Cultivated meat is grown from animal cells in a lab, not on a farm. To grow, these cells need nutrients delivered through a controlled system. Here's how it works:
- Nutrient Delivery Systems: Cells need a mix of glucose, amino acids, salts, and vitamins to survive, multiply, and form muscle, fat, and connective tissue. These are provided through a liquid called cell culture media.
- Key Components: Media includes basal nutrients (like glucose and amino acids) and additives (like growth factors and hormones) to guide cell growth and development.
- Cost Challenges: Media traditionally made up 55–95% of costs, but serum-free, food-grade options now cost under £0.76 per litre, with goals to reduce this to £0.19 per litre.
- Growth Methods: Cells grow on microcarriers (tiny beads) in suspension or on scaffolds in 3D structures, mimicking natural environments.
- Production Systems: Nutrients are delivered in batch, fed-batch, or perfusion systems, each with trade-offs in cost, efficiency, and scalability.
- Oxygen Delivery: Oxygen is critical for cell growth but challenging to provide in dense cultures. Solutions include using oxygen-binding proteins to improve efficiency.
Why It Matters: Nutrient delivery affects the cost, quality, flavour, and safety of cultivated meat. Advances in serum-free media, food-grade ingredients, and scalable systems are making production more affordable and efficient.
| System | Cost (£/kg) | Capital (£M) | Reactor Volume (m³) | Yield (kTA) | Advantage | Challenge |
|---|---|---|---|---|---|---|
| Batch | £30 | £262 | 649 | 6.8 | Lower costs | Larger reactor volumes |
| Perfusion | £41 | £530 | 197 | 6.9 | Higher cell density | Complex equipment needs |
Takeaway: The industry is rapidly improving nutrient delivery systems to make cultivated meat more affordable and scalable while maintaining quality and safety.
Key Components of Cell Culture Media
Cell culture media is made up of two main elements: basal media and specialised additives. Basal media provides the essential nutrients cells need to survive, while the additives - like growth factors and hormones - help cells multiply and form tissues [1].
Basal Media: The Nutritional Foundation
Basal media is essentially a buffered solution containing glucose, salts, vitamins, and essential amino acids [1]. Glucose serves as the primary energy source and is typically used in concentrations ranging from 5.5 to 55 mM [2]. According to Eagle's Minimum Essential Medium, 13 amino acids are considered essential in vitro, though these differ from what cells require in living organisms [2].
Inorganic components, including macro- and micro-nutrients, are carefully measured to meet cellular needs [5]. Minor elements like lipids and antioxidants also play a role in supporting cell health. Once these foundational nutrients are in place, the next step involves guiding cell development with growth factors.
Growth Factors and Additives
Cells in cultivated meat production need more than just basic nutrition - they also require signals to grow, multiply, and develop into tissues. Growth factors and hormones provide these signals, ensuring proper cell function, structural integrity, and differentiation [8]. Frequently used growth factors include:
- Fibroblast Growth Factor (FGF)
- Insulin-like Growth Factors (IGF-1 and IGF-2)
- Transforming Growth Factor-beta (TGF-β)
- Platelet-Derived Growth Factor (PDGF)
- Hepatocyte Growth Factor (HGF) [8]
The cost of these additives has historically been a challenge, but recent advancements are making them more affordable. For instance, a 2024 study in Cell Reports Sustainability showcased a breakthrough where immortalised bovine satellite cells were engineered to produce their own FGF2, potentially eliminating the need for expensive external growth factors [9].
"These kinds of systems offer the potential to dramatically lower the cost of cultured meat production by enlisting the cells themselves to work with us in the processes, requiring fewer external inputs (added ingredients), and therefore fewer secondary production processes for those inputs." – Andrew Stout, Lead Researcher [9]
Interestingly, non-meat components like scaffolding and residual growth factors typically account for a small fraction - just 1% to 5% - of the final product [7]. These developments are paving the way for serum-free, food-grade media.
Moving to Serum-Free and Food-Grade Media
With the push for cost efficiency and ethical practices, the industry is moving towards serum-free, food-grade media. This shift eliminates the need for animal-derived components like fetal bovine serum (FBS), which has been a major concern due to ethical and contamination risks. The financial advantages are clear: Believer Meats has shown that serum-free media can be produced for as little as £0.48 per litre, and further advancements could bring costs down to less than £0.19 per litre [10] [1].
Food-grade components offer another cost-cutting opportunity. On average, they are 82% cheaper than reagent-grade alternatives when purchased at a 1 kg scale [10]. Replacing basal medium ingredients with food-grade options could potentially reduce costs by about 77% [10]. Regulatory approvals are also reinforcing this trend. For example:
- In January 2023, the Singapore Food Agency approved GOOD Meat's serum-free cultivated chicken.
