If you have worked in traditional bioprocessing, you already know that scale-up is never as simple as moving to a larger tank. It is always a balancing act of oxygen transfer, nutrient distribution, and process stability. In cultivated meat production, this challenge grows even sharper. Early on, many people assumed that lessons from monoclonal antibody or vaccine production would translate directly to growing meat. That assumption has proven to be misleading. The muscle and fat cells needed for food are less tolerant, more demanding, and behave very differently under industrial conditions.

The Adhesion Barrier in Meat Cell Culture

The first fundamental challenge is cell adhesion. The mammalian cells most widely used in pharmaceuticals, such as CHO or HEK, live freely in suspension. They are well-suited to stirred tank bioreactors where impellers create mixing, because they can tolerate the shear forces associated with that environment (Eibl et al., 2009). Muscle cells and adipocytes are different. They are anchorage dependent and need a scaffold or surface to remain viable (Specht et al., 2018).

That dependency introduces what researchers sometimes call the shear stress paradox. Mixing is required to distribute oxygen and nutrients evenly, yet the physical shear forces inherent to stirring dislodge myoblasts from the surfaces where they need to remain adhered (Allan et al., 2019). In antibody bioreactors, impeller design is a tuning parameter. In cultivated meat, the same mixing strategy risks erasing your culture altogether.

In conventional bioprocesses, tanks of twenty thousand liters are possible and even routine (Jacquemart et al., 2016). For meat cell culture, expanding to anything close to that scale in a stirred tank is impractical. At larger volumes, mixing has to be stronger, and therefore the cells experience greater shear. The bottleneck is not steel and infrastructure but the biology of adhesion.

The Trade Off Between Volume and Density

Another problem emerges when you calculate what volume of culture is required to simply generate one kilogram of biomass. Depending on the type of reactor, you arrive at strikingly different numbers.

• Stirred tanks require about 570 liters.
• Packed beds come down to about 110 liters.
• Fluidized beds are around 48 liters.
• Hollow fibers, at least theoretically, need only 1.4 liters (Allan et al., 2019).

At first glance, hollow fiber reactors look extraordinary. One kilogram of tissue in a flask-sized vessel is appealing. The problem is that reaching the ultra-high densities those numbers assume, in the order of 10⁸ to 10⁹ cells per milliliter, is not a dependable outcome in practice. Real systems struggle with waste buildup, gradients in pH, and insufficient oxygen (Jossen et al., 2018).

This balance between total working volume and achievable cell density lies at the heart of cost modeling. Pharmaceutical production can absorb inefficiencies since the products sell for thousands of dollars per gram. In food, inefficiencies mean you cannot reach a retail price per kilogram that makes sense. Cultivated meat must compete with animal agriculture, and the cost per unit of protein is unforgiving.

The Scaffold as a Central Part of the Process

Scaffolds receive attention in public discussions for their role in texture and bite. Less often stressed is their upstream importance for bioprocess design. Edible scaffolds built from food-grade polymers or plant-derived proteins act not only as attachment points but also as structural components of the final food (Allan et al., 2019). Non-edible scaffolds, on the other hand, may provide more reliable performance during expansion but complicate cell harvest.

This immediately raises the technical issue of passaging. In lab-scale work, enzymatic dissociation using trypsin is common practice (Masters and Stacey, 2007). Trypsin, however, is animal-derived and subject to variation. For large-scale food production, those risks are unacceptable. Recombinant products such as TrypLE avoid the animal origin issue but impact cost. Other chemical or mechanical methods reduce batch variability yet introduce their own limits to efficiency. Every choice in scaffold design filters through the economics and reproducibility of the overall process.

For this reason, scaffold engineering is not just a parallel track of research. It is the central constraint dictating how viable a cultivated meat bioprocess becomes.

Oxygen Transfer as an Inescapable Limitation

Among the least visible yet most damaging problems is oxygen delivery. Muscle cells consume oxygen at relatively high rates. Yet the common approach in stirred tank reactors, sparging gas directly into the medium, simply cannot be used. The bubbles and associated turbulence detach cells and create lethal shear (Allan et al., 2019).

That forces engineers to adopt less familiar methods. Options include silicone tubing that permeates gas, pre-oxygenating medium before it enters the bioreactor, or employing membrane-based oxygenation surfaces. Each method avoids bubbles but comes at a higher cost or operational complexity.

In certain systems, the oxygen supply hardware ends up being more complex and more expensive than the basic tank. This inversion illustrates why cultivated meat cannot just scale through larger vats. The oxygen limitation redefines what the vessel even looks like.

The Economics of Food Versus Pharma

Single-use bioreactors, or SUBs, transformed biomanufacturing for therapeutic proteins. They simplified operations, reduced cross-contamination risks, and increased flexibility between products (Jacquemart et al., 2016). Yet their application in cultivated meat raises problems. A single cycle in a SUB generates a significant amount of mixed plastics that are difficult to recycle, and the cost of replacement is only viable when your revenue per gram is extremely high.

