Small-diameter synthetic vascular grafts that have improved hemocompatibility and patency remain an unmet clinical need due to thrombosis. A surface modification that has potential to attenuate these failure mechanisms while promoting an endothelial layer is the micropatterning of luminal surfaces. Anisotropic features have been shown to downregulate smooth muscle cell proliferation, direct endothelial migration, and attenuate platelet adhesion and activation. However, the effect of micropatterning feature size and orientation relative to whole blood flow has yet to be investigated within a systematic study. In this work, hemocompatibility of micropattern grating sizes of 2, 5, and 10 µm were investigated. The thrombogenicity of the micropattern surface modifications were characterized by quantifying FXIIa activity, fibrin formation, and static platelet adhesion . Additionally, dynamic platelet attachment and end-point fibrin formation were quantified using an established, flowing whole blood non-human primate shunt model without antiplatelet or anticoagulant therapies. We observed a higher trend in platelet attachment and significantly increased fibrin formation for larger features. We then investigated the orientation of 2 µm gratings relative to whole blood flow and found no significant differences between the various orientations for platelet attachment, rate of linear platelet attachment, or end-point fibrin formation. MicroCT analysis of micropatterned grafts was utilized to quantify luminal patency. This work is a significant step in the development of novel synthetic biomaterials with improved understanding of hemocompatibility for use in cardiovascular applications.
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http://dx.doi.org/10.3389/fphys.2022.983187 | DOI Listing |
Alzheimers Dement
December 2024
Gladstone Institutes, UCSF, San Francisco, CA, USA.
Background: Cerebrovascular alterations and innate immune activation are key features of Alzheimer's disease (AD). However, the mechanisms that link blood-brain barrier disruption to neurodegeneration are poorly understood and well-defined druggable targets at the neurovascular interface are limited.
Method: By developing a multiomic and genetic loss-of-function pipeline, we reported the transcriptomic and global phosphoproteomic landscape of blood-induced microglia activation and the causal role for fibrin in induction of neurodegenerative genes and oxidative stress pathways in innate immune cells.
Alzheimers Dement
December 2024
The UC Irvine Institute for Memory Impairments and Neurological Disorders (UCI MIND), Irvine, CA, USA.
Background: Individuals with Down syndrome (DS) have an increased genetic risk of developing Alzheimer's disease (AD), with most adults developing AD neuropathology in their 40s. Despite having a low frequency of systemic vascular risk factors such as hypertension and atherosclerosis, adults with DS display cerebrovascular pathology, including microbleeds, microinfarcts, and cerebral amyloid angiopathy. This suggests that blood-brain barrier (BBB) integrity may be compromised allowing the extravasation of blood proteins in the brain parenchyma.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Dongcheng, Beijing, 100000, China.
There are inconsistent results pertaining to risk factors for venous thromboembolism (VTE) in patients following urologic surgeries. We attempted to establish a visualization model to shed further light upon this topic. Consequently, a total of 436 patients who were tested for VTE following urologic surgeries were retrospectively enrolled.
View Article and Find Full Text PDFMediators Inflamm
January 2025
Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
Antiphospholipid antibody syndrome (APS) is an autoimmune disease characterized by the presence of 2-glycoprotein I (2-GPI)-targeting antiphospholipid antibodies (aPLs) and vascular thrombosis or obstetrical complications. One of its severe manifestations is nephropathy. To examine the role of type I interferon (IFN) and therapeutic potential of tyrosine kinase 2 (Tyk2) inhibition, we administered BMS-986202, a novel Tyk2 inhibitor, in a mouse model of APS nephropathy.
View Article and Find Full Text PDFNeurol Neurochir Pol
December 2024
Department of Thromboembolic Diseases, Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland.
Clinical Rationale For Study: We have reported that intracerebral haemorrhage (ICH) of unknown cause at a young age is associated with lower prothrombin and factor VII and higher antithrombin activity, along with the formation of looser fibrin networks displaying enhanced lysability. Patients with mild-to-moderate bleeding of unknown cause have elevated levels of free plasma tissue factor pathway inhibitor alpha (fTFPIα), inhibiting the tissue factor-factor VII complex and prothrombinase.
Aim Of Study: We hypothesised that patients with an intracerebral haemorrhage (ICH) of unknown cause may also exhibit higher fTFPIα.
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