Veganuary: Culturing an appetite; advances in 3D bioprinting

Throughout Veganuary, we are looking at the technologies that are taking us beyond animal agriculture. As a walk around any supermarket in the UK will attest, the number of plant-based alternatives to meat and dairy products is growing almost daily. No longer confined to the specialist shops of 20 years ago, plant-based alternatives have spread and fully colonised the mainstream, driven by an increased awareness of the ethical and environmental ramifications of animal agriculture. However, for many consumers, these products are not yet convincing enough for them to make the switch away from slaughter-derived products. If closer facsimiles were possible, with lower environmental impacts and without the need to kill, consumer uptake could increase further.

Whilst this may sound like wishful thinking, Louise Atkins explores how cutting-edge bioprinting could one day bring truly revolutionary products to a shelf near you.

Global livestock production makes up nearly 15% of all human-caused emissions annually, and is the single largest user of land resources, using almost 80% of all agricultural land. Much of these land and energy inputs are wasted as the energy needed to grow, fatten, and keep alive a whole cow is vastly higher than that obtained from the (fairly limited) portions we eat. And yet, consumer appetites for meat – and particular high-end steaks and premium seafood – remain unsated.

Given the choice, could you be tempted by no-kill meat and fish products, sidestepping the ethical concerns alongside yielding lower wastage and reduced environmental costs? If so, 3D printed meat created from cultured animal cells fits this bill.

What is bioprinting?

Similar to 3D printing, bioprinting involves a printer, a digital blueprint, and ink which is printed to form a 3D construct. The difference? Bioprinting utilises “bio-inks” which comprise living cells. By depositing layers of different bio-inks, three-dimensional tissues can be assembled through additive manufacturing. Whilst bioprinting is already widely used in tissue research, the technique can also be used to create tissues and organs for transplant or, potentially, consumption.

Stem cells are harvested from animals, cultured and then differentiated to form bio-inks which can be printed to mimic meat texture. By combining various cell types – including myoblasts, fibroblasts, adipocytes, or precursor cells programmed towards these fates – complex meat tissues can be produced with native-like flavour and texture. The ratio of components in the digital blueprint will vary depending on the cut of meat being created. For example, the blueprint for a fat-marbled Japanese wagu steak will be completely different to that of a sirloin steak.

Raising the steaks and making a splash – bioprinted beef and fish

Many innovators are focussing on producing bioprinted “whole cuts” and steaks. The reason for this is simple – these are premium cuts of meat which fetch high prices and, unlike highly processed foods such as burgers, have complex structures which are otherwise difficult to produce through direct culture.

In 2018, Israeli start-up Aleph Farms printed the first ever slaughter-free steak by printing living bovine cells onto plant-based matrices. The use of an edible, supporting matrix allows improved shape fidelity – whilst plant-based matrices were initially employed, it may become possible to “print” scaffolds which more closely resemble the extracellular matrix (ECM) found in natural tissue. Aleph Farms also made history when they produced the first ever cultivated meat in space aboard the International Space Station in 2019. Whilst comparisons to Star Trek’s replicator may be premature, being able to “grow” meat on demand and in situ may prove useful for remote locations where resupply is difficult or infrequent.

Also in the cultured steak market. Steakholder Foods (formerly known as MeaTech 3D Ltd.) are developing steaks made solely from printed animal cells which are almost indistinguishable from real steaks. In 2021, MeaTech 3D Ltd. succeeded in producing a 104 g printed steak: the largest cultivated steak to date. Steakholder Foods’ production method involves harvesting bovine umbilical cord stem cells from cows and growing them in a bioreactor to create cell lines capable of continuous reproduction. Cells then differentiate into adipose, muscle and scaffold bio-inks which are printed following a template. Following incubation and cellular maturation, the muscle cells can spontaneously contract just like non-lab grown muscle cells.

A new wave of cultured fish and seafood products are also in development. In a bid to make people “sea-food differently”, the global leader in aquaculture (BlueNalu Inc.) has partnered with Japan’s largest sushi chain. Together they aim to develop and seek regulatory approval for cultured fish products, such as cultured bluefin tuna, to solve supply chain issues caused by overfishing – a major issue for over one-third of world fish stocks already, even as demand rises. 3D printed fish would avoid issues such as bones and the accumulation of mercury, microplastics and antibiotics.

Opportunities and challenges in bioprinted food

Thanks to advancements in 3D bioprinting, the cultured meat industry is entering a new realm, where lab-grown products can better mimic animal tissue texture and structure. Innovators wanting to secure their position have multiple ways to obtain robust patent protection around their inventions. Improved animal cell lines, cell culture methods, and scaffolds, or (looking beyond the realm of “hard” cell biology) bioreactors, manufacturing processes to finish the product, bioprinters and components thereof will all be subject of development and can be protected. An IP portfolio such as this with overlapping layers of protection, covering all aspects of the production chain, will provide significant value to innovators. This is especially true as the challenge of obtaining broad protection for the end products increases as the field becomes more crowded, and as the ever-improving end products become less distinguishable from those produced by conventional agriculture.

However, even if this mimicry is achieved, the public may still be apprehensive about consuming lab-grown meat. In addition, these products aren’t vegetarian and, despite recent advances, still need to obtain regulatory approval.

A major obstacle for these cell culturing methods is the continued use of FBS (foetal bovine serum) from foetuses of slaughtered pregnant cows. In addition to ethical concerns, FBS is expensive and represents a significant cost within cell culture. It is however indispensable, providing essential nutrients and conditions for growing cells. It is hoped that FBS will be replaced with an alternative serum when production moves from the research to commercialisation stage. However, a viable alternative to FBS is yet to be found, and the race to develop one is well underway. The prize for being first is significant, as early movers will be able to leverage this position widely.

One major bottleneck for bioprinted meats is the availability of suitable animal cell lines. Amongst other characteristics, it is necessary that cell lines are genetically stable, immortal (i.e. able to divide repeatedly), and vigorous, with a short “doubling time” in culture. This is a tall order, and although many human cell lines with these characteristics have been developed for use in the medical field, it can be non-trivial to transfer this into other animals. The Good Food Institute (GFI) recognised that the absence of suitable animal cell lines is a major barrier to the development of cultured meat and, in 2021,instigated an initiative to increase access and funding for the development of cultured meat cell lines by creating an openly accessible cell line library. However, due to the high costs associated with cell line development, there will likely be a reluctance to deposit in this repository.

Moreover, companies may be unwilling to publicly disclose their cell lines at all, choosing instead to protect them as trade secrets. There may be a view that, if a cell line is disclosed, it may be easily copied and, without access to competitor’s factories, patents covering the cell line will be hard to enforce. If so, we might expect a low number of patents filed towards deposited cell lines. However, many characteristics of the cell lines may be directly detectable in the final products, in particular genetic traits and alterations that underly the desirable properties, and infringement of patents protecting these aspects may be easily detected. Patents still have a major role to play in this field as part of broad IP strategy, and innovators at the platform level may be able to licence their technology broadly to multiple creators of individual cell lines.

The future

There is still long way to go before we’ll be seeing cultured meat products, such as 3D bioprinted steaks and sushi, on our supermarket shelves. However, the cultured meat market is predicted to reach nearly $25 billion globally by 2030 with the World’s largest meat company investing £100 million in cultivated meat products and partnering with one of the largest cell-based meat companies to build a cell-based production plant. This is likely to pave the way for further investment and innovation in this area of future food.