Surface-Modifying Polymers for Blood-Contacting Polymeric Biomaterials

  • Chung-Man Lim
  • Mei-Xian Li
  • Yoon Ki JoungEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1250)


Bulk blending is considered as one of the most effective and straightforward ways to improve the hemo-compatibility of blood-contacting polymeric biomaterials among many surface modification methods. Zwitterionic structure-, glycocalyx-like structure-, and heparin-like structure-based oligomers have been synthesized as additives and blended with base polymers to improve the blood compatibility of base polymers. Fluorinated end- and side-functionalized oligomers could promote the migration of functionalized groups to the surface of biomedical polymers without changing their bulk properties, and it highly depends on the number and concentration of functional groups. Moreover, oligomers having both zwitterion and fluorine are receiving considerable attention due to their desirable phase separation, which can avoid undesired protein adsorption and platelet adhesion. The surface analysis of the surface-modified materials is usually investigated by analytical tools such as contact angle measurement, atomic force microscopy (AFM), and X-ray photoelectron spectroscopy (XPS). Blood compatibility is mainly evaluated via platelet adhesion and protein adsorption test, and the result showed a significant decrease in the amount of undesirable adsorption. These analyses indicated that surface modification using bulk blending technique effectively improves blood compatibility of polymeric biomaterials.


Surface modification Bulk blending Additives Oligomers Blood-contact Hemo-compatibility Biocompatibility Protein Adsorption Polymers Biomaterials Zwitterion Fluorine 


  1. 1.
    Li S, Henry JJ (2011) Nonthrombogenic approaches to cardiovascular bioengineering. Annu Rev Biomed Eng 13:451–475PubMedGoogle Scholar
  2. 2.
    Moellering RC Jr (2011) MRSA: the first half century. J Antimicrob Chemother 67(1):4–11PubMedGoogle Scholar
  3. 3.
    Tu Q, Shen X, Liu Y et al (2019) A facile metal–phenolic–amine strategy for dual-functionalization of blood-contacting devices with antibacterial and anticoagulant properties. Mater Chem Front 3(2):265–275Google Scholar
  4. 4.
    Vogler EA, Siedlecki CA (2009) Contact activation of blood-plasma coagulation. Biomaterials 30(10):1857–1869PubMedPubMedCentralGoogle Scholar
  5. 5.
    Frost MC, Reynolds MM, Meyerhoff ME (2005) Polymers incorporating nitric oxide releasing/generating substances for improved biocompatibility of blood-contacting medical devices. Biomaterials 26(14):1685–1693PubMedGoogle Scholar
  6. 6.
    Surman F, Riedel T, Bruns M et al (2015) Polymer brushes interfacing blood as a route toward high performance blood contacting devices. Macromol Biosci 15(5):636–646PubMedGoogle Scholar
  7. 7.
    Hucknall A, Rangarajan S, Chilkoti A (2009) In pursuit of zero: polymer brushes that resist the adsorption of proteins. Adv Mater 21(23):2441–2446Google Scholar
  8. 8.
    Rodriguez-Emmenegger C, Brynda E, Riedel T, Houska M et al (2011) Polymer brushes showing non fouling in blood plasma challenge the currently accepted design of protein resistant surfaces. ISO: Macromol Rapid Commun 32(13):952–957Google Scholar
  9. 9.
    Mosher DF (1993) Adhesive proteins and their cellular receptors. Cardiovasc Pathol 2(3):149–155Google Scholar
  10. 10.
    Lopez-Donaire ML, Santerre JP (2014) Surface modifying oligomers used to functionalize polymeric surfaces: consideration of blood contact applications. J Appl Polym Sci 131(14)Google Scholar
  11. 11.
    Alves NM, Pashkuleva I, Reis RL et al (2010) Controlling cell behavior through the design of polymer surfaces. Small 6(20):2208–2220PubMedGoogle Scholar
  12. 12.
    Kingshott P, Andersson G, McArthur SL et al (2011) Surface modification and chemical surface analysis of biomaterials. Curr Opin Chem Biol 15(5):667–676PubMedGoogle Scholar
  13. 13.
