TY - JOUR
T1 - Bioresorbable Mesenchymal Stem Cell-Loaded Electrospun Polymeric Scaffold Inhibits Neointimal Hyperplasia Following Arteriovenous Fistula Formation in a Rat Model of Chronic Kidney Disease
AU - Barcena, Allan John R.
AU - Perez, Joy Vanessa D.
AU - Bernardino, Marvin R.
AU - Damasco, Jossana A.
AU - Cortes, Andrea
AU - Del Mundo, Huckie C.
AU - San Valentin, Erin Marie D.
AU - Klusman, Carleigh
AU - Canlas, Gino Martin
AU - Heralde, Francisco M.
AU - Avritscher, Rony
AU - Fowlkes, Natalie
AU - Bouchard, Richard R.
AU - Cheng, Jizhong
AU - Huang, Steven Y.
AU - Melancon, Marites P.
N1 - Publisher Copyright:
© 2023 Wiley-VCH GmbH.
PY - 2023/10/18
Y1 - 2023/10/18
N2 - 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, an electrospun perivascular scaffold from polycaprolactone (PCL) to support mesenchymal stem cell (MSC) attachment and gradual elution at the AVF's outflow vein is fabricated. Chronic kidney disease (CKD) in Sprague-Dawley rats is induced by performing 5/6th nephrectomy, then AVFs for scaffold application are created. The following groups of CKD rats are compared: no perivascular scaffold (i.e., control), PCL alone, and PCL+MSC scaffold. PCL and PCL+MSC significantly improve 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 reduces 18F-fluorodeoxyglucose uptake on positron emission tomography. These findings suggest that adding MSCs promotes greater luminal expansion and potentially reduces the inflammatory process underlying NIH. The results demonstrate the utility of mechanical support loaded with MSCs at the outflow vein immediately after AVF formation to support maturation by minimizing NIH.
AB - 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, an electrospun perivascular scaffold from polycaprolactone (PCL) to support mesenchymal stem cell (MSC) attachment and gradual elution at the AVF's outflow vein is fabricated. Chronic kidney disease (CKD) in Sprague-Dawley rats is induced by performing 5/6th nephrectomy, then AVFs for scaffold application are created. The following groups of CKD rats are compared: no perivascular scaffold (i.e., control), PCL alone, and PCL+MSC scaffold. PCL and PCL+MSC significantly improve 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 reduces 18F-fluorodeoxyglucose uptake on positron emission tomography. These findings suggest that adding MSCs promotes greater luminal expansion and potentially reduces the inflammatory process underlying NIH. The results demonstrate the utility of mechanical support loaded with MSCs at the outflow vein immediately after AVF formation to support maturation by minimizing NIH.
KW - arteriovenous fistula
KW - end-stage renal diseases
KW - mesenchymal stem cells
KW - polymers
KW - positron emission tomography
KW - ultrasonography
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U2 - 10.1002/adhm.202300960
DO - 10.1002/adhm.202300960
M3 - Article
C2 - 37395729
AN - SCOPUS:85165261914
SN - 2192-2640
VL - 12
JO - Advanced Healthcare Materials
JF - Advanced Healthcare Materials
IS - 26
M1 - 2300960
ER -