Engineering cell instructive microenvironments for in vitro replication of functional barrier organs

Multicellular organisms exhibit synergistic effects among their components, giving rise to emergent properties crucial for their genesis and overall functionality and survival. Morphogenesis, the formation of an organism's shape, involves and relies upon intricate and biunivocal interactions among cells and their environment, i.e., the extracellular matrix (ECM). Cells secrete their own ECM which, in turn regulates their morphogenetic program by controlling time and space presentation of matricellular signals. The ECM, once perceived as a passive structure, is now acknowledged as an informative space where both biochemical (eg, growth factors, cytokines, matricellular cues) and biophysical (eg, morphophysical, mechanical) signals are tightly orchestrated. Replicating this sophisticate and highly interconnected informative media in a synthetic scaffold for tissue engineering is unattainable with our current technology and this limits our capability to engineering functional human tissues/organs in vitro and in vivo. This review explores current limitation to in vitro organ morphogenesis, emphasizing the interplay of gene regulatory networks, mechanical factors, and tissue microenvironment cues. In vitro efforts to replicate biological processes, particularly for barrier organs like the lung and intestine, are examined. The importance of maintaining cells within their native microenvironmental context is highlighted to accurately replicate organ-specific morphogenic properties. The review underscores the necessity for microphysiological systems that faithfully reproduce cell-native interactions, emphasizing spatial and temporal signaling cues between cells and the ECM. This approach is vital to improve such microphysiological systems used to for advancing our understanding of developmental disorders and disease progression. This article is protected by copyright. All rights reserved.