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

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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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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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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