Snake Venom-Based Rapid Wound Sealant
Abstract
Background: In a military setting, there is an extreme need for improved casualty care in the premedical facility phase of care, as currently the proportion of deaths associated with bleeding are 90.9% of casualties sustaining potentially survivable injuries. Death due to bleeding is considered a preventable death. The Current Tactical Combat Casualty Care guidelines (2017) recommend the use of hemostatic (stop bleeding) agents to control bleeding in the premedical facility phase of care. We propose to improve the trauma casualty outcomes by controlling bleeding using a portable, efficacious, snake venom-based gelating hemostatic agent. Our proposal is founded on a novel approach to control bleeding, by incorporating two snake venom proteins, one to clot the blood and the second to stop the blood clot from breaking down. Thus, we have taken the novel approach to use the deadly power of nature to kill, to save lives, by combining these snake venom proteins with a synthetic temperature-responsive hydrogel (a gel-based scaffold), that reinforces the blood clot, to bring about rapid and stable blood clot formation controlling bleeding. Objective: To produce a gel-based agent to rapidly control bleeding, suitable for all wounds with a special focus on irregular and non-compressible wounds. In this proposal, we will bind a snake venom blood clotting protein to the hydrogel anchoring it to the site of application and concentrating its effect to bring about rapid blood clotting. This will be combined with a second snake venom protein to stop the blood clot from breaking down. The effectiveness of this treatment will be tested in lab-based blood clotting experiments and followed by more realistic tests in an animal model of bleeding. Specific Aims: (1) Establish a streamlined strategy for bonding the snake venom proteins to the hydrogel. (2) Fully characterize the effectiveness of the proposed hemostatic agent using blood clotting tests. (3) Demonstrate the effectiveness of our potent snake venom protein-based haemostatic agent to control bleeding in an animal model of bleeding. Study Design: Our current data characterizing the performance of these snake venom proteins demonstrates that a simple mixture of the components of the proposed hemostatic agent, the hydrogel and the two potent snake venom proteins, can rapidly clot blood in seconds, forming a dense blood clot that shows to be resistant to subsequent blood clot breakdown. In this research, we will extend upon these preliminary studies and permanently bind the snake venom clotting protein to the hydrogel, thus retaining this protein at the site of the wound preventing it from moving to other parts of the body. We will then trial the activity of the hydrogel-bonded clotting protein in blood clotting assays to investigate the speed of clotting, clot strength, and resistance of clot breakdown in the presence of the second snake venom protein that stops the body from breaking down the clot. This second protein does not need to be anchored to the wound, as its activity would not affect the body, where current therapies (tranexamic acid) that stop the clot breakdown are administered systematically (to the whole body). After these model studies, we will progress to trialing the hemostatic agent in a more realistic situation of hemorrhage using an animal-based model for bleeding. Innovation and Impact: There are several fundamental approaches in this design that make it not only unique, but also, as we believe, will make a huge impact on the outcomes of military casualties. Firstly, the use of snake venom proteins that can potently clot blood and, once formed, resist the body’s natural mechanisms to break the clot down. None of the currently employed hemostatic agents by the US military use an agent to stop clot breakdown, relying on systemically administered tranexamic acid to stop the clot breakdown, which is technically difficult to administer until m
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810740
Entities
People
- Alan E. Rowan
Organizations
- United States Army
- University of Queensland