Carotid single- and dual-layer stents reduce the wall adhesion of platelets by influencing flow and cellular transport.

An ongoing thrombosis on a ruptured atherosclerotic plaque in the carotid may cause stroke. The primary treatment for patients with tandem lesion is stenting. Dual-layer stents have been introduced as an alternative to single-layer stents for elective and emergent carotid artery stenting.

Clot Accumulation in 3D Microfluidic Bifurcating Microvasculature Network.

The microvasculature, which makes up the majority of the cardiovascular system, plays a crucial role in the process of thrombosis, with the pathological formation of blood clots inside blood vessels. Since blood microflow conditions significantly influence platelet activation and thrombosis, accurately mimicking the structure of bifurcating microvascular networks and emulating local physiological blood flow conditions are valuable for understanding blood clot formation. In this work, we present an in vitro model for blood clotting in microvessels, focusing on 3D bifurcations that align with Murray's law, which guides vascular networks by maintaining a constant wall shear rate throughout.

A double-edged sword: The complex interplay between engineered nanoparticles and platelets.

Nanoparticles (NP) play a crucial role in nanomedicine, serving as carriers for localized therapeutics to allow for precise drug delivery to specific disease sites and conditions. When injected systemically, NP can directly interact with various blood cell types, most critically with circulating platelets. Hence, the potential activation/inhibition of platelets following NP exposure must be evaluated a priori due to possible debilitating outcomes.

A continuum model for the elongation and orientation of Von Willebrand factor with applications in arterial flow.

The blood protein Von Willebrand factor (VWF) is critical in facilitating arterial thrombosis. At pathologically high shear rates, the protein unfolds and binds to the arterial wall, enabling the rapid deposition of platelets from the blood. We present a novel continuum model for VWF dynamics in flow based on a modified viscoelastic fluid model that incorporates a single constitutive relation to describe the propensity of VWF to unfold as a function of the scalar shear rate.

A macrofluidic model to investigate the intrinsic thrombogenicity of clinically used stents and develop less thrombogenic stents.

Microfluidic blood flow models have been instrumental to study the functions of blood platelets in hemostasis and arterial thrombosis. However, they are not suited to investigate the interactions of platelets with the foreign surfaces of medical devices such as stents, mainly because of the dimensions and geometry of the microfluidic channels. Indeed, the channels of microfluidic chips are usually rectangular and rarely exceed 50 to 100 μm in height, impairing the insertion of clinically used stents.

A Fibrin-Thrombin Based In Vitro Perfusion System to Study Flow-Related Prosthetic Heart Valves Thrombosis.

Prosthetic heart valve (PHV) replacement has increased the survival rate and quality of life for heart valve-diseased patients. However, PHV thrombosis remains a critical problem associated with these procedures. To better understand the PHV flow-related thrombosis problem, appropriate experimental models need to be developed.

Exploring pulmonary distribution of intratracheally instilled liquid foams in excised porcine lungs.

The applicability of inhalation therapy to some severe pulmonary conditions is often compromised by limited delivery rates (i.e. total dose) and low deposition efficiencies in the respiratory tract, most notably in the deep pulmonary acinar airways.

A micro-channel array in a tissue engineered vessel graft guides vascular morphogenesis for anastomosis with self-assembled vascular networks.

Vascularization of 3D engineered tissues poses a great challenge in the field of tissue engineering. One promising approach for vascularizing engineered tissue is cocultivation with endothelial cells (ECs), which spontaneously self-assemble into a natural capillary network in the presence of supportive cells. However, the ECs do not self-assemble according to physiological hierarchy which is required to support blood supply.

Micro-particle entrapment dynamics in microfluidic pulmonary capillary networks.

The journey of vascular targeted carriers (VTC) in the circulatory system is highly intricate and includes navigation through different vessel structures, such as the vast pulmonary capillary network (PCN) in the lungs where particles can get entrapped and lead to blockage. Here, we leverage microfluidic PCN models to explore, for the first time, micro-particle capillary entrapment, in a well-controlled biophysical environment mimicking human physiological hemodynamics at true scale. This in vitro strategy mimics the challenges of vascular carrier transport during their journey in the smallest capillaries of the body (∼5 µm).

Human Multi-Compartment Platform for Emulating Respiratory Airborne Transmission: From Nose to Pulmonary Acini.

The past decade has witnessed tremendous endeavors to deliver novel preclinical lung models for pulmonary research endpoints, including foremost with the advent of and . With growing interest in aerosol transmission and infection of respiratory viruses within a host, most notably the SARS-CoV-2 virus amidst the global COVID-19 pandemic, the importance of crosstalk between the different lung regions (i.e.

Biophysical targeting of high-risk cerebral aneurysms.

