Design of Multifunctional Soft Biomaterials: Based on the Intermediate Water Concept

  • Masaru TanakaEmail author


There are numerous parameters of polymeric biomaterials that can affect the protein adsorption and cell adhesion. The mechanisms responsible for the polymer/protein/cell interactions at the molecular level have not been clearly demonstrated, although many experimental and theoretical efforts have been made to understand these mechanisms. Water interactions have been recognized as fundamental for the protein and cell response to contact with polymers. This chapter focuses on the interfacial water at the polymer/protein/cell interfaces and specific water structure in hydrated biopolymers and bio-inspired water in hydrated synthetic polymers. Additionally, it highlights recent developments in the use of biocompatible polymeric biomaterials for medical devices and provides an overview of the progress made in the design of multifunctional element-block polymers by controlling the bio-inspired water structure through precision polymer synthesis.


Biocompatibility Blood compatibility Water structure Protein adsorption Cell adhesion 



The authors are very grateful to Professor Emeritus Teiji Tsuruta (University of Tokyo) for his valuable advice. The author also would like to thank all members of the Tsuruta Forum for their helpful comments.


  1. 1.
    a). Hoffman AS (2002) Hydrogels for biomedical applications. Adv Drug Deliv Rev 43:3–13. b). Ratner BD, Hoffman AS, Schoen FJ, Lemons JE (2004) Biomaterials science; an introduction to materials in medicine. Academic, London. c) Special Issue of Prof. T. Tsuruta (2010) J Biomater Sci Polym Ed 21:1827–1970Google Scholar
  2. 2.
    Tanaka M, Mochizuki A, Ishii N, Motomura T, Hatakeyama T (2002) Study on blood compatibility of poly(2-methoxyethylacrylate). Relationship between water structure and platelet compatibility in poly(2-methoxylethylacrylate-co-2-hydroxyethylmethacrylate). Biomacromolecules 3:36–41CrossRefGoogle Scholar
  3. 3.
    Peppas NA (1987) Hydrogel in medicine and pharmacy, vol 2. CRC Press, Boca RatonGoogle Scholar
  4. 4.
    Okano T, Nishiyama S, Shinohara I, Akaike T, Sakurai Y, Kataoka K, Tsuruta T (1981) Effect of hydrophilic and hydrophobic microdomains on mode of interaction between block copolymer and blob platelets. J Biomed Mater Res 15:393–403CrossRefGoogle Scholar
  5. 5.
    Ishihara K, Nomura H, Mihara T, Kurita K, Iwasaki Y, Nakabayashi N (1998) Why do phospholipid polymers reduce protein adsorption? J Biomed Mater Res 39:323–330CrossRefGoogle Scholar
  6. 6.
    Holmlin RE, Chen X, Chapman RG, Takayama S, Whitesides GM (2001) Zwitterionic SAMs that resist nonspecific adsorption of protein from aqueous buffer. Langmuir 17:2841–2850CrossRefGoogle Scholar
  7. 7.
    Kitano H, Tada S, Mori T, Takaha K, Gemmei-Ide M, Tanaka M, Fukuda M, Yokoyama Y (2005) Correlation between the structure of water in the vicinity of carboxybetaine polymers and their blood-compatibility. Langmuir 21:11932–11940CrossRefGoogle Scholar
  8. 8.
    Tanaka M, Motomura T, Kawada M, Anzai T, Kasori Y, Shiroya T, Shimura K, Onishi M, Mochizuki A (2000) Blood compatible aspects of poly(2-methoxyethylacrylate) (PMEA)--relationship between protein adsorption and platelet adhesion on PMEA surface. Biomaterials 21(14):1471–1481CrossRefGoogle Scholar
  9. 9.
    Tanaka M, Motomura T, Ishii N, Shimura K, Onishi M, Mochizuki A, Hatakeyama T (2000) Cold crystallization of water in hydrated poly(2‐methoxyethyl acrylate) (PMEA). Polym Int 49:1709–1713CrossRefGoogle Scholar
  10. 10.
    Tanaka M, Mochizuki A (2004) Effect of water structure on blood compatibility: thermal analysis of water in poly(meth)acrylate. J Biomed Mater Res 68A:684–695CrossRefGoogle Scholar
  11. 11.
