Advertisement

Hydrogel Properties and Characterization Techniques

  • Michael J. Majcher
  • Todd HoareEmail author
Reference work entry
Part of the Polymers and Polymeric Composites: A Reference Series book series (POPOC)

Abstract

The unique structure of hydrogels as materials, including their soft mechanical properties, their typically high water contents, their capacity to respond to changes in their solvent environment, and their tunable and often multi-scale porosity, offers both significant challenges and specific opportunities in terms of their characterization. Herein, we describe the key properties associated with hydrogels (from both qualitative and quantitative perspectives) and review the major analytical techniques used to probe those properties, highlighting the strengths and weaknesses of various available strategies. Chemical, physical, and biological properties are all reviewed, with an emphasis on the techniques developed specific to hydrogels to measure swelling, mechanics, gelation time, and porosity.

Abbreviations

AAS

Atomic absorption spectroscopy

DLS

Dynamic light scattering

FTIR

Fourier transform infrared spectroscopy

IR

Infrared spectroscopy

JKR

Johnson-Kendall-Roberts

NMR

Nuclear magnetic resonance

NTA

Nanoparticle tracking analysis

PGSE-NMR

Pulsed gradient spin-echo nuclear magnetic resonance

SANS

Small-angle neutron scattering

SEM

Scanning electron microscopy

TEM

Transmission electron microscopy

TRPS

Tunable resistive pulse sensing

UV

Ultraviolet

Vis

Visible light (as in UV/vis spectroscopy)

