Background: Protein adsorption on medical devices in contact with blood is a significant issue during renal replacement therapy. Main forces determining fouling are the electrostatic interactions between membrane and charged protein, but the dialysis membrane surface charges can be adjusted by modifying the polymer matrix to decrease the blood plasma protein adsorption.
Methods: In this study, polysulfone membranes (PSU) were modified by incorporation of carbon nanoparticles such as: multiwall carbon nanotubes (2 wt.% MWCNT), graphene oxide (1 wt.% GO), and graphite (5 wt.% GR) during manufacturing process (nonsolvent-induced phase separation, NIPS). The PSU flat sheet membrane was the reference sample.
Results: Observed morphology of nanocomposite membranes was similar (SEM imaging); all of them had finger-like pore structure with unimodal distribution of pore size and similar skin-to-support ratio (1:3). The carbon nanoadditives also influenced the surface wettability: hydrophobicity and surface free energy of membranes increased (polar components of energy were reduced, while the dispersive components were increased).
Conclusion: The surface charge of nanocomposite membranes increased, when the polymer matrix has been modified with CNT or GR. This significantly affects the adsorption of proteins such as chicken (CSA) and bovine serum albumin (BSA) and reduces blood clotting on the membrane.
背景:蛋白质吸附在与血液接触的医疗设备上是肾脏替代治疗过程中的一个重要问题。决定污垢产生的主要因素是膜与带电蛋白质之间的静电相互作用,但透析膜表面的电荷可通过改性聚合物基质来调整,以减少血浆蛋白质的吸附:本研究在聚砜膜(PSU)的制造过程中加入了碳纳米颗粒,如:多壁碳纳米管(2 wt.% MWCNT)、氧化石墨烯(1 wt.% GO)和石墨(5 wt.% GR)(非溶剂诱导相分离,NIPS)。PSU 平板膜为参考样品:观察到的纳米复合膜形态相似(扫描电子显微镜成像);所有纳米复合膜都具有指状孔隙结构,孔隙大小呈单峰分布,表皮与支撑物的比例相似(1:3)。碳纳米添加剂还影响了表面润湿性:膜的疏水性和表面自由能增加(能量的极性成分减少,而分散成分增加):结论:用 CNT 或 GR 对聚合物基质进行改性后,纳米复合膜的表面电荷增加。结论:用 CNT 或 GR 对聚合物基质进行改性后,纳米复合膜的表面电荷增加,这极大地影响了膜对鸡肉(CSA)和牛血清白蛋白(BSA)等蛋白质的吸附,并减少了膜上的血液凝结。
{"title":"Dialysis nanocomposite membranes based on carbon nanoforms inhibiting blood plasma protein adsorption.","authors":"Dominika Wójtowicz, Roksana Kurpanik, Dominika Nguyen Ngoc, Joanna Wessley-Szponder, Ewa Stodolak-Zych","doi":"10.1177/03913988241269440","DOIUrl":"10.1177/03913988241269440","url":null,"abstract":"<p><strong>Background: </strong>Protein adsorption on medical devices in contact with blood is a significant issue during renal replacement therapy. Main forces determining fouling are the electrostatic interactions between membrane and charged protein, but the dialysis membrane surface charges can be adjusted by modifying the polymer matrix to decrease the blood plasma protein adsorption.</p><p><strong>Methods: </strong>In this study, polysulfone membranes (PSU) were modified by incorporation of carbon nanoparticles such as: multiwall carbon nanotubes (2 wt.% MWCNT), graphene oxide (1 wt.% GO), and graphite (5 wt.% GR) during manufacturing process (nonsolvent-induced phase separation, NIPS). The PSU flat sheet membrane was the reference sample.</p><p><strong>Results: </strong>Observed morphology of nanocomposite membranes was similar (SEM imaging); all of them had finger-like pore structure with unimodal distribution of pore size and similar skin-to-support ratio (1:3). The carbon nanoadditives also influenced the surface wettability: hydrophobicity and surface free energy of membranes increased (polar components of energy were reduced, while the dispersive components were increased).</p><p><strong>Conclusion: </strong>The surface charge of nanocomposite membranes increased, when the polymer matrix has been modified with CNT or GR. This significantly affects the adsorption of proteins such as chicken (CSA) and bovine serum albumin (BSA) and reduces blood clotting on the membrane.</p>","PeriodicalId":13932,"journal":{"name":"International Journal of Artificial Organs","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-08-08DOI: 10.1177/03913988241266088
Ana M Muñoz-Gonzalez, Sara Leal-Marin, Dianney Clavijo-Grimaldo, Birgit Glasmacher
