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Cytocompatible Hydrogel Composed of Phospholipid Polymers for Regulation of Cell Functions

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Polymers in Nanomedicine

Part of the book series: Advances in Polymer Science ((POLYMER,volume 247))

Abstract

We propose a cell encapsulation matrix for use with a cytocompatible phospholipid polymer hydrogel system for control of cell functions in three-dimensional (3D) cell engineering and for construction of well-organized tissue in vivo. In cell engineering fields, it is important to produce cells with highly cell-specific functions. To realize this, we consider that new devices are needed for cell culture. So, we have designed soft biodevices using a spontaneously forming and cytocompatible polymer hydrogel system. A water-soluble phospholipid polymer bearing a phenylboronic acid unit, poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate-co-p-vinylphenylboronic acid) (PMBV), was prepared. This polymer, in aqueous solution, spontaneously converted to a hydrogel by addition of poly(vinyl alcohol) (PVA) aqueous solution due to reversible bonding between the boronate groups in PMBV and the hydroxyl groups in PVA. The PMBV/PVA hydrogel was dissociated by an exchange reaction with low molecular weight diol compounds such as d-fructose, which have high binding affinity to the phenylboronic acid unit. Cells were encapsulated easily in the PMBV/PVA hydrogel, and the cells in the hydrogel kept their original morphology and slightly proliferated during the preservation period. After dissociation of the hydrogel, the cells could be recovered as a cell suspension and cultured under conventional cell culture conditions as usual. Embryonic stem cells could be encapsulated without any adverse effects from the polymer hydrogel, i.e., the cells maintained their undifferentiated character during preservation in the PMBV/PVA hydrogel. Cell preservation and activity in the hydrogel were also investigated using microfluidic chips. The results clearly indicated that the PMBV/PVA hydrogels provide a useful platform for 3D encapsulation of cell culture systems without any reduction of their bioactivity.

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References

  1. Lutolf MP, Hubbell JA (2005) Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering. Nat Biotechnol 23:47–55

    Article  CAS  Google Scholar 

  2. Lutolf MP (2009) Spotlight on hydrogels. Nat Mater 8:451–453

    Article  CAS  Google Scholar 

  3. Lutolf MP (2009) Integration column: artificial ECM: expanding the cell biology toolbox in 3D. Integr Biol 1:235–241

    Article  CAS  Google Scholar 

  4. Peppas NA, Hilt JZ, Khademhosseini A et al (2006) Hydrogels in biology and medicine: from molecular principles to bionanotechnology. Adv Mater 18:1345–1360

    Article  CAS  Google Scholar 

  5. Slaughter BV, Khurshid SS, Fisher OZ et al (2009) Hydrogels in regenerative medicine. Adv Mater 21:3307–3329

    Article  CAS  Google Scholar 

  6. Hoffman AS (2002) Hydrogels for biomedical applications. Adv Drug Deliv Rev 54(1):3–12

    Article  CAS  Google Scholar 

  7. Lee KY, Mooney DJ (2001) Hydrogels for tissue engineering. Chem Rev 101:1869–1880

    Article  CAS  Google Scholar 

  8. Takahashi K, Tanabe K, Yamanaka S et al (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872

    Article  CAS  Google Scholar 

  9. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676

    Article  CAS  Google Scholar 

  10. Evans MJ, Kaufman MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292:154–156

    Article  CAS  Google Scholar 

  11. Tsang VL, Bhatia N (2004) Three-dimensional tissue fabrication. Adv Drug Deliv Rev 56:1635–1647

    Article  Google Scholar 

  12. Liu C, Xia Z, Czernuszka JT (2007) Design and development of three-dimensional scaffolds for tissue engineering. Trans IChemE, Part A, Chem Eng Res Des 85:1051–1064

    Article  CAS  Google Scholar 

  13. Stoop R (2008) Smart biomaterials for tissue engineering of cartilage. Inj Int J Care Injured 3951:577–587

    Google Scholar 

  14. Drury JL, Mooney DJ (2003) Hydrogels for tissue engineering: scaffold design variables and applications. Biomaterials 24:4337–4351

    Article  CAS  Google Scholar 

  15. Peppas NA, Bures P, Leobandung W et al (2000) Hydrogels in pharmaceutical formulations. Eur J Pharm Biopharm 50:27–46

    Article  CAS  Google Scholar 

  16. Zhu J (2010) Bioactive modification of poly(ethylene glycol) hydrogels for tissue engineering. Biomaterials 31:4639–4656

