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.
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The datasets used and/or analyzed in this study are available from the corresponding author upon reasonable request.
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This research was funded by the National Institutes of Health—National Heart, Lung, and Blood Institute (5HL141831-05 and 1R01HL159960-01A1), a Radiological Society of North America Research Seed Grant (RSD2012), a Society of Interventional Radiology Pilot Research Grant, an MD Anderson Center for Advanced Biomedical Imaging Pilot Project Program Research Grant, and the National Institutes of Health—National Cancer Institute through MD Anderson's Cancer Center Support Grant (P30CA016672; used the Research Animal Support Facility and Small Animal Imaging Facility). The authors would like to acknowledge Sunita C. Patterson in MD Anderson’s Research Medical Library for editing the manuscript, Dr. James Gu at the Electron Microscopy Core at Houston Methodist Research Institute for assisting with the conduct of scanning electron microscopy, and Dunn Lab personnel (i.e., Amanda McWatters, Malea L. Williams, and Steve D. Parrish) for assisting with animal experiments, and Small Animal Imaging Facility personnel for assisting with animal imaging.
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Klusman, C., Martin, B., Perez, J.V.D. et al. Rosuvastatin-Eluting Gold-Nanoparticle-Loaded Perivascular Wrap for Enhanced Arteriovenous Fistula Maturation in a Murine Model. Adv. Fiber Mater. 5, 1986–2001 (2023). https://doi.org/10.1007/s42765-023-00315-2