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

Arteriovenous fistulas (AVFs) are a vital form of AV access for patients requiring hemodialysis, but they link to overall morbidity and mortality when they fail to mature. The most common cause of AVF non-maturation is neointimal hyperplasia (NIH). To minimize the deleterious effects of NIH, a perivascular wrap composed of polycaprolactone (PCL), rosuvastatin (ROSU), and gold nanoparticles (AUNPs) was constructed. This study assessed the impact of ROSU-eluting, radiopaque resorbable perivascular wraps on pathologic NIH in a chronic kidney disease (CKD) rodent model of AVF. Electrospun PCL wraps containing AuNPs and/or ROSU were monitored for in vitro tensile strength, AuNP release, ROSU elution, and effect on cellular viability. The wraps were then implanted around an AVF in a CKD rodent model for in vivo ultrasound (US) and micro-computed tomography (mCT) imaging. AVF specimens were collected for histological analyses. Cell viability was preserved in the presence of both AuNP- and ROSU-containing wraps. In vitro release of ROSU and AuNPs correlated with in vivo findings of decreasing radiopacity on mCT over time. AuNP-loaded wraps had higher radiopacity (1270.0-1412.0 HU at week 2) compared with other wraps (103.5-456.0 HU), which decreased over time. The addition of ROSU decreased US and histologic measurements of NIH. The reduced NIH seen with ROSU-loaded perivascular wraps suggests a synergistic effect between mechanical support and anti-hyperplasia medication. Furthermore, AuNP loading increased wrap radiopacity. Together, our results show that AuNP- and ROSU-loaded PCL wraps induce AVF maturation and suppress NIH while facilitating optimal implanted device visualization.