Anu Rajendran Warford Wed 2pm WRIT 340 Illumin Article Bloody Vengeance No More! A Closer Look at New Biomedical Technologies in Field Medicine Abstract- Uncontrolled blood loss is the leading cause of traumatic death in military and civilian settings and can potentially lead to organ failure if left untreated for long periods of time. The body’s response to blood loss results in hypovolemic shock, the leading cause of organ failure. Therefore, there exists a crucial need to find new ways to prevent blood loss for patients in need of immediate trauma care. New biotechnologies in field medicine are focusing on controlling excessive blood loss. Some of the medical technologies currently in research are injectable polymer foams, biological film layers, chemical coatings, and high-intensity ultrasounds. Although these methods are still in testing phases, they show a promising future for blood loss control and saving the lives of soldiers and civilians. Introduction Every two seconds, someone in the United States needs a blood transfusion, resulting in more than 38,000 blood donations everyday [1]. The leading cause of traumatic death in military and civilian settings is by excessive blood loss. [2]. A healthy human body has a constant circulation of blood and is capable of withstanding small amounts of blood loss. When trauma occurs, excessive blood loss can cause many complications and time becomes an essential factor. The severity of a patient’s condition also rapidly increases when treatment is delayed. Controlling blood loss has become an important topic of interest, and military research has turned its focus to improving field treatment. Currently used techniques, such as bandages and tourniquets, have a relatively low success rate for serious injuries. Recent advances in military biotechnology show a promising outlook in combat survival and blood loss prevention. These new biotechnologies can also be utilized for treating the general public. For example, with these biotechnologies, paramedics can better treat patients who have internal bleeding and lower their risk of death if they cannot reach a hospital quickly. Before discussing innovative biomedical technologies in field medicine, it is important to understand the human body and its response to blood loss. By developing new methods to prevent blood loss in trauma patients, doctors and medics can save more lives with fewer complications. Mechanics of the Circulatory System Imagine the human body as a sophisticated machine with many components. In order for the machine to successfully run, all of its components have to cooperate with each other. Similarly, the human body has many components, or systems, that must do their jobs to keep the human alive and functioning properly. Of these systems, the circulatory system is one of the largest and most crucial systems of the body. It is responsible for transporting the necessary nutrients, oxygen, water, and hormones needed for the cells in the body to maintain homeostasis [4]. Homeostasis occurs when an internal environment is regulated and maintains a stable state [5]. Three organs in the human circulatory system help to maintain this state: the heart, blood vessels, and blood. These organs work together in harmony to keep the body healthy [4], and while all three 1 Anu Rajendran Warford Wed 2pm WRIT 340 Illumin Article are important, blood will be the main focus of this article. Blood, a liquid connective tissue, is pumped by the heart to the rest of the body [4]. Cells need a constant circulation of blood to maintain normal conditions, and when this blood is lost due to internal or external bleeding, the body reacts to compensate for this loss. However, if too much blood is lost, the body can go into shock and eventually start to fail. Body’s