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Invention and global impact of bioinspired 2-methacryloyloxyethyl phosphorylcholine polymers: molecular design, functions, and implementation in medical devices

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Abstract

Medical devices are indispensable in modern medicine for saving patients with injuries or illnesses and improving their quality of life. The development of polymers that elicit minimal biological reactions upon contact with tissues or biological components is critical for the safe and effective use of these devices. 2-Methacryloyloxyethyl phosphorylcholine (MPC) polymers, invented in Japan, represent a milestone in bioinspired materials science because they have been designed to mimic the phosphorylcholine groups naturally present on cell membranes, endowing them with excellent biocompatibility and resistance to nonspecific protein adsorption. Diverse MPC polymer architectures have been synthesized to optimize functional expression and tailor surface properties. Moreover, molecular designs have enabled the modification of conventional polymers, metals, and ceramics, thereby expanding their utility in diverse biomedical applications. This review highlights the molecular design concept, interfacial properties, and current status of MPC polymers as highly reliable surface treatment materials and summarizes their broad implementation in medical devices.

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References

  1. Fang RH, Jiang Y, Fang JC, Zhang L. Cell membrane-derived nanomaterials for biomedical applications. Biomaterials. 2017;128:69–83.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Zhao J, Ruan J, Lv G, Shan Q, Fan Z, Wang H, et al. Cell membrane-based biomimetic nanosystems for advanced drug delivery in cancer therapy: a comprehensive review. Colloids Surf B Biointerfaces. 2022;215:112503.

    Article  PubMed  CAS  Google Scholar 

  3. Miyata Y, Segawa K. Protocol to analyze lipid asymmetry in the plasma membrane. STAR Protoc. 2022;3:101870.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Weinstein JN, Leserman LD. Liposomes as drug carriers in cancer chemotherapy. Pharm Ther. 1984;24:207–33.

    Article  CAS  Google Scholar 

  5. Yamaguchi T, Mizushima Y. Lipid microspheres for drug delivery from the pharmaceutical viewpoint. Crit Rev Ther Drug Carr Syst. 1994;11:215–29.

    CAS  Google Scholar 

  6. Hub HH, Hupfer B, Koch H, Ringsdorf H. Polymerizable phospholipid analogues—New stable biomembrane and cell models. Angew Chem Int Ed Engl. 1980;19:938–40.

    Article  PubMed  CAS  Google Scholar 

  7. Hayward JA, Johnston DS, Chapman D. Polymeric phospholipids as new biomaterials. Ann N Y Acad Sci. 1985;446:267–81.

    Article  PubMed  CAS  Google Scholar 

  8. Ishihara K, Ueda T, Nakabayashi N. Preparation of phospholipid polymers and their properties as polymer hydrogel membranes. Polym J. 1990;23:355–60.

    Article  Google Scholar 

  9. Bonte F, Hsu MJ, Papp A, Wu K, Regen SL, Juliano RL. Interactions of polymerizable phosphatidylcholine vesicles with blood components: relevance to biocompatibility. Biochim Biophys Acta. 1987;900:1–9.

    Article  PubMed  CAS  Google Scholar 

  10. Ishihara K. Revolutionary advances in 2-methacryloyloxyethyl phosphorylcholine polymers as biomaterials. J Biomed Mater Res A. 2019;107:933–43.

    Article  PubMed  CAS  Google Scholar 

  11. Ueda T, Oshida H, Kurita K, Ishihara K, Nakabayashi N. Preparation of 2-methacryloyloxyethyl phosphorylcholine copolymers with alkyl methacrylates and their blood compatibility. Polym J. 2002;24:1259–69.

    Article  Google Scholar 

  12. Lobb EJ, Ma I, Billingham NC, Armes SP, Lewis AL. Facile synthesis of well-defined, biocompatible phosphorylcholine-based methacrylate copolymers via atom transfer radical polymerization at 20 °C. J Am Chem Soc. 2001;123:7913–14.

    Article  PubMed  CAS  Google Scholar 

  13. Ma I, Lobb EJ, Billingham NC, Armes SP, Lewis AL, Lloyd AW, et al. Synthesis of biocompatible polymers. 1. Homopolymerization of 2-methacryloyloxyethyl phosphorylcholine via ATRP in protic solvents: an optimization study. Macromolecules. 2002;35:9306–14.

    Article  CAS  Google Scholar 

  14. Adibnia V, Olszewski M, De Crescenzo G, Matyjaszewski K, Banquy X. Superlubricity of zwitterionic bottlebrush polymers in the presence of multivalent ions. J Am Chem Soc. 2020;142:14843–47.

    Article  PubMed  CAS  Google Scholar 

  15. Chantasirichot S, Inoue Y, Ishihara K. Photoinduced atom transfer radical polymerization in a polar solvent to synthesize a water-soluble poly(2-methacryloyloxyethyl phosphorylcholine) and its block-type copolymers. Polymer. 2015;61:55–60.

