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.

Fluorine-containing bio-inert polymers: Roles of intermediate water.

Fluorine-containing polymers are used not only in industrial processes but also in medical applications, because they exhibit excellent heat, weather, and chemical resistance. As these polymers are not easily degraded in our body, it is difficult to use them in applications that require antithrombotic properties, such as artificial blood vessels. The material used for medical applications should not only be stable in vivo, but it should also be inert to biomolecules such as proteins or cells. In this review, this property is defined as "bio-inert," and previous studies in this field are summarized. Bio-inert materials are less recognized as foreign substances by proteins or cells in the living body, and they must be covered at interfaces designed with the concept of intermediate water (IW). On the basis of this concept, we present here the current understanding of bio-inertness and unusual blood compatibility found in fluoropolymers used in biomedical applications. IW is the water that interacts with materials with moderate strength and has been quantified by a variety of analytical methods and simulations. For example, by using differential scanning calorimetry (DSC) measurements, IW was defined as water frozen at around -40°C. To consider the role of the IW, quantification methods of the hydration state of polymers are also summarized. These investigations have been conducted independently because of the conflict between hydrophobic fluorine and bio-inert properties that require hydrophilicity. In recent years, not many materials have been developed that incorporate the good points of both aspects, and their properties have seldom been linked to the hydration state. This has been critically performed now. Furthermore, fluorine-containing polymers in medical use are reviewed. Finally, this review also describes the molecular design of the recently reported fluorine-containing bio-inert polymers for controlling their hydration state. STATEMENT OF SIGNIFICANCE: A material covered with a hydration layer known as intermediate water that interacts moderately with other objects is difficult to be recognized as a foreign substance and exhibits bio-inert properties. Fluoropolymers show high durability, but conflict with bio-inert characteristics requiring hydrophilicity as these research studies have been conducted independently. On the other hand, materials that combine the advantages of both hydrophobic and hydrophilic features have been developed recently. Here, we summarize the molecular architecture and analysis methods that control intermediate water and provide a guideline for designing novel fluorine-containing bio-inert materials.

Understanding the Effect of Hydration on the Bio-inert Properties of 2-Hydroxyethyl Methacrylate Copolymers with Small Amounts of Amino- or/and Fluorine-Containing Monomers.

Materials exhibiting "bio-inert properties" are essential for developing medical devices because they are less recognized as foreign substances by proteins and cells in the living body. We have reported that the presence of intermediate water (IW) with the water molecules loosely bound to a polymer is a useful index of the bio-inertness of materials. Here, we analyzed the hydration state and the responses to biomolecules of poly(2-hydroxyethyl methacrylate) (PHEMA) copolymers including small amounts of 2-(dimethylamino)ethyl methacrylate (DMAEMA) (N-series) or/and 2,2,2-trifluoroethyl methacrylate (TFEMA) (F-series). The hydration structure was analyzed by differential scanning calorimetry (DSC), the molecular mobility of the produced copolymers by temperature derivative of DSC (DDSC), and the water mobility by solid 1H pulse nuclear magnetic resonance (NMR). Although the homopolymers did not show bio-inert properties, the binary and ternary PHEMA copolymers with low comonomer contents showed higher bio-inert properties than those of PHEMA homopolymers. The hydration state of PHEMA was changed by introducing a small amount of comonomers. The mobility of both water molecules and hydrated polymers was changed in the N-series nonfreezing water (NFW) with the water molecules tightly bound to a polymer and was shifted to high-mobility IW and free water (FW) with the water molecules scarcely bound to a polymer. On the other hand, in the F-series, FW turned to IW and NFW. Additionally, a synergetic effect was postulated when both comonomers coexist in the copolymers of HEMA, which was expressed by widening the temperature range of cold crystallization, contributing to further improvement of the bio-inert properties.

Controlling the Hydration Structure with a Small Amount of Fluorine To Produce Blood Compatible Fluorinated Poly(2-methoxyethyl acrylate).

Poly(2-methoxyethyl acrylate) (PMEA) shows excellent blood compatibility because of the existence of intermediate water. Various modifications of PMEA by changing its main or side chain's chemical structure allowed tuning of the water content and the blood compatibility of numerous novel polymers. Here, we exploit a possibility of manipulating the surface hydration structure of PMEA by incorporation of small amounts of hydrophobic fluorine groups in MEA polymers using atom-transfer radical polymerization and the (macro) initiator concept. Two kinds of fluorinated MEA polymers with similar molecular weights and the same 5.5 mol % of fluorine content were synthesized using the bromoester of 2,2,3,3,4,4,5,5,6,6,7,7,8,8-pentadecafluoro-1-octanol (F15) and poly(2,2,2-trifluoroethyl methacrylate) (PTFEMA) as (macro) initiators, appearing liquid and solid at room temperature, respectively. The fibrinogen adsorption of the two varieties of fluorinated MEA polymers was different, which could not be explained only by the bulk hydration structure. Both polymers show a nanostructured morphology in the hydrated state with different sizes of the features. The measured elastic modulus of the domains appearing in atomic force microscopy and the intermediate water content shed light on the distinct mechanism of blood compatibility. Contact angle measurements reveal the surface hydration dynamics-while in the hydrated state, F15- b-PMEA reorients easily to the surface exposing its PMEA part to the water, the small solid PTFEMA block with high glass-transition temperature suppresses the movement of PTFEMA- b-PMEA and its reconstruction on the surface. These findings illustrate that in order to make a better blood compatible polymer, the chains containing sufficient intermediate water need to be mobile and efficiently oriented to the water surface.

