Towards sustainable serum-free media development from alternative sources for cultivated meat.

The economic feasibility and scalability of cultivated meat (CM) is critically hindered by the high manufacturing costs, particularly the cost associated with cell culture media. Therefore, numerous studies have proposed the use of sustainable alternatives to replace the expensive cell culture media components, especially animal serum. In this review, we comprehensively surveyed such developments and interpreted the opportunities and limitations of animal serum-reduction or replacement methodologies in designing culture media for CM production. Among the various alternative sources investigated, plant-derived sources and recombinant proteins have been the most extensively studied. We also highlight the critical gaps in existing studies such as the lack of demonstration of scalability, cost-effectiveness and long-term applicability of proposed alternative sources. Subsequently, we provide a roadmap for future studies on how to demonstrate the proposed alternative does not have adverse effects on cellular long-term stability, as well as comply with food safety and regulatory standards while being cost-effective which are critical for large scale CM manufacturing. We further propose a two-pronged framework based on high-throughput screening, systems biology, and Machine Learning (ML) tools to optimize serum-free CM media formulations using alternative sources in a rapid and scalable manner.