A hybrid poly(dimethylsiloxane) microsystem for on-chip whole blood filtration optimized for steroid screening

Miniaturized biochemical devices in glass, silicon and polymer materials are starting to find their way from the academic laboratories to real-life applications. However, most attention has been given to miniaturize the downstream functions of various microfluidic systems, leaving the sample introduction and preparation steps to more conventional, bulkier solutions. For point-of-care diagnostics in particular, it becomes crucial to be able to handle complex human samples in a miniaturized format. In this work, we report on a microsystem for on-chip sample preparation that is able to remove blood cells from whole blood. The hybrid system consists of a commercially available membrane filter incorporated into a poly(dimethylsiloxane) (PDMS) casted device. Membrane materials were evaluated on the bases of low nonspecific adsorption of free and protein-bound testosterone as analyte substance. The hybrid system including a hydrophilic polypropylene filter successfully removed blood cells from diluted human whole blood. Surface oxidation was sufficient to make the plasma filtrate flow through the membrane filter and the channel system by capillary force alone and thus no external pumping source was needed.     

Synthesis,Characterization and Biomedical Properties of UV-Cured Polyurethane Acrylates Containing a Phosphorylcholine Structure

Abstract

In order to develop a simple, economical and rapid approach to incorporate 2-methacryloyloxyethyl phosphorylcholine (MPC) with other monomers without any solvent, we prepared a series of ultraviolet cured poly(urethane acrylate) (PUA) membranes containing different MPC content. Their chemical structure and surface properties were investigated by FT-IR, XPS, water swelling ratio and water contact angle measurement, while the biocompatibilities were evaluated through fibrinogen adsorptions, platelet adhesion and plasma recalcification time determination. The results demonstrate that the phosphorylcholine (PC) groups were successfully introduced into the PUA system by the UV-curing approach and the all PC-containing membranes showed better biocompatibility than those without PC moiety. The UV-curing method is potentially to be applied in the coating of medical devices which require biocompatibility and manufacturing efficiency.     

A novel biomaterial: Poly(dimethylsiloxane)-polyamide multiblock copoly mer I. Synthesis and evaluation of blood compatibility

Aramid-silicone resins (PASs) consisting of aromatic polyamide (aramid) and poly(dimethylsiloxane) (PDMS) segments were synthesized by low temperature solution polycondensation. For the evaluation of blood compatibility in vitro, two kinds of experiments were carried out. One was the thromboxane B₂(TXB₂) release test from platelets attaching to PAS and Biomer®. The other was the observation of the platelet adhesion on the surfaces of PAS by scanning electron microscopy (SEM). The results indicated that PAS was bio-inert in vitro. The surface chemical composition of PAS films was investigated by means of electron probe micro analysis (EPMA), X-ray photoelectron spectroscopy (XPS), and dynamic contact angle measurements. The relationship between blood compatibility and surface composition of PAS is discussed.     

Synthesis,Characterization and Properties of Poly(butylene succinate) Reinforced by Trimellitic Imide Units

Summary: A series of high molecular weight poly(butylene succinate) copolyester containing rigid imide units were synthesized in this paper. The chemical structure and composition of the copolyesters were determined by ¹H NMR spectroscopy and Fourier transform infrared spectroscopy (FT‐IR). Gel permeation chromatography (GPC) was employed to determine the molecular weight and molecular weight distribution. The differential scanning calorimetry (DSC) technique showed that the melting temperature (T_m) of the copolyester decreased slightly with the increment in trimellitic imide unit content. When the imide unit content was increased to 6.3 mol‐%, it had an elongation at break of 510% (83% higher than that of PBS) and a tensile strength of 37 MPa (7% higher than that of PBS). The changes in mechanical properties of the copolyester might be owed to the compositive effects of spherulitic morphology and imide units.

FT‐IR spectra of PBS and PBST.     

