Why A Making Lab-Grown Steak is So Difficult
The world’s first lab-grown steak was produced last December by an Isreali company, Aleph Farms. Despite costing $50 and being only 5mm thick, food critics were pleasantly surprised by the familiar taste, texture and smell of the meat that was almost indistinguishable from farmed beef.
It was an amazing accomplishment, but the first lab-grown burger was made in 2013. That means there was a 5-year gap between the making of the first cultured burger and making a cultured steak. As improbable as that seems, this time gap makes sense; growing a cultured steak is very difficult.
Compared to ground beef or chicken nuggets, the architecture of a steak is complex and hard to replicate in vitro (outside of a living organism). In order to make ‘3D structured’ meats like a steak, chicken breast or pork chop, entirely new elements of tissue engineering have to be added. To grow 3D cultures, specified starting points, scaffolds, stimulus mechanisms, and even artificial blood vessel networks have to be developed.
Before I go any further, if you are not familiar with the basics of cellular agriculture (including growth mediums and scaffolds) I would recommend giving my other article a read first 😊
Why is growing a steak so hard?
You can think of growing a cultured burger like going to Chipotle in mid-afternoon. You walk in, get your food, enjoy every last bite and leave a happy customer. But growing a steak is like going to Chipotle… at rush hour.
Let’s set the scene: It’s 5:10 on a Friday afternoon. Everyone comes in and the line of people starts to grow and grow and you end up at the back of this crowd of people waiting for a burrito. You are willing to wait because you need that burrito. Eventually, it’s just taken too long and you give up and go home sad.
Now imagine this line is a lab-grown steak. Each person in line is a cell, and the burrito is the essential nutrients that they need to stay alive.
The problem is, steak is thick. There are too many cells crammed into a petri dish and the nutrients just can’t get to them. Thus, it takes advanced engineering to find ways to get a burrito to every person before they leave… or in the cell’s case, die.
Due to the thickness and complex cell structure of a steak, the cells die quickly. As the thickness of a culture increases, the structure gets more complex and our current methods for culturing cells fail to support the cells. In vivo (inside a living organism), bodies have blood vessels that carry oxygen as well as extracellular matrices to support the cell and keep them alive. Replicating these factors in vitro is called 3D biofabrication.
Making Cellular Agriculture 3D
3D biofabrication is the collection of methods and technologies needed to make 3D structured meats. It includes nutrient and oxygen supply and waste removal systems within the meat as well as carefully constructed scaffolds and ways to make the muscle contract.
These methods are still being perfected and have a long way to go before they are scalable. Luckily for the world of lab-grown meat, there are a few interesting technologies and techniques being developed right now to make 3D structured meat possible and efficient in the near future.
Kick-starting the process
There are two possible ways to start the process of growing a steak.
Option 1: The traditional way
The first way to start growing the culture is by taking a biopsy from a cow (removing a small sample of living cells without harming the animal) and isolating satellite cells. These will differentiate into myocytes, the most prominent type of muscle cell in meat. Although satellite cells are primarily being researched right now, multipotent stem cells are a promising start point for the cultures.
Option 1 is simple but still relays on a living aminal, which is not ideal.
Option 2: Immortalizing meat cells
Another option is to never ‘start’ the process at all, but rather have cells collected from one initial biopsy replicate forever and use those to produce endless beef. Unfortunately, creating a never-ending reservoir of cells that grows at an exponential rate has its challenges.
The first batch of cells created directly from the satellite cells is called the primary cell line. After the first batch has used up all the nutrient-containing medium, it’s transferred to a new medium. This is now the secondary cell line. This naming system continues indefinitely.
The problem is, over this time, the cells get unintentionally genetically altered. The medium in which they are placed (FBS) plays a large role in this. The genetic and phenotypic change in the cells is known as subculturing. Cell lines will be examined and certain “good” cells will be removed from the cell line to replicate separately while the rest are trashed. This new culture of “good” cells is called a cell strain.
Having to separate these subcultures is not ideal for large-scale production and will become overwhelming once the immortal cell line gets too big. Researchers are putting an intense focus on making immortal cell lines a reality, but for now, it’s a work in progress.
It’s in Their Blood to Survive
Cells want to survive… it’s in their blood. Literally.
