Merging Natural Biopolymers with Supramolecular Chemistry: Emulating the Native Extracellular Matrix's Complexity

The extracellular matrix (ECM) is one of the most striking natural self-assembled landscapes, essential for tissue integrity and cellular functions, where it orchestrates cell fate through a dynamic interplay of noncovalent interactions. Despite decades of research, there is still no scaffold that can replicate its nanostructural elegance and functional dynamic behavior. In this Perspective, we summarize cutting-edge approaches to reconstruct the ECM, putting an emphasis on either dynamic supramolecular designs or naturally sourced biopolymers. We then propose merging the natural with the synthetic world to enable hybrid cell-instructive materials that combine the dynamic mechanical profile, biomolecular composition and structural features of the ECM at all scales, from the nano- to the mesoscale, aiming to create a fully functional artificial ECM.