The Experts below are selected from a list of 213 Experts worldwide ranked by ideXlab platform
William R. Wagner - One of the best experts on this subject based on the ideXlab platform.
-
decreased Platelet Deposition in sis based vascular grafts via covalent conjugation of raft polymers
2018 IX International Seminar of Biomedical Engineering (SIB), 2018Co-Authors: Karen T Valenciarivero, Juan C Cruz, Juan C Briceno, Antonio Dramore, Jonathan Vande P Geest, William R. WagnerAbstract:The marked tendency to promote thrombogenesis is a major obstacle for the implementation at the clinical level, of regenerative vascular grafts derived from extracellular matrices such as the small intestinal submucosa (SIS). SIS has around 66% (w/w) content of the extremely thrombogenic type I Collagen, which is appropriate for regeneration purposes, but still problematic for cardiovascular applications. To overcome this major hurdle, we covalently conjugated addition–fragmentation chain-transfer (RAFT) polymerized macromolecules of Zwitterionic Phosphorylcholine (PC) on dried SIS tubes previously formed from decellularized wet sheets. Our results indicate that even after a low covalent conjugation yield via 1-Ethyl-3-(3dimethylaminopropyl) carbodiimide (EDC), Platelet Deposition decreased by about 94% with respect to the unmodified surface. This was also the case when compared with the commercially available vascular graft material expanded polytetrafluoroethylene (ePTFE), where Platelet Deposition decreased by nearly 93% Thermal stability of modified SIS as well as regenerative and proliferation abilities remained unchanged as evidenced by constant melting temperatures and high growth levels of HUVEC cells after 3 and 8 days. Low cytotoxic levels were detected, and mechanical properties were improved, resembling the mechanical behavior of the native carotid artery. The combination of attributes of the modified material make it attractive for the next generation of regenerative vascular grafts.
-
real time visualization and characterization of Platelet Deposition under flow onto clinically relevant opaque surfaces
Journal of Biomedical Materials Research Part A, 2015Co-Authors: Megan A. Jamiolkowski, Joshua R. Woolley, Marina V. Kameneva, James F. Antaki, William R. WagnerAbstract:Although the thrombogenic nature of the surfaces of cardiovascular devices is an important aspect of blood biocompatibility, few studies have examined Platelet Deposition onto opaque materials used for these devices in real time. This is particularly true for the metallic surfaces used in current ventricular assist devices (VADs). Using hemoglobin depleted red blood cells (RBC ghosts) and long working distance optics to visualize Platelet Deposition, we sought to perform such an evaluation. Fluorescently labeled Platelets mixed with human RBC ghosts were perfused across six opaque materials (a titanium alloy (Ti6Al4V), silicon carbide (SiC), alumina (Al2O3), 2-methacryloyloxyethyl phosphorylcholine polymer coated Ti6Al4V (MPC-Ti6Al4V), yttria partially stabilized zirconia (YZTP), and zirconia toughened alumina (ZTA)) for 5 min at wall shear rates of 400 and 1000 s−1. Ti6Al4V had significantly increased Platelet Deposition relative to MPC-Ti6Al4V, Al2O3, YZTP, and ZTA at both wall shear rates (p < 0.01). For all test surfaces, increasing the wall shear rate produced a trend of decreased Platelet adhesion. The described system can be a utilized as a tool for comparative analysis of candidate blood-contacting materials with acute blood contact. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1303–1311, 2015.
-
Real time visualization and characterization of Platelet Deposition under flow onto clinically relevant opaque surfaces.
