Besides stopping the spreading of Sars-Cov2, finding the right treatment to cure patients with Covid-19 has become an urgent need to save lives. Pharmaceutical Industries need innovative and efficient tools to speed up the drug screening process to find treatments. This is especially true to fight this virus, since it seems difficult to induce the pathology in most of the small animal models commonly used for in vivo research. Our team wants to propose an innovative miniaturized platform, the BeatingCovidOnChip, designed by merging interdisciplinary competences in biology, engineering and drug regulatory processes. By combining different functional human in vitro models, we provide more efficient means to test drug safety and efficacy on more representative human systems. The potentiality to lower the currently too high attrition rate for compounds approval is fundamental to fast provide people with a cure and promptly respond to this crisis, without however impairing safety.
What it does
The proposed BeatingCovidOnChip reproduces in vitro miniaturized single human tissues in a physiological and\or pathological state, and combines them to provide a complete and more versatile product to assess whether new compounds are safe and effective for the organism. Within the BeatingCovidOnChip, we specifically implemented three fundamental organ models: heart, liver and lung. These organs are combined in the platform to specifically test anti-Covid-19-drugs, especially for cardiotoxicity and hepatotoxicity (i.e. safety assay) and capacity of therapeutic potential at lung level (i.e., efficacy assay). Moreover, thanks to the liver model, specific tests of cardiotoxicity and efficacy of the main reactive drug metabolite can be also performed. The exploitation of the BeatingCovidOnChip at the preclinical phases would results in an improvement of safety at the clinical trial level, minimizing cost and time to bring a new compound into the market.
How we built it
Out team was previously involved in the development of functional single tissue models of the heart and the liver, through peculiar technologies, and took part in a project to conceive an innovative method to selectively connect them to obtain a multi-organ-like organization.
Thanks to a patent protected technology (i.e., a means to stretch 3D microtissues cultured within microfluidic devices), we are able to generate a synchronous beating human physiological cardiac model, whose electrophysiological parameters can be directly recorded on-line. This platform was already exploited to screen structural and functional cardiotoxicity of known drugs.
We also developed a method to efficiently generate functional hepatic domains within microfluidic chambers, demonstrating high expression of the cytochrome CYP3A4, which is an hepatic enzyme involved in the metabolism of the 60% of commercialized drugs.
These two models have already been integrated into a new microfluidic platform able to selectively connect and control the diffusion of molecules between the two organs, providing a tool to asses drug safety by testing hepatotoxicity and cardiotoxicity of both the drug and its main reactive metabolite. Our versatile technologies allowed us to design the implementation of the third organ model, the pathological lung, which integrates in-vivo like mechanical cues, to complete our tool to test the safety and efficacy of anti-Covid19-related molecules and metabolites.
Challenges we ran into
The BeatingCovidOnChip is composed by three microtissues, but just two of them (i.e., the heart and the liver) were already fully developed, exploited and connected in a microfluidic platform. The lung model can be easily integrated from the technical point of view but the biological model needs to be fully developed, by envisioning also the collaboration of a virologist/clinician to set up a pathological lung fully recapitulating the features of cells infected by Sars-Cov-2. Our BeatingCovidOnChip, to fully reply to the needs of Pharmaceutical Companies, would need to make its way into the industrialization process to become a more automatized and user-friendly platform.
Accomplishments that we're proud of
We are proud that our multidisciplinary team found a technical solution to design a platform, the BeatingCovidOnChip, which can be applied to meet the urgent needs of Pharmaceutical Companies and CROs engaged in the pre-clinical safety and efficacy tests of new compounds against Covid-19 disease.
What we learned
Having merged different competences of the team members coming from academia, research and industries we strongly believe that the designed BeatingCovidOnChip could be used as a real versatile platform. Here we focus on developing a tool for Pharmaceutical Industries and CROs, but its use should not be limited to this. Indeed, details of the cellular responses to this virus are not known but are paramount to discover an efficient treatment. By tailoring the cell components and complexity of the cultures, we understood that our models can be used to shed light on the pathogenesis of SARS-Cov 2 virus not only on the primary target organ (i.e., the lung), but also in other districts (i.e., myocardium and liver), which seems to be affected too.
What's next for BeatMyCovid
To fully exploit the potential of the platform in impacting this crisis, we will need to contact expert virologist to fully understand the Covid-19-induced pathology on the lung, to develop a robust pathological model.
We will also build strong collaborations with clinicians to compare with clinical data the results of our biological validation campaign, which is envisioned to be performed among our CRO network.
Moreover, we will need competences and funding from investors who believe in BeatingCovidOnChip potential to scale up the production of this innovative solution and make an automatized and user-friendly platform ready and available for Pharma Industries.