    Article  CAS  Google Scholar 

  17. Van Tomme SR, Storm G, Hennink WE (2008) In situ gelling hydrogels for pharmaceutical and biomedical applications. Int J Pharm 355:1–18

    Article  Google Scholar 

  18. Grinnell F (2003) Fibroblast biology in three-dimensional collagen matrices. Trends Cell Biol 13:264–269

    Article  CAS  Google Scholar 

  19. Tabata Y, Hijikata S, Ikada Y (1994) Enhanced vascularization and tissue granulation by basic fibroblast growth factor impregnated in gelatin hydrogels. J Control Rel 31:189–199

    Article  CAS  Google Scholar 

  20. Khademhosseini A, Suh KY, Yang JM et al (2004) Layer-by-layer deposition of hyaluronic acid and poly-l-lysine for patterned cell co-cultures. Biomaterials 25:3583–3592

    Article  CAS  Google Scholar 

  21. Watanabe J, Nederberg F, Atthoff B et al (2007) Cytocompatible biointerface on poly(lactic acid) by enrichment with phosphorylcholine groups for cell engineering. Mater Sci Eng 27:227–231

    Article  CAS  Google Scholar 

  22. Watanabe J, Eriguchi T, Ishihara K (2002) Stereocomplex formation by enantiomeric poly(lactic acid) graft-type phospholipid polymers for tissue engineering. Biomacromolecules 3:1109–1114

    Article  CAS  Google Scholar 

  23. Watanabe J, Eriguchi T, Ishihara K (2002) Cell adhesion and morphology in porous scaffold based on enantiomeric poly(lactic acid) graft-type phospholipid polymers. Biomacromolecules 3:1375–1383

    Article  CAS  Google Scholar 

  24. Watanabe J, Ishihara K (2005) Cell engineering biointerface focusing on cytocompatibility using phospholipid polymer with an isomeric oligo(lactic acid) segment. Biomacromolecules 6:1797–1802

    Article  CAS  Google Scholar 

  25. Watanabe J, Ishihara K (2003) Phosphorylcholine and Poly(D, L-lactic acid) containing copolymers as substrates for cell adhesion. Artif Organs 27:242–248

    Article  CAS  Google Scholar 

  26. Jeong B, Choi YK, Bae YH et al (1999) New biodegradable polymers for injectable drug delivery systems. J Control Release 62:109–114

    Article  CAS  Google Scholar 

  27. Li Z, Ramay HR, Hauch KD et al (2005) Chitosan-alginate hybrid scaffolds for bone tissue engineering. Biomaterials 26:3919–3928

    Article  CAS  Google Scholar 

  28. Ling Y, Rubin J, Deng Y et al (2007) A cell-laden microfluidic hydrogel. Lab Chip 7:756–762

    Article  CAS  Google Scholar 

  29. Chenite A, Chaput C, Wang D et al (2000) Novel injectable neutral solutions of chitosan form biodegradable gels in situ. Biomaterials 21:2155–2161

    Article  CAS  Google Scholar 

  30. Jeong B, Kim SW, Bae YH (2002) Thermosensitive sol-gel reversible hydrogels. Adv Drug Deliv Rev 54:37–51

    Article  CAS  Google Scholar 

  31. Nuttelman CR, Mortisen DJ, Henry SM et al (2001) Attachment of fibronectin to poly(vinyl alcohol) hydrogels promotes NIH3T3 cell adhesion, proliferation and migration. J Biomed Mater Res 57:217–223

    Article  CAS  Google Scholar 

  32. Kitano S, Kataoka K, Koyama Y et al (1991) Glucose-responsive complex formation between poly(viny1 alcohol) and poly(N-vinyl-2-pyrrolidone) with pendent phenylboronic acid moieties. Makromol Chem Rapid Commun 12:227–233

    Article  CAS  Google Scholar 

  33. Lutolf MP, Raeber GP, Zisch AH (2003) Cell-responsive synthetic hydrogels. Adv Mater 15:888–892

    Article  CAS  Google Scholar 

  34. Lutolf MP, Hubbell JA (2003) Synthesis and physicochemical characterization of end-linked poly(ethylene glycol)-co-peptide hydrogels formed by michael-type addition. Biomacromolecules 4:713–722

