Biochemical Engineering Journal 132 (2018) 161–168

Contents lists available at ScienceDirect

Biochemical Engineering Journal

journal homepage: www.elsevier.com/locate/bej

Regular article

Opportunities for applying biomedical production and manufacturing

methods to the development of the clean meat industry
Elizabeth A. Specht ∗ , David R. Welch, Erin M. Rees Clayton, Christie D. Lagally
The Good Food Institute, Washington, DC, 20010, United States

a r t i c l e i n f o a b s t r a c t

Article history: Clean meat (meat grown in cell culture rather than obtained from animal slaughter) is an emerging
Received 4 August 2017 biotechnology industry that will ameliorate the serious environmental, sustainability, global public
Received in revised form 8 December 2017 health, and animal welfare concerns of industrial animal agriculture. While many technologies and prod-
Accepted 15 January 2018
ucts developed for the cell therapy industry can already be applied to clean meat, significant opportunities
Available online 3 February 2018
exist to expand product lines to supply this emerging industry. Large-scale cell culture for clean meat
production presents a number of unique requirements that are not currently met by existing prod-
Keywords:
ucts and processes from the biomedical industry − most notably related to cost constraints and scale
Clean meat
Cultured meat
requirements. Developing these tools for clean meat would simultaneously advance the technology and
Tissue culture reduce costs for biomedical and therapeutic applications. We will discuss new applications of current
Meat alternatives biomedical products and manufacturing methods for clean meat, as well as opportunities for synergistic
Cellular agriculture product development through partnerships between academic researchers, established industry players
Sustainability in cell-based therapeutics, and the emerging clean meat industry.
© 2018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license
(http://creativecommons.org/licenses/by/4.0/).

1. Introduction: what is clean meat? meat have advanced in recent years. It also signals that the clean
meat industry is likely to transition from a pre-competitive space
Clean meat entails producing the cell types present in meat – to a highly competitive field within a short timeframe and that the
muscle cells, fat cells, connective tissue, etc. – through a cell culture present moment represents a pivotal period for the emergence of
platform, using cells derived from meat-relevant species including this technology.
avian, mammalian, and piscine cell lines. While food applications
of animal cell culture have appeared in the literature since the early 1.1. Motivation: comparison with industrial animal meat
2000 s [1], in recent years this field has experienced a surge of
interest among academics [2–4] and the for-profit sector. In the Animal agriculture poses substantial threats to human health,
past two years more than a half-dozen companies have formed to the environment, and animal welfare. It is a leading cause of envi-
commercialize clean meat, moving this endeavor from the realm ronmental destruction – including deforestation, ocean dead zones,
of academic inquiry into rapid industrial scale-up and manufac- and water and air pollution – and it contributes more greenhouse
turing. Concerted efforts to achieve commercialization within the gas emissions than the entire global transportation sector [6]. Fur-
coming half-decade will require considerations for scale-up and thermore, rearing animals poses significant public health threats
large-scale manufacturing, even in strategic early-stage research from antibiotic resistance [7,8] and zoonotic disease epidemics [9]
and development decisions. as well as acute consumer risk in the form of foodborne illness
In a report released earlier this year, the National Academies from fecal contamination introduced during slaughter and render-
of Science, Engineering, and Medicine (NASEM) identified clean ing [10]. Finally, consumers are increasingly concerned about the
meat as an emerging biotechnology area with high growth poten- treatment of farmed animals, as evidenced by a growing number of
tial and commercial relevance within the next five to ten years legal reforms and governmental mandates to improve conditions
[5]. The NASEM report, compiled and peer reviewed by more than [11,12].
two dozen esteemed scientists in biotechnology, is a reflection of Producing meat via large-scale cell culture significantly allevi-
the extent to which the underlying technologies that enable clean ates all of these burdens. In the case of the public health and animal
welfare concerns, these issues are virtually eliminated by clean
meat as animal rearing, slaughter, and antibiotic use are absent
∗ Corresponding author. from the process. The resource burden is also likely to be signifi-
E-mail address: lizs@gfi.org (E.A. Specht). cantly reduced relative to industrial animal meat production. While

https://doi.org/10.1016/j.bej.2018.01.015
1369-703X/© 2018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
162 E.A. Specht et al. / Biochemical Engineering Journal 132 (2018) 161–168

