Programmed shape transformations in cell-laden granular composites

Tissues form during development through mechanical compaction of their extracellular matrix (ECM) and shape morphing, processes that result in complex-shaped structures that contribute to tissue function. While observed in vivo, control over these processes in vitro to understand both tissue development and guide tissue formation has remained challenging. Here, we use combinations of mesenchymal stromal cell spheroids and hydrogel microparticles (microgels) with varied hydrolytic stability to fabricate programmable and dynamic granular composites that control compaction and tissue formation over time. Mixed microgel populations of varying stability provide a further handle to alter compaction, and the level of compaction guides the uniformity and level of ECM deposition within tissues. Last, spatially patterned granular composites of varying compaction enable shape transformations (i.e., bending/curvature) that are stable with culture and are predicted by finite element models.