Biomimetic recombinant collagen with multicopy dual-targeted hemostatic motifs for enhanced hemostasis in surgical trauma.

Collagen has superior bioactivity in hemostasis but is limited by a few active amino acids and noncustomizable motifs. Here, we propose a biosynthetic strategy to construct multicopy dual-targeted recombinant collagen. Using human collagen type III alpha 1 chain (COL3α1) as a template, we integrated hemostatic motifs GFPGER and GPP, which bind integrin α2β1 and glycoprotein VI to enhance platelet adhesion, activation, and red blood cell (RBC) capture. The multicopy design further improves binding affinity, stability, and hemostatic activity. The recombinant collagen significantly promotes platelet and RBC adhesion, platelet activation, fibrin network formation and exhibits good biocompatibility. In rat liver, spleen, and femoral artery bleeding models, it markedly reduces blood loss and bleeding time. Proteomic, molecular docking, and surface plasmon resonance analyses confirm motif-target interactions and activation of both primary and secondary hemostasis. This biomimetic recombinant collagen shows strong potential as a hemostatic raw material and provides a strategy for functional collagen synthesis.