Redesigning aortic endograft: enabling in-situ personalized aneurysm healing

Introduction

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.

Challenges

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 for AoA healing even for compounds that were preclinically promising.

Hypothesis

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.

Methodology

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.

Aim 2

Create a customizable EG to carry drug in-situ.

Aim 3

Assess in-vitro the regenerative power of the mesenchymal stem cells’ secretome to heal AoA.

Conclusion

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.