Fig. 1. The clean meat industry mind map illustrates critical technology sectors and contributing technologies for clean meat commercialization. Adapted from [15].

only a limited number of life cycle analyses have been performed they encompass a wide variety of approaches, both in terms of
to date – and these are highly speculative as they make myriad production process and product focal area. These considerations
assumptions and projections about large-scale process attributes determine the extent to which the companies require technology
and material sourcing – the consensus at present is that land use, from each of the critical technology areas identified above. Some
water use, and greenhouse gas emissions will be reduced by one to companies are exploring cultured animal cells as ingredients for
two orders of magnitude [13,14]. Removing animals from the pro- incorporation into predominantly plant-based products, in which
cess also eliminates fecal waste, a leading cause of environmental case they have little need for scaffolding. Others are focusing exclu-
pollution of both air and water, and associated methane production, sively on ground meat products for their initial market entry, only
which is a significant contributor to animal agriculture’s climate requiring scaffolding sufficient for supporting the development of
impact. individual muscle fibers – perhaps microcarriers in suspension, for
example.
1.2. Critical technology elements for the clean meat industry Ultimately, however, the aim of this approach is to create prod-
ucts that are – for all intents and purposes – genuine cuts of meat
Many of the critical technologies necessary to bring clean meat exhibiting multiple cell types within thick, vascularized tissues.
to fruition are the same as those that have been pioneered for These are the types of meat products that are unlikely to be satis-
other large-scale cell culture applications such as antibody protein factorily mimicked by plant-based meat analogues, and thus clean
therapeutics, cell-based therapies, and regenerative medicine. The meat offers a more environmentally sound and humane production
industry mind map (Fig. 1) illustrates several critical technology method for satisfying consumer demand for these products.
elements of cell lines, culture media, scaffolding, and bioreac- Due to the pre-competitive nature of the field and these differ-
tors that are necessary for the process, as well as considerations ences in technological focus, there is tremendous opportunity to
for supply chain and distribution as the clean meat industry will foster collaboration among the clean meat companies themselves
entail substantially greater input and product volumes relative as well as with established companies in the biomedical and life
to biomedical cell culture industries. Note that while this article sciences. These companies can serve as vendors, service providers,
covers the critical technologies necessary for the successful com- or contract researchers to address shared needs among the clean
mercialization of clean meat, it is not an exhaustive list. A deeper meat companies, as discussed in Section 3.
dive into each of the technology areas will be required to address
the details in each step of the production process. 1.4. Regulatory and food safety considerations

1.3. The competitive landscape Given that commercial interest in clean meat is still nascent, the
regulatory framework for this industry has not been fully estab-
Virtually all of the companies that have emerged to commer- lished but is expected to vary from country to country. Authorities
cialize clean meat have arisen within the last two to three years, responsible for food safety – rather than those with oversight of
including several in the past year alone. There are nearly a dozen medical applications – will have the most appropriate expertise
companies pursuing this technology at the time of publication and to oversee clean meat production. They should communicate clear
 E.A. Specht et al. / Biochemical Engineering Journal 132 (2018) 161–168 163

Table 1
Design requirements and parallels within the cell-based therapeutics industry for clean meat critical technology elements. QC, Quality Control.

