Fig. 1: The DECIPHER system.

a, Murine cardiac tissue (young and aged) was sliced with a vibratome, placed on a hydrophobic glass slide (i) and incubated in a hydrogel stabilization solution consisting of acrylamide pretreated with formaldehyde, bis-acrylamide and Irgacure 2959 of soft (~10 kPa) or stiff (~40 kPa) formulations (ii). Crosslinking of the hydrogel mesh was carried out with UV (iii). At this step, the tissue is stabilized in the hydrogel mesh (as indicated in the box below) and samples are referred to as ‘pre-DECIPHER’. Subsequent decellularization is carried out using SDC and DNase (iv) and samples are referred to as ‘DECIPHER’. The scaffolds are seeded with young or aged CFs (v). b, DECIPHER maintains the native tissue architecture and mechanics, compared with conventional dECM hybrid materials. c, Images of pre-DECIPHER and DECIPHER samples with a tissue/ECM scaffold indicated by the dashed lines, surrounded by a coverslip/pure PA gel. d, SEM images of native tissue and DECIPHER samples with arrows indicating the ECM fibres versus the hydrogel mesh. Scale bars, 200 nm. e, Three-dimensional confocal reconstruction of DECIPHER samples with Nile Blue-tagged acrylamide and labelled collagen. Scale bars, 50 µm.