Cardiovascular diseases, particularly myocardial infarction, have significant healthcare challenges due to the limited regenerative capacity of injured heart tissue. Cardiac tissue engineering (CTE) offers a promising approach to repairing myocardial damage using biomaterials that mimic the heart's extracellular matrix. This study investigates the potential of graphene nanopowder (Gnp)-enhanced polycaprolactone (PCL) scaffolds fabricated via electrospinning to improve the properties necessary for effective cardiac repair. This work aimed to analyze scaffolds with varying graphene concentrations (0.5%, 1%, 1.5%, and 2% by weight) to determine their morphological, chemical, mechanical, and biocompatibility characteristics. The results presented that incorporating graphene improves PCL scaffolds' mechanical properties and cellular interactions. The optimal concentration of 1% graphene significantly enhanced mechanical properties and biocompatibility, promoting cell adhesion and proliferation. These findings suggest that Gnp-enhanced PCL scaffolds at this concentration can serve as a potent substrate for CTE providing insights into designing more effective biomaterials for myocardial restoration.
{"title":"Graphene-enhanced PCL electrospun nanofiber scaffolds for cardiac tissue engineering.","authors":"Ana M Muñoz-Gonzalez, Sara Leal-Marin, Dianney Clavijo-Grimaldo, Birgit Glasmacher","doi":"10.1177/03913988241266088","DOIUrl":"10.1177/03913988241266088","url":null,"abstract":"<p><p>Cardiovascular diseases, particularly myocardial infarction, have significant healthcare challenges due to the limited regenerative capacity of injured heart tissue. Cardiac tissue engineering (CTE) offers a promising approach to repairing myocardial damage using biomaterials that mimic the heart's extracellular matrix. This study investigates the potential of graphene nanopowder (Gnp)-enhanced polycaprolactone (PCL) scaffolds fabricated via electrospinning to improve the properties necessary for effective cardiac repair. This work aimed to analyze scaffolds with varying graphene concentrations (0.5%, 1%, 1.5%, and 2% by weight) to determine their morphological, chemical, mechanical, and biocompatibility characteristics. The results presented that incorporating graphene improves PCL scaffolds' mechanical properties and cellular interactions. The optimal concentration of 1% graphene significantly enhanced mechanical properties and biocompatibility, promoting cell adhesion and proliferation. These findings suggest that Gnp-enhanced PCL scaffolds at this concentration can serve as a potent substrate for CTE providing insights into designing more effective biomaterials for myocardial restoration.</p>","PeriodicalId":13932,"journal":{"name":"International Journal of Artificial Organs","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-08-21DOI: 10.1177/03913988241268000
Isabell Esslinger, Michael Lommel, Florian Kießlich, Ulrich Kertzscher, Tim Bierewirtz
Thromboembolic complications still arise on blood contacting surfaces. Surface charge and topography influence the subsequent deposition of proteins and platelets, potentially leading to thrombi. Research showed a correlation of surface charge and nanoscale roughness, and a negative surface charge as well as a smooth surface finish are associated with lower thrombogenicity. The aim of this study was to compare the platelet adhesion on titanium with different nanoscale roughnesses and to examine if those roughness variations caused a change in surface charge. Titanium samples were polished and roughened to four different nanoscale roughness levels. Platelet adhesion (covered surface area (CSA), N = 8) was tested in flow chambers with human whole blood using fluorescence imaging. ζ-potential was measured over a broad range of pH-values and interpolated to obtain the ζ-potential for pHBlood (7.4). Platelet adhesion tests were evaluated in terms of p-values and the Wilcoxon test effect size and the trend of the ζ-potential at pHBlood and the CSA was compared. Ra-values ranged between 35 (polished) and 156 nm. Regarding platelet adhesion, the polished sample showed the lowest mean CSA with a medium or strong effect size compared to the roughened samples. The interpolated ζ-potentials for pHBlood follow a similar trend as the CSA, with the lowest ζ-potential measured for the polished surface. These findings suggest that the decreasing ζ-potential due to lower nanoscale roughness might be an additional explanation for the improved hemocompatibility besides the smoother topography.
