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Fast-forming hydrogel with ultralow polymeric content as an artificial vitreous body

Nature Biomedical Engineering volume 1, Article number: 0044 (2017) | Download Citation

Abstract

Degradation-induced swelling in implanted hydrogels can cause severe adverse reactions in surrounding tissues. Here, we report a new class of hydrogel with extremely low swelling pressure, and demonstrate its use as an artificial vitreous body. The hydrogel has ultralow polymer content (4.0 g l−1), low cytotoxicity, and forms in situ in 10 minutes via the crosslinking of clusters of highly branched polymers of tetra-armed poly(ethylene glycol) prepolymers. After injection and gelation in the eyes of rabbits, the hydrogel functioned as an artificial vitreous body for over a year without adverse effects, and proved effective for the treatment of retinal detachment. The properties of the hydrogel make it a promising candidate as an infill biomaterial for a range of biomedical applications.

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References

  1. 1.

    , & Injectable and biodegradable hydrogels: gelation, biodegradation and biomedical applications. Chem. Soc. Rev. 41, 2193–2221 (2012).

  2. 2.

    In situ forming degradable networks and their application in tissue engineering and drug delivery. J. Control. Release 78, 199–209 (2002).

  3. 3.

    , , & Hyaluronic acid hydrogels formed in situ by transglutaminase-catalyzed reaction. Biomacromolecules 17, 1553–1560 (2016).

  4. 4.

    . et al.An infectable thiol-acrylate poly(ethylene glycol) hydrogel for sustained release of methylprednisolone sodium succinate. Biomaterials 32, 587–597 (2011).

  5. 5.

    , , & Anomalous volume phase transition in a polymer gel with alternative hydrophilic-amphiphilic sequence. Soft Matter 8, 6876–6879 (2012).

  6. 6.

    , , & Degradation behavior of polymer gels caused by nonspecific cleavages of network strands. Chem. Mater. 26, 5352–5357 (2014).

  7. 7.

    , , & Design of hydrogels for biomedical applications. Adv. Healthcare Mater. 4, 2360–2374 (2015).

  8. 8.

    , , , & “Nonswellable” hydrogel without mechanical hysteresis. Science 343, 873–875 (2014).

  9. 9.

    , , & The MAI hydrophilic implant for scleral buckling: a review. Ophthalmic Surg. 15, 511–515 (1984).

  10. 10.

    , , & Hydrogel implant for scleral buckling. Long-term observations. Retina 5, 38–41 (1985).

  11. 11.

    , , & Long-term complications of the MAI hydrogel intrascleral buckling implant. Arch. Ophthalmol. 110, 86–88 (1992).

  12. 12.

    , , , & MIRAgel: hydrolytic degradation and long-term observations. Arch. Ophthalmol. 125, 511–514 (2007).

  13. 13.

    & Statistical mechanics of cross-linked polymer networks II. Swelling. J. Chem. Phys. 11, 521–526 (1943).

  14. 14.

    Scaling Concepts in Polymer Physics (Cornell Univ. Press, 1979).

  15. 15.

    et al. Design and fabrication of a high-strength hydrogel with ideally homogeneous network structure from tetrahedron-like macromonomers. Macromolecules 41, 5379–5384 (2008).

  16. 16.

    Experimental verification of homogeneity in polymer gels. Polym. J. 46, 517–523 (2014).

  17. 17.

    & Relaxation patterns of nearly critical gels. Macromolecules 29, 7221–7229 (1996).

  18. 18.

    & Rheology of polymers near liquid-solid transitions. Adv. Polym. Sci. 134, 165–234 (1997).

  19. 19.

    , , & Hyperbranched polymers: advances from synthesis to applications. Chem. Soc. Rev. 44, 4091–4130 (2015).

  20. 20.

    , , & Synthesis, characterization, and viscoelastic properties of high molecular weight hyperbranched polyglycerols. Macromolecules 39, 7708–7717 (2006).

  21. 21.

    , , & Sol-gel transition behavior near critical concentration and connectivity. Polymer J. 48, 629–634 (2016).