    Chen H, Yuan L, Song W et al (2008) Biocompatible polymer materials: role of protein–surface interactions. Prog Polym Sci 33(11):1059–1087Google Scholar
  14. 14.
    Amiji M, Park K (1992) Prevention of protein adsorption and platelet adhesion on surfaces by PEO/PPO/PEO triblock copolymers. Biomaterials 13(10):682–692PubMedGoogle Scholar
  15. 15.
    Chang Y, Chen WY, Yandi W et al (2009) Dual-thermoresponsive phase behavior of blood compatible zwitterionic copolymers containing nonionic poly (N-isopropyl acrylamide). Biomacromolecules 10(8):2092–2100PubMedGoogle Scholar
  16. 16.
    Yang Z, Tu Q, Maitz MF et al (2012) Direct thrombin inhibitor-bivalirudin functionalized plasma polymerized allylamine coating for improved biocompatibility of vascular devices. Biomaterials 33(32):7959–7971PubMedGoogle Scholar
  17. 17.
    Wang L-F, Wei Y-H, Chen K-Y et al (2004) Properties of phospholipid monolayer deposited on a fluorinated polyurethane. J Biomater Sci Polym Ed 15(8):957–969PubMedGoogle Scholar
  18. 18.
    Hossfeld S, Nolte A, Hartmann H et al (2013) Bioactive coronary stent coating based on layer-by-layer technology for siRNA release. Acta Biomater 9(5):6741–6752PubMedGoogle Scholar
  19. 19.
    Lim C-M, Hur J, Jang H et al (2019) Developing a thermal grafting process for zwitterionic polymers on cross-linked polyethylene with geometry-independent grafting thickness. Acta Biomater 85:180–191PubMedGoogle Scholar
  20. 20.
    Lim C-M, Seo J, Jang H et al (2018) Optimizing grafting thickness of zwitterionic sulfobetaine polymer on cross-linked polyethylene surface to reduce friction coefficient. Appl Surf Sci 452:102–112Google Scholar
  21. 21.
    Jiang H, Wang X, Li C et al (2011) Improvement of hemocompatibility of polycaprolactone film surfaces with zwitterionic polymer brushes. Langmuir 27(18):11575–11581PubMedGoogle Scholar
  22. 22.
    Flores JD, Xu X, Treat NJ et al (2009) Reversible “self-locked” micelles from a zwitterion-containing triblock copolymer. Macromolecules 42(14):4941–4945Google Scholar
  23. 23.
    Seo J-H, Matsuno R, Lee Y et al (2009) Conformational recovery and preservation of protein nature from heat-induced denaturation by water-soluble phospholipid polymer conjugation. Biomaterials 30(28):4859–4867PubMedGoogle Scholar
  24. 24.
    Hedayati M, Neufeld MJ, Reynolds MM et al (2019) The quest for blood-compatible materials: recent advances and future technologies. Mater Sci Eng R Rep 138:118–152Google Scholar
  25. 25.
    Ishihara K (2019) Revolutionary advances in 2-methacryloyloxyethyl phosphorylcholine polymers as biomaterials. J Biomed Mater Res Part A 107(5):933–943Google Scholar
  26. 26.
    Shimizu T, Goda T, Minoura N et al (2010) Super-hydrophilic silicone hydrogels with interpenetrating poly (2-methacryloyloxyethyl phosphorylcholine) networks. Biomaterials 31(12):3274–3280PubMedGoogle Scholar
  27. 27.
    Liu P-S, Chen Q, Liu X et al (2009) Grafting of zwitterion from cellulose membranes via ATRP for improving blood compatibility. Biomacromolecules 10(10):2809–2816PubMedGoogle Scholar
  28. 28.
    Jiang S, Cao Z (2010) Ultralow-fouling, functionalizable, and hydrolyzable zwitterionic materials and their derivatives for biological applications. Adv Mater 22(9):920–932PubMedGoogle Scholar
  29. 29.
    Seo J-H, Matsuno R, Takai M et al (2009) Cell adhesion on phase-separated surface of block copolymer composed of poly (2-methacryloyloxyethyl phosphorylcholine) and poly (dimethylsiloxane). Biomaterials 30(29):5330–5340PubMedGoogle Scholar
  30. 30.