XPS

X-ray photoelectron spectroscopy

References

  1. 1.
    L.P. Lindeman, J.Q. Adams, Chemical shifts for the paraffins through C9. Anal. Chem. 43(10), 1245–1252 (1971)CrossRefGoogle Scholar
  2. 2.
    J.U. Izunobi, C.L. Higginbotham, Polymer molecular weight analysis by 1H NMR spectroscopy. J. Chem. Ed. 88(8), 1098–1104 (2011)CrossRefGoogle Scholar
  3. 3.
    A.M. Mathur, A.B.. Scranton, Characterization of hydrogels using nuclear magnetic resonance spectroscopy. Biomacromolecules 17, 547–557 (1997)Google Scholar
  4. 4.
    C.M. Nolan, L.T. Gelbaum, L.A. Lyon, 1H NMR investigation of thermally triggered insulin release from poly(N-isopropylacrylamide) microgels. Biomacromolecules 7, 2918–2922 (2006)CrossRefGoogle Scholar
  5. 5.
    S. Van Vlierberghe, B. Fritzinger, J.C. Martins, P. Dubruel, Hydrogel network formation revised: high-resolution magic angle spinning nuclear magnetic resonance as a powerful tool for measuring absolute hydrogel cross-link efficiencies. Appl. Spect. 64(10), 1176–1180 (2010)CrossRefGoogle Scholar
  6. 6.
    D.L. Wise, Handbook of Pharmaceutical Controlled Release Technology (Marcel Dekker, New York, 2000)CrossRefGoogle Scholar
  7. 7.
    Q. Wu, J. Wei, B. Xu, X. Liu, H. Wang, W. Wang, Q. Wang, W. Liu, A robust, highly stretchable supramolecular polymer conductive hydrogel with self-healability and thermo-processability. Sci. Rep. 7, 41566 (2017)CrossRefGoogle Scholar
  8. 8.
    X. Deng, N.M.B. Smeets, C. Sicard, Y. Wang, J.D. Brennan, C.D.M. Filipe, T. Hoare, Poly(oligoethylene glycol methacrylate) dip-coating: turning cellulose paper into a protein-repellent platform for biosensors. J. Am. Chem. Soc. 136(37), 12852–12855 (2014)CrossRefGoogle Scholar
  9. 9.
    J. Zhu, C. Tang, K. Kottke-Marchant, R.E. Marchant, Design and synthesis of biomimetic hydrogel scaffolds with controlled organization of cyclic RGD peptides. Bioconjug. Chem. 20(2), 333–339 (2009)CrossRefGoogle Scholar
  10. 10.
    C.S. Fadley, X-ray photoelectron spectroscopy: progress and perspectives. J. Electron. Spect. Rel. Phenom. 178–179, 2–32 (2010)CrossRefGoogle Scholar
  11. 11.
    R.S. Tomar, I. Gupta, R. Singhal, A.K. Nagpal, Synthesis of poly(acrylamide-co-acrylic acid)-based super-absorbent hydrogels by gamma radiation: study of swelling behaviour and network parameters. Des. Monomers Polym. 10(1), 49–66 (2007)CrossRefGoogle Scholar
  12. 12.
    P.J. Flory, Principles of Polymer Chemistry (Cornell University Press, Ithaca, 1953)Google Scholar
  13. 13.
    J. Hasa, M. Ilavsky, K. Dusek, Deformational, swelling, and potentiometric behavior of ionized poly(methacrylic acid) gels. I. Theory. J. Polym. Sci. Polym. Phys. 13, 253–262 (1975)CrossRefGoogle Scholar
  14. 14.
    A. Katchalsky, I. Michaeli, Polyelectrolyte gels in salt solution. J. Polym. Sci. XV, 69–86 (1955)CrossRefGoogle Scholar
  15. 15.
    T. Hoare, R. Pelton, Functionalized microgel swelling: comparing theory and experiment. J. Phys. Chem. B 111, 11895–11906 (2007)CrossRefGoogle Scholar
  16. 16.
    J.E. Silva, R. Geryak, D.A. Loney, P.A. Kottke, R.R. Naik, V.V. Tsukruk, A.G. Fedorov, Stick-slip water penetration into capillaries coated with swelling hydrogel. Soft. Matter. 11(29), 5933–5939 (2015)CrossRefGoogle Scholar
  17. 17.
    M. Patenaude, S. Campbell, D. Kinio, T. Hoare, Tuning gelation time and morphology of injectable hydrogels using ketone-hydrazide cross-linking. Biomacromolecules 15(3), 781–790 (2014)CrossRefGoogle Scholar
  18. 18.
