Research on vitreous substitutes has advanced from conventional gases and silicone oils to third-generation biomimetic hydrogels. While existing substitutes provide short-term retinal tamponade, they typically require strict postoperative positioning and carry risks of cataract formation, ocular hypertension, and silicone oil emulsification. These materials therefore fall short of meeting the essential requirements for long-term tissue support, matched physicochemical properties, and high biocompatibility simultaneously. Recently, polymer-based hydrogels have gained prominence as ideal candidates owing to their high water content, optical transparency, adjustable viscoelasticity, and favorable biocompatibility. They have diversified into several forms, including uncrosslinked solutions, preformed hydrogels systems, and in-situ crosslinked systems. Biopolymer hydrogels, such as those derived from hyaluronic acid, collagen, or alginate, demonstrate high safety but often exhibit inadequate mechanical strength and poor stability in vivo. Synthetic polymer hydrogels, including polyethylene glycol, polyvinyl alcohol, and polyvinylpyrrolidone, allow tunable properties yet raise concerns regarding monomer toxicity and degradation-related safety. Future research is shifting from simple material replacement toward functional reconstruction and intelligent regulation. Increasing efforts aim to develop smart hydrogels capable of sustained drug release and cell encapsulation, alongside advanced strategies employing biodegradable scaffolds to promote native vitreous regeneration, with the ultimate goal of achieving full functional restoration.
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.