    Article  CAS  Google Scholar 

  16. Yusa SI, Fukuda K, Yamamoto T, Ishihara K, Morishima Y. Synthesis of well-defined amphiphilic block copolymers having phospholipid polymer sequences as a novel biocompatible polymer micelle reagent. Biomacromolecules. 2005;6:663–70.

    Article  PubMed  CAS  Google Scholar 

  17. Inoue Y, Watanabe J, Takai M, Yusa SI, Ishihara K. Synthesis of sequence-controlled copolymers from extremely polar and apolar monomers by living radical polymerization and their phase-separated structures. J Polym Sci Part A: Polym Chem. 2005;43:6073–83.

    Article  CAS  Google Scholar 

  18. Bhuchar N, Deng Z, Ishihara K, Narain R. Detailed study of the reversible addition-fragmentation chain transfer polymerization and co-polymerization of 2-methacryloyloxyethyl phosphorylcholine. Polym Chem. 2011;2:632–39.

    Article  CAS  Google Scholar 

  19. Ishihara K, Iwasaki Y, Nakabayashi N. Polymeric lipid nanosphere consisting of water soluble poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate). Polym J. 1999;31:1231–6.

    Article  CAS  Google Scholar 

  20. Monge S, Canniccioni B, Graillot A, Robin JJ. Phosphorus-containing polymers: a great opportunity for the biomedical field. Biomacromolecules. 2011;12:1973–82.

    Article  PubMed  CAS  Google Scholar 

  21. Iwasaki Y. Photoassisted Surface modification with zwitterionic phosphorylcholine polymers for the fabrication of ideal biointerfaces. Langmuir. 2023;39:15417–30.

    Article  PubMed  CAS  Google Scholar 

  22. Seetasang S, Xu Y. Recent progress and perspectives in applications of 2-methacryloyloxyethyl phosphorylcholine polymers in biodevices at small scales. J Mater Chem B. 2022;10:2323–37.

    Article  PubMed  CAS  Google Scholar 

  23. Matsuno R, Takami K, Ishihara K. Simple synthesis of a library of zwitterionic surfactants via Michael-type addition of methacrylate and alkane thiol compounds. Langmuir. 2010;26:13028–32.

    Article  PubMed  CAS  Google Scholar 

  24. Takami K, Matsuno R, Ishihara K. Synthesis of polyurethanes by polyaddition using diol compounds with methacrylate-derived functional groups. Polymer. 2011;52:5445–51.

    Article  CAS  Google Scholar 

  25. Ye SH, Jang YS, Yun YH, Shankarraman V, Woolley JR, Hong Y, et al. Surface modification of a biodegradable magnesium alloy with phosphorylcholine (PC) and sulfobetaine (SB) functional macromolecules for reduced thrombogenicity and acute corrosion resistance. Langmuir. 2013;29:8320–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Kadoma Y, Nakabayashi N, Masuhara E, Yamauchi J. Synthesis and hemolysis test of the polymer containing phosphorylcholine groups. Kobunshi Ronbunshu. 1978;35:423 (Japanese Journal of Polymer Science and Technology)(in Japanese).

    Article  CAS  Google Scholar 

  27. Fukushima S, Kadoma Y, Nakabayashi N. Interaction between polymer containing phosphorylcholine group and cells. Kobunshi Ronbunshu. 1983;40:785–93. (Japanese Journal of Polymer Science and Technology)(in Japanese).

    Article  CAS  Google Scholar 

  28. Nakaya T, Toyoda H, Imoto M. Polymeric phospholipid analogues XIII. Synthesis and properties of vinyl polymers containing phosphatidyl choline groups. Polym J. 1986;18:881–5.

    Article  CAS  Google Scholar 

  29. Yang H, Zheng Q, Cheng R. New insight into “polyelectrolyte effect. Colloids Surf A Physicochem Eng Asp. 2012;407:1–8.

    Article  CAS  Google Scholar 

  30. Ratner BD. Surface modification of polymers: chemical, biological and surface analytical challenges. Biosens Bioelectron. 1995;10:797–804.

    Article  PubMed  CAS  Google Scholar 

  31. Amoako K, Ukita R, Cook KE. Antifouling zwitterionic polymer coatings for blood-bearing medical devices. Langmuir. 2025;41:2994–3006.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Iwashita H, Itokawa T, Suzuki T, Okajima Y, Kakisu K, Hori Y. Evaluation of in vitro wettability of soft contact lenses using tear supplements. Eye Contact Lens. 2021;47:244–8.

    Article  PubMed  Google Scholar 

  33. Fujiwara N, Yumoto H, Miyamoto K, Hirota K, Nakae H, Tanaka S, et al. 2-Methacryloyloxyethyl phosphorylcholine(MPC)-polymer suppresses an increase of oral bacteria: a single-blind, crossover clinical trial. Clin Oral Investig. 2019;23:739–6.