{"title":"Influence of titanium surface roughness on a nanoscale on the zeta potential and platelet adhesion.","authors":"Isabell Esslinger, Michael Lommel, Florian Kießlich, Ulrich Kertzscher, Tim Bierewirtz","doi":"10.1177/03913988241268000","DOIUrl":"10.1177/03913988241268000","url":null,"abstract":"<p><p>Thromboembolic complications still arise on blood contacting surfaces. Surface charge and topography influence the subsequent deposition of proteins and platelets, potentially leading to thrombi. Research showed a correlation of surface charge and nanoscale roughness, and a negative surface charge as well as a smooth surface finish are associated with lower thrombogenicity. The aim of this study was to compare the platelet adhesion on titanium with different nanoscale roughnesses and to examine if those roughness variations caused a change in surface charge. Titanium samples were polished and roughened to four different nanoscale roughness levels. Platelet adhesion (covered surface area (CSA), <i>N</i> = 8) was tested in flow chambers with human whole blood using fluorescence imaging. ζ-potential was measured over a broad range of pH-values and interpolated to obtain the ζ-potential for pH<sub>Blood</sub> (7.4). Platelet adhesion tests were evaluated in terms of <i>p</i>-values and the Wilcoxon test effect size and the trend of the ζ-potential at pH<sub>Blood</sub> and the CSA was compared. <i>R</i><sub>a</sub>-values ranged between 35 (polished) and 156 nm. Regarding platelet adhesion, the polished sample showed the lowest mean CSA with a medium or strong effect size compared to the roughened samples. The interpolated ζ-potentials for pH<sub>Blood</sub> follow a similar trend as the CSA, with the lowest ζ-potential measured for the polished surface. These findings suggest that the decreasing ζ-potential due to lower nanoscale roughness might be an additional explanation for the improved hemocompatibility besides the smoother topography.</p>","PeriodicalId":13932,"journal":{"name":"International Journal of Artificial Organs","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-08-21DOI: 10.1177/03913988241268105
Elena Carrara, Luca Soliveri, Sofia Poloni, Michela Bozzetto, Chiara Emma Campiglio
Mechanical forces related to blood pressure and flow patterns play a crucial role in vascular homeostasis. Perturbations in vascular stresses and strain resulting from changes in hemodynamic may occur in pathological conditions, leading to vascular dysfunction as well as in vascular prosthesis, arteriovenous shunt for hemodialysis and in mechanical circulation support. Turbulent-like blood flows can induce high-frequency vibrations of the vessel wall, and this stimulus has recently gained attention as potential contributors to vascular pathologies, such as development of intimal hyperplasia in arteriovenous fistula for hemodialysis. However, the biological response of vascular cells to this stimulus remains incompletely understood. This review provides an analysis of the existing literature concerning the impact of high-frequency stimuli on vascular cell morphology, function, and gene expression. Morphological and functional investigations reveal that vascular cells stimulated at frequencies higher than the normal heart rate exhibit alterations in cell shape, alignment, and proliferation, potentially leading to vessel remodeling. Furthermore, vibrations modulate endothelial and smooth muscle cells gene expression, affecting pathways related to inflammation, oxidative stress, and muscle hypertrophy. Understanding the effects of high-frequency vibrations on vascular cells is essential for unraveling the mechanisms underlying vascular diseases and identifying potential therapeutic targets. Nevertheless, there are still gaps in our understanding of the molecular pathways governing these cellular responses. Further research is necessary to elucidate these mechanisms and their therapeutic implications for vascular diseases.