Novel Poly(L-lactide) PLLA/SWNTs Nanocomposites for Biomedical Applications: Material Characterization and Biocompatibility Evaluation

Poly(L-lactide) (PLLA)/single-walled carbon nanotubes (SWNTs) nanocomposite films were produced using the solvent casting method, and morphological, thermal and mechanical properties were investigated. Biocompatibility was evaluated by using human bone cells, performing adhesion and proliferation studies. The role of single-walled nanotube incorporation and functionalization on PLLA bio-polymers was investigated. Pristine (SWNTs) and carboxylated (SWNTs–COOH) carbon nanotubes were considered in order to control the interaction between PLLA and nanotubes. SWNTs and SWNTs–COOH showed a good dispersion in the polymer matrix and improved the PLLA crystallinity. Thermal, morphological and dynamic-mechanical analyses revealed that carboxylic groups on the tube sidewalls increased compatibility between PLLA and nanostructures. Mechanical properties demonstrated an enhancement related to introduction and functionalization of carbon nanotubes. Biological investigations showed osteoblasts cultured on PLLA/SWNTs–COOH nanocomposites has higher cell adhesion and proliferation than osteoblasts cultured on PLLA and PLLA/SWNTs nanocomposites. These studies suggest that combination of biodegradable polymers and SWNTs opens a new perspective in the self-assembly of nanomaterials and nanodevices for biomedical applications with tunable properties.     

Adhesion of Escherichia coli on to a series of poly(methacrylates) differing in charge and hydrophobicity

The adhesion of three Escherichia coli strains on to six poly(methacrylates) differing in hydrophobicity and surface charge was measured as a function of time under laminar flow conditions. Polymers used were poly(methy) methacrylate) (PMMA), poly(hydroxyethy) methacrylate) (PHEMA) and copolymers of MMA or HEMA with either 15% methacrylic acid (MAA) or 15% trimethylaminoethyl methacrylate-HCl salt (TMAEMA-CI). Bacterial and polymer surfaces were characterized by means of water contact angles and zeta potentials. Both the sessile drop contact angles and the zeta potentials of the bacterial surfaces were significantly different. No significant differences in the sessile drop contact angles of the polymer surfaces were observed. Using the Wilhelmy plate technique large contact angle hysteresis was observed for the different polymer surfaces. Surfaces of copolymers with MAA had more negative zeta potentials than those of the corresponding homopolymers. Surfaces of copolymers with TMAEMA-CI had positive zeta potentials. The highest numbers of adherent bacteria were found on materials with positive zeta potentials, irrespective of the bacterial strain used. Bacterial adhesion on to copolymers with MAA was less than on to the corresponding homopolymers. Bacterial equilibrium adhesion values correlate with the zeta potentials of the polymer surfaces (r > 0.85). On substrates with less negative zeta potentials high numbers of adhered bacteria were observed. Additionally, the equilibrium bacterial adhesion values could be related with receding contact angles of polymer surfaces with negative zeta potentials (r > 0.86). High equilibrium adhesion values were obtained for polymers with high contact angles. No correlation between the zeta potentials and contact angles of the bacteria with the adhesion values was found.     

Characterization of partially saturated poly(propylene fumarate) for orthopaedic application

A partially saturated linear polyester based on poly(propylene fumarate) (PPF) was synthesized for potential application in filling skeletal defects. The synthesis was carried out according to a two-step reaction scheme. Propylene glycol and fumaryl chloride were first combined to form an intermediate fumaric diester. The intermediate was then subjected to a transesterification to form the PPF-based polymer. This method allowed for production of a polymer with a number average molecular weight up to 1500 and a polydispersity index of 2.8 and below. The polymeric backbone structure was investigated through the use of FTIR and NMR. Kinetic studies of the transesterification allowed mapping of the molecular weight increase with reaction time. The final product was also characterized by thermal and solubility analysis.     

The nanocomposite scaffold of poly(lactide-co-glycolide) and hydroxyapatite surface-grafted with l-lactic acid oligomer for bone repair

