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 designed an intelligent multifunctional biomimetic targeting and self-assembling peptide, i.e. SDGRG-C₁₂-KLVFF-GRGDS (SC₁₂FS). This peptide first self-assembled into nanoparticles mimicking fibrinogen to specifically target the activated platelet membrane glycoprotein GPIIb-IIIa receptor, inducing platelet aggregation and forming a loose primary hemostatic plug. Then, the nanoparticles would transform into nanofibers and further form 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 in the hypofibrinogenemia models of rats and rabbits following intravenous injection. This study provides a novel biomimetic material for safe, accessible hemostatic therapy, overcoming the dependence on human plasma sources for alleviating hypofibrinogenemia.