Transcriptomic profiling of radiopaque nanoparticle-loaded, bioresorbable polymeric perivascular wrap for arteriovenous fistula maturation.

Arteriovenous fistula (AVF) failure remains a significant clinical problem for hemodialysis access. It is driven by hemodynamic changes which promote inflammatory responses leading to neointimal hyperplasia and ultimately stenosis. Perivascular wraps have proved to be a promising intervention for mitigating hemodynamics stress. However, the molecular impact of perivascular wraps on the venous wall is not fully understood. This study aims to evaluate the molecular effects of polycaprolactone (PCL) perivascular wraps and PCL wraps embedded with radiopaque bismuth nanoparticles (PCL-Bi) on the outflow vein. Chronic kidney disease (CKD) was induced in female Sprague-Dawley rats through 5/6th nephrectomy. After CKD induction, AVFs were created via end-to-side anastomosis of the external jugular vein to the common carotid artery. The AVFs were treated with either a PCL wrap, a PCL-Bi wrap, or left as unwrapped controls (n = 3 each group). The outflow veins were harvested for bulk RNA sequencing after 8 weeks. Differential expression and pathway enrichment analyses were performed to evaluate differences between the groups. Compared to the unwrapped controls, the PCL-wrapped AVFs showed significant downregulation of pathways related to vascular smooth muscle cell processes, endothelial cell processes, and cell adhesion. Conversely, pathways related to phagocytosis and lysosomal activity were upregulated, reflecting a controlled response to the bioresorbable scaffold. Few differences were observed between the PCL and PCL-Bi wrapped AVFs, demonstrating that the addition of bismuth nanoparticles does not negate the beneficial effects of the PCL scaffold.