Nanohydroxyapatite (op-HA) surface-modified with l-lactic acid oligomer (LAc oligomer) was prepared by LAc oligomer grafted onto the hydroxyapatite (HA) surface. The nanocomposite of op-HA/PLGA with different op-HA contents of 5, 10, 20 and 40 wt.% in the composite was fabricated into three-dimensional scaffolds by the melt-molding and particulate leaching methods. PLGA and the nanocomposite of HA/PLGA with 10 wt.% of ungrafted hydroxyapatite were used as the controls. The scaffolds were highly porous with evenly distributed and interconnected pore structures, and the porosity was around 90%. Besides the macropores of 100–300 μm created by the leaching of NaCl particles, the micropores (1–50 μm) in the pore walls increased with increasing content of op-HA in the composites of op-HA/PLGA. The op-HA particles could disperse more uniformly than those of pure HA in PLGA matrix. The 20 wt.% op-HA/PLGA sample exhibited the maximum mechanical strength, including bending strength (4.14 MPa) and compressive strength (2.31 MPa). The cell viability and the areas of the attached osteoblasts on the films of 10 wt.% op-HA/PLGA and 20 wt.% op-HA/PLGA were evidently higher than those on the other composites. For the animal test, there was rapid healing in the defects treated with 10 and 20 wt.% op-HA/PLGA, where bridging by a large bony callus was observed at 24 weeks post-surgery. There was non-union of radius defects implanted with PLGA and in the untreated group. This was verified by the Masson’s trichrome staining photomicrographs of histological analysis. All the data extrapolated that the composite with 10 and 20 wt.% op-HA exhibited better comprehensive properties and were the optimal composites for bone repairing.     

Calcium effect on the membrane preparation of segmented poly (ether/urethane/amide) (PEUN) as a biomedical material

Poly(ether/urethane/amide) (PEUN), a segmented polyurethane, was characterized concerning phase relationship, viscosity in solution, hydraulic permeability, mechanical properties, and in vivo biocompatibility with tissue and blood. PEUN was dissolved at the highest concentration of 0.5% in N,N-dimethylformamide (DMF). Addition of calcium chloride at concentrations up to 3.1% progressively increased the solubility of PEUN in DMF. PEUN2 membrane was prepared by casting from mixtures of PEUN, 3% calcium chloride, and DMF, from which calcium chloride was sufficiently removed. The PEUN2 membrane thus obtained was compared with PEUN membrane which was prepared by casting from DMF solution without the addition of calcium chloride. The water permeability across PEUN2 membrane was higher than that across PEUN membrane. PEUN2 membrane in the swollen state exhibited a lower tensile modulus and much greater elastic property than PEUN membrane. Tissue compatibility of PEUN2 membrane was better than that of PEUN membrane. Thromboresistance of PEUN membrane was good, while PEUN2-coated surface was thrombogenic to some extent in vivo. Our characterization suggested that PEUN2 membrane is more hydrophilic than PEUN membrane, possibly because of the assembly of polar groups on the segments of PEUN molecules which show affinity to calcium chloride in membrane processing.     

Preparation and Fluorescent and Magnetic Properties of Polyurethane/Eu(MA)3 Films

Europium(III) (Eu³⁺)‐doped polyurethane films were prepared by mixing Eu‐methacrylic acid complex (Eu(MA)₃) with aliphatic polyurethane oligomer and subsequently curing under UV irradiation. Transmission electron microscopy photos and the appearance of the resulting hybrid films showed that phase separation occurred only at an Eu(MA)₃ content above 20 wt.‐%. Fluorescence spectra indicated that the fluorescence of Eu³⁺ was barely influenced by the polyurethane matrix and its intensity increased with an Eu(MA)₃ content in the range of approximately 0 to 10 wt.‐%. An obvious applied external‐field‐dependent magnetization (M) of polyurethane/Eu(MA)₃ films, namely, an increasing M at low field and a decreasing M at high field, was observed at room temperature from the hysteresis loops, which was influenced by both the Eu(MA)₃ content and the ultrasonication imposed on the coatings before curing. It seems that ultrasonication leads to a thermodynamically‐unstable structure of Eu³⁺ in hybrid films, which can be fixed by UV curing but gradually rearranges to its original form during the thermal‐curing process, and enhances the diamagnetic part of the hybrid film. Thus, the magnetic property of Eu³⁺‐doped polyurethane film at room temperature can be adjusted by simply changing the preparation method and the Eu(MA)₃ content instead of the type of Eu³⁺‐organic complex.

