“…22 In vitro models use a wide variety of methods to induce/inhibit dormancy 21,29 by exposing cells to soluble/insoluble cues 16,[30][31][32] (e.g., thrombospondin-1 exposure, 22 inhibitors for integrin β1, 31 and type-I TGF-β, changes in extracellular matrix [ECM] protein composition 33 ), or to stresses (e.g., serum starvation, 34 hypoxia, 35 exposure to chemotherapeutic agents, 36,37 and physical immobilization to inhibit proliferation 38,39 ). In vitro models mostly rely on 3D culture/encapsulation methods 40 using materials of biological origin (e.g., collagen, 30,41 Matrigel, 42 tissue extracts 31,43 ), synthetic materials (e.g., polyethylene glycol [PEG], 44,45 silica-PEG 39,46 ), and organic-synthetic materials (e.g., PEG-collagen, 47 and PEG-collagen/integrin 45 ). For recent comprehensive reviews of in vitro models, please see papers by Pradhan et al, 29 and Montagner et al 21 Shortcomings of 3D matrices that use materials of biological origin include unknown composition, batch-to-batch variability, limited control over chemical and mechanical properties, and inability to recover the dormant cells for downstream analysis.…”