Bioprocess Design Considerations for Cultured Meat Production With a Focus on the Expansion Bioreactor

Abstract

Cultured meat, as a cellular agriculture product, utilizes tissue engineering techniques and consequently faces not only cell culture challenges but also scale-up limitations. To ensure cultured meat is financially viable, efficient bioprocess design for scale-up is required. In this mini-review we focus on the design of the expansion bioreactor, and put it in context of the entire bioprocess by providing an overview of the upstream and downstream process considerations. As a full-scale cultured meat bioprocess is still hypothetical we include a review of the key factors and fundamental cell biology parameters required as input data for the design of a process with a product that is not only viable but price competitive. This review highlights the vital aspects of a cultured meat bioreactor design that are often overlooked when parallels are drawn against fermentation processes such as brewing or recombinant protein production in the pharmaceutical industry. Practical application and awareness of the concepts presented here will enable more accurate estimation of the production expenses and raw material requirements. This will form a basis for both further academic research and the design of industrial-scale processes in the field of cultured meat and the wider field of tissue engineering-based cellular agriculture.

Muscle stem cell isolation and in vitro culture for meat production: A methodological review

“…The bioreactor is a device to culture microcarrier‐attached cells or cell aggregates maintaining the optimized conditions through regulating the conditions of their in vitro environment, such as pH, temperature, gas, and metabolite or nutrition concentrations. Various factors including cell density, bioreactor volume, inoculation efficiency, media requirements, cleaning scaffold source, passaging, inoculation, and cell removal methods should be considered for the mass production of muscle stem cells using bioreactors (Allan, De Bank, & Ellis, 2019). Several studies have employed the bioreactors for an upscaled muscle stem cell production as described in Table 4.…”

Techno-economic assessment of animal cell-based meat

“…Scenario 1 represents a baseline scenario a based on existing ACBM production, including 2019 cost estimates for animal serumfree media and growth factors (12). Scenario 4 was designed as a bookend scenario, where nearly all technical challenges are resolved, including reduced growth factor costs, increased MSC/myoblast tolerance to glucose concentrations, decreased MSC/myoblast doubling and maturation time, and reduced basal media costs (6,12,14,17). Scenario 2 represents a mid-point scenario between Scenarios 1 and 4, and Scenario 3 adapts Scenario 2 by eliminating FGF-2 growth factor costs.…”

“…A number of technological hurdles to lower production cost have been identified but not extensively quantified (e.g. cell senescence, high cost of growth factors, time and nutrients required for cell growth/differentiation/ maturation, and scalable scaffolding processes) (14,17,18) Figure 1B illustrates a potential ACBM production system similar to monoclonal antibody production for bovine myoblasts/MSC expansion (6,19). We limit our analysis here to the core bioreactor system (section "C" in Figure 1B) since industrial-scale scaffolding and maturation systems have not been defined in detail by ACBM producers.…”

Cellular agriculture in the UK: a review

“…Ellis began her research career in regenerative medicine and has applied her bioprocess design techniques to the expansion of muscle cells for CM. Given her experience with in vitro liver models (Luetchford et al, 2018;Storm et al, 2016) and her earlycareer work on scaffold development for mesenchymal stem cell expansion (Morgan et al, 2007), she has positioned herself to develop platform technologies for a wide range of tissue engineered cellular agriculture products, specifically based around scalable bioreactor design (Allan et al, 2019). She has a research group, with funding from New Harvest amongst others, developing bioreactors and scaffolds for CM, and gives Chemical Engineering undergraduate students the opportunity to carry out major project work in this space, having now supervised over 30 Masters of Engineering student projects on the topic of cultured meat bioprocess design.…”