Independent Control of Topography for 3D Patterning of the ECM Microenvironment.

Tissues display highly anisotropic, heterogeneous, nonlinear physical properties that vary widely and depend on the composition, architecture, and pathology.1 Within these tissues, cells reside in a complex 3D environment composed of heterogeneous biological building blocks in a variety of arrangements featuring diverse geometries, dimensionalities, and material properties.1 The biophysical interactions between cells and these architectures have a profound impact on cell processes such as differentiation, migration, and proliferation.2, 3, 4, 5, 6, 7 One major tissue component is the extracellular matrix (ECM), which serves as a physical scaffold but also controls chemical cues, serving as a reservoir for cytokines and nutrients, and as a patchbay for integrin‐mediated mechano‐signals.8, 9 At the epithelia–stroma interface, dynamically regulated ECM proteins of the basement membrane program tissue polarization, and compartmentalize epithelial tissue from the stroma via the interstitial matrix. Structurally diverse ECM architectures composed of proteins such as laminins (LN), collagens, and fibronectin (FN) are topographically distinct, thus playing a primary role in providing physical and spatial cues to which cells respond in combination with biochemical cues.1, 10