     

Preparation,mechanical properties and in vitro cytocompatibility of multi-walled carbon nanotubes/poly(etheretherketone) nanocomposites

Desired bone repair material must have excellent biocompatibility and high bioactivity. Moreover, mechanical properties of biomaterial should be equivalent to those of human bones. For developing an alternative biocomposite for load-bearing orthopedic application, combination of bioactive fillers with polymer matrix is a feasible approach. In this study, a series of multi-walled carbon nanotubes (MWCNTs)/poly(etheretherketone) (PEEK) bioactive nanocomposites were prepared by a novel coprecipitation-compounding and injection-molding process. Scanning electron microscope (SEM) images revealed that MWCNTs were adsorbed on the surface of PEEK particles during the coprecipitation-compounding process and dispersed homogeneously in the nanocomposite because the conjugated PEEK polymers stabilized MWCNTs by forming strong π–π stack interactions. The mechanical testing revealed that mechanical performance of PEEK was significantly improved by adding MWCNTs (2–8 wt%) and the experimental values obtained were close to or higher than that of human cortical bone. In addition, incorporation of MWCNTs into PEEK matrix also enhanced the roughness and hydrophilicity of the nanocomposite surface. In vitro cytocompatibility tests demonstrated that the MWCNTs/PEEK nanocomposite was in favor of cell adhesion and proliferation of MC3T3-E1 osteoblast cells, exhibiting excellent cytocompatibility and biocompatibility. Thus, this MWCNTs/PEEK nanocomposite may be used as a promising bone repair material in orthopedic implants application.     

The Effect of Hydrolysis Degree on the Properties of Antibacterial Polymeric Films Based on Poly(vinyl alcohol) and Zinc Sulphate for Biomedical Applications

Fully and partially hydrolyzed poly(vinyl alcohol) (PVA) was modified with zinc sulphate in the concentration range from 0 to 9 wt% of recalculated zinc content using the solvent cast technique. The resulting polymeric films were characterized by optical microscopy, stress–strain analysis, differential scanning calorimetry and Fourier transform infrared spectroscopy (FT-IR–ATR). In addition, agar diffusion test and dilution and spread plate technique were used for determination of antibacterial properties of the films against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae) bacterial strains. A mathematical model was applied on the measured data and parameters characterizing the antibacterial efficiency of the material were calculated and discussed. The results revealed that the PVA hydrolysis degree can play an important role in all studied properties, including antibacterial activity of the all PVA-based materials.     

Molecular dynamics simulation study of P (VP-co-HEMA) hydrogels: Effect of water content on equilibrium structures and mechanical properties

Poly (N-vinyl-2-pyrrolidone-co-2-hydroxyethyl methacrylate) (P(VP-co-HEMA)) hydrogel system with a composition of VP:HEMA = 37:13 was studied using molecular dynamics simulations in order to investigate the effect of the water content on the equilibrium structures and the mechanical properties. The degree of randomness of the monomer sequence for the random and the blocky copolymers, were 1.170 and 0.104, respectively, and the degree of polymerization was fixed at 50. The equilibrated density of the hydrogel was found to be larger for the random sequence than for the blocky sequence at low water contents (<40 wt%), but this density difference decreased with increasing water content. The pair correlation function analysis shows that VP is more hydrophilic than HEMA and that the random sequence hydrogel is solvated more than the blocky sequence hydrogel at low water content, which disappears with increasing water content. Correspondingly, the water structure is more disrupted by the random sequence hydrogel at low water content but eventually develops the expected bulk water-like structure with increasing water content. From mechanical deformation simulations, stress–strain analysis showed that the VP is found to relax more efficiently, especially in the blocky sequence, so that the blocky sequence hydrogel shows less stress levels compared to the random sequence hydrogel. As the water content increases, the stress level becomes identical for both sequences. The elastic moduli of the hydrogels calculated from the constant strain energy minimization show the same trend with the stress–strain analysis.     

Synthesis,Phase Behaviour and Mechanical Properties of Poly(2‐methyl‐1,3‐propanediol‐4,4′‐bibenzoate)

The synthesis and phase behaviour of PB32 is reported. The results indicate that PB32 develops a low‐ordered smectic mesophase of the type SmC_alt. The slow formation of such a mesophase allows the quenching of the isotropic melt into an amorphous state so that both amorphous glass and smectic glass can be obtained, which exhibit different glass‐transition temperatures. Mechanical tests indicate that the macromolecular chains in the mesophase of PB32 can be oriented either parallel or perpendicularly in relation to the streching direction, depending on the deformation conditions. Solid‐state ¹³C NMR spectroscopy results show that the mobility of the chains is rather similar in both phases.