The key challenge in regenerative medicine is to re-establish a physiological tissue organization as this is conditional for proper tissue functionality. In the cardiovascular field, tissue engineering of blood vessels and heart valves requires the development of a tri-laminar structure. Previous attempts to establish this organization have been mainly trial-and-error based. Therefore, to force breakthroughs and accelerate clinical translation, computational modeling is critical to understand and predict the process of neo-tissue regeneration starting from non-living biodegradable materials (i.e. scaffolds).
The main drivers of regeneration are (1) hemodynamic loads that trigger mechanically-driven tissue growth and remodeling, and (2) signaling interactions between cells that control the emergence of global tissue organization (e.g. layering of vessels and valves). While the first aspect currently receives vast attention, the modeling of cell signaling in the context of tissue engineering remains an unexplored area. In this project, I aim to obtain a mechanistic understanding of how a critical pathway in the cardiovascular system, i.e. the Notch signaling pathway, drives the emergence of global tissue organization while interacting with mechanical cues. I will adopt a unique, multi-disciplinary approach, where quantitative in vitro experiments will be performed to inform novel multi-scale computational models of Notch signaling and its consequences on regeneration. I will leverage these models to understand and predict in vivo regeneration of engineered cardiovascular tissues starting from various initial conditions.
If successful, this project will have a tremendous impact on the development of rational guidelines for ensuring functional tissue regeneration, which represents a breakthrough towards creating cardiovascular replacements that are superior to current treatment options. Moreover, it enables me to start my own independent research group in this field.
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