Journal of biomedical materials research. Part A, 2014Co-Authors: Megan A. Jamiolkowski, Joshua R. Woolley, Marina V. Kameneva, James F. Antaki, William R. WagnerAbstract:Although the thrombogenic nature of the surfaces of cardiovascular devices is an important aspect of blood biocompatibility, few studies have examined Platelet Deposition onto opaque materials used for these devices in real time. This is particularly true for the metallic surfaces used in current ventricular assist devices (VADs). Using hemoglobin depleted red blood cells (RBC ghosts) and long working distance optics to visualize Platelet Deposition, we sought to perform such an evaluation. Fluorescently labeled Platelets mixed with human RBC ghosts were perfused across six opaque materials (a titanium alloy (Ti6Al4V), silicon carbide (SiC), alumina (Al2O3), 2-methacryloyloxyethyl phosphorylcholine polymer coated Ti6Al4V (MPC-Ti6Al4V), yttria partially stabilized zirconia (YZTP), and zirconia toughened alumina (ZTA)) for 5 min at wall shear rates of 400 and 1000 s−1. Ti6Al4V had significantly increased Platelet Deposition relative to MPC-Ti6Al4V, Al2O3, YZTP, and ZTA at both wall shear rates (p
-
Polyethylene Glycol Diisocyanate Decreases Platelet Deposition After Balloon Injury of Rabbit Femoral Arteries
Journal of thrombosis and thrombolysis, 2002Co-Authors: J.e.b. Burchenal, Christopher Deible, Timothy E. Deglau, Alan J. Russell, Eric J. Beckman, William R. WagnerAbstract:Background: Platelet Deposition after angioplasty remains problematic and may contribute to intimal hyperplasia and restenosis. We proposed that polyethylene glycol diisocyanate (PEG-DISO), a polymer that rapidly forms covalent linkages with amine residues on proteins, could mask thrombogenic vascular wall proteins from Platelets, thereby abrogating acute Platelet Deposition. Methods and Results: To test this hypothesis, we isolated the femoral arteries of 10 New Zealand White rabbits and injured them with 3 passes of a 2F Fogarty catheter which was inserted through a distal arteriotomy. Immediately after balloon injury, 111indium-labeled autologous Platelets were infused peripherally and the injured femoral arteries were randomly treated for 1 minute with a PEG-DISO solution in one artery and a control solution of the phosphate buffered saline vehicle in the contralateral artery. Following treatment, reflow was initiated. The vessels were harvested after 1 hour and radioactivity was quantified in a gamma counter. Platelet counts were standardized by weight and expressed as Platelets/mg (mean ± SEM). Platelet Deposition onto arteries treated with PEG-DISO was (1.2 ± 0.5) × 106 Platelets/mg compared to (5.6 ± 4.2) × 106 Platelets/mg onto the contralateral control arteries treated with vehicle (P < 0.005). Scanning electron micrographs of the injured vessel segment confirmed qualitatively less Platelet Deposition on the treated segments than on the control segments. Conclusion: Treatment with PEG-DISO significantly inhibited Platelet Deposition after vascular injury. These data support the hypothesis that treatment with PEG-DISO masks surface adhesive proteins from Platelet receptors in vivo and that the resulting molecular barrier significantly reduces Platelet Deposition onto the damaged vessel wall for at least one hour. The formation of a molecularly thin barrier to Platelet Deposition may thus be a novel and effective treatment to abrogate acute intravascular thrombosis and may have value in the treatment of restenosis.
-
Computational simulation of Platelet Deposition and activation: II. Results for Poiseuille flow over collagen.
Annals of biomedical engineering, 1999Co-Authors: Erik N. Sorensen, William R. Wagner, Gregory Burgreen, James F. AntakiAbstract:We have previously described the development of a two-dimensional computational model of Platelet Deposition onto biomaterials from flowing blood (Sorensen et al., Ann. Biomed. Eng. 27:436–448, 1999). The model requires estimation of four parameters to fit it to experimental data: shear-dependent Platelet diffusivity and three Platelet-Deposition-related reaction rate constants. These parameters are estimated for Platelet Deposition onto a collagen substrate for simple parallel-plate flow of whole blood in both the presence and absence of thrombin. One set of experimental results is used as a benchmark for model-fitting purposes. The “trained” model is then validated by applying it to additional test cases from the literature for parallel-plate Poiseuille flow over collagen at both higher and lower wall shear rates, and in the presence of various anticoagulants. The predicted values agree very well with the experimental results for the training cases, and good reproduction of Deposition trends and magnitudes is obtained for the heparin, but not the citrate, validation cases. The model is formulated to be easily extended to synthetic biomaterials, as well as to more complex flows. © 1999 Biomedical Engineering Society.
Lina Badimon - One of the best experts on this subject based on the ideXlab platform.
-
A comprehensive study on different modelling approaches to predict Platelet Deposition rates in a perfusion chamber
Scientific reports, 2015Co-Authors: Jordi Pallares, Lina Badimon, Oriol Senan, Roger Guimerà, Anton Vernet, Antoni Aguilar-mogas, Gemma Vilahur, Marta Sales-pardo, Salvatore CitoAbstract:Thrombus formation is a multiscale phenomenon triggered by Platelet Deposition over a protrombotic surface (eg. a ruptured atherosclerotic plaque). Despite the medical urgency for computational tools that aid in the early diagnosis of thrombotic events, the integration of computational models of thrombus formation at different scales requires a comprehensive understanding of the role and limitation of each modelling approach. We propose three different modelling approaches to predict Platelet Deposition. Specifically, we consider measurements of Platelet Deposition under blood flow conditions in a perfusion chamber for different time periods (3, 5, 10, 20 and 30 minutes) at shear rates of 212 s−1, 1390 s−1 and 1690 s−1. Our modelling approaches are: i) a model based on the mass-transfer boundary layer theory; ii) a machine-learning approach; and iii) a phenomenological model. The results indicate that the three approaches on average have median errors of 21%, 20.7% and 14.2%, respectively. Our study demonstrates the feasibility of using an empirical data set as a proxy for a real-patient scenario in which practitioners have accumulated data on a given number of patients and want to obtain a diagnosis for a new patient about whom they only have the current observation of a certain number of variables.
