A novel bioengineered platform to investigate blood-retinal barrier physiopathology

The blood–retinal barrier plays a crucial role in maintaining retinal homeostasis, but it also represents a major obstacle for the effective delivery of drugs to the posterior segment of the eye. Dysfunctions of the BRB are involved into several retinal diseases and in-vivo, in-vitro, and ex-vivo models are currently used in the ophthalmic research field but present several limitations, despite their cutting-edge biomimetic features. This PhD thesis presents the development and validation of a novel bioengineered 3D in vitro platform designed to mimic the outer blood-retinal barrier. The proposed device integrates a biomimetic Bruch’s membrane scaffold, fabricated via electrospinning, with a microfluidic network bioinspired by a human choroidal vasculature. A modular design approach was adopted to improve usability, reproducibility, and future scalability, while enabling the integration of sensing elements for real-time monitoring. The complete device was biologically validated through retinal pigmented epithelium cell culture, demonstrating the formation of a functional barrier and the capability to investigate drug efficacy. Overall, this work introduces a cost-effective, physiologically relevant in vitro, the proposed platform represents a promising tool for investigating BRB pathophysiology and for the preclinical evaluation of novel ophthalmic therapies, contributing to the reduction of animal experimentation in accordance with the 3R principles.