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 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 research on vitreous substitutes aims to find materials that can replace the functions of natural vitreous and be used to treat vitreoretinal diseases. Traditional substitutes such as gases and silicone oil have many drawbacks. However, hydrogels are regarded as highly potential substitutes due to their high water content, good biocompatibility, adjustable physical and chemical properties, and potential for controlled drug release. Researchers have developed two types of in-situ cross-linked hydrogels: chemical cross-linking and physical cross-linking. Chemical cross-linked hydrogels achieve in-situ gelation by forming chemical covalent bonds, showing good stability and degradability, but still require precise control of the degradation rate and the safety of degradation products. Physical cross-linked hydrogels utilize physical or supramolecular interactions between polymer chains to achieve in-situ gelation, having low toxicity and self-repairing properties, but they degrade too quickly and require a combination of physical and chemical cross-linking to extend the material's retention time. Additionally, researchers have explored in-situ cross-linked hydrogels loaded with anti-inflammatory, antioxidant, or anti-proliferative drugs for vitreoretinal disease, elevating vitreous substitutes from simple physical filling to an active treatment level. Future research needs to further optimize the comprehensive performance of hydrogels and deeply study their long-term biological activity impact on the intraocular microenvironment to promote their clinical translation.