-
Monomerization of C-reactive protein requires glycoprotein IIb-IIIa activation: pentraxins and Platelet Deposition.
Journal of thrombosis and haemostasis : JTH, 2013Co-Authors: R. De La Torre, Esther Peña, G. Vilahur, Mark Slevin, Lina BadimonAbstract:Summary Background Pentraxins are inflammatory mediators linked to cardiovascular disease; however, their role in thrombosis remains to be fully elucidated. Aims We investigated the role of pentraxins in thrombus formation on different vascular substrates under flow conditions. Methods Native C-reactive protein (nCRP) and serum amyloid P (SAP) effects on thrombosis were evaluated under flow conditions on substrates placed in flat perfusion chambers. nCRP and dissociated monomeric CRP (mCRP) distributions were visualized by use of confocal microscopy. The effects of nCRP on vascular substrates were tested in the Badimon chamber. Results mCRP, but not nCRP, induced a significant activation in Platelet Deposition, whereas SAP induced an activation only on fibrinogen-coated substrates. The effects of CRP on Platelet Deposition were significantly reduced by statin treatment. mCRP resulting from recirculation of blood containing nCRP over a thrombogenic vessel wall induced increased Platelet Deposition. Blocking glycoprotein IIb-IIIa prevented the effects of CRP dissociation and significantly reduced Platelet Deposition. Annexin V treatment did not block monomerization of CRP on activated Platelets. Conclusions Under flow conditions, Platelet deposited on all tested biological substrates support nCRP dissociation into mCRP. The effect is dependent on the thrombogenic potency of the substrate to trigger initial Platelet Deposition. Exposure of glycoprotein IIb-IIIa in the Platelet surface supports nCRP dissociation. CRP monomerization was not dependent on the aminophospholipid exposed on the surface of activated Platelets. The dissociated mCRP is trapped in the growing Platelet aggregate and stimulates further Platelet Deposition. SAP increases Platelet Deposition only on fibrin monolayers. Therefore, pentraxins induce a Platelet activation effect linking inflammation and thrombosis.
-
Glucose-Regulated Protein 78 and Platelet Deposition Effect of Rosuvastatin
Arteriosclerosis thrombosis and vascular biology, 2010Co-Authors: Blanca Molins, Esther Peña, Teresa Padró, Laura Casaní, Carlos Mendieta, Lina BadimonAbstract:Objective— To investigate the effect of rosuvastatin on Platelet Deposition under controlled shear rate conditions and to identify new Platelet proteins involved in the interaction with the activating substrate. Methods and Results— Platelet-vessel wall interaction and thrombosis take place under dynamic conditions involving the interaction of the exposed damaged vascular wall with the circulating blood cells and proteins. Blood was perfused over type I collagen at different wall shear rates, and Platelet Deposition was measured by confocal microscopy. Perfused effluent blood was collected, Platelets were sequentially extracted based on differential protein solubility, and proteins were separated by 2D gel electrophoresis. Blockade of 3-hydroxy-3-methylglutaryl–coenzyme A reductase significantly reduced Platelet Deposition and modulated the expression pattern of 18 proteins in the Platelet subproteome. Among them, an increase in Platelet surface 78-kDa glucose-regulated protein (GRP78), a stress-inducible multifunctional endoplasmic reticulum protein, was clearly apparent. Immunoprecipitation of Platelet GRP78 revealed its interaction with tissue factor. Moreover, blockade of surface GRP78 resulted in a substantial increase in Platelet Deposition and tissue factor procoagulant activity and in a decrease in clotting time. Conclusion— These findings demonstrate that blockade of 3-hydroxy-3-methylglutaryl–coenzyme A reductase reduces Platelet Deposition and inhibits GRP78 translocation from the Platelet surface after shear and collagen activation. For the first time to our knowledge, this study reports on the presence and functional role of GRP78 in Platelets and indicates that GRP78 has additional functions beyond those of a molecular chaperone.
-
Platelet Deposition on eroded vessel walls at a stenotic shear rate is inhibited by lipid lowering treatment with atorvastatin
Arteriosclerosis Thrombosis and Vascular Biology, 1999Co-Authors: J Alfon, Teresa Royo, Xavier Garciamoll, Lina BadimonAbstract:Abstract—Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase are widely used in the treatment of dyslipemias and have shown beneficial effects in the primary and secondary prevention of cardiovascular diseases. However, regression studies with lipid-lowering drugs have not shown significant lesion reduction associated with the improvement in clinical events. Therefore, our objective has been to study whether treatment with a lipid-lowering drug of this family, atorvastatin, could reduce Platelet Deposition on the damaged vessel wall at different shear stress conditions, simultaneously with retardation of the development of atherosclerotic lesions. Using cholesterol-fed swine as the model, we found that atorvastatin significantly diminished Platelet Deposition on the mildly damaged vessel wall at high shear rates (50%, P<0.01), but it did not have any effect in preventing Platelet Deposition triggered by a severely injured vessel wall. Development of coronary lesions was also reduced by treatment...