    Hasegawa T, Iwasaki Y, Ishihara K (2001) Preparation and performance of protein-adsorption-resistant asymmetric porous membrane composed of polysulfone/phospholipid polymer blend. Biomaterials 22(3):243–251PubMedGoogle Scholar
  31. 31.
    Anderson JM, Shive MS (1997) Biodegradation and biocompatibility of PLA and PLGA microspheres. Adv Drug Deliv Rev 28(1):5–24PubMedGoogle Scholar
  32. 32.
    Iwasaki Y, Sawada S-i, Ishihara K et al (2002) Reduction of surface-induced inflammatory reaction on PLGA/MPC polymer blend. Biomaterials 23(18):3897–3903PubMedGoogle Scholar
  33. 33.
    Ye SH, Watanabe J, Iwasaki Y et al (2002) Novel cellulose acetate membrane blended with phospholipid polymer for hemocompatible filtration system. J Membr Sci 210(2):411–421Google Scholar
  34. 34.
    Zhao Y-F, Zhu L-P, Yi Z et al (2013) Improving the hydrophilicity and fouling-resistance of polysulfone ultrafiltration membranes via surface zwitterionicalization mediated by polysulfone-based triblock copolymer additive. J Membr Sci 440:40–47Google Scholar
  35. 35.
    Meng S, Guo Z, Wang Q et al (2011) Studies on a novel multi-sensitive hydrogel: influence of the biomimetic phosphorylcholine end-groups on the PEO–PPO–PEO tri-block co-polymers. J Biomater Sci Polym Ed 22(4–6):651–664PubMedGoogle Scholar
  36. 36.
    Huang J, Gu S, Zhang R et al (2013) Synthesis, spectroscopic, and thermal properties of polyurethanes containing zwitterionic sulfobetaine groups. J Therm Anal 12(3):1289–1295Google Scholar
  37. 37.
    Cao J, Yang M, Lu A et al (2013) Polyurethanes containing zwitterionic sulfobetaines and their molecular chain rearrangement in water. J Biomed Mater Res Part A 101(3):909–918Google Scholar
  38. 38.
    Sechriest VF, Miao YJ, Niyibizi C et al (2000) GAG-augmented polysaccharide hydrogel: a novel biocompatible and biodegradable material to support chondrogenesis. J Biomed Mater Res 49(4):534–541PubMedGoogle Scholar
  39. 39.
    Jeon S, Lee J, Andrade J et al (1991) Protein—surface interactions in the presence of polyethylene oxide: I. Simplified theory. J Colloid Interface Sci 142(1):149–158Google Scholar
  40. 40.
    Jeon S, Andrade J (1991) Protein—surface interactions in the presence of polyethylene oxide: II. Effect of protein size. J Colloid Interface Sci 142(1):159–166Google Scholar
  41. 41.
    Ji J, Zhu H, Shen J (2004) Surface tailoring of poly (DL-lactic acid) by ligand-tethered amphiphilic polymer for promoting chondrocyte attachment and growth. Biomaterials 25(10):1859–1867PubMedGoogle Scholar
  42. 42.
    Tamada Y, Murata M, Makino K et al (1998) Anticoagulant effects of sulphonated polyisoprenes. Biomaterials 19(7–9):745–750PubMedGoogle Scholar
  43. 43.
    Silver JH, Hart AP, Williams EC et al (1992) Anticoagulant effects of sulphonated polyurethanes. Biomaterials 3(6):339–344Google Scholar
  44. 44.
    Tamada Y, Murata M, Hayashi T et al (2002) Anticoagulant mechanism of sulfonated polyisoprenes. Biomaterials 23(5):1375–1382PubMedGoogle Scholar
  45. 45.
    Nie S, Xue J, Lu Y (2012) Improved blood compatibility of polyethersulfone membrane with a hydrophilic and anionic surface. Colloid Surf B Biointerfaces 100:116–125PubMedGoogle Scholar
  46. 46.
