Purpose: Hyaluronic acid (HA)-based hydrogels are promising vitreous substitutes, but clinical translation requires more than biocompatibility alone. Key determinants such as intraocular swelling, enzymatic stability, and cellular interactions must be precisely controlled. This study investigated strategies to further refine an advanced HA-hydrogel towards these requirements. Methods: UV-crosslinked HA hydrogels were tested as chunks and injectable extrudates under varying osmolarities. Swelling behavior was analyzed in physiological media, including a dehydration-rehydration protocol. Enzymatic degradation assays with hyaluronidase, trypsin, and collagenase were performed, and fibroblast adhesion/proliferation was evaluated in the context of proliferative vitreoretinopathy (PVR). Results: Swelling was formulation- and format-dependent, with pre-dehydrated extrudates reaching up to 1.8-fold baseline weight. Only hyaluronidase induced degradation, while proteases had no effect. Fibroblasts showed reduced proliferation on the hydrogel surface. Conclusion: Systematic tuning of swelling, enzymatic stability, and antifibrotic properties advances HA-hydrogels towards clinical application as customizable vitreous substitutes.
Mueller et al. (Mon,) studied this question.