Modeling the Maturation of the Vocal Fold Lamina Propria Using a Bioorthogonally Tunable Hydrogel Platform

Zou, Xiaoyu; Zhang, He; Benson, Jamie M.; Gao, Hanyuan; Burris, David L.; Fox, Joseph. M.; Jia, Xinqiao

doi:10.1002/adhm.202301701

Cited by 2 publications

(1 citation statement)

References 55 publications

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“…Further spatial patterning of biochemical signaling factors could be achieved within this model using laminar flow patterning by interstitial perfusion of signaling molecules into each individual stromal region through the hydrogel injection ports (65)(66)(67). Coupling patterned interstitial flow of soluble molecules with advanced synthetic hydrogel systems capable of bioorthogonal crosslinking (68) would enable in situ post-polymerization modification and patterning of the hydrogel's biochemical or biophysical properties.…”

Section: Discussionmentioning

confidence: 99%

Zonal Patterning of Extracellular Matrix and Stromal Cell Populations Along a Perfusable Cellular Microchannel

Chernokal,

Ferrick,

Gleghorn

2024

Preprint

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The spatial organization of biophysical and biochemical cues in the extracellular matrix (ECM) in concert with reciprocal cell-cell signaling is vital to tissue patterning during development. However, elucidating the role an individual microenvironmental factor plays using existingin vivomodels is difficult due to their inherent complexity. In this work, we have developed a microphysiological system to spatially pattern the biochemical, biophysical, and stromal cell composition of the ECM along an epithelialized 3D microchannel. This technique is adaptable to multiple hydrogel compositions and scalable to the number of zones patterned. We confirmed that the methodology to create distinct zones resulted in a continuous, annealed hydrogel with regional interfaces that did not hinder the transport of soluble molecules. Further, the interface between hydrogel regions did not disrupt microchannel structure, epithelial lumen formation, or media perfusion through an acellular or cellularized microchannel. Finally, we demonstrated spatially patterned tubulogenic sprouting of a continuous epithelial tube into the surrounding hydrogel confined to local regions with stromal cell populations, illustrating spatial control of cell-cell interactions and signaling gradients. This easy-to-use system has wide utility for modeling three-dimensional epithelial and endothelial tissue interactions with heterogeneous hydrogel compositions and/or stromal cell populations to investigate their mechanistic roles during development, homeostasis, or disease.

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