Serum-Free Media Development Strategies for Cultivated Meat: A Machine Learning-Assisted Systematic Scoping Review

Growing global population and environmental concerns associated with conventional meat production demand sustainable alternatives. Cultivated meat holds significant promise, yet its scalability remains constrained by reliance on fetal bovine serum (FBS) that raises critical ethical, economic, and environmental concerns. This systematic scoping review conducted following PRISMA-ScR guidelines across Scopus, Web of Science, and PubMed (2000-September 2025), synthesizes sustainable strategies for serum-free media development in cellular agriculture. Two principal approaches were identified: circular cell culture (CCC) systems and agrifood side stream valorisation. CCC systems integrate microalgae or cyanobacteria with mammalian myoblasts, enabling medium recycling. Growth rates were comparable to FBS-supplemented controls, with ammonia reduced by 98% and lactate by 68%. However, gradual nutrient depletion and system complexity limit current applicability. Side stream valorisation showed that protein isolates from agricultural by-products can support myoblast proliferation. Rapeseed protein isolate outperformed recombinant albumin by 15%, and enzymatic extraction increased protein yields up to 930% over conventional methods. Remaining challenges include suboptimal proliferation relative to 10% FBS, premature differentiation, extended nutrient depletion, and a critical lack of life cycle assessments. Integrating standardized extraction protocols with optimized culture conditions will be essential to unlock commercial-scale cultivated meat production.