Abstract Cultivated meat production requires bioprocess optimization to achieve cell densities that are multiple orders of magnitude higher compared to conventional cell culture techniques. These processes must maximize resource efficiency and cost-effectiveness by attaining high cell growth productivity per unit of medium. Microcarriers, or carriers, are compatible with large-scale bioreactor use, and offer a large surface-area-to-volume ratio for the adhesion and proliferation of anchorage-dependent animal cells. An ongoing challenge persists in the efficient retrieval of cells from the carriers, with conflicting reports on the effectiveness of trypsinization and the need for additional optimization measures such as carrier sieving. To surmount this issue, edible carriers have been proposed, offering the advantage of integration into the final food product while providing opportunities for texture, flavor, and nutritional incorporation. Recently, a proof of concept (POC) utilizing inactivated mycelium biomass derived from edible filamentous fungus demonstrated its potential as a support structure for myoblasts. However, this POC relied on a model mammalian cell line combination with a single mycelium species, limiting realistic applicability to cultivated meat production. This study aims to advance the POC. We found that the species of fungi composing the carriers impacts C2C12 myoblast cell attachment—with carriers derived fromAspergillus oryzaepromoting the best proliferation. C2C12 myoblasts effectively differentiated on mycelium carriers when induced in myogenic differentiation media. Mycelium carriers also supported proliferation and differentiation of bovine satellite cells. These findings demonstrate the potential of edible mycelium carrier technology to be readily adapted in product development within the cultivated meat industry.
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Multi‐objective Bayesian algorithm automatically discovers low‐cost high‐growth serum‐free media for cellular agriculture application
Abstract In this work, we applied a multi‐information source modeling technique to solve a multi‐objective Bayesian optimization problem involving the simultaneous minimization of cost and maximization of growth for serum‐free C2C12 cells using a hyper‐volume improvement acquisition function. In sequential batches of custom media experiments designed using our Bayesian criteria, collected using multiple assays targeting different cellular growth dynamics, the algorithm learned to identify the trade‐off relationship between long‐term growth and cost. We were able to identify several media with more growth of C2C12 cells than the control, as well as a medium with 23% more growth at only 62.5% of the cost of the control. These algorithmically generated media also maintained growth far past the study period, indicating the modeling approach approximates the cell growth well from an extremely limited data set.
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- Award ID(s):
- 2021132
- PAR ID:
- 10466545
- Publisher / Repository:
- Wiley
- Date Published:
- Journal Name:
- Engineering in Life Sciences
- Volume:
- 23
- Issue:
- 8
- ISSN:
- 1618-0240
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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