In the body, arteries carry blood to the cells, delivering oxygen and nutrients, while veins carry away waste. Cell cultures lack a circulatory system to perform those essential functions.
Because steaks are so thick, cells in the centre of the meat do not have access to oxygen, meaning most die of hypoxia (aka, they suffocate). Without a circulatory system, those cells have no way to access oxygen or nutrients, so they die. In other words, these cells are at Chipotle during rush hour.
In order to produce a lab-grown steak or any other 3D culture, a network of artificial blood vessels has to be integrated into the culture.
These blood vessels would likely be 3D printed and integrated into the growing cell culture to support the muscle tissue. Similar techniques are already being used to 3D print functional human organs.
Playing Mind Games
An important aspect of any type of cellular agriculture is the scaffold. The scaffold mimics the extracellular matrix that is present in vivo. It works to trick the cell into thinking it is in a living organism and therefore should survive. Scaffolds are so important, in fact, that cell cultures are only defined as 3D once the scaffold has a 3D structure as well.
Currently, scaffolds for 3D cell cultures are animal derived to optimize for factors like cell-adhesion, fibre alignment and compatibility with the in vitro environment. Ideally, these scaffolds should be synthetic while still remaining biocompatible. The most important substances in a scaffold are collagen and fibronectin.
There are a few really interesting options surfacing for 3D scaffolds:
A Scaffold with Control
Scaffolds produced using a synthetic biodegradable polymer can use a new process called electrospinning which adds a lot of really interesting features to the 3D scaffold. Using electrospinning, parameters such as fibre thickness and orientation can be adjusted to positively influence the architecture of the steak. These scaffolds can encourage muscle fibres to orient themselves in one direction only, exactly how they do in vivo. The major benefit of this type of scaffold is that it is easily replicated.
A Promising Experimental Scaffold
Hydrogels are similar to a traditional scaffold… but a little different. A major advantage of hydrogels is that they force the cells to set in a dense, spatially uniform pattern. All scaffolds have ‘achors’. These anchors are usually made of collagen and are where the muscle fibres physically attach to the scaffold. Hydrogels have a unique anchoring system that allows for active force generation and therefore helps with in vitro muscle contraction (more on that later). The major barrier to these gels is that they will possibly degrade in early phases of 3D culture growth.
3D Printed Meat Tunnels
In a thick, 3D cultured product, it is difficult to have a scaffold effectively dispersed throughout the culture. One possible solution that is being researched is to create scaffolds that are integrated into a nano-tunnel network in the meat. This would be achieved by using 3D printing to structure the cells and the tunnels and having the scaffold set up base camp within the nano-tunnels. In fact, they are already using 3D printed nano-tunnels for in vitro leather production.
The Muscle Tissue Needs to Flex
In vitro muscle contraction is a key ingredient to producing lab-grown meat. That’s right; this muscle tissue can flex inside a petri dish.
Promoting muscle contraction stimulates protein synthesis in the culture to help the cells fuse together. Normally, this can be done by adding simple chemical agents to the medium. Unfortunately, this is more complicated in 3D cultures. The two most promising options are using electrical and mechanical stimulation.
Electrical Stimulation
Electrical stimulation is fairly simple, well-researched and cost-effective. The major downfall is that it promotes subculturing in 3D cultures… which we really do not want.
Mechanical Stimulation
Mechanical stimulation is a newer idea in cellular agriculture. Mechanotransduction is the process by which cells react to mechanical stimuli. Through anchors on the scaffold, a mechanical force is applied to the tissue, forcing it to contract.
Not Quite There, But Certainly on the Mooove
Despite being an impressive accomplishment, Aleph farms has a long way to go before we have a steak that looks like this:
3D structured meats require a complex network of scaffolding, artificial blood vessels and contraction mechanisms to survive in vitro. The technology may not be here quite yet, but it’s certainly coming upstream, and it’s pretty darn cool; 3D printed arteries to deliver oxygen to lab-grown cells and scaffolds that can make the muscle tissue contract… That’s sick!
It may take a few years, but start looking forward to a ‘petri dish special’ at The Keg.
Thanks for Reading! If you liked the article, reach out on LinkedIn :)