{"title":"Effects of high-frequency mechanical stimuli on flow related vascular cell biology.","authors":"Elena Carrara, Luca Soliveri, Sofia Poloni, Michela Bozzetto, Chiara Emma Campiglio","doi":"10.1177/03913988241268105","DOIUrl":"10.1177/03913988241268105","url":null,"abstract":"<p><p>Mechanical forces related to blood pressure and flow patterns play a crucial role in vascular homeostasis. Perturbations in vascular stresses and strain resulting from changes in hemodynamic may occur in pathological conditions, leading to vascular dysfunction as well as in vascular prosthesis, arteriovenous shunt for hemodialysis and in mechanical circulation support. Turbulent-like blood flows can induce high-frequency vibrations of the vessel wall, and this stimulus has recently gained attention as potential contributors to vascular pathologies, such as development of intimal hyperplasia in arteriovenous fistula for hemodialysis. However, the biological response of vascular cells to this stimulus remains incompletely understood. This review provides an analysis of the existing literature concerning the impact of high-frequency stimuli on vascular cell morphology, function, and gene expression. Morphological and functional investigations reveal that vascular cells stimulated at frequencies higher than the normal heart rate exhibit alterations in cell shape, alignment, and proliferation, potentially leading to vessel remodeling. Furthermore, vibrations modulate endothelial and smooth muscle cells gene expression, affecting pathways related to inflammation, oxidative stress, and muscle hypertrophy. Understanding the effects of high-frequency vibrations on vascular cells is essential for unraveling the mechanisms underlying vascular diseases and identifying potential therapeutic targets. Nevertheless, there are still gaps in our understanding of the molecular pathways governing these cellular responses. Further research is necessary to elucidate these mechanisms and their therapeutic implications for vascular diseases.</p>","PeriodicalId":13932,"journal":{"name":"International Journal of Artificial Organs","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-09-19DOI: 10.1177/03913988241267797
Joseph Bornoff, Shaikh Faisal Zaman, Azad Najar, Thomas Finocchiaro, Ina Laura Perkins, Andrew N Cookson, Katharine H Fraser
The assessment and reduction of haemolysis within mechanical circulatory support (MCS) remains a concern with regard to device safety and regulatory approval. Numerical methods for predicting haemolysis have typically been applied to rotary MCS devices and the extent to which these methods apply to positive-displacement MCS is unclear. The aim of this study was to evaluate the suitability of these methods for assessing haemolysis in positive-displacement blood pumps. Eulerian scalar-transport and Lagrangian particle-tracking approaches derived from the shear-based power-law relationship were used to calculate haemolysis in a computational fluid dynamics model of the Realheart total artificial heart. A range of power-law constants and their effect on simulated haemolysis were also investigated. Both Eulerian and Lagrangian methods identified the same key mechanism of haemolysis: leakage flow through the bileaflet valves. Whilst the magnitude of haemolysis varied with different power-law constants, the method of haemolysis generation remained consistent. The Eulerian method was more robust and reliable at identifying sites of haemolysis generation, as it was able to capture the persistent leakage flow throughout the entire pumping cycle. This study paves the way for different positive-displacement MCS devices to be compared across different operating conditions, enabling the optimisation of these pumps for improved patient outcomes.
