Bioresorbable Mesenchymal Stem Cell-Loaded Electrospun Polymeric Scaffold Inhibits Neointimal Hyperplasia Following Arteriovenous Fistula Formation in A Rat Model of Chronic Kidney Disease.

Bioresorbable perivascular scaffolds loaded with antiproliferative agents have been shown to enhance arteriovenous fistula (AVF) maturation by inhibiting neointimal hyperplasia (NIH). These scaffolds, which can mimic the three-dimensional architecture of the vascular extracellular matrix, also have an untapped potential for the local delivery of cell therapies against NIH. Hence, we fabricated an electrospun perivascular scaffold from polycaprolactone (PCL) to support mesenchymal stem cell (MSC) attachment and gradual elution at the AVF's outflow vein. We induced CKD in Sprague-Dawley rats by performing 5/6 th nephrectomy, then created AVFs for scaffold application. We compared the following groups of CKD rats: no perivascular scaffold (i.e., control), PCL alone, and PCL+MSC scaffold. PCL and PCL+MSC significantly improved ultrasonographic (i.e., luminal diameter, wall-to-lumen ratio, and flow rate) and histologic (i.e., neointima-to-lumen ratio, neointima-to-media ratio) parameters compared to control, with PCL+MSC demonstrating further improvement in these parameters compared to PCL alone. Moreover, only PCL+MSC significantly reduced 18 F-fluorodeoxyglucose uptake on positron emission tomography. These findings suggest that adding MSCs promoted greater luminal expansion and potentially reduced the inflammatory process underlying NIH. Our results demonstrate the utility of mechanical support loaded with MSCs at the outflow vein immediately after AVF formation to support maturation by minimizing NIH. This article is protected by copyright. All rights reserved.