ACROBAT · Adsorbent carbons for the removal of biologically active toxins

Adsorbent carbons for the removal of biologically active toxins

The removal of certain classes of biotoxins, bacterial products and inflammatory molecules including hepatic and uraemic toxins, exotoxins, endotoxins and cytokines using adsorbent technologies remains an ongoing clinical challenge. These molecules are responsible for systemic toxicity effects and their removal is often negligible or unsustained in current systems available for the treatment of renal disease, hepatic disease, life-threatening infection and multiple organ failure related to sepsis. Within the ACROBAT project a cross-disciplinary consortium with experience in the development, analysis and clinical implementation of adsorbent biomaterials have developed a range of smart polymer and activated carbon adsorbents for biomedical use. The project’s objectives were to address gaps in the capacity of current technology to reduce inflammatory biotoxin led pathophysiology aiming to optimise the synthesis, processing and coating strategies for synthetic resin derived nanoporous activated carbon bead and monolith adsorbents, to develop bioligand bound macroporous polymer monoliths, to characterise the haemocompatibility and adsorptive efficacy of these materials for biotoxin adsorption using perfusion models, to design appropriate device iterations for testing in models of liver, kidney and life-threatening bacillus anthracis infectious disease and for use in organ perfusion systems for optimised donor organ recovery. Within the project it has been possible to optimise activated carbon bead and monolith synthesis strategies through exchange of best practice between industrial partners. It has been possible to demonstrate optimal adsorptive profile for marker biotoxins related to kidney, liver failure and organ ischaemic injury using small prototypes and then scale up these prototypes for equivalency testing for relevance in the clinical setting. It has been possible to test nanoporous activated carbon monoliths using an in vivo model of liver cirrhosis and demonstrate for the first time safety and ability to reduce bacterial endotoxin levels. It has been possible to synthesise B anthracis exotoxin antibody bound and bioligand bound macroporous polymer perfusion columns and demonstrate for the first time using both in vitro and in vivo models efficacy in the removal of anthrax protective antigen. Such technologies may be further developed for use in a number of organ and haemoperfusion applications related to augmentation of liver and kidney dialysis, transplantable organ preservation and life threatening infection related to anthrax. Such adsorbent based medical device technologies have significant potential for clinical impact through the improved removal of inflammatory and infectious molecules which currently drive tissue damage and produce life-threatening clinical complications. Figure 1: Adsorbent monolith image showing the macroscale channel structure in addition to the nanoporosity within the channel walls enabling adsorption of inflammatory biomolecules such as the cytokines For more information see the project website at https://www.brighton.ac.uk/research/our-research/life-health-and-physical-sciences/research-groups/biomaterials-and-medical-devices/acrobat.aspx

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