Critical Technology Element (CTE) Design requirements for clean meat Relevant technologies and advances within the cell-based
therapeutics industry

Cell line development • Derived from agriculturally-relevant species • Development of small molecule cocktails that can replace
• Capable of differentiation into meat-relevant cell types the need for genetic approaches to induce pluripotency
(muscle, fat, fibroblast, etc.) and to facilitate maintenance of pluripotency
• Genetically stable and immortalized • Footprint-free methods of cell line engineering using
• Optimized for large-scale growth (tolerate suspension, RNA or protein delivery or excisable transposons
controlled differentiation, etc.) • Improved protocols for cell freezing to maintain viability
and phenotypic fidelity
Cell culture media • Animal component-free, antibiotic-free, ideally • Development of methods for streamlining iterative
chemically defined optimization of animal component-free media
• Optimized for meat-relevant cell lines and co-culture of formulations
multiple cell types • Immobilizing growth factors on beads to prevent
• Extremely low cost and high-volume production capacity depletion in the media via perfusion
• Engineered or synthetic growth factors
Scaffolding materials • Edible and/or biodegradable and food grade materials • Biocompatible, non-animal-derived scaffolding materials
• Support cell adherence pioneered in the regenerative medicine field
• Support vascularization and media perfusion • Use of tunable scaffold parameters (stiffness, etc.) to
• Biomechanical properties suitable for tissue maturation spatially direct differentiation
• Scalable production capacity • Degradable materials that enable cell migration and
vascularization after patient implantation
Large-scale bioreactors • Support cell proliferation as well as tissue • Integrated, closed systems with increasing automation to
maturation/perfusion reduce errors and contamination risk associated with
• Large volume, low maintenance human handling
• High-yield cell harvesting • In-line monitoring of media components to adjust
• Real-time, in-line cell monitoring for QC perfusion in real time
• Integrated media filtration and recycling system • Novel technologies to improve efficiency of cell
• Highly automated; closed system separation and harvesting

expectations about necessary regulatory submissions, with the goal 2. Application of cell-based therapy technologies to clean
of allowing clean meat to come to market quickly while ensuring meat
safety and consumer confidence. Fundamentally, clean meat should
be held to the same safety standard as industrial animal meat; how- Aside from biologics production (vaccines, antibodies, etc.), cell-
ever, some components of clean meat, such as scaffolds and cell based therapy is the largest commercial application of animal cell
culture media, may require additional safety reviews if they are culture. Perhaps more importantly, it is the only commercial indus-
not otherwise used in the food supply. try in which cultured cells are the desired end product, in contrast
While food safety will need to be demonstrated conclusively, with biologics where the cells themselves are production hosts and
the clean meat production process poses several notable advan- discarded at the conclusion of the production run. Thus, all of the
tages from the perspective of food safety. It is free of microbial critical technologies for clean meat draw heavily from technologies
contamination – which is omnipresent in industrial animal meat developed for the cell-based therapeutics industry (Table 1).
as a result of slaughter – and the cell cultures can be monitored The schematic below (Fig. 2) provides an illustrative base case
continuously and immediately treated or aborted if contamina- process design as a reference for delving into the contributions of
tion is detected. With the exception of the bacterial load and very each critical technology in Sections 2.1 through 2.4. The companies
low-abundance cell types like nerves and white blood cells, the presently in the clean meat sector are in the early stages of product
cellular and molecular composition of the final product will mirror development and continue to evaluate a wide variety of production
the composition of industrial animal meat, which already exhibits approaches. While they have not publicly disclosed their meth-
tremendous variability between various animals, cuts, and prod- ods in detail, we will likely see multiple variants of the process
ucts. Thus, the nutritional value and the digestive response by the described below. Note that while proliferation and differentiation
consumer are projected to be the same as for meat derived through are spatially distinct stages of the process in this schematic, it is
animal slaughter. All of the media components can be sourced as possible that these stages may be simply temporally distinct rather
food ingredients, and even recombinant growth factors would not than spatially separated.
pose a novel protein risk because they are identical to the proteins The process illustrated above is anticipated to require between
and hormones that are naturally found in meat from an animal. ten days and six weeks for production-scale batches in the range of
Finally, clean meat exhibits no risk to the consumer regard- 20,000 L, depending on several operating parameters. The largest
ing the meat cells taking residence in the consumer’s gut because influence on the process timescale derives from assumptions about
all meat cells – whether derived from animal slaughter or a cul- the degree to which the seed train is run continuously – thus allow-
tured production process – are non-viable by the time they are ing the production-scale reactor to be inoculated directly at the
ingested. Animal cells of this nature do not survive longer than start of each production cycle – as opposed to scaling every batch
a few minutes or, at most, hours outside the context of an ani- from a frozen vial to full scale. Most estimates of the yield (pounds of
mal body or a bioreactor, so they are non-viable by the time they meat per batch) conducted by industry experts range from 4,000 Lb
reach a consumer’s plate even if they are never cooked or frozen. to over 10,000 Lb per 20,000 L batch (see [16] for one estimation in
Clean meat versions of steak tartar or tuna sashimi will be equally the peer-reviewed literature; most are conducted internally by the
safe to consume raw or cooked because the only cells that cur- companies).
rently survive in uncooked meat – microbial cells – will simply Some relevant proxies for assessing the validity of these esti-
not be present in clean meat; the animal cells in these products mates include scale-up of CHO cells, for which a 29-day cycle is
are not alive at the point of consumption regardless of production sufficient to scale a frozen vial of 106 cells to two tons of cell mass
method. in a 20,000 L tank [17]. Note that the relevant cell types for meat
164 E.A. Specht et al. / Biochemical Engineering Journal 132 (2018) 161–168

