Bioprocess development for scalable production of cultivated meat

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World population is predicted to reach 10 billion by 2050. There is an increased need to find sustainable food alternatives to support this rapidly growing population. Livestock meat is not sustainable and it comes with detrimental effects on the environment, risks of food-borne diseases and antibiotic resistant bugs1. Alternative food technologies such as cultivated meat can provide a solution to this growing problem, while offering many advantages over livestock meat. It is animal meat but produced without the animal in a controlled environment in a cultivator. It doesn't require animal slaughter as it is produced from cells obtained from a small tissue sample from the animal. Cultivated meat is meat that is free from antibiotics, zoonotic bacteria and viruses and even with a customisable nutritional profile (e.g. enriched in omega fatty acids, reduced cholesterol)1-2. This is a relatively new concept that still requires significant research to reach satisfy scale requirements for production, reach affordability, and to mimic texture and nutritional profile of livestock meat. This project aims to develop scalable bioprocesses to produce cultivated meat through a multidisciplinary approach that uses engineering and biological principles. It uses biomaterials (e.g. food grade hydrogels) to encapsulate cells, thus providing a 3D environment; it uses cultivators (bioreactors) for culture and it addresses the complexity of meat tissue through co-culture of different cell types.Similar to livestock meat, cultivated meat will have a complex structure comprising muscle, fat and other connective cells. This complex combination is what gives the taste and nutritional value. Bovine adipose-derived stem cells (bASCs) will be used in this project as a starting cell source for production of cultivated meat as they are easy to isolate, easy and cheap to grow in the lab, their expansion is scalable3,4 and they can differentiate to fat and muscle cells. bASCs will be encapsulated in food-grade hydrogels where they will be first expanded and differentiated. Hydrogel capsules of uniform sizes and narrow size distribution will be produced by using emulsification. Parameters such as hydrogel injection rate and shear force necessary to form the capsules will be investigated. Different size ranges will be produced and tested for optimal cell survival and growth inside the capsules. Hydrogels such as alginate, methylcellulose, gellan gum and others will be investigated. The optimal hydrogels will be selected and used in conjunction with molecular cues to induce cell differentiation. Bioprocesses using encapsulated cells will be developed in small bioreactors such as spinner flasks. Process parameters to be investigated include cell seeding densities, feeding regimes, agitation strategies and their influence on cost-efficiency.This project fits within the Manufacturing the Future theme and fits 3 of the 4 priority research visions within this theme: 21st century products, sustainable industries as cultivated meat has the potential to provide food security in a sustainable manner and new industrial systems as this is a newly formed industry. It also addresses the following research areas: biomaterials and tissue engineering as it uses hydrogels for cell encapsulation; manufacturing technologies as it will utilize bioreactors and process systems as it will develop bioprocesses for the production of the cultivated meat microtissuesReferences:1Stephens, N. et al. (2018) Trends in Food Science & Tech, 78, 155-166.2Post MJ. (2014) J Sci Food Agric.; 94(6):1039-41.3Hanga MP et al (2020) Biotech Bioeng; 117(10):3029-3039.4Hanga MP et al (2021) Biotech Bioeng; https://doi.org/10.1002/bit.27842.