Biology subjects

Redaelli, A.

Publications and source records attributed to Redaelli, A..

3 recordsLinked to original sources

bioRxiv2025

A Microfluidic Blood Vessel-On-Chip Model of Thrombosis

BackgroundThrombus formation is regulated by the interplay between endothelial cells (EC), platelets and coagulation factors. However, most in vitro assays used to study thrombosis and develop anti-thrombotic therapies do not include the endothelium. ObjectiveTo develop a thrombus-on-chip model that includes endothelium and whole blood and allows for manipulation of extracellular matrix (ECM), shear stress and the addition of multiple cell types. MethodsA cylindrical vessel was created in a collagen matrix using the needle-based fabrication technique in a microfluidic device. Human umbilical vein EC (HUVEC) or endothelial colony-forming cells (ECFC) were cultured in the channel, with continuous monodirectional media turnover. Immunostaining and permeability measurement validated confluence and integrity of the monolayer. To investigate thrombosis, whole blood from healthy donors was perfused through TNF--activated or untreated EC-lined vessels. Image analysis and time-lapse microscopy were used to quantify labelled platelet adhesion and fibrin deposition. ResultsTNF- treatment resulted in increased platelet adhesion and fibrin deposition compared to control vessels. TNF-induced endothelial activation was confirmed by upregulation of adhesion molecules ICAM-1, E-selectin and tissue factor (TF). Thrombus formation in TNF- treated vessels was inhibited by an anti-TF antibody. In ECFC vessels, platelet adhesion and fibrin deposition were comparable to HUVEC, supporting feasibility of patient-based studies. ConclusionsWe developed a perfused thrombus-on-chip model that combines key elements of thrombus formation including endothelium. The model is amenable to independent control of microenvironmental stimuli, crosstalk with tissue-specific cells, and the inclusion of patients own cells and blood for precision medicine studies. ESSENTIALS- The endothelium is a key contributor to thrombosis - Standard in vitro methods to study thrombosis do not include the endothelium - We have developed a thrombus-on-a-chip model of thromboinflammation to measure live platelet adhesion and fibrin deposition on activated endothelium - Using endothelial colony forming cells (ECFC), we show that the method is suitable for patient studies with autologous endothelium and blood

bioengineering↗

bioRxiv2024

Computational hemodynamic indices to identify Transcatheter Aortic Valve Implantation degeneration

PurposeStructural Valve Deterioration (SVD) is the main limiting factor to the long-term durability of bioprosthetic valves, which are used for Transcatheter Aortic Valve Implantation (TAVI). The aim of this study is to perform a patient-specific computational analysis of post-TAVI blood dynamics to identify hemodynamic indices that correlate with a premature onset of SVD. MethodsThe study population comprises two subgroups: patients with and without SVD at long-term follow-up exams. Starting from pre-operative CT images, we created reliable post-TAVI scenarios by virtually inserting the bioprosthetic valve (stent and leaflets), and we performed numerical simulations imposing realistic inlet conditions based on patient-specific data. The numerical results were post-processed to build suitable synthetic scores based on normalized hemodynamic indices. ResultsWe defined three synthetic scores, based on hemodynamic indices evaluated in different contexts: on the leaflets, in the ascending aorta, and in the whole domain. Our proposed synthetic scores are able to clearly isolate the SVD group. Notably, we found that leaflets OSI individually shows statistically significant differences between the two subgroups of patients. ConclusionThe results of this computational study suggest that blood dynamics may play an important role in creating the conditions that lead to SVD. More-over, the proposed synthetic scores could provide further indications for clinicians in assessing and predicting TAVI valves long-term performance.

bioengineering↗

bioRxiv2021

Physiologic flow-conditioning limits vascular dysfunction in engineered human capillaries

Hemodynamics play a central role in the health and disease of the coronary and peripheral vascular systems. Vessel-lining endothelial cells are known mechanosensors, responding to disturbances in flow - with mechanosensitivity hypothesized to change in response to metabolic demands. The health of our smallest microvessels have been lauded as a prognostic marker for cardiovascular health. Yet, despite numerous animal models, studying these small vessels has proved difficult. Microfluidic technologies have allowed a number of 3D vascular models to be developed and used to investigate human vessels. Here, two such systems are employed for examining 1) interstitial flow effects on neo-vessel formation, and 2) the effects of flow-conditioning on vascular remodelling following sustained static culture. Interstitial flow is shown to enhance early vessel formation via significant remodeling of vessels and interconnected tight junctions of the endothelium. In formed vessels, continuous flow maintains a stable vascular diameter and causes significant remodeling, contrasting the continued anti-angiogenic decline of statically cultured vessels. This study is the first to couple complex 3D computational flow distributions and microvessel remodeling from microvessels grown on-chip (exposed to flow or no-flow conditions). Flow-conditioned vessels (WSS < 1Pa for 30 micron vessels) increase endothelial barrier function, result in significant changes in gene expression and reduce reactive oxygen species and anti-angiogenic cytokines. Taken together, these results demonstrate microvessel mechanosensitivity to flow-conditioning, which limits deleterious vessel regression in vitro, and could have implications for future modeling of reperfusion/no-flow conditions.

bioengineering↗