Rosuvastatin-Eluting Gold Nanoparticle-Loaded Perivascular Implantable Wrap for Enhanced Arteriovenous Fistula Maturation in a Murine Model

Abstract

AbstractBackgroundArteriovenous fistulas (AVFs) are a vital intervention for patients requiring hemodialysis, but they also contribute to overall mortality due to access malfunction. The most common cause of both AVF non-maturation and secondary failure is neointimal hyperplasia (NIH). Absorbable polycaprolactone (PCL) perivascular wraps can address these complications by incorporating drugs to attenuate NIH, such as rosuvastatin (ROSU), and metallic nanoparticles for visualization and device monitoring.ObjectivesThis study aimed to assess the impacts of gold nanoparticle (AuNP) and ROSU-loaded perivascular wraps on vasculature NIH and AVF maturation and patency in a chronic kidney disease rat model.MethodsElectrospun wraps containing combinations of PCL, AuNP, and ROSU were monitored forin vitrodrug elution, nanoparticle release, tensile strength, and cell viability. Perivascular wraps were implanted in chronic kidney disease rats forin vivoultrasound (US) and micro-computed tomography (mCT) imaging. AVF specimens were collected for histological analyses.ResultsNo difference in cell line viability was observed in ROSU-containing grafts.In vitrorelease studies of ROSU and AuNPs correlated with decreasing radiopacity over time onin vivomCT analysis. The mCT study also demonstrated increased radiopacity in AuNP-loaded wraps compared with PCL and control. The addition of ROSU demonstrated decreased US and histologic measurements of NIH.ConclusionsThe reduced NIH seen with ROSU-loading of perivascular wraps suggests a synergistic effect between mechanical support and anti-hyperplasia medication. Furthermore, the addition of AuNPs increased wrap radiopacity. Together, our results show that radiopaque, AuNP-, and ROSU-loaded PCL grafts induce AVF maturation and suppress NIH while facilitating optimal implanted device visualization.