    Article  PubMed  Google Scholar 

  34. Ayaki M, Iwasawa A, Niwano Y. Cytotoxicity assays of new artificial tears containing 2-methacryloyloxyethyl phosphorylcholine polymer for ocular surface cells. Jpn J Ophthalmol. 2011;55:541–6.

    Article  PubMed  CAS  Google Scholar 

  35. Kanekura T, Nagata Y, Miyoshi H, Ishihara K, Nakabayashi N, Kanzaki T. Beneficial effects of synthetic phospholipid polymer, poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate), on stratum corneum function. Clin Exp Dermatol. 2002;27:230–4.

    Article  PubMed  CAS  Google Scholar 

  36. Cho Lee AR, Moon H, Ishihara K. Stabilization of lipid lamellar bilayer structure of stratum corneum modulated by poly(2-methacryloyloxyethyl phosphorylcholine) in relation to skin hydration and skin protection. Tissue Eng Regen Med. 2021;18:953–62.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Kihara S, Yamazaki K, Litwak KN, Litwak P, Kameneva MV, Ushiyama H, et al. In vivo evaluation of a MPC polymer coated continuous flow left ventricular assist system. Artif Organs. 2003;27:188–92.

    Article  PubMed  Google Scholar 

  38. Fujii K, Matsumoto HN, Koyama Y, Iwasaki Y, Ishihara K, Takakuda K. Prevention of biofilm formation with a coating of 2-methacryloyloxyethyl phosphorylcholine polymer. J Vet Med Sci. 2008;70:167–73.

    Article  PubMed  CAS  Google Scholar 

  39. Kaneko T, Saito T, Shobuike T, Miyamoto H, Matsuda J, Fukazawa K, et al. 2-Methacryloyloxyethyl phosphorylcholine polymer coating inhibits bacterial adhesion and biofilm formation on a suture: An in vitro and in vivo study. Biomed Res Int. 2020;2020:5639651.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Pappalardo F, Della Valle P, Crescenzi G, Corno C, Franco A, Torracca L, et al. Phosphorylcholine coating may limit thrombin formation during high-risk cardiac surgery: a randomized controlled trial. Ann Thorac Surg. 2006;81:886–91.

    Article  PubMed  Google Scholar 

  41. Iida Y, Hongo K, Onoda T, Kita Y, Ishihara Y, Takabayashi N, et al. Use of catheter with 2-methacryloyloxyethyl phosphorylcholine polymer coating is associated with long-term availability of central venous port. Sci Rep. 2021;11:5385.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Nishida K, Sakakida M, Ichinose K, Uemura T, Uehara M, Kajiwara K, et al. Development of a ferrocene-mediated needle-type glucose sensor covered with newly designed biocompatible membrane, 2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate. Med Prog Technol. 1995;21:91–103.

    PubMed  CAS  Google Scholar 

  43. Ranucci M, Isgrò G, Soro G, Canziani A, Menicanti L, Frigiola A. Reduced systemic heparin dose with phosphorylcholine coated closed circuit in coronary operations. Int J Artif Organs. 2004;27:311–9.

    Article  PubMed  CAS  Google Scholar 

  44. Marguerite S, Levy F, Quessard A, Dupeyron JP, Gros C, Steib A. Impact of a phosphorylcholine-coated cardiac bypass circuit on blood loss and platelet function: a prospective, randomized study. J Extra Corpor Technol. 2012;44:5–9.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Ishihara K, Fukumoto K, Miyazaki H, Nakabayashi N. Improvement of hemocompatibility on a cellulose dialysis membrane with a novel biomedical polymer having a phospholipid polar group. Artif Organs. 1994;18:559–64.

    Article  PubMed  CAS  Google Scholar 

  46. Whelan DM, van der Giessen WJ, Krabbendam SC, van Vliet EA, Verdouw PD, Serruys PW, et al. Biocompatibility of phosphorylcholine coated stents in normal porcine coronary arteries. Heart. 2000;83:338–45.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Collingwood R, Gibson L, Sedlik S, Virmani R, Carter AJ. Stent-based delivery of ABT-578 via a phosphorylcholine surface coating reduces neointimal formation in the porcine coronary model. Catheter Cardiovasc Inter. 2005;65:227–32.

    Google Scholar 

  48. Hagen MW, Girdhar G, Wainwright J, Hinds MT. Thrombogenicity of flow diverters in an ex vivo shunt model: effect of phosphorylcholine surface modification. J Neurointerv Surg. 2017;9:1006–11.

    Article  PubMed  Google Scholar 

  49. Ikeya K, Iwasa F, Inoue Y, Fukunishi M, Takahashi N, Ishihara K, et al. Inhibition of denture plaque deposition on complete dentures by 2-methacryloyloxyethyl phosphorylcholine polymer coating: A clinical study. J Prosthet Dent. 2018;119:67–74.

