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bioRxiv · 10.1101/2021.02.10.430691

Niche-guided tissue patterning by chemomechanical flow lithography

Newman, P. L. H.·Osteil, P.·Anderson, T. A.·Sun, J. Q. J.·Kempe, D.·Biro, M.·Tam, P. P. L.·Shin, J.-W.·Zreiqat, H.
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Abstract

Stem-cell derived tissue models are commonly cultured under globally-delivered stimuli that trigger histogenesis via self-organizing activity. However, the culture of such tissue models is prone to stochastic behavior, limiting the reproducibility of cellular composition and resulting in non-physiological architectures. To overcome these shortcomings, we developed a method for printing cell niche microenvironments with microstructured cues that mediate local histogenic processes, including mechanosensing and differentiation of selected cell types. Microstructured cues include independently tunable mechano-chemical properties, with conjugated peptides, proteins, and morphogens across a range of Youngs moduli. By rationally designing niches, we mediate the structure of tissues derived from stem-cell-progenitor sources, including a bone-fat assembly from stromal mesenchyme, and embryonic tissues derived from hiPSC. We show that microstructured cues can recapitulate mechano-chemical signals resembling early embryonic histogenesis. This outcome includes a role for niche mechanics in human embryonic organization, where soft niche mechanics bias markers of mesendodermal differentiation and epithelial-to-mesenchymal-transition (EMT), as well as a demonstration of a material-mediated morphogen signaling centers able to induce foci of mesenchymal and EMT differentiation. Thus, microstructured materials can mediate local histogenic processes to enhance the structure and composition of tissue models.

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Newman, P. L. H., Osteil, P., Anderson, T. A., Sun, J. Q. J., Kempe, D., Biro, M., Tam, P. P. L., Shin, J.-W., Zreiqat, H.. 2021-02-11. Niche-guided tissue patterning by chemomechanical flow lithography. https://doi.org/10.1101/2021.02.10.430691

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