Tissue engineering the heart by replicating cell populations and ECM of the developing heart
Description: Cardiovascular diseases are the leading cause of death in developed countries like the United States and Switzerland. The heart's limited regenerative capacity prevents effective myocardial repair after injury, leading to heart failure and death. Understanding cardiac repair mechanisms and developing tissue grafts for damaged cardiac tissue are therefore imperative.A promising starting point for understanding the heart’s regenerative capacity is the fetal heart, which, unlike adult cardiac tissue, can regenerate substantial damage. Recapitulating embryonic conditions has therefore substantial potential for cardiac tissue engineering. Particularly cardiac cell ratios have gained considerable traction due to the intricate cell interactions in the heart and their role in cardiac morphogenesis and regeneration. In addition, the developing cardiac ECM was shown to play a crucial role in cardiac repair.This project aims to recreate the cell ratios of the fetal and adult human heart in cardiac spheroids/building blocks using orthogonally differentiable human induced pluripotent stem cells (Aim 1) which can be efficiently differentiated into cardiomyocytes, endothelial cells, and fibroblasts. Building on this knowledge, we aim to bioprint a perfusable left ventricle using a bioink that mimics the developing cardiac jelly based on hyaluronan transglutaminase, incorporating the cell ratio determined in Aim 1 (Aim 2). The vasculature will be printed into the left ventricle using sacrificial writing into functional tissue.By recapitulating the cell ratios of the fetal heart, we expect to better mature cardiac building blocks into functional cardiac tissue. Using a bioink mimicking the developing cardiac jelly, we anticipate to be able to successfully fuse our cardiac building blocks into a functional left ventricle. Printing vasculature within the ventricle will help meet the metabolic demands of the cell populations. Ultimately, we expect this project to make a significant contribution to heart tissue regeneration and advancing its clinical application.Dr. Mark Skylar-Scott has extensive expertise in cardiac tissue engineering and orthogonal iPSC differentiation while Dr. Fisch has extensive expertise in hyaluronan-based biomaterials and precise bioprinting techniques. Together, their combined expertise positions them well to tackle the challenges cardiac tissue engineering.
Amount: CHF 19,000
Funding type: grant
Funder scheme: Scientific Exchanges
Start date: 2024-10-01
End date: 2025-03-31
Investigator: Fisch, Philipp
Institution: ETH Zurich – ETHZ
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Funded outputs count: 0
Funder award ID: 229825
OpenAlex ID: G4656891499