{"title":"Assessment of haemolysis models for a positive-displacement total artificial heart.","authors":"Joseph Bornoff, Shaikh Faisal Zaman, Azad Najar, Thomas Finocchiaro, Ina Laura Perkins, Andrew N Cookson, Katharine H Fraser","doi":"10.1177/03913988241267797","DOIUrl":"10.1177/03913988241267797","url":null,"abstract":"<p><p>The assessment and reduction of haemolysis within mechanical circulatory support (MCS) remains a concern with regard to device safety and regulatory approval. Numerical methods for predicting haemolysis have typically been applied to rotary MCS devices and the extent to which these methods apply to positive-displacement MCS is unclear. The aim of this study was to evaluate the suitability of these methods for assessing haemolysis in positive-displacement blood pumps. Eulerian scalar-transport and Lagrangian particle-tracking approaches derived from the shear-based power-law relationship were used to calculate haemolysis in a computational fluid dynamics model of the Realheart total artificial heart. A range of power-law constants and their effect on simulated haemolysis were also investigated. Both Eulerian and Lagrangian methods identified the same key mechanism of haemolysis: leakage flow through the bileaflet valves. Whilst the magnitude of haemolysis varied with different power-law constants, the method of haemolysis generation remained consistent. The Eulerian method was more robust and reliable at identifying sites of haemolysis generation, as it was able to capture the persistent leakage flow throughout the entire pumping cycle. This study paves the way for different positive-displacement MCS devices to be compared across different operating conditions, enabling the optimisation of these pumps for improved patient outcomes.</p>","PeriodicalId":13932,"journal":{"name":"International Journal of Artificial Organs","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-08-21DOI: 10.1177/03913988241268033
Nicolas Rivoallan, Marc Mueller, Timothée Baudequin, Pascale Vigneron, Anne Hébraud, Rachid Jellali, Quentin Dermigny, Anne Le Goff, Guy Schlatter, Birgit Glasmacher, Cécile Legallais
Thick honeycomb-like electrospun scaffold with nanoparticles of hydroxyapatite (nHA) recently demonstrated its potential to promote proliferation and differentiation of a murine embryonic cell line (C3H10T1/2) to osteoblasts. In order to distinguish the respective effects of the structure and the composition on cell differentiation, beads-on-string fibers were used to manufacture thick honeycomb-like scaffolds without nHA. Mechanical and biological impacts of those beads-on string fibers were evaluated. Uniaxial tensile test showed that beads-on-string fibers decreased the Young Modulus and maximal stress but kept them appropriate for tissue engineering. C3H10T1/2 were seeded and cultured for 6 days on the scaffolds without any growth factors. Viability assays revealed the biocompatibility of the beads-on-string scaffolds, with adequate cells-materials interactions observed by confocal microscopy. Alkaline phosphatase staining was performed at day 6 in order to compare the early differentiation of cells to bone fate. The measure of stained area and intensity confirmed the beneficial effect of both honeycomb structure and nHA, independently. Finally, we showed that honeycomb-like electrospun scaffolds could be relevant candidates for promoting bone fate to cells in the absence of nHA. It offers an easier and faster manufacture process, in particular in bone-interface tissue engineering, permitting to avoid the dispersion of nHA and their interaction with the other cells.