-
A Sudden Increase in Plasma Epinephrine Levels Transiently Enhances Platelet Deposition on Severely Damaged Arterial Wall
Thrombosis and Haemostasis, 1999Co-Authors: José Martínez-gonzález, Riitta Lassila, Teresita Royo, José Juan Badimon, Lina BadimonAbstract:SummaryEpidemiologic evidence has shown that sympathoadrenal activation plays a triggering role in the onset of acute coronary syndromes. However, its mechanism is not yet clearly understood. The aim of this study was to assess the effect of a sudden increase in epinephrine on Platelet Deposition on severely damaged vessel wall at shear rate conditions modelling stenotic vessels in the porcine model. The selected epinephrine concentrations (0.5 μmol/l-1 mmol/l) alone or in combination with collagen or ADP did not affect Platelet aggregation in vitro either in whole blood or in PRP, although porcine Platelets express α2-adrenergic receptors as assessed by PCR. In vitro and ex vivo perfusion experiments were performed using the Badimon chamber at high shear rate conditions (1690 s-1). In vitro, epinephrine (130 nmol/l) increased Platelet Deposition on severely damaged vessel wall (exposing tunica media; ≈1.6-fold, p <0.05) or immobilized collagen (2.2-fold, p <0.01). Ex vivo perfusion experiments were performed from animals that received intravenous epinephrine infusion for one hour at a low (0.3 μg/kg/min; ≈17 nmol/l in plasma, at 20 min of the infusion) and a high dose (1.0 μg/kg/min; ≈106 nmol/l in plasma, at 20 min of the infusion). Only the low dose temporarily increased Platelet Deposition on severely damaged vessel wall during the first 30 min of infusion [2.4-fold (p <0.05) and 4.2-fold (p <0.01) at 10 and 30 min of the infusion respectively] declining afterwards. Thus, in flow conditions typical of atherosclerotic arteries, a sudden physiological release of epinephrine can temporarily enhance Platelet Deposition on severely damaged vessel wall while an extensive exposure leads to refractoriness.
Stephen R Hanson - One of the best experts on this subject based on the ideXlab platform.
-
small caliber heparin coated eptfe grafts reduce Platelet Deposition and neointimal hyperplasia in a baboon model
Annual Meeting of the Association for Academic Surgery, 2004Co-Authors: Changyi Chen, Ruth L Bush, Alan B Lumsden, Stephen R HansonAbstract:Purpose: Intimal hyperplasia and graft thrombosis are major causes of graft failure. Heparin prolongs graft patency and inhibits neointimal hyperplasia in animal models. The purpose of this study was to evaluate the effect of a heparin-coated expanded polytetrafluoroethylene (ePTFE) graft on Platelet Deposition and anastomotic neointimal hyperplasia after aortoiliac bypass grafting in a baboon model. Methods: Heparin-coated ePTFE grafts (4-mm diameter) were incorporated into exteriorized femoral arteriovenous shunts placed in five baboons. Platelet Deposition was analyzed by measuring the accumulation of indium 111-labeled Platelets on the grafts, with dynamic scintillation camera imaging. Eight adult male baboons (mean weight, 9.3 kg) underwent bilateral aortoiliac bypass grafting with ePTFE grafts (4-mm internal diameter). In each animal a heparin-coated ePTFE graft was placed in one aortoiliac artery, and an uncoated graft, which served as the control, was placed in the contralateral aortoiliac artery. All grafts were harvested at 4 weeks, and were analyzed quantitatively for neointimal hyperplasia at graft-vessel anastomoses. Results: Early Platelet Deposition on heparin-coated grafts after 1 to 4 hours of ex vivo circuitry was significantly reduced. All the harvested aortoiliac grafts were patent at 4 weeks. There was a significant reduction in neointimal area at both proximal (0.26 ± 0.11 mm 2 ) and distal (0.29 ± 0.14 mm 2 ) anastomoses in the heparin-coated grafts, compared with proximal (0.56 ± 0.18 mm 2 ) and distal (0.63 ± 0.21 mm 2 ) anastomoses in the untreated control grafts (P <.05). In addition, neointimal cell proliferation assayed with bromodeoxyuridine (BrdU) incorporation was reduced in the graft neointima (3.47% ± 0.43%) in heparin-coated grafts compared with the graft neointima (6.21% ± 0.59%) in untreated control grafts (P <.05). Conclusions: Small-caliber heparin-coated ePTFE grafts significantly reduce Platelet Deposition and anastomotic neointimal hyperplasia and cell proliferation, without measurable side effects, in baboons. Surface coating with heparin in small-caliber ePTFE grafts is useful for improving prosthetic bypass graft patency. (J Vasc Surg 2004;39:1322-8.) Clinical Relevance: An autologous vein graft is the ideal bypass conduit in peripheral arterial reconstruction; however, many patients who undergo bypass grafting do not have adequate or available autologous vein graft. As a result surgeons often must rely on prosthetic grafts as an alternative conduit in arterial bypass procedures. Clinical outcomes with prosthetic grafts in peripheral arterial reconstruction are generally inferior to those with autologous vein bypass grafts, in part because of anastomotic neointimal hyperplasia. This study evaluated the effect of small-caliber heparin-coated expandable polytetrafluoroethylene (ePTFE) grafts in aortoiliac reconstruction in a baboon model. The study found that heparin-ciated ePTFE grafts resulted in less intimal hyperplasia and less Platelet Deposition after implantation, compared with noncoated control ePTFE grafts.
