Peripheral artery diseases (PAD) significantly impair quality of life and functional status causing limb amputation. Drug eluting stents (DES) have revolutionized the field of interventional cardiology preventing coronary artery restenosis. However, heavily calcified peripheral arteries are associated with worse clinical outcomes after DES than for non-calcified lesions due unsuitable drugs as well the low penetration of drug in theses arteries.  Trans retinoic acid (ATRA) inhibits smooth muscle cells (SMC) proliferation and migration, modulates SMC phenotypes switching, limits inflammatory cytokines production and plays a crucial role in the inhibition of calcification processes. ATRASTENT aims the topical delivery of Cyclodextrin/ATRA complex directly in a calcified section of a vessel by electrospun nanofibers coated on a metallic vascular stent. ATRA will be combined with cyclodextrins, which improve its systemic bioavailability and photostability. The objective is to regulate the release of ATRA for treating de novo calcified stenosis and stimulating vascular tissue regeneration through the use of the silk nanofibrous membrane after implantation.

The ATRASTENT methodology will consist in

1) Developing and characterizing the silk fibroin-based electrospun membrane loaded with the CD/ATRA complex showing a release profile within the therapeutic window (UMET/U1008)

2) Evaluating in vitro the cytocompatibility of the coated stent with 2D/3D cell culture techniques and microfluidics using a suitable model (U1011/IEMN)

3) Evaluating in vivo efficacy on an original hypercholesterolemic rabbit model by identifying biological factors and ATRA diffusion in arteries (U1008/U1011).

The ATRASTENT multidisciplinary consortium reunites a team of renowned researchers with complementary expertise to achieve the project objectives.

 

Coordinator

U 1365 - ADDS - Systèmes avancés de délivrance de principes actifs - Advanced Drug Delivery Systems (Nicolas BLANCHEMAIN)

Project funded by the French Research Agency

Appel à projets générique 2025

CE17 - Recherche translationnelle en santé

Projet de Recherche Collaborative PRC

Duration of the project

Start date: October 2025

End date: October 2029