Final Report Summary - MONACO-EXTRA (Monolithic Adsorbent Columns for Extracorporeal Medical Devices and Bioseparations) The aim of this project was to manufacture novel composite 3D monolithic adsorbent columns for use in extracorporeal medical devices for blood purification (haemoperfusion), therapeutic apheresis and cytapheresis and in bioseparations for analytical and commercial applications. The participating partners were: University of Brighton, Brighton, UK, co-ordinator; MAST Carbon International Ltd, Basingstoke, Hampshire, UK; Protista Biotechnology AB, Bjuv, Sweden; Polymerics GmbH, Berlin, Germany; Lund University, Lund, Sweden; Universität für Weiterbildung, Krems, Austria, and Brighton and Sussex University Hospitals NHS Trust, Brighton, UK. The project brought together a multidisciplinary consortium of specialists in different areas of synthetic, polymer and surface chemistry, biomedical and biological sciences, engineers and bioengineers, immunologists and medics united by the aim of developing new and efficient means of treatment for patients with organ failure, including renal and hepatic failure, currently incurable diseases such as cancer and autoimmune diseases. The main objectives of the project were: to synthesise a range of novel composite adsorbents with interconnected macropores, using natural and synthetic polymers, polymer cryogels and activated carbon; to design adsorption columns for extracorporeal blood purification from molecular solutes and metastatic cells; to explore applications of these materials in bioseparations for analytical and commercial purposes and in critical care medicine. These objectives were achieved through the knowledge transfer activities between academic, medical and industrial partners involved in this project.Over the course of the project, the project partners have developed a range of processes that have allowed (i) the synthesis of porous polymer microbeads suitable for application within extracorporeal systems (ii) the production of bead and monolithic activated carbons with micro/mesoporous structure for enhanced molecular adsorption in extracorporeal haemoperfusion (iii) the manufacture of monolithic super-macroporous 3-D polymer cryogels suitable for blood cell separation and (iv) the synthesis of composite cryogel/activated carbon adsorbents and cryogel/polymer adsorbent composites. The efficacy of the materials and composite materials has been optimised for each of the different clinical situations. In order to achieve this, carbon-based adsorbents have been developed with increased adsorptive capacity for a range of renal toxins, liver toxins and cytokines through the engineering of their porosity. In addition, polymer-based adsorbent bead materials have been produced and modified to increase their efficiency for a range of adsorption and cell separation applications, including the specific targeting of tumour cells. Furthermore, methods have been developed within the consortium to overcome problems associated with the coating of these adsorbents with polymer once incorporated into composite cryogels. This breakthrough has enabled the production of composite materials that significantly retain their adsorptive capabilities. During their reiterative development the materials have undergone appropriate physical and physicochemical characterisation as well as biocompatibility and cytotoxicity assessment using the complementary expertise from across the consortium. Significantly, selected materials and composites prepared by members of the consortium were successfully subjected to a range of in vitro toxicity and biocompatibility studies specifically developed within the consortium. The results obtained indicated there were no toxic effects from the materials themselves. Biocompatibility and molecular adsorption studies were also successfully undertaken in simulated clinical conditions using blood from patients with renal failure at the Royal Sussex County Hospital. The project consortium disseminated its activities via scientific presentations, publications in international peer reviewed journals and through the organising of scientific events. Four very successful events have been run throughout the course of the project including i) a Summer School 'Porous Hydrogels for Biomedical Applications: from Cytapheresis to Tissue Engineering' was organised in Antalya, Turkey, in October 2009 with participants from 15 different countries. The School gave excellent research training and networking opportunities for researchers of all levels ii) A specialised Workshop on Biomaterials for Medical Applications was held in April 2010 at Brighton organised by the Brighton and Sussex University Hospitals NHS Trust together with the Brighton and Sussex Medical School. Here, project participants discussed the use of medical adsorbents in the treatment of sepsis, renal and hepatic failure and world leaders gave invited lectures iii) Krems University organised a Satellite Symposium at the Winter School of the European Society for Artificial Organs. The topic was ‘Advancing Roles: Biomaterials in Artificial Organs and Regenerative Medicine, Passive to Active to Bioreactive’. The event was held at the Artis Hotel in Semmering, Austria in January 2011. The event attracted 120 participants from 19 countries. There were 23 lectures plus one round table discussion. In addition, 51 posters were presented iv) The University of Brighton organised a meeting entitled ‘Medical Devices and Carbon Materials: Current Issues in Health and the Environment’ in September 2011. The meeting was held at the University and attracted an international field of speakers and poster presenters over the 2 days of the conference. The event was attended by approximately 90 participants. The project consortium represented a critical mass needed to cover the gap between "knowledge production" and "knowledge use" enabling commercialisation of the new developments achieved in the project. The new materials and techniques developed in this project will significantly strengthen the European industry of biomedical materials and medical devices. The project outcomes will reach out to the wider community and have strong societal implications as they are aimed at tackling serious health conditions and complications, particularly in elderly patients. By producing novel and more efficient materials for medical applications and potentially reducing hospital stay of the patients, the project outcomes will contribute to the reduction of financial burden on national health care providers across Europe. For all correspondence related to the MONACO-EXTRA project please email:monaco@brighton.ac.uk; MONACO-EXTRA website address: http://www.brighton.ac.uk/monaco/
