Improving the mechanical properties of gelatin for use as an in vitro model for cornea

Details

Supervisors

Dupont-Gillain, Christine C. ; Franco, Alexis

Faculty

Faculté des bioingénieurs

Degree label

Master [120] : bioingénieur en chimie et bioindustries, à finalité spécialisée

Abstract

enThe number of patients affected by eye disease or degeneration is rising worldwide, with more than one million new patients each year. As the outermost layer of the eye, the cornea plays a crucial role in both protecting the eye and contributing to its refractive power. Developing effective drugs for corneal diseases is therefore a clinical priority. Before reaching clinical trials, new drugs are tested using in vitro cell culture and in vivo animal models. However, these models are unable to replicate the complexity of human organs effectively, which contributes to the low clinical success rate: only 10 % of drugs that pass preclinical animal tests reach the market. As a result, organ-on-a-chip technologies have emerged as promising solutions, offering more physiologically-relevant models. This master's thesis is part of a wider research project that aims to develop a cornea-on-a chip as an alternative to traditional preclinical models. In this project, two modified gelatin based hydrogels, methacrylated gelatin (GelMA) and norbornene gelatin (GelNB), are used to replicate the structure and function of the cornea. The objective was to evaluate the ability of these materials to mimic the mechanical behaviour of the cornea and explore ways to improve their properties for this purpose. Tensile testing and rheology were used to obtain quantitative insights into the materials' stiffness, tensile strength, and elongation at break, as well as their viscoelastic properties. The influence of polymer concentration on these properties was systematically studied. Additionally, tensile tests were conducted on porcine and human corneas to compare them. The main findings confirm that polymer concentration significantly influences hydrogel properties. However, the mechanical gap between the hydrogels and corneal tissue remains substantial, indicating that the concentration is not sufficient to replicate the behaviour of the cornea. Another key factor is the crosslinking mechanism, which differs between GelMA, exhibiting higher stiffness, and GelNB, showing greater ductility. These differences highlight the importance of network structure in tuning the performance of hydrogel. The parameters investigated in this study did not lead to sufficient improvements in the hydrogels' properties replicating corneal tissue. Therefore, alternative strategies must be explored to achieve mechanical behaviours that more closely mimic those of the target organs. However, as the aim of this project is to incorporate cells into hydrogels, it is essential to strike a balance between mimicking native tissue properties and maintaining conditions suitable for cell viability and function within the scaffold.