Multiscale, High-Throughput Cardiac Fibrosis-on-Chip Platform with Integrated Sensing for Disease Modelling and AI-Enabled Drug Screening

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.