Stable oxime-crosslinked hyaluronan-based hydrogel as a biomimetic vitreous substitute

Alexander E G Baker; Hong Cui; Brian G Ballios; Sonja Ing; Peng Yan; Joe Wolfer; Thomas Wright; Mickael Dang; Nicola Y Gan; Michael J Cooke; Arturo Ortín-Martínez; Valerie A Wallace; Derek van der Kooy; Robert Devenyi; Molly S Shoichet

doi:10.1016/j.biomaterials.2021.120750

Stable oxime-crosslinked hyaluronan-based hydrogel as a biomimetic vitreous substitute

Biomaterials. 2021 Apr:271:120750. doi: 10.1016/j.biomaterials.2021.120750. Epub 2021 Mar 4.

Authors

Affiliations

¹ Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College St, Toronto, ON, M5S 3E5, Canada; Institute of Biomedical Engineering, University of Toronto, 160 College St, Toronto, ON, M5S 3E1, Canada.
² Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College St, Toronto, ON, M5S 3E5, Canada.
³ Department of Ophthalmology and Vision Sciences, University of Toronto, 340 College St, Toronto, ON, L0J 1C0, Canada.
⁴ Institute of Biomedical Engineering, University of Toronto, 160 College St, Toronto, ON, M5S 3E1, Canada.
⁵ Kensington Eye Institute, 340 College St, Toronto, ON, M5T 3A9, Canada.
⁶ Toronto Animal Eye Clinic, 150 Norseman St, Etobicoke, ON, M8Z 2R4, Canada.
⁷ Kensington Eye Institute, 340 College St, Toronto, ON, M5T 3A9, Canada; Department of Ophthalmology and Vision Sciences, University of Toronto, 340 College St, Toronto, ON, L0J 1C0, Canada.
⁸ Department of Ophthalmology, Tock Seng Hospital, National Healthcare Group Eye Institute, 11 Jln Tan Tock Seng, 308433, Singapore.
⁹ Donald K Johnson Eye Institute, Krembil Research Institute, University Health Network, 399 Bathurst St, Toronto, ON, M5T 2S8, Canada.
¹⁰ Department of Ophthalmology and Vision Sciences, University of Toronto, 340 College St, Toronto, ON, L0J 1C0, Canada; Donald K Johnson Eye Institute, Krembil Research Institute, University Health Network, 399 Bathurst St, Toronto, ON, M5T 2S8, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, ON, M5S 1A8, Canada.
¹¹ Department of Molecular Genetics, University of Toronto, 1 King's College Circle, ON, M5S 1A8, Canada; Institute of Medical Sciences, University of Toronto, 1 King's College Circle, ON, M5S 1A8, Canada.
¹² Department of Ophthalmology and Vision Sciences, University of Toronto, 340 College St, Toronto, ON, L0J 1C0, Canada; Donald K Johnson Eye Institute, Krembil Research Institute, University Health Network, 399 Bathurst St, Toronto, ON, M5T 2S8, Canada; Toronto Western Hospital, 399 Bathurst St, Room 6 E W 438, Toronto, ON, M5T 2S8, Canada.
¹³ Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College St, Toronto, ON, M5S 3E5, Canada; Institute of Biomedical Engineering, University of Toronto, 160 College St, Toronto, ON, M5S 3E1, Canada; Institute of Medical Sciences, University of Toronto, 1 King's College Circle, ON, M5S 1A8, Canada. Electronic address: molly.shoichet@utoronto.ca.

PMID: 33725584
DOI: 10.1016/j.biomaterials.2021.120750

Abstract

Vitreous substitutes are clinically used to maintain retinal apposition and preserve retinal function; yet the most used substitutes are gases and oils which have disadvantages including strict face-down positioning post-surgery and the need for subsequent surgical removal, respectively. We have engineered a vitreous substitute comprised of a novel hyaluronan-oxime crosslinked hydrogel. Hyaluronan, which is naturally abundant in the vitreous of the eye, is chemically modified to crosslink with poly(ethylene glycol)-tetraoxyamine via oxime chemistry to produce a vitreous substitute that has similar physical properties to the native vitreous including refractive index, density and transparency. The oxime hydrogel is cytocompatible in vitro with photoreceptors from mouse retinal explants and biocompatible in rabbit eyes as determined by histology of the inner nuclear layer and photoreceptors in the outer nuclear layer. The ocular pressure in the rabbit eyes was consistent over 56 d, demonstrating limited to no swelling. Our vitreous substitute was stable in vivo over 28 d after which it began to degrade, with approximately 50% loss by day 56. We confirmed that the implanted hydrogel did not impact retina function using electroretinography over 90 days versus eyes injected with balanced saline solution. This new oxime hydrogel provides a significant improvement over the status quo as a vitreous substitute.

Keywords: Hyaluronan; Hydrogel; Retinal detachment; Retinal tamponade; Vitreous substitute.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biomimetics
Hyaluronic Acid*
Hydrogels*
Mice
Oximes
Rabbits
Retina
Vitreous Body

Substances

Hydrogels
Oximes
Hyaluronic Acid