Re-engineered cell-derived extracellular matrix as a new approach to clarify the role of native ECM

An extracellular matrix (ECM) has both biochemical and mechanophysical characteristics obtained from multiple components, which provides cells a dynamic microenvironment. During reciprocal interactions with ECM, the cells actively remodel the matrix, including synthesis, degradation, and chemical modification, which play a pivotal role in various biological events such as disease progression or tissue developmental processes. Since a cell-derived decellularized ECM (cdECM) holds in vivo-like compositional heterogeneity and interconnected fibrillary architecture, it has received much attention as a promising tool for developing more physiological in vitro model systems. Despite these advantages, the cdECM has obvious limitations to mimic versatile ECMs precisely, suggesting the need for improved in vitro modeling to clarify the functions of native ECM. Recent studies propose to tailor the cdECM via biochemically, biomechanically, or incorporation with other systems as a new approach to address the limitations. In this chapter, we summarize the studies that re-engineered the cdECM to examine the features of native ECM in-depth and to increase physiological relevancy.