Photoreactive Initiator for Surface-Initiated ATRP on Versatile

Sep 13, 2016 - We synthesized 4-azidophenylcarbonyloxyethyl-2-bromoisobutyrate (AzEBI) for construction of a polymer brush layer on a desired area on ...
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Photoreactive Initiator for Surface-Initiated ATRP on Versatile Polymeric Substrates Kyoko Fukazawa,† Aiko Nakao,‡ Mizuo Maeda,‡ and Kazuhiko Ishihara*,†,§ †

Department of Materials Engineering, School of Engineering, and §Department of Bioengineering, School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8656, Japan ‡ Bioengineering Laboratory, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan S Supporting Information *

ABSTRACT: We synthesized 4-azidophenylcarbonyloxyethyl2-bromoisobutyrate (AzEBI) for construction of a polymer brush layer on a desired area on various polymeric substrates. After 3.0 min of exposure to UV irradiation, the phenylazide groups of AzEBI decomposed and formed covalent bonds with the polymeric substrate surfaces to introduce an initiator of atom transfer radical polymerization (ATRP). The reaction area of AzEBI was regulated using a photomask during photoreaction and surface initiated ATRP of 2-methacryloyloxyethyl phosphorylcholine (MPC) occurred on the desired part of the surface. In the area with poly(MPC), the surface was superhydrophilic and the adhesion of HeLa cell was effectively suppressed. The AzEBI allows the construction of polymer brush layer in anywhere and would expand the potential application of ATRP to prepare polymer brush layer on polymeric substrates. KEYWORDS: surface modification, surface-initiated ATRP, photochemistry, phospholipid polymer brush layer, wettability

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surfaces, so they react easily with photoreactive groups. Matyjaszewski et al. synthesized an ATRP initiator with benzophenone groups, and used a photoreaction to introduce the initiation sites on the polypropylene surface.13 Tsujii et al. synthesized a macroinitiator having both ATRP initiating groups and phenylazide groups.14 The phenylazide groups were decomposed by photoirradiation, thereby generating highly active nitrene groups that formed covalent bonds with the alkyl groups. These authors demonstrated that the SI-ATRP of poly(ethylene glycol) monomethacrylate from various polymeric substrates immobilized the macroinitiator. However, the macroinitiator is not soluble in alcohol, which does not affect most polymeric substrates, and hence selection of an appropriate solvent is required. To overcome this solubility issue, we synthesized 4-azidophenylcarbonyloxyethyl-2-bromoisobutyrate (AzEBI), which is soluble in alcohol. AzEBI was synthesized using the Schotten-Baumann reaction between 2hydroxythyl 2-bromoisobutyrate (HEBI) and 4-azidobenzoyl chloride obtained by a previously reported method.15 The obtained AzEBI (45% yield) was a light-yellow solid with a melting point of 31.7−32.6 °C. It was not soluble in water but was soluble in methanol, ethanol, 2-propanol, acetone, chloroform, hexane, toluene, and diethyl ether. Its chemical structure was analyzed using 1H NMR in CDCl3 (400 MHz NMR spectrometer; JEOL Ltd., Tokyo, Japan) and Fourier transform infrared spectroscopy (FT-IR; FT-IR-6300, JASCO, Tokyo, Japan). The 1H NMR results are as follows (ppm): 1.86

urface modification by grafting of polymer chains is an effective methodology to control the surface properties, such as wettability, friction, and adhesion, of the original substrate. Among the grafting processes, surface-initiated atom transfer radical polymerization (SI-ATRP) is a promising approach to construct well-defined polymer brush layers on the substrate surface.1−4 In SI-ATRP, the polymerization of monomers is initiated from the surface immobilized initiator. The polymer chain length and grafting density can be controlled finely. Immobilization of the initiator on the substrate is a key first step in achieving SI-ATRP. For this purpose, the use alkyl halide initiators with functional groups appropriate for various substrates has been reported.5−7 In particular, immobilization of the initiator onto the substrate by chemical bonding imparts excellent solvent resistance to the initiator and it can be used in the surface modification of biosensors and medical devices. SIATRP initiators with alkanethiol, alkoxysilane, and catechol groups are commonly used for reactions on metals and metal oxides.8−10 These initiators are directly immobilized on the substrate’s surface through surface-specific reactions. 2Bromoisobutyrate compounds are also commonly used as initiators,11,12 but activation of the polymeric surface is needed for their introduction, i.e., a two-step chemical reaction is employed. A photoreaction is a promising approach for immobilizing the ATRP initiator on polymeric substrates. The aryl ketones, carbene-generating and nitrene-generating compounds are widely recognized as photoreactive groups capable of abstracting hydrogen from a hydrocarbon. General polymeric substrates have a high density of hydrocarbon groups at the © XXXX American Chemical Society