Cultivated meat will exist in the exact opposite environment. The expectation is mass production at very low margins. In this setting, stainless steel vessels that can be cleaned and reused may hold more promise than disposable plastic systems. However, that requires revisiting cleaning validation and contamination protocols that pharma has gradually moved away from. Economic drivers in food force a different set of compromises.

Even beyond cost, the optics matter. One of the central justifications for investing in cultivated meat is the environmental benefit. Large volumes of non-recyclable plastic effluent create an environmental contradiction and undercut consumer confidence.

Why Published Parameters Do Not Equal Ready Protocols

Academic papers have helped map the foundational boundaries of the problem. Key values, such as cell-specific growth rates, yield coefficients, oxygen uptake, carbon dioxide generation, and tolerance ranges for pH and osmolality, are openly listed (Allan et al., 2019). What is often overlooked is how these numbers translate poorly across systems.

Two cell lines that look similar can respond very differently when scaffold surface area changes slightly or when hydrodynamics vary. A process optimized in one group’s hollow fiber system may collapse entirely for another team using a packed bed (Specht et al., 2018). Every cultivated meat company is essentially building its own cell factory from first principles.

The field is now experiencing the same reality that stem cell therapies faced in the last decade: protocols that worked in academic labs rarely survived once they encountered the rigors of regulatory manufacturing or the economics of scale (Jossen et al., 2018). Cultivated meat is replaying this journey, though the end product is food rather than medicine.

Future Directions and Hybrid Solutions

Some start-ups are already adjusting their strategies toward hybrid models. Combining plant proteins for bulk texture with cell-derived components for flavor and realism reduces the number of cells required and thus lowers cost (Specht et al., 2018). This is likely to be a practical near-term approach.

Others are focusing on seafood. Fish muscle tissues generally have lower oxygen demands and may be more forgiving in culture. That, along with potentially less stringent consumer expectations around texture, explains why seafood is attracting attention (Good Food Institute, 2023).

Regulatory approvals have started to arrive, with Singapore, the United States, and Australia opening the door to cultivated poultry products (Good Food Institute, 2023). This demonstrates that safety frameworks can be satisfied. It does not, however, resolve the engineering bottlenecks or the need for cost reduction.

Final Thoughts

The excitement around cultivated meat is justified. It represents both a technological frontier and a chance at reshaping how protein reaches human diets. Yet optimism must sit alongside realism. Marketing visuals often present gleaming large tanks and exaggerated density projections. The engineering reality is different. The sector is constrained not by imagination but by shear stress, oxygen diffusion, scaffold functionality, and the underlying economics of food production.

For engineers entering the space, the fundamentals do not change. Mass transfer, fluid dynamics, metabolic waste removal, and cost per unit volume remain the core focus areas. What is different is that context strips away the high margins that made biologics manufacturing flexible. In cultivated meat, every inefficiency is exposed by the price of chicken in a supermarket.

Success will not come from simply scaling up familiar biologics systems. It will come from reimagining the process entirely for anchors, scaffolds, oxygen, and food-grade economics. Until then, bigger tanks remain more of a distraction than a solution.

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References:

• Allan, S. J., De Bank, P. A., & Ellis, M. J. (2019). Bioprocess design considerations for cultured meat production with a focus on the expansion bioreactor. Frontiers in Sustainable Food Systems, 3, 44. https://doi.org/10.3389/fsufs.2019.00044
• Eibl, R., Eibl, D., Pörtner, R., Catapano, G., & Czermak, P. (2009). Cell and tissue reaction engineering. Springer.
• Jacquemart, R., Vandersluis, M., Zhao, M., Sukhija, K., Sidhu, N.,
  & Stout, J. (2016). A single-use strategy to enable manufacturing of affordable biologics. Computational and Structural
  Biotechnology Journal, 14, 309–318. https://doi.org/10.1016/j.csbj.2016.06.007
• Jossen, V., van den Bos, C., Eibl, R., & Eibl, D. (2018). Manufacturing human mesenchymal stem cells at clinical scale: process and regulatory challenges. Applied Microbiology and Biotechnology, 102, 3981–3994. https://doi.org/10.1007/s00253-018-8912-x
• Masters, J. R., & Stacey, G. N. (2007). Changing medium and passaging cell lines. Nature Protocols, 2, 2276–2284. https://doi.org/10.1038/nprot.2007.319
• Specht, E. A., Welch, D. R., Rees Clayton, E. M., & Lagally, C. D. (2018). Opportunities for applying biomedical production and manufacturing methods to the development of the clean meat industry. Biochemical Engineering Journal, 132, 161–168. https://doi.org/10.1016/j.bej.2018.01.015
• Good Food Institute. (2023). GOOD Meat and UPSIDE Foods approved to sell cultivated chicken following landmark USDA action. Retrieved from https://gfi.org/press/