-
Small-caliber heparin-coated ePTFE grafts reduce Platelet Deposition and neointimal hyperplasia in a baboon model
Journal of vascular surgery, 2004Co-Authors: Peter H. Lin, Changyi Chen, Ruth L Bush, Alan B Lumsden, Qizhi Yao, Stephen R HansonAbstract:Abstract Purpose Intimal hyperplasia and graft thrombosis are major causes of graft failure. Heparin prolongs graft patency and inhibits neointimal hyperplasia in animal models. The purpose of this study was to evaluate the effect of a heparin-coated expanded polytetrafluoroethylene (ePTFE) graft on Platelet Deposition and anastomotic neointimal hyperplasia after aortoiliac bypass grafting in a baboon model. Methods Heparin-coated ePTFE grafts (4-mm diameter) were incorporated into exteriorized femoral arteriovenous shunts placed in five baboons. Platelet Deposition was analyzed by measuring the accumulation of indium 111–labeled Platelets on the grafts, with dynamic scintillation camera imaging. Eight adult male baboons (mean weight, 9.3 kg) underwent bilateral aortoiliac bypass grafting with ePTFE grafts (4-mm internal diameter). In each animal a heparin-coated ePTFE graft was placed in one aortoiliac artery, and an uncoated graft, which served as the control, was placed in the contralateral aortoiliac artery. All grafts were harvested at 4 weeks, and were analyzed quantitatively for neointimal hyperplasia at graft-vessel anastomoses. Results Early Platelet Deposition on heparin-coated grafts after 1 to 4 hours of ex vivo circuitry was significantly reduced. All the harvested aortoiliac grafts were patent at 4 weeks. There was a significant reduction in neointimal area at both proximal (0.26 ± 0.11 mm 2 ) and distal (0.29 ± 0.14 mm 2 ) anastomoses in the heparin-coated grafts, compared with proximal (0.56 ± 0.18 mm 2 ) and distal (0.63 ± 0.21 mm 2 ) anastomoses in the untreated control grafts ( P P Conclusions Small-caliber heparin-coated ePTFE grafts significantly reduce Platelet Deposition and anastomotic neointimal hyperplasia and cell proliferation, without measurable side effects, in baboons. Surface coating with heparin in small-caliber ePTFE grafts is useful for improving prosthetic bypass graft patency.
-
Phosphorylcholine Coating of ePTFE Reduces Platelet Deposition and Neointimal Hyperplasia in Arteriovenous Grafts
The Journal of surgical research, 1998Co-Authors: Changyi Chen, Stephen R Hanson, John C. Ofenloch, Yiannakis P. Yianni, Alan B LumsdenAbstract:In an attempt to reduce Platelet Deposition and inhibit neointimal hyperplasia, we evaluated the effect of coating expanded polytetrafluoroethylene (ePTFE) grafts with phosphorylcholine (PC), a lipid found in animal cell membranes, in a dog model of femoral arteriovenous (AV) grafts. Eight mongrel dogs underwent placement of a PC-coated femoral AV graft on one side and an untreated control graft on the contralateral side. Platelet Deposition was measured by autologous 111Indium-labeling and scintillation camera imaging analysis. Platelet Deposition on the PC-coated grafts at 30 and 90 min. was 9.32 +/- 4.35 x 10(9) and 10.00 +/- 4.38 x 10(9), respectively, as compared with 10.26 +/- 4.36 x 10(9) and 11.64 +/- 5.08 x 10(9) Platelet Deposition on control grafts (P < 0.05). All grafts were patent at 4 weeks. There was a significant reduction of neointimal area at both arterial (0.07 +/- 0.05 mm2) and venous (0. 18 +/- 0.09 mm2) anastomoses in the treated grafts as compared with arterial (0.15 +/- 0.05 mm2) and venous (0.43 +/- 0.22 mm2) anastomoses in the control grafts (P < 0.05). In addition, neointimal cell proliferation assayed by bromodeoxyuridine (BrdU) incorporation was reduced in both arterial (2.05 +/- 0.81%) and venous (3.25 +/- 0.17%) anastomoses of treated grafts compared with arterial (3.12 +/- 1.23%) and venous (5.36 +/- 1.18%) anastomoses of control grafts (P < 0.05). These data demonstrated that PC coating of ePTFE grafts significantly reduced Platelet Deposition, anastomotic neointimal hyperplasia, and neointimal cell proliferation in a dog model of AV grafts. This may represent a new strategy for prolonging hemodialysis graft patency.
