Project description
A heart-on-chip platform for discovering antifibrotic drugs
Excessive scarring of heart tissue, called cardiac fibrosis, is a major driver of heart failure affecting millions of people worldwide. As scar-forming cells deposit excessive structural proteins, the heart stiffens and loses function. No approved therapy directly targets this process, and existing laboratory models fail to capture the complexity of human cardiac tissue. With the support of the Marie Skłodowska-Curie Actions programme, the FIBROC project aims to develop a heart-on-chip platform that integrates human stem cell-derived heart cells, immune cells and fibroblasts in a three-dimensional, mechanically active environment. Integrated sensors and artificial intelligence will monitor disease progression and drug responses in real time. The platform will be used to investigate mechanisms of fibrosis and screen novel therapeutic compounds.
Objective
FIBROC aims to develop a multiscale, human-relevant cardiac fibrosis-on-chip platform with integrated sensing and AI-enabled analytics for mechanistic studies and high-throughput drug screening. Cardiac fibrosis stiffens the heart as scar-forming cells lay down excess extracellular matrix (ECM), yet no approved therapy directly targets this process, and prevailing animal/2D models miss human multicellular and mechanical complexity and lack screening throughput. The platform will integrate stiffness-graded 3D microtissues, crosstalk among human cardiomyocytes (hiPSC-CMs), fibroblasts, and macrophages, and heartbeat-like loading, with continuous mechanical/metabolic sensing, imaging, and label-free spectroscopic readouts. AI models will integrate these readouts to stage disease and quantify responses. Mechanistic focus is on how matrix stiffness and TGF-β/Smad signalling sustain myofibroblast activation and collagen remodelling. In brief, I will 3D-print a gelatin methacryloyl (GelMA)-based bioink containing hiPSC-CMs, fibroblasts, and macrophages to generate 96 microtissues in one run, preset to healthy, mild, and severe stiffness; cyclic strain and soluble cues (e.g. TGF-β1) will be used to induce fibrosis. The system will first be validated with reference TGF-β/Smad pathway inhibitors, then used to prioritise novel compounds in partnership with the Oxford Target Discovery Institute. The project will be hosted in Oxford’s Department of Physiology, Anatomy and Genetics (DPAG), under the supervision of Dr Filipa Simões (cardio-immunology), with Prof Dame Molly Stevens as a collaborator (biosensing) within DPAG. Building on my track record in biofabrication and in vitro disease modelling, this project extends into cardiology and advanced quantitative phenotyping, expands my cross-disciplinary network and leadership, and positions me to launch an independent, translational research agenda while delivering an open, screening-grade resource for antifibrotic discovery.
Fields of science (EuroSciVoc)
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CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- engineering and technology environmental biotechnology biosensing
- medical and health sciences basic medicine anatomy and morphology
- medical and health sciences basic medicine physiology
- medical and health sciences clinical medicine cardiology
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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(opens in new window) HORIZON-MSCA-2025-PF
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OX1 2JD Oxford
United Kingdom
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