Structuring of gellan hydrogel enables the production of inherently antifibrotic, lubricating eye drops.

Abstract

Gellan is an anionic polysaccharide that forms optically clear hydrogels, making it suitable for use in ocular applications. Previous research has demonstrated that gellan fluid gels, when used alongside standard treatments (antibiotics and corticosteroid eye drops), reduce corneal scarring in models of microbial keratitis. This study investigated the potential mechanisms behind the enhanced corneal healing observed with drug-free gellan fluid gels. The impact of varying formulation parameters, such as polymer concentration and applied shear rate, on the physical properties of the fluid gels, including viscosity, stiffness, and lubricity, was examined to optimise gellan fluid gels for use as therapeutic eye drops. Biological analyses were undertaken that highlighted the capacity of gellan fluid gels to provide corneal cells with effective lubrication preventing cell removal on the application of shear. Additionally, gellan fluid gels were shown to sequester TGFβ1, a pro-fibrotic cytokine. Sequestration of the TGFβ1 resulted from electrostatic interactions between the negatively charged gellan and positively charged TGFβ1. As a consequence of this, gellan fluid gels inhibit TGFβ1-induced pro-fibrotic gene expression in corneal fibroblasts, contributing to reduced scarring and improved wound healing. The results suggest that gellan fluid gels, through modulation of physical properties and biological interactions, offer a mechanism for promoting ocular healing and mitigating inflammation-induced scarring, even in the absence of pharmaceutical actives. STATEMENT OF SIGNIFICANCE: This study presents the development of gellan fluid gel eye drops designed to prevent ocular fibrosis after damage. The formulation achieved lubricity comparable to commercial eye drops but with significantly enhanced viscosity and superior capacity to shield cells from damaging shear forces. By optimising gellan concentration and fabrication parameters, the eye drops exhibited reduced ocular friction and improved therapeutic efficacy. Additionally, the fluid gels sequestered TGFβ1, a key fibrosis molecule, with higher gellan concentrations showing enhanced absorption. Importantly, the formulations maintained ease of application through droppers, making them practical for daily use. This work highlights a cost-effective and patient-friendly solution, advancing biomaterial-based therapies for ocular therapies.