Mondelo García, CristinaBandín Vilar, EnriqueGarcía Quintanilla, LauraCastro Balado, AnaAmo, Eva María delGil Martínez, MaríaBlanco Teijeiro, María JoséGonzález Barcia, LuisZarra Ferro, IreneFernández Ferreiro, AnxoOtero Espinar, Francisco Javier2021-05-192021-05-192021Mondelo-García, C., Bandín-Vilar, E., García-Quintanilla, L., Castro-Balado, A., del Amo, E.M., Gil-Martínez, M., Blanco-Teijeiro, M.J., González-Barcia, M., Zarra-Ferro, I., Fernández-Ferreiro, A. and Otero-Espinar, F.J. (2021), Current Situation and Challenges in Vitreous Substitutes. Macromol. Biosci. 2100066. https://doi.org/10.1002/mabi.202100066http://hdl.handle.net/10347/26224Vitreo-retinal disorders constitute a significant portion of treatable ocular diseases. These pathologies often require vitreo-retinal surgery and, as a consequence, the use of vitreous substitutes. Nowadays, the vitreous substitutes that are used in clinical practice are mainly divided into gases (air, SF6, C2F6, C3F8) and liquids (perfluorocarbon liquids, silicone oils, and heavy silicone oils). There are specific advantages and drawbacks to each of these, which determine their clinical indications. However, developing the ideal biomaterial for vitreous substitution continues to be one of the most important challenges in ophthalmology, and a multidisciplinary approach is required. In this sense, recent research has focused on the development of biocompatible, biodegradable, and injectable hydrogels (natural, synthetic, and smart), which also act as medium and long-term internal tamponade agents. This comprehensive review aims to cover the main characteristics and indications for use of the extensive range of vitreous substitutes that are currently used in clinical practice, before going on to describe the hydrogels that have been developed recently and which have emerged as promising biomaterials for vitreous substitutioneng© 2021 The Authors. Macromolecular Bioscience published by Wiley‐VCH GmbH This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposesAtribución-NoComercial 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc/4.0/BiomaterialsHydrogelsPerfluorocarbon liquidsSilicone oilsVitreous substitutionjournal article10.1002/mabi.2021000661616-5195open access