Hemostatic Hydrogels from Self-Assembling Amino Acid Derivatives
Abstract
The purpose of this proposal is to develop novel materials that can be used to stop traumatic bleeding. This proposal is submitted in response to the Topic Area of Hemorrhage Control. The leading cause of death in combat is uncontrolled bleeding due to traumatic injuries. Materials that can be used to quickly arrest bleeding in pre-hospital emergency environments are urgently needed to improve survival of injured Soldiers in combat situations. So-called “hemostatic” materials for this purpose must be easily administered without the need for direct pressure to the wound and be able to stop bleeding from both surface and internal injuries in minutes. In addition, these materials should be inexpensive to produce and have long shelf-lives under a variety of environmental conditions. Existing products used to treat traumatic bleeding in combat and emergency situations include QuikClot, Celox, Hemcon, XStat, and others. These products are composed of materials that stop bleeding by a variety of methods. Most are chemical agents that are adsorbed onto gauze materials. Administration of these materials to bleeding wounds typically requires direct pressure and may take up to 10 minutes to stop bleeding. Internal wounds are often not accessible by these materials. In addition, these materials can often complicate surgery and subsequent healing. Thus, there is an urgent need for improved materials to rapidly stop traumatic hemorrhage in emergency conditions. These types of materials will not only be of critical value for military applications but will also be useful to control bleeding by civilian pre-hospital medical technicians and in surgical settings. In this application, we propose the development of next-generation emergency agents to stop traumatic bleeding. Specifically, we will use innovative molecules that dissolve in water but that rapidly self-assemble, or aggregate, into fibers when the salt concentration in the solution surpasses a selected threshold. We have selected molecules that have been shown to self-assemble into fibers at salt concentrations that are equal to that found in blood. Thus, when a solution of these molecules is applied to a bleeding wound, self-assembly into fibers will occur and these fibers will entangle to cause the blood to assume a gel state that will act as an artificial clot to halt the hemorrhage. These agents can be applied simply by emptying a syringe of the hemostatic agent onto or into the wound. As part of this work, we will optimize the proposed agents to undergo self-assembly and gel formation in seconds without the need for compression or direct pressure. We will use inexpensive and biocompatible amino acids as the basis for these studies. Thus, the proposed agents will satisfy the demanding requirements for ideal hemostatic materials in that they can be conveniently applied, will stop bleeding rapidly without compression, will not cause further harm or risk of infection to the wound site, and are inexpensive and chemically stable. The successful completion of this work will provide proof of concept that inexpensive amino acids can form the basis for innovative hemostatic agents that meet the criteria for ideal materials to stop traumatic bleeding. The proposed studies will be carried out using benchtop experiments to refine the materials followed by validation of hemostasis in small animal models (mice). This work will lead to significant opportunities for further research and development. Future work will include studies in large animal models to demonstrate that these agents have the potential to be used in humans. In addition, development of strategies to modify these molecules to impart antibacterial properties to protect wounds from infection. These key innovations will ultimately lead to materials that have the potential to be considered for use in humans. As stated above, these materials will be useful in both military and civilian applications. On
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010112
Entities
People
- Bradley L Nilsson
Organizations
- United States Army
- University of Rochester