Co-Assembled Supramolecular Hydrogelators Enhance Glomerulogenesis in Kidney Organoids Through Cell-Adhesive Motifs

Soluble biochemical agents are being employed to generate kidney organoids from human-induced pluripotent stem cells. However, this soluble factor approach does not consider the effect of the mechanical environment on lineage commitment. Here, a mechanoresponsive nano-environment with cell-adhesive properties composed of supramolecular hydrogelators that co-assemble into fibrous superstructures to form a transient network is presented, which is used to encapsulate kidney organoids. The delayed sol-gel transition of the transient network enables fibrous superstructures to diffuse into the densely packed extracellular organoid space during the encapsulation procedure. This allows the mechanoresponsive matrix to induce a biological response beyond the organoid-hydrogel border, and tune glomerulogenesis inside kidney organoids. In this manner, biomaterials are used as a complementary tool to soluble biochemical agents in tuning lineage commitment and refining organoid maturation. Mechanoresponsive nano-environments composed of supramolecular hydrogelators are used to encapsulate kidney organoids. A delayed sol-gel transition is engineered into the supramolecular matrix, enabling fibrous superstructures to permeate into the extracellular organoid space. These supramolecular fibers elicit a mechano-biological response beyond the organoid-hydrogel border and induce a shift in the nephron segmentation, which enhances glomerulogenesis in the kidney organoid. image