Bismuth-Infused Perivascular Wrap Facilitates Delivery of Mesenchymal Stem Cells and Attenuation of Neointimal Hyperplasia in Rat Arteriovenous Fistulas

Authors

Allan John R Barcena
Joy Vanessa D Perez
Marvin R Bernardino
Jossana A Damasco
Erin Marie D San Valentin
Carleigh Klusman
Benjamin Martin
Gino Martin Canlas
Francisco M Heralde
Natalie Fowlkes
Richard R Bouchard
Jizhong Cheng
Steven Y Huang
Marites P Melancon

Language

English

Publication Date

1-1-2025

Journal

Biomaterials Advances

DOI

10.1016/j.bioadv.2024.214052

PMID

39341164

PMCID

PMC11725062

PubMedCentral® Posted Date

1-1-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

BACKGROUND: Mesenchymal stem cells (MSCs) have emerged as novel therapies for supporting arteriovenous fistula (AVF) maturation, and bioresorbable polymeric scaffolds have enabled sustained MSC delivery into maturing AVFs. However, the radiolucency of biopolymeric wraps prevents in vivo monitoring of their integrity and location, hindering long-term preclinical investigations.

METHODS: We infused bismuth nanoparticles (BiNPs) into polycaprolactone (PCL) to fabricate an electrospun perivascular wrap capable of MSC delivery and conducive to longitudinal monitoring using conventional imaging. We tested the wraps' effects on the attenuation of markers of neointimal hyperplasia (i.e., endothelial dysfunction, hypoxia, and inflammation), the leading cause of AVF failure, in rats with induced chronic kidney disease (n = 3 per time point) for the following groups: control (no wrap), PCL wrap, PCL with MSCs, PCL-Bi (BiNP-infused wrap), and PCL-Bi with MSCs.

RESULTS: Physicochemical characterization and in vitro biocompatibility tests revealed that BiNP infusion did not alter the wrap's non-cytotoxicity toward vascular cells, hemocompatibility, and capacity for MSC loading but facilitated long-term monitoring via micro-computed tomography. After 8 weeks, all treatment groups demonstrated significant improvement in wall-to-lumen ratio on ultrasonography (P <  0.001), neointima-to-lumen ratio on histomorphometry (P <  0.001), and attenuation of neointimal hypoxia on immunohistochemistry (P <  0.05). Compared to non-MSC wraps, MSC-loaded wraps not only attenuated endothelial dysfunction and neointimal inflammation but also reduced hypoxia and inflammation across all vascular layers.

CONCLUSION: These results demonstrate that MSC delivery through a radiopaque polymeric wrap could enhance AVF patency outcomes through the inhibition of multiple pathways inducing AVF failure.

Keywords

Animals, Rats, Hyperplasia, Mesenchymal Stem Cells, Neointima, Mesenchymal Stem Cell Transplantation, Bismuth, Polyesters, Arteriovenous Fistula, Rats, Sprague-Dawley, Male, Nanoparticles

Published Open-Access

yes

Recommended Citation

Barcena, Allan John R; Perez, Joy Vanessa D; Bernardino, Marvin R; et al., "Bismuth-Infused Perivascular Wrap Facilitates Delivery of Mesenchymal Stem Cells and Attenuation of Neointimal Hyperplasia in Rat Arteriovenous Fistulas" (2025). Faculty, Staff and Student Publications. 5370.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5370