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Vitreous endotamponades play essential roles in facilitating retina recovery following vitreoretinal surgery, yet existing clinically standards are suboptimal as they can cause elevated intra-ocular pressure, temporary loss of vision, and cataracts while also requiring prolonged face-down positioning and removal surgery. These drawbacks have spurred the development of next-generation vitreous endotamponades, of which supramolecular hydrogels capable of in-situ gelation have emerged as top contenders. Herein, we demonstrate thermogels formed from hyper-branched amphiphilic copolymers as effective transparent and biodegradable vitreous endotamponades for the first time. These hyper-branched copolymers are synthesised via polyaddition of polyethylene glycol, polypropylene glycol, poly(ε-caprolactone)-diol, and glycerol (branch inducing moiety) with hexamethylene diisocyanate. The hyper-branched thermogels are injected as sols and undergo spontaneous gelation when warmed to physiological temperatures in rabbit eyes. We found that polymers with an optimal degree of hyper-branching showed excellent biocompatibility and was able to maintain retinal function with minimal atrophy and inflammation, even at absolute molecular weights high enough to cause undesirable in-vivo effects for their linear counterparts. The hyper-branched thermogel is cleared naturally from the vitreous through surface hydrogel erosion and negates surgical removal. Our findings expand the scope of polymer architectures suitable for in-vivo intraocular therapeutic applications beyond linear constructs., (Copyright © 2021. Published by Elsevier Ltd.)

Vitreous endo-tamponades are commonly used in the treatment of retinal detachments and tears. They function by providing a tamponading force to support the retina after retina surgery. Current clinical vitreous endo-tamponades include expansile gases (such as sulfur hexafluoride (SF 6 ) and perfluoropropane (C 3 F 8 )) and also sislicone oil (SiO). They are effective in promoting recovery but are disadvantaged by their lower refractive indices and lower densities as compared to the native vitreous, resulting in immediate blurred vision after surgery and necessitating patients to assume prolonged face-down positioning respectively. While the gas implants diffuse out over time, the SiO implants are non-biodegradable and require surgical removal. Therefore, there is much demand to develop an ideal vitreous endo-tamponade that can combine therapeutic effectiveness with patient comfort. Polymeric hydrogels have since attracted much attention due to their favourable properties such as high water content, high clarity, suitable refractive indices, suitable density, tuneable rheological properties, injectability, and biocompatibility. Many design strategies have been employed to design polymeric hydrogel-based vitreous endo-tamponades and they can be classified into four main strategies. This review seeks to analyse these various strategies and evaluate their effectiveness and also propose the key criteria to design successful polymeric hydrogel vitreous endo-tamponades., (Copyright © 2020 Elsevier Ltd. All rights reserved.)