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Morphogenetic Micro Engineering

Morphogenetic Micro Engineering

Decoding morphogenesis in vitro using micro engineered systems and a developmental biology approach

The term morphogen (Greek: ‘form-giver’) was coined by Alan Turing back in 1952. Morphogens play a pivotal role in organogenesis and homeostasis and represent soluble molecules, which emanate from restricted regions of a tissue and act as graded positional cues that control cell fate specification.

The name of our multidisciplinary lab ‘Morphogenetic Micro Engineering’ emphasizes our approach of using 3D micro engineered/microfluidic systems to control the number, position, polarization, migration, behavior, and fate of cells in advanced stem cell-derived 3D in vitro models (e.g., blastoids, gastruloids, embryoid bodies and organoids). This includes e.g. exposing selected regions or the whole multicellular construct to spatiotemporally defined gradients of soluble molecules/morphogens. We are intrigued by the idea to recapitulate and guide self-organizational processes in multicellular 3D systems on multiple scales by creating artificial signaling centers and creating an extrinsic coordinate system for cells in vitro. Such advanced micro engineered systems help us to mimic morphogenetic events in vitro, to gain new insights into early embryonic developmental processes, and to better understand how positional information is processed by cells in a multicellular construct. By combining micro engineering and 3D stem cell biology, we are exploring new perspectives on self-organizing biological systems to identify and elucidate intrinsic rules and key regulatory mechanisms, which are vital to form complex tissues and organs. In the long term, we will use this newly acquired knowledge in more applied contexts to better control wound healing and tissue repair to set the stage for next-generation Regenerative Medicine solutions.

Selected publications

  • Luijkx DG, Ak A, Guo G, van Blitterswijk CA, Giselbrecht S, Vrij EJ. Monochorionic Twinning in Bioengineered Human Embryo Models. Advanced Materials. Published online April 9, 2024. https://doi.org/10.1002/adma.202313306
  • Carvalho DJ, Kip AM, Tegel A, et al. A Modular Microfluidic Organoid Platform Using LEGO-Like Bricks. Advanced Healthcare Materials 2024;13(13):e2303444. https://doi.org/10.1002/adhm.202303444
  • Kakni P, Jutten B, Teixeira Oliveira Carvalho D, et al. Hypoxia-tolerant apical-out intestinal organoids to model host-microbiome interactions. Journal of Tissue Engineering 2023;14:20417314221149208. Published 2023 Jan 18. https://doi.org/10.1177/20417314221149208
  • Teixeira Carvalho DJ, Moroni L, Giselbrecht S. Clamping strategies for organ-on-a-chip devices. Nature Reviews Materials 2023, 8, 147–164. https://doi.org/10.1038/s41578-022-00523-z
  • Samal P, Maurer P, van Blitterswijk C, Truckenmüller R, Giselbrecht S. A New Microengineered Platform for 4D Tracking of Single Cells in a Stem-Cell-Based In Vitro Morphogenesis Model. Advanced Materials 2020;32(24):e1907966. https://doi.org/10.1002/adma.201907966
  • Neuzil P, Giselbrecht S, Länge K, Huang TJ, Manz A. Revisiting lab-on-a-chip technology for drug discovery. Nature Reviews Drug Discovery 2012, 11, 620–632. http://dx.doi.org/10.1038/nrd3799