A precision microgel platform to direct vascular morphogenesis in vitro

The dynamic organization of tissue development is reciprocally controlled by localized gradients of morphogens emanating from distinct clusters of cells that act as signaling centers. While microgels have shown promise to recapitulate this process in engineered tissue constructs, their capacity to tailor morphogen distribution in space and time remained limited. 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. ### Competing Interest Statement V.M., S.K., A.S., U.F. and C.W.have filed a patent application for various aspects of this work.