Fig. 1. Biomaterials inspired by the extracellular matrix, and cell-mediated matrix remodelling.

The extracellular matrix (ECM) — the physiological material that surrounds cells in tissues — provides tissues with a three-dimensional physical structure and with bioactive ligands (such as adhesive motifs and growth factors). ECM-mimicking biomaterials can be rendered cell-instructive by incorporating protein-based or peptide-based motifs that recapitulate key features of the native ECM. However, cells encapsulated within hydrogels remodel their surroundings through a combination of matrix secretion and degradation. Over time, the cell-secreted matrix can override cues provided by the hydrogel. This behaviour parallels the phenomenon of dynamic reciprocity observed in tissues, by which cells modulate their surroundings biochemically and mechanically, regulating intracellular signalling, gene expression, and ultimately cell behaviour.