    Article  PubMed  CAS  Google Scholar 

  50. Moro T, Takatori Y, Ishihara K, Konno T, Takigawa Y, Matsushita T, et al. Surface grafting of artificial joints with a biocompatible polymer for preventing periprosthetic osteolysis. Nat Mater. 2004;3:829–36.

    Article  PubMed  CAS  Google Scholar 

  51. Ishihara K, Nakabayashi N, Fukumoto K, Aoki J. Improvement of blood compatibility on cellulose dialysis membrane. I. Grafting of 2-methacryloyloxyethyl phosphorylcholine on to a cellulose membrane surface. Biomaterials. 1992;13:145–9.

    Article  PubMed  CAS  Google Scholar 

  52. Kyomoto M, Ishihara K. Self-initiated surface graft polymerization of 2-methacryloyloxyethyl phosphorylcholine on poly(ether ether ketone) by photoirradiation. ACS Appl Mater Interfaces. 2009;1:537–42.

    Article  PubMed  CAS  Google Scholar 

  53. Shi X, Cantu-Crouch D, Sharma V, Pruitt J, Yao G, Fukazawa K, et al. Surface characterization of a silicone hydrogel contact lens having bioinspired 2-methacryloyloxyethyl phosphorylcholine polymer layer in hydrated state. Colloids Surf B Biointerfaces. 2021;199:111539.

    Article  PubMed  CAS  Google Scholar 

  54. Yoneyama T, Ishihara K, Nakabayashi N, Ito M, Mishima Y. Short-term in vivo evaluation of small-diameter vascular prosthesis composed of segmented poly(etherurethane)/2-methacryloyloxyethyl phosphorylcholine polymer blend. J Biomed Mater Res. 1998;43:15–20.

    Article  PubMed  CAS  Google Scholar 

  55. Hasegawa T, Iwasaki Y, Ishihara K. Preparation and performance of protein-adsorption-resistant asymmetric porous membrane composed of polysulfone/phospholipid polymer blend. Biomaterials. 2001;22:243–51.

    Article  PubMed  CAS  Google Scholar 

  56. Ueda H, Watanabe J, Konno T, Takai M, Saito A, Ishihara K. Asymmetrically functional surface properties on biocompatible phospholipid polymer membrane for bioartificial kidney. J Biomed Mater Res A. 2006;77:19–27.

    Article  PubMed  Google Scholar 

  57. Ishihara K, Nishiuchi D, Watanabe J, Iwasaki Y. Polyethylene/phospholipid polymer alloy as an alternative to poly(vinylchloride)-based materials. Biomaterials. 2004;25:1115–22.

    Article  PubMed  CAS  Google Scholar 

  58. Iwasaki Y, Nakabayashi N, Ishihara K. In vitro and ex vivo blood compatibility study of 2-methacryloyloxyethyl phosphorylcholine (MPC) copolymer-coated hemodialysis hollow fibers. J Artif Organs. 2003;6:260–6.

    Article  PubMed  CAS  Google Scholar 

  59. Ye SH, Watanabe J, Takai M, Iwasaki Y, Ishihara K. In situ Modification on Cellulose Acetate Hollow Fiber Membrane Modified Phospholipid Polymer for Biomedical Application. J Membr Sci. 2005;249:133–45.

    Article  CAS  Google Scholar 

  60. Konno T, Ito T, Takai M, Ishihara K. Enzymatic photochemical sensing using luciferase-immobilized polymer nanoparticles covered with artificial cell membrane. J Biomater Sci Polym Ed. 2006;17:1347–57.

    Article  PubMed  CAS  Google Scholar 

  61. Shimizu T, Goda T, Minoura N, Takai M, Ishihara K. Super-hydrophilic silicone hydrogels with interpenetrating poly(2-methacryloyloxyethyl phosphorylcholine) networks. Biomaterials. 2010;31:3274–80.

    Article  PubMed  CAS  Google Scholar 

  62. Iwasaki Y, Aiba Y, Morimoto N, Nakabayashi N, Ishihara K. Semi-interpenetrating polymer networks composed of biocompatible phospholipid polymer and segmented polyurethane. J Biomed Mater Res. 2000;52:701–8.

    Article  PubMed  CAS  Google Scholar 

  63. Ishihara K. Highly lubricated polymer interfaces for advanced artificial hip joint through biomimetic design. Polym J. 2015;47:585–97.

    Article  CAS  Google Scholar 

  64. Iwata R, Suk-In P, Hoven VP, Takahara A, Akiyoshi K, Iwasaki Y. Control of nanobiointerfaces generated from well-defined biomimetic polymer brushes for protein and cell manipulations. Biomacromolecules. 2004;5:2308–14.

    Article  PubMed  CAS  Google Scholar 

  65. Feng W, Zhu S, Ishihara K, Brash JL. Adsorption of fibrinogen and lysozyme on silicon grafted with poly(2-methacryloyloxyethyl phosphorylcholine) via surface-initiated atom transfer radical polymerization. Langmuir. 2005;21:5980–7.