Localized delivery of diagnostic/therapeutic agents to cerebral aneurysms, lesions in brain arteries, may offer a new treatment paradigm. Since aneurysm rupture leading to subarachnoid hemorrhage is a devastating medical emergency with high mortality, the ability to noninvasively diagnose high-risk aneurysms is of paramount importance. Moreover, treatment of unruptured aneurysms with invasive surgery or minimally invasive neurointerventional surgery poses relatively high risk and there is presently no medical treatment of aneurysms.

Characterization of GPVI- or GPVI-CD39-Coated Nanoparticles and Their Impact on In Vitro Thrombus Formation.

Traditional antithrombotic agents commonly share a therapy-limiting side effect, as they increase the overall systemic bleeding risk. A novel approach for targeted antithrombotic therapy is nanoparticles. In other therapeutic fields, nanoparticles have enabled site-specific delivery with low levels of toxicity and side effects.

Heparin and Arginine Based Plasmin Nanoformulation for Ischemic Stroke Therapy.

Ischemic stroke is the most common type of stroke and thrombolytic therapy is the only approved treatment. However, current thrombolytic therapy with tissue plasminogen activator (tPA) is often hampered by the increased risk of hemorrhage. Plasmin, a direct fibrinolytic, has a significantly superior hemostatic safety profile; however, if injected intravenously it becomes rapidly inactivated by anti-plasmin.

3D Bioprinting of Engineered Tissue Flaps with Hierarchical Vessel Networks (VesselNet) for Direct Host-To-Implant Perfusion.

Engineering hierarchical vasculatures is critical for creating implantable functional thick tissues. Current approaches focus on fabricating mesoscale vessels for implantation or hierarchical microvascular in vitro models, but a combined approach is yet to be achieved to create engineered tissue flaps. Here, millimetric vessel-like scaffolds and 3D bioprinted vascularized tissues interconnect, creating fully engineered hierarchical vascular constructs for implantation.

Wall shear rates in human and mouse arteries: Standardization of hemodynamics for in vitro blood flow assays: Communication from the ISTH SSC subcommittee on biorheology.

Hemodynamics play a central role in hemostasis and thrombosis by affecting all aspects linked to platelet functions and coagulation. In vitro flow devices are extensively used in basic research, pharmacological studies, antiplatelet agent screening, and development of diagnostic tools. Because hemodynamic conditions vary tremendously throughout the vascular tree and among different (patho)physiological processes, it is important to use flow conditions based on relevant biorheological reference ranges.

In vitro flow-based assay: From simple toward more sophisticated models for mimicking hemostasis and thrombosis.

In vitro flow-based assays are widely used to investigate the role of platelets and coagulation in hemostasis and thrombosis. Their main advantage over other assays relies on the fact that they integrate blood flow that regulates many aspects of platelet function, including adhesion, activation, and aggregation. Blood flow is also central in the regulation of coagulation through its ability to modulate the local concentrations of coagulation factors within and around thrombi.

Synthetic neural-like computing in microbial consortia for pattern recognition.

Complex biological systems in nature comprise cells that act collectively to solve sophisticated tasks. Synthetic biological systems, in contrast, are designed for specific tasks, following computational principles including logic gates and analog design. Yet such approaches cannot be easily adapted for multiple tasks in biological contexts.

Continuous Measurement of Biological Noise in Escherichia Coli Using Time-lapse Microscopy.

The protocol developed here offers a tool to enable computer tracking of Escherichia coli division and fluorescent levels over several hours. The process starts by screening for colonies that survive on minimal media, assuming that only Escherichia coli harboring the correct plasmid will be able to thrive in the specific conditions. Since the process of building large genetic circuits, requiring the assembly of many DNA parts, is challenging, circuit components are often distributed between multiple plasmids at different copy numbers requiring the use of several antibiotics.

Transforming a well into a chip: A modular 3D-printed microfluidic chip.

Organ-on-a-Chip platforms provide rich opportunities to observe interactions between different cell types under -like conditions, i.e., in the presence of flow.

In Vitro 3D Cell-Cultured Arterial Models for Studying Vascular Drug Targeting Under Flow.

The use of three-dimensional (3D) models of human arteries, which are designed with the correct dimensions and anatomy, enables the proper modeling of various important processes in the cardiovascular system. Recently, although several biological studies have been performed using such 3D models of human arteries, they have not been applied to study vascular targeting. This paper presents a new method to fabricate real-sized, reconstructed human arterial models using a 3D printing technique, line them with human endothelial cells (ECs), and study particle targeting under physiological flow.

A converging artery-sized model for shear adhesion mapping of particles.

Drug carriers for targeting cardiovascular diseases have been gaining a respectable attention, however, designing such carriers is challenging due to the biophysical complexity of the vascular system. Wall shear stress (WSS), exerted by blood flow on the endothelium surface, is a crucial factor in the circulatory system. WSS affects the adhesion and preferential accumulation of drug carriers.