    Chen HF, Ren YJ (2015) Design, synthesis, and anti-thrombotic evaluation of some novel fluorinated thrombin inhibitor derivatives. Arch Pharm 348(6):408–420Google Scholar
  47. 47.
    Nowatzki PJ, Koepsel RR, Stoodley P et al (2012) Salicylic acid-releasing polyurethane acrylate polymers as anti-biofilm urological catheter coatings. Acta Biomater 8(5):1869–1880PubMedGoogle Scholar
  48. 48.
    Nouman M, Jubeli E, Saunier J et al (2016) Exudation of additives to the surface of medical devices: impact on biocompatibility in the case of polyurethane used in implantable catheters. J Biomed Mater Res Part A 104(12):2954–2967Google Scholar
  49. 49.
    Suk DE, Chowdhury G, Matsuura T et al (2002) Study on the kinetics of surface migration of surface modifying macromolecules in membrane preparation. Macromolecules 35(8):3017–3021Google Scholar
  50. 50.
    Rana D, Matsuura T, Narbaitz RM (2006) Novel hydrophilic surface modifying macromolecules for polymeric membranes: polyurethane ends capped by hydroxy group. J Membr Sci 282(1–2):205–216Google Scholar
  51. 51.
    Theron JP, Knoetze JH, Sanderson RD et al (2010) Modification, crosslinking and reactive electrospinning of a thermoplastic medical polyurethane for vascular graft applications. Acta Biomater 6(7):2434–2447PubMedGoogle Scholar
  52. 52.
    Joung YK, Hwang IK, Park KD et al (2010) CD34 monoclonal antibody-immobilized electrospun polyurethane for the endothelialization of vascular grafts. Macromol Res 18(9):904–912Google Scholar
  53. 53.
    Sundaram HS, Cho YJ, Dimitriou MD et al (2011) Fluorinated amphiphilic polymers and their blends for fouling-release applications: the benefits of a triblock copolymer surface. ACS Appl Mater Interfaces 3(9):3366–3374PubMedGoogle Scholar
  54. 54.
    Pinchuk L (1994) A review of the biostability and carcinogenicity of polyurethanes in medicine and the new-generation of biostable polyurethanes. J Biomater Sci Polym Ed 6(3):225–267PubMedGoogle Scholar
  55. 55.
    Xie XY, Tan H, Li JH et al (2008) Synthesis and characterization of fluorocarbon chain end-capped poly(carbonate urethane)s as biomaterials: a novel bilavered surface structure. J Biomed Mater Res Part A 84A(1):30–43Google Scholar
  56. 56.
    Massa TM, Yang ML, Ho JYC et al (2005) Fibrinogen surface distribution correlates to platelet adhesion pattern on fluorinated surface-modified polyetherurethane. Biomaterials 26(35):7367–7376PubMedGoogle Scholar
  57. 57.
    Krafft MP, Riess JG (2007) Perfluorocarbons: life sciences and biomedical uses – dedicated to the memory of professor Guy Ourisson, a true RENAISSANCE man. J Polym Sci A Polym Chem 45(7):1185–1198Google Scholar
  58. 58.
    Tan H, Li JH, Guo M et al (2005) Phase behavior and hydrogen bonding in biomembrane mimicing polyurethanes with long side chain fluorinated alkyl phosphatidylcholine polar head groups attached to hard block. Polymer 46(18):7230–7239Google Scholar
  59. 59.
    Khulbe KC, Feng C, Matsuura T (2010) The art of surface modification of synthetic polymeric membranes. J Appl Polym Sci 115(2):855–895Google Scholar
  60. 60.
    Tang YW, Santerre JP, Labow RS et al (1996) Synthesis of surface-modifying macromolecules for use in segmented polyurethanes. J Appl Polym Sci 62(8):1133–1145Google Scholar
  61. 61.
    Hutchings LR, Narrianen AP, Thompson RL et al (2008) Modifying and managing the surface properties of polymers. Polym Int 57(2):163–170Google Scholar
  62. 62.
    Tang YW, Santerre JP, Labow RS et al (1997) Use of surface-modifying macromolecules to enhance the biostability of segmented polyurethanes. J Biomed Mater Res 35(3):371–381PubMedGoogle Scholar
  63. 63.