    Article  PubMed  CAS  Google Scholar 

  66. Zhang Z, Morse AJ, Armes SP, Lewis AL, Geoghegan M, Leggett GJ. Effect of brush thickness and solvent composition on the friction force response of poly(2-(methacryloyloxy)ethylphosphorylcholine) brushes. Langmuir. 2011;27:2514–21.

    Article  PubMed  CAS  Google Scholar 

  67. Jiang Y, Su Y, Zhao L, Meng F, Wang Q, Ding C, et al. Preparation and antifouling properties of 2-(meth-acryloyloxy)ethyl cholinephosphate based polymers modified surface with different molecular architectures by ATRP. Colloids Surf B Biointerfaces. 2017;156:87–94.

    Article  PubMed  CAS  Google Scholar 

  68. Futamura K, Matsuno R, Konno T, Takai M, Ishihara K. Rapid development of hydrophilicity and protein adsorption resistance by polymer surfaces bearing phosphorylcholine and naphthalene groups. Langmuir. 2008;24:10340–4. 16.

    Article  PubMed  CAS  Google Scholar 

  69. Kobayashi M, Terayama Y, Hosaka N, Kaido M, Suzuki A, Yamada N, et al. Friction behavior of high-density poly(2-methacryloyloxyethyl phosphorylcholine) brush in aqueous media. Soft Matter. 2007;3:740–6.

    Article  PubMed  CAS  Google Scholar 

  70. Ishihara K, Mu M, Konno T, Inoue Y, Fukazawa K. The unique hydration state of poly(2-methacryloyloxyethyl phosphorylcholine). J Biomater Sci Polym Ed. 2017;28:884–99.

    Article  PubMed  CAS  Google Scholar 

  71. Kitano H, Imai M, Mori T, Gemmei-Ide M, Yokoyama Y, Ishihara K. Structure of water in the vicinity of phospholipid analogue copolymers as studied by vibrational spectroscopy. Langmuir. 2003;19:10260–6.

    Article  CAS  Google Scholar 

  72. Kitano H. Characterization of polymer materials based on structure analyses of vicinal water. Polym J. 2016;48:15–24.

    Article  CAS  Google Scholar 

  73. Shiomoto S, Inoue K, Higuchi H, Nishimura SN, Takaba H, Tanaka M, et al. Characterization of hydration water bound to choline phosphate-containing polymers. Biomacromolecules. 2022;23:2999–3008.

    Article  PubMed  CAS  Google Scholar 

  74. Ishihara K. Biomimetic polymers with phosphorylcholine groups as biomaterials for medical devices. Proc Jpn Acad, Ser B. 2024;100:579–606.

    Article  CAS  Google Scholar 

  75. Holmlin RE, Chen X, Chapman RG, Takayama S, Whitesides GM. Zwitterionic SAMs that resist nonspecific adsorption of protein from aqueous buffer. Langmuir. 2001;17:2841–50.

    Article  PubMed  CAS  Google Scholar 

  76. Ostuni E, Chapman RG, Holmlin RE, Takayama S, Whitesides GM. A survey of structure−property relationships of surfaces that resist the adsorption of protein. Langmuir. 2001;17:5605–20.

    Article  CAS  Google Scholar 

  77. Ishihara K. Biomimetic materials based on zwitterionic polymers toward human-friendly medical devices. Sci Technol Adv Mater. 2022;23:498–524.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Ishihara K, Nomura H, Mihara T, Kurita K, Iwasaki Y, Nakabayashi N. Why do phospholipid polymers reduce protein adsorption?. J Biomed Mater Res. 1998;39:323–30.

    Article  PubMed  CAS  Google Scholar 

  79. Ishihara K, Ziats NP, Tierney BP, Nakabayashi N, Anderson JM. Protein adsorption from human plasma is reduced on phospholipid polymers. J Biomed Mater Res. 1991;25:1397–407.

    Article  PubMed  CAS  Google Scholar 

  80. Ishihara K. Blood-compatible surfaces with phosphorylcholine-based polymers for cardiovascular medical devices. Langmuir. 2019;35:1778–87.

    Article  PubMed  CAS  Google Scholar 

  81. Çelebioğlu EC, Blevrakis E, Yilmaz M, Doğan İ, Erkent FD, Kortun Ş, et al. Efficacy and performance of the new pipeline vantage flow diverter stent with shield technology: Short-term results of a single-center experience. Sci Prog. 2025;108:368504251349714.

    Article  PubMed  Google Scholar 

  82. Campbell EJ, O’Byrne V, Stratford PW, Quirk I, Vick TA, Wiles MC, et al. Biocompatible surfaces using methacryloylphosphorylcholine laurylmethacrylate copolymer. ASAIO J. 1994;40:M853–7.

    Article  PubMed  CAS  Google Scholar 

  83. Snyder TA, Tsukui H, Kihara S, Akimoto T, Litwak KN, Kameneva MV, et al. Preclinical biocompatibility assessment of the EVAHEART ventricular assist device: coating comparison and platelet activation. J Biomed Mater Res A. 2007;81:85–92.

