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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) Cite this article

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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.

The maximum Πsw that can be exerted by a hydrogel is Πos. Hence, to eliminate problems caused by swelling, Πos should be reduced. The simplest procedure for reducing Πos is to decrease polymer concentration13,14. However, the slower gel formation that results from lower polymer content often precludes the use of such a gel in biomedical applications. For example, for tetra-armed poly(ethylene glycol) (Tetra-PEG) gels at the lowest polymer concentration for gel formation, 6.0 g l−1, gelation takes about 7 hours15,16, which far exceeds possible surgical timescales. Here we describe a hydrogel with extremely low polymer content (~4.0 g l−1) that forms in situ within 10 minutes, and demonstrate the application of the hydrogel as an artificial vitreous body for treating retinal detachment.

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Figure 1: Gelation process and properties of the conventional Tetra-PEG hydrogel and of the oligo-Tetra-PEG hydrogel.
Figure 2: Synthesis and phase diagram of the oligo-Tetra-PEG hydrogel.
Figure 3: Characterization of the oligo-Tetra-PEG and Tetra-PEG hydrogels.
Figure 4: Biocompatibility of the oligo-Tetra-PEG hydrogels.
Figure 5: Applicability of the oligo-Tetra-PEG hydrogels as artificial vitreous bodies.
Figure 6: Fundus photography of rabbit eyes, with or without retinal detachment, after injection of the oligo-Tetra-PEG hydrogel.

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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.).

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Author notes

  1. Kaori Hayashi and Fumiki Okamoto: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-8656, Tokyo, 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, 305-8575, Ibaraki, Japan

    Fumiki Okamoto, Sujin Hoshi & Tetsuro Oshika

  3. Department of Macromolecular Science, Graduate School of Science, Osaka University, 1-1 Machikaneyama-cho, Toyonaka, 560-0043, Osaka, Japan

    Takuya Katashima

  4. Institute for Solid State Physics, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, 277-8583, Chiba, 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, Tokyo 113-0033, Bunkyo-ku, Japan

    Ung-il Chung

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

    Takamasa Sakai

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  1. Kaori Hayashi
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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.

Corresponding authors

Correspondence to Fumiki Okamoto or Takamasa Sakai.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

Supplementary figures and video captions. (PDF 1513 kb)

Supplementary Video 1

Oligo-TetraPEG hydrogel in a glass vial. (MOV 25225 kb)

Supplementary Video 2

Surgical procedures in the left eye of a normal Dutch pigmented rabbit model. (MOV 64484 kb)

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Hayashi, K., Okamoto, F., Hoshi, S. et al. Fast-forming hydrogel with ultralow polymeric content as an artificial vitreous body. Nat Biomed Eng 1, 0044 (2017). https://doi.org/10.1038/s41551-017-0044

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