Biology subjects

Rodrigues, P. B.

Publications and source records attributed to Rodrigues, P. B..

5 recordsLinked to original sources

bioRxiv2026

Gelatin coating enhances flow diverting stent endothelial cell coverage, parent vessel healing and aneurysm occlusion

BackgroundFlow diversion stent treatment of cerebral aneurysms has demonstrated high rates of aneurysm occlusion and long-term durability. However, complete endothelization of the flow diverting stent is required for parent vessel healing which closes the aneurysm and metal stent from the circulation. Therefore, stent coatings which enhance endothelial migration and attachment may increase the rate of aneurysm occlusion and reduce complications associated with flow diversion treatment. Here we investigate the use of gelatin as a stent surface coating to enhance the rate of stent endothelialization and coverage and increase aneurysm healing. MethodsNitinol- Neuroform stents (Stryker, Kalamazoo, MI) and cobalt-chromium-Pipeline Flex flow diverting stents (Medtronic, Minneapolis, MN) were used for this study. The stents were coated with gelatin and endothelial cell attachment, proliferation and stent coverage were determined in vitro and compared to uncoated stent controls. A rabbit elastase-aneurysm model was used to determine the effects of endothelial cell seeded-gelatin coated flow diverting stents on aneurysm obliteration and parent vessel healing. ResultsIn vitro, gelatin coating of nitinol stents did not significantly alter endothelial cell attachment, proliferation, or stent coverage. However, gelatin coating of cobalt-chromium stents significantly increased endothelial cell attachment, proliferation and migration. In fact, gelatin coating significantly (p< 0.001) increased the rate of complete stent endothelization by 33% compared to unmodified controls. In vivo, treating aneurysm with endothelial cell seeded-gelatin coated stents resulted in aneurysm occlusion in 8 of 8 (100%) rabbit aneurysms at 90 days compared to only 4 of 7 (57%) in unmodified controls (p< 0.001). Histologically, there were trends in increased neoarterial wall thickness across the aneurysm neck and neointimal formation in the parent artery. Angiographic assessment demonstrated strong parent and side branch patency. ConclusionsGelatin coating enhances EC attachment and stent coverage which is dependent upon the type of stent. Endothelial cell seeded-gelatin coated-flow diverting stents allowed 100% aneurysm obliteration and neoarterial formation without affecting side branch patency or parent artery perfusion. Gelatin coating therefore represents a valuable strategy to enhance stent cellularization and aneurysm occlusion rates.

neuroscience↗

bioRxiv2025

Coil and flow diverting stents as drug delivery platforms for cerebral aneurysm treatment

Cerebral aneurysm occlusion with coils and flow diverting stents has become the first line treatment for both unruptured and ruptured cerebral aneurysms. As these technologies have advanced, there have been changes in device shape and surface coating to enhance aneurysm embolization while reducing stent thrombogenicity. Drug eluting stents have been used with great success in the targeted delivery of rapamycin, a mTOR complex 1 inhibitor to prevent restenosis in coronary and peripheral artery disease. However, few studies have investigated the use of coils and stents as delivery platforms for sustained drug release to cerebral aneurysm tissue. In this study, we used the bio-compatible and degradable polymers, gelatin and PLGA and a simple evaporative coating technique to investigate the release of rapamycin over time from coated platinum coils and Pipeline flow diverting stents. Rapamycin coated coils were incubated with human vascular endothelial cells in vitro to confirm therapeutic levels of rapamycin release. The rate of rapamycin release was similar in both gelatin and PLGA coated coils and was sustained for more than three weeks. Rapamycin was bioactive, at a therapeutic dose and inhibited mTOR complex 1 in human brain endothelial cells treated with a rapamycin coated coil. The relative degree of mTOR complex 1 inhibition was greater in PLGA compared to gelatin coated coils. Coating flow diverting stents with a rapamycin-PLGA coating demonstrated continuous rapamycin release over a 35 day period. Reducing the percent PLGA polymer concentration caused a robust and sustainable release of rapamycin. The PLGA coating was resilient enough to allow device recapturing without affecting rapamycin eluting rates or device deployment and expansion. This work provides a simple, feasible and tunable method to coat occlusion devices for preclinical studies investigating targeted drug delivery for improved parent vessel healing and aneurysm obliteration.

