Biology subjects

Del Mundo, H. C.

Publications and source records attributed to Del Mundo, H. C..

3 recordsLinked to original sources

bioRxiv2023

Gold Nanoparticles for Monitoring of Mesenchymal Stem Cell-Loaded Bioresorbable Polymeric Wraps for Arteriovenous Fistulas

BackgroundTo address high rates of arteriovenous fistula (AVF) failure, a mesenchymal stem cell (MSC)-seeded polymeric perivascular wrap has been developed to reduce neointimal hyperplasia (NIH) and enhance AVF maturation in a rat model. However, the wraps radiolucency makes its placement and integrity difficult to monitor. PurposeIn this study, we infused gold nanoparticles (AuNPs) into the polymeric perivascular wrap to improve its radiopacity and tested the effect of infusion on the previously reported beneficial effects of the polymeric wrap on the AVF outflow vein. Materials and MethodsWe fabricated a polymeric perivascular wrap made of polycaprolactone (PCL) infused with AuNPs via electrospinning. Sprague-Dawley rat mesenchymal stem cells (MSCs) were seeded on the surface of the wraps. We then compared the effect of five AVF treatments--no perivascular wrap (i.e., control), PCL wrap, PCL+MSC wrap, PCL-Au wrap, and PCL-Au+MSC wrap--on AVF maturation in a Sprague-Dawley rat model of chronic kidney disease (n=3 per group). Statistical significance was defined as p<.05, and one-way analysis of variance was performed using GraphPad Prism software. ResultsOn micro-CT, AuNP-infused wraps demonstrated significantly higher radiopacity compared to wraps without AuNPs. On ultrasonography, wraps with and without AuNPs equally reduced the wall-to-lumen ratio of the outflow vein, a marker of vascular stenosis. On histomorphometric analysis, wraps with and without AuNPs equally reduced the neointima-to- lumen ratio of the outflow vein, a measure of NIH. On immunofluorescence analysis, representative MSC-seeded wraps demonstrated reduced neointimal staining for markers of smooth muscle cells (-SMA), inflammatory cells (CD45), and fibroblasts (vimentin) infiltration when compared to control and wraps without MSCs. ConclusionGold nanoparticle infusion allows the in vivo monitoring via micro-CT of a mesenchymal stem cell-seeded polymeric wrap over time without compromising the benefits of the wrap on arteriovenous fistula maturation. Summary StatementGold nanoparticle infusion enables in vivo monitoring via micro-CT of the placement and integrity over time of mesenchymal stem cell-seeded polymeric wrap supporting arteriovenous fistula maturation. Key ResultsO_LIGold nanoparticle (AuNP)-infused perivascular wraps demonstrated higher radiopacity on micro-CT compared with wraps without AuNPs after 8 weeks. C_LIO_LIAuNP-infused perivascular wraps equally improved the wall-to-lumen ratio of the outflow vein (a marker of vascular stenosis) when compared with wraps without AuNPs, as seen on US. C_LIO_LIAuNP-infused perivascular wraps equally reduced the neointima-to-lumen ratio of the outflow vein (a measure of neointimal hyperplasia) when compared with wraps without AuNPs, as seen on histomorphometry. C_LI

bioengineering↗

bioRxiv2023

Rosuvastatin-Eluting Gold Nanoparticle-Loaded Perivascular Implantable Wrap for Enhanced Arteriovenous Fistula Maturation in a Murine Model

BackgroundArteriovenous fistulas (AVFs) are a vital intervention for patients requiring hemodialysis, but they also contribute to overall mortality due to access malfunction. The most common cause of both AVF non-maturation and secondary failure is neointimal hyperplasia (NIH). Absorbable polycaprolactone (PCL) perivascular wraps can address these complications by incorporating drugs to attenuate NIH, such as rosuvastatin (ROSU), and metallic nanoparticles for visualization and device monitoring. ObjectivesThis study aimed to assess the impacts of gold nanoparticle (AuNP) and ROSU-loaded perivascular wraps on vasculature NIH and AVF maturation and patency in a chronic kidney disease rat model. MethodsElectrospun wraps containing combinations of PCL, AuNP, and ROSU were monitored for in vitro drug elution, nanoparticle release, tensile strength, and cell viability. Perivascular wraps were implanted in chronic kidney disease rats for in vivo ultrasound (US) and micro-computed tomography (mCT) imaging. AVF specimens were collected for histological analyses. ResultsNo difference in cell line viability was observed in ROSU-containing grafts. In vitro release studies of ROSU and AuNPs correlated with decreasing radiopacity over time on in vivo mCT analysis. The mCT study also demonstrated increased radiopacity in AuNP-loaded wraps compared with PCL and control. The addition of ROSU demonstrated decreased US and histologic measurements of NIH. ConclusionsThe reduced NIH seen with ROSU-loading of perivascular wraps suggests a synergistic effect between mechanical support and anti-hyperplasia medication. Furthermore, the addition of AuNPs increased wrap radiopacity. Together, our results show that radiopaque, AuNP-, and ROSU-loaded PCL grafts induce AVF maturation and suppress NIH while facilitating optimal implanted device visualization.

bioengineering↗

bioRxiv2023

Acoustically Targeted Noninvasive Gene Therapy in Large Brain Regions

Focused Ultrasound Blood-Brain Barrier Opening (FUS-BBBO) can deliver adeno-associated viral vectors (AAVs) to treat genetic disorders of the brain. However, such disorders often affect large brain regions. Moreover, the applicability of FUS-BBBO in the treatment of brain-wide genetic disorders has not yet been evaluated. Herein, we evaluated the transduction efficiency and safety of opening up to 105 sites simultaneously. Increasing the number of targeted sites increased gene delivery efficiency at each site. We achieved transduction of up to 60% of brain cells with comparable efficiency in the majority of the brain regions. Furthermore, gene delivery with FUS-BBBO was safe even when all 105 sites were targeted simultaneously without negative effects on animal weight, neuronal loss, or astrocyte activation. To evaluate the application of multi-site FUS-BBBO for gene therapy, we used it for gene editing using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system, and found effective gene editing, but also a loss of neurons at the targeted sites. Overall, this study provides a brain-wide map of transduction efficiency and the first example of gene editing after site-specific noninvasive gene delivery to a large brain region.

bioengineering↗