# Biological and Technical Challenges Related to Cultured Meat Production
## 4 Technical Challenges in Cultured Meat Production
### Industrial Process Scaling-Up  
In cultured meat production, there are several technological challenges to reach an appropriate scaling-up. Within this context, the key issue is related to large-scale bioreactors for a high volume of cell production and tissue maturation. According to [PERSON] et al., the research will test other configurations and bioreactor types to achieve higher cell densities by minimizing bioresources utilization and costs to make cultured meat a commodity [27]. According to the same author, the initial cell production and tissue maturation will be two separate and different stages with different problems involved. The first is related to cell proliferation by a suitable multiplier factor--not lower than \(\times 10^{9}\)--and aims to maintain cells in an exponential growth state and prevent them from undergoing precocious differentiation. The second is related to providing correct stimuli and providing nutrients in an efficient way [88]. The industry standard for mammalian cell bioreactors is stirred tanks, in which cells are in suspension, aggregated, or attached to microcarriers [21; 31]. To establish efficient and cost-effective microcarriers-based culture systems, several challenges must be faced, the first being the surface and physical properties of the microcarriers: charge, coating, surface, and size [88]. Moreover, according to the outlook provided by [PERSON] et al., the relationship between the microcarriers and the final product must be addressed, considering technological possibilities. The temporary microcarriers scenario presents the unsolved problem of cell separation and recovery, while for the other two scenarios (non-edible but degradable microcarriers and edible microcarriers embedded in the final product), the edible or biodegradable materials to be used and production technologies are the primary issues [89]. In the case of scaffolds or cell-laden constructs in the maturation process, the main challenges are related to the correct mechanical stimulation cells requiring correct alignment and, eventually, mechanical tension, and an increase in material transport for efficient medium utilization, introducing recycling techniques [24; 87; 88]. According to [PERSON] et al., the transition from a laboratory batch to an industrial bioreactor will require the transition from flexible bioreactors to highly specialized systems, optimized and standardized from the bioprocess point of view [24].  
The industrial scaling up also represents an essential step to obtain a competitive product on the market. The first example of a cultivated burger was presented in 2013 in the Netherlands, and it required a total fabrication cost of 300.000 $ [42]. After that presentation, several companies and research groups sought to address this complex challenge. According to [PERSON] et al., the current (2020) estimated cost for cultivated meat or fish products ranges from 66.4 $/kg to 2200.5 $/kg compared to a few dollars per kilogram for the conventional meat, and most of the cost is attributed to the cell and tissue culturing [122].  
From the abovementioned discussion, the main goal of achieving cultured meat could be accomplished only if new approaches for affordable, scalable, and sustainable culturing systems will be found. These must be implemented by exploiting several design methods, including in silico models for the bioreactor production process [92]. The process must be cost-effective, hence materials used must come from abundant and animal-free sources, and the production process must be scalable, economical, and sustainable, with minimal waste production [27].