Received: June 14, 2016 Accepted: September 13, 2016

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DOI: 10.1021/acsami.6b07145 ACS Appl. Mater. Interfaces XXXX, XXX, XXX−XXX

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ACS Applied Materials & Interfaces

Figure 1. Synthetic route of AzEBI initiator and schematic representation of initiator immobilization followed by surface-initiated ATRP.

(s, 6H, −C(CH3)2), 4.44−4.52 (m, 4H, −CH2CH2), 6.99−7.01 (d, 2H, benzyl), 7.96−7.98 (d, 2H, benzyl) (Figure S1). The FT-IR results are as follows (cm−1): 1601 (p-Ar), 2126 (C− N3), 1727 (CO) (Figure S2). Figure 1 shows an outline for the preparation of polymer brushes on the polymeric substrates through the photoreaction process. The AzEBI was first immobilized on various polymeric substrates by spin-coating and UV irradiation. Then the substrate was placed in contact with a monomer solution of MPC and SI-ATRP was conducted. MPC was selected as the monomer due to its excellent polymerization ability via ATRP.16 The poly(MPC) (PMPC) brush layer exhibits superhydrophilicity and effective suppression of protein adsorption and cell adhesion.17−20 The AzEBI allows the construction of a PMPC brush layer in the desired area of various polymeric substrates. The living polymerization performance of the MPC using the AzEBI initiator was examined. MPC was polymerized in methanol at 20 °C using AzEBI initiator, copper(I) bromide (CuBr) as a catalyst, and 2, 2′-bipyridyl (bpy) as a ligand. The monomer conversion and the molecular weight of the polymer formed were evaluated for a given polymerization period by removing a small sample of the polymer solution and analyzing it by 1H NMR and gel permeation chromatography (GPC) (JASCO, Tokyo, Japan). The relationship between ln([M0]/ [M]) and polymerization time as well as the relationship between molecular weight and conversion were almost linear, and the polydispersity of PMPC remained low, at around 1.3 (Figure S3). Various substrates, including polystyrene (PS), cross-linked polyethylene (CLPE; KYOCERA Medical Corp., Osaka, Japan), cyclic polyolefin (CPO; Sumitomo Bakelite Co., Ltd., Tokyo, Japan), and poly(ethylene terephthalate) (PET), were used to demonstrate the versatility of AzEBI immobilization. 50 mg/mL of AzEBI in ethanol was spin-coated onto each polymeric substrate at 3000 rpm for 20 s. After the ethanol was vaporized, the surfaces were irradiated with a UV lamp for 3.0 min (254 nm, 10 mW cm−2). Surface immobilization of AzEBI was confirmed by FT-IR spectroscopy with attenuated total

Figure 2. FT-IR spectra obtained on the AzEBI-coated ethanolwashed CLPE substrate before and after UV irradiation.

reflection equipment (FT-IR/ATR; IMV-4000, JASCO, Tokyo, Japan) at a resolution of 4 cm−1 over 128 scans. Figure 2 shows the FT-IR spectra obtained for the AzEBI-coated CLPE substrates before and after UV irradiation. Before UV irradiation, a high peak was observed at 2124 cm −1 corresponding to the azide groups. This peak first decreased and then disappeared completely after 3.0 min of UV irradiation. Other FT-IR absorption peaks assigned to AzEBI were not altered even after the substrates were washed with ethanol. Because AzEBI is soluble in ethanol, these results indicate that AzEBI was covalently immobilized on the CLPE substrate by UV irradiation. The AzEBI immobilization was also confirmed on the other substrates used in this study (data not shown). The influence of UV irradiation on the chemical structure of 2-bromoisobutyl groups in the ATRP-initiator was analyzed by B

