LAUSR

To overcome the complications connected to the treatment of coronary atherosclerosis by means of percutaneous transluminal angioplasty followed by stent implantation, the in situ release of antiproliferative nucleic acid based drugs (NABD) seems a promising approach. For their fragile nature, NABD cannot be released from drug eluting stents but they need to be embedded in a soft gel coating the coronary wall (endoluminal gel paving). This article deals with the thermal fate, once in the catheter, of a polymer blend composed by pluronic, giving rise to a soft gel in water upon temperature rise, and alginate, a natural polysaccharide giving origin to a strong gel in the presence of divalent cations. Simulations reveal that while the formation of a pregel is rapidly achieved, the formation of a mature gel takes a much longer time with respect to the residence time of the polymer blend inside the catheter. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48539. DOI: 10.1002/app.48539 capacity. In addition, the increased number of VSMCs also depends on the movement of progenitor cells from the bone marrow to the injured vessel area. Finally, macrophages, able to differentiate into myofibroblasts, also contribute to the hypercellularity. VSMCs proliferation, although slowing down in time, persists months after stent implantation and is accompanied by an increased production of the extracellular matrix. The appearance of ISR was the reason why BMSs were substituted by first generation drug eluting stents (DESs), scaffolds designed for the localized delivery of antiproliferative drugs using stent walls (naked or covered by thin layers of degradable polymer) as the loading site. While first generation DESs did reduce ISR down to about 10% of the treated cases, they were responsible for the increased incidence of in-stent thrombosis (IST) probably due to an incomplete endothelialization of the stented zone in comparison with uncoated stents. Indeed, it became evident that the antiproliferative and pro-apoptotic actions of the FDA-approved antiproliferative drugs, Sirolimus (immune-suppressor of Tlymphocytes capable of reducing the inflammatory response, of downmodulating VSMCs proliferation and promoting VSMCs apoptosis) and Paclitaxel (microtubule stabilizing agent which reduces the concentration of free tubulin required for new tubulin formation. INTRODUCTION Traditionally, coronary stenosis, a common atherosclerosis complication, has been treated by means of percutaneous transluminal coronary angioplasty (PTCA), a maneuver leading to the enlargement of the coronary stenotic portion by means of an expanding balloon. However, in about 30–50% of treated patients, PTCA has been shown to induce the development of symptomatic re-occlusion (restenosis) caused by early elastic recoil, intimal hyperplasia (exuberant proliferation of vascular smooth muscle cells, VSMCs), late constricting remodeling of the vessel, and formation of mural thrombus. Accordingly, alternative approaches were undertaken and the use of bare-metal stents (BMSs), rigid scaffolds located in correspondence of the coronary vessel stenotic portion, emerged as an interesting therapeutic strategy due to the significant reduction (down to 20–30% of the treated patients) of restenosis occurrence with respect to the simple PTCA treatment. While BMSs could really prevent the coronary wall early elastic recoil and late remodeling, they could not solve the problem of neointima hyperplasia (In Stent Restenosis—ISR) due to the VSMCs hyperproliferation. It was proposed that VSMCs switch from the contractile to the synthetic phenotype plays a key role in triggering VSMC proliferative ar Ts Università degli Studi di Trieste Archivio della ricerca – postprint