Collagen type I mimicking peptide additives to functionalize synthetic supramolecular hydrogels

Small bioactive peptide sequences derived from extracellular matrix proteins possess the ability to interact with cell receptors. As such, these peptide additives are excellent mimics to develop materials for 3D cell culture. Two types of supramolecular modified collagen type I mimicking peptide additives are presented; UPy-GFOGER (39 amino acids), with a novel superstructure, and the more simplistic UPy-DGEA (7 amino acids). Here, we studied the impact of the conformational differences between both peptide additives, on their biological performance. Various analyzing techniques demonstrated the ability of the supramolecular UPy-GFOGER to self-assemble into short nanofibers with brush-like outer features, suggesting trimerization into a triple helix. UPy-DGEA is a short additive without a complex structure. Since, collagen type I is a major component of the human corneal stroma, primary keratocytes (PKs) are encapsulated within the functionalized hydrogels to provide insights in the induced bioactivity of both additives. Incorporation of UPy-GFOGER supported an elongated morphology and (re-)differentiation of the encapsulated PKs, while tiny round-shaped cells were observed within the hydrogels functionalized with UPy-DGEA. This difference in biological success between UPy-GFOGER and UPy-DGEA indicates the difficulty of using short peptide additives without a complex structure to mimic the complex structure of natural collagen.