Artificial peptides that mimic fibrin, the body’s blood clot-forming protein, have been designed by researchers at IISER Kolkata and Saha Institute of Nuclear Physics.
Under lab conditions, the new “sealants” formed clots nearly twice as fast as fibrin, and were found to be safe to use with living cells. The sealants closely resemble fibrin’s make-up, but with added ingredients that confer durability and faster clotting.
“What we are aiming at is designing nature-inspired artificial sealants that are supposed to be better than what is available in nature, with the aim that it can be translated to clinics for handling difficult cases related to impaired blood clotting,” says Rituparna Sinha Roy, Assistant Professor, IISER Kolkata, who is one of the senior authors. Such sealants could prove useful during times of profuse bleeding such as traumatic accidents and battlefield injuries, or help patients who are unable to produce enough fibrin, the researchers say.
The study was published in Scientific Reports.
When blood spurts during an injury, a protein called fibrinogen is first converted to fibrin. Fibrin then forms long, tough threads entrapping blood cells and platelets into a mesh that hardens to form the clot. The clot’s structure is reinforced by interconnecting bonds that bring different fibrin strands together.
In one of the two sealants developed, the team constructed two strings of amino acids that bind together to form a fibrin-like mesh in the presence of a clot-forming enzyme. For added strength, the researchers inserted specific amino acids with opposite charges at matching sites on the strings to form strong interconnecting bonds. In another sealant, the researchers added amino acids that would make it resistant to peptide-cleaving enzymes.
Microscopic analysis showed that the sealants were able to form thread-like structures connected by nano-sized bridges and entrap blood cells, similar to fibrin. One of the sealants was able to trap blood cells almost twice as fast as fibrin. The sealants also showed greater stiffness than the functional portion of natural fibrin. Tests also revealed that they were not harmful to living cells.
The team also used computer models to analyze the 3D structures formed by the sealants. “We tried to mimic the physiological environment and see how these molecules will behave,” says Dhananjay Bhattacharyya, Professor, Saha Institute of Nuclear Physics, Kolkata, another senior author. The analysis gave them insights into how the sealants arrange themselves under simulated natural conditions, which could guide future design, the authors say.
“I think it is a good attempt to synthesize a peptide-based sealant to prevent bleeding, however, more experiments are needed to validate the adhesive in real life situations,” says Jayakrishnan, Professor, Department of Biotechnology, IIT Madras, who was not involved with the study.
Previously used artificial sealants such as fibrin glue have several issues, he points out. The components come from outdated human blood and bovine sources and care has to be taken to ensure their quality. “Fibrin glue is a 2-component affair and the sealant is not good for stopping bleeding from large incisions. It has poor mechanical and adhesive strength and large quantities are prohibitively expensive,” he explains.
Roy cautions, however, that the new sealants have only been tested in simulated conditions and not yet in animal models or clinical studies. The team hopes to collaborate with clinical researchers to test the sealants’ effectiveness further.