Artificial Lithographic MODel for COrNeal drug Screening

The cornea is the transparent window to the eye and as such, eye drops are an interesting route of drug administration. In this project, we propose the development of a 3D corneal cell model that can be used to investigate corneal drug interaction. Studies that aim to simulate the pharmacokinetics and toxicological properties of drugs are mainly based on oversimplified 2D monocultures or animal studies that suffer from interspecies differences. These limitations skew proper predictive power during preclinical drug investigation.

We propose the development of a 3D corneal model that includes all three cell layers and integrated microfluidics to simulate relevant physiological flows such as the tear film. In this way, we reduce the need for animal studies, while simultaneously introducing the in vivo complexity of 3D cell environments. The materials used will be fabricated (photocrosslinkable biopolymers) and printed in-chip using 2PP bioprinting that can simultaneously integrate corneal cells. The interfaces between materials and corneal cells are characterized in depth using molecular spectroscopy techniques, while detailed protein expression of cells in the 3D ECM are benchmarked to ex vivo cadaveric donor corneas with proteomics. TEER, flow rate and cell viability will be measured real-time by integrated sensors. The project finally aims for a proof-of-concept to determine permeability coefficients of common ocular drugs in the fully assembled 3D cell culture chip.