DOI: 10.1021/acsami.6b07145 ACS Appl. Mater. Interfaces XXXX, XXX, XXX−XXX

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ACS Applied Materials & Interfaces

Figure 3. (a) Water contact angle under dry condition and (b) air contact angle in an aqueous medium for various substrates.

ellipsometric analysis (Si-PET).22 For its preparation, the silicon substrates were first treated using oxygen plasma (PR500 plasma reactor; Yamato Science, Tokyo, Japan) (300 W, 100 mL/min flow) for 3.0 min and immersed for 1.0 h in toluene solution containing 5.0 mM of 3-aminopropyltriethoxysilane. After drying, 1.0 wt % of PET in o-chlorophenol was spin-coated at 3000 rpm for 20 s. The substrates were heated at 120 °C for 1.0 h. The thickness of the PMPC grafting layer on AzEBI immobilized-Si-PET was determined using a spectroscopic ellipsometer (FE-5000S, Otsuka Electronics Co., Ltd., Osaka, Japan). The measurement was carried out at an incidence angle of 70° in the visible region and the analysis was performed using the Cauchy layer model with an assumed refractive index of 1.49 at 632.8 nm. The thickness of the grafted PMPC layer was measured to be 9.5 nm. The graft density was calculated from the ellipsometric thickness and molecular weight of polymer chains on the surface, which was obtained from the degree of polymerization determined using the 1H NMR spectrum of each free polymer. Inoue et al. reported that the polymerization kinetics from the initiatorimmobilized substrates would almost be the same as that for a polymerization solution with free initiator.23 The obtained value of 0.25 chains/nm2 indicated the formation of a dense polymer brush layer (>0.10 chains/nm2). The new binding state was confirmed in the Br 3d region after UV irradiation by XPS measurement, but it did not have a significant effect on the following ATRP reaction. Hydrophilic nature is one of the most important characteristics of PMPC grafted surface. The water contact angles under dry condition and the air contact angles in an aqueous medium were measured by a previously reported method24 using a static contact angle goniometer (CA-W; Kyowa Interface Science Co., Tokyo, Japan). All contact angles were directly measured from the photographic images. Figure 3 shows the water contact angle on the substrate under dry condition and the air contact angle at the interface in an aqueous medium before and after grafting of PMPC chains onto the various substrates. The water contact angles decreased from more than 85° to less than 40°. In particular, on Si-PET, the water contact angle was below 5°. We evaluated the amount of immobilized-AzEBI on Si-PET and PET (Figure S6). After AzEBI was spin-coated, the substrates before and after UV irradiation were put in the glass bottle and added 1.0 mL of ethanol. Physically adsorbed AzEBI molecules were washed away from the substrate into the solution by sonication for 5.0 min. The UV absorbance at 280 nm attributed to the released AzEBI in the solution was measured by UV spectroscopy. The amounts of immobilized-

