Skip to main content

Novel medical adsorbents for extracorporeal treatment of life threatening conditions

Final Report Summary - MEAD-ET (Novel medical adsorbents for extracorporeal treatment of life threatening conditions.)

The main objectives of the MEAD-ET project encompass developing and then investigating coated nanostructured adsorbents which have a potential for use as a medical device for blood purification to remove toxic molecules from the blood of patients and treat a variety of life threatening and chronic conditions such as; renal and hepatic insufficiency, sepsis and systemic inflammatory response syndrome and immuno-dependent diseases. These objectives include the synthesis and optimization of nanoporous resin derived activated carbon adsorbents with defined pore structure followed by the development and optimization of dextran coating of these adsorbents for improved haemocompatibility. Once the materials were optimized their adsorptive capacity for both small and large toxins relevant to hepatic/renal insufficiency and sepsis were investigated to study the relationship between their structure and their adsorption properties. The joint investigations were carried out via transfer of knowledge and networking activities between the University of Brighton (UB), University of d’Auvergne (UC) and the team from the National Academy of Sciences of Ukraine (IEPOR).

The project work included the synthesis, optimization and characterization of nanostructured carbon adsorbents. Activated carbon materials (ACM) were prepared from different pre-cursors and further activated using the super-heated steam activation process developed at IEPOR. The characterization and comparison of these ACM was conducted using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analysis and both low temperature nitrogen and mercury porosimetry to establish the effect of activation on the carbon materials. The project results showed successful transfer of the super-heated steam activation to the ACM (prepared in the UK), gaining materials with further developed pore structure and increased surface areas as evidenced by the porosimetry results. These ACM were tested for adsorption against a range of molecules and showed similar capacity in comparison to the IEPOR ACM. There are a number of important reasons why the project aimed to transfer the ACM technology from IEPOR to the ACM produced by the European based MAST Carbon International. The patented MAST technology of manufacturing ACM from phenol-formaldehyde resins is more versatile and environmentally friendly than the technology of manufacturing the IEPOR ACM as the current stringent legislation will not allow their manufacturing in the EU. In addition the versatility of the chemical composition of phenol-formaldehyde resins allows manufacturing of porous resins with a range of pore sizes and fine tuning of the pore size distribution is more accurate and can be adapted to a wide range of adsorbates with different molecular weight.

The ACM were grafted with various biocompatible polymers such as dextran and heparin using parenteral injectable solutions, these materials were then tested to establish the effect of the coating on their porous characteristics and on their production of dust particles (fines). Results indicated that coating led to a decrease in material surface area and pore volume, which correlated to the amount of coating and the underlying ACM. Coating with dextran reduced the production of fines, with even the lowest amount of coating showing an effect which would be beneficial for an extracorporeal material in contact with blood.

Carbon adsorbent cytotoxicity was then carried out in vitro in accordance to EN ISO 10993 part 5 and a complete range of haemocompatibility tests were conducted on the coated and uncoated materials this included the coagulation tests; prothrombin time (PT) and Activated partial thromboplastin time (APTT), thrombin generation time and fibrinogen adsorption, the complement C3a, C4a activation and blood cell activation and haemolysis testing. The cytotoxicity results for ACM demonstrated the difficulty of testing an adsorbent material as they can adsorb nutrients from the media, the assay was modified and 50% extracts were used to determine cytotoxicity and to circumvent the ACM adsorptive properties. The findings suggested that the ACM were not cytotoxic to cells and that materials with varying surface area did not have any significant effect on the results obtained. The results for the uncoated and coated ACM with Voluven, Intralipid, Gelafusin, dextran and dextran/heparin, as expected showed that these materials were not cytotoxic to cells. The complete range of haemocompatibility tests conducted on the coated and uncoated materials determined that compared to the controls the ACM did not activate the inflammatory response to any further degree or cause haemolysis. This suggests that the activated carbon material in particularly with a dextran coating, is a suitable material for blood contact extracorporeal applications.

A comprehensive range of marker molecules of sizes ranging from 113 Da- 67kDa were tested for their adsorption by the materials and the influence of coating on their adsorption properties determined. The uncoated materials showed good adsorption characteristics and as expected the coatings decreased adsorption kinetics and capacity to a lesser extent, for the various marker molecules, due in part to the influence on the surface area and pore volume of the materials. Adsorption capacity demonstrated no difference in adsorption of the important protein bound bilirubin compared to the uncoated, but demonstrated a beneficial reduction in albumin adsorption. Also coating with dextran was shown to maintain the removal of anti-ss-DNA antibodies from the serum of patients with Systemic lupus erythematosus, whilst reducing the non-selective protein adsorption. The project concluded that choosing the optimal material for a blood purification application is a balance between quantity of coating to ensure good haemocompatibility and low fine production without hindering adsorption properties.

The project findings have contributed towards an improved performance of the ACM through optimization of physiochemical parameters and coating of the materials to improve haemocompatibility and adsorption of selected toxin molecules. The ACM show real potential for development as a medical device and will lead to a strengthening in the European biomaterials industry and offer a stepping stone to the lucrative worldwide market. In addition, to offering a therapeutic intervention to chronic disease and the ageing population thus contributing to achieving an EU policy on dealing with an ageing society. The project will significantly strengthen the European industry of biomedical materials and medical devices and provide a competitive advantage in this highly competitive area dominated by the Japanese and the US. Development of the materials beyond the current state of the art, will allow the future design, production and testing of small prototypes. Coated nanostructured adsorbents have a potential for medical applications as an extracorporeal device to treat a variety of life threatening and chronic conditions. The overall research output would predominantly be measured by a significant impact on the improvement in haemodynamic parameters and the well being of patients. The subject of this inter- and multidisciplinary project as well as its objectives reach out to the wider community and have strong societal element as they are aimed at tackling serious health conditions and improving patient quality of life, as well as reducing the cost burden to the health service. By producing novel and more efficient specialized adsorbents for therapeutic medical applications and potentially reducing hospital stay of the patients, the Consortium will indirectly contribute to the reduction of financial burden on national health care providers.