Hydration States and Blood Compatibility of Hydrogen-Bonded Supramolecular Poly(2-methoxyethyl acrylate).

The practical use of the viscous liquid polymer, poly(2-methoxyethyl acrylate) (PMEA), was expanded from thin films with excellent blood compatibility to thick coatings and free-standing films without essentially sacrificing its blood compatibility. This was undertaken by creating multiple hydrogen-bonding polymer networks by introducing a functional methacrylic monomer bearing a 6-methyl-2-ureido-4[1H]-pyrimidone group in the PMEA backbone via free radical copolymerization. The hydrogen-bonded PMEA (H-PMEA) contained about 6 mol % of the functional monomer in the copolymer. These functional monomers as physical cross-links are distributed in the PMEA matrix with a Tg of -35 °C, making H-PMEA a solid rubber-like material with recoverable tensile strain. Additionally, mechanical tests revealed its tensile strength, and thermogravimetric analyses confirmed its higher thermostability. The dry and hydration states of H-PMEA were assessed by differential scanning calorimetry, contact angle, and atomic force microscopy measurements. Comparison with viscous PMEA was made. For the first time, we included PVC alongside PET, the surface we usually use as a negative control, in the platelet adhesion test with human blood, and found out that 1.5 times more platelets adhered onto the PVC surface than onto the PET surface, while H-PMEA proved to have a clear edge. Thus, H-PMEA may serve as a suitable replacement for polymers in products contacting blood as it shows potential for making free-standing films, thick coatings, implants, and articles with various geometries for the medicinal industry.

Stability of Asp(B28) Insulin Exposed to Modified and Unmodified Polypropylene.

Polypropylene (PP) plates have been modified with two different hydrophilic polymeric materials, poly(N,N-dimethylacrylamide) (poly(DMAAm)) and poly(poly(ethylene glycol)methacrylate) (poly(PEGMA)) in order to reduce insulin adsorption when the plates were exposed to insulin aspart (Asp(B28) insulin). The influence of surface modification on the chemical and physical stability of Asp(B28) insulin was evaluated by two chromatographic methods, size exclusion chromatography (SEC) and reverse phase high pressure liquid chromatography (RP-HPLC) and the Thioflavin T assay. A clear difference in the stability of Asp(B28) insulin was observed between the three tested surfaces. PP coated with poly(DMAAm) resulted in a poor chemical stability and a significantly improved physical stability compared with unmodified PP. In addition to this a lower phenol concentration was observed for the poly(DMAAm) coating. The results from the poly(PEGMA) coating looked very promising with respect to the stability of Asp(B28) insulin in comparison with the data from unmodified PP and the poly(DMAAm) coating. Two hydrophilic coatings have been tested and surprisingly a difference in Asp(B28) insulin stability was observed. Therefore, Asp(B28) insulin adsorption and stability will be influenced by more than the hydrophilicity of the surface.

Adsorption and aqueous lubricating properties of charged and neutral amphiphilic diblock copolymers at a compliant, hydrophobic interface.

We have investigated the adsorption and lubricating properties of neutral and charged amphiphilic diblock copolymers at a hydrophobic polydimethylsiloxane (PDMS) interface in an aqueous environment. The diblock copolymers consist of a hydrophilic block of either neutral poly(ethylene glycol) (PEG) or negatively charged poly(acrylic acid) (PAA) and of a hydrophobic block of polystyrene (PS) or poly(2-methoxyethyl acrylate) (PMEA), thus generating PEG-b-X or PAA-b-X, where X block is either PS or PMEA. The molecular weight ratios were roughly 1:1 with each block ca. 5 kDa. Comparing the neutral PEG and charged PAA buoyant blocks with all other conditions identical, the former showed superior adsorption onto nonpolar, hydrophobic PDMS surfaces from a neutral aqueous solution. PEG-based copolymers showed substantial adsorption for both PS and PMEA as the anchoring block, whereas PAA-based copolymers showed effective adsorption only when PMEA was employed as the anchoring block. For PAA-b-PS, the poor adsorption properties are chiefly attributed to micellization due to the high interfacial tension between the PS core and water. The poor lubricating properties of PAA-b-PS diblock copolymer for a PDMS-PDMS sliding contact was well correlated with the poor adsorption properties. PAA-b-PMEA copolymers, despite their sizable amount of adsorbed mass, showed insignificant lubricating effects. When the charges of the PAA-b-PMEA diblock copolymers were screened by either adding NaCl to the aqueous solution or by lowering the pH, both the adsorption and lubricity improved. We ascribe the poor adsorption and inferior aqueous lubricating properties of the PAA-based diblock copolymers compared to their PEG-based counterparts mainly to the electrostatic repulsion between charged PAA blocks, hindering the facile formation of the lubricating layer under cyclic tribological stress at the sliding PDMS-PDMS interface.

