The vascular endothelium and shear stress are critical determinants of physiological hemostasis and platelet function in vivo, yet current diagnostic and monitoring devices do not fully incorporate endothelial function under flow in their assessment and, therefore, they can be unreliable and inaccurate. It is challenging to include the endothelium in assays for clinical laboratories or point-of-care settings because living cell cultures are not sufficiently robust. Here, we describe a microfluidic device that is lined by a human endothelium that is chemically fixed, but still retains its ability to modulate hemostasis under continuous flow in vitro even after few days of storage. This device lined with a fixed endothelium supports formation of platelet-rich thrombi in the presence of physiological shear, similar to a living arterial vessel. We demonstrate the potential clinical value of this device by showing that thrombus formation and platelet function can be measured within minutes using a small volume (0.5 mL) of whole blood taken from subjects receiving antiplatelet medications. The inclusion of a fixed endothelial microvessel will lead to biomimetic analytical devices that can potentially be used for diagnostics and point-of-care applications.Electronic supplementary materialThe online version of this article (doi:10.1007/s10544-016-0095-6) contains supplementary material, which is available to authorized users.

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International audienceIn the present article, we report the synthesis of titanate nanotubes and nanoribbons with controlled morphology, structure, and chemical composition depending on the main parameters of the synthesis. Hydrothermal processing time, grain size of the precursor, type of agitation, and acid treatment were investigated, and the principal controversies mentioned in the literature such as nanotube crystallographic structure, their chemical composition, and acid treatment impact are discussed. These controversies may be due to the heterogeneities present in all the samples and are rarely considered in the literature. These nanostructures were characterized by Raman spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction (XRD), and transmission electron microscopy. A careful desummation of the first XRD peaks revealed the presence of both nanosheets and nanotubes and allowed an estimation of their proportions. In addition, the titanate nanotube section is observed to be not perfectly circular but rather elliptic. Moreover, the first acid treatment effect is shown to remove any trace of sodium and structural water. The second effect of acid washing is a morphological evolution

Actively contractile cardiomyocyte (CM) monolayer represents an interesting tool to study both cardiac diseases and injuries. However, this model is poorly transfectable with conventional agents. Consequently, there is a need to develop new carriers that could overcome this problem. Titanate nanotubes (TiONts) could be a potential candidate due to possibly higher cell uptake as a direct consequence of their shape. On the basis of this rationale, TiONts were assessed for their cytotoxicity and internalization pathways. Cytotoxicity was assessed for TiONts either functionalized with PEI or unfunctionalized and its spherical counterpart P25 TiO2. No cytotoxic effect was observed under TiONts, TiONts-PEI1800 and P25 TiO2 exposed conditions. The tubular morphology was found to be an important parameter promoting internalization while reversing the charge was assessed as non-additional. Internalization was found to occur by endocytosis and diffusion through the membrane. A preliminary transfection study indicated the potential of TiONts as a nanocarrier.

In the present study, we report the dispersion of titanate nanotubes (TiONts) via polymer grafting (PolyEthylene Glycol, PEG) or polymer adsorption (polyethylene imine, PEI) where different TiONts/polymer ratios have been investigated. The TiONts/PEI and TiONts/PEG nanohybrids were characterized by scanning and transmission electron microscopy as well as by zeta potential measurements in order to determine both their dispersion state and stability in water (at different pH for zetametry). The nature of the chemical bonds at the surface of these nanohybrids was investigated by Fourier-transformed infrared (FTIR) spectroscopy while the grafting densities of PEG on the nanotubes were quantified by thermogravimetric analyses (TGA). The nanohybrids reported here are promising tools for biotechnology applications due to their tubular morphology, their very good dispersion in water and the reactivity of their surface.

Esophagitis is the principle dose-limiting toxicity of weekly paclitaxel and thoracic radiation in the outpatient setting. A phase II trial using concurrent radiation and paclitaxel at the MTD of 60 mg/m2/wk is underway.

