Serum-free media for cultivated meat: from cellular mechanisms to cost-effective bioprocess design

Serum-free media (SFM) determine whether cultivated meat (CM) can progress from pilot studies to scalable, food-grade manufacturing. Replacing fetal bovine serum (FBS) requires food-grade media that supply nutrients, maintain ionic balance, provide defined signaling cues, and mitigate shear stress. This review charts the development of SFM for CM and critically discusses how these component modules interact across relevant cell types, highlighting where evidence is robust and where translation across species, cell lines, and production scale remains uncertain. We assess plant-, microbial-, and microalgal-derived protein hydrolysates as pragmatic supplements or partial substitutes, emphasizing compositional characterization, batch consistency, and supply-chain feasibility, and summarize strategies to curb dependence on high-cost growth factors through improved production and cell-intrinsic support. AI- and systems biology-enabled optimization is highlighted to link formulation with bioprocess performance, cost, and sustainability. Finally, we synthesize current safety assessment and regulatory governance for complex media and propose priorities for industrial translation, including hydrolysate quality standards, expansion of food-grade raw-material pipelines, and tighter integration of formulation design with manufacturing and compliance constraints.