Bioprocess development for scalable production of cultivated meat

培育肉规模化生产的生物工艺开发

• 批准号: 2568599
• 金额: --
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2568599
• 关键词: Bioprocess; development; scalable; production; cultivated

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.

预计到2050年世界人口将达到100亿。越来越需要找到可持续的食物替代品来支持这一迅速增长的人口。牲畜肉是不可持续的，它对环境有不利影响，存在食源性疾病和抗生素耐药性细菌的风险1。替代食品技术，如人造肉，可以为这一日益严重的问题提供解决方案，同时提供许多优于牲畜肉的优势。它是动物的肉，但生产没有动物在一个受控制的环境中培养。它不需要屠宰动物，因为它是从动物的小组织样本中获得的细胞中产生的。养殖肉是不含抗生素、人畜共患病细菌和病毒的肉，甚至具有可定制的营养特征（例如富含ω脂肪酸、降低胆固醇）1-2。这是一个相对较新的概念，仍然需要大量的研究来满足生产的规模要求，达到可负担性，并模仿牲畜肉的质地和营养特征。该项目旨在开发可扩展的生物工艺，通过使用工程和生物学原理的多学科方法生产养殖肉类。它使用生物材料（例如食品级水凝胶）封装细胞，从而提供3D环境;它使用培养器（生物反应器）进行培养，并通过共培养不同类型的细胞来解决肉组织的复杂性。与牲畜肉类似，培养肉将具有由肌肉，脂肪和其他结缔细胞组成的复杂结构。这种复杂的组合赋予了味道和营养价值。牛脂肪干细胞（bASC）将在该项目中用作生产培养肉的起始细胞来源，因为它们易于分离，易于在实验室中生长且价格低廉，它们的扩增是可扩展的3，4并且它们可以分化为脂肪和肌肉细胞。bASC将被封装在食品级水凝胶中，在那里它们将首先被扩增和分化。采用乳化法制备粒径均匀、粒径分布窄的水凝胶胶囊。将研究形成胶囊所需的参数如水凝胶注射速率和剪切力。将生产不同尺寸范围的胶囊，并测试胶囊内的最佳细胞存活和生长。水凝胶如藻酸盐、甲基纤维素、结冷胶等将被研究。将选择最佳的水凝胶并与分子线索结合使用以诱导细胞分化。将在小型生物反应器（如转瓶）中开发使用包封细胞的生物工艺。待研究的工艺参数包括细胞接种密度、补料制度、搅拌策略及其对成本效率的影响。该项目符合未来制造主题，并符合该主题4个优先研究愿景中的3个：21世纪世纪产品，可持续的工业，如养殖肉类，有可能以可持续的方式提供粮食安全，新的工业系统，因为这是一个新的形成产业。它还涉及以下研究领域：生物材料和组织工程，因为它使用水凝胶进行细胞封装;制造技术，因为它将利用生物反应器和工艺系统，因为它将开发用于生产培养肉类微组织的生物工艺参考文献：1 Stephens，N.等（2018）食品科学与技术趋势，78，155-166.2Post MJ.（2014）J Sci Food Agric.; 94（6）：1039-41.3Hanga MP等人（2020）Biotech Bioeng; 117（10）：3029-3039.4Hanga MP等人（2021）Biotech Bioeng; https://doi.org/10.1002/bit.27842.