Satyam et al. from National University of Ireland, Galway (NUI Galway) proposed macromolecular crowding as means to create ECM-rich tissue equivalents. The principle of  macromolecular crowding is derived from the notion that in vivo cells reside in a highly crowded/dense extracellular space and therefore the conversion of the de novo synthesised procollagen to collagen I is rapid. However, in the even substantially more dilute than body fluids (e.g., urine: 36–50 g/L; blood: 80 g/L) culture conditions (e.g., HAM F10 nutrient medium: 16.55 g/L; DMEM/ F12 medium: 16.78 g/L; DMEM high glucose and L-glutamine medium: 17.22 g/L), the rate limiting conversion of procollagen to collagen I is very slow. It was confirmed that the addition of inert polydispersed macromolecules (presented as spherical objects of variable diameter) in the culture media will facilitate amplified production of ECM-rich living substitutes. Macromolecular crowding, by imitating native tissue localised density, can be utilised to effectively modulate in vitro microenvironments and ultimately produce ECM-rich cell substitutes, within hours rather than days or months in culture, without compromising fundamental cellular functions.  A recent study by researchers from the University of Twente has shown that emulating physiological molecular crowding may enhance chondrogenic properties of damaged chondrocytes.