Magnetic nanoparticles in a non-woven composite for therapy of paravalvular leakage in transcatheter heart valve replacement (TAVR-MADEN)

• Applicants: Dr.-Ing. Sebastian Jansen; Professorin Dr. Ioana Slabu; Professor Dr. Felix Vogt
• Subject Area: Medical Physics, Biomedical Technology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 544612223

The 2-year mortality rate of aortic valve stenosis as a chronic progressive disease with a prevalence of 2 % - 7 % of over 65-year-olds in Germany is still at a very high level of 50 %. Transcatheter Aortic Valve Replacement, TAVR, has come into focus as a minimally invasive therapy over the last 20 years with over 350,000 procedures worldwide since 2002. However, TAVR also induces new forms of complications, such as paravalvular leakage (PVL). Despite the manufacturers' efforts to reduce PVL by using sealing cuffs that encase the stent frame of the valve prosthesis, the incidence of PVL is 29.4% in the TAVR group compared to 2.1% in the comparison group with conventional surgical heart valve replacement (SAVR). The herein proposed project deals with the research question of how a novel nonwoven composite consisting of a thermally responsive biodegradable and drug-loaded component can be inserted into the sealing cuff so that controlled heating achieves targeted degradation with corresponding drug release to stimulate connective tissue growth and thus seal the leakage. Such a nonwoven composite as a novel active sealing cuff of a TAVR prosthesis can represent a targeted, demand-based and non-invasive therapy in cases of diagnosed PVL. Magnetic nanoparticles (MNP) are a good option for the demand-based release of active substances. MNPs are embedded in biodegradable materials and then heated by external magnetic excitation, which leads to accelerated degradation of the surrounding material with a corresponding release of the active ingredient. The nonwoven composite proposed here consists of PU and PLGA, in which iron oxide MNP and PDGF are embedded. Within the project, the basic properties of the nonwoven in combination with the MNP and the PDGF will be analyzed. The degradation behavior and the associated release of PDGF will be investigated experimentally and numerically in order to develop prediction models. A prototype of a TAVR prosthesis with the novel active sealing cuff will be constructed and the effect demonstrated in vitro and in vivo.

• DFG Programme: Research Grants