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

Abstract

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.

Graphical Abstract