Fig. 2. Schematic for the base case process design for structured clean meat products. The first stage of the process is the proliferation stage, in which undifferentiated or
semi-differentiated cells reproduce to increase cell density and mass. In the second stage, the cells are seeded onto a scaffold on which they differentiate into the relevant
final cell types (muscle, fat, etc.) and mature to reflect the morphology and physiology of these desired cell types. Adapted from [15].

(muscle and fat) are much larger than CHO cells, so two tons of wet muscle without intermediate transitions [22], suggesting that sim-
cell weight is likely an underestimate of the comparable figure for ilar approaches could be used to substantially increase both the
clean meat cultivation. Also note that this production cycle length efficiency and the speed of skeletal muscle derivation for clean
does not make any assumptions about maintaining the stability of meat.
the cell line longer than about 25 generations, though the overall Cell line development may encompass a number of additional
production cycle length could be shortened significantly (and thus approaches to increase the robustness of clean meat cells for
drastically increase yield per reactor per year) if the seed train can large-scale cultivation, improve their metabolic efficiency, and
be maintained in a semi-continuous fashion. reduce the cost or design requirements of other critical technol-
ogy elements. For example, one strategy for reducing the cost of
2.1. Cell line development and banking growth factors in the media (see Section 2.2) is to adapt or engi-
neer cell lines such that they require lower levels of exogenous
While cultivation of primary cells is possible for small-scale growth factor signals to proliferate and/or differentiate in vitro
clean meat applications, ultimately the process is best suited for [23]. Gene editing techniques like CRISPR have already been used
robust cell lines that exhibit consistent performance over many to accelerate cellular adaptation to conditions such as suspen-
production cycles, rather than primary cell harvests, which intro- sion growth [24], and it is likely that additional signaling pathway
duce variability and increased risk of contamination from the editing can increase tolerance to other stressful conditions of
isolation protocol. Long-term cultivation is critical for reducing large-scale growth. Microfluidic screening techniques to select
costs for clean meat because it allows for continuous cultivation for metabolic efficiency or robust activity of various metabolic
of the seed train with only the final scaling and maturation stages pathways have largely been applied to microbe selection for indus-
of the production process requiring batch processes. It is likely that trial biotechnology applications [25], but these methods can also
clean meat cell lines will be utilized in a similar fashion to fermen- be applied to clean meat cell lines to select for high perform-
tation strains in brewing: cultures can be used continuously for ers.
some number of generations, but periodically they are re-started Once cell lines for clean meat have been established, cell bank-
from frozen stocks to avoid genetic drift. One barrier to long-term ing best practices derived from the use of sensitive stem cell lines
culture of proliferative cells has been maintaining stem-ness in con- in biomedicine [26,27] can be applied to clean meat cell stocks
tinuous culture, but recent work has shed light on a number of to enhance their stability, reproducibility, and long-term mainte-
strategies for maintaining stem-ness including subjecting cells to nance.
hypoxic conditions [18] and modulating parameters like scaffold
stiffness [19]. 2.2. Animal component-free cell culture media
While cell line immortalization is not common in cell-based
therapies, there exists a wealth of experience in developing genet- Animal component-free media has advanced considerably in
ically stable, immortalized cell lines for the biologics industry. the past ten years due in large part to the needs of the cell-based
However, the cell-based therapy industry, with an eye towards therapy industry, for which media containing animal compo-
personalized medicine and gene therapy, has been the impetus nents is problematic from a reproducibility, contamination, and
behind much of the research on induction of stable pluripotent regulatory perspective. Currently hundreds of formulations of com-
stem cell (iPSC) lines from an individual patient including footprint- mercially available animal-free media exist [28], resulting from a
free methods rather than classical transgenesis [20]. Epigenetic push within the cell culture community to designate serum-free,
memory, which influences the efficiency with which iPSCs dif- chemically defined media as an integral part of good cell cul-
ferentiate into various lineages [21], should be considered when ture practice (GCCP) [29]. The demonstration that serum-free and
selecting donor cells from which to derive iPSC lines for clean animal-origin-free media can support cell survival, proliferation,
meat. Epigenetic influences have also been harnessed to differenti- and differentiation is perhaps the single most significant advance-
ate human cells directly from embryonic stem cell lines to skeletal ment that has allowed clean meat progress to proceed, as a serum
 E.A. Specht et al. / Biochemical Engineering Journal 132 (2018) 161–168 165

