Material-mediated histogenesis using mechano-chemically microstructured cell niches

Abstract

Pluripotent-stem-cell-derived tissue-models have been established with increasingly physiological shape, size and function. However, the histogenic and morphogenetic processes present in these models proceed stochastically. This reflects an absence of technologies able to produce complex supportive cell niches that can reproducibly guide tissue patterning and generate well-defined tissue structures. To address this, we have developed chemomechanical flow lithography (CMFL), a printing technology that delivers orthogonally programmable chemical and mechanical properties to microstructured niches that drive the differentiation of selective cell types and spatial emplacement of these cells in a micropattern. We print microstructured niches conjugated with peptides, proteins and macromolecular morphogens across a range of Young's Modulus. Using such niches, we generated tissue patterned constructs from a single cell source with regionalised cell differentiation, including a bone-fat osteoid from stromal mesenchyme, and a patterned assembly of germ-layer tissues derived from pluripotent stem cells. Thus, CMFL is a valuable tool for generating orthogonally and chemomechanically defined niches able to guide spatially defined tissue patterns. This approach enables studies to better understand how extrinsic niche factors regulate histogenic and morphogenetic processes, towards engineering complex structured tissue and organ systems with higher-level emergent function.