- In January 2024, Israel's Ministry of Health approved Aleph Farms' serum-free cultivated beef.
- In July 2024, Meatly received UK approval for its cultivated pet food [10].
Additionally, Mosa Meat, in collaboration with Nutreco, successfully replaced 99.2% of basal cell feed by weight with food-grade components, achieving cell growth comparable to pharmaceutical-grade media [10].
Switching to serum-free, food-grade media offers more than just economic benefits. It addresses ethical concerns, reduces the risk of contamination, ensures consistent quality, and simplifies downstream processing [2] [6] [11]. This transition marks a key step forward in making cultivated meat production more efficient and sustainable.
Methods for Delivering Nutrients to Cultivated Meat Cells
Once the composition of cell culture media is defined, the next challenge is figuring out how to deliver nutrients effectively to sustain cell growth. The method used for nutrient delivery largely depends on the cultivation system and how the cells are grown. Different systems require specific approaches to ensure cells receive the nourishment they need throughout their growth cycle.
Suspension and Adherent Cultures
In cultivated meat production, cells are typically grown using either suspension cultures or adherent cultures. Each method comes with its own way of delivering nutrients.
In suspension cultures, microcarriers - tiny floating beads - are used to provide surfaces for anchor-dependent cells. These beads increase the surface area available for cell growth, allowing for higher cell densities. As the medium circulates through the bioreactor, cells attached to the microcarriers absorb nutrients directly from their surroundings. Companies like Matrix Meats and Tantti Laboratory have even developed edible microcarriers for cultivated meat production. These edible carriers can be integrated directly into the final product, eliminating the need for a separation step required with non-edible carriers.
On the other hand, adherent cultures use scaffolds to create a three-dimensional structure that mimics the natural environment of cells within living tissue. These scaffolds must be biocompatible and either biodegradable or edible, with mechanical properties that support cell growth. The 3D structure improves nutrient and oxygen flow throughout the tissue, replicating conditions closer to those found in living organisms.
These methods influence how nutrients are initially distributed. Suspension cultures with microcarriers are often ideal for early-stage cell expansion, while adherent cultures with scaffolds are better suited for tissue formation and differentiation during later stages of production.
Batch, Fed-Batch, and Perfusion Systems
The timing and method of nutrient delivery play a major role in cell growth, product quality, and production costs. Cultivated meat production typically uses one of three systems:
| System | Nutrient Delivery | Advantages | Best Used For |
|---|---|---|---|
| Batch | All nutrients added at the start (closed system) | Simple and quick for experiments | Short, rapid culture processes |
| Fed-Batch | Nutrients supplied continuously during growth | Higher yields with more flexibility | High-density, adaptable production |
| Perfusion | Fresh medium added while waste is removed | Supports stable, high-density environments | Long-term, controlled production scenarios |
Batch systems are straightforward: all the nutrients are added at the start, and no further additions are made. This simplicity makes them ideal for quick experiments, though they often result in limited biomass yields.
Fed-batch systems involve adding nutrients gradually throughout the cultivation process. This approach can boost overall yields but may also lead to longer processing times and the accumulation of by-products that could inhibit cell growth.
Perfusion systems take things a step further. Fresh medium is continuously supplied while waste products and dead cells are removed. This keeps the culture environment stable and supports high cell densities over extended periods, making it particularly suited for large-scale production.
The choice of system depends on factors like budget, production goals, and the desired balance between yield and quality. This nutrient delivery strategy naturally ties into the next challenge: oxygen delivery.
Oxygen Delivery in Bioreactors
Delivering oxygen effectively is one of the biggest challenges in cultivated meat production. Aerobic respiration generates 19 times more energy per glucose molecule than lactic acid fermentation, making oxygen critical for efficient cell metabolism [12].
However, culture media carry far less dissolved oxygen than blood - about 45 times less - creating a bottleneck as cell density increases [12]. Efficient oxygen delivery, along with the removal of carbon dioxide, is therefore essential.
Traditional oxygenation methods, like mixing and gas sparging, can introduce mechanical stress that damages cells. To address this, researchers have explored using oxygen-binding proteins such as haemoglobin to improve oxygen delivery without the need for aggressive mixing. For instance, Hemarina, a company specialising in oxygen-binding proteins, developed HEMBoost for food fermentation and HEMOXCell (from Alitta virens) for mammalian cell culture. Studies have shown promising results; one example saw a 4.6-fold increase in cell density in CHO cells when HEMOXCell was added [12].
