Development of a Biomimetic Vitreous Substitute with Built-in Antiadhesive Properties for Potential Prevention of...

Herein, we report the development of an in situ-forming hydrogel-based vitreous substitute designed to provide long-term optical and viscoelastic support while exhibiting intrinsic antiproliferative properties. The material is formed by strain-promoted azide-alkynecycloaddition (SPAAC) cross-linking of a copolymer made of four different monomers, including methacrylamide, methacrylic acid, 2-methacryloyloxyethyl phosphorylcholine, and azido-PEG3-methacrylamide, which were selected to impart desired physical, chemical, and biological properties. The use of SPAAC enables rapid gelation under physiological conditions while minimizing potential unwanted interactions with biomolecules naturally present in the vitreous. The resulting hydrogel closely matches key properties of the natural vitreous, including density, refractive index, viscoelasticity, and optical transparency. In vitro cytocompatibility studies confirm that the material is nontoxic to retinal pigment epithelial (RPE) cells and fibroblast cells. Importantly, incorporation of a zwitterionic methacrylate monomer imparts strong antifouling behavior that resulted in reducing both RPE and fibroblast cells proliferation, a major driver of proliferative vitreoretinopathy. Degradation studies further demonstrated that the hydrogel remains stable for at least 16 weeks under physiological conditions, which supports its potential use as a long-term vitreous substitute.