{"title":"Comparison of hydroxyapatite and honeycomb micro-structure in bone tissue engineering using electrospun beads-on-string fibers.","authors":"Nicolas Rivoallan, Marc Mueller, Timothée Baudequin, Pascale Vigneron, Anne Hébraud, Rachid Jellali, Quentin Dermigny, Anne Le Goff, Guy Schlatter, Birgit Glasmacher, Cécile Legallais","doi":"10.1177/03913988241268033","DOIUrl":"10.1177/03913988241268033","url":null,"abstract":"<p><p>Thick honeycomb-like electrospun scaffold with nanoparticles of hydroxyapatite (nHA) recently demonstrated its potential to promote proliferation and differentiation of a murine embryonic cell line (C3H10T1/2) to osteoblasts. In order to distinguish the respective effects of the structure and the composition on cell differentiation, beads-on-string fibers were used to manufacture thick honeycomb-like scaffolds without nHA. Mechanical and biological impacts of those beads-on string fibers were evaluated. Uniaxial tensile test showed that beads-on-string fibers decreased the Young Modulus and maximal stress but kept them appropriate for tissue engineering. C3H10T1/2 were seeded and cultured for 6 days on the scaffolds without any growth factors. Viability assays revealed the biocompatibility of the beads-on-string scaffolds, with adequate cells-materials interactions observed by confocal microscopy. Alkaline phosphatase staining was performed at day 6 in order to compare the early differentiation of cells to bone fate. The measure of stained area and intensity confirmed the beneficial effect of both honeycomb structure and nHA, independently. Finally, we showed that honeycomb-like electrospun scaffolds could be relevant candidates for promoting bone fate to cells in the absence of nHA. It offers an easier and faster manufacture process, in particular in bone-interface tissue engineering, permitting to avoid the dispersion of nHA and their interaction with the other cells.</p>","PeriodicalId":13932,"journal":{"name":"International Journal of Artificial Organs","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-07-23DOI: 10.1177/03913988241262901
Gerd Klinkmann, Sophie Brabandt, Marlene Möller, Thomas Wild, Benjamin Heskamp, Jens-Christian Schewe, Martin Sauer, Jens Altrichter, Steffen Mitzner
Background: Immune cell dysfunction plays a central role in sepsis-induced immunoparalysis. Targeted treatment using healthy donor immune cell transfusions, particularly granulocyte concentrates (GC) potentially induces tissue damage. Initial trials using GC in an extracorporeal immune cell perfusion system provided evidence for beneficial effects with fewer side effects, by separating patient and donor immune cell compartments. A multicenter clinical trial is exploring feasibility and effects of a 6-h treatment (NCT06143137). This ex vivo study examines technical feasibility and cellular effects of an extended treatment interval up to 24 h.
Methods: Standard GC were purified to increase the potential storage time and subsequently implemented in the extracorporeal immune cell perfusion system. Parameters assessed included cell viability, phagocytosis activity, oxidative burst, cytokine release, and metabolic parameters of purified. GC during an extended circulation time of up to 24 h.
Results: After storage of 72 h granulocytes were viable throughout the study period and exhibited preserved functionality and metabolic activity. The findings highlight a time-dependent nature of cytokine release by neutrophils in the extracorporeal circuit, as cytokine secretion patterns showed IL-8 peaking within 6 h, while MCP-1, IL-6, IL-1β, and TNF-α increased after 24 h of circulation.
Conclusion: Purified GC remain functional after 72 h of storage and additional 24 h in the circulating treatment model. Cytokine secretion patterns revealed a significant increase, especially between 10 and 24 h of treatment. Extending treatment time holds promise for enhancing immune response against sepsis-induced immunoparalysis. These findings provide valuable insights for optimizing immune-targeted therapeutic interventions.
