Mechanobiology in Stem Cell-Based Bioprinting

Bioprinting with stem cells is an emerging technique for creating human tissues from scratch, transforming our understanding of biology and its biomedical applications. While significant attention has been paid to biochemical cues, mechanobiology is emerging as an equally important regulator in stem cell-based bioprinting, yet it has long been unexplored. Recent advances in elucidating mechanotransduction pathways underscore the need to comprehend bioink mechanics to bridge printability and stem cell fate regulation. This review emphasises the central role of mechanobiology in stem cell-based bioprinting: ensuring adequate printability while maintaining and programming stem cell functionality through biomechanical signals. We discuss how the mechanical properties of bioinks influence stem cell behaviour, with a focus on mechanosensitive stem cells, including pluripotent, mesenchymal, neural, hepatic and lung stem cells. Special attention is given to stem cell-based organoids and their associated mechanotransduction signalling pathways. We further identify four key mechanobiological requirements that define the relationship between print fidelity and the mechanical cues governing stem cell mechanosensing. We propose integrative strategies drawing from innovations in materials science and bioprinting to reframe mechanics as a tunable parameter rather than a constraint. Our roadmap aims to leverage bioink mechanics not only to facilitate biofabrication but also to guide stem cell fate and functional remodelling of engineered tissues for potential clinical applications.