Many advanced cell therapies and tissue-engineered products require large numbers of high-quality cells. However, producing these cells reliably, reproducibly and at clinically relevant scale remains a major challenge. Traditional flat plastic culture vessels are useful for laboratory-scale experiments, but they are difficult to scale efficiently and can require large incubator space, extensive manual handling and repeated processing steps.

Microcarriers offer one route to overcoming this limitation. These small particles provide a large surface area for adherent cells, such as mesenchymal stromal/stem cells, to attach, grow and interact with their surrounding material environment. By transferring cell expansion from flat two-dimensional surfaces into three-dimensional suspension culture, microcarriers can support higher-density cell production in a more scalable format.

Bioreactors provide the controlled culture environment needed to make this approach practical. In stirred, rocking, vertical-wheel or packed-bed systems, cells and carriers can be cultured under defined and monitored conditions. Parameters such as mixing, oxygen transfer, nutrient supply, waste accumulation and shear stress can all influence cell growth and quality. Understanding and controlling these factors is essential for developing robust manufacturing processes.

Within MAINSTREAM, we are exploring how the design of microcarriers and the use of bioreactors can be brought together to improve the scalable manufacture of cell-based products. This includes investigating new carrier materials, surface chemistries, mechanical properties and geometries, alongside bioreactor-based culture strategies. A key aim is to understand not only how many cells can be produced, but whether those cells retain the biological properties required for downstream therapeutic or tissue-engineering applications.

Alongside this, MAINSTREAM is developing and evaluating sensing and monitoring technologies that could provide real-time information about cell culture performance. These approaches may help track key features such as cell growth, carrier aggregation, nutrient use, waste accumulation and overall culture health without relying solely on manual sampling and end-point assays. Integrating sensors with bioreactor systems could support better process control and more reproducible cell manufacturing.

This work brings together expertise in biomaterials, stem cell biology, bioprocessing, engineering, sensor development and real-time monitoring. By integrating advanced microcarrier design with scalable bioreactor platforms and in-line monitoring technologies, MAINSTREAM aims to develop manufacturing approaches that are more efficient, reproducible and suitable for future translation.