Targeting and self-assembling peptides mimic fibrinogen coagulation for alleviating hypofibrinogenemia

Abstract

The treatment of fibrinogen deficiency-related bleeding disorders and acquired hypofibrinogenemia remains heavily reliant on blood-derived products such as fibrinogen concentrate, a mainstay therapy constrained by limited supply, viral contamination risks, and high cost. Inspired by the natural blood clotting mechanism, this study has designed an intelligent multifunctional biomimetic targeting and self-assembling peptide, I.e. SDGRG-C12-KLVFF-GRGDS (SC12FS). This peptide firstly self-assembled into nanoparticles mimicking fibrinogen to specifically target the activated platelet membrane glycoprotein GPIIb-IIIa receptor and induce platelet aggregation and form a loose primary hemostatic plug. Then the nanoparticles would transform into nanofibers and further formed interwoven fibrous networks with fibrin-like functionality by ligand-receptor induced fibrillogenesis. These networks effectively entrap platelet aggregates and red blood cells, leading to the formation of a stable secondary clot. The biomimetic peptide showed the recovered hemostatic functionality and biosafety for the hypofibrinogenemia model of rats and rabbits by intravenous injection. This study provides a novel biomimetic material for safe, accessible hemostatic therapy overcoming the dependence on human plasma sources for alleviating hypofibrinogenemia.