    T. Gilbert, N.M.B. Smeets, T. Hoare, Injectable interpenetrating network hydrogels via kinetically orthogonal reactive mixing of functionalized polymeric precursors. ACS. Macro. Lett. 4(10), 1104–1109 (2015)CrossRefGoogle Scholar
  19. 19.
    G. Lin, S. Chang, H. Hao, P. Tathireddy, M. Orthner, J. Magda, F. Solzbacher, Osmotic swelling pressure response of smart hydrogels suitable for chronically-implantable glucose sensors. Sens. Actuators B Chem. 144(1), 332–336 (2010)CrossRefGoogle Scholar
  20. 20.
    F. Horkaya, M.H. Han, I.S. Han, I.S. Bang, J.J. Maqda, Separation of the effects of pH and polymer concentration on the swelling pressure and elastic modulus of a pH-responsive hydrogel. Polymer 47(21), 7335–7338 (2006)CrossRefGoogle Scholar
  21. 21.
    E. Bakaic, N.M.B. Smeets, H. Dorrington, T. Hoare, “Off-the-shelf” thermoresponsive hydrogel design: tuning hydrogel properties by mixing precursor polymers with different lower-critical solution temperatures. RSC Adv. 5(42), 33364–33376 (2015)CrossRefGoogle Scholar
  22. 22.
    B. Zhang, H. Tao, B. Wei, Z. Jin, X. Xu, Y. Tian, Characterization of different substituted carboxymethyl starch microgels and their interactions with lysozyme. PLoS One 9(12), e114634 (2014)CrossRefGoogle Scholar
  23. 23.
    L.R. Kesselman, S. Shinwary, P.R. Selvanganapathy, T. Hoare, Synthesis of monodisperse, covalently cross-linked, degradable “smart” microgels using microfluidics. Small 8(7), 1092–1098 (2012)CrossRefGoogle Scholar
  24. 24.
    A.H. Colby, Y.L. Colson, M.W. Grinstaff, Microscopy and tunable resistive pulse sensing characterization of the swelling of pH-responsive, polymeric expansile nanoparticles. Nanoscale 5(8), 3496–3504 (2013)CrossRefGoogle Scholar
  25. 25.
    V. Filipe, A. Hawe, W. Jiskoot, Critical evaluation of nanoparticle tracking analysis (NTA) by nanosight for the measurement of nanoparticles and protein aggregates. Pharm. Res. 27(5), 796–810 (2010)CrossRefGoogle Scholar
  26. 26.
    X. Liu, Y. Yang, Y. Li, X. Niu, B. Zhao, Y. Wang, C. Bao, Z. Xie, Q. Lin, L. Zhu, Integration of stem cell-derived exosomes with in situ hydrogel glue as a promising tissue patch for articular cartilage regeneration. Nanoscale 9(13), 4430–4438 (2017)CrossRefGoogle Scholar
  27. 27.
    O.S. Lawal, J. Storz, H. Storz, D. Lohmann, D. Lechner, W.M. Kulicke, Hydrogels based on carboxymethyl cassava starch cross-linked with di- or polyfunctional carboxylic acids: Synthesis, water absorbent behavior and rheological characterizations. Eur. Polym. J. 45(12), 3399–3408 (2009)CrossRefGoogle Scholar
  28. 28.
    N.R. Langley, K.E. Polmanteer, Relation of elastic modulus to crosslink and entanglement concentrations in rubber networks. J. Polym. Sci. Polym. Phys. 12, 1023–1034 (1974)CrossRefGoogle Scholar
  29. 29.
    F. Xu, H. Sheardown, T. Hoare, Reactive electrospinning of degradable poly(oligoethylene glycol methacrylate)-based nanofibrous hydrogel networks. Chem. Commun. 52(7), 1451–1454 (2016)CrossRefGoogle Scholar
  30. 30.
    A.J. Ranta-Eskola, Use of the hydraulic bulge test in biaxial tensile testing. Int. J. Mech. Sci. 21, 457–465 (1979)CrossRefGoogle Scholar
  31. 31.
    D.C. Lin, B. Yurke, N.A. Langrana, Use of rigid spherical inclusions in Young’s moduli determination: application to DNA-crosslinked gels. J. Biomech. Eng. 127, 571–579 (2005)CrossRefGoogle Scholar
  32. 32.
    M.L. Previtera, U. Chippada, R.S. Schloss, B. Yurke, N.A. Langrana, Mechanical properties of DNA-crosslinked polyacrylamide hydrogels with increasing crosslinker density. Biores. Open Access 1(5), 256–259 (2012)CrossRefGoogle Scholar
