Publications

Neuromechanobiology has emerged as a multidisciplinary field at the interface of neuroscience and mechanobiology, aiming to elucidate how mechanical forces influence the development, organization, and function of the nervous system. This review offers a comprehensive overview of the historical evolution of the discipline, its molecular and biophysical foundations, and the experimental strategies employed to investigate it. Recent advances have revealed the pivotal roles of substrate stiffness, mechanical signaling, and force transduction in neural stem proliferation, axon guidance, synapse formation, and neural circuit maturation. All these effects originate at the molecular level and extend to the mesoscopic scale. Disrupted mechanotransduction has been increasingly implicated in neurodevelopmental disorders and neurodegenerative diseases, underscoring its clinical relevance. Key unresolved questions and future directions are also highlighted, with emphasis on the need for integrative approaches to decipher the complex interplay between mechanical forces and neural function.

JTD Keywords: Axon guidance, Brain development, Central-nervous-system, Contact inhibition, Force transmission, Hippo pathway, Human brain-development, Mechanical forces, Mechanical-properties, Mechanotransduction, Neural migration and regional specification, Neuromechanobiology, Patterned neural-tube, Pluripotent stem-cells, Signaling pathway, Synaptic activity, Tau mislocalization

In recent years considerable progress has been made in the development of faithful procedures for the differentiation of human pluripotent stem cells (hPSCs). An important step in this direction has also been the derivation of organoids. This technology generally relies on traditional three-dimensional culture techniques that exploit cell-autonomous self-organization responses of hPSCs with minimal control over the external inputs supplied to the system. The convergence of stem cell biology and bioengineering offers the possibility to provide these stimuli in a controlled fashion, resulting in the development of naturally inspired approaches to overcome major limitations of this nascent technology. Based on the current developments, we emphasize the achievements and ongoing challenges of bringing together hPSC organoid differentiation, bioengineering and ethics. This Review underlines the need for providing engineering solutions to gain control of self-organization and functionality of hPSC-derived organoids. We expect that this knowledge will guide the community to generate higher-grade hPSC-derived organoids for further applications in developmental biology, drug screening, disease modelling and personalized medicine. This Review provides an overview of bioengineering technologies that can be harnessed to facilitate the culture, self-organization and functionality of human pluripotent stem cell-derived organoids.

JTD Keywords: Bioengineering, Differentiation, Embryonic-tissues, Extracellular-matrix, Humans, In-vitro, Kidney organoids, Model, Neural-tube, Organoids, Pluripotent stem cells, Pluripotent stem-cells, Reconstitution, Self-organization