Homepage: http://www.bioart-fp7.eu/

Description of the project:

The joint research project deals with an innovative surgical dressing for the treatment of burns and chronic wounds. The concept is based on a special membrane to be used in the sterile wound cover enabling the continuous supply with essential nutrients for the skin cells. This forms optimal ambient conditions for regenerating cells and improved wound healing, without exhibiting the negative properties of gauze or non-woven pads. Fewer complications are expected in future through accelerated healing and reduced keloid formation resulting in a considerably augmented of quality of life for the patients affected. Both from the medical and the economic point of view the new wound management system should show significant improvements.

In the project eXcorLab is a sub contractor of Membrana GmbH. The work packages comprise cytotoxicity and pyrogenicity testing of the wound dressing and its influence on wound healing in an in vitro skin model

Description of the project:

Patients with chronic kidney disease (CKD) and also those on dialysis (CKD-5D) show an increased cardiovascular mortality and morbidity due to several risk factors including hyperphosphataemia, diabetes mellitus, hypertension, anaemia, dyslipidemia and uremic retention solutes toxicity. Protein-bound uremic toxins, such as phenylacetic acid, indoxyl sulfate and p-cresylsulfate contribute substantially to the progression of chronic kidney disease and cardiovascular disease (CVD). However, based on their protein-binding these hydrophobic toxins are poorly cleared during conventional hemodialysis or even hemodiafiltration and thus accumulate in CKD-5Dpatients. Therefore, this project aims at the development, characterisation and validation of adsorbant particles for the removal of uremic toxins from plasma of chronic renal failure patients.

The consortium is composed of four partners covering synthetic, analytical and bio-safety and compatability aspects. HZG will develop new adsorbant particles and will modify already available (patent-protected) materials for the adsorption of uremic toxins. CHA will characterise the particles regarding their chemical and biochemical properties. EXC will use its strong experience in testing of biomaterials for biocompatibility aspects. UNH will test side effects, if any, of the particles on cultured human- blood cells (monocytes) and vascular endothelial and smooth muscle cells.

Description of the sub-project (eXcorLab GmbH):

The main goal of the subproject is to characterize the interaction of silver nanoparticles with biological systems. We are focussed on the interaction with blood cells, vascular and skin cells.

Our first approach was to establish appropriate test systems to determine the cytotoxicity of silver nanoparticles for cultered human primary cells. In different bioassays sterility and pyrogenic behaviour of the newly developed nanoproducts was tested after contact with human donor blood. Another objective was to investigate the possible influence of silver nanoparticles on irritation and wound healing processes with the aid of an in vitro skin model. One main aspect during the development of the various test systems was the ability to discriminate between the effect of the applied silver nanoparticles and metallic silver and silver ions.

Description of the project:

On the basis of existing (established) polymer membranes manufactured from polyethersulfon (PES) and polyvinylpyrrolidone (PVP) novel molecular and bio-mimetic technologies of functionalization of this membrane system shall be developed which allow the directed tuning of separation characteristics and biocompatibility parameters. Working packages will focus to distinctly and systematically vary the features of the PES/PVP membranes which are important for separation behaviour (performance) and the specific and non-specific interaction of molecular and cellular blood components. The resulting membrane samples will be intensively characterized with respect to physico-chemical (surface) parameters and the interaction with biopolymers and cells.
Finally it shall be possible to develop membranes which allow significantly improved blood purification and showing improved lifetime with minimal activation of the patients clotting system over a period of 24 hours. The intended properties will considerably improve the qualification of the resulting membranes for applications in intensive care medicine (acute dialysis). Particularly, the advanced purification capacity will result in the removal of hydrophobic substances that up to now could not be removed adequately. The latter feature shall improve the situation of chronic patients with cardio-vascular complications.

Publication: https://www.ncbi.nlm.nih.gov/pubmed/23505419

Description of the project:

Uremic patients suffer from infections and are in a state of permanent microinflammation. Since many metabolic products can neither be cleared by the kidney nor by extracorporeal elimination they are accumulating in these patients. In this subproject we want to address the question if small proteins in the molecular weight range between β2-microglobulin and retinol binding protein can activate granulocytes/monocytes leading to vascular inflammation and damage. Uremic proteins will be isolated from hemofiltrates and compared to entire and fractionated hemofiltrate, to uremic and to normal plasma. Functional assays of inflammatory cells will be used to explain the effect of these molecules on immune suppression. Cocultures of granulocytes/monocytes with endothelial monolayers will be performed to establish a model of vascular inflammation and damage. To assess nonspecific toxic effects a cytotoxicity assay using human fibroblast cell lines will be used. Finally, we are aiming to answer the question if current extracorporeal therapies and hemodialyis membranes, in particular, should be improved in order to remove proteins in the molecular weight range studied more efficiently.

Projektinhalt der eXcorLab GmbH:

Main task of the kidney is to remove metabolic waste products, which have to be obligatory excreted by urine. In patients with end stage renal disease this important function cannot be fulfilled by the kidney, which leads, if not treated, to acute poisoning with lethal outcome. Hemodialysis is the treatment of choice to the acute disease and serves as a bridging to find a suitable organ for transplantation. Hemodialysis is based on the principle of diffusion and filtration by suitable membrane filters. The bulk of the toxic substances accumulating in the plasma of patients with chronic renal failure is bound to proteins and thus, by their resulting molecular size, cannot be removed by dialysis. Examples for these toxins are indoxyl sulphate, p-cresyl sulphate, phenylen acetic acid, dimethyl guanosin and phenylen ethyl amine.
In the course of the project procedures shall be developed, which allow the removal of uremic toxins by improved separation from patients blood. Consecutively approaches and methods shall lead to the use of the findings gained in the development and production of hemodialysis membranes.

Publication: https://www.ncbi.nlm.nih.gov/pubmed/24469432