  33. 33.
    K.K. Liu, B.F. Ju, A novel technique for mechanical characterization of thin elastomeric membrane. J. Phys. D. Appl. Phys. 34, L91–L94 (2001)CrossRefGoogle Scholar
  34. 34.
    C. Yu, A. Kornmuller, C. Brown, T. Hoare, L.E. Flynn, Decellularized adipose tissue microcarriers as a dynamic culture platform for human adipose-derived stem/stromal cell expansion. Biomaterials 120, 66–80 (2017)CrossRefGoogle Scholar
  35. 35.
    T. Boudou, J. Ohayon, Y. Arntz, G. Finet, C. Picart, P. Tracqui, An extended modeling of the micropipette aspiration experiment for the characterization of the Young’s modulus and Poisson’s ratio of adherent thin biological samples: numerical and experimental studies. J. Biomech. 39(9), 1677–1685 (2006)CrossRefGoogle Scholar
  36. 36.
    X. Peng, J. Huang, H. Deng, C. Xiong, J. Fang, A multi-sphere indentation method to determine Young’s modulus of soft polymeric materials based on the Johnson–Kendall–Roberts contact model. Meas. Sci. Tech. 22(2), 027003 (2011)CrossRefGoogle Scholar
  37. 37.
    A.V. Salsac, L. Zhang, J.M. Gherbezza, Measurement of mechanical properties of alginate beads using ultrasound. 19eme Congres Francais de Mecanique, 2009Google Scholar
  38. 38.
    I. Lee, K. Akiyoshi, Single molecular mechanics of a cholesterol-bearing pullulan nanogel at the hydrophobic interfaces. Biomaterials 25(15), 2911–2918 (2004)CrossRefGoogle Scholar
  39. 39.
    K.J. De France, K.J.W. Chan, E.D. Cranston, T. Hoare, Enhanced mechanical properties in cellulose nanocrystal-poly(oligoethylene glycol methacrylate) injectable nanocomposite hydrogels through control of physical and chemical cross-linking. Biomacromolecules 17(2), 649–660 (2016)CrossRefGoogle Scholar
  40. 40.
    X. Hu, J. Fan, C.Y. Yue, Rheological study of crosslinking and gelation in bismaleimide/cyanate ester interpenetrating polymer network. J. Appl. Polym. Sci. 80, 2437–2445 (2000)CrossRefGoogle Scholar
  41. 41.
    L. Weng, X. Chen, W. Chen, Rheological characterization of in situ crosslinkable hydrogels formulated from oxidized dextran and N-carboxyethyl chitosan. Biomacromolecules 8(4), 1109–1115 (2007)CrossRefGoogle Scholar
  42. 42.
    N.A. Peppas, J.Z. Hilt, A. Khademhosseini, R. Langer, Hydrogels in biology and medicine: from molecular principles to bionanotechnology. Adv. Mater. 18(11), 1345–1360 (2006)CrossRefGoogle Scholar
  43. 43.
    W. Wu, S. Zhou, Hybrid micro−/nanogels for optical sensing and intracellular imaging. Nano. Rev. 1, 5730 (2010).  https://doi.org/10.3402/nano.v1i0.5730CrossRefGoogle Scholar
  44. 44.
    M. Carme Coll Ferrer, P. Sobolewski, R.J. Composto, D.M. Eckmann, Cellular uptake and intracellular cargo release from dextran based nanogel drug carriers. J. Nanotechnol. Eng. Med. 4(1), 110021–110028 (2013)CrossRefGoogle Scholar
  45. 45.
    M.C.C. Ferrer, R.C. Ferrier Jr., D.M. Eckmann, R.J. Composto, A facile route to synthesize nanogels doped with silver nanoparticles. J. Nanopart. Res. 15, 1323 (2012).  https://doi.org/10.1007/s11051-012-1323-5CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    B. Sternberg, F.L. Sorgi, L. Huang, New structures in complex formation between DNA and cationic liposomes visualized by freeze-fracture electron microscopy. FEBS Lett. 356, 361–366 (1994)CrossRefGoogle Scholar
  47. 47.
    L.L. Muller, T.J. Jacks, Rapid chemical dehydration of samples for electron microscopic investigations. J. Histochem. Cytochem. 23(2), 107–110 (1975)CrossRefGoogle Scholar
