The vitreous body is a gel-like ocular tissue essential for maintaining intraocular structure and visual function. Degeneration of the vitreous, including age-related liquefaction and structural collapse, can result in vitreoretinal disorders that require vitrectomy with substitute materials. Conventional vitreous substitutes, such as gases and silicone oils, are limited by single-functionality, suboptimal biocompatibility, and complications including cataract formation and elevated intraocular pressure. In contrast, hydrogels, owing to their high water content, favorable biocompatibility, tunable physicochemical properties, and potential for sustained and controlled drug delivery, have emerged as highly promising vitreous substitutes. This review summarizes recent advances in in situ crosslinked hydrogels for vitreous replacement, focusing on chemically crosslinked and physically crosslinked systems. Chemically crosslinked hydrogels offer good stability and biodegradability through covalent network formation, although precise control of degradation behavior and byproduct safety remains challenging. Physically crosslinked hydrogels, formed via physical or supramolecular interactions, exhibit low toxicity and self-healing capability but often suffer from rapid degradation, necessitating combined crosslinking strategies to prolong intraocular residence. Furthermore, drug-loaded in situ hydrogels incorporating anti-inflammatory, antioxidant, or anti-proliferative vitreoretinopathy agents represent a shift from passive fillers toward active therapeutic platforms. Future studies should further optimize hydrogel performance and systematically evaluate their long-term biological effects within the intraocular microenvironment to facilitate clinical translation.
