a ∣ The composition of Matrigel is unamenable to modifications, ill-defined, complex and highly variable, resulting in heterogeneities in both biological and mechanical properties. As it is animal-derived, Matrigel may also contain xenogenic contaminants, and the presence of growth factors (GFs) and other biological proteins can lead to undesirable cellular effects. b ∣ Synthetic scaffolds are highly tunable and chemically defined. The mechanical, physical and biological properties of these scaffolds can be modified to direct cellular response while eliminating undesirable matrix-induced effects.