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Poly(N-isopropylacrylamide)-based thermo-responsive surfaces with controllable cell adhesion

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  • Special Issue Recent Research Progress of Biomedical Polymers
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Abstract

Poly(N-isopropylacrylamide) (PNIPAAm)-based thermo-responsive surfaces can switch their wettability (from wettable to non-wettable) and adhesion (from sticky to non-sticky) according to external temperature changes. These smart surfaces with switchable interfacial properties are playing increasingly important roles in a diverse range of biomedical applications; these controlling cell-adhesion behavior has shown great potential for tissue engineering and disease diagnostics. Herein we reviewed the recent progress of research on PNIPAAm-based thermo-responsive surfaces that can dynamically control cell adhesion behavior. The underlying response mechanisms and influencing factors for PNIPAAm-based surfaces to control cell adhesion are described first. Then, PNIPAAm-modified two-dimensional flat surfaces for cell-sheet engineering and PNIPAAm-modified three-dimensional nanostructured surfaces for diagnostics are summarized. We also provide a future perspective for the development of stimuli-responsive surfaces.

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References

  1. Yamada KM. Cell surface interactions with extracellular materials. Annu Rev Biochem, 1983, 52: 761–799

    Article  CAS  Google Scholar 

  2. Vilches J, Vilches-Perez J, Salido M. In: Méndez-Vilas A, Díaz J, eds. Modern Research and Educational Topics in Mircroscopy. Formatex, 2007

  3. Hong S. Quantitative analysis of cell-surface interactions and cell adhesion process in real-time. Dissertation for the Doctoral Degree. Philadelphia: Drexel University, 2008

    Google Scholar 

  4. Stuart MAC, Huck WTS, Genzer J, Müller M, Ober C, Stamm M, Sukhorukov GB, Szleifer I, Tsukruk VV, Urban M, Winnik F, Zauscher S, Luzinov I, Minko S. Emerging applications of stimuliresponsive polymer materials. Nat Mater, 2010, 9: 101–113

    Article  CAS  Google Scholar 

  5. Liu Y, Mu L, Liu B, Kong J. Controlled switchable surface. ChemEur J, 2005, 11: 2622–2631

    CAS  Google Scholar 

  6. Zhao Y, Xie Z, Gu H, Zhu C, Gu Z. Bio-inspired variable structural color materials. Chem Soc Rev, 2012, 41: 3297–3317

    Article  CAS  Google Scholar 

  7. Pan Y, Du X, Zhao F, Xu B. Magnetic nanoparticles for the manipulation of proteins and cells. Chem Soc Rev, 2012, 41: 2912–2942

    Article  CAS  Google Scholar 

  8. Li Y, Wang X, Sun J. Layer-by-layer assembly for rapid fabrication of thick polymeric films. Chem Soc Rev, 2012, 41: 5998–6009

    Article  CAS  Google Scholar 

  9. Xia F, Jiang L. Bio-inspired, smart, multiscale interfacial materials. Adv Mater, 2008, 20: 2842–2858

    Article  CAS  Google Scholar 

  10. Brun-Graeppi AKAS, Richard C, Bessodes M, Scherman D, Merten, OW. Thermoresponsive surfaces for cell culture and enzyme-free cell detachment. Prog Polym Sci, 2010, 35: 1311–1324

    Article  CAS  Google Scholar 

  11. Sun T, Wang G, Feng L, Liu B, Ma Y, Jiang L, Zhu D. Reversible switching between superhydrophilicity and superhydrophobicity. Angew Chem Int Ed, 2004, 43: 357–360

    Article  CAS  Google Scholar 

  12. Azzaroni O, Brown AA, Huck WTS. UCST wetting transitions of polyzwitterionic brushes driven by self-association. Angew Chem Int Ed, 2006, 45: 1770–1774

    Article  CAS  Google Scholar 

  13. Heskins M, Guillet JE. Solution properties of poly(N-isopropylacrylamide). J Macromol Sci: Part A-Chem, 1968, 2: 1441–1455

    Article  CAS  Google Scholar 

  14. Schild H. Poly(N-isopropylacrylamide): experiment, theory and application. Prog Polym Sci, 1992, 17: 163–249

    Article  CAS  Google Scholar 

  15. Cole MA, Voelcker NH, Thissen H, Griesser HJ. Stimuli-responsive interfaces and systems for the control of protein-surface and cellsurface interactions. Biomaterials, 2009, 30: 1827–1850