    Article  PubMed  Google Scholar 

  84. Yamabe T. Artificial organs with nano-technology and development of the new diagnosis tool. Ann NanoBME. 2009;2:1–10.

    Google Scholar 

  85. https://www.evaheart-usa.com/clinical-trial?utm_source=chatgpt.com

  86. Chen HB, Wang XQ, Du J, Shi J, Ji BY, Shi L, et al. Long-term outcome of EVAHEART I implantable ventricular assist device for the treatment of end stage heart failure: clinical 3-year follow-up results of 15 cases. Zhonghua Xin Xue Guan Bing Za Zhi. Chin J Cardiovascular Dis). 2023;51:393–99. (in Chinese).

    CAS  Google Scholar 

  87. Lewis AL, Stratford PW. A review on phosphorylcholine-coated stents. J Long Term Eff Med Implants. 2017;27:233–52.

    Article  PubMed  Google Scholar 

  88. Song PS, Hahn JY, Kim DI, Song YB, Choi SH, Choi JH, et al. Duration of clopidogrel-based dual antiplatelet therapy and clinical outcomes after endeavor sprint zotarolimus eluting stent implantation in patients presenting with acute coronary syndrome. Eur J Intern Med. 2015;26:521–7.

    Article  PubMed  CAS  Google Scholar 

  89. Caroff J, Tamura T, King RM. Phosphorylcholine surface modified flow diverter associated with reduced intimal hyperplasia. J Neurointerv Surg. 2018;10:1097–101.

    Article  PubMed  Google Scholar 

  90. Ishihara K, Iwasaki Y, Ebihara S, Shindo Y, Nakabayashi N. Photoinduced graft polymerization of 2-methacryloyloxyethyl phosphorylcholine on polyethylene membrane surface for obtaining blood cell adhesion resistance. Colloids Surf B Biointerfaces. 2000;18:325–35.

    Article  PubMed  CAS  Google Scholar 

  91. Kyomoto M, Moro T, Saiga K, Hashimoto M, Ito H, Kawaguchi H, et al. Biomimetic hydration lubrication with various polyelectrolyte layers on cross-linked polyethylene orthopedic bearing materials. Biomaterials. 2012;33:4451–9.

    Article  PubMed  CAS  Google Scholar 

  92. Moro T, Takatori Y, Kyomoto M, Ishihara K, Hashimoto M, Ito H, et al. Long-term hip simulator testing of the artificial hip joint bearing surface grafted with biocompatible phospholipid polymer. J Orthop Res. 2014;32:369–76.

    Article  PubMed  CAS  Google Scholar 

  93. Moro T, Takatori Y, Tanaka S, Ishihara K, Oda H, Kim YT, et al. Clinical safety and wear resistance of the phospholipid polymer-grafted highly cross-linked polyethylene liner. J Orthop Res. 2017;35:2007–16.

    Article  PubMed  CAS  Google Scholar 

  94. Kyomoto M, Moro T, Yamane S, Watanabe K, Hashimoto M, Takatori Y, et al. Poly(2-methacryloyloxyethyl phosphorylcholine) grafting and vitamin E blending for high wear resistance and oxidative stability of orthopedic bearings. Biomaterials. 2014;35:6677–86.

    Article  PubMed  CAS  Google Scholar 

  95. Kyomoto M, Moro T, Yamane S, Takatori Y, Tanaka S, Ishihara K. A hydrated phospholipid polymer-grafted layer prevents lipid-related oxidative degradation of cross-linked polyethylene. Biomaterials. 2017;112:122–32.

    Article  PubMed  CAS  Google Scholar 

  96. Kyomoto M, Moro T, Yamane S, Watanabe K, Hashimoto M, Tanaka S, et al. A phospholipid polymer graft layer affords high resistance for wear and oxidation under load bearing conditions. J Mech Behav Biomed Mater. 2018;79:203–12.

    Article  PubMed  CAS  Google Scholar 

  97. Goda T, Ishihara K. Soft contact lens biomaterials from bioinspired phospholipid polymers. Expert Rev Med Devices. 2006;3:167–74.

    Article  PubMed  CAS  Google Scholar 

  98. Walsh K, Jones LW, Morgan P, Papas EB, Sulley A. Topical review: Twenty-five years of silicone hydrogel soft contact lenses. Optom Vis Sci. 2025;102:361–74.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Ishihara K, Shi X, Fukazawa K, Yamaoka T, Yao G, Wu JY. Biomimetic-engineered silicone hydrogel contact lens materials. ACS Appl Bio Mater. 2023;6:3600–16.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  100. Capote-Puente R, Sánchez-González JM, Sánchez-González MC, Bautista-Llamas MJ. Evaluation of Celligent® biomimetic water gradient contact lens effects on ocular surface and subjective symptoms. Diagnostics (Basel). 2023;13:1258.

