Supramolecular assembly of multi-purpose tissue engineering platforms from human extracellular matrix

Recapitulating the biophysical and biochemical complexity of the extracellular matrix (ECM) remains a major challenge in tissue engineering. Hydrogels derived from decellularized ECM provide a unique opportunity to replicate the architecture and bioactivity of native ECM, however, they exhibit limited long-term stability and mechanical integrity. In turn, materials assembled through supramolecular interactions have achieved considerable success in replicating the dynamic biophysical properties of the ECM. Here, we merge both methodologies by promoting the supramolecular assembly of decellularized human amniotic membrane (hAM), mediated by host-guest interactions between hAM proteins and acryloyl-β-cyclodextrin (AcβCD). Photopolymerization of the cyclodextrins results in the formation of soft hydrogels that exhibit tunable stress relaxation and strain-stiffening. Disaggregation of bulk hydrogels yields an injectable granular material that self-reconstitutes into shape-adaptable bulk hydrogels, supporting cell delivery and promoting neovascularization. Additionally, cells encapsulated within bulk hydrogels sense and respond to the biophysical properties of the surrounding matrix, as early cell spreading is favored in hydrogels that exhibit greater susceptibility to applied stress, evidencing proper cell-matrix interplay. Thus, this system is shown to be a promising substitute for native ECM in tissue repair and modelling.