    Article  CAS  Google Scholar 

  16. Elloumi-Hannachi I, Yamato M, Okano T. Cell sheet engineering: a unique nanotechnology for scaffold-free tissue reconstruction with clinical applications in regenerative medicine. J Intern Med, 2010, 267: 54–70

    Article  CAS  Google Scholar 

  17. Cooperstein MA, Canavan HE. Biological cell detachment from poly(N-isopropyl acrylamide) and its applications. Langmuir, 2010, 26: 7695–7707

    Article  CAS  Google Scholar 

  18. Kumashiro Y, Yamato M, Okano T. Cell attachment-detachment control on temperature-responsive thin surfaces for novel tissue engineering. Ann Biomed Eng, 2010, 38: 1977–1988

    Article  Google Scholar 

  19. Prime KL, Whitesides GM. Adsorption of proteins onto surfaces containing end-attached oligo(ethylene oxide): a model system using self-assembled monolayers. J Am Chem Soc, 1993, 115: 10714–10721

    Article  CAS  Google Scholar 

  20. Chen SF, Zheng J, Li LY, Jiang SY. Strong resistance of phosphorylcholine self-assembled monolayers to protein adsorption: insights into nonfouling properties of zwitterionic materials. J Am Chem Soc, 2005, 127: 14473–14478

    Article  CAS  Google Scholar 

  21. Sigal GB, Mrksich M, Whitesides GM. Effect of surface wettability on the adsorption of proteins and detergents. J Am Chem Soc, 1998, 120: 3464–3473

    Article  CAS  Google Scholar 

  22. Mizutani A, Kikuchi A, Yamato M, Kanazawa H, Okano T. Preparation of thermoresponsive polymer brush surfaces and their interaction with cells. Biomaterials, 2008, 29: 2073–2081

    Article  CAS  Google Scholar 

  23. Matsuda N, Shimizu T, Yamato M, Okano T. Tissue engineering based on cell sheet technology. Adv Mater, 2007, 19: 3089–3099

    Article  CAS  Google Scholar 

  24. Yamada N, Okano T, Sakai H, Karikusa F, Sawasaki Y, Sakurai Y. Thermo-responsive polymeric surfaces: control of attachment and detachment of cultured cells. Makromol Chem Rapid Commun, 1990, 11: 571–576

    Article  CAS  Google Scholar 

  25. Takezawa T, Mori Y, Yoshizato K. Cell culture on a thermoresponsive polymer surface. Nat Biotech, 1990, 8: 854–856

    Article  CAS  Google Scholar 

  26. Okano T, Kikuchi A, Sakurai Y, Takei Y, Ogata N. Temperatureresponsive poly(N-Isopropylacrylamide) as a modulator for alteration of hydrophilic-hydrophobic surface-properties to control activationinactivation of platelets. J Controlled Release, 1995, 36: 125–133

    Article  CAS  Google Scholar 

  27. Okano T, Yamada N, Okuhara M, Sakai H, Sakurai, Y. Mechanism of cell detachment from temperature-modulated, hydrophilichydrophobic polymer surfaces. Biomaterials, 1995, 16: 297–303

    Article  CAS  Google Scholar 

  28. Takei YG, Aoki T, Sanui K, Ogata N, Sakurai Y, Okano T. Temperature-modulated platelet and lymphocyte interactions with poly(N-Isopropylacrylamide)-grafted surfaces. Biomaterials, 1995, 16: 667–673

    Article  CAS  Google Scholar 

  29. Sawa Y, Miyagawa S, Sakaguchi T, Fujita T, Matsuyama A, Saito A, Shimizu T, Okano T. Tissue engineered myoblast sheets improved cardiac function sufficiently to discontinue LVAS in a patient with DCM: report of a case. Surg Today, 2012, 42: 181–184

    Article  Google Scholar 

  30. Nithya J, Kumar PRA, Tilak P, Leena J, Sreenivasan K, Kumary TV. Intelligent thermoresponsive substrate from modified overhead projection sheet as a tool for construction and support of cell sheets in vitro. Tissue Eng Part C-Methods, 2011, 17: 181–191

