Introducing 3R in drug development and toxicology: recent breakthroughs and perspectives from the lung-on-chip technology

Since the first introduction of the 3R concept in 1959 by Russell and Burch, there has been an increasing interest in finding alternatives to animal testing for ethical and economic reasons. Only looking at the landscape in drug development, millions are invested every year but only a few of all drug candidates make their way to the clinics. Although the amount of knowledge generated from animal models is unquestionable, in terms of translation, rising evidence suggests that non-animal methods can be as valuable and even more predictive for human. Proving that a molecule is safe for the human respiratory tract and distal lung area is essential in the pipeline of drug and molecule development. Especially inhaled drugs are gaining more and more attention, and fitting in-vitro systems for testing them are missing. Simulating the lung environment in vitro poses a significant challenge, especially when it comes to distal airways. The lack of established cell models for the alveolus and its dynamic microenvironment have led to the generation of microphysiological systems (MPS). MPS gather key features of the organ microenvironment, including mechanical cues, human primary cells and extracellular matrix. In this talk, we will recapitulate the short but remarkable history of the “lung-on-chip”, its key elements and how this technology has changed the paradigm of in vitro testing whilst representing a promising 3R alternative to conventional animal-based research.

Learning objectives:

1. Key features of lung MPS systems – What makes a good in vitro model for the alveolus?

2. Lung-on-chip applications in toxicology, safety and efficacy testing: benefits, shortcomings and outlook