The International Journal of Artificial Organs

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Editorial
Restricted accessEditorialFirst published January, 2017pp. 1-3
Materials,Surfaces,and Systems for Extracorporeal Therapies and Beyond
Viktoria WeberThomas Groth
Research article
Restricted accessResearch articleFirst published January, 2017pp. 4-8
A New Integrated Technique for the Supportive Treatment of Sepsis
Jens HartmannStephan Harm
Abstract
Although there has been continuous, intensive research for many years in the field of sepsis treatment, currently available treatment options are limited, and there is still a lack of systems that efficiently remove endotoxins as well as mediators. Here, we discuss a newly developed, integrated technique that combines different aspects for their use in extracorporeal blood purification for the supportive treatment of liver failure and sepsis.
Review article
Restricted accessReview articleFirst published January, 2017pp. 9-14
Mechanisms of Endothelial Activation in Sepsis and Cell Culture Models to Study the Heterogeneous Host Response
Tanja EichhornMichael B. FischerViktoria Weber
Abstract
Sepsis is currently viewed as a fundamental disintegration of control functions from intracellular signalling to immunoregulatory and neuroendocrine mechanisms. The immediate threat in sepsis is invasive infection, and the need to activate immune defense mechanisms to clear the pathogen before irreparable damage occurs. In the process of pathogen elimination, however, the systemic host response to infection may cause collateral damage to the endothelium and may lead to the destruction of host tissues.

A number of experimental models have been developed to monitor endothelial activation and to study endothelial dysfunction under septic conditions. Here, we review the application of these models to assess the highly variable host response in sepsis and to investigate the efficacy of adsorbent-based extracorporeal therapies. We also highlight the need for efficient diagnostic tools, which are indispensable to select patients who are likely to benefit from distinct adjunctive therapies.
Research article
Restricted accessResearch articleFirst published January, 2017pp. 15-21
The Role of Ionized Calcium and Magnesium in Regional Citrate Anticoagulation and its Impact on Inflammatory Parameters
Karin StroblStephan HarmViktoria Weber
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Abstract
Introduction
Regional anticoagulation with citrate has been found to be superior to heparin in terms of biocompatibility, and numerous protocols for regional citrate anticoagulation have been published, while a consensus on the target concentration of ionized calcium (Ca²⁺) in the extracorporeal circuit has not been reached so far.
Methods
The aim of this in vitro study was to assess the impact of different citrate concentrations on coagulation as well as on complement activation and cytokine secretion and to investigate the impact of ionized magnesium (Mg²⁺) on these parameters.
Results
We found that citrate effectively reduced coagulation, complement activation, and cytokine secretion in a dose-dependent manner and that a target Ca²⁺ concentration of 0.2–0.25 mM was required for efficient anticoagulation. Mg²⁺ triggered complement activation as well as interleukin (IL)-1β secretion in lipopolysaccharide (LPS)-stimulated whole blood in a dose-dependent manner and independently of Ca²⁺. Additionally, it was found to reduce activated clotting time (ACT) in samples with low Ca²⁺ levels, but not at physiological Ca²⁺.
Conclusions
Taken together, our data support the notion that regional citrate anticoagulation results in decreased release of inflammatory mediators in the extracorporeal circuit, requiring the depletion of both, Ca²⁺ and Mg²⁺.
Review article
Restricted accessReview articleFirst published January, 2017pp. 22-30
Biomimetic Principles to Develop Blood Compatible Surfaces
Vladislav SemakMichael B. FischerViktoria Weber
Abstract
Functionalized biomaterial surface patterns capable of resisting nonspecific adsorption while retaining their bioactivity are crucial in the advancement of biomedical technologies, but currently available biomaterials intended for use in whole blood frequently suffer from nonspecific adsorption of proteins and cells, leading to a loss of activity over time. In this review, we address two concepts for the design and modification of blood compatible biomaterial surfaces, zwitterionic modification and surface functionalization with glycans – both of which are inspired by the membrane structure of mammalian cells – and discuss their potential for biomedical applications.
Research article
Restricted accessResearch articleFirst published January, 2017pp. 31-39
Effect of Thiolated Glycosaminoglycans on the Behavior of Breast Cancer Cells: Toward the Development of in vitro Models of Cancer
Alexander KöwitschAnkur ChhalotreThomas Groth
Abstract
Purpose
The influence of extracellular matrix components like glycosaminoglycans (GAG) or adhesive proteins on the migration of cancer cells and the progression of tumorigenesis remains a challenging task. Therefore, this study aims to give insight into the interaction of cancer cells exhibiting different metastatic potential (MDA-MB-231, MDA-MB-468) with surface immobilized GAG interacting with serum proteins like fibronectin.
Methods
Model substrata were covalently coated with different thiolated GAG (hyaluronan (HA), chondroitin sulfate (CS), heparin (Hep)) and investigated for the adsorption of fibronectin (FN) with surface plasmon resonance. Then, adhesion of breast cancer cells in the presence of and without serum proteins was studied. Further, the outgrow behavior of confluent cancer cells was examined with the help of cell migration chambers and single-cell migration with time-lapse microscopy.
Results
FN adsorption revealed that the Hep-coated surfaces were able to adsorb significantly more protein than CS and HA. Generally, initial adhesion of breast cancer cells on GAG-coated substrata was inhibited for HA- and CS-coated substrata in the presence of serum proteins for both cell lines in comparison to serum-free conditions. The cell size was also significantly decreased by the influence of serum proteins. The outgrow studies clearly confirmed the different migration speed of both cancer cells while single-cell migration was particularly enhanced on HA-coated surfaces.
Conclusions
The results reveal that adsorption of serum proteins (e.g. albumin) possess an inhibiting effect on the adhesion of breast cancer cells and that single-cell migration is enhanced for both breast cancer cell lines on HA.
Review article
Restricted accessReview articleFirst published January, 2017pp. 40-42
The International Hypothermia Registry (IHR): Dieter's ESAO Winter Schools and Beat's International Hypothermia Registry
Beat H. WalpothMarie MeyerChristophe Gaudet-Blavignac
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Abstract
Accidental hypothermia could be listed as an ‘orphan disease,’ since mild hypothermia is common but has no severe medical consequences, whereas severe hypothermia is rare and life-threatening. In order to increase our knowledge, find new outcome predictors, and propose better guidelines for the treatment of deep accidental hypothermia victims, we created the International Hypothermia Registry (IHR: https://www.hypothermia-registry.org), which will allow us to gather a large number of cases in order to achieve statistical significance and issue evidence-based recommendations.

Volume 40, Issue 1, January 2017

Materials,Surfaces,and Systems for Extracorporeal Therapies and Beyond

A New Integrated Technique for the Supportive Treatment of Sepsis

Mechanisms of Endothelial Activation in Sepsis and Cell Culture Models to Study the Heterogeneous Host Response

The Role of Ionized Calcium and Magnesium in Regional Citrate Anticoagulation and its Impact on Inflammatory Parameters

Biomimetic Principles to Develop Blood Compatible Surfaces

Effect of Thiolated Glycosaminoglycans on the Behavior of Breast Cancer Cells: Toward the Development of in vitro Models of Cancer

The International Hypothermia Registry (IHR): Dieter's ESAO Winter Schools and Beat's International Hypothermia Registry