Mechanotransduction and corneal endothelium homeostasis: Application in tissue engineering

Abstract

Aim: Globally, there is a significant shortage of corneas available in the eye banks. This high demand has triggered a new platform for addressing the issue by using biomaterials. Mechanical cues play a key role in regulating fundamental cellular functions, as demonstrated by numerous studies conducted on many types of cells. This project's goal is to engineer an effective Descemet's membrane (DM) by changing the stiffness of compressed collagen scaffolds so that it maximizes the functional properties of Descemet's membrane to fully support endothelial cells.Methods: This study entails creation of collagen substrates of varying stiffness which enabled to scrutinize the effect of different biomechanical signals on human corneal endothelial cells (HCECs) behaviour. Thereafter, the viability, function, and responses of HCECs were compared to determine the best scaffold to support corneal endothelial cells. Collagen scaffolds were characterized: light transmittance, scaffold stiffness values, and surface topography by Atomic Force Microscope. Studying HCECs' responses and behaviour on scaffolds of different stiffness has been done by assessing the cell viability and immunofluorescence labelling for Yes‐associated protein (YAP), ZO‐1, and Na/K ATPase.Results: The study found higher growth rate of stiff scaffolds and a confluent monolayer of HCECs in comparison to soft scaffolds. This was accompanied by an increase in nuclear YAP. Typical functional markers were expressed by HCECs on a stiff collagen scaffold compared to a softer scaffold. Collagen scaffolds with a different stiffness do affect nuclear YAP, therefore demonstrating mechanosensitivity of corneal endothelial cells.Conclusion: In conclusion, these results convey that tissue engineering of the human corneal endothelium can determine the scaffold which mimics the best DM biomechanical properties. Hence, very soon scaffold improvements is viable if the role of mechanotransduction is explained for endothelial cell homeostasis.