Post-surgery failure of open vascular reconstructions, Intimal hyperplasia, Vein graft, Arteriovenous fistula, Perivascular drug delivery, Pericelle, Materials of engineering and construction. Mechanics of materials, TA401-492, Biology (General), QH301-705.5

Open vascular reconstructions (OVR), including bypass grafts and dialysis access, are standard treatments for cardiovascular and renal diseases. Unfortunately, OVR often fail largely due to intimal hyperplasia (IH), and there are no clinical methods to prevent this complication. Perivascular drug administration during OVR presents a promising strategy for IH suppression. However, durations of drug release from carriers are generally short whereas sustained efficacy is essential for clinical success. This raises a critical question in clinical translation: can IH suppression be realistically maintained long-term (e.g., over 6 months) with short-term perivascular interventions? To address this question, we modified a rat vein-graft model to prolong IH progression. We then applied Pericelle, a nanoparticle/hydrogel hybrid system that we developed for perivascular delivery of rapamycin, an established IH-inhibitory drug. Surprisingly, despite short (∼3-month) drug release, Pericelle demonstrated IH suppression throughout 3, 6, and 9 months with IH reduced from 115.58 ± 27.89 to 40.34 ± 5.18 at 9 months (P