Cell detachment: A review of techniques, challenges, and opportunities for advancing biomedical research and applications

Culturing living cells outside the body is a complex process involving various techniques. Despite advances, harvesting cells remains challenging, especially in light of new emerging and scaled-up cell culture technologies. Enzymatic adherent cell harvesting is the most used and robust technology but can harm cells. Non-enzymatic detachment methods offer advantages but also present challenges. Thermo-responsive polymers require precise control of the molecular characteristics and thickness of the thermoresponsive films, which makes this method less robust and more expensive. This review highlights the importance of controlling harvested cell quality and its relationship to cell binding and detachment mechanisms. Many alternative methods have not been extensively analyzed, and their impact on cell quality beyond standard viability assays is not yet known. Developing robust cell harvesting methods for bioreactor microcarriers is a rapidly growing challenge as the cell manufacturing industry expands. Microcarriers with stimuli-responsive coatings face challenges similar to those observed for laboratory-scale cell dishes and bring an additional aspect of the need for microbead recycling consideration. All that together underlines the importance of the research in biomaterials and biotechnology for cell manufacturing.