Self-sorting Double Network Hydrogels with Photo-Definable Biochemical Cues As Artificial Synthetic Extracellular Matrix

In soft connective tissues,the extracellular matrix(ECM)provides spatiotemporally well-defined mechanical and chemical cues that regulate the functions of residing cells.However,it remains challenging to replicate these essential features in synthetic biomaterials.Here,we develop a self-sorting double network hydrogel(SDNH)with spatially well-defined bioactive ligands as synthetic ECM.Specifically,the SDNH is made of two peptides that can independently self-assemble into fibers of different microscopic features,mimicking the hierarchical protein assemblies in ECM.Each peptide contains a photo-reactive moiety for orthogonally patterning bioactive molecules(i.e.,cyclic arginine-glycine-aspartate(cRGD)and osteogenic growth peptide(OGP))using UV and visible light.As a proof-of-principle,we demonstrate the engineering of SDNH with spatially separated or colocalized cRGD and OGP molecules to control the response of encapsulated stem cells.Our study represents an important step towards defining the mechanical and biochemical cues of synthetic ECM using advanced chemical biology tools.