Project Detail |
Forty years ago, the endograft (EG) enabled the endovascular treatment of aortic aneurysm (AoA) and revolutionized vascular surgery. Still, since then, its technological concept has remained substantially unchanged: EG is a passive device aimed at treating the AoA in its late stage, not to cure the disease, even when discovered early. This proposal introduces a bio-engineered process to redesign EGs as 3D bio-printed, bioresorbable devices loaded with active drug components and validated in-vitro to enable the paradigm shift: from end-stage treatment to early personalized healing.
To this aim, EPEIUS must tackle three open challenges: 1) available (animal) models often fail to predict human safety and efficacy for candidate therapies; 2) potentially effective drugs are challenging to deliver in therapeutic concentrations at the target; 3) consequently, there is a limited capacity of AoA healing even for compounds that were preclinically promising.
We hypothesize that these challenges can be solved simultaneously by designing and fabricating a human in-vitro model of AoA where we can track AoA progression in the presence/absence of bioengineered EG, delivering therapeutic drugs. Grounded on a multi-disciplinary approach, EPEIUS will act as the “trojan horse” to enable the local healing of arterial walls.
To verify our hypothesis, we will integrate 3D bioprinting and computational biomechanics to:
Aim 1. Create an in-vitro model of AoA recapitulating dysfunction of endothelial and vascular smooth muscle cells, degeneration of extra-cellular matrix, overall driven by inflammatory state.
Aims 2. Create a customizable EG to carry drug in-situ.
Aims 3. Assess in-vitro the regenerative power of the mesenchymal stem cells’ secretome to heal AoA.
EPEIUS will directly tackle a prominent medical issue but we are convinced that this innovation in computer-aided engineering, additive manufacturing, and in-vitro pharmacology will create the next generation endovascular device. |