    Article  CAS  Google Scholar 

  31. Nitschke M, Gramm S, Goetze T, Valtink M, Drichel J, Voit B, Engelmann K, Werner C. Thermo-responsive poly(NIPAAm-co-DEGMA) substrates for gentle harvest of human corneal endothelial cell sheets. J Biomed Mater Res Part A, 2007, 80A: 1003–1010

    Article  CAS  Google Scholar 

  32. Lai JY, Chen KH, Hsu WM, Hsiue GH, Lee YH. Bioengineered human corneal endothelium for transplantation. Arch Ophthalmol, 2006, 124: 1441–1448

    Article  CAS  Google Scholar 

  33. Ohki T, Yamato M, Ota M, Takagi R, Murakami D, Kondo M, Sasaki R, Namiki H, Okano T, Yamamoto M. Prevention of esophageal stricture after endoscopic submucosal dissection using tissue-engineered cell sheets. Gastroenterology, 2012, 143: 582–588

    Article  Google Scholar 

  34. Ishikawa I, Iwata T, Washio K, Okano T, Nagasawa T, Iwasaki K, Ando T. Cell sheet engineering and other novel cell-based approaches to periodontal regeneration. Periodontology, 2009, 51: 220–238

    Article  Google Scholar 

  35. Iwata T, Yamato M, Tsuchioka H, Takagi R, Mukobata S, Washio K, Okano T, Ishikawa I. Periodontal regeneration with multi-layered periodontal ligament-derived cell sheets in a canine model. Biomaterials, 2009, 30: 2716–2723

    Article  CAS  Google Scholar 

  36. Ebihara G, Sato M, Yamato M, Mitani G, Kutsuna T, Nagai T, Ito S, Ukai T, Kobayashi M, Kokubo M. Cartilage repair in transplanted scaffold-free chondrocyte sheets using a minipig model. Biomaterials, 2012, 33: 3846–3851

    Article  CAS  Google Scholar 

  37. Tsuda Y, Kikuchi A, Yamato M, Nakao A, Sakurai Y, Umezu M, Okano T. The use of patterned dual thermoresponsive surfaces for the collective recovery as co-cultured cell sheets. Biomaterials, 2005, 26: 1885–1893

    Article  CAS  Google Scholar 

  38. Li L, Zhu Y, Li B, Gao C. Fabrication of thermoresponsive polymer gradients for study of cell adhesion and detachment. Langmuir, 2008, 24: 13632–13639

    Article  CAS  Google Scholar 

  39. Li L, Wu J, Gao C. Gradient immobilization of a cell adhesion RGD peptide on thermal responsive surface for regulating cell adhesion and detachment. Colloids Surf B, 2011, 85: 12–18

    Article  CAS  Google Scholar 

  40. Li L, Wu J, Gao C. Surface-grafted block copolymer brushes with continuous composition gradients of poly(poly(ethylene glycol)-monomethacrylate) and poly(N-isopropylacrylamide). Sci China Chem, 2011, 54: 334–342

    Article  CAS  Google Scholar 

  41. Haraguchi K, Takehisa T, Ebato M. Control of cell cultivation and cell sheet detachment on the surface of polymer/clay nanocomposite hydrogels. Biomacromolecules, 2006, 7: 3267–3275

    Article  CAS  Google Scholar 

  42. Tong Z, Wang T, Liu D, Lan C, Zheng S, Liu X, Wang C. Rapid cell sheet detachment from alginate semi-interpenetrating nanocomposite hydrogels of PNIPAm and hectorite clay. React Funct Polym, 2011, 71: 447–454

    Article  CAS  Google Scholar 

  43. Pan G, Guo Q, Ma Y, Yang H, Li, B. Thermo-responsive hydrogel layers imprinted with RGDS peptide: a system for harvesting cell sheets. Angew Chem Int Ed, 2013, 52: 6907–6911

    Article  CAS  Google Scholar 

  44. Bettinger CJ, Langer R, Borenstein JT. Engineering substrate topography at the micro- and nanoscale to control cell function. Angew Chem Int Ed, 2009, 48: 5406–5415

    Article  CAS  Google Scholar 

  45. Curtis A, Wilkinson C. Topographical control of cells. Biomaterials, 1997, 18: 1573–1583

    Article  CAS  Google Scholar 

  46. Wang S, Wang H, Jiao J, Chen K, Owens GE, Kamei K, Sun J, Sherman DJ, Behrenbruch CP, Wu H, Tseng HR. Three-dimensional nanostructured substrates toward efficient capture of circulating tumor cells. Angew Chem Int Ed, 2009, 48: 8970–8973