X-ray photoelectron spectroscopy (XPS) (ESCALAB 250/ Thermo Fisher Scientific K.K.) using monochromatic Al K Xray radiation. The system was operated at 15 kV and 200 W with the takeoff angle of photoelectrons maintained at 90° and the base pressure of the analysis chamber maintained at less than 1 × 10−8 Pa. The (11-(2-bromo-2-methyl)propionyloxy)undecyl- trichlorosilane (BrC10TCS) immobilized-silicon substrate was prepared because AzEBI was sublimated under vacuum prior to UV irradiation. The peak assigned to Br 3d5/2 was observed at 70.0 eV before UV irradiation, while another small peak was observed at 67.5 eV after UV irradiation. This result indicates that the new binding state was generated by UV irradiation. Generally, the peak located at the lower binding energy is attributed to the ionic state of Br;21 however, the occurrence of the ionic state is considered extremely difficult in this case. Although we do not know the binding state at 67.5 eV, we know that the peak generated by UV irradiation was only 10% of the total Br 3d peak (Figure S4). The SI-ATRP of MPC from AzEBI-immobilized PS, CLPE, CPO, and PET substrates was carried out in methanol in the presence of free AzEBI initiator. The polymerization condition is the same as the kinetics experiment above-mentioned (Figure S3). Briefly, MPC, CuBr and bpy were dissolved in degassed methanol and argon gas was bubbled for 5.0 min to eliminate the effect of oxygen on polymerization. Then, AzEBIimmobilized substrates were immersed in the solution, and AzEBI methanol solution was simultaneously added as the free initiator. The glass tube was sealed after argon was bubbled for 10 min, polymerization was performed at 20 °C with starring for 24 h. The substrates were removed from the polymerization solutions, rinsed with methanol. The degree of polymerization was set at 100 by controlling the [monomer]/[initiator] ratio in the feed. After graft polymerization of MPC, each surface was analyzed by XPS (AXIS-His165 Kratos/Shimadzu, Kyoto, Japan) with 15 kV Mg Kα radiation source at the anode. The takeoff angle of photoelectrons was maintained at 90°. On the PMPC grafting substrates, the peaks assigned to natural carbon, ether bond, and ester bond were observed at 285.0, 287.0, and 289.0 eV in the C 1s region, respectively. Furthermore, clear peaks were observed at 403.0 and 399.0 eV in the N 1s region and at 134.0 eV in the P 2p region. The peak at 399.0 eV was assigned to the azide group of AzEBI. The peaks at 399.0 and 134.0 eV were assigned to ammonium nitrogen and phosphate groups in the MPC unit, respectively. Thus, it can be concluded that grafting of PMPC was accomplished on the various polymeric substrates (Figure S5). A thin PET film was prepared on the silicon substrate for C

DOI: 10.1021/acsami.6b07145 ACS Appl. Mater. Interfaces XXXX, XXX, XXX−XXX

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ACS Applied Materials & Interfaces AzEBI on Si-PET and PET substrates were calculated from the concentration of released AzEBI using a standard calibration curve of AzEBI solution, and they were 0.060 and 0.040 mmol, respectively. From this result, it is considered that the graft density of PMPC on Si-PET is higher than that on the PET, and induces the low contact angle value. The air contact angles increased from less than 40° to more than 160° in all substrates after grafting of PMPC chains. Grafting of PMPC converted all the polymeric substrate surfaces from hydrophobic to hydrophilic. A remarkable characteristic of photoreaction is the ability to easily regulate the reaction area. This can be achieved using a photomask during the photoreaction, resulting in polymerization only on the desired part of the surface. Herein, AzEBI was immobilized on the CPO substrate in a stripe pattern using the photomask (mask width: 200 μm, window width: 160 μm). The AzEBI that did not react was washed off using ethanol and then PMPC was grafted on the substrate. A protein adsorption and cell adhesion behavior was evaluated using the substrates having a patterned structure with a PMPC brush layer. A protein adsorption test was performed by a previously reported method using a mixture of Alexa Fluor 488 conjugated fibrinogen from human plasma (Excitation wavelength and emission wavelength are 495 and 519 nm, respectively) and fibrinogen from bovine plasma in phosphate buffered saline (PBS) (pH 7.4).25 The substrate was observed using the fluorescence mode of an Olympus phase-contrast microscope (model IX 71, Tokyo, Japan). The green fluorescence from fibrinogen was observed only at the original CPO substrate area (Figure S7). This result indicates that the fibrinogen adsorption was suppressed at the PMPC brush layer. The cell adhesion test was performed using Hela cells. The substrates were placed in a 24-well tissue culture plate that was previously sterilized with ethanol, and the cells (2.0 × 104 cells cm−2) were cultured on the substrates in Dulbecco’s modified Eagle’s medium (Gibco, Grand Island, USA) containing 10% fetal bovine serum at 37 °C in 5% CO2. After incubation for 2 days, the medium was removed and the substrates were rinsed with PBS. The cells on the surface were observed using an Olympus phase-contrast microscope. Figure 4 shows a microscopy image of HeLa cell adhesion on CPO substrates having a patterned structure with a PMPC brush layer. The cells adhered only at the original CPO substrate area, revealing that the PMPC brush layer suppressed the adhesion of cell adhesive proteins from the cell culture medium and did not induce cell adhesion. These results indicated that the PMPC brush layer was constructed on the desired area using a photomask. Various MPC polymers with hydrophobic group and photoreactive group have been reported for controlling cell adhesion.25,26 In the area covered with MPC polymer, the cell adhesion is completely suppressed. Herein, we demonstrated to control cell adhesion by construction of PMPC brush layer using photoreaction process. In conclusion, we have synthesized a photoreactive ATRP initiator (AzEBI) that could modify the surface of various polymeric substrates with a polymer brush layer using a photoreaction process. Since AzEBI is soluble in alcohol, it was possible to carry out surface modification under mild conditions, which did not affect the bulk properties of the polymer substrate. The PMPC brush layers were successfully constructed from AzEBI immobilized on various substrates, resulting in superhydrophilic surfaces. More importantly, the reaction area and location for modification could be controlled using a photomask. On the patterned structure with the PMPC

