Replacing the vitreous body with hydrogels: Rationale and strategies

During vitreoretinal surgery, the vitreous body is removed and requires a suitable replacement to ensure ocular homeostasis, as the native vitreous does not regenerate. An ideal vitreous substitute should mimic the optical, mechanical, and biochemical properties of the natural vitreous while maintaining long-term biocompatibility. Currently, clinically used substitutes such as gases and silicone oils facilitate retinal reattachment but deviate significantly from the native vitreous, leading to complications such as cataract formation, increased intraocular pressure, and emulsification. Given these limitations, there is a growing interest in hydrogels as potential vitreous substitutes due to their similarity to the native vitreous. This review therefore aspires to provide a comprehensive and detailed overview of current knowledge on the structural and biochemical composition of the vitreous, the challenges associated with existing substitutes, and recent advancements in vitreous replacement technologies. Particular attention is given to preformed and in-situ forming hydrogels, based on biopolymers and synthetic polymers, discussing their chemical composition, diverse characteristics with regard to the multiple requirements for vitreous substitutes, and clinical applicability. Finally, future challenges and opportunities in developing an ideal vitreous substitute are highlighted, including vitreous substitutes as drug delivery systems as well as cellularized vitreous substitutes by combining advanced hydrogel systems with hyalocytes as vitreous cells to further replicate the versatile characteristics and functions of the native vitreous.