responsive “A” block could form physical gels above their lower critical...

The technique of cell patterning on a substrate is of great importance for platforms in cell-based assays. Chemical treatment of the substrate is commonly performed for cell patterning using cationic polymers, extracellular matrices, and antibodies. However, cell patterning could be easier if there is an approach to immobilize cells without treating the substrate surface. We previously reported that cell adhesion could be induced by the modification of the cellular surface with a cell-penetrating peptide (CPP)-conjugated poly(ethylene glycol)-phospholipid (CPP-PEG-lipid). This approach does not require chemical modification of the substrate surface, such as polystyrene or glass, and can be used for the cell patterning of floating cells. Here, we aimed to study the mechanism of induced cell adhesion using a representative CPP, Tat peptide (Tat-PEG-lipid). We found that cell adhesion was induced via electrostatic interactions between the Tat peptide and the substrate surface, which could be induced more efficiently by increasing the molecular weight of PEG together with CPPs but not with cationic peptides. The excluded volume effect between neighboring PEG chains could stretch the cell shape better than PEG with lower molecular weight, allowing the cell to spread firmly. In addition, Tat-PEG-lipid did not activate actin filament formation and did not influence the expression of focal adhesion kinase. Thus, the induced cell adhesion by CPP-PEG-lipid did not affect internal cell signaling.

Materials taking advantage of the characteristics of biological tissues are strongly sought after in medical science and bioscience. On the natural corneal tissue surface, the highly soft and lubricated surface is maintained by composite structures composed of hydrophilic biomolecules and substrates. To mimic this structure, the surface of a silicone hydrogel contact lens was modified with a biomimetic phospholipid polymer, poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), and the nanoscaled morphology and mechanical properties of the surface were confirmed with advanced surface characterization and imaging techniques under an aqueous medium. Concavities and convexities on the nanometer order were recognized on the surface. The surface was completely covered with a PMPC layer and remained intact even after 30 days of clinical use in a human ocular environment. The mechanical properties of the natural corneal tissue and the PMPC-modified surface were similar in the living environment, that is, low modulus and frictional properties comparable to natural tissues. These results show the validity of material preparation by biomimetic methods. The methodologies developed in this study may contribute to future development of human-friendly medical devices.

Intermediate filaments (IF) bind to various proteins and regulate cell function in the cytoplasm. Recently, IFs were found to regulate gene expression by acting as capture scaffolds for transcription-related proteins and preventing their translocation into the nucleus. To reveal such transcriptional regulatory mechanisms controlled by IFs, a method to analyze the interaction between IFs and transcription-related proteins is necessary. Although there are many methods to observe interactions in living cells, it is still challenging to measure protein-protein interactions in living cells in their unmodified and native state. In this study, we utilized a nanoneedle that can access the cytosol by insertion into the cell. Modification of antibody recognizing transcription-related proteins allows the needle to detect mechanical force required to unbind the interaction between antibody and target proteins interacting with IFs during retraction of the needle from the cell. We focused on IF vimentin, a marker of epithelial-mesenchymal transition, to mechanically detect transcription-related proteins trapped by vimentin filaments. Prohibitin 2 (PHB2), a transcription-related factor, was selected as the candidate vimentin-binding protein. We conducted mechanical detection of PHB2 using atomic force microscopy and anti-PHB2 antibody-modified nanoneedles in vimentin-expressing mouse breast cancer and vimentin-knockout (VKO) cells. Significantly larger unbinding forces were detected in the vimentin-expressing cells than in the VKO cells. The results demonstrate that this method is useful for in-cell mechanical detection of IF-binding proteins.

Background/aim Pancreatic cancer, which exhibits resistance to cytotoxic and molecular targeted drugs, has an extremely poor prognosis. Nuclear factor-κB (NF-κB) is constitutively activated in many pancreatic cancer cases. Although the NF-κB inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) has exhibited anti-cancer effects in pancreatic cancer models, its poor solubility limits its use to intraperitoneal administration. Materials and methods Poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) (PMB) forms stable polymer aggregates with DHMEQ. The stability of DHMEQ aggregated with PMB in the human blood was measured by high-performance liquid chromatography-mass spectrometry (HPLC-MS) ex vivo. Anti-pancreatic cancer effects in AsPC-1 and MIA PaCa-2 pancreatic cancer cells were evaluated by cell growth inhibition assay in vitro and tumor growth inhibition assay in vivo. Results DHMEQ aggregated with PMB (PMB-DHMEQ) remained detectable after 60 min of incubation in the human blood, whereas DHMEQ aggregated with carboxymethyl cellulose (CMC-DHMEQ) was barely detectable. PMB-DHMEQ significantly inhibited AsPC-1 and MIA PaCa-2 cell growth in vitro compared to CMC-DHMEQ. Intravenous administration of PMB-DHMEQ reduced the tumor volume and liver metastasis compared to untreated or CMC-DHMEQ-treated mice. Conclusion Aggregation with PMB improved the solubility of DHMEQ, and effectively inhibited pancreatic cancer cell growth both in vitro and in vivo.

We report on a cost-effective synthesis method for copolymers containing bioinspired phenolic and phosphorylcholine groups in the side chain. Adsorption of the gallol group bearing polymers onto surfaces was compared with reference polymers containing catechol, phenol, phenyl or n-butyl groups. We found that the gallol group was the most effective functional group among those tested to immobilize the low-fouling phospholipid polymer on surfaces. The adlayer exhibited the same degree of low-fouling properties as the commercially available phospholipid polymer (LIPIDURE®-PMB), while exhibiting better solvent resistance, especially in water and alcohol. Thus we expect that the reported method may be advantageous in biomedical applications that often involve an alcohol sterilization process.