16 July 2021

Snake Venom glue

Bio glue with an enzyme from snake venom healed rat wounds

Victoria Baranovskaya, N+1

Chinese researchers and colleagues from Canada have developed a wound healing glue from modified gelatin and an enzyme from snake venom Bothrops atrox. Biocompatible glue under the influence of visible light promotes wound healing and stops bleeding in less than a minute. According to such indicators as bioadhesion, strength and blood clotting time, the "snake" glue turned out to be more effective than the standard fibrin glue. In a paper published in the journal Science Advances (Guo et al. Snake extract–laden hemostatic bioadhesive gel cross-linked by visible light), scientists tested their development on rat wounds.

Surgical adhesives can be synthetic, for example, cyanoacrylates or adhesives based on polyethylene glycol, as well as natural origin – based on fibrin, polysaccharides, albumin or gelatin. However, synthetic adhesives can be toxic. For example, the decomposition of cyanoacrylates releases cyanoacetate and formaldehyde, which can cause an inflammatory reaction. And natural bioadhesives have excellent biocompatibility, but often have low strength and adhesion, including the gold standard of surgical adhesives – fibrin glue. There is another problem – bleeding from wounds weakens the adhesive interaction of glue with tissues.

Inspired by the ability of snake venom to curdle blood, researchers led by Yicheng Guo and Ying Wang from the Army Medical University in Chongqing have developed a bio-glue based on modified gelatin containing the enzyme hemocoagulase extracted from the venom of a snake of the kaisaka species (Bothrops atrox), which is one of the most venomous snakes of the South America. It is known that the venom of this snake contributes to the rapid transformation of fibrinogen into fibrin – the basis of a clot during blood clotting.

 The scientists incorporated hemocoagulase into methacrylated gelatin. By itself, gelatin can accelerate the formation of clots, but it does not cope with severe bleeding. When the glue is applied to the wound, it penetrates deeply into the tissues, and then under the influence of visible light (from 430 to 530 nanometers), gelation occurs, and polymer chains intertwine with the tissues, and the snake enzyme helps to stop the blood.

As tests have shown, "snake" glue has 10 times greater adhesive strength than fibrin glue, and its tensile strength is 35.64 kilopascals, while fibrin glue has 2.93. Moreover, in in vitro tests, the glue coagulated blood in about 45 seconds, and fibrin glue needed 2 times more time.

 The researchers conducted in vivo tests on rats. With the help of a surgical knife, the animals were made an incision of two centimeters. One rat's wounds were treated with 20 microliters of glue under the influence of light for one minute, another with methacrylated gelatin, and the third with fibrin glue. The wounds were examined daily for 20 days. On the fifth day, the wound treated with snake enzyme glue healed, unlike wounds treated with gelatin and fibrin glue. In addition, the "snake" glue was tested on deep cuts of the skin of rats, rupture of the aorta and damaged liver.

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(A) Schematic representation of the skin incision; (B) photographs of the wound on different days; (C) hematoxylin-eosin staining on the 5th and 20th days. Figure from the article by Guo et. al.

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