  48. 48.
    S.M. Liff, N. Kumar, G.H. McKinley, High-performance elastomeric nanocomposites via solvent-exchange processing. Nat. Mater. 6(1), 76–83 (2007)CrossRefGoogle Scholar
  49. 49.
    H. Bai, A. Polini, B. Delattre, A.P. Tomsia, Thermoresponsive composite hydrogels with aligned macroporous structure by ice-templated assembly. Chem. Mater. 25(22), 4551–4556 (2013)CrossRefGoogle Scholar
  50. 50.
    M.V. Dinu, M. Pradny, E.S. Dragan, J. Michalek, Ice-templated hydrogels based on chitosan with tailored porous morphology. Carbohydr. Polym. 94(1), 170–178 (2013)CrossRefGoogle Scholar
  51. 51.
    K.M. Pawelec, A. Husmann, S.M. Best, R.E. Cameron, Understanding anisotropy and architecture in ice-templated biopolymer scaffolds. Mater. Sci. Eng. C Mater. Biol. Appl. 37, 141–147 (2014)CrossRefGoogle Scholar
  52. 52.
    X. Yang, E. Bakaic, T. Hoare, E.D. Cranston, Injectable polysaccharide hydrogels reinforced with cellulose nanocrystals: morphology, rheology, degradation, and cytotoxicity. Biomacromolecules 14(12), 4447–4455 (2013)CrossRefGoogle Scholar
  53. 53.
    J.J. Crassous, M. Ballauff, Imaging the volume transition in thermosensitive core-shell particles by cryo-transmission electron microscopy. Langmuir 22(6), 2403–2406 (2006)CrossRefGoogle Scholar
  54. 54.
    G. Fundueanu, C. Nastruzzi, A. Carpov, J. Desbrieres, M. Rinaudo, Physico-chemical characterization of Ca-alginate microparticles produced with different methods. Biomaterials 20, 1427–1435 (1999)CrossRefGoogle Scholar
  55. 55.
    L. Bromberg, M. Temchenko, T.A. Hatton, Smart microgel studies. Polyelectrolyte and drug-absorbing properties of microgels from polyether-modified poly(acrylic acid). Langmuir 19, 8675–8684 (2003)CrossRefGoogle Scholar
  56. 56.
    G.M. Eichenbaum, P.F. Kiser, A.V. Dobrynin, S.A. Simon, D. Needham, Investigation of the swelling response and loading of ionic microgels with drugs and proteins: the dependence on cross-link density. Macromolecules 32, 4867–4878 (1999)CrossRefGoogle Scholar
  57. 57.
    J.-Y. Xiong, J. Narayana, X.-Y. Liu, T.K. Chong, S.B. Chen, T.S. Chung, Topology evolution and gelation mechanism of agarose gel. J. Phys. Chem. B 109, 5638–5643 (2005)CrossRefGoogle Scholar
  58. 58.
    S.K. Lai, Y.Y. Wang, K. Hida, R. Cone, J. Hanes, Nanoparticles reveal that human cervicovaginal mucus is riddled with pores larger than viruses. Proc. Natl. Acad. Sci. 107(2), 598–603 (2010)CrossRefGoogle Scholar
  59. 59.
    W.S. Price, Pulsed-field gradient nuclear magnetic resonance as a tool for studying translational diffusion: part 1. Concepts Magn. Reson. A 9(5), 299–336 (1997)CrossRefGoogle Scholar
  60. 60.
    B. Sierra-Martín, M.S. Romero-Cano, T. Cosgrove, B. Vincent, A. Fernandez-Barbero, Solvent relaxation of swelling PNIPAM microgels by NMR. Colloids Surf. A Physicochem. Eng. Asp. 270–271, 296–300 (2005)CrossRefGoogle Scholar
  61. 61.
    P.Y. Ghi, D.J.T. Hill, A.K. Whittaker, PFG-NMR measurements of the self-diffusion coefficients of water in equilibrium poly(HEMA-co-THFMA) hydrogels. Biomacromolecules 3(3), 554–559 (2002)CrossRefGoogle Scholar
  62. 62.
    L. Galantini, A.A. D’Archivioa, S. Lorab, S. Legnaro, An ESR and PGSE-NMR evaluation of the molecular accessibility of poly (vinyl alcohol) hydrogels. J. Mol. Catal. B 6, 505–508 (1999)CrossRefGoogle Scholar
  63. 63.
    H.Y.I. Ando, Dynamic behavior of water in hydro-swollen crosslinked polymer gel as studied by PGSE 1H NMR and pulse 1H NMR. Polym. Gels. Netw. 1, 83–92 (1993)CrossRefGoogle Scholar