    Article  CAS  Google Scholar 

  35. Kimura M, Fukumoto K, Watanabe J et al (2005) Spontaneously forming hydrogel from water-soluble random- and block-type phospholipid polymers. Biomaterials 26:6853–6862

    Article  CAS  Google Scholar 

  36. Kimura M, Fukumoto K, Watanabe J et al (2004) Hydrogen-bonding-driven spontaneous gelation of water-soluble phospholipid polymers in aqueous medium. J Biomater Sci Polym Edn 15:631–644

    Article  CAS  Google Scholar 

  37. Nam KW, Watanabe J, Ishihara K (2002) Characterization of the spontaneously forming hydrogels composed of water-soluble phospholipid polymers. Biomacromolecules 3:100–105

    Article  CAS  Google Scholar 

  38. Nam KW, Watanabe J, Ishihara K (2004) Modeling of swelling and drug release behavior of spontaneously forming hydrogels composed of phospholipid polymers. Int J Pharm 275:259–269

    Article  CAS  Google Scholar 

  39. Ishiyama N, Moro T, Ishihara K et al (2010) The prevention of peritendinous adhesions by a phospholipid polymer hydrogel formed in situ by spontaneous intermolecular interactions. Biomaterials 31:4009–4016

    Article  CAS  Google Scholar 

  40. Konno T, Ishihara K (2007) Temporal and spatially controllable cell encapsulation using a water-soluble phospholipid polymer with phenylboronic acid moiety. Biomaterials 28:1770–1777

    Article  CAS  Google Scholar 

  41. Choi J, Konno T, Matsuno R et al (2008) Surface immobilization of biocompatible phospholipid polymer multilayered hydrogel on titanium alloy. Colloids Surf B Biointerfaces 67:216–223

    Article  CAS  Google Scholar 

  42. Matthew JE, Nazario YL, Roberts SC et al (2002) Effect of mammalian cell culture medium on the gelation properties of Pluronic F127. Biomaterials 23:4615–4619

    Article  CAS  Google Scholar 

  43. Ishihara K, Ueda T, Nakabayashi N (1990) Preparation of phospholipid polymers and their properties as polymer hydrogel membrane. Polym J 22:355–360

    Article  CAS  Google Scholar 

  44. Ishihara K (1997) Novel polymeric materials for obtaining blood compatible surfaces. Trends in Polym Sci 5:401–407

    CAS  Google Scholar 

  45. Lewis AL (2000) Phosphorylcholine-based polymers and their use in the prevention of biofouling. Colloid Surf B Biointerfaces 18:261–275

    Article  CAS  Google Scholar 

  46. Ishihara K (2000) Bioinspired phospholipid polymer biomaterials for making high performance artificial organs. Sci Technol Adv Mater 1:131–138

    Article  CAS  Google Scholar 

  47. Iwsaki Y, Ishihara K (2005) Phosphorylcholine-containing polymers for biomedical applications. Ann Bioanal Chem 381:534–546

    Article  Google Scholar 

  48. Ishihara K, Takai M (2009) Bioinspired interfaces for nanobiodevices based on phospholipid polymer chemistry. J R Soc Interface 6:S279–S291

    Article  CAS  Google Scholar 

  49. Ishihara K, Oshida H, Endo Y et al (1992) Hemocompatibility of human whole blood on polymers with a phospholipid polar group and its mechanism. J Biomed Mater Res 26:1543–1552

    Article  CAS  Google Scholar 

  50. Ishihara K, Nomura H, Mihara T et al (1998) Why do phospholipid polymers reduce protein adsorption? J Biomed Mater Res 39:323–330

    Article  CAS  Google Scholar 

  51. Myers GJ, Johnstone DR, Swyer WJ et al (2003) Evaluation of mimesys phosphorylcholine(PC)-coated oxygenators during cardiopulmonary bypass in adults. J Extra Corpor Technol 35:6–12

    Google Scholar 

  52. Bakhai A, Booth J, Delahunty N et al (2005) The SV stent study: a prospective, multicentre, angiographic evaluation of the BiodivYasio phosphorylcholine coated small vessel stent in small coronary vessels. Int J Cardiol 102:95–102

    Article  CAS  Google Scholar 

  53. Snyder TA, Tsukui H, Kihara S et al (2007) Preclinical biocompatibility assessment of the EVAHEART ventricular assist device: coating comparison and platelet activation. J Biomed Mater Res A 81:85–92