bioengineering↗

bioRxiv2025

Cerebral vascular tortuosity and aneurysm formation and rupture: a novel vessel tortuosity scale

Cerebral aneurysm (CA) rupture is the most common cause of nontraumatic subarachnoid hemorrhage. Recent data suggests that tortuosity is associated with aneurysm formation and rupture risk. We aimed to determine if tortuosity correlates with CA development and rupture in a mouse CA model and to develop a novel tortuosity scale to be used for in vivo CA studies. A highly validated, elastase-mouse CA model was used to assess cerebral vessel tortuosity with CA formation and rupture in sham and elastase groups. A 4-point ordinal scale was created to evaluate predictive capacity for vessel tortuosity level and CA formation and rupture. Nearly all sham animals (92%) had little to no vessel tortuosity on the visual scale (median, IQR: 1, [1-2]), compared to 24% in the elastase groups (2, [2-3]) (p=0.001). Sham cohorts had zero animals with highly tortuous vessels, while 3.5mU and 35mU cohorts had >35% of animals with significant visual tortuosity, p=0.003 and p<0.000, respectively. CA formation and rupture was higher in the elastase groups compared to the sham group (p=0.002). Both the visual scale and tortuosity index significantly predicted CA formation (p<0.001) and rupture (p<0.001). A novel tortuosity scale is highly predictive of CA formation and rupture in vivo. It may offer a new measurement to better understand vessel stress in the pathogenesis and progression of CAs.

neuroscience↗

bioRxiv2024

Metaproteomics reveals age-specific alterations of gut microbiome in hamsters with SARS-CoV-2 infection

The gut microbiomes pivotal role in health and disease is well-established. SARS-CoV-2 infection often causes gastrointestinal symptoms and is associated with changes of the microbiome in both human and animal studies. While hamsters serve as important animal models for coronavirus research, there exists a notable void in the functional characterization of their microbiomes with metaproteomics. In this study, we present a workflow for analyzing the hamster gut microbiome, including a metagenomics-derived hamster gut microbial protein database and a data-independent acquisition metaproteomics method. Using this workflow, we identified 32419 protein groups from the fecal microbiomes of young and old hamsters infected with SARS-CoV-2. We showed age-specific changes in the expressions of microbiome functions and host proteins associated with microbiomes, providing further functional insight into the dysbiosis and aberrant cross-talks between the microbiome and host in SARS-CoV-2 infection. Altogether this study established and demonstrated the capability of metaproteomics for the study of hamster microbiomes.

microbiology↗

bioRxiv2024

Integrative metagenomics and metabolomics reveal age-associated gut microbiota and metabolite alterations in experimental COVID-19

Aging is a key contributor of morbidity and mortality during acute viral pneumonia. The potential role of age-associated dysbiosis on disease outcomes is still elusive. In the current study, we used high-resolution shotgun metagenomics and targeted metabolomics to characterize SARS-CoV-2-associated changes in the gut microbiota from young (2-month-old) and aged (22-month-old) hamsters, a valuable model of COVID-19. We show that age-related dysfunctions in the gut microbiota are linked to disease severity and long-term sequelae in older hamsters. Our data also reveal age-specific changes in the composition and metabolic activity of the gut microbiota during both the acute phase (day 7 post-infection, D7) and the recovery phase (D22) of infection. Aged hamsters exhibited the most notable shifts in gut microbiota composition and plasma metabolic profiles. Through an integrative analysis of metagenomics, metabolomics, and clinical data, we identified significant associations between bacterial taxa, metabolites and disease markers in the aged group. On D7 (high viral load and lung epithelial damage) and D22 (body weight loss and fibrosis), numerous amino acids, amino acid-related molecules, and indole derivatives were found to correlate with disease markers. In particular, a persistent decrease in phenylalanine, tryptophan, glutamic acid, and indoleacetic acid in aged animals positively correlated with poor recovery of body weight and/or lung fibrosis by D22. In younger hamsters, several bacterial taxa (Eubacterium, Oscillospiraceae, Lawsonibacter) and plasma metabolites (carnosine and cis-aconitic acid) were associated with mild disease outcomes. These findings support the need for age-specific microbiome-targeting strategies to more effectively manage acute viral pneumonia and long-term disease outcomes.

immunology↗