Development of a Multi-Modal StimulationPlatform for the 3D Culture of Wholly EdibleSkeletal Muscle Tissue

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This project falls within the EPSRC Innovative technologies for regenerative medicine research area, within the Healthcare Technologies Theme.ndustrial livestock farming is responsible for approximately 14.5 % of global greenhouse gas emissions.With an increasing number of nations committing to net zero carbon targets by 2050, covering 88 % of totalglobal emissions, reducing the impact of meat production is critical to meeting these aims. For productionto match the ramping demand, widespread deforestation has been deployed. In the first 6 months of 2022over 1200 square kilometers of the Brazilian Amazon were cleared, with 36 % of agricultural deforestationallotted to cattle pastures alone, the largest single utilisation case for the cleared land. This has disastrouseffects on local ecosystems and biodiversity as well as removing one of the largest global carbon sinks.Additionally, there are significant ethical dilemmas attached to the rearing and slaughter of animals forhuman consumption, with over 70 billion animals killed each year.One of the methods proposed to tackle the environmental and ethical issues associated with meat production is the development of cultured meat. Cultured meat is produced by taking a biopsy from a livinganimal and, using tissue engineering techniques, these cells are cultivated to form a product which replicates traditionally available meat options. Ivy Farm are a company at the forefront of this research andare the industrial partner for this project.This project proposes that hollow fibre membrane bioreactors are deployed for this application. Theseoffer a scalable, low-cost platform for cultured meat production when compared to 3D bioprinting alternatives. Additionally, stirred tank bioreactors are used for large volume cell production, but lack the differentiation potential of other bioreactor designs, making them less well suited to replicating the complexstructures and textures of meat.The overarching aim for the project is to design a hollow fibre membrane bioreactor platform which utilisesa wholly edible internal structure and requires minimal downstream processing before it is suitable fora cultured meat product. Hollow fibre membrane bioreactors are ideally suited to this application asthey facilitate the replication of the in-vivo environment. Hollow fibres serve the role of blood vessels for1nutrient and oxygen transport, while providing a scaffold onto which cells can be seeded.Multiple models of cell stimulation, such as electrical signalling, will be utilised to promote cell differentiation to achieve the desired final structure and texture. The application of these techniques to culturedmeat production is highly novel and will be developed from the ground up alongside Ivy Farm.The central steps are seen as the evaluation of different materials and manufacturing techniques for thehollow fibre membranes. These must be compared against a set of parameters that best represent theperformance of genuine animal tissue. This is also a unique challenge to cultured meat, as considerationsof texture and flavour are not required for strictly biomedical applications. Consequently, bioreactor designand manufacture can be commenced, factoring in stimulation methods to best facilitate differentiation.Furthermore, there will be a significant mathematical modelling aspect, enabling future design iterationsto optimised. Building on mass transport models developed by collaborators, these will be applied tothe specific conditions within each bioreactor, and validated experimentally. Additionally, this project isclosely linked to the Oxford humanoid bioreactor lab group. Not only does this bring expertise in the fieldof in-vitro modelling techniques, but also a close link to the biomedical industry, meaning any potentialapplications to novel therapy development can be explored.