James F. Antaki - One of the best experts on this subject based on the ideXlab platform.
-
real time visualization and characterization of Platelet Deposition under flow onto clinically relevant opaque surfaces
Journal of Biomedical Materials Research Part A, 2015Co-Authors: Megan A. Jamiolkowski, Joshua R. Woolley, Marina V. Kameneva, James F. Antaki, William R. WagnerAbstract:Although the thrombogenic nature of the surfaces of cardiovascular devices is an important aspect of blood biocompatibility, few studies have examined Platelet Deposition onto opaque materials used for these devices in real time. This is particularly true for the metallic surfaces used in current ventricular assist devices (VADs). Using hemoglobin depleted red blood cells (RBC ghosts) and long working distance optics to visualize Platelet Deposition, we sought to perform such an evaluation. Fluorescently labeled Platelets mixed with human RBC ghosts were perfused across six opaque materials (a titanium alloy (Ti6Al4V), silicon carbide (SiC), alumina (Al2O3), 2-methacryloyloxyethyl phosphorylcholine polymer coated Ti6Al4V (MPC-Ti6Al4V), yttria partially stabilized zirconia (YZTP), and zirconia toughened alumina (ZTA)) for 5 min at wall shear rates of 400 and 1000 s−1. Ti6Al4V had significantly increased Platelet Deposition relative to MPC-Ti6Al4V, Al2O3, YZTP, and ZTA at both wall shear rates (p < 0.01). For all test surfaces, increasing the wall shear rate produced a trend of decreased Platelet adhesion. The described system can be a utilized as a tool for comparative analysis of candidate blood-contacting materials with acute blood contact. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1303–1311, 2015.
-
Real time visualization and characterization of Platelet Deposition under flow onto clinically relevant opaque surfaces.
Journal of biomedical materials research. Part A, 2014Co-Authors: Megan A. Jamiolkowski, Joshua R. Woolley, Marina V. Kameneva, James F. Antaki, William R. WagnerAbstract:Although the thrombogenic nature of the surfaces of cardiovascular devices is an important aspect of blood biocompatibility, few studies have examined Platelet Deposition onto opaque materials used for these devices in real time. This is particularly true for the metallic surfaces used in current ventricular assist devices (VADs). Using hemoglobin depleted red blood cells (RBC ghosts) and long working distance optics to visualize Platelet Deposition, we sought to perform such an evaluation. Fluorescently labeled Platelets mixed with human RBC ghosts were perfused across six opaque materials (a titanium alloy (Ti6Al4V), silicon carbide (SiC), alumina (Al2O3), 2-methacryloyloxyethyl phosphorylcholine polymer coated Ti6Al4V (MPC-Ti6Al4V), yttria partially stabilized zirconia (YZTP), and zirconia toughened alumina (ZTA)) for 5 min at wall shear rates of 400 and 1000 s−1. Ti6Al4V had significantly increased Platelet Deposition relative to MPC-Ti6Al4V, Al2O3, YZTP, and ZTA at both wall shear rates (p
-
Computational simulation of Platelet Deposition and activation: II. Results for Poiseuille flow over collagen.
Annals of biomedical engineering, 1999Co-Authors: Erik N. Sorensen, William R. Wagner, Gregory Burgreen, James F. AntakiAbstract:We have previously described the development of a two-dimensional computational model of Platelet Deposition onto biomaterials from flowing blood (Sorensen et al., Ann. Biomed. Eng. 27:436–448, 1999). The model requires estimation of four parameters to fit it to experimental data: shear-dependent Platelet diffusivity and three Platelet-Deposition-related reaction rate constants. These parameters are estimated for Platelet Deposition onto a collagen substrate for simple parallel-plate flow of whole blood in both the presence and absence of thrombin. One set of experimental results is used as a benchmark for model-fitting purposes. The “trained” model is then validated by applying it to additional test cases from the literature for parallel-plate Poiseuille flow over collagen at both higher and lower wall shear rates, and in the presence of various anticoagulants. The predicted values agree very well with the experimental results for the training cases, and good reproduction of Deposition trends and magnitudes is obtained for the heparin, but not the citrate, validation cases. The model is formulated to be easily extended to synthetic biomaterials, as well as to more complex flows. © 1999 Biomedical Engineering Society.
