Project PED615/2022

Project Executive Summary

This work was supported by a grant of the:

 Ministry of Research, Innovation and Digitalization, CCCDI – UEFISCDI,
project number PN-III-P2-2.1-PED-2021-2049, within PNCDI III

Project period: June 2022 – June 2024

Project Title:

Preclinical validation of the prevention of the intrastent restenosis by the cumulative effect of functionalized magnetoresponsive nanocomposite particles and magnetic stent in the presence of the external magnetic fieldMNPs2STENT

Rapid endothelialization and healing are critical for successful blood vessel reconstruction following vascular injury (stent placement). Our recent research efforts have demonstrated the ability of our novel technologies, including magnetic stents and PEG-coated magnetic nanoparticles, to enable magnetic targeting and retention of injected particles to diseased artery segments. This approach promotes rapid healing after implantation and may alleviate the need for long-term dual antiplatelet therapy and improve long-term patency.

The present proposal focuses on (1) demonstrating the feasibility of functionalized magnetic nanocluster, to controllably delivered and maintained at the site of stent implantation (both on the surface of the implanted magnetic/non-magnetic stent and the surrounding arterial wall); (2) facilitated stented arterial wall endothelialization to mitigate eliminate or reduce ,yltnacfiingis as well as restenosis, and thrombosis the need for long-term dual antiplatelet therapy. The project novelty consists in (i) Synthesis and comprehensive characterization of ten PEGylated SPIONs samples with different crystal sizes and PEG lengths; (ii) EX_ VIVO investigations (Seeding efficacy will be studied in the presence and the absence of a magnetic field by placing a magnet (single or array) near the implanted stent (magnetic and non-magnetic stent) in the umbilical artery; (iii) Construction of phantom sets for experimental investigations (made of glass and transparent silicone to highlight the effect of wall roughness for particle deposition); special attention will be paid to the Nanoparticle agglomeration which is a factor with solid adverse consequences in vivo; computational fluid dynamics can model and clarify the entire process of drug administration and drug delivery from the injection site to absorption site in terms of nanoparticles volume fraction, magnetization, artery–magnet distance, size and shape of the coated nanoparticles.

The present proposal focuses on the implementation of different MIONs, which will be assessed due to their suitability in magnetically controlled cell seeding and their ability to be produced under lab-scaled conditions. Whereas many different MIONs have been developed so far, only scarce possibilities of these products are already available for clinical applications, and none of them are appropriate for regenerative medicine or to be deployed in the arteriosclerotic and intrastent disease pattern