{"title":"Purified granulocytes in extracorporeal cell therapy: A multifaceted approach to combat sepsis-induced immunoparalysis.","authors":"Gerd Klinkmann, Sophie Brabandt, Marlene Möller, Thomas Wild, Benjamin Heskamp, Jens-Christian Schewe, Martin Sauer, Jens Altrichter, Steffen Mitzner","doi":"10.1177/03913988241262901","DOIUrl":"10.1177/03913988241262901","url":null,"abstract":"<p><strong>Background: </strong>Immune cell dysfunction plays a central role in sepsis-induced immunoparalysis. Targeted treatment using healthy donor immune cell transfusions, particularly granulocyte concentrates (GC) potentially induces tissue damage. Initial trials using GC in an extracorporeal immune cell perfusion system provided evidence for beneficial effects with fewer side effects, by separating patient and donor immune cell compartments. A multicenter clinical trial is exploring feasibility and effects of a 6-h treatment (NCT06143137). This ex vivo study examines technical feasibility and cellular effects of an extended treatment interval up to 24 h.</p><p><strong>Methods: </strong>Standard GC were purified to increase the potential storage time and subsequently implemented in the extracorporeal immune cell perfusion system. Parameters assessed included cell viability, phagocytosis activity, oxidative burst, cytokine release, and metabolic parameters of purified. GC during an extended circulation time of up to 24 h.</p><p><strong>Results: </strong>After storage of 72 h granulocytes were viable throughout the study period and exhibited preserved functionality and metabolic activity. The findings highlight a time-dependent nature of cytokine release by neutrophils in the extracorporeal circuit, as cytokine secretion patterns showed IL-8 peaking within 6 h, while MCP-1, IL-6, IL-1β, and TNF-α increased after 24 h of circulation.</p><p><strong>Conclusion: </strong>Purified GC remain functional after 72 h of storage and additional 24 h in the circulating treatment model. Cytokine secretion patterns revealed a significant increase, especially between 10 and 24 h of treatment. Extending treatment time holds promise for enhancing immune response against sepsis-induced immunoparalysis. These findings provide valuable insights for optimizing immune-targeted therapeutic interventions.</p>","PeriodicalId":13932,"journal":{"name":"International Journal of Artificial Organs","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-09-05DOI: 10.1177/03913988241268067
Vincenz Crone, Mario Hahne, Finn Knüppel, Frank-Hendrik Wurm, Benjamin Torner
Medical advancements, particularly in ventricular assist devices (VADs), have notably advanced heart failure (HF) treatment, improving patient outcomes. However, challenges such as adverse events (strokes, bleeding and thrombosis) persist. Computational fluid dynamics (CFD) simulations are instrumental in understanding VAD flow dynamics and the associated flow-induced adverse events resulting from non-physiological flow conditions in the VAD.This study aims to validate critical CFD simulation parameters for accurate VAD simulations interacting with the cardiovascular system, building upon the groundwork laid by Hahne et al. A bidirectional coupling technique was used to model dynamic (pulsatile) flow conditions of the VAD CFD interacting with the cardiovascular system. Mesh size, time steps and simulation method (URANS, LES) were systematically varied to evaluate their impact on the dynamic pump performance (dynamic curve) of the HeartMate 3, aiming to find the optimal simulation configuration for accurately reproduce the dynamic curve. The new Overlapping Ratio (OR) method was developed and applied to quantify dynamic curves.In particular, mesh and time step sizes were found to have the greatest influence on the calculated pump performance. Therefore, small time steps and large mesh sizes are recommended to obtain accurate dynamic curves. On the other hand, the influence of the simulation method was not significant in this study. This study contributes to advancing VAD simulations, ultimately enhancing clinical efficacy and patient outcomes.
医学的进步,尤其是心室辅助装置(VAD)的进步,显著推进了心力衰竭(HF)的治疗,改善了患者的预后。然而,不良事件(中风、出血和血栓)等挑战依然存在。计算流体动力学(CFD)模拟有助于了解 VAD 的流动动力学以及 VAD 中非生理流动条件导致的相关流动诱发不良事件。本研究旨在 Hahne 等人奠定的基础上,验证关键 CFD 模拟参数,以准确模拟与心血管系统相互作用的 VAD。系统地改变了网格大小、时间步长和模拟方法(URANS、LES),以评估它们对 HeartMate 3 动态泵性能(动态 H-Q 曲线)的影响,目的是找到精确再现动态 H-Q 曲线的最佳模拟配置。开发并应用了新的重叠率(OR)方法来量化动态 H-Q 曲线。因此,建议采用小时间步长和大网格尺寸来获得精确的动态 H-Q 曲线。另一方面,本研究中模拟方法的影响并不显著。这项研究有助于推进 VAD 模拟,最终提高临床疗效和患者预后。