-
Computational Simulation of Platelet Deposition and Activation: I. Model Development and Properties
Annals of biomedical engineering, 1999Co-Authors: Erik N. Sorensen, William R. Wagner, Gregory Burgreen, James F. AntakiAbstract:To better understand the mechanisms leading to the formation and growth of mural thrombi on biomaterials, we have developed a two-dimensional computational model of Platelet Deposition and activation in flowing blood. The basic formulation is derived from prior work by others, with additional levels of complexity added where appropriate. It is comprised of a series of convection-diffusion-reaction equations which simulate Platelet-surface and Platelet-Platelet adhesion, Platelet activation by a weighted linear combination of agonist concentrations, agonist release and synthesis by activated Platelets, Platelet-phospholipid-dependent thrombin generation, and thrombin inhibition by heparin. The model requires estimation of four parameters to fit it to experimental data: shear-dependent Platelet diffusivity and resting and activated Platelet-surface and Platelet-Platelet reaction rate constants. The model is formulated to simulate a wide range of biomaterials and complex flows. In this article we present the basic model and its properties; in Part II (Sorensen et al., Ann. Biomed. Eng. 27:449–458, 1999) we apply the model to experimental results for Platelet Deposition onto collagen. © 1999 Biomedical Engineering Society.
-
Simulation of Platelet Deposition in disturbed flow
Proceedings of the Second Joint 24th Annual Conference and the Annual Fall Meeting of the Biomedical Engineering Society] [Engineering in Medicine and, 1Co-Authors: Erik N. Sorensen, William R. Wagner, Gregory Burgreen, James F. AntakiAbstract:We have developed a two-dimensional computational model of Platelet-mediated biomaterial thrombosis. When applied to plane Poiseuille flow over collagen, it showed very good agreement with experimental results. Here, we attempt to simulate Platelet Deposition onto collagen in the presence of disturbed flow in a tubular expansion. At 0% hematocrit, good agreement with experiments is obtained for the recirculation zone, but not for the fully-developed downstream zone At 20% hematocrit, poor agreement is observed unless the Platelet-surface reaction coefficients are altered. In both cases, it appears the deficiencies are due to incomplete modeling of Platelet transport mechanisms.
Alan B Lumsden - One of the best experts on this subject based on the ideXlab platform.
-
small caliber heparin coated eptfe grafts reduce Platelet Deposition and neointimal hyperplasia in a baboon model
Annual Meeting of the Association for Academic Surgery, 2004Co-Authors: Changyi Chen, Ruth L Bush, Alan B Lumsden, Stephen R HansonAbstract:Purpose: Intimal hyperplasia and graft thrombosis are major causes of graft failure. Heparin prolongs graft patency and inhibits neointimal hyperplasia in animal models. The purpose of this study was to evaluate the effect of a heparin-coated expanded polytetrafluoroethylene (ePTFE) graft on Platelet Deposition and anastomotic neointimal hyperplasia after aortoiliac bypass grafting in a baboon model. Methods: Heparin-coated ePTFE grafts (4-mm diameter) were incorporated into exteriorized femoral arteriovenous shunts placed in five baboons. Platelet Deposition was analyzed by measuring the accumulation of indium 111-labeled Platelets on the grafts, with dynamic scintillation camera imaging. Eight adult male baboons (mean weight, 9.3 kg) underwent bilateral aortoiliac bypass grafting with ePTFE grafts (4-mm internal diameter). In each animal a heparin-coated ePTFE graft was placed in one aortoiliac artery, and an uncoated graft, which served as the control, was placed in the contralateral aortoiliac artery. All grafts were harvested at 4 weeks, and were analyzed quantitatively for neointimal hyperplasia at graft-vessel anastomoses. Results: Early Platelet Deposition on heparin-coated grafts after 1 to 4 hours of ex vivo circuitry was significantly reduced. All the harvested aortoiliac grafts were patent at 4 weeks. There was a significant reduction in neointimal area at both proximal (0.26 ± 0.11 mm 2 ) and distal (0.29 ± 0.14 mm 2 ) anastomoses in the heparin-coated grafts, compared with proximal (0.56 ± 0.18 mm 2 ) and distal (0.63 ± 0.21 mm 2 ) anastomoses in the untreated control grafts (P <.05). In addition, neointimal cell proliferation assayed with bromodeoxyuridine (BrdU) incorporation was reduced in the graft neointima (3.47% ± 0.43%) in heparin-coated grafts compared with the graft neointima (6.21% ± 0.59%) in untreated control grafts (P <.05). Conclusions: Small-caliber heparin-coated ePTFE grafts significantly reduce Platelet Deposition and anastomotic neointimal hyperplasia and cell proliferation, without measurable side effects, in baboons. Surface coating with heparin in small-caliber ePTFE grafts is useful for improving prosthetic bypass graft patency. (J Vasc Surg 2004;39:1322-8.) Clinical Relevance: An autologous vein graft is the ideal bypass conduit in peripheral arterial reconstruction; however, many patients who undergo bypass grafting do not have adequate or available autologous vein graft. As a result surgeons often must rely on prosthetic grafts as an alternative conduit in arterial bypass procedures. Clinical outcomes with prosthetic grafts in peripheral arterial reconstruction are generally inferior to those with autologous vein bypass grafts, in part because of anastomotic neointimal hyperplasia. This study evaluated the effect of small-caliber heparin-coated expandable polytetrafluoroethylene (ePTFE) grafts in aortoiliac reconstruction in a baboon model. The study found that heparin-ciated ePTFE grafts resulted in less intimal hyperplasia and less Platelet Deposition after implantation, compared with noncoated control ePTFE grafts.