    Article  PubMed  CAS  Google Scholar 

  101. Shi X, Sharma V, Cantu-Crouch D, Yao G, Fukazawa K, Ishihara K, et al. Nanoscaled morphology and mechanical properties of a biomimetic polymer surface on a silicone hydrogel contact lens. Langmuir. 2021;37:13961–7.

    Article  PubMed  CAS  Google Scholar 

  102. Sharma V, Shi XC, Yao G, Zheng Y, Spencer ND, Wu JY. Fluid confinement within a branched polymer structure enhances tribological performance of a poly(2-methacryloyloxyethyl phosphorylcholine)-surface-modified contact lens. R Soc Open Sci. 2024;11:240957.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  103. Liang S, Zheng Y, Sharma V, Shows A, Dunbar DC, Shi X, et al. Surface and antifouling properties of a biomimetic reusable contact lens material. ACS Omega. 2025;10:19697–704.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  104. Ishihara K, Fukazawa K, Sharma V, Liang S, Shows A, Dunbar DC, et al. Antifouling silicone hydrogel contact lenses with a bioinspired 2-methacryloyloxyethyl phosphorylcholine polymer surface. ACS Omega. 2021;6:7058–67.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  105. Harris V, Pifer R, Shannon P, Crary M. Comparative evaluation of pseudomonas aeruginosa adhesion to a poly-(2-methacryloyloxyethyl phosphorylcholine)-modified silicone hydrogel contact lens. Vis (Basel). 2023;7:27.

    Google Scholar 

  106. Mimura T, Nakagomi R. Comparison of non-water proof mascara adhesion on the surface of different two-week frequent replacement silicone hydrogel contact lenses. Clin Optom (Auckl). 2025;17:73–82.

    Article  PubMed  Google Scholar 

  107. Mimura T, Nakagomi R, Fujishima H. Comparison of asian dust adhesion on the urface of different reusable silicone hydrogel contact lenses. Int Ophthalmol. 2025;45:226.

    Article  PubMed  Google Scholar 

  108. Sin MC, Chen SH, Chang Y. Hemocompatibility of zwitterionic interfaces and membranes. Polym J. 2014;46:436–43.

    Article  CAS  Google Scholar 

  109. Hiranphinyophat S, Iwasaki Y. Controlled biointerfaces with biomimetic phosphorus-containing polymers. Sci Technol Adv Mater. 2021;22:301–16.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  110. Moayedi S, Xia W, Lundergan L, Yuan H, Xu J. Zwitterionic polymers for biomedical applications: Antimicrobial and antifouling strategies toward implantable medical devices and drug delivery. Langmuir. 2024;40:23125–45.

    Article  PubMed  CAS  Google Scholar 

  111. Lv W, Wang Y, Fu H, Liang Z, Huang B, Jiang R, et al. Recent advances of multifunctional zwitterionic polymers for biomedical application. Acta Biomater. 2024;181:19–45.

    Article  PubMed  CAS  Google Scholar 

  112. Ahmed ST, Madinya JJ, Leckband DE. Ionic strength dependent forces between end-grafted Poly (sulfobetaine) films and mica. J Colloid Interface Sci. 2022;606:298–306.

    Article  PubMed  CAS  Google Scholar 

  113. Lien C-C, Chen P-J, Venault A, Tang S-H, Fu Y, Dizon GV, et al. A zwitterionic interpenetrating network for improving the blood compatibility of polypropylene membranes applied to leukodepletion. J Membr Sci. 2019;584:148–60.

    Article  CAS  Google Scholar 

  114. Ye SH, Orizondo RA, De BN, Kim S, Frankowski BJ, Federspiel WJ, et al. Epoxy silane sulfobetaine block copolymers for simple, aqueous thromboresistant coating on ambulatory assist lung devices. J Biomed Mater Res A. 2024;112:99–109.

    Article  PubMed  CAS  Google Scholar 

  115. Xiang Y, Xu RG, Leng Y. Molecular understanding of ion effect on polyzwitterion conformation in an aqueous environment. Langmuir. 2020;36:7648–57.

    Article  PubMed  CAS  Google Scholar 

  116. Venault A, Ye CC, Lin YC, Tsai CW, Jhong JF, Ruaan RC, et al. Zwitterionic fibrous polypropylene assembled with amphiphatic carboxybetaine copolymers for hemocompatible blood filtration. Acta Biomater. 2016;40:130–41.

    Article  PubMed  CAS  Google Scholar 

  117. Lin X, Wu K, Zhou Q, Jain P, Boit MO, Li B, et al. Photoreactive carboxybetaine copolymers impart biocompatibility and inhibit plasticizer leaching on polyvinyl chloride. ACS Appl Mater Interfaces. 2020;12:41026–37.

    Article  PubMed  CAS  Google Scholar 

  118. Ryujin T, Shimizu T, Miyahara R, Asai D, Shimazui R, Yoshikawa T, et al. Blood retention and antigenicity of polycarboxybetaine-modified liposomes. Int J Pharm. 2020;586:119521.

