Bernardino, M. | bioRxiv Science

bioRxiv2023

Image-guided deployment and monitoring of a novel tungsten nanoparticle-infused radiopaque absorbable inferior vena cava filter in pig

The use of absorbable inferior vena cava filters (IVCFs) constructed with poly-p-dioxanone (PPDO) eliminates risks and complications associated with the use of retrievable metallic filters. Radiopacity of radiolucent PPDO IVCFs can be improved with the incorporation of nanoparticles (NPs) made of high-atomic number materials such as gold and bismuth. In this study, we focused on incorporating tungsten NPs (WNPs), along with polyhydroxybutyrate (PHB), polycaprolactone (PCL), and polyvinylpyrrolidone (PVP) polymers to increase the surface adsorption of the WNPs. We compared the imaging properties of WNPs with single-polymer PHB (W-P) and WNPs with polymer blends consisting of PHB, PCL, and PVP (W-PB). Our in vitro analyses using PPDO sutures showed enhanced radiopacity with either W-P or W-PB coating, without compromising the inherent physico-mechanical properties of the PPDO sutures. We observed a more sustained release of WNPs from W-PB-coated sutures than W-P-coated sutures. We successfully deployed W-P- and W-PB-coated IVCFs into the inferior vena cava of pig models, with monitoring by fluoroscopy. At the time of deployment, W-PB-coated IVCFs showed a 2-fold increase in radiopacity compared to W-P-coated IVCFs. Longitudinal monitoring of in vivo IVCFs over a 12-week period showed a drastic decrease in radiopacity at week 3 for both filters. Results of this study highlight the utility of NPs and polymers for enhancing radiopacity of medical devices; however, different methods of incorporating NPs and polymers can still be explored to improve the efficacy, safety, and quality of absorbable IVCFs.

bioengineering↗

bioRxiv2022

Bioresorbable mesenchymal stem cell-loaded electrospun polymeric scaffold inhibits neointimal hyperplasia following arteriovenous fistula formation in a rat model of chronic kidney disease

In the setting of chronic kidney disease (CKD), the periadventitial injection of mesenchymal stem cells (MSCs) has shown significant potential in improving arteriovenous fistula (AVF) maturation by inhibiting neointimal hyperplasia (NIH). However, the rapid clearance of MSCs remains a challenge. Hence, we fabricated an electrospun perivascular scaffold from polycaprolactone (PCL) to support MSC attachment and allow gradual MSC elution at the outflow vein, the AVF site most prone to NIH. We performed a 5/6th nephrectomy to induce CKD in Sprague-Dawley rats, followed by direct AVF formation and perivascular scaffold application. We then compared the following groups of CKD rats: no perivascular scaffold (i.e., control), PCL scaffold, and PCL+MSC scaffold. On ultrasonography, the PCL and PCL+MSC groups showed significantly reduced wall thickness and wall-to-lumen ratio and increased luminal diameter and flow rate. Of note, the PCL+MSC group showed greater improvement in luminal diameter and flow rate compared to PCL alone. Moreover, 18F-fluorodeoxyglucose positron emission tomography showed that only PCL+MSC resulted in a significant reduction in uptake. On histology, the PCL and PCL+MSC groups showed significantly reduced neointima-to-lumen and neointima-to-media ratios and reduced neointimal CD45, -SMA, and vimentin fluorescence staining compared to the control. Although the two scaffold treatments did not differ significantly in histology, in vivo imaging suggested that the addition of MSCs promoted greater luminal expansion and blood flow and 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.

bioengineering↗