Microalgal Co-Cultivation meets Media Recycling: A Circular Pathway to Serum and Amino-Acid Reduction in Cultivated Meat

Our increasing global population combined with the UN Sustainable Development Goals of zero hunger and good health require greater protein intake per capita and higher protein production. Consequently, sustainable food alternatives such as cultivated meat (CM) are urgently required. However, large-scale CM cell-systems face key challenges, particularly high media costs driven by amino acids and the need for ethically-sourced growth factors. Microalgae offer promising solutions, producing high protein yields with all essential amino acids simply from light, CO2, water and nutrients or spent CM media. Here we present Chlorella BDH-1 grown in spent CM media waste as a substitute-source for reduced amino acids and fetal bovine serum in cell culture media, enabling a circular strategy through beneficial mammalian cell-algae co-cultivation. We identified optimal algal growth conditions for maximum protein yield and demonstrated that two recycling rounds using industry-derived spent CM media maximize microalgal biomass yield per unit volume of waste media. We obtained algal lysate, determined thermal processing as the most cost-effective and mammalian cell-beneficial approach, and identified consumed lysate components. Compared to standard media, our lysate increased mammalian cell proliferation over 2-fold in reduced serum and amino acid conditions, replacing costly cell media components. We finally closed the loop by demonstrating a synergistic effect of the algal lysate with our co-cultivation - which co-produces algal biomass. The combination boosted mammalian cell proliferation 1.45-fold, conservatively estimating a media cost reduction by [~]66%. These findings establish parameters to advance the field towards cost-effective sustainable circular cell culture systems with applications in CM production and other biotechnology fields requiring large-scale tissue culture. Technology Readiness: