scholarly journals The Role of Biodegradable Poly-(L-lactide)-Based Polymers in Blood Cell Activation and Platelet-Monocyte Interaction

2021 ◽  
Vol 22 (12) ◽  
pp. 6340
Author(s):  
Anne Strohbach ◽  
Friedemann Maess ◽  
Katharina Wulf ◽  
Svea Petersen ◽  
Niels Grabow ◽  
...  
Keyword(s):  
Blood Cell ◽  
Cell Activation ◽  
Light Transmission ◽  
Blood Compatibility ◽  
Biological Response ◽  
Shear Rates ◽  
High Shear Rates ◽  
Biomaterial Surfaces ◽  
Biodegradable Poly

The main purpose of new stent technologies is to overcome unfavorable material-related incompatibilities by producing bio- and hemo-compatible polymers with anti-inflammatory and anti-thrombogenic properties. In this context, wettability is an important surface property, which has a major impact on the biological response of blood cells. However, the influence of local hemodynamic changes also influences blood cell activation. Therefore, we investigated biodegradable polymers with different wettability to identify possible aspects for a better prediction of blood compatibility. We applied shear rates of 100 s−1 and 1500 s−1 and assessed platelet and monocyte activation as well as the formation of CD62P+ monocyte-bound platelets via flow cytometry. Aggregation of circulating platelets induced by collagen was assessed by light transmission aggregometry. Via live cell imaging, leukocytes were tracked on biomaterial surfaces to assess their average velocity. Monocyte adhesion on biomaterials was determined by fluorescence microscopy. In response to low shear rates of 100 s−1, activation of circulating platelets and monocytes as well as the formation of CD62P+ monocyte-bound platelets corresponded to the wettability of the underlying material with the most favorable conditions on more hydrophilic surfaces. Under high shear rates, however, blood compatibility cannot only be predicted by the concept of wettability. We assume that the mechanisms of blood cell-polymer interactions do not allow for a rule-of-thumb prediction of the blood compatibility of a material, which makes extensive in vitro testing mandatory.

scholarly journals In vitro blood compatibility evaluation method: incubating while rotating hemodialyzers filled with fresh human blood

2020 ◽  
Author(s):  
Kinue Kamata ◽  
Yoshihiro Hatanaka ◽  
Hiromi Tanaka ◽  
Satoru Inoue ◽  
Yusuke Tokimizu ◽  
...  
Keyword(s):  
Vitamin E ◽  
Blood Cell ◽  
Experimental Method ◽  
Human Blood ◽  
Evaluation Method ◽  
Blood Compatibility ◽  
In Vitro Evaluation ◽  
Dialysis Membranes ◽  
Anti Inflammatory

AbstractOne of the often-used methods for in vitro evaluation of the blood compatibility of hemodialysis membranes is the circulation of human blood through a miniaturized hemodialyzer. The use of a rather small amount of human blood in its evaluation is one advantage of this method. However, because it is manufactured by a different process than actual ones, a miniaturized hemodialyzer membrane cannot always preserve the properties of actual hemodialyzers. To address this problem, we established a new experimental method that uses a relatively small amount of human blood and actual dialyzers. In this method, a test hemodialyzer and a control hemodialyzer filled with human blood obtained from the same donor is slowly rotated to prevent spontaneous blood cell sedimentation for 4 h at 37 °C. By use of this method, we were able to compare blood compatibility between a polysulfone (PS) membrane and a vitamin E (VE)-bonded PS membrane in terms of their relative antithrombotic, antioxidative, and anti-inflammatory properties. Consistent with many previous reports, the results clearly showed that compared with the PS membrane, VE-bonded PS membrane is more blood compatible. These findings suggest that our method is applicable, at least to in vitro blood compatibility evaluation of PS type dialysis membranes.

scholarly journals A novel nucleotide-based thrombin inhibitor inhibits clot-bound thrombin and reduces arterial platelet thrombus formation

Blood ◽  
1994 ◽  
Vol 83 (3) ◽  
pp. 677-682 ◽  
Author(s):  
WX Li ◽  
AV Kaplan ◽  
GW Grant ◽  
JJ Toole ◽  
LL Leung
Keyword(s):  
Ex Vivo ◽  
Platelet Rich Plasma ◽  
Thrombus Formation ◽  
Thrombin Inhibitors ◽  
Thrombin Inhibitor ◽  
Shear Rates ◽  
High Shear Rates ◽  
Dependent Inhibition ◽  
Platelet Thrombus

