Novel Drug-Testing Platform for Vascular Injury-induced Intimal Hyperplasia Using a Microphysiological System

Abstract

Drug-coated balloons (DCBs) and drug-eluting stents (DESs) with antiproliferative drugs have been developed to prevent restenosis. However, some patients who undergo DCB or DES procedures still experience restenosis. Therefore, it is essential to explore therapeutic agents for DCBs and DESs. Furthermore, alternative platforms addressing current experimental model limitations are necessary for disease research. Here, a 3D model of vascular injury-induced intimal hyperplasia is developed by using a microphysiological system (MPS). This model effectively replicated the endothelial denudation, proliferation, and migration of vascular smooth muscle cells (VSMCs), and vascular inflammation associated with the disease. Using this disease model, it is shown that antiproliferative drugs suppress VSMC proliferation but worsen endothelial denudation. In addition, potential alternatives are investigated to antiproliferative drugs and tested various drugs aimed at reducing inflammation. Partial improvements are found in VSMCs treated with DPI and in the endothelium treated with quercetin. When diphenyleneiodonium (DPI) and quercetin are combined, VSMC proliferation, migration, and vascular inflammation are reduced without impairing re-endothelialization. This disease model shows promise; this study may offer new treatment insights for DCBs and DESs.

Keywords: diphenyleneiodonium; intimal hyperplasia; microphysiological system; quercetin; vascular injury.