  64. 64.
    P.C. Griffiths, P. Stilbs, B.Z. Chowdhry, M.J. Snowden, PGSE-NMR studies of solvent diffusion in poly(N-isopropylacrylamide) colloidal microgels. Colloid Polym. Sci. 273, 405–411 (1995)CrossRefGoogle Scholar
  65. 65.
    A. Guillermo, J.P. Cohen Addad, J.P. Bazile, D. Duracher, A. Elasissari, C. Pichot, NMR investigations into heterogeneous structures of thermosensitive microgel particles. J. Polym. Sci. B Polym. Phys. 38, 889–898 (2000)CrossRefGoogle Scholar
  66. 66.
    K.A. Heisel, J.J. Goto, V.V. Krishnan, NMR chromatography: molecular diffusion in the presence of pulsed field gradients in analytical chemistry applications. Amer. J. Anal. Chem. 3, 401–409 (2012)CrossRefGoogle Scholar
  67. 67.
    M. Shibayama, Small-angle neutron scattering on polymer gels: phase behavior, inhomogeneities and deformation mechanisms. Polym. J. 43(1), 18–34 (2010)CrossRefGoogle Scholar
  68. 68.
    S. Takata, T. Norisuye, Small-angle neutron-scattering study on preparation temperature dependence of thermosensitive gels. Macromolecules 35, 4779–4784 (2002)CrossRefGoogle Scholar
  69. 69.
    J. Tian, T.A.P. Seery, D.L. Ho, R.A. Weiss, Physically cross-linked alkylacrylamide hydrogels: a SANS analysis of the microstructure. Macromolecules 37, 10001–10008 (2004)CrossRefGoogle Scholar
  70. 70.
    B. Hammouda, D. Ho, S. Kline, SANS from poly(ethylene oxide)/water systems. Macromolecules 35, 8578–8585 (2002)CrossRefGoogle Scholar
  71. 71.
    P. Sheikholeslami, B. Muirhead, D.S. Baek, H. Wang, X. Zhao, D. Sivakumaran, S. Boyd, H. Sheardown, T. Hoare, Hydrophobically-modified poly(vinyl pyrrolidone) as a physically-associative, shear-responsive ophthalmic hydrogel. Exp. Eye Res. 137, 18–31 (2015)CrossRefGoogle Scholar
  72. 72.
    J.M. González-Méijome, M. Lira, A. Lopez-Alemany, J.B. Almeida, M.A. Parafita, M.F. Refojo, Refractive index and equilibrium water content of conventional and silicone hydrogel contact lenses. Ophthalmic Physiol. Opt. 26, 57–64 (2006)CrossRefGoogle Scholar
  73. 73.
    S.R. Caliari, J.A. Burdick, A practical guide to hydrogels for cell culture. Nat. Methods 13(5), 405–414 (2016)CrossRefGoogle Scholar
  74. 74.
    J.M. Anderson, Biological responses to materials. Ann. Rev. Mater. Res. 31, 81–110 (2001)CrossRefGoogle Scholar
  75. 75.
    T.A. Horbett, J.L. Brash, Chapter 1, Proteins at interfaces: current issues and future prospects, in Proteins at Interfaces. ACS Symposium Series, vol 343 (American Chemical Society, Washington, DC (1987), pp. 1–33.  https://doi.org/10.1021/bk-1987-0343.ch001
  76. 76.
    J.L. Brash, T.A. Horbett, Proteins at interfaces, in Proteins at Interfaces II: Fundamentals and Applications, vol 602 (Washington, DC, 1995), pp. 1–23.  https://doi.org/10.1021/bk-1995-0602
  77. 77.
    S.M. Russell, G. Carta, Multicomponent protein adsorption in supported cationic polyacrylamide hydrogels. AICHE J. 51(9), 2469–2480 (2005)CrossRefGoogle Scholar
  78. 78.
    Q. Garrett, B.K. Milthorpe, Human serum albumin adsorption on hydrogel contact lenses in vitro. Invest. Ophthalmol. Vis. Sci. 37(13), 2594–2602 (1996)PubMedGoogle Scholar
  79. 79.
    D. Luensmann, M.A. Glasier, F. Zhang, V. Bantseev, T. Simpson, L. Jones, Confocal microscopy and albumin penetration into contact lenses. Invest. Ophthalmol. Vis. Sci. 84(9), 839–847 (2007)Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Chemical EngineeringMcMaster UniversityHamiltonCanada

Personalised recommendations