Project Portugal 2030

Summary

The proposed research addresses a significant challenge within the cardiovascular drug development sector: the need for reliable and ethically sound pre-clinical testing models that closely mimic human heart tissue. The prevalence of cardiovascular diseases alongside the considerable rate of drug withdrawals due to unforeseen cardiac side effects underscores the critical demand for more accurate and human-relevant models in pre-clinical phases. This challenge is vital not only for drug safety but also for the financial and ethical aspects of drug development, as current models either fail to accurately predict human responses (as seen in animal models) or lack physiological relevance (like monolayer cultures of cardiac cells). The project focuses on three primary objectives. Firstly, it aims to develop a bioink using human placenta and platelet lysates to create a bioactive and viscoelastic material mirroring native tissue properties. Secondly, the project involves constructing a 3D bioprinted cardiac model to accurately represent cardiac physiology, while recreating healthy and fibrotic conditions. Lastly, integrating this model into a microfluidic chip enhances its physiological relevance by emulating the rhythmic flow of a functional heart, ultimately facilitating realistic drug testing and offering insights into drug responses in a more physiologically representative context. The objectives set out in this project are ambitious and clearly push the boundaries of the current state of the art, proposing a novel approach by leveraging advancements in 3D cell culture, microfluidics, and biomaterials derived from human native proteins to create a humanized "heart-on-a-chip" platform. This model aims to faithfully replicate the microarchitecture and dynamic functionality of the human heart, both in healthy and diseased states, presenting a significant leap beyond existing methodologies. The integration of a photopolymerizable, yet viscoelastic, hydrogel derived from human proteins to establish a microenvironment that mimics the dynamism of the cardiac ECM is a novel concept that introduces a new level of physiological relevance to in vitro models. This is complemented by the ambitious goal of integrating these tissues into a microfluidic system that not only supports the tissues' viability and functionality but also allows for the dynamic assessment of drug effects over time, opening up a new avenue to improve the predictivity of pharmacokinetic responses in the human body. Moreover, the project is interdisciplinary, blending fields such as tissue engineering, materials science, microfabrication, and pharmacology, to develop a platform that could fundamentally transform how drugs are screened for safety and efficacy before clinical trials. The prospect of creating a scalable, sustainable, and ethically sound alternative to animal testing that can accurately predict human physiological responses represents a novel intersection of these disciplines, offering promising solutions to long-standing challenges in pharmaceutical research and development. In summary, the research addresses highly important challenges by proposing objectives that are both ambitious and innovative, promising to advance the current state of the art. If successful, this project could lead to a paradigm shift in pre-clinical drug testing, enhancing both the safety and efficiency of drug development processes and decreasing the number of animals used in experimentation.