    Tonelli C, Ajroldi G, Turturro A et al (2001) Synthesis methods of fluorinated polyurethanes. 1. Effects on thermal and dynamic-mechanical behaviours. Polymer 42(13):5589–5598Google Scholar
  64. 64.
    Li JH, Zhang Y, Yang J et al (2013) Synthesis and surface properties of polyurethane end-capped with hybrid hydrocarbon/fluorocarbon double-chain phospholipid. J Biomed Mater Res Part A 101(5):1362–1372Google Scholar
  65. 65.
    El-Shehawy AA, Yokoyama H, Sugiyama K et al (2005) Precise synthesis of novel chain-end-functionalized polystyrenes with a definite number of perfluorooctyl groups and their surface characterization. Macromolecules 38(20):8285–8299Google Scholar
  66. 66.
    Hutchings LR, Narrainen AP, Eggleston SM et al (2006) Surface-active fluorocarbon end-functionalized polylactides. Polymer 47(24):8116–8122Google Scholar
  67. 67.
    Bergius WNA, Hutchings LR, Sarih NM et al (2013) Synthesis and characterisation of end-functionalised poly(N-vinylpyrrolidone) additives by reversible addition-fragmentation transfer polymerisation. Polym Chem 4(9):2815–2827Google Scholar
  68. 68.
    Hutchings LR, Sarih NM, Thompson RL (2011) Multi-end functionalised polymer additives synthesised by living anionic polymerisation-the impact of additive molecular structure upon surface properties. Polym Chem 2(4):851–861Google Scholar
  69. 69.
    Ge Z, Zhang XY, Dai JB et al (2009) Synthesis, characterization and properties of a novel fluorinated polyurethane. Eur Polym J 45(2):530–536Google Scholar
  70. 70.
    Tan H, Liu J, Li JH et al (2006) Synthesis and hemocompatibility of biomembrane mimicing poly (carbonate urethane)s containing fluorinated alkyl phosphatidylcholine side groups. Biomacromolecules 7(9):2591–2599PubMedGoogle Scholar
  71. 71.
    Tan H, Xie XY, Li JH et al (2004) Synthesis and surface mobility of segmented polyurethanes with fluorinated side chains attached to hard blocks. Polymer 45(5):1495–1502Google Scholar
  72. 72.
    Lin YH, Chou NK, Chang CH et al (2007) Blood compatibility of fluorodiol-containing polyurethanes. J Polym Sci A Polym Chem 45(15):3231–3242Google Scholar
  73. 73.
    Zhang XQ, Jiang X, Li JH et al (2008) Largely improved blood compatibility of polyurethane by blending with fluorinated phosphatidylcholine polyurethane. Chin J Polym Sci 26(2):203–211Google Scholar
  74. 74.
    Krishnan S, Ayothi R, Hexemer A et al (2006) Anti-biofouling properties of comblike block copolymers with amphiphilic side chains. Langmuir 22(11):5075–5086PubMedGoogle Scholar
  75. 75.
    Zhao XT, Su YL, Li YF et al (2014) Engineering amphiphilic membrane surfaces based on PEO and PDMS segments for improved antifouling performances. J Membr Sci 450:111–123Google Scholar
  76. 76.
    Lin C, Pan RM, Xing P et al (2018) Synthesis and surface activity study of novel branched zwitterionic heterogemini fluorosurfactants with CF3CF2CF2C(CF3)(2) group. J Fluor Chem 214:35–41Google Scholar
  77. 77.
    Zhang GF, Gao F, Zhang QH et al (2016) Enhanced oil-fouling resistance of poly(ether sulfone) membranes by incorporation of novel amphiphilic zwitterionic copolymers. RSC Adv 6(9):7532–7543Google Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2020

Authors and Affiliations

  1. 1.Center for Biomaterials, Biomedical Research InstituteKorea Institute of Science and Technology (KIST)SeoulRepublic of Korea
  2. 2.Division of Bio-Medical Science and TechnologyKorea University of Science and Technology (UST)DeajeonRepublic of Korea

Personalised recommendations