Neves SC, Moroni L, Barrias CC, Granja PL. Trends Biotechnol 2020;3:292–315.
Native tissue mimicry is still a major challenge in TERM. Extracellular matrix (ECM) analogs should ideally provide biologically relevant biochemical/biophysical cues, in an adequate spatial-temporal manner, to properly stimulate cultured and/or recruited cells towards functional tissue formation. Hydrogels are the most attractive ECM analogs, but it is difficult to tune them to mimic most of the native tissue-specific features alone without concomitantly hindering key biological processes. One promising strategy to overcome this relies on the use of hybrid systems, combining hydrogels with other structures. Providing structural/mechanical reinforcement, spatial patterning/guidance, and/or stimuli responsiveness to hydrogel-based systems emerged as effective methodologies to more closely replicate the plethora of features and signals that native ECM presents to cells.