Project description
A novel computer-aided design platform for cardiac tissues fills in the gaps
The billions of cells in our body rely not only on their intracellular components to carry out their myriad intricate functions but also on the extracellular matrix (ECM). The ECM provides physical scaffolding for the cells and participates to the chemical and mechanical signaling among cells to orchestrate tissue development in homeostasis and disease. Yet, despite tremendous progress in cell engineering, we continue to engineer synthetic tissues and organs by trial-and-error, without an actionable, quantitative understanding of ECM-cell interactions. The EU-funded project SYNBIO.ECM plans to fill this important gap in cardiac tissue engineering. Bottom-up experiments will inform models leading to a computer-aided design and manufacturing (CAD/M) platform for creating replicas of healthy and diseased human hearts and heart parts.
Objective
To meet medical needs worldwide, tissue engineering must move from successful pre/clinical products towards an effective process to meet Worldwide medical needs, but this is challenging since a quantitative design framework has not emerged, yet. Synthetic biology (SYNBIO) was the solution that genetic engineers found to the same problem: “Despite tremendous individual successes in genetic engineering and biotechnology […], why is the engineering of useful synthetic biological systems still an expensive, unreliable and ad hoc research process?” asked Dr. Endy in a 2005 letter to Nature. The SYNBIO solution included: i) libraries of DNA parts with well-characterized effect on cells; ii) tools to computationally design system-level assemblies, or designer-DNA; and, iii) bottom-up engineering of cell functions using progressively more complex designer-DNA. Effectively, SYNBIO introduced a computer-aided design and manufacturing (CAD/M) platform that transformed the process of engineering cells. However, since inputs from the extracellular matrix (ECM) have largely been ignored, progress towards programmable tissue-level behavior have been more modest.
Here, we will build on my experience with computational and experimental models in cardiac tissue engineering to develop a CAD/M framework for engineering cardiac tissues with computationally predictable properties, or designer-ECM. To characterize ECM-cell interactions, we will use traction force and super-resolution microscopy with fluorescence in-situ sequencing. To model multiscale ECM-cell interactions, we will use ordinary differential equations and subcellular element models. Finally, we will leverage ECM parts and human induced pluripotent stem cells to bioprint designer-ECM that recapitulate three phases of heart development: trabeculation, compaction, and maturation.
With synthetic matrix biology (SYNBIO.ECM) we will develop a CAD/M-based process and a new class of products for cardiac
tissue engineering.
Fields of science
- natural sciencesmathematicspure mathematicsmathematical analysisdifferential equations
- medical and health sciencesmedical biotechnologygenetic engineering
- natural sciencesphysical sciencesopticsmicroscopysuper resolution microscopy
- medical and health sciencesmedical biotechnologytissue engineering
- medical and health sciencesmedical biotechnologycells technologiesstem cells
Programme(s)
Topic(s)
Funding Scheme
ERC-STG - Starting GrantHost institution
27100 Pavia
Italy