A novel thrombin inhibitor based on single-stranded (ss) deoxynucleotides with the sequence GGTTGGTGTGGTTGG (thrombin aptamer) has been recently discovered. In this study, we tested its efficacy in inhibiting clot-bound thrombin activity and platelet thrombus formation in an ex vivo whole artery angioplasty model. The thrombin aptamer showed a specific dose-dependent inhibition of thrombin-induced platelet aggregation (0.5 U/mL) in human platelet-rich plasma, with an IC50 of approximately 70 to 80 nmol/L. In an in vitro clot-bound thrombin assay system, heparin, used at clinically relevant concentrations of 0.2 U/mL and 0.4 U/mL, was ineffective in inhibiting clot-bound thrombin (6.5% and 34.9% inhibition at 0.2 U/mL and 0.4 U/mL, respectively). In contrast, the thrombin aptamer at an equivalent anticoagulant concentration inhibited clot-bound thrombin (79.7% inhibition). In an ex vivo whole artery angioplasty model, the thrombin aptamer markedly suppressed the generation of fibrinopeptide A (FPA), whereas heparin at 2 U/mL was ineffective. Compared with a scrambled ssDNA control, the thrombin aptamer reduced platelet deposition by 34.5% +/- 5% (mean +/- SEM, n = 4, P = .09) at low shear rates (approximately 200 s-1) and 61.3% +/- 11% (mean +/- SEM, n = 4, P = .05) at high shear rates (approximately 850 s-1). Thrombin aptamers based on ssDNA molecules represent a new class of thrombin inhibitors with potent anticoagulant and antithrombotic properties.

scholarly journals Preparation of phospholipid-based polycarbonate urethanes for potential applications of blood-contacting implants

2020 ◽  
Vol 7 (5) ◽  
pp. 491-504
Author(s):  
Peichuang Li ◽  
Wanhao Cai ◽  
Xin Li ◽  
Kebing Wang ◽  
Lei Zhou ◽  
...  
Keyword(s):  
Microphase Separation ◽  
Blood Compatibility ◽  
Ex Vivo ◽  
Raw Materials ◽  
Direct Synthesis ◽  
Animal Experiments ◽  
Biological Response ◽  
Superior Performance ◽  
Scanning Calorimetry

Abstract Polyurethanes are widely used in interventional devices due to the excellent physicochemical property. However, non-specific adhesion and severe inflammatory response of ordinary polyurethanes may lead to severe complications of intravenous devices. Herein, a novel phospholipid-based polycarbonate urethanes (PCUs) were developed via two-step solution polymerization by direct synthesis based on functional raw materials. Furthermore, PCUs were coated on biomedical metal sheets to construct biomimetic anti-fouling surface. The results of stress–strain curves exhibited excellent tensile properties of PCUs films. Differential scanning calorimetry results indicated that the microphase separation of such PCUs polymers could be well regulated by adjusting the formulation of chain extender, leading to different biological response. In vitro blood compatibility tests including bovine serum albumin adsorption, fibrinogen adsorption and denaturation, platelet adhesion and whole-blood experiment showed superior performance in inhibition non-specific adhesion of PCUs samples. Endothelial cells and smooth muscle cells culture tests further revealed a good anti-cell adhesion ability. Finally, animal experiments including ex vivo blood circulation and subcutaneous inflammation animal experiments indicated a strong ability in anti-thrombosis and histocompatibility. These results high light the strong anti-adhesion property of phospholipid-based PCUs films, which may be applied to the blood-contacting implants such as intravenous catheter or antithrombotic surface in the future.

In Vitro Blood Damage by High Shear Flow: Human versus Porcine Blood

2002 ◽  
Vol 25 (4) ◽  
pp. 306-312 ◽  
Author(s):  
S. Klaus ◽  
S. Körfer ◽  
K. Mottaghy ◽  
H. Reul ◽  
B. Glasmacher
Keyword(s):  
Human Blood ◽  
Heart Valves ◽  
High Shear ◽  
Blood Damage ◽  
Shear Rates ◽  
Porcine Blood ◽  
High Shear Rates ◽  
Blood Pumps ◽  
Artificial Heart Valves