Different oxygen carriers have unique properties. Mammalian haemoglobins have shown mixed results in cell culture, while plant phytoglobins, though having a higher oxygen affinity, may not be as effective for certain processes in cultivated meat production.
Interestingly, oxygen delivery needs to be carefully adjusted to match the cells' requirements at different stages. For example, skeletal muscle cells thrive at oxygen levels much lower than atmospheric conditions - partial pressures of 15 to 76 mmHg compared to 160 mmHg at sea level [12]. In some cases, mild hypoxia can even encourage cell proliferation and improve satellite cell renewal. This highlights the importance of tailoring oxygen delivery to optimise cell growth and development, complementing the nutrient delivery methods discussed earlier.
Advances and Challenges in Nutrient Delivery
Recent strides in nutrient delivery systems are reshaping the cultivated meat industry, offering ways to cut costs and scale up production. While these developments are promising, the road to commercial success is still fraught with challenges. Progress in serum-free media (SFM) and scaling technologies is revolutionising how nutrients are delivered to cells, but large-scale production continues to push existing systems to their limits.
Progress in Serum-Free Media and Cost Reduction
One of the most impactful changes in nutrient delivery has been the move away from fetal bovine serum (FBS). Serum-free media now accounts for at least half of the variable operating costs in cultivated meat production [10]. Companies are finding innovative ways to reduce these costs. For example, Believer Meats has managed to produce serum-free media for just $0.63 per litre by replacing albumin and fine-tuning media components [10].
Switching to food-grade components has also proven to be a game-changer. Research shows that food-grade components are, on average, 82% cheaper than reagent-grade alternatives at a 1 kg scale [10]. Mosa Meat, in collaboration with Nutreco, replaced 99.2% of its basal cell feed with food-grade components, achieving cell growth comparable to pharmaceutical-grade media [10]. Similarly, Nutreco and Blue Nalu demonstrated that bluefin tuna muscle cells thrive equally well in both food-grade and pharmaceutical-grade media [10].
"Replacing basal medium components with bulk, food-grade, equivalents could reduce basal media cost by 77%." – Liz Specht [10]
However, growth factor costs remain a major hurdle. For example, nearly 98% of the cost of Essential 8 medium is linked to FGF-2 and TGF-β [10]. To tackle this, companies like BioBetter are exploring innovative methods, such as producing growth factors in tobacco plants, with costs expected to drop to $1 per gram of protein [10]. Regulatory approvals in countries like Singapore, Israel, and the UK further support these advancements [10].
Scaling Up Nutrient Delivery Systems
Scaling up nutrient delivery from lab settings to commercial production is a complex challenge. With manufacturers targeting production volumes of around 300,000 pounds annually by 2027 [4], the focus is on ensuring uniform nutrient distribution and efficient waste management. These factors directly influence both cell growth and the quality of the final product.
Maintaining consistent conditions in large-scale systems is particularly tricky. Stirred tank reactors, widely used for their scalability, often face issues like oxygen and shear stress gradients, which can disrupt cell growth as reactor size increases [13].
To address these challenges, media recycling and continuous processing are gaining traction. Perfusion bioreactors, for instance, allow for continuous harvesting and waste removal while recycling media, which improves efficiency and reduces costs [4]. However, these reactors are smaller and harder to scale compared to stirred tank systems, creating trade-offs between operational efficiency and production capacity [4].
Facility design also plays a crucial role. Closed processing systems can minimise the need for expensive clean rooms, but they demand advanced monitoring and control systems to maintain sterility. As the industry evolves, companies are increasingly specialising in areas like animal-free media development, growth factor production, and bioprocess design to enhance flexibility and cut costs [4][14].
Comparing Nutrient Delivery Strategies
The choice of nutrient delivery strategy has a significant impact on both costs and scalability. Common approaches include fed-batch systems, continuous processing, and perfusion systems, each with its own set of trade-offs.
| System | Fed-Batch | Perfusion |
|---|---|---|
| Production Cost | £30/kg | £41/kg |
| Total Capital Investment | £262M | £530M |
| Total Bioreactor Volume | 649 m³ | 197 m³ |
| Production Rate | 6.8 kTA | 6.9 kTA |
| Key Advantage | Lower capital costs | Higher cell density |
| Main Challenge | Larger reactor volumes | Complex equipment needs |
Fed-batch systems are more cost-effective, with production costs of around £30/kg compared to £41/kg for perfusion systems [15]. However, perfusion systems require much smaller reactor volumes (197 m³ versus 649 m³) and can achieve up to four times the cell mass yield per reactor volume [17]. On the downside, perfusion systems come with higher capital costs, with total investment reaching about £530M, including £71M for specialised equipment [15].
