Serum-Free Media in Cellular Agriculture: Current Challenges, Design Strategies, and Future Prospects.

Cellular agriculture (CA), an emerging and sustainable agricultural paradigm, offers a promising solution to global challenges in food security and environmental sustainability. However, the large-scale manufacturing of CA is hindered by its dependence on serum-based culture media, which are costly and compositionally variable and raise biosafety and animal welfare concerns. Addressing this bottleneck requires the development of affordable, reliable, and ethically compliant serum-free media (SFM). This perspective elucidates the functional roles of serum components, summarizes recent advances in serum substitutes, and highlights microorganism-derived substitutes as particularly promising because of their low cost, compositional stability, and scalability. Furthermore, we outline the evolution of SFM formulation from empirical and design-of-experiment-based optimization to multiomics-driven formulation and artificial intelligence (AI)-assisted design. Overall, this review provides a focused framework for understanding current challenges, design strategies, and future directions of SFM development for CA.