    Article  PubMed  CAS  Google Scholar 

  119. Hu G, Emrick T. Functional choline phosphate polymers. J Am Chem Soc. 2020;138:1828–31.

    Article  Google Scholar 

  120. Mukai M, Ihara D, Chu CW, Cheng CH, Takahara A. Synthesis and hydration behavior of a hydrolysis-resistant quasi-choline phosphate zwitterionic polymer. Biomacromolecules. 2020;21:2125–31.

    Article  PubMed  CAS  Google Scholar 

  121. Yu X, Yang X, Horte S, Kizhakkedathu JN, Brooks DE. A thermoreversible poly(choline phosphate) based universal biomembrane adhesive. Macromol Biosci. 2014;14:334–9.

    Article  PubMed  CAS  Google Scholar 

  122. Yao Y, Dang X, Qiao X, Li R, Chen J, Huang Z, et al. Crosslinked biomimetic coating modified stainless-steel-mesh enables completely self-cleaning separation of crude oil/water mixtures. Water Res. 2022;224:119052.

    Article  PubMed  CAS  Google Scholar 

  123. He K, Duan H, Chen GY. Cleaning of oil fouling with water enabled by zwitterionic polyelectrolyte coatings: Overcoming the imperative challenge of oil-water separation membranes. ACS Nano. 2015;9:9188–98.

    Article  PubMed  CAS  Google Scholar 

  124. Niu J, Wang H, Chen J. Bio-inspired zwitterionic copolymers for antifouling surface and oil-water separation. Colloids Surf A Physicochemical Eng Asp. 2021;626:127016.

    Article  CAS  Google Scholar 

  125. Liu Q, Locklin J. Transparent grafted zwitterionic copolymer coatings that exhibit both antifogging and self-cleaning properties. ACS Omega. 2018;3:17743–50.

    Article  CAS  Google Scholar 

  126. Ma MQ, Zhang C, Chen TT, Yang J, Wang JJ, Ji J, et al. Bioinspired polydopamine/polyzwitterion coatings for underwater anti-oil and -freezing surfaces. Langmuir. 2019;35:1895–901.

    Article  PubMed  CAS  Google Scholar 

  127. Taylor ME, Panzer MJ. Fully-zwitterionic polymer-supported ionogel electrolytes featuring a hydrophobic ionic liquid. J Phys Chem. 2018;122:8469–76.

    Article  CAS  Google Scholar 

  128. Yoshizawa-Fujita M, Ohno H. Applications of zwitterions and zwitterionic polymers for Li-ion batteries. Chem Rec. 2023;23:e202200287.

    Article  PubMed  CAS  Google Scholar 

  129. Tadesse MY, Zhang Z, Marioni N, Zofchak ES, Duncan TJ, Ganesan V. Mechanisms of ion transport in lithium salt-doped zwitterionic polymer-supported ionic liquid electrolytes. J Chem Phys. 2024;160:024905.

    Article  PubMed  CAS  Google Scholar 

  130. Alsaedi MK, Tadesse MY, Ganesan V. Zwitterionic polymer ionogel electrolytes supported by coulombic cross-links: Impacts of alkali metal cation identity. J Phys Chem B. 2024;128:3273–81.

    Article  PubMed  CAS  Google Scholar 

  131. Kim H, Hight-Huf N, Kang JH, Bisnoff P, Sundararajan S, Thompson T, et al. Polymer zwitterions for stabilization of CsPbBr3 perovskite nanoparticles and nanocomposite films. Angew Chem Int Ed Engl. 2020;59:10802–6.

    Article  PubMed  CAS  Google Scholar 

  132. Zhang L, Gao J, You Z. A multifunctional phosphorylcholine-based polymer reduces energy loss for efficient perovskite solar cells. J Mater Chem C. 2022;10:16781–8.

    Article  CAS  Google Scholar 

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Acknowledgements

The author would like to thank the Guest Editor of this special issue, Prof. Chie Kojima, Institute of Science Tokyo, for the invitation to contribute to the manuscript. The author deeply appreciates Dr. Kyoko Fukazawa of Alcon Research, LLC, for reviewing the draft manuscript and providing significant suggestions. Additionally, the author thanks Prof. Yasuhiko Iwasaki, Kansai University; Dr. Kenji Yamazaki, Hokkaido Cardiovascular Hospital; Prof. Toru Moro, The University of Tokyo; and Dr. Masayuki Kyomoto, Kyocera Co., for providing important information used in this review manuscript. The author would also like to thank all the staff, students, and collaborators who supported the execution of this research.

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    Kazuhiko Ishihara

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Ishihara, K. Invention and global impact of bioinspired 2-methacryloyloxyethyl phosphorylcholine polymers: molecular design, functions, and implementation in medical devices. Polym J (2025). https://doi.org/10.1038/s41428-025-01109-6

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