To strike a balance between cost and complexity, many companies are opting for hybrid products that combine cultivated meat with plant-based ingredients, reducing the required cell mass [17]. Others are moving towards undifferentiated or minimally differentiated cell products, which simplify nutrient delivery [17].
"Due to the specific requirements of each cell type and product, a universal bioprocess and scaling solution may not be feasible. Consequently, there's a demand for additional techno-economic models and experimental data to fine-tune bioprocesses for each specific product type." – The Good Food Institute [16]
Selecting the right nutrient delivery strategy is critical. Companies must weigh their production goals, cost targets, and product requirements to find approaches that balance scalability with the precision needed for high-quality, safe cultivated meat.
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How Nutrient Delivery Affects Product Quality and Safety
Nutrient delivery plays a central role in shaping cultivated meat. It influences not just cell growth but also the flavour, texture, nutritional value, and safety of the final product. As covered earlier in the discussion on cell culture media, having precise control over nutrient delivery allows producers to fine-tune these aspects like never before.
Effects on Nutritional and Sensory Profiles
Cultivated meat is often nutritionally comparable to traditional meat, but its production process offers a unique advantage: the ability to tweak the cell culture medium to enhance specific nutrients. Dana Hunnes, PhD, MPH, RD, a clinical dietitian at Ronald Reagan UCLA Medical Center, highlights this potential:
"In principle, cultivated meat is almost nutritionally identical to farm- or ranch-raised meat. But with cultivated meat, you can adjust the medium in which the living cells are grown to add certain vitamins and nutrients that would alter, and perhaps improve, its nutritional quality." [18]
By modifying nutrient delivery, producers can adjust protein levels, amino acid profiles, and fat compositions, potentially creating healthier fat structures compared to those in conventional meat. However, while adding vitamins to the medium might support cell growth, it’s not yet clear if this results in a noticeable increase in vitamin content in the final product [19].
The sensory qualities of cultivated meat - its taste, texture, and appearance - are also shaped by nutrient delivery. For instance, Mark Post’s 2013 lab-grown burger incorporated beetroot juice for colour, saffron and caramel for flavour, and binders for texture [1]. The tasting panel found the burger slightly dry, an issue tied to its lower fat content, illustrating how nutrient delivery directly impacts mouthfeel.
Appearance, particularly colour, presents a unique challenge. Cultured muscle tissue often looks pale due to suppressed myoglobin expression under standard oxygen conditions [1]. When metmyoglobin was added, the result was a brown hue resembling cooked beef rather than the vibrant red of fresh meat [1].
Flavour complexity is heavily reliant on compounds generated during production. For example, benzaldehyde, a compound with a bitter almond taste, has been identified in cultivated meat, especially in samples containing differentiated muscle cells [22]. Similarly, 2,5-dimethylpyrazine, which gives a roasted beef-like flavour, appeared only in samples with well-differentiated muscle cells [22].
Texture remains a significant hurdle. Laboratory-grown muscle fibres tend to feature embryonic or neonatal proteins rather than the mature proteins found in traditional meat. Techniques like electrical or mechanical stimulation can improve protein quality by increasing myofibre diameter, but scaling these methods for commercial production is still under investigation [1].
These customisations in nutrition and sensory qualities highlight the importance of maintaining strict safety protocols, which are addressed through regulatory measures.
Regulatory Requirements for Nutrient Delivery
The way nutrients are delivered during production doesn’t just impact quality - it directly affects safety. This makes regulatory oversight a critical part of the process. Risks include potential chemical contamination from media ingredients, bioreactor materials, and residues left during processing [20].
Sterility is a top priority. Mycoplasma, a pathogenic bacterium, is found in 5% to 35% of cell lines worldwide [21], making rigorous screening and disinfection essential. Bioreactors must incorporate sterilisation systems like steam-in-place and clean-in-place technologies to maintain aseptic conditions [3].
The industry is also shifting towards serum-free media, partly to address safety concerns. For example, GOOD Meat transitioned to serum-free media for its cultivated chicken, earning approval in Singapore in early 2023 [1]. This move reduces contamination risks tied to animal-derived components and aligns with stricter safety standards.
Chemical residue testing is another critical area. Studies on conventional meat have revealed antibiotic residues - such as ciprofloxacin and tetracycline - at levels exceeding recommended limits [3]. Similarly, cultivated meat producers must implement stringent testing protocols to detect residues from growth media, antibiotics, and other chemicals used during production.