requirement for this process would render it completely infeasible cally regulated throughout the clean meat production process to
at scale. facilitate unique cellular demands as cells transition from prolif-
A number of studies have outlined best practices for developing eration to differentiation to maturation. Nano-scale incorporation
new animal-origin-free media formulations, serving as roadmaps of additional materials within hydrogel scaffolds can enhance the
for expanding formulations to meat-relevant cell lines and species scaffolds’ ability to induce directed differentiation in the absence of
[30]. Recent advances in multiwell microfluidics devices for animal exogenous growth factors [51], or the growth factors can be phys-
cell culture can drastically accelerate the media screening process ically integrated and immobilized within the scaffold to assist in
by parallelizing hundreds or thousands of conditions and facili- differentiation with high spatial resolution [52]. Scaffolds could also
tating screening for sophisticated phenotypes through automated be used as carriers for molecules that contribute to the flavor or
image analysis [31]. nutritional value of the product.
While in vitro skeletal muscle differentiation has historically The use of edible or biodegradable scaffolds will be required for
struggled with low efficiency in the absence of transgenic lines, clean meat applications. Significant work has already been done to
recent studies have tested serum-free media formulations, growth develop tunable scaffolds made of food-safe, plant-derived poly-
conditions, and supplements for their capacity to support myo- mers like gellan gum [53], alginate [54,55], pectin, and modified
genic differentiation, even from fully pluripotent stem cell lineages cellulose [56], which may be ideal for clean meat applications.
[32–35]. Ideally, fabrication of these hydrogel scaffolds can be directly
Special media considerations at scale include not only optimiz- integrated into the closed-system process design to reduce the risk
ing parameters like viscosity and pH in accordance with the fluid of contamination from introducing a prefabricated scaffold – which
dynamics of large bioreactors, but also the addition of components can be difficult to sterilize by traditional methods without damag-
to improve cell survival within the context of unique stressors ing the material – in the middle of the process. This will require
within the large-scale growth environment. For example, ROCKI concerted engineering efforts and considerable collaboration with
(Rho-associated kinase inhibitors) can increase cell viability in sus- bioreactor developers.
pension growth during the proliferation phase [36], while perfusion
within thick tissues may require an oxygen carrier to facilitate oxy- 2.4. Large-scale bioreactors
gen transfer [37,38].
To reach price parity with conventional meat, drastic cost reduc- Bioreactor technology has benefitted from advances in biolog-
tions of both the basal media and the growth factors will be ics and vaccine production using animal cell lines as well as in
required. Demonstrations of growth factor engineering approaches the cell-based therapy industry. A wealth of published literature in
for improved stability or potency have recently been exten- this area, including systematic comparisons among various biore-
sively reviewed [39]. Alternatively, small molecule libraries can be actor types and process design considerations [57,58], facilitates
screened to identify molecules that mimic the activity of growth decision-making for new large-scale cell culture applications like
factors, eliminating the need to produce them recombinantly clean meat. Large-scale growth of CHO cells is routine, but recent
[40,41]. Transcriptome [42] and proteome [43] analyses can be used work to improve perfusion systems – including tangential flow and
to identify which media components are limiting cellular growth, alternating tangential flow filtration – has significantly increased