  22. 22.

    et al. High-water-content mouldable hydrogels by mixing clay and a dendritic molecular binder. Nature 463, 339–343 (2010).

  23. 23.

    & Replacement of the liquid vitreous with sodium hyaluronate in monkeys. I. Short-term evaluation. Exp. Eye Res. 31, 81–99 (1980).

  24. 24.

    et al. Rabbit study of an in situ forming hydrogel vitreous substitute. Invest. Ophth. Vis. Sci. 50, 4840–4846 (2009).

  25. 25.

    et al. Evaluation of viscoelastic poly(ethylene glycol) sols as vitreous substitutes in an experimental vitrectomy model in rabbits. Acta Biomater. 7, 936–943 (2011).

  26. 26.

    et al. Evaluation of an in situ chemically crosslinked hydrogel as a long-term vitreous substitute material. Acta Biomater. 9, 5022–5030 (2013).

  27. 27.

    , & Experimental vitreous tamponade using polyalkylimide hydrogel. Graef. Arch. Clin. Exp. 249, 1167–1174 (2011).

  28. 28.

    et al. In vivo and in vitro feasibility studies of intraocular use of polyethylene glycol-based synthetic sealant to close retinal breaks in porcine and rabbit eyes. Invest. Ophthalmol. Vis. Sci. 56, 4705–4711 (2015).

  29. 29.

    Precision measurements of osmotic pressure in concentrated polymer solutions. Eur. Polym. J. 7, 1411–1419 (1971).

  30. 30.

    , & Osmotic swelling of polyacrylate hydrogels in physiological salt solutions. Biomacromolecules 1, 84–91 (2000).

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Acknowledgements

This work was supported by the Japan Society for the Promotion of Science (JSPS) through Grants-in-Aid for the Graduate Program for Leaders in Life Innovation (GPLLI), by the International Core Research Center for Nanobio, Core-to-Core Program A. Advanced Research Networks, and Grants-in-Aid for Young Scientists (A) grant number 23700555 to T.S., Scientific Research (S) grant number 16H06312 to U.C., and Scientific Research (C) grant number 26462631 to F.O. This work was also supported by the Japan Science and Technology Agency (JST) through the S-innovation program and Center of Innovation program (to U.C.) and PREST (to T.S.).

Author information

Author notes

    • Kaori Hayashi
    •  & Fumiki Okamoto

    These authors contributed equally to this work.

Affiliations

  1. Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan

    • Kaori Hayashi
    • , Denise C. Zujur
    • , Ung-il Chung
    • , Shinsuke Ohba
    •  & Takamasa Sakai
  2. Department of Ophthalmology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575 Japan

    • Fumiki Okamoto
    • , Sujin Hoshi
    •  & Tetsuro Oshika
  3. Department of Macromolecular Science, Graduate School of Science, Osaka University, 1-1 Machikaneyama-cho, Toyonaka, Osaka 560-0043, Japan

    • Takuya Katashima
  4. Institute for Solid State Physics, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8583, Japan

    • Xiang Li
    •  & Mitsuhiro Shibayama
  5. Australian Centre for Neutron Scattering, Australian Nuclear Science and Technology Organisation, Locked Bag 2001, Kirrawee DC, New South Wales 2232, Australia

    • Elliot P. Gilbert
  6. Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

    • Ung-il Chung
  7. Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, (JST),4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan

    • Takamasa Sakai

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Contributions

T.S. planned and supervised the project. K.H., F.O., S.H., T.K., D.C.Z., X.L., M.S., E.G. and S.O. designed and performed the experiments. U.C. and T.O. contributed to discussions throughout the project.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Fumiki Okamoto or Takamasa Sakai.

Supplementary information

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    Supplementary Information

    Supplementary figures and video captions.

Videos

  1. 1.

    Supplementary Video 1

    Oligo-TetraPEG hydrogel in a glass vial.

  2. 2.

    Supplementary Video 2

    Surgical procedures in the left eye of a normal Dutch pigmented rabbit model.

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DOI

https://doi.org/10.1038/s41551-017-0044