    Google Scholar 

  54. Goda T, Ishihara K (2006) Soft contact lens biomaterials from bioinspired phospholipid polymers. Expert Rev Med Devices 3:167–174

    Article  CAS  Google Scholar 

  55. Moro T, Takatori Y, Ishihara K et al (2004) Surface grafting of artificial joints with a biocompatible polymer for preventing periprosthetic osteolysis. Nat Mater 3:829–836

    Article  CAS  Google Scholar 

  56. Kikuchi A, Suzuki K, Okabayashi O et al (1996) Glucose-sensing electrode coated with polymer complex gel containing phenylboronic acid. Anal Chem 68:823–828

    Article  CAS  Google Scholar 

  57. Shiino D, Murata Y, Kubo A et al (1995) Amine containing phenylboronic acid gel for glucose-responsive insulin release under physiological pH. J Control Release 37:269–276

    Article  CAS  Google Scholar 

  58. Lorand JP, Edwards JO (1959) Polyol complexes and structure of the benzeneboronate ion. J Org Chem 24:769–774

    Article  CAS  Google Scholar 

  59. Zhang E, Li X, Zhang S et al (2005) Cell cycle synchronization of embryonic stem cells: effect of serum deprivation on the differentiation of embryonic bodies in vitro. Biochem Biophys Res Commun 333:1171–1177

    Article  CAS  Google Scholar 

  60. Chang T, Hughes-Fulford (2009) Monolayer and spheroid culture of human liver hepatocellular carcinoma cell line cells demonstrate distinct global gene expression patterns and functional phenotypes. Tissue Eng Part A 15:559–567

    Article  CAS  Google Scholar 

  61. Mooney D, Hansen L, Vaccanti J et al (1992) Switching from differentiation to growth in hepatocytes: control by extracellular matrix. J Cell Physiol 151:497–505

    Article  CAS  Google Scholar 

  62. Ohno K, Tachikawa K, Manz A (2008) Microfluidics: applications for analytical purposes in chemistry and biochemistry. Electrophoresis 29:4443–4453

    Article  CAS  Google Scholar 

  63. El-Ali J, Sorger PK, Jensen KF (2006) Cells on chips. Nature 442:403–411

    Article  CAS  Google Scholar 

  64. Griffith LG, Swartz MA (2006) Capturing complex 3D tissue physiology in vitro. Nat Rev Mol Cell Biol 7:211–224

    Article  CAS  Google Scholar 

  65. Sato K, Mawatari K, Kitamori T (2008) Microchip-based cell analysis and clinical diagnosis system. Lab Chip 8:1992–1998

    Article  CAS  Google Scholar 

  66. Lion N, Rohner TC, Dayon L et al (2003) Microfluidic systems in proteomics. Electrophoresis 24:3533–3562

    Article  CAS  Google Scholar 

  67. Andersson H, van den Berg A (2003) Microfluidic devices for cellomics: a review. Sensor Actuat B-Chem 92:315–325

    Article  Google Scholar 

  68. Xu Y, Sato K, Konno T et al (2009) An on-chip living cell bank. Proc in Micro-TAS 2009:W82F

    Google Scholar 

  69. Xu Y, Sato K, Mawatari K et al (2010) A microfluidic hydrogel capable of cell preservation without perfusion culture under cell-based assay conditions. Adv Mater 22: 3017–3021

    Google Scholar 

  70. Wang Z, Kim MC, Marquez M et al (2007) High-density microfluidic arrays for cell cytotoxicity analysis. Lab Chip 7:740–745

    Article  CAS  Google Scholar 

  71. de Souza N (2010) Single-cell methods. Nat Methods 7:35

    Article  Google Scholar 

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Acknowledgments

The authors appreciate Prof. Madoka Takai, Dr. Ryosuke Matsuno, Dr. Yuuki Inoue and Prof. Takehiko Kitamori at The University of Tokyo for helpful discussions during preparation of the manuscript. One of the authors, Dr. Xu Yan, moved to Osaka Prefecture University, Osaka, Japan in April 2011.

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Correspondence to Kazuhiko Ishihara .

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Ishihara, K., Xu, Y., Konno, T. (2011). Cytocompatible Hydrogel Composed of Phospholipid Polymers for Regulation of Cell Functions. In: Kunugi, S., Yamaoka, T. (eds) Polymers in Nanomedicine. Advances in Polymer Science, vol 247. Springer, Berlin, Heidelberg. https://doi.org/10.1007/12_2011_151

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