05/03/2025
This blog is part of a series on innovations in the alternative protein sector, continuing the discussion of problems and innovations in the cultivated meat sector. To read the previous articles in the series, please see here.
Bioprocesses: Cell Expansion, Differentiation, Growth, Propagation and Harvesting
Cells must be seeded at high enough density in order to be able to grow in culture. They are therefore frequently grown in a series of progressively larger bioreactors, propagating in number with each step until they reach a production bioreactor.
The most commonly used bioreactors are stirred tank bioreactors, in which cells are typically suspended in the growth media (more on this later) which is stirred by an impeller. Other bioreactors in which cells are suspended in the growth media include air-lift bioreactors (in which oxygen is bubbled through) and rocking platform bioreactors. Alternatively, there are fixed-bed bioreactors, in which the cells attach to fixed scaffolds within the reactor, while the media is pumped through the reactor and flows past the cells. The cells can be harvested by exposure to reagents that dissociate them from the scaffolding.1
Oxygenation, biomass, the levels of glucose, various metabolites, carbon dioxide and pH are all important factors when cultivating cells and must be carefully monitored and controlled. Oxygen, in particular, is critical, but this is not to say that the other factors are unimportant –metabolites such as lactate and ammonia, for instance, are toxic and can inhibit cell growth and proliferation.2
There are different strategies for feeding and oxygenating cells and eliminating waste from bioreactors. These include batch processes, fed-batch processes and continuous processes. In a batch process, media is added to the bioreactor only at the start of the process and the cells are grown to their maximum density before being harvested – no additional media is added during the process. In a fed-batch process, additional fresh media is added throughout the process to keep the availability of nutrients from being a limiting factor in the proliferation of the cells. In a continuous process, while fresh media is being added to the bioreactor, media is being removed and cells are being harvested. In a perfusion process (which is a subset of a continuous process), cells are retained in the bioreactor while the media is removed.2,3
Finally, due to the risk of contamination, there is an overarching need for sterility in all components involved in these processes. Bioreactors can be either single-use or sterlisable.2
Relevant patent families relating to bioprocesses include Cellular Agriculture Ltd’s WO2023/118872, WO2024/038281 and WO2024/224105 to perfusion bioreactors and to hollow-fibre membranes and constructs for them; CellRev’s (formerly CellulaREvolution’s) WO2024/134178, WO2024/134176 and WO2022/129862 to bioprocesses for continuous culture systems; Ospin’s WO2016/198423 to a modular perfusion bioreactor system; Hoxton Farms’ WO2024/002851 to a system for cell-culture with a movable compression means; and Mission Barns’ WO2021/207293 to a scalable bioreactor system.
Scaffolding
Most animal cells are “anchorage dependent,” meaning that they cannot be grown directly in suspension and require a substrate on which to grow.4 In vivo, the proteins and carbohydrates of the extracellular matrix (ECM) provide structural support to the cells and facilitate intracellular communication by cell signalling, which may drive growth, division and differentiation. Moreover, animal cells in suspension are very sensitive to shear forces within bioreactors and require structural support to mitigate these effects. Scaffolding materials must address these issues.
The composition of the scaffolding and properties such as porosity, stiffness and biodegradability are all relevant. For instance, the scaffold must have a certain porosity to allow the cells to penetrate into it so that they may adhere to it and grow. The scaffold must allow for penetration of oxygen and nutrients to appropriate depths within the cells and removal of wastes from the cells.1 Properties of the scaffold such as its stiffness, along with the composition of the media, can drive the differentiation of cells into fat or muscle, for instance, as well as cellular growth. The cells must be able to be harvested from the scaffold with dissociation reagents, or the scaffold must be biodegradable or edible so that it can be consumed in the final product. If the scaffold is to be eaten, it must not negatively affect the properties of the final product.
Types of scaffolds include microcarriers, hydrogels, porous materials and fibrous materials. Technologies such as 3D printing are being utilised to by some companies to produce scaffolding, particularly to create more structured cuts of meat.
Finally, the use of scaffolding can be avoided with certain cells and under certain conditions. Cells have some ability to create their own ECM and to self-assemble as aggregates, and sometimes even into small organised tissues resembling organs known as organoids.4
Relevant patent families relating to scaffolding include Ever After Food’s WO2025/012910 to a packed bed microreactor, in which scaffolding may comprise edible microcarriers formed from decellularized plant material; Novel Farms’ WO2023/146852 to bioencapsulation with filamentous fungus and yeast cells, which may express ECM proteins; Tantti’s US2023/013733 to porous microcarriers produced from biocompatible polymers; BioBetter’s WO2022/043991 and WO2024/154138 to cellulose-based scaffolding materials with surfaces modified with recombinant ECM proteins produced by plant molecular farming; Sophie’s Bionutrients’ WO2023/031839 to using fibre scaffolds formed from proteins produced by microalgae; and Luyef’s WO2023/102083 to edible scaffolding produced from decellularized seaweed.
Product formulation
As alluded to previously, whole cuts of meat are challenging to make. Two approaches to this problem include a bottom-up approach and a top-down approach.
In a bottom-up approach, modular units of scaffolds and cells are used to construct the final shape of a product, to create a whole cut of meat such as a steak.
