Snake Venom Hydrogels as a Rapid Hemostatic Agent for Uncontrolled Bleeding

Abstract

Uncontrolled bleeding from traumatic injury remains the leading cause of preventable death with loss of balance between blood clotting (coagulation) and blood clot breakdown (fibrinolysis). A major limitation of existing hemostatic agents is that they require a functioning clotting system to control the bleeding and are largely based on gauze delivery scaffolds. Herein, a novel rapid wound sealant, composed of two recombinant snake venom proteins, the procoagulant ecarin, to rapidly initiate blood clotting and the antifibrinolytic textilinin, to prevent blood clot breakdown within a synthetic thermoresponsive hydrogel scaffold is developed. In vitro, it is demonstrated that clotting is rapidly initiated with only nanomolar concentrations of venom protein and clot breakdown is effectively inhibited by textilinin. A stable clot is formed within 60 s compared to normal clot formation in 8 min. In vivo studies reveal that the snake venom hydrogel rapidly controls warfarin-induced bleeding, reducing the bleed volume from 48% to 12% and has demonstrated immune compatibility. A new class of hemostatic agents that achieve formation of rapid and stable blood clots even in the presence of blood thinners is demonstrated here.

Bioactive Hydrogels with Pro‐coagulation Effect for Hemostasis†

“…Snake venom is a highly intricate amalgamation of various active constituents, including snake venom thrombin‐like enzymes (SVTLEs), [ 129‐130 ] prothrombin activator, [ 131‐132 ] factor Va‐like protein, and antifibrinolytic snake venom protein. These components exhibit the potential to stimulate blood coagulation or impede fibrinolysis.…”

Why losing Australia's biodiversity matters for human health: insights from the latest State of the Environment assessment

“…More than half of commercially available medicines are based on bioactive compounds either extracted or patterned from non‐human species. For example, angiotensin‐converting enzyme inhibitors were derived from Brazilian pit viper venom, and the venom of Australia's eastern brown snake is a component of a newly developed innovative gel that acts as a haemostatic wound sealant 9,10 …”

“…For example, angiotensinconverting enzyme inhibitors were derived from Brazilian pit viper venom, and the venom of Australia's eastern brown snake is a component of a newly developed innovative gel that acts as a haemostatic wound sealant. 9,10 Coral reefs have the highest density of biodiversity globally. 11 This results in intense species competition and evolution of complex defensive chemicals, many of which have pharmacological value.…”

Preparation and Hemostatic Effect of Micro-Nanograded Porous Particles Doped with Dopamine-Based Water-Triggered Intelligent Composite Adhesives

“…8,9 In the treatment of massive bleeding wounds, by only using powder hemostatic materials, the materials are easy to be washed away and cannot play a better role in hemostasis. 10 Considering the superiority of powder-based materials for hemostasis, a large number of studies have been conducted to solve this problem by combining powder-based hemostatic materials with gel adhesive-based materials that can quickly seal wounds to provide hemostasis. Zhang properties.…”