The plasma protein fibrinogen is a key player in blood coagulation and tissue repair. Fibrinogen can be processed into nano- and microstructured scaffolds, which support the growth of different stem cell types. To facilitate successful tissue integration of fibrinogen scaffolds it is important to avoid any scaffold-related thrombogenic reactions originating from interactions with blood platelets.

We recently introduced a new class of nanofibrous fibrinogen scaffolds that is prepared by salt-induced self-assembly and can be tailored with regard to the scaffold dimensions and secondary structure [1,2] (see Fig. 1). In the present study we analyzed how these self-assembled fibrinogen nanofibers interact with platelets and with mesenchymal stem cells (MSCs) to evaluate their potential for future applications in soft tissue engineering.

Platelet-rich plasma (PRP) or washed platelets were incubated on nanofibrous fibrinogen using planar fibrinogen as reference scaffolds. The samples were fixed, stained and imaged by confocal microscopy or scanning electron microscopy (SEM). Images were analysed to assess platelet adhesion and activation based on their adhesion morphology (F-actin organization). Platelets in PRP remained round on planar fibrinogen but spread and formed small clots on nanofibrous scaffolds. In contrast, washed platelets adhered and spread on both fibrinogen scaffolds and developed similar adhesion morphologies. Our results suggest that platelets interact stronger with nanofibrous fibrinogen than with smooth surfaces. In parallel, we studied whether human bone marrow-derived MSCs were able to adhere and proliferate on fibrinogen nanofibers. During 7 days of culture, MSCs spread on the fibrinogen scaffolds to an almost confluent cell layer and adhered well as evidenced by SEM analysis and phalloidin immunostaining of the actin filaments.
In conclusion, our findings highlight the importance of scaffold topography for steering the interaction of fibrinogen scaffolds with platelets and the future potential of self-assembled fibrinogen nanofibers for the differentiation of MSCs.