    Article  CAS  Google Scholar 

  47. Zhang P, Chen L, Xu T, Liu H, Liu X, Meng J, Yang G, Jiang L, Wang S. Programmable fractal nanostructured interfaces for specific recognition and electrochemical release of cancer cells. Adv Mater, 2013, 25: 3566–3570

    Article  CAS  Google Scholar 

  48. Liu X, Chen L, Liu H, Yang G, Zhang P, Han D, Wang S, Jiang L. Bio-inspired soft polystyrene nanotube substrate for rapid and highly efficient breast cancer-cell capture. NPG Asia Mater, 2013, 5: e63

    Article  CAS  Google Scholar 

  49. Liu H, Liu X, Meng J, Zhang P, Yang G, Su B, Sun K, Chen L, Han D, Wang S, Jiang L. Hydrophobic interaction-mediated capture and release of cancer cells on thermoresponsive nanostructured surfaces. Adv Mater, 2013, 25: 922–927

    Article  CAS  Google Scholar 

  50. Hou S, Zhao H, Zhao L, Shen Q, Wei KS, Suh DY, Nakao A, Garcia MA, Song M, Lee T, Xiong B, Luo SC, Tseng HR, Yu H. Capture and stimulated release of circulating tumor cells on polymer-grafted silicon nanostructures. Adv Mater, 2013, 25: 1547–1551

    Article  CAS  Google Scholar 

  51. Kim YJ, Ebara M, Aoyagi T. A smart nanofiber web that captures and releases cells. Angew Chem Int Ed, 2012, 51: 10537–10541

    Article  CAS  Google Scholar 

  52. Lutz JF. Thermo-switchable materials prepared using the OEGMA-platform. Adv Mater, 2011, 23: 2237–2243

    Article  CAS  Google Scholar 

  53. Wischerhoff E, Uhlig K, Lankenau A, Borner HG, Laschewsky A, Duschl C, Lutz, JF. Controlled cell adhesion on PEG-based switchable surfaces. Angew Chem Int Ed, 2008, 47: 5666–5668

    Article  CAS  Google Scholar 

  54. Na K, Jung J, Kim O, Lee J, Lee TG, Park YH, Hyun J. “Smart” biopolymer for a reversible stimuli-responsive platform in cell-based biochips. Langmuir, 2008, 24: 4917–4923

    Article  CAS  Google Scholar 

  55. Zhu J, Nguyen T, Pei R, Stojanovic M, Lin Q. Specific capture and temperature-mediated release of cells in an aptamer-based microfluidic device. Lab on a Chip, 2012, 12: 3504–3513

    Article  CAS  Google Scholar 

  56. Silva AKA, Richard C, Ducouret G, Bessodes M, Scherman D, Merten OW. Xyloglucan-derivatized films for the culture of adherent cells and their thermocontrolled detachment: a promising alternative to cells sensitive to protease treatment. Biomacromolecules, 2012, 14: 512–519

    Article  CAS  Google Scholar 

  57. Xia F, Feng L, Wang S, Sun T, Song W, Jiang W, Jiang L. Dualresponsive surfaces that switch between superhydrophilicity and superhydrophobicity. Adv Mater, 2006, 18: 432–436

    Article  CAS  Google Scholar 

  58. Xia F, Ge H, Hou Y, Sun T, Chen L, Zhang G, Jiang L. Multiresponsive surfaces change between superhydrophilicity and superhydrophobicity. Adv Mater, 2007, 19: 2520–2524

    Article  CAS  Google Scholar 

  59. Liu H, Li Y, Sun K, Fan J, Zhang P, Meng J, Wang S, Jiang L. Dualresponsive surfaces modified with phenylboronic acid-containing polymer brush to reversibly capture and release cancer cells. J Am Chem Soc, 2013, 135: 7603–7609

    Article  CAS  Google Scholar 

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  1. Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China

    HongLiang Liu & ShuTao Wang

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Correspondence to ShuTao Wang.

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Liu, H., Wang, S. Poly(N-isopropylacrylamide)-based thermo-responsive surfaces with controllable cell adhesion. Sci. China Chem. 57, 552–557 (2014). https://doi.org/10.1007/s11426-013-5051-1

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