Figure 4. Cell adhesion on a CPO substrate having a patterned structure with a PMPC brush layer. Magnification (a) × 350 (b) × 1000.

brush layer, the cell adhesion area was completely regulated based on the characteristics of PMPC. We conclude that AzEBI as a photoreactive ATRP initiator would expand the potential application of SI-ATRP on polymeric substrates.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsami.6b07145. Figures S1−S7 and additional experimental details (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Tel.: 81-3-5841-7124. Fax: 81-3-5841-8647. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This research was partially supported by the AMED Sinnovation-Program for the development of biofunctional materials for the realization of innovative medicine.

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REFERENCES

(1) Siegwart, D. J.; Oh, J. K.; Matyjaszewski, K. ATRP in the Design of Functional Materials for Biomedical Applications. Prog. Polym. Sci. 2012, 37, 18−37. (2) Olivier, A.; Meyer, F.; Raquez, J.-M.; Damman, P.; Dubois, P. Surface-Initiated Controlled Polymerization as a Convenient Method for Designing Functional Polymer Brushes: From Self-Assembled Monolayers to Patterned Surfaces. Prog. Polym. Sci. 2012, 37, 157− 181.

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ACS Applied Materials & Interfaces (3) Ran, J.; Wu, L.; Zhang, Z.; Xu, T. Atom Transfer Radical Polymerization (ATRP): A Versatile and Forceful Tool for Functional Membranes. Prog. Polym. Sci. 2014, 39, 124−144. (4) Matyjaszewski, K. Atom Transfer Radical Polymerization: From Mechanisms to Applications. Isr. J. Chem. 2012, 52, 206−220. (5) Edmondson, S.; Armes, S. P. Synthesis of Surface-initiated Polymer Brushes Using Macro-Initiators. Polym. Int. 2009, 58, 307− 316. (6) Krishnamoorthy, M.; Hakobyan, S.; Ramstedt, M.; Gautrot, J. E. Surface-Initiated Polymer Brushes in the Biomedical Field: Applications in Membrane Science, Biosensing, Cell Culture, Regenerative Medicine and Antibacterial Coatings. Chem. Rev. 2014, 114, 10976− 11026. (7) Watanabe, H.; Fujimoto, A.; Yamamoto, R.; Nishida, J.; Kobayashi, M.; Takahara, A. Scaffold for Growing Dense Polymer Brushes from a Versatile Substrate. ACS Appl. Mater. Interfaces 2014, 6, 3648−3653. (8) Fan, X.; Lin, L.; Dalsin, J. L.; Messersmith, P. B. Biomimetic Anchor for Surface-Initiated Polymerization form Metal Substrates. J. Am. Chem. Soc. 2005, 127 (45), 15843−15847. (9) Zhao, C.; Li, L.; Zheng, J. Achieving Highly Effective Nonfouling Performance for Surface-Grafted Polu(HPMA) via Atom-Transfer Radical Polymerization. Langmuir 2010, 26 (22), 17375−17382. (10) Ejaz, M.; Ohno, K.; Tsujii, Y.; Fukuda, T. Controlled Grafting of a Well-Defined Glycopolymer on a Solid Surface by Surface-Initiated Atom Transfer Radical Polymerization. Macromolecules 2000, 33, 2870−2874. (11) Ishida, N.; Biggs, S. Effect of Grafting Density on Phase Transition Behavior for Poly(N-isopropylacryamide) Brushes in Aqueous Solutions Studied by AFM and QCM-D. Macromolecules 2010, 43, 7269−7276. (12) Król, P.; Chmielarz, P. Recent Advances in ATRP Methods in Relation to the