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Redesigning aortic endograft: enabling in-situ personalized aneurysm healing

Project description

Innovative endograft for personalised aortic aneurysm healing

Forty years ago, the endograft (EG) revolutionised vascular surgery by enabling endovascular treatment of aortic aneurysms (AoA). However, its technological concept has remained essentially unchanged: the EG is a passive device aimed at treating aortic aneurysms in their later stages rather than curing the disease, even when detected early. The ERC-funded Epeius project will develop 3D bioprinted, bioresorbable endovascular grafts loaded with active drug components to enable early personalised healing. The project will address challenges in predicting human safety and efficacy of therapies and in delivering drugs at therapeutic concentrations. It will create an in vitro AoA model and integrate 3D bioprinting and computational biomechanics to develop the next-generation endovascular device.

Objective

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.

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Host institution

UNIVERSITA DEGLI STUDI DI PAVIA
Net EU contribution
€ 1 991 225,00
Address
STRADA NUOVA 65
27100 Pavia
Italy

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Region
Nord-Ovest Lombardia Pavia
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 1 991 225,00

Beneficiaries (1)