RAFT copolymerization of itaconic anhydride and 2-methoxyethyl acrylate: a multifunctional scaffold for preparation of "clickable" gold nanoparticles.

RAFT copolymerization of 2-methoxyethyl acrylate and itaconic anhydride - a monomer derived from renewable resources - is carried out in a controlled fashion. The copolymer allows preparation of gold nanoparticles with abundant surficial carboxyl and alkyne functional groups that are dendronized via Cu(I)-mediated "click" reaction.

Polysulfone functionalized with phosphonated poly(pentafluorostyrene) grafts for potential fuel cell applications.

A multi-step synthetic strategy to polysulfone (PSU) grafted with phosphonated poly(pentafluorostyrene) (PFS) is developed. It involves controlled radical polymerization resulting in alkyne-end functional PFS. The next step is the modification of PSU with a number of azide side groups. The grafting of PFS onto PSU backbone is performed via the "click"-chemistry approach. In a final step, the PFS-grafts are subjected to the post phosphonation. The copolymers are evaluated as membranes for potential fuel cell applications through thermal analyses, water uptake, and conductivity measurements. The proposed synthetic route opens the possibility to tune copolymers' hydrophilic-hydrophobic balance to obtain membranes with an optimal balance between proton conductivity and mechanical properties.

Synthesis of graft copolymers based on poly(2-methoxyethyl acrylate) and investigation of the associated water structure.

Graft copolymers composed of poly(2-methoxyethyl acrylate) are prepared employing controlled radical polymerization techniques. Linear backbones bearing atom transfer radical polymerization (ATRP) initiating sites are obtained by reversible addition-fragmentation chain transfer copolymerization of 2-methoxyethyl acrylate (MEA) and 2-(bromoisobutyryloxy)ethyl methacrylate (Br(i) BuEMA) as well as 2-hydroxyethyl methacrylate and Br(i) BuEMA in a controlled manner . MEA is then grafted from the linear macroinitiators by Cu (I)-mediated ATRP. Fairly high molecular weights (>120 000 Da) and low polydispersity indices (1.17-1.38) are attained. Thermal investigations of the graft copolymers indicate the presence of the freezing bound water, and imply that the materials may exhibit blood compatibility.

Surface modification of nanoporous 1,2-polybutadiene by atom transfer radical polymerization or click chemistry.

Surface-initiated atom transfer radical polymerization (ATRP) and click chemistry were used to obtain functional nanoporous polymers based on nanoporous 1,2-polybutadiene (PB) with gyroid morphology. The ATRP monolith initiator was prepared by immobilizing bromoester initiators onto the pore walls through two different methodologies: (1) three-step chemical conversion of double bonds of PB into bromoisobutyrate, and (2) photochemical functionalization of PB with bromoisobutyrate groups. Azide functional groups were attached onto the pore walls before click reaction with alkynated MPEG. Following ATRP-grafting of hydrophilic polyacrylates and click of MPEG, the originally hydrophobic samples transformed into hydrophilic nanoporous materials. The successful modification was confirmed by infrared spectroscopy, contact angle measurements and measurements of spontaneous water uptake, while the morphology was investigated by small-angle X-ray scattering and transmission electron microscopy.

Modification of jute fibers with polystyrene via atom transfer radical polymerization.

Atom transfer radical polymerization (ATRP) was investigated as a method of covalently bonding polystyrene to jute (Corchorus capsularis) and as a possible approach to fiber composites with enhanced properties. Jute fibers were modified with a brominated initiator and subsequently ATRP modified to attach polystyrene and then examined using SEM, DSC, TGA, FTIR, XPS, elemental analysis, and Py-GC-MS. These techniques confirmed that polystyrene had been covalently bound to the fibers and consequently ATRP-modified jute fiber mats were used to prepare hot-pressed polystyrene composites. Composite specimens were tensile tested and fracture surfaces examined using SEM. Although SEM examination suggested different fracture modes between unmodified fiber and ATRP-modified samples, the tensile strength of modified samples was slightly lower on average than that of unmodified samples. For fiber composite applications, we conclude that further optimization of the ATRP method is required, possibly targeting higher and more uniform loading of polystyrene on the fibers.