{"title":"Dynamic VAD simulations: Performing accurate simulations of ventricular assist devices in interaction with the cardiovascular system.","authors":"Vincenz Crone, Mario Hahne, Finn Knüppel, Frank-Hendrik Wurm, Benjamin Torner","doi":"10.1177/03913988241268067","DOIUrl":"10.1177/03913988241268067","url":null,"abstract":"<p><p>Medical advancements, particularly in ventricular assist devices (VADs), have notably advanced heart failure (HF) treatment, improving patient outcomes. However, challenges such as adverse events (strokes, bleeding and thrombosis) persist. Computational fluid dynamics (CFD) simulations are instrumental in understanding VAD flow dynamics and the associated flow-induced adverse events resulting from non-physiological flow conditions in the VAD.This study aims to validate critical CFD simulation parameters for accurate VAD simulations interacting with the cardiovascular system, building upon the groundwork laid by Hahne et al. A bidirectional coupling technique was used to model dynamic (pulsatile) flow conditions of the VAD CFD interacting with the cardiovascular system. Mesh size, time steps and simulation method (URANS, LES) were systematically varied to evaluate their impact on the dynamic pump performance (dynamic <math><mrow><mi>H</mi><mo>-</mo><mi>Q</mi></mrow></math> curve) of the HeartMate 3, aiming to find the optimal simulation configuration for accurately reproduce the dynamic <math><mrow><mi>H</mi><mo>-</mo><mi>Q</mi></mrow></math> curve. The new Overlapping Ratio (OR) method was developed and applied to quantify dynamic <math><mrow><mi>H</mi><mo>-</mo><mi>Q</mi></mrow></math> curves.In particular, mesh and time step sizes were found to have the greatest influence on the calculated pump performance. Therefore, small time steps and large mesh sizes are recommended to obtain accurate dynamic <math><mrow><mi>H</mi><mo>-</mo><mi>Q</mi></mrow></math> curves. On the other hand, the influence of the simulation method was not significant in this study. This study contributes to advancing VAD simulations, ultimately enhancing clinical efficacy and patient outcomes.</p>","PeriodicalId":13932,"journal":{"name":"International Journal of Artificial Organs","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2024-06-13DOI: 10.1177/03913988241259963
Chunyan Wang, Shilong Xiang
In this study, we investigated the effectiveness of regional citrate anticoagulation continuous renal replacement therapy (RCA-CRRT) in reducing blood calcium levels in three patients with hypercalcemia crisis caused by different etiologies. The sodium citrate chelation of calcium ions was utilized as an anticoagulant for treating severely affected patients. By adjusting the citrate anticoagulant dose and monitoring treatment indicators, RCA-CRRT parameters were actively modified to alleviate the hypercalcemia crisis and provide time for surgery or specialized treatment. Two patients experienced rapid and effective reductions in blood calcium levels, allowing for further treatment, while the third patient exhibited a repeated increase in blood calcium, which eventually decreased after parathyroid adenoma resection, leading to clinical discharge. Our findings suggest that RCA-CRRT can help alleviate hypercalcemia crisis, stabilize the patient's internal environment, and provide valuable time for clinical treatment in cases of various medical conditions causing abnormal blood calcium elevations.
{"title":"Clinical effect of regional citrate anticoagulation continuous renal replacement therapy in three patients with hypercalcemic crisis.","authors":"Chunyan Wang, Shilong Xiang","doi":"10.1177/03913988241259963","DOIUrl":"10.1177/03913988241259963","url":null,"abstract":"<p><p>In this study, we investigated the effectiveness of regional citrate anticoagulation continuous renal replacement therapy (RCA-CRRT) in reducing blood calcium levels in three patients with hypercalcemia crisis caused by different etiologies. The sodium citrate chelation of calcium ions was utilized as an anticoagulant for treating severely affected patients. By adjusting the citrate anticoagulant dose and monitoring treatment indicators, RCA-CRRT parameters were actively modified to alleviate the hypercalcemia crisis and provide time for surgery or specialized treatment. Two patients experienced rapid and effective reductions in blood calcium levels, allowing for further treatment, while the third patient exhibited a repeated increase in blood calcium, which eventually decreased after parathyroid adenoma resection, leading to clinical discharge. Our findings suggest that RCA-CRRT can help alleviate hypercalcemia crisis, stabilize the patient's internal environment, and provide valuable time for clinical treatment in cases of various medical conditions causing abnormal blood calcium elevations.</p>","PeriodicalId":13932,"journal":{"name":"International Journal of Artificial Organs","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}