Devices for modern heart support are minimized to reduce priming blood volume and contact area with foreign surfaces. Their flow fields are partly governed by very high velocity gradients. In order to investigate blood damage, porcine and human blood was passed through a narrow Couette type shear gap applying defined high shear rates within the typical range for devices such as blood pumps or artificial heart valves (γ = 1800/s to 110,000/s for 400 ms). Traumatization profiles of both blood species were recorded in terms of hemolysis and platelet count. Sublethal damage in terms of platelet (PF4) and complement activation (C5a) was additionally measured for human blood. Results for porcine and human blood were very similar. Hemolysis was not started until critical shear rates of about 80,000/s. Impact on platelets was severe with drops in cell count of up to 65% (at γ = 55,000/s to 110,000/s) likely to set stronger limits to the design layout of devices than hemolysis. Concentrations of PF4 and C5a clearly increased with shear rate exhibiting stronger gradients where hemolysis started. Due to the similar results of porcine and human blood for hemolysis and platelet drop, porcine blood seems to be suitable for device testing. Selection of blood species would thus depend on handling, availability and analysis demands.

scholarly journals Effect of Air Exposure and Suction on Blood Cell Activation and Hemolysis in an In Vitro Cardiotomy Suction Model

ASAIO Journal ◽  
2013 ◽  
Vol 59 (5) ◽  
pp. 474-479 ◽  
Author(s):  
Ahmed M. El-Sabbagh ◽  
Cory J. Toomasian ◽  
John M. Toomasian ◽  
Guerlain Ulysse ◽  
Terry Major ◽  
...  
Keyword(s):  
Blood Cell ◽  
Cell Activation ◽  
Air Exposure ◽  
Cardiotomy Suction

scholarly journals Biorheology of occlusive thrombi formation under high shear: in vitro growth and shrinkage

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Britt J. M. van Rooij ◽  
Gábor Závodszky ◽  
Alfons G. Hoekstra ◽  
David N. Ku
Keyword(s):  
Platelet Rich Plasma ◽  
Lag Time ◽  
Flow Chamber ◽  
High Shear ◽  
Shear Rates ◽  
High Shear Rates ◽  
Dependent Behavior ◽  
Platelet Aggregate ◽  
Contraction Angle

Abstract Occlusive thrombi formed under high flow shear rates develop very rapidly in arteries and may lead to myocardial infarction or stroke. Rapid platelet accumulation (RPA) and occlusion of platelet-rich thrombi and clot shrinkage have been studied after flow arrest. However, the influence of margination and shear rate on occlusive clot formation is not fully understood yet. In this study, the influence of flow on the growth and shrinkage of a clot is investigated. Whole blood (WB) and platelet-rich plasma (PRP) were perfused at high shear rates (> 3,000 s−1) through two microfluidic systems with a stenotic section under constant pressure. The stenotic section of the two devices are different in stenotic length (1,000 vs 150 μm) and contraction angle of the stenosis (15° vs 80°). In all experiments, the flow chamber occluded in the stenotic section. Besides a significantly increased lag time and decreased RPA rate for PRP compared to WB (p < 0.01), the device with a shorter stenotic section and steeper contraction angle showed a shear-dependent occlusion and lag time for both PRP and WB. This shear-dependent behavior of the platelet aggregate formation might be caused by the stenotic geometry.

scholarly journals Interaction of Human Platelets with Subndotrelium: Implications for Measurement of Defects in Platelet Function

1977 ◽  
Author(s):  
V.T. Turitto ◽  
H.J. Weiss ◽  
D.S. Cohen
Keyword(s):  
Platelet Reactivity ◽  
Blood Platelets ◽  
Human Platelets ◽  
Shear Rates ◽  
High Shear Rates ◽  
Contact Adhesion ◽  
Human Blood Platelets ◽  
Low Shear ◽  
Platelet Transport

An in Vitro perfusion technique introduced by Baumgartner has been used to investigate the interaction of human blood platelets with subendothelium of rabbit aortas. Platelet contact, adhesion (spreading) and the formation of ndcxothrombi were measured directly by use of a morphometric technique for a variety of exposure times (1 to 40 min) and a physiological range of flow rates (shear rates varying from 50 to 830 sec-1). A theory accounting for platelet transport through the blood and the platelet reactivity at the vessel surface Indicated platelet transport to be the controlling influence on platelet attachment. Under low shear conditions platelet attachment is unaltered by moderate changes in platelet reactivity. The results suggest that high shear rates (greater than 800 sec-1) are necessary for a sensitive measurement of defects in platelet attachment and that experimental devices which employ low shear conditions are limited in measuring such defects.

