Poly (ethylene glycole)-Fibrinogen (PF) hybrid scaffold are prepared by the cross-linking of PEGylated fibrinogen precursors molecules. The fibrinogen provides to this hydrogel an inherent enzymatic degradability and cell-specific interactions, while the poly (ethylene glycole) (PEG) provides mechanical strength and a means to control the cross-linking density of the scaffold. It was previously shown that variations in the molecular weight of the PEG, the protein concentration, or the addition of PEG cross-linker, can be used to alter the biochemistry and physical properties of the scaffold. Following recent studies that demonstrated the effect of scaffold nanostructuring on cell behavior, we hypothesize that nanostructuring of PF scaffold could provide an additional means to control both their physical properties and their interaction with cells. In the current study we have developed a methodology for the nanostructuring of PF hydrogels. Our experimental approach utilizes the self-assembly tendency of the biocompatible amphiphilic block-copolymers poly(ethylene oxide)/poly(propylene oxide) (Pluronic ^® ), and is based on embedding micelles within the gel. Small angle x-ray scattering (SAXS) and cryo- transmission electron microscopy (cryo-TEM) experiments have verified existence of structural features of nanometric size within the scaffold. Cell seeding assays have demonstrated faster cell growth within the nanostructured scaffolds. Furthermore, the cell morphology was affected from the nanostructuring. This research is expected to lead a better understanding of the influence of structural modification on the cell activity to improved properties of PF scaffolds.

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