-
Small-caliber heparin-coated ePTFE grafts reduce Platelet Deposition and neointimal hyperplasia in a baboon model
Journal of vascular surgery, 2004Co-Authors: Peter H. Lin, Changyi Chen, Ruth L Bush, Alan B Lumsden, Qizhi Yao, Stephen R HansonAbstract:Abstract Purpose Intimal hyperplasia and graft thrombosis are major causes of graft failure. Heparin prolongs graft patency and inhibits neointimal hyperplasia in animal models. The purpose of this study was to evaluate the effect of a heparin-coated expanded polytetrafluoroethylene (ePTFE) graft on Platelet Deposition and anastomotic neointimal hyperplasia after aortoiliac bypass grafting in a baboon model. Methods Heparin-coated ePTFE grafts (4-mm diameter) were incorporated into exteriorized femoral arteriovenous shunts placed in five baboons. Platelet Deposition was analyzed by measuring the accumulation of indium 111–labeled Platelets on the grafts, with dynamic scintillation camera imaging. Eight adult male baboons (mean weight, 9.3 kg) underwent bilateral aortoiliac bypass grafting with ePTFE grafts (4-mm internal diameter). In each animal a heparin-coated ePTFE graft was placed in one aortoiliac artery, and an uncoated graft, which served as the control, was placed in the contralateral aortoiliac artery. All grafts were harvested at 4 weeks, and were analyzed quantitatively for neointimal hyperplasia at graft-vessel anastomoses. Results Early Platelet Deposition on heparin-coated grafts after 1 to 4 hours of ex vivo circuitry was significantly reduced. All the harvested aortoiliac grafts were patent at 4 weeks. There was a significant reduction in neointimal area at both proximal (0.26 ± 0.11 mm 2 ) and distal (0.29 ± 0.14 mm 2 ) anastomoses in the heparin-coated grafts, compared with proximal (0.56 ± 0.18 mm 2 ) and distal (0.63 ± 0.21 mm 2 ) anastomoses in the untreated control grafts ( P P Conclusions Small-caliber heparin-coated ePTFE grafts significantly reduce Platelet Deposition and anastomotic neointimal hyperplasia and cell proliferation, without measurable side effects, in baboons. Surface coating with heparin in small-caliber ePTFE grafts is useful for improving prosthetic bypass graft patency.
-
Phosphorylcholine Coating of ePTFE Reduces Platelet Deposition and Neointimal Hyperplasia in Arteriovenous Grafts
The Journal of surgical research, 1998Co-Authors: Changyi Chen, Stephen R Hanson, John C. Ofenloch, Yiannakis P. Yianni, Alan B LumsdenAbstract:In an attempt to reduce Platelet Deposition and inhibit neointimal hyperplasia, we evaluated the effect of coating expanded polytetrafluoroethylene (ePTFE) grafts with phosphorylcholine (PC), a lipid found in animal cell membranes, in a dog model of femoral arteriovenous (AV) grafts. Eight mongrel dogs underwent placement of a PC-coated femoral AV graft on one side and an untreated control graft on the contralateral side. Platelet Deposition was measured by autologous 111Indium-labeling and scintillation camera imaging analysis. Platelet Deposition on the PC-coated grafts at 30 and 90 min. was 9.32 +/- 4.35 x 10(9) and 10.00 +/- 4.38 x 10(9), respectively, as compared with 10.26 +/- 4.36 x 10(9) and 11.64 +/- 5.08 x 10(9) Platelet Deposition on control grafts (P < 0.05). All grafts were patent at 4 weeks. There was a significant reduction of neointimal area at both arterial (0.07 +/- 0.05 mm2) and venous (0. 18 +/- 0.09 mm2) anastomoses in the treated grafts as compared with arterial (0.15 +/- 0.05 mm2) and venous (0.43 +/- 0.22 mm2) anastomoses in the control grafts (P < 0.05). In addition, neointimal cell proliferation assayed by bromodeoxyuridine (BrdU) incorporation was reduced in both arterial (2.05 +/- 0.81%) and venous (3.25 +/- 0.17%) anastomoses of treated grafts compared with arterial (3.12 +/- 1.23%) and venous (5.36 +/- 1.18%) anastomoses of control grafts (P < 0.05). These data demonstrated that PC coating of ePTFE grafts significantly reduced Platelet Deposition, anastomotic neointimal hyperplasia, and neointimal cell proliferation in a dog model of AV grafts. This may represent a new strategy for prolonging hemodialysis graft patency.