Synthesis of Copolymer Coating Materials. Prog. Org. Coat. 2014, 77, 913−948. (13) Huang, J.; Murata, H.; Koepsel, R. R.; Russell, A. J.; Matyjaszewski, K. Antibacterial Polypropylene via Surface-Initiated Atom Transfer Radical Polymerization. Biomacromolecules 2007, 8, 1396−1399. (14) Ohno, K.; Kayama, Y.; Ladmiral, V.; Fukuda, Y.; Tsujii, Y. A Versatile Method of Initiator Fixation for Surface-Initiated Living Radical Polymerization on Polymeric Substrates. Macromolecules 2010, 43, 5569−5574. (15) Tsuda, M.; Tanaka, H.; Tagami, H.; Hori, F. Schotten-Baumann Esterification of Poly(vinyl alcohol) III. Preparation of Some Photosensitive Polymers and the Effects of Surface Active Agents on the Interfacial Esterification. Makromol. Chem. 1973, 167, 183−190. (16) Feng, W.; Brash, J.; Zhu, S. Atom-Transfer Radical Grafting Polymerization of 2-Methacryloyloxyethyl Phosphorylsholine from Silicon Wafer Surfaces. J. Polym. Sci., Part A: Polym. Chem. 2004, 42, 2931−2942. (17) Feng, W.; Zhu, S.; Ishihara, K.; Brash, J. L. Adsorption of Fibrinogen and Lysozyme on Silicon Grafted with Poly(2methacryloyloxyethyl Phosphorylcholine) via Surface-Initiated Atom Transfer Radical Polymerization. Langmuir 2005, 21, 5980−5987. (18) Inoue, Y.; Nakanishi, T.; Ishihara, K. Elastic Repulsion from Polymer Brush Layers Exhibiting High Protein Repellency. Langmuir 2013, 29, 10752−10758. (19) Iwata, R.; Suk-In, P.; Hoven, V. P.; Takahara, A.; Akiyoshi, K.; Iwasaki, Y. Control of Nanobiointerfaces Generated from WellDefined Biomimetic Polymer Brushes for Protein and Cell Manipulations. Biomacromolecules 2004, 5, 2308−2314. (20) Inoue, Y.; Ishihara, K. Reduction of Protein Adsorption on WellCharacterized Polymer Brush Layers with Varying Chemical Structures. Colloids Surf., B 2010, 81, 350−357. (21) Li, J.; Vaisman, L.; Marom, G.; Kim, J.-K. Br Treated Graphite Nanoplatelets for Improved Electrical Conductivity of Polymer Composites. Carbon 2007, 45, 744−750.

(22) Choi, S.-H.; Zhang Newby, B. Suppress Polystyrene Thin Film Dewetting by Modifying Substrate Surface with Aminopropyltriethoxysilane. Surf. Sci. 2006, 600, 1391−1404. (23) Inoue, Y.; Onodera, Y.; Ishihara, K. Preparation of a Thick Polymer Brush Layer Composed of Poly(2-methacryloyloxyethyl phosphorylcholine) by Surface-Initiatedatom Transfer Eadical Polymerization and Analysis of Protein Adsorption Resistance. Colloids Surf., B 2016, 141, 507−512. (24) Fukazawa, K.; Ishihara, K. Synthesis of Photoreactive Phospholipid Polymers for Use in Versatile Surface Modification of Various Materials to Obtain Extreme Wettability. ACS Appl. Mater. Interfaces 2013, 5, 6832−6836. (25) Lin, X.; Fukazawa, K.; Ishihara, K. Photoreactive Polymer Bearing a Zwitterionic Phosphorylcholine Group for Surface Modification of Biomaterials. ACS Appl. Mater. Interfaces 2015, 7, 17489−17498. (26) Iwasaki, Y.; Ishihara, K. Cell Membrane-inspired Phospholipid Polymers for Developing Medical Devices with Excellent Biointerfaces. Sci. Technol. Adv. Mater. 2012, 13, 064101.

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DOI: 10.1021/acsami.6b07145 ACS Appl. Mater. Interfaces XXXX, XXX, XXX−XXX