A novel biodegradable external stent regulates vein graft remodeling via the Hippo-YAP and mTOR signaling pathways

Coronary artery bypass graft (CABG) has been confirmed to effectively improve the prognosis of coronary artery disease, which is a major public health concern worldwide. As the most frequently used conduits in CABG, saphenous vein grafts have the disadvantage of being susceptible to restenosis due to intimal hyperplasia. To meet the urgent clinical demand, adopting external stents (eStents) and illuminating the potential mechanisms underlying their function are important for preventing vein graft failure. Here, using 4-axis printing technology, we fabricated a novel biodegradable and flexible braided eStent, which exerts excellent inhibitory effect on intimal hyperplasia. The stented grafts downregulate Yes-associated protein (YAP), indicating that the eStent regulates vein graft remodeling via the Hippo-YAP signaling pathway. Further, as a drug-delivery vehicle, a rapamycin (RM)-coated eStent was designed to amplify the inhibitory effect of eStent on intimal hyperplasia through the synergistic effects of the Hippo and mammalian target of rapamycin (mTOR) signaling pathways. Overall, this study uncovers the underlying mechanisms of eStent function and identifies a new therapeutic target for the prevention of vein graft restenosis.