Hyaluronic acid–based in situ injectable crosslinked hydrogels as next-generation vitreous substitutes: A review

This review addresses the development of next-generation vitreous substitutes based on injectable hydrogels that undergo in situ gelation within the eye. Current tamponade agents, such as gases and silicone oils, provide only mechanical support and are associated with significant clinical limitations, including emulsification, secondary glaucoma, and the need for additional surgery.

The authors demonstrate that hyaluronic acid (HA)-based hydrogels represent the most promising class of materials due to their intrinsic biocompatibility, optical transparency, and tunable physicochemical properties. The review provides a structured, concept-driven comparison of hydrogel systems, with a particular focus on in situ crosslinking strategies and their translational relevance. Special emphasis is placed on emerging process-level innovations, particularly the use of microfluidic systems and micromixers for controlled precursor preparation. These approaches enable precise control over mixing, reaction kinetics, and reproducibility, representing a critical step toward scalable and clinically applicable hydrogel systems.

Overall, the study identifies in situ forming HA-based hydrogels as a leading direction for future vitreous substitutes while outlining key challenges related to long-term stability, degradation, and successful clinical translation.

• Kamenická B., Rajs P., Veith M., Klusoň P.: Hyaluronic acid–based in situ injectable crosslinked hydrogels as next-generation vitreous substitutes: A review. Int. J. Biol. Macromol. 2026, 151509. doi.org/10.1016/j.ijbiomac.2026.151509