Search bioRxiv⌕ Search

Biology subjects

Procopio, E.

Publications and source records attributed to Procopio, E..

2 recordsLinked to original sources

Development of a clot-adhesive coating to improve the performance of thrombectomy devices

BackgroundThe first-pass complete recanalization by mechanical thrombectomy (MT) for the treatment of stroke remains limited due to the poor integration of the clot within current devices. Aspiration can help retrieval of the main clot but fails to prevent secondary embolism in the distal arterial territory. The dense meshes of extracellular DNA, recently described in stroke-related clots, might serve as an anchoring platform for MT devices. ObjectiveEvaluate the potential of DNA reacting surface to aid the retention of the main clot as well as of its small fragments within the thrombectomy device and improve the potential of MT procedures. MethodsDevice-suitable alloy experimental samples were coated with 15 different compounds and contacted with extracellular DNA or with human peripheral whole blood, to compare their binding to DNA versus flowing blood elements, in vitro. Clinical-grade MT devices were coated with two selected compounds and evaluated in functional bench tests aiming to studying clot retrieval and distal emboli release, concomitant with contact aspiration, using an M1 occlusion model. ResultsBinding properties of samples coated with all compounds were increased for DNA ({approx} 3-fold) and decreased ({approx} 5-fold) for blood elements, essentially platelet, as compared to the bare alloy samples, in vitro. Functional testing showed that surface modification with DNA-binding compounds improved clot retrieval and significantly reduced secondary embolism during experimental recanalization of occluded artery 3D model by thrombectomy procedures. ConclusionOur results suggest that device coating with DNA-binding compounds can considerably improve the outcome of MT procedures in stroke patients. What is already known on this topic - New mechanical thrombectomy device are being improved on the conformation and shape to increase the interaction clot on the physical point of view. However, none interact specifically with the structure or composition of the clot. What this study adds - The design of a chemical surface modification of the device opens the way for a specific targeting tool to increase the interaction with the clot on the molecular level. How this study might affect research, practice or policy - This new surface modification, which can be applied to all commercially available mechanical thrombectomy devices, leads to a decrease in secondary embolization which cannot and is not monitored during the procedure and responsible for new territory damage.

bioengineering↗

Involvement of an IgE/Mast cell/B cell amplification loop in abdominal aortic aneurysm progression

AimsIgE type immunoglobulins and their specific effector cells, mast cells (MCs), are associated with abdominal aortic aneurysm (AAA) progression. In parallel, immunoglobulin-producing B cells, organised in tertiary lymphoid organs (TLOs) within the aortic wall, have also been linked to aneurysmal progression. We aimed at investigating the potential role and mechanism linking local MCs, TLO B cells, and IgE production in aneurysmal progression. Methods and ResultsThrough histological assays conducted on human surgical samples from AAA patients, we uncovered that activated MCs were enriched at sites of unhealed haematomas, due to subclinical aortic wall fissuring, in close proximity to adventitial IgE+ TLO B cells. Remarkably, in vitro the IgEs deriving from these samples enhanced MC production of IL-4, a cytokine which favors IgE class-switching and production by B cells. Finally, the role of MCs in aneurysmal progression was further analysed in vivo in ApoE-/- mice subjected to angiotensin II infusion aneurysm model, through MC-specific depletion after the establishment of dissecting aneurysms. MC-specific depletion improved intramural haematoma healing and reduced aneurysmal progression. ConclusionsOur data suggest that MC located close to aortic wall fissures are activated by adventitial TLO B cell-produced IgEs and participate to their own activation by providing support for further IgE synthesis through IL-4 production. By preventing prompt repair of aortic subclinical fissures, such a runaway MC activation loop could precipitate aneurysmal progression, suggesting that MC-targeting treatments may represent an interesting adjunctive therapy for reducing AAA progression.

pathology↗