Preclinical evaluation of recombinant type III collagen-based contact lens rewetting drops.

Abstract

Purpose: To evaluate the physicochemical properties, contact lens compatibility, in vitro cytocompatibility, and repeated-dose ocular safety of a recombinant type III collagen-based contact lens rewetting drop formulation (Col RD).

Methods: Physicochemical properties were characterized using rheological testing and contact angle measurements. Total residual protein on rigid gas-permeable contact lenses was evaluated using an artificial tear fluid model, followed by non-enzymatic and enzymatic cleaning procedures. In vitro cytocompatibility was assessed using human corneal epithelial cells, including cell viability, adhesion, and migration assays. A one-month repeated-dose ocular safety study was conducted in New Zealand rabbits. Outcomes included slit-lamp examination, fluorescein staining, hematological and serum immunological analysis, and histopathological evaluation.

Results: Col RD exhibited shear-thinning rheological behavior and a hydrophilic sequence profile, with viscosity close to that of human tears under blinking-associated shear conditions. Contact angle analysis showed no significant differences compared with commercial lubricants. In the in vitro rigid gas-permeable lens model, Col RD did not increase total residual protein after enzymatic cleaning and showed significantly lower post-cleaning residual protein than the hyaluronic acid-based comparator under the tested conditions. In vitro, Col RD showed no significant adverse effects on corneal epithelial cell viability, adhesion, or migration compared with controls. In vivo, no evident ocular irritation, epithelial damage, inflammatory response, or structural abnormality was observed during the 30-day administration period. Hematological and serum immunological parameters showed no significant differences among groups. Histological analysis revealed no necrosis, fibrosis, neovascularization, or abnormal collagen deposition. Sirius Red showed no evident alteration in type I/III collagen distribution.

Conclusions: Recombinant collagen-based contact lens rewetting drops showed favorable rheological properties, acceptable in vitro cytocompatibility, and no evident ocular irritation after repeated topical administration in rabbits. In an in vitro rigid gas-permeable lens model, Col RD showed low total residual protein after enzymatic cleaning compared with the hyaluronic acid-based formulation. These findings support the preliminary safety and feasibility of incorporating recombinant type III collagen into a PVA-containing lubricating formulation for contact lens rewetting drops. Further studies are needed to evaluate clinical rewetting performance, broader lens-material compatibility, long-term formulation stability, and the relative contribution of recombinant collagen and PVA.