The Circular Economy (CE) is gaining mainstream attention, but not in all sectors. The linear model, from cradle to grave, still prevails for small Medical Devices (MDs). The perception of cross contamination dominates management and processing practice after first use, but studies show that only a minority of healthcare waste is infectious. Potential innovations in product design, materials, procedure management and post-use processing offer effective infection control to enable a far higher percentage of material to enter additional cycles of functionality beyond first use. With savings from reprocessing reported at around 50%, NHS costs would reduce by hundreds of millions of pounds if such circular use of resources is fully implemented. Additional cycles may be in closed loops of MD functionality, remaining legally compliant, or open loops, where material is used in other sectors. This project aims to develop these technical and non-technical solutions and bring them together in a coherent 'whole system' to demonstrate operation of the Circular Economy for four representative small MDs. This will require a multidisciplinary approach to utilise the expertise of product designers, manufacturers, clinical staff, waste management companies and waste processors. Wider adoption will need the engagement of professionals in health service procurement and intermediary organisations from the commercial and non-profit sectors, such as trade bodies, consultancies and health NGOs. The project will last 2.5 years. Based on a well-defined understanding of the problem, it will start with stakeholder workshops to conduct a deep dive on the planned innovations in product design (including materials) and reprocessing technologies as well as operational and management systems. Separate but coordinated work tracks and teams will then develop innovations in these fields and produce full specifications. These will then be brought together in proof-of-concept experiments to evaluate the whole circular system. The engineering innovations related to adapted or novel small MDs designs, materials and material selection methods, and reprocessing technologies (re-use, remanufacturing or recycling) will be encapsulated in targeted CE specifications for four reference products as well as more abstracted CE guidelines for application to each product category. The specifications for each part of the circular system and the evaluation results will be published in a variety of media and be available for project partners and others to develop into large scale systems. The project will expand knowledge of the principles of effective Circular Economy systems in a part of the healthcare sector and integrate learning from the few previous waste management projects on specific medical devices into a 'whole system' approach. In this way we hope to significantly influence the development of a UK circular Economy for small medical devices.

Aim: This project aims to provide fundamental understanding to underpin the design and early development of new generation lipid emulsions for intravenous application in clinic, which are based on components of interest to the industrial sponsor. It will provide new and fundamental understanding of emulsion formulations from new components and connect this with the biological properties of the formulations relevant for clinical application. Background: Intravenous emulsions are oil-in-water emulsions of triglycerides and are clinically applied as vehicles for administration of drugs or as the parenteral nutrition in patients, and particularly, premature neonates. In the last decade, and based on increased understanding of lipid emulsion metabolism, the typical compositions of intravenous emulsions have been changed to reduce adverse effects (eg 20% vs 10% composition as the latter has higher level of free lipids causing oversaturation of the lipoprotein lipase). The current notion in the field is to replace typically used triglycerides and to explore new components to reduce adverse effects (eg reduce inflammatory eicosanoids or avoid linoleic acid overload) and/or to provide a positive therapeutic effect (eg omega-3 acids effects on retinal and cognitive development of foetus and infants). However, a number of recent publications use classical formulation protocols with an ad hoc addition of new components, without evidence of study at the fundamental level what effects these new additions have on the emulsion formulation and properties. Moreover, studies on the effect of these new additions on the lipolysis, cellular uptake and pathways, and immunology will be required to assess the potential clinical usefulness of the new formulations. The aim of the proposed project will be achieved in three phases. Phase 1. Formulation and physicochemical characterisation: Experimental design and laboratory analyses will be applied to assess the effect that mixing of several different lipids (including compounds of interest to Baxter) has on (i) interfacial behaviour, (ii) lipid phase viscosity and its impact on the efficiency of the comminution process, (iii) charge and size distribution of the emulsion droplets (iv) emulsion stability, viscosity and emulsion 'break-down'. The physicochemical characterisation will include: particle size, zeta potential, morphology, rheology, interfacial tension and interfacial rheology. Phase 2. In vitro biological characterisation: A number of factors, including lipids composition, have been identified to impact the clearance and metabolism of lipid emulsions. Phase 2 hence focuses on in vitro studies of lipolysis and cellular metabolism of lipid emulsions from 'Phase 1'. The level of free lipids will be measured. Cellular association and internalization will be studied following incorporation of 3H-cholesteryl oleoyl ether, and/or a fluorescent probe. Labelled emulsions will be applied to the cells in culture (J774 macrophage, HUVEC endothelial and primary hepatocytes) under different conditions (eg exogenous apoE). Cell deposition and utilization of lipids will be assessed. Phase 3. Analyses of potential immuno-modulatory effects: The potential adverse immune-modulatory properties of new intravenous emulsions present a safety concern, particularly as these are often used in immune-compromised patients. Immune-modulatory effects for emulsions from 'Phase 1' will be assessed through their impact on monocytes, T cells, dendritic cells (DC) and neutrophils, as follows. Peripheral blood monocytes will be stimulated with emulsion samples and intracellular cytokine staining and multi-colour FACS analysis will be used to measure the level of cytokine production. DCs functional properties (endocytosis and T cell activation) after treatment with emulsion samples will be assessed. The impact of emulsions on neutrophils' respiratory burst, phagocytic ability and cytokine profile will be studied.