Monitoring genetic stability is equally important. Over time, mutations or genetic drift in cell cultures can lead to the loss of essential functions, reduced nutritional quality, or even potentially harmful changes. Regular genetic checks help ensure that cultured cells maintain their intended characteristics throughout production cycles [3].
The regulatory framework for cultivated meat is evolving rapidly. In 2022, UPSIDE Foods became the first company to receive FDA approval for its cell-based chicken in the U.S. [20]. Singapore, Israel, and the UK are also advancing their approval processes [10]. However, comprehensive guidelines covering all aspects of production are still being developed, requiring close collaboration between researchers and regulatory bodies [3].
To support these efforts, digital food safety technologies are becoming vital. Advanced monitoring systems integrated into bioreactors can detect contamination in real time, ensuring consistent quality and compliance with regulations [3].
Conclusion
The delivery of nutrients is at the heart of cell growth, flavour, texture, and safety in cultivated meat production. At the core of this process lies cell culture media, which plays a critical role in shaping the industry's near-term success. Both economic and technical aspects of nutrient delivery set the stage for the opportunities and hurdles discussed here.
One of the most pressing goals is reducing the cost of media. Current medical-grade formulations can cost around £320 per litre, but the aim is to bring this down to less than £0.20 per litre [1]. Companies have already made strides by transitioning to serum-free production systems, proving that animal-free nutrient delivery is not only possible but also commercially feasible.
However, scaling up production introduces new challenges. Large-scale bioreactors, for instance, must maintain sterility and ensure uniform oxygen delivery - problems that require innovative engineering solutions. The industry's move towards food-grade ingredients, as demonstrated by Nutreco’s specialised facility launched in 2024 [23], highlights a commitment to scaling up sustainably.
Nutrient delivery also allows producers to fine-tune nutritional profiles and sensory qualities, paving the way for healthier and more appealing products. The real challenge, however, is not just phasing out animal-derived components but doing so affordably while refining formulations to maximise productivity [1].
As discussed, nutrient delivery is a cornerstone of cell growth, product quality, and scalability. To meet these demands, collaboration among researchers, manufacturers, and regulators is vital. By working together, the industry can develop cost-effective and scalable nutrient delivery systems that meet strict safety standards and align with consumer expectations. The groundwork has been laid; now, it’s about building the infrastructure to support the growing appetite for sustainable protein.
FAQs
What challenges arise in getting oxygen to cultivated meat cells, and how are they overcome?
Delivering oxygen to cultivated meat cells presents unique challenges. Dense cell structures often limit how well oxygen can diffuse, and mixing techniques aimed at improving oxygen transfer can sometimes harm the cells instead.
To address these hurdles, researchers are exploring cutting-edge solutions. These include sophisticated bioreactor designs that enhance oxygen distribution and specialised oxygen carriers to ensure cells get the oxygen required for proper growth. These efforts are paving the way for a more efficient and sustainable approach to cultivated meat production.
What are the benefits of switching to serum-free, food-grade media in cultivated meat production?
Switching to serum-free, food-grade media in the production of cultivated meat comes with some major benefits. For starters, it slashes production costs by removing the need for expensive animal-derived serum - historically one of the priciest parts of the process. This change makes cultivated meat more affordable and easier to scale, paving the way for it to reach more people.
But the benefits don’t stop there. This shift also aligns with ethical and environmentally friendly practices. By eliminating animal-derived ingredients, it supports cruelty-free production while reducing the environmental impact. Plus, cultivated meat produced this way is free of antibiotics, offering a cleaner, more ethical protein choice for those who care about what’s on their plate and how it got there.
What are the differences between batch, fed-batch, and perfusion systems in cultivated meat production, and how do they impact scalability?
The method of delivering nutrients to cells is a key factor in the growth and efficiency of cultivated meat production. Let’s break down the main approaches:
- Batch systems: These involve adding all the necessary nutrients at the start. While straightforward, they have a downside - nutrients get used up over time, which limits how much the cells can grow.
- Fed-batch systems: Here, fresh nutrients are added at intervals during the cultivation process. This approach supports higher cell densities and yields, making it a more practical option for scaling up production.
- Perfusion systems: These continuously supply nutrients while also removing waste. This setup allows for even greater cell densities and consistent product quality. However, it comes with added complexity and higher costs.
When it comes to large-scale production, fed-batch and perfusion systems are often favoured, as they maintain higher productivity levels and are better suited for commercial use. That said, the choice between these systems ultimately hinges on finding the right balance between scalability, complexity, and cost.
