Programming of Multicellular Patterning with Mechano‐Chemically Microstructured Cell Niches

Abstract

Multicellular patterning of stem‐cell‐derived tissue models is commonly achieved via self‐organizing activities triggered by exogenous morphogenetic stimuli. However, such tissue models are prone to stochastic behavior, limiting the reproducibility of cellular composition and forming non‐physiological architectures. To enhance multicellular patterning in stem cell‐derived tissues, a method for creating complex tissue microenvironments endowed with programmable multimodal mechano‐chemical cues, including conjugated peptides, proteins, morphogens, and Young's moduli defined over a range of stiffnesses is developed. The ability of these cues to spatially guide tissue patterning processes, including mechanosensing and the biochemically driven differentiation of selected cell types, is demonstrated. By rationally designing niches, the authors engineered a bone‐fat assembly from stromal mesenchyme cells and regionalized germ layer tissues from pluripotent stem cells. Through defined niche‐material interactions, mechano‐chemically microstructured niches enable the spatial programming of tissue patterning processes. Mechano‐chemically microstructured cell niches thereby offer an entry point for enhancing the organization and composition of engineered tissues, potentiating structures that better recapitulate their native counterparts.

Abstract

Stem‐cell‐derived tissue models exhibit stochastic cellular compositions with malformed architectures. To enhance such tissues, a method for orthogonal programming of material microstructure with biochemicals across a range of Young's moduli is developed. Through designed niche‐material interactions the authors can spatially program tissue patterning processes, enabling the enhancement of tissue organization and composition, potentiating structures that better recapitulate their native counterparts.