The Rise of Mechanobiology for Advanced Cell Engineering and Manufacturing.

The rise of cell-based therapies, regenerative medicine, and synthetic biology, has created an urgent need for efficient cell engineering, which involves the manipulation of cells for specific purposes. This demand is driven by breakthroughs in cell manufacturing, from fundamental research to clinical therapies. These innovations have come with a deeper understanding of developmental biology, continued optimization of mechanobiological processes and platforms, and the deployment of advanced biotechnological approaches. Induced pluripotent stem cells and immunotherapies like chimeric antigen receptor T cells enable personalized, scalable treatments for regenerative medicine and diseases beyond oncology. But continued development of cell manufacturing and its concomitant clinical advances is hindered by limitations in the production, efficiency, safety, regulation, cost-effectiveness, and scalability of current manufacturing routes. Here, recent developments are examined in cell engineering, with particular emphasis on mechanical aspects, including biomaterial design, the use of mechanical confinement, and the application of micro- and nanotechnologies in the efficient production of enhanced cells. Emerging approaches are described along each of these avenues based on state-of-the-art fundamental mechanobiology. It is called on the field to consider mechanical cues, often overlooked in cell manufacturing, as key tools to augment or, at times, even to replace the use of traditional soluble factors.