Biology subjects

San Valentin, E. M. D.

Publications and source records attributed to San Valentin, E. M. D..

6 recordsLinked to original sources

bioRxiv2025

Oral microbial signatures of head and neck cancer patients highlight diverse longitudinal patterns of oral mucositis severity

BackgroundOral mucositis is a painful complication commonly observed in head and neck cancer patients receiving cancer treatment. Emerging evidence suggests that changes in the oral microbiome can contribute to oral mucositis development, making microbial signatures potential targets for therapeutic inter-ventions. This study aimed to: (1) characterize longitudinal microbial patterns of oral mucositis severity among head and neck cancer patients; (2) determine clinically relevant patient clusters based on oral mucositis severity trajectories; and (3) identify microbial signatures specific to these clusters. ResultsWe derived a calibrated oral mucositis score by applying non-negative sparse principal component analysis to seven oral mucositis related symptom ratings, using longitudinal microbiome data from 140 head and neck cancer patients. Functional data analysis and hierarchical clustering identified three distinct patient clusters with differing microbial trajectories of oral mucositis progression. One cluster exhibited patients with a rapid increase in oral mucositis severity following treatment initiation, while the other clusters displayed more gradual increase. Demographic comparisons revealed significant differences in age and weight distributions between clusters, with older, lighter patients more common in clusters experiencing more gradual oral mucositis progression. Partial least squares knockoff analysis identified cluster-specific microbial signatures: notably, Prevotella spp. positively associated with calibrated oral mucositis score across all clusters, while Alloprevotella (Alloprevotella0302) was significantly enriched only in patients experiencing rapid oral mucositis progression. Conversely, genera associated with oral health, including Haemophilus, Rothia, and Actinomyces, were negatively correlated with calibrated oral mucositis score. ConclusionsDistinct trajectories of oral mucositis scores in head and neck cancer patients are linked to specific oral microbial profiles and demographic factors. The identification of cluster-specific microbial profiles highlights the potential for microbiome-targeted interventions to manage oral mucositis severity. While most taxa were cluster-specific, Prevotella consistently ranked among the top taxa positively associated with the calibirated oral mucositis score across clusters, suggesting it may not differentiate between patient groups but rather reflects overall disease severity.

bioinformatics↗

bioRxiv2025

Fabrication of radiopaque, drug-loaded resorbable polymer for medical device development

Resorbable medical devices provide temporary functionality before degrading into safe byproducts. One application is absorbable inferior vena cava filters (IVCFs), which prevent pulmonary embolism (PE) in high-risk patients with contraindications to anticoagulants. However, current absorbable IVCFs are limited by radiolucency and local clot formation risks. This study aimed to develop radiopaque, drug-loaded resorbable IVCFs with enhanced imaging and therapeutic capabilities. Poly-p-dioxanone (PPDO) sutures were infused with gadolinium nanoparticles (GdNPs) and dipyridamole (DPA), an anti-thrombotic agent. GdNPs were synthesized with an average diameter of 35.76 {+/-} 3.71 nm. Gd content was 371 {+/-} 1.6 mg/g (PPDO-Gd) and 280 {+/-} 0.3 mg/g (PPDO-Gd+DPA), while DPA content was 18.20 {+/-} 5.38 mg/g (PPDO-DPA) and 12.91 {+/-} 0.83 mg/g (PPDO-Gd+DPA). Suture thickness (0.39-0.49 cm, P = 0.0143) and melting temperature (103.61-105.90, P = 0.0002) statistically differed among the different groups, while load-at-break did not (4.39-5.38, P = 0.2367). Although suture thickness and melting temperatures differed significantly, load-at-break was preserved and did not alter the mechanical and degradation properties of the various IVCFs. Micro-CT imaging revealed enhanced radiopacity for Gd-containing IVCFs (2,713 {+/-} 105 HU for PPDO-Gd, 1,516 {+/-} 281 HU for PPDO-Gd+DPA). Radiopacity decreased gradually over 10-12 weeks. Clot-trapping efficacy was maintained, and no hemolysis or cellular toxicity was observed. In conclusion, the GdNP- and DPA-infused PPDO IVCFs demonstrated improved radiopacity, anti-thrombotic potential, and compatibility with routine imaging, without compromising mechanical strength or safety.

bioengineering↗

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↗

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↗

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↗