An In Vitro Study of Transendothelial Albumin Transport in a Steady State Pipe Flow at High Shear Rates

1976 ◽  
Vol 98 (3) ◽  
pp. 488-493 ◽  
Author(s):  
Thomas H. Reif ◽  
Robert M. Nerem ◽  
Francis A. Kulacki
Keyword(s):  
Steady State ◽  
Shear Rate ◽  
Pressure Drop ◽  
Vessel Wall ◽  
High Shear ◽  
Flow Measurements ◽  
Shear Rates ◽  
High Shear Rates ◽  
Wall Shear

The effect of high wall shear rates on the uptake of 131I-albumin by the arterial wall has been studied in vitro using common carotid arteries excised from anesthetized dogs and perfused with a steady state flow of homologous serum. Wall uptake was found to depend nearly linearly upon wall shear rate. The overall transport of 131I-albumin from the perfusing fluid to the vessel wall appears to be rate controlled by a shear dependent fluid-wall interface process. This study was carried out at high shear rates for flows which were transitional and turbulent. Because of the complexity of such flows, direct measurements of pressure drop were used to determine the shear rate at the vessel wall. Simultaneous pressure drop and flow measurements allowed the determination of the friction factor as a function of Reynolds number; results obtained at the higher Reynolds numbers correspond to those for a rigid pipe with a relative roughness of 0.05.

Platelet Birth.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. sci-39-sci-39
Author(s):  
Elisabeth Cramer-Bordé ◽  
Ian M. Morison ◽  
Claude Capron ◽  
Claire Dunois-Lardé ◽  
Dominique Baruch
Keyword(s):  
Bone Marrow ◽  
Cytochrome C ◽  
High Shear ◽  
Shear Forces ◽  
Platelet Production ◽  
Shear Rates ◽  
High Shear Rates ◽  
Apoptotic Activity ◽  
Platelet Formation

Abstract How and where human platelets get born are two questions still harboring great mystery. In vivo and in vitro approaches have contributed to a better understanding of the phenomenon. The recent study of a family with congenital autosomal-dominant thrombocytopenia showed ectopic platelet release in the bone marrow of the affected individuals. Further, molecular studies identified a new mutation in the gene encoding cytochrome c, which yields a cytochrome c with enhanced apoptotic activity. It is known that platelet birth occurs when megakaryocytes (MKs) undergo compartmentalized apoptotic activity. In this family case, enhanced apoptosis in MKs led to the premature release of platelets in the bone marrow, preventing their natural birth into the circulation after MK migration and causing thrombocytopenia. A similar finding, i.e., platelet birth in the marrow, was made in Wiskott Aldrich syndrome, providing a pathophysiological explanation for the thrombocytopenia, related to impaired migration capacities of MKs upon SDF chemotaxis. Indeed, direct platelet delivery in the human bone marrow space is not currently observed. However, maturing MKs are located close to the marrow sinusoids whose barrier they are able to cross, and entire MKs have been seen in the circulating blood where they become exposed to circulatory shear forces. Since the rate of platelet shedding in culture systems is remarkably low, we hypothesised that a missing element for efficient platelet production in static culture systems would be shear stress. Thus, we exposed human MKs, cultured in vitro until full maturation, to a substrate of matrix protein and high shear rates equivalent to those encountered in capillaries and small arteries. Cells were observed by real-time videomicroscopy, immunofluorescence, and electron microscopy. Shear forces specifically induced a sequence of morphological changes, converting mature MKs into proplatelets, and platelets, which consistently detached from the mother cells into the flow,, at a rate 20 times higher than static culture conditions. Using specific antibody inhibition, we showed the major involvement of GPIb in platelet formation, since its blockade inhibited MK adhesion and subsequent platelet formation. In addition, aIIbb3 was essential for firm MK anchorage, which was required for subsequent platelet formation. These experiments show that MK exposure to high shear rates promotes platelet production via GPIb (and secondarily aIIbb3) interactions with vascular matrix proteins. In conclusion, the above studies converge to present evidence that platelet birth takes place in circulating blood, being regulated by the migratory and apoptotic capacities of MKs and dependent on GPIb and hemodynamic forces.

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