Snake venom is a complex mixture of proteins, enzymes, and other bioactive molecules that are produced by venomous snakes for the purpose of immobilizing and/or killing their prey. Understanding the specific components of different types of venom is important for developing effective therapeutic agents. Indeed, snake venoms have been shown to have some medical benefits. For instance, some snake venoms contain proteins and peptides that can act as painkillers and therefore has the potential to treat chronic pain. Other venom peptides can lower blood pressure by relaxing blood vessels, which can be useful for treating hypertension.
Uncontrolled bleeding, or hemorrhage, is a serious medical emergency that can result in significant morbidity and mortality if not promptly and effectively treated. When blood is lost faster than it can be replaced, the body may go into shock, which can cause organ failure and even death. Uncontrolled bleeding can be caused by a variety of factors, including trauma, surgical complications, and certain medical conditions. In some cases, bleeding may be so severe that it cannot be stopped by conventional means such as pressure or sutures. Existing hemostatic agents act either upstream in the clotting cascade or nonspecifically as tissue glues. Due to their mode of action, these agents are highly prone to failure. The commonly available antifibrinolytic agents like tranexamic acid and aprotinin have been used to solve this problem with minimal success. Another major limitation of these hemostatic agents is that they require a functioning clotting system to control bleeding and do not have antifibrinolytic agent to counter fibrinolysis by plasmin.
To this note, PhD candidate Ramanathan Yegappan, Dr. Jan Lauko, PhD candidate Zhao Wang, Emeritus Professor Martin Lavin, Dr. Amanda Kijas and Professor Alan Rowan from The University of Queensland developed a novel wound sealant comprising two recombinants snake venom proteins: procoagulant ecarin and an antifibrinolytic textilinin. Specifically, a synthetic thermoresponsive hydrogel scaffold was engineered to facilitate the delivery of these recombinant venom proteins to target wound sites. Their work is currently published in the peer-reviewed journal, Advanced Healthcare Materials.
The research team showed that ecarin and textilinin were responsible for rapidly initiating blood clotting and preventing blood clot breakdown, respectively. The authors tested the snake venom hydrogel in vitro using human platelet poor plasma and whole blood tests and showed rapid initiation of clotting and effective inhibition of clot breakdown. Moreover, when they conducted animal studies using a mouse tail amputation model, they demonstrated its immunocompatibility and its ability to rapidly control coagulopathic bleeding. This new class of hemostatic agents could form rapid and stable blood clots even in the presence of blood thinners with no performance degradation.
The venom hydrogels formed stable clot within 60 seconds compared to eight minutes associated with endogenous clotting. The addition of the synthetic polyisocyanopeptide polymer did not affect the clot initiation time but did show some protection of blood clot breakdown in a hypofibrinolytic mimic condition. The snake venom hydrogel could reduce bleed volume from 48% to 12% with excellent immunocompatibility. According to the authors the main advantages of this innovative thermoreversible hydrogel scaffold are its biocompatibility and easy application to irregular wounds and subsequent easy removal. It was worth noting that under heavy bleeding, this hydrogel would require a gauze over dressing to retain its localized condition to achieve adhesion.
In summary, this is the first study to successfully demonstrate the application of two recombinant snake venom proteins as a rapid hemostatic agent for uncontrolled bleeding. The employed thermoresponsive hydrogel functionalization strategy established a technology pipeline for delivering the potent bioactive components to target sites. In a statement to Advances in Engineering, Professor Alan Rowan explained that the presented new approach would contribute to developing the next generation of bleeding control products, exploring alternative delivery scaffolds to meet both clinical needs and function in the extreme austere conditions, such as faced by Military casualties.
Yegappan, R., Lauko, J., Wang, Z., Lavin, M. F., Kijas, A. W., & Rowan, A. E. (2022). Snake Venom Hydrogels as a rapid hemostatic agent for uncontrolled bleeding. Advanced Healthcare Materials, 11(15), 2200574.