    Tanaka M, Mochizuki A, Motomura T, Shimura K, Onishi M, Okahata Y (2001) In situ studies on protein adsorption onto a poly(2-methoxyethyl acrylate) surface by a quartz crystal microbalance. Colloids Surf A Physicochem Eng Asp 193:145–152CrossRefGoogle Scholar
  12. 12.
    Tanaka M, Mochizuki A, Shiroya T, Motomura T, Shimura K, Onishi M, Okahata Y (2002) Study on kinetics of early stage protein adsorption and desorption on poly(2-methoxyethyl acrylate) (PMEA) surface. Colloids Surf A Physicochem Eng Asp 203:195–204CrossRefGoogle Scholar
  13. 13.
    Hayashi T, Tanaka Y, Koide Y, Tanaka M, Hara M (2012) Mechanism underlying bioinertness of self-assembled monolayers of Oligo(ethyleneglycol)-terminated alkanethiols on gold: protein adsorption, platelet adhesion, and surface forces. Phys Chem Chem Phys 14:10194–10206CrossRefGoogle Scholar
  14. 14.
    Sekine T, Tanaka Y, Sato C, Tanaka M, Hayashi T (2015) Evaluation of factors to determine platelet compatibility by using self-assembled monolayers with a chemical gradient. Langmuir 31:7100–7105CrossRefGoogle Scholar
  15. 15.
    Hazlewood CF, Nichols BL, Chamberlain NF (1969) Evidence for the existence of a minimum of two phases of ordered water in skeletal muscle. Nature 222:747CrossRefGoogle Scholar
  16. 16.
    Kuntz ID Jr, Brassfield TS, Law GD, Purcell GV (1969) Hydration of macromolecules. Science 163(3873):1329–1331CrossRefGoogle Scholar
  17. 17.
    Uedaira H (1980) In: Pullman B, Yagi K (eds) Water and metal cations in biological systems. Japan Scientific Societies Press, Tokyo, p 47Google Scholar
  18. 18.
    Pal SK, Peon J, Zewail AH (2002) Biological water at the protein surface: dynamical solvation probed directly with femtosecond resolution. Proc Natl Acad Sci U S A 99:1763CrossRefGoogle Scholar
  19. 19.
    Morita S, Tanaka M, Ozaki Y (2007) Time-resolved in-situ ATRIR observations of the process of water into a poly(2-methoxyethyl acrylate) (PMEA) film. Langmuir 23:3750–3761CrossRefGoogle Scholar
  20. 20.
    Morita S, Tanaka M (2014) Effect of sodium chloride on hydration structures of PMEA and P(MPC-r-BMA). Langmuir 30:10698–10703CrossRefGoogle Scholar
  21. 21.
    Miwa Y, Ishida H, Saitô H, Tanaka M, Mochizuki A (2009) Network structures and dynamics of dry and swollen poly(acrylate)s. Polymer 50:6091–6099CrossRefGoogle Scholar
  22. 22.
    Hatakayama T, Tanaka M, Hatakayama H (2010) Studies on bound water restrained by poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC): comparison of the polysaccharides-water systems. Acta Biomater 6:2077–2082CrossRefGoogle Scholar
  23. 23.
    Tanaka M, Hayashi T, Morita S (2013) The roles of water molecules at the biointerface of medical polymers. Polym J 45:701–710CrossRefGoogle Scholar
  24. 24.
    Sato K, Kobayashi S, Kusakari M, Watahiki S, Oikawa M, Hoshiba T, Tanaka M (2015) The relationship between water structure and blood compatibility in poly (2-methoxyethyl Acrylate) (PMEA) analogues. Macromol Biosci 15:1296–1303CrossRefGoogle Scholar
  25. 25.
    Tanaka M, Sato K, Kitakami E, Kobayashi S, Hoshiba T, Fukushima K (2015) Design of biocompatible and biodegradable polymers based on intermediate water concept. Polym J 47:114–121CrossRefGoogle Scholar
  26. 26.
    Hoshiba T, Nemoto E, Sato K, Orui T, Otaki T, Yoshihiro A, Tanaka M (2015) Regulation of the contribution of integrin to cell attachment on poly(2-Methoxyethyl Acrylate) (PMEA) analogous polymers for attachment-based cell enrichment. PLoS One 10:e0136066CrossRefGoogle Scholar
  27. 27.
    Kobayashi S, Fukuda K, Kataoka M, Tanaka M (2016) Regioselective ring-opening metathesis polymerization of 3-substituted cyclooctenes with ether side chains. Macromolecules 49:2493–2501CrossRefGoogle Scholar
  28. 28.
