From pharmaceutical paradigms to scalable production: Re-engineering growth factor production for cultivated meat

Background Cultivated meat (CM) production relies on defined, serum-free culture media to achieve scalability and ensure ethical acceptability, wherein recombinant growth factors (GFs) are essential components regulating cell proliferation, differentiation, and metabolic activity. However, their high production costs and continued reliance on mammalian-cell-based recombinant production systems remain significant bottlenecks to the commercial implementation of CM technologies. Scope and approach This review examines the biological functions and molecular features of GFs used in CM, focusing on physicochemical properties that constrain recombinant production. Mammalian (e.g., Chinese hamster ovary cells (CHO) and human embryonic kidney (HEK) 293 cells) and non-mammalian expression platforms (e.g., bacterial, yeast, plant, photosynthetic microbial, and cell-free systems) are compared with respect to manufacturability, scalability, and regulatory considerations. Key engineering strategies improving recombinant yield, secretory efficiency, post-translational modifications, and host robustness are also discussed. Key findings and conclusions Non-mammalian expression platforms provide viable alternatives to conventional pharmaceutical manufacturing paradigms, enhancing the scalability and affordability of GFs production. Nonetheless, challenges in downstream processing, functional stability and regulatory integration remain to be addressed. Advances in system-level approaches, including multiplex GFs production in microbes, autocrine signalling, receptor modulation, and the use of functional substitutes, such as peptidomimetics and plant protein hydrolysates, could further reduce reliance on recombinant GFs. Collectively, these insights outline a roadmap for transitioning GFs supply toward scalable, cost-effective systems that support the commercialisation of CM.