as well as to optimize the basal media formulation to compensate maximum attainable cell densities (above 1 × 108 cells/ml) and cell
for various cell stresses. performance [59,60]. Similar systems will likely be applied to clean
meat production at scale.
2.3. Tissue engineering scaffolds from regenerative medicine The filtration criteria (membrane size, flow rates, etc.) may be
more sophisticated for clean meat applications as the parameters
Scaffolding is paramount for clean meat, as it provides the basis may change depending on the stage of the process – for example,
for structured, thick-tissue products that are more complex than different factors will need to be removed and added in the prolifer-
simple ground meat mimics or cells used as ingredients. Scaffolds ation versus the differentiation phase. Systems to monitor not only
need to support co-cultures of multiple cell types, perfusion of the concentration of media components but also the cell density
media through the material directly or via a pore or vascular net- should be incorporated in the bioreactor design at this stage, which
work [44], and ideally help guide differentiation to allow spatial may entail including parameters like impedance for inferring cell
heterogeneity in the final product that will resemble the natural density within solid tissues where turbidity cannot be measured.
structure and marbling of meat. Scaffolding can guide cell differen- The cell-based therapy industry has pioneered several aspects
tiation either through its biomechanical properties or by physically of automation of the cell manufacturing process, both as a result of
anchoring specific signaling moieties or growth factors, or a combi- the necessity of closed systems to reduce contamination risk under
nation of these approaches [45]. The elasticity of the scaffold plays antibiotic-free conditions and to reduce variability from human
a well documented role in skeletal muscle renewal and maturation handling. Functionally closed systems have been described for a
in particular [46]. number of cell types and applications, including adipose-derived
Scaffolds for tissue engineering have historically been derived cells [61], bone marrow-derived cells [62], and T-cells [63]. A suite
from animal sources, but recently significant activity has focused on of technologies for in-line, real-time monitoring of system perfor-
developing alternative materials ranging from synthetic hydrogels mance, media conditions, and cell viability has been developed [64],
to decellularized vascular plant scaffolds [47]. 3D printed and elec- including sophisticated Raman-based methods for in situ monitor-
trospun materials have also been used for tissue engineering and ing [65]. These controls and monitoring platforms will be critical
can even harbor nanocarriers for controlled growth factor release for clean meat production to enable real-time system modulation
[48], but these scaffold fabrication methods may be less amenable to address production variability.
to the scaling required for clean meat applications. The choice of cell type during both the proliferation and matu-
Hydrogel scaffolds show perhaps the most promise both for ration phase, in addition to the level of sophistication of the target
low-cost, large-scale production and for precise fine-tuning of the product, will dictate the optimal bioreactor system. For proliferat-
biomechanical properties to suit the various needs of co-cultured ing cells with minimal structure, suspension cells or adherent cells
cells for clean meat. These parameters can be modulated with that can be cultured in aggregates or with biodegradable micro-
3D spatial specificity using light [49], and this modulation can carriers are suitable for systems such as stirred-tank or air-lifted
be reversible [50], meaning that the scaffold may be dynami- bioreactors currently used in other large-scale cell culture indus-
166 E.A. Specht et al. / Biochemical Engineering Journal 132 (2018) 161–168

