Development of physiologically relevant synthetic thrombus for use in visual analysis of in vitro mechanical thrombectomy device testing.

BACKGROUND: Ischemic stroke is a leading cause of death and significant long-term disability worldwide. Mechanical thrombectomy is emerging as a standard treatment for eligible patients. As clinical implementation of stent retrieval and aspiration thrombectomy increases, there is a need for physiologically relevant in vitro device efficacy testing. Critical to this testing is the development of standardized 'soft' and 'hard' synthetic blood clots that mimic the properties of human thrombi and are compatible with imaging technologies. Synthetic clots allow researchers to extract information regarding clot integration, model hemodynamics, and quantify the physics of thrombectomy. METHODS: This work develops polyacrylamide and alginate-based synthetic clots that are compatible with particle image velocimetry (PIV) and radiographic imaging techniques while maintaining mechanical properties of 'soft' and 'hard' human clots. Dynamic mechanical analysis testing using an HR2-Rheometer demonstrates comparable mechanical properties to human clots previously tested by this research group and provided in existing literature. RESULTS: The synthetic clots are formulated with either 0.5% w/v polyethylene microspheres for PIV visualization or 20% w/v barium sulfate for angiographic visualization, enabling real-time imaging of clot behavior during thrombectomy simulations. The soft formulation shows compressive and shear properties of ~12 kPa and 2-3 kPa, respectively. The hard clots are 3-4 times stiffer, with compressive and shear properties of 41-42 kPa and 8-9 kPa, respectively. CONCLUSION: Standardized synthetic clots offer a platform for reproducible device testing. This provides a greater understanding of mechanical thrombectomy device efficacy, which may lead to quantifiable advances in device development and eventual improved clinical outcomes.

Coral mucus as a reservoir of bacteriophages targeting Vibrio pathogens.

The increasing trend in sea surface temperature promotes the spread of Vibrio species, which are known to cause diseases in a wide range of marine organisms. Among these pathogens, Vibrio mediterranei has emerged as a significant threat, leading to bleaching in the coral species Oculina patagonica. Bacteriophages, or phages, are viruses that infect bacteria, thereby regulating microbial communities and playing a crucial role in the coral's defense against pathogens. However, our understanding of phages that infect V. mediterranei is limited. In this study, we identified two phage species capable of infecting V. mediterranei by utilizing a combination of cultivation and metagenomic approaches. These phages are low-abundance specialists within the coral mucus layer that exhibit rapid proliferation in the presence of their hosts, suggesting a potential role in coral defense. Additionally, one of these phages possesses a conserved domain of a leucine-rich repeat protein, similar to those harbored in the coral genome, that plays a key role in pathogen recognition, hinting at potential coral-phage coevolution. Furthermore, our research suggests that lytic Vibrio infections could trigger prophage induction, which may disseminate genetic elements, including virulence factors, in the coral mucus layer. Overall, our findings underscore the importance of historical coral-phage interactions as a form of coral immunity against invasive Vibrio pathogens.

Large, Wide-Neck, Side-Wall Aneurysm Treatment in Canines Using NeuroCURE: A Novel Liquid Embolic.

BACKGROUND: Untreated intracranial aneurysms can rupture and result in high rates of morbidity and mortality. Although there are numerous approved endovascular aneurysm treatment devices, most require dual anti-platelet therapy, are minimally biocompatible, or are prone to recanalization. Neurovascular Controlled Uniform Rapid Embolic (NeuroCURE) is an innovative polymer gel material with long-term stability, biocompatibility, and hemocompatibility developed for the treatment of large, wide-neck aneurysms. METHODS: Sidewall aneurysms were surgically created in 10 canines and NeuroCURE was injected through a 0.025 microcatheter under a single balloon inflation period. Aneurysm treatment was angiographically assessed post-embolization and pre-term with Raymond-Roy occlusion classification and a qualitative flow grade scale. Aneurysm neck stability and biocompatibility was histologically assessed to grade platelet/fibrin thrombus, percent endothelialization, and neointimal formation. Aneurysm sac stability was assessed by NeuroCURE sac content, inflammation, and neo-angiogenesis scales. RESULTS: Explanted aneurysms exhibited a smooth surface at the aneurysm neck with nearly complete neointimal coverage at 3-months. By 6-months, neck endothelialization was 100% in all animals (average Raymond-Roy occlusion classification of 1.2), with no instances of aneurysm recanalization or parent vessel flow compromise. Biocompatibility assessments verified a lack of inflammatory response, neo-angiogenesis, and platelet/fibrin thrombus formation. CONCLUSION: The NeuroCURE material promotes progressive occlusion of wide-necked side wall aneurysms over time without the need for dual antiplatelet agents. NeuroCURE also promotes neointimal tissue infill without dependence on thrombus formation and thus resists aneurysm recanalization. NeuroCURE remains a compelling investigational device for the treatment of intracranial aneurysms.