    Osawa K, Kobayashi S, Tanaka M (2016) Synthesis of sequence-specific polymers with amide side chains via regio-/stereoselective ring-opening metathesis polymerization of 3-substitutedcis-cyclooctene. Macromolecules 49:8154–8161CrossRefGoogle Scholar
  29. 29.
    Sato K, Kobayashi S, Sekishita A, Wakui M, Tanaka M (2017) Synthesis and thrombogenicity evaluation evaluation of poly(3-methoxypropionic acid vinyl ester): a candidate for blood compatible polymer. Biomacromolecules 18:1609–1616CrossRefGoogle Scholar
  30. 30.
    Hoshiba T, Nikaido M, Tanaka M (2014) Characterization of the attachment mechanisms of tissue-derived cell lines to blood-compatible polymers. Adv Healthc Mater 3:775–784CrossRefGoogle Scholar
  31. 31.
    Choi H, Tanaka M, Hiragun T, Hide M, Sugimoto K (2014) Non-tumor mast cells cultured in vitro on a honeycomb-like structured film proliferate with multinucleated formation. Nanomedicine 10:313–319CrossRefGoogle Scholar
  32. 32.
    Hirata T, Matsuno H, Kawaguchi D, Hirai T, Yamada N, Tanaka M, Tanaka K (2015) Effect of local chain dynamics on a bio-inert interface. Langmuir 31:3661–3667CrossRefGoogle Scholar
  33. 33.
    Hoshiba T, Otaki T, Nemoto E, Maruyama H, Tanaka M (2015) Blood com- patible polymer for hepatocyte culture with high hepatocyte-specific functions toward bioartificial liver development. ACS Appl Mater Interfaces 7:18096–18103CrossRefGoogle Scholar
  34. 34.
    Khan F, Tanaka M, Ahmad SR, Mater J (2015) Fabrication of polymeric biomaterials: a strategy for tissue engineering and medical devices. Chem B 3:8224–8249Google Scholar
  35. 35.
    Sato C, Aoki M, Tanaka M (2016) Blood-compatible poly(2-methoxyethyl acrylate) for the adhesion and proliferation of endothelial and smooth muscle cells. Colloids Surf B: Biointerfaces 145:586–596CrossRefGoogle Scholar
  36. 36.
    Hoshiba T, Nikaido M, Yagi S, Konno I, Yoshihiro A, Tanaka M, Bioact J (2016) Blood compatible poly(2-methoxyethyl acrylate) (PMEA) for the adhesion and proliferation of lung cancer cells toward the isolation and analysis of circulating tumor cells. Compat Polym 31:361–372Google Scholar
  37. 37.
    Kono K, Hiruma H, Kobayashi S, Sato Y, Tanaka M, Sawada R, Niimi S (2016) In vitro endothelialization test of biomaterials using immortalized endothelial cells. PLoS One 11:e01582898Google Scholar
  38. 38.
    Hoshiba T, Orui T, Endo C, Sato K, Yoshihiro A, Minagawa Y, Tanaka M (2016) Adhesion-based simple capture and recovery of circulating tumor cells using a blood-compatible and thermo-responsive polymer-coated substrate. RSC Adv 6:89103–89112CrossRefGoogle Scholar
  39. 39.
    Murakami D, Kobayashi S, Tanaka M (2016) Interfacial structures and fibrinogen adsorption at blood-compatible polymer/water interfaces. ACS Bimater Sci Eng 2(12):2122–2126CrossRefGoogle Scholar
  40. 40.
    Hoshiba T, Nemoto E, Sato K, Maruyama H, Endo C, Tanaka M (2016) Promotion of adipogenesis of 3T3-L1 cells on protein adsorption-suppressing poly(2-methoxyethyl acrylate) analogs. Biomacromolecules 17:3808–3815CrossRefGoogle Scholar
  41. 41.
    Fukushima K, Tsai M, Ota T, Haga Y, Matsuzaki K, Inoue Y, Tanaka M (2015) Evaluation of haemocompatibility of hydrated biodegradable aliphatic carbonyl polymers with a subtle difference in a backbone structure on the basis of intermediate water concept and surface hydration. Polym J 47:469–473CrossRefGoogle Scholar
  42. 42.
    Basterretxea A, Haga Y, Sanchez-Sanchez A, Isik M, Irusta L, Tanaka M, Fukushima K, Sardon H (2016) Biocompatibility and hemocompatibility evaluation of polyether urethanes synthesized using DBU organocatalyst. Eur Polym J 84:750–758CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Institute for Materials Chemistry and EngineeringKyushu UniversityFukuokaJapan
  2. 2.Frontier Center for Organic MaterialsYamagata UniversityYamagataJapan

Personalised recommendations