Encoding cell-instructive cues to PEG-based hydrogels via triple helical peptide assembly

Effective synthetic tissue engineering scaffolds mimic the structure and composition of the natural extracellular matrix (ECM) to promote optimal cellular adhesion, proliferation, and differentiation. Among many proteins of the ECM, collagen and fibronectin are known to play a key role in the structural integrity of the scaffold as well as its ability to support cell adhesion. Here, we present photocrosslinked poly(ethylene glycol) diacrylate (PEGDA) hydrogels displaying collagen mimetic peptides (CMPs) that can be further conjugated to bioactive molecules via a CMP–CMP triple helix association. Pre-formed PEGDA–CMP hydrogels can be encoded with varying concentrations of cell-signaling CMP–RGD peptides similar to cell adhesive fibronectin decorating the collagen fibrous network by non-covalent binding. Furthermore, the triple helix mediated encoding allows facile generation of spatial gradients and patterns of cell-instructive cues across the cell scaffold that simulate the distribution of insoluble factors in the natural ECM.