T he majority of the patients having an emergent large vessel occlusion (ELVO) may develop severe and permanent neurological morbidity or death without urgent and successful treatment. Recently published randomized clinical trials have all shown that intra-arterial (IA) treatments in combination with intravenous recombinant tissuetype plasminogen activator (r-tPA) when indicated leads to improved clinical outcomes as compared with standard medical therapy alone. [1][2][3][4] Compared with prior randomized trials that showed no benefit for IA treatment, 5-7 most patients enrolled in these studies received stent-retriever mechanical thrombectomy (MT) that resulted in higher rates of modified thrombolysis in cerebral infarction score (mTICI) 2b or 3 recanalization. Despite high rates of successful recanalization, nearly half of the patients remained functionally dependent (mRS≥3) after 90 days.Background and Purpose-The goal of this study is to combine temporary endovascular bypass (TEB) with a novel shearactivated nanotherapeutic (SA-NT) that releases recombinant tissue-type plasminogen activator (r-tPA) when exposed to high levels of hemodynamic stress and to determine if this approach can be used to concentrate r-tPA at occlusion sites based on high shear stresses created by stent placement. Methods-A rabbit model of carotid vessel occlusion was used to test the hypothesis that SA-NT treatment coupled with TEB provides high recanalization rates while reducing vascular injury. We evaluated angiographic recanalization with TEB alone, intra-arterial delivery of soluble r-tPA alone, or TEB combined with 2 doses of intra-arterial infusion of either the SA-NT or soluble r-tPA. Vascular injury was compared against stent-retriever thrombectomy. Results-Shear-targeted delivery of r-tPA using the SA-NT resulted in the highest rate of complete recanalization when compared with controls (P=0.0011). SA-NT (20 mg) had a higher likelihood of obtaining complete recanalization as compared with TEB alone (odds ratio 65.019, 95% confidence interval 1.77, >1000; P=0.0231), intra-arterial r-tPA alone (odds ratio 65.019, 95% confidence interval 1.77, >1000; P=0.0231), or TEB with soluble r-tPA (2 mg; odds ratio 18.78, 95% confidence interval 1. 28, 275.05; P=0.0322). Histological analysis showed circumferential loss of endothelium restricted to the area where the TEB was deployed; however, there was significantly less vascular injury using a TEB as compared with stent-retriever procedure (odds ratio 12.97, 95% confidence interval 8.01, 21.02; P<0.0001). Conclusions-A novel intra-arterial, nanoparticle-based thrombolytic therapy combined with TEB achieves high rates of complete recanalization. Moreover, this approach reduces vascular trauma as compared with stent-retriever thrombectomy. 14 This observation is supported by results of histopathologic exams from animal studies, where extensive endothelial damage was observed after stent retriever usage. [15][16][17] Focal denudation of the vascular endothelium results in exposure of a hi...

Platelets are crucial for normal hemostasis; however, their hyperactivation also contributes to many potentially lethal pathologies including myocardial infarction, stroke, and cancer. We hypothesized that modified platelets lacking their aggregation and activation capacity could act as reversible inhibitors of platelet activation cascades. Here, we describe the development of detergent-extracted human modified platelets (platelet decoys) that retained platelet binding functions but were incapable of functional activation and aggregation. Platelet decoys inhibited aggregation and adhesion of platelets on thrombogenic surfaces in vitro, which could be immediately reversed by the addition of normal platelets; in vivo in a rabbit model, pretreatment with platelet decoys inhibited arterial injury–induced thromboembolism. Decoys also interfered with platelet-mediated human breast cancer cell aggregation, and their presence decreased cancer cell arrest and extravasation in a microfluidic human microvasculature on a chip. In a mouse model of metastasis, simultaneous injection of the platelet decoys with tumor cells inhibited metastatic tumor growth. Thus, our results suggest that platelet decoys might represent an effective strategy for obtaining antithrombotic and antimetastatic effects.