Temperature-induced fibrillogenesis and gelation of fibrinogen mediated by calcium salts

The blood clotting protein fibrinogen is known for its excellent biocompatibility and cell adhesion. The usual strategy to use its full potential is to create fibers and/or hydrogels out of it, most commonly enzymatically in form of fibrin. There are, however, many pathways to create fibrinogen-based materials via enzyme-free approaches. In this study, we investigate these possibilities even further and present a temperature-induced method to obtain enzyme-free fibrous hydrogels from a precursor within 30 min. The keys to create these gels are the addition of calcium salts and a defined temperature program. Successful gelation first requires an incubation period at 37°C for approximately 10 h. This leads to the formation of a ready-to-gel precursor, which remains stable for 2.5 days when the temperature is unchanged. When lowering the temperature to 25 – 10°C, the mixture irreversibly gels within 30 min. If the incubation period is, however, canceled earlier, the precursor will not gel at all. Additionally, this process succeeds only with Ca 2+ ions; if Mg 2+ is used instead, the solution remains unchanged while the addition of Sr 2+ leads to amorphous precipitation over time. In this study, this remarkable process is characterized regarding optimal reaction conditions by means of scanning electron microscopy, rheology, and dynamic light scattering.