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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Lutolf MP, Hubbell JA (2005) Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering. Nat Biotechnol 23:47–55
Lutolf MP (2009) Spotlight on hydrogels. Nat Mater 8:451–453
Lutolf MP (2009) Integration column: artificial ECM: expanding the cell biology toolbox in 3D. Integr Biol 1:235–241
Peppas NA, Hilt JZ, Khademhosseini A et al (2006) Hydrogels in biology and medicine: from molecular principles to bionanotechnology. Adv Mater 18:1345–1360
Slaughter BV, Khurshid SS, Fisher OZ et al (2009) Hydrogels in regenerative medicine. Adv Mater 21:3307–3329
Hoffman AS (2002) Hydrogels for biomedical applications. Adv Drug Deliv Rev 54(1):3–12
Lee KY, Mooney DJ (2001) Hydrogels for tissue engineering. Chem Rev 101:1869–1880
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
Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676
Evans MJ, Kaufman MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292:154–156
Tsang VL, Bhatia N (2004) Three-dimensional tissue fabrication. Adv Drug Deliv Rev 56:1635–1647
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
Stoop R (2008) Smart biomaterials for tissue engineering of cartilage. Inj Int J Care Injured 3951:577–587
Drury JL, Mooney DJ (2003) Hydrogels for tissue engineering: scaffold design variables and applications. Biomaterials 24:4337–4351
Peppas NA, Bures P, Leobandung W et al (2000) Hydrogels in pharmaceutical formulations. Eur J Pharm Biopharm 50:27–46
Zhu J (2010) Bioactive modification of poly(ethylene glycol) hydrogels for tissue engineering. Biomaterials 31:4639–4656
Van Tomme SR, Storm G, Hennink WE (2008) In situ gelling hydrogels for pharmaceutical and biomedical applications. Int J Pharm 355:1–18
Grinnell F (2003) Fibroblast biology in three-dimensional collagen matrices. Trends Cell Biol 13:264–269
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
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
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
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
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
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
Watanabe J, Ishihara K (2003) Phosphorylcholine and Poly(D, L-lactic acid) containing copolymers as substrates for cell adhesion. Artif Organs 27:242–248
Jeong B, Choi YK, Bae YH et al (1999) New biodegradable polymers for injectable drug delivery systems. J Control Release 62:109–114
Li Z, Ramay HR, Hauch KD et al (2005) Chitosan-alginate hybrid scaffolds for bone tissue engineering. Biomaterials 26:3919–3928
Ling Y, Rubin J, Deng Y et al (2007) A cell-laden microfluidic hydrogel. Lab Chip 7:756–762
Chenite A, Chaput C, Wang D et al (2000) Novel injectable neutral solutions of chitosan form biodegradable gels in situ. Biomaterials 21:2155–2161
Jeong B, Kim SW, Bae YH (2002) Thermosensitive sol-gel reversible hydrogels. Adv Drug Deliv Rev 54:37–51
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
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
Lutolf MP, Raeber GP, Zisch AH (2003) Cell-responsive synthetic hydrogels. Adv Mater 15:888–892
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
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
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
Nam KW, Watanabe J, Ishihara K (2002) Characterization of the spontaneously forming hydrogels composed of water-soluble phospholipid polymers. Biomacromolecules 3:100–105
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
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
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
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
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
Ishihara K, Ueda T, Nakabayashi N (1990) Preparation of phospholipid polymers and their properties as polymer hydrogel membrane. Polym J 22:355–360
Ishihara K (1997) Novel polymeric materials for obtaining blood compatible surfaces. Trends in Polym Sci 5:401–407
Lewis AL (2000) Phosphorylcholine-based polymers and their use in the prevention of biofouling. Colloid Surf B Biointerfaces 18:261–275
Ishihara K (2000) Bioinspired phospholipid polymer biomaterials for making high performance artificial organs. Sci Technol Adv Mater 1:131–138
Iwsaki Y, Ishihara K (2005) Phosphorylcholine-containing polymers for biomedical applications. Ann Bioanal Chem 381:534–546
Ishihara K, Takai M (2009) Bioinspired interfaces for nanobiodevices based on phospholipid polymer chemistry. J R Soc Interface 6:S279–S291
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
Ishihara K, Nomura H, Mihara T et al (1998) Why do phospholipid polymers reduce protein adsorption? J Biomed Mater Res 39:323–330
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
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
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
Goda T, Ishihara K (2006) Soft contact lens biomaterials from bioinspired phospholipid polymers. Expert Rev Med Devices 3:167–174
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
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
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
Lorand JP, Edwards JO (1959) Polyol complexes and structure of the benzeneboronate ion. J Org Chem 24:769–774
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
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
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
Ohno K, Tachikawa K, Manz A (2008) Microfluidics: applications for analytical purposes in chemistry and biochemistry. Electrophoresis 29:4443–4453
El-Ali J, Sorger PK, Jensen KF (2006) Cells on chips. Nature 442:403–411
Griffith LG, Swartz MA (2006) Capturing complex 3D tissue physiology in vitro. Nat Rev Mol Cell Biol 7:211–224
Sato K, Mawatari K, Kitamori T (2008) Microchip-based cell analysis and clinical diagnosis system. Lab Chip 8:1992–1998
Lion N, Rohner TC, Dayon L et al (2003) Microfluidic systems in proteomics. Electrophoresis 24:3533–3562
Andersson H, van den Berg A (2003) Microfluidic devices for cellomics: a review. Sensor Actuat B-Chem 92:315–325
Xu Y, Sato K, Konno T et al (2009) An on-chip living cell bank. Proc in Micro-TAS 2009:W82F
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
Wang Z, Kim MC, Marquez M et al (2007) High-density microfluidic arrays for cell cytotoxicity analysis. Lab Chip 7:740–745
de Souza N (2010) Single-cell methods. Nat Methods 7:35
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.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
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
Download citation
DOI: https://doi.org/10.1007/12_2011_151
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-27855-6
Online ISBN: 978-3-642-27856-3
eBook Packages: Chemistry and Materials ScienceChemistry and Material Science (R0)