Development of gelatin-based fibrous composites for corneal stroma mimicry

Details

Supervisors

Delcorte, Arnaud ; Dupont-Gillain, Christine C.

Faculty

Ecole polytechnique de Louvain

Degree label

Master [120] : ingénieur civil biomédical, à finalité spécialisée

Abstract

enCorneal blindness affects approximately 10 million people worldwide. While corneal transplantation remains the primary treatment, only 1 in 70 patients can receive a graft. In parallel, the cost to develop one ophthalmic drug is about 2 billion €, a large share of which is attributed to failure in clinical trials. Preclinical models currently used for pharmacological testing often fail to replicate the complexity of native tissue, limiting their predictive capacity. This master's thesis is carried out within the framework of the ALMODCONS project, which aims to develop a cornea-on-a-chip model replicating the main layers and functions of the human cornea. The development of materials mimicking the corneal stroma would be valuable in both corneal transplants and as models for preclinical testing. To overcome shortcomings in mechanical and transport properties of gelatin hydrogels used in the project, this master's thesis aims to develop gelatin-based fibrous composites. Fibrous composites can decouple mechanics from solute transport. Three gelatin fiber fabrication strategies were explored : a polymer hollow tube stretch and fold approach, manual fiber drawing, and electrospinning. The resulting fibers were crosslinked with glutaraldehyde, and turned into materials either through weaving, gel embedding, or additional hyaluronic acid treatment. Swelling, mechanics, and morphology of the materials were characterized, and preliminary cytocompatibility tests were carried out using human corneal epithelial cells (HCE-T). The results demonstrate that transitioning from hydrogels to fibrous composites improves mechanical performance. Among all investigated strategies, electrospinning combined with hyaluronic acid treatment emerged as the most promising approach, combining the highest Young's modulus of all tested materials (~2.3 MPa), a substantial degree of optical transparency, and allowing high-throughput fabrication of nanoscale fibers. Although a gap with the native stroma remains, these results constitute a solid basis for further development, both for corneal tissue engineering and for the cornea-on-a-chip model of the EOS project.