imizing the licensable opportunities for intellectual property (IP)

that is developed by each clean meat company. Models for pooling
IP or establishing patent pledges that reduce the risk of litigation
have proven successful for fostering open collaboration in other
fast-moving, disruptive technology sectors [69–71].
Taking a TRL-guided, systems-level perspective of industry
growth not only allows for strategic coordination among all par-
ties but also enables forecasting of long-term hurdles. While many
parallels exist between the needs of the clean meat industry and
those of the cell-based therapy industry, it is important to acknowl-
edge where entirely new developments are needed. Development
Fig. 3. The “valley of death” for research and development funding along the of supply chains specific for the clean meat industry is one such
technology readiness level (TRL) trajectory towards commercialization. Early-stage
area, as both the scale and the regulatory specifications of the media
research is attractive for public funding and exploratory grants, while a commer-
cially viable proof of concept is competitive for private investment. Leading-edge
components for clean meat will be unique. For instance, food-
technologies have a well-documented risk of failing to launch due to an inability to grade components may be acceptable for clean meat applications,
attract funding from either source to achieve TRLs 4 through 6 [72]. whereas current cell culture media suppliers are only working with
more expensive pharma-grade or research-grade materials.

tries. For maturing cells into more complex three-dimensional

tissues, perfusion bioreactors that facilitate even nutrient flow 4. Conclusion and future directions
through a porous scaffold will be required. For both of these types
of reactors, fluid dynamics will be taken into account to ensure Clean meat is rapidly emerging as an area of tremendous com-
that the desired cell types can tolerate the hydrodynamic forces to mercial interest and growth, presenting significant opportunities
which they are exposed in these systems. In fact, computational for both academic researchers and industry partners to utilize
modeling of fluid dynamics [66] may allow these parameters to be their large-scale cell culture and tissue engineering expertise to
leveraged to support directed cellular differentiation [67,68]. advance a novel field. Likewise, many research advances made
For intact tissue perfusion platforms, there is considerable need in pursuit of commercializing clean meat will exhibit significant
to engineer systems for automated harvesting of large-scale intact cross-applicability to other industries that utilize large-scale cell
tissues. Automated large-scale harvesting of single cells or aggre- culture, including biologics, cell-based therapy, and regenerative
gates has been pioneered for cell therapy applications [73], but medicine. The number of prototypes, demonstrations, and tast-
tissues for regenerative medicine are currently produced at vol- ings in the last two years indicate that there are no fundamental
umes no larger than what is needed for a single patient. Thus, technological flaws that are prohibitive to the feasibility of the
automating the harvesting and downstream processing of intact endeavor. As clean meat comes to fruition, the main challenges
tissue for clean meat applications will be a novel area of develop- will reside in scale-up and cost reduction, with an abundance of
ment within bioreactor design and process engineering. opportunities within each critical technology element to increase
the efficiency of the process and continuously decrease the cost.
The growing clean meat field is fertile ground for developing
3. Opportunities for accelerating the path to collaborative partnerships, exploring licensing opportunities, and
commercialization pioneering paradigm-shifting technologies that catapult cell cul-
ture from the exclusive realm of the bench and the bedside to the
The nascency of the clean meat field represents an opportu- scale of industrial agriculture.
nity to develop strategic partnerships and collaboratively navigate
the pathway to commercialization. This includes strategic plans for
Competing interests statement
conducting basic research, bolstering supply chains to proactively
address material bottlenecks, developing a robust talent pipeline
The authors do not declare any competing financial interests.
for future industry growth, and achieving regulatory approval.
The Good Food Institute is a donor-supported 501(c)(3) nonprofit
As all of the companies that have emerged in recent years
and does not receive any compensation from industry partners.
to commercialize clean meat are still relatively small and early-
stage, there is considerable advantage to leveraging expertise
through contracted research – especially with companies that have Acknowledgments
provided contract work, including contract development and man-
ufacturing, for the cell-based therapy industry. There is also ample This work was conducted by The Good Food Institute through
opportunity to involve academic collaborators at this early stage, as generous support from private donors and philanthropic founda-
a plethora of basic research questions with significant downstream tions.
importance are not urgent priorities for the clean meat companies,
which have limited time and resources. References
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