Aleph Farms, for instance, describes a bottom-up approach in WO2022/162662 to 3D printing of bioink scaffolds. The company is using this technology to produce structured steaks, with a bioink that includes muscle and fat cells, and a pea protein scaffold.5 TissenBioFarm produces steaks with a 3D bioprinting process using a plurality of nozzles to enable improvements in speed,6 and has filed WO2023/063468, as well as Korean patents KR102747533, KR102747536 and KR102590675 directed to 3D bioprinting processes. Swiss start-up Mirai Foods is also producing steaks through an extrusion process (see, for instance EP4328296.)7 And Steakholder Foods (previously MeaTech 3D Ltd) has also filed WO2021/007359 and WO2021/055996 to a bottom-up approach using bioprinting. Interestingly, the latter family of applications is directed to manipulating a resilient container of cultured bioprinted muscle tissue over 4 dimensions (torsion, elongation, compression and shear). This process, similar to exercising a muscle, is stated to aid in cell differentiation, growth and nutrient efficiency.
A top-down approach relies upon using a previously assembled structure, which can either be a prefabricated scaffold infused with cells, or cells that have self-assembled to create a tissue structure, to produce a whole cut of meat. There are numerous technical challenges involved.
Upside Foods and SuperMeat have both filed patent applications to using a top-down approach to produce cultivated chicken, without any scaffolding material: WO2023/242230 and WO2022/149142. Forsea Foods is using organoid technology to produce meat that is scaffold-free and self-assembling.8,9 WO2023/187771 and WO2022/201147 relate to the use of bovine cells and cells from other species more generally, respectively, to produce cultivated meat through self-assembly of organoids. (Forsea Foods is also producing a cultivated eel product and will be discussed more extensively in the next blog in this series.)
The production costs involved in the cultivation of meat must be brought down to provide consumers with affordable options. To this end, many companies are currently formulating hybrid products that contain both cultivated animal cells and plant-based components,10 such as Good Meat 3. Another company, Vital Meat, has filed WO2021/048325 to a food product comprising duck or chicken cells with other food components. Some companies are also targeting hybrid products that mix cultivated cells with conventional meat.11
Conclusion
Aside from the above technical concerns, there are regulatory implications. As cultivated meat is a novel food, it must meet regulatory standards before it can be brought to market.
In 2024, the Food Standards Agency (FSA) announced plans that may help expedite the regulatory process for novel foods within the UK. The plans include 1) removing the need for renewal authorisations for certain classes of previously approved foods, in order to provide the agency with more resources for reviewing novel food applications, and 2) creating a new public register that replaces the system of requiring a statutory instrument of Parliament for the approval of novel foods. If agreed by Parliament, it is expected that these changes will become law in 2025.12
The FSA granted the first-ever market authorisation for a cultivated meat product in the UK to Meatly’s pet food in July 2024. As of March 2025, three other cultivated meat companies have submitted novel food applications to the FSA for approval. These applications are currently under review. Aleph Farms has submitted an application for its cultivated steak, Gourmey has submitted one for its cultivated foie gras, and Vital Meat has submitted one for its cultivated chicken. The European Food Safety Authority (EFSA) has received applications for cultivated foie gras (from Gourmey) and cultivated beef fat (from Mosa Meat), but to date, no cultivated meat products are approved for sale within the EU.13-17
Whether cultivated meat will ultimately gain acceptance by consumers is another concern. While there are many consumers that are willing to try cultivated meat, there are also some that aren’t – for instance, because the products contain animal cells and are therefore not vegetarian/vegan, because of concerns that their production raises ethical questions or is unnatural, or because of issues with taste or texture.
As evidenced by the numerous patent families discussed above, companies are making technological advances, yet the cultivated meat industry is still nascent and the barriers facing it remain substantial. Questions remain over whether cultivated meat will capture the enthusiasm of investors and consumers alike, whether the political climate and regulatory framework continue to be favourable (following recent bans in Italy and in the US states of Alabama and Florida18) and whether the industry will create viable, economical solutions to the considerable problems involved in scale-up to bring affordable products to market for consumers.
This article is for general information only. Its content is not a statement of the law on any subject and does not constitute advice. Please contact Reddie & Grose LLP for advice before taking any action in reliance on it.
References
2 Cultivated meat bioprocess design | Deep dive | GFI
3 The difference between batch, fed-batch, and continuous processes | INFORS HT
4 Cultivated meat scaffolding | Deep dive | GFI
5 A Deep Dive into the Role of 3D Scaffolds as the Building Blocks for Cultivated Meat – Cultivated X
7 Swiss Start-Up Mirai Foods Debuts the World’s First Cultivated Tenderloin Steak
8 Lab-Grown Eel Producer Achieves ‘Record-Breaking’ Development
9 Forsea Foods creates eel meat using patented organoid technology
10 The science of cultivated meat | GFI
11 Products Overview | Peace of Meat
12 Market Authorisation Service: Progress Report | Food Standards Agency
13 Lab-grown meat in pet food: UK to allow sales of Meatly product – BBC News
14 Aleph Farms requests UK approval for cell-based meat – Just Food
15 Vital Meat Files for UK Regulatory Approval of Cultivated Chicken
16 Gourmey seeks cultivated foods approval in five key markets
17 Mosa Meat submits application to EU
18 6 Places That Have Approved Cultivated Meat And 5 That Have Banned It
