The slow formation and poor mechanical strength of natural blood clots limit their haemostatic performance under settings of severe haemorrhage. A new study published in Nature reports that novel engineered blood clots, generated via the rapid crosslinking of red blood cells (RBCs) into tough cytogels, are superior to native blood clots in fracture toughness and adherence to tissues. This finding demonstrates the potential of ‘click clotting’ technology in the management of haemorrhage, surgical bleeding and bleeding disorders.

To generate an RBC cytogel, the investigators combined RBCs with trans-cyclooctene molecules attached to a polymer with tetrazines attached. Importantly, the covalent linkage of trans-cyclooctene and tetrazine is ultrafast and biorthogonal (that is, the tetrazines and trans-cyclooctenes do not react with any of the chemical groups found in biological molecules). At the same time, fibrinogen polymerizes into fibrin networks, creating an engineered blood clot that is made up of an RBC cytogel interspersed by fibrin. Compared with native blood clots, the engineered blood clot had a 13-fold increase in fracture toughness, a 4-fold increase in adhesion energy to biological tissues, improved elastic recovery on loading, and superior tensile and compressive strength. This superior mechanical performance is attributable to the crosslinking of RBCs, which can dissipate energy through membrane deformation and rupture when the engineered blood clot is stressed, unlike native fibrin-dominated clots. When subcutaneously implanted into rats, the engineered blood clot demonstrated excellent biocompatibility, with no evidence of an increased inflammatory response, as well as gradual degradation over time.