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A precision microgel platform to direct vascular morphogenesis in vitro

Kuehn, S.; Magno, V.; Zimmermann, R.; Limasale, Y.; Atallah, P.; Stoppa, A.; Maennel, M.; Thiele, J.; Freudenberg, U.; Werner, C.

2024-01-07 bioengineering
10.1101/2024.01.05.574387 bioRxiv
Show abstract

The dynamic organization of tissue development is reciprocally controlled by localized gradients of morphogens emanating from distinct clusters of cells that act as signaling centers1. While microgels2,3 have shown promise to recapitulate this process in engineered tissue constructs, their capacity to tailor morphogen distribution in space and time remained limited4-7. Here, we introduce a library of sulfated glycosaminoglycan (sGAG)-based microgels that offer unprecedented control over morphogen affinity (GUIDe, Gel Units to Instruct Development), thus enabling precise formation of concentration gradients. Multiparametric adjustment of the microgel charge patterns resulting from sGAG ionization was key to programmable morphogen release. The potential of our microgel system to guide tissue morphogenesis is demonstrated through the local administration of VEGF gradients in a microgel-in-gel in vitro vasculogenesis model and in hiPSC-derived kidney organoid cultures. Our micromaterials-based methodology offers valuable new options to mimic and modulate morphogen signaling centers, thereby advancing tissue/organ development research.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.