Lens refilling is the replacement of the lens with a silicone polymer in an otherwise intact lens capsule. However, capsular opacification (CO), resulting in reduced visual acuity, is a major complication of these injectable accommodating lenses. Opacification is due to differentiation of lens epithelial cells (LES) into myfibroblasts via epithelial to mesenchymal transformation (EMT). In this paper using a porcine eye model, after the removal of natural lens fibres, nanofiber-based hydrogels decorated with signaling peptides chosen for their potential to influence molecules such as laminin, fibronectin and collagen, were injected. Interaction between the peptides and LEC were assessed for the ability to inhibit EMT. Compared to hyaluronan controls hydrogel-treated eyes had less CO by α-smooth muscle actin expression. LEC differentiation was further reduced in hydrogels linked to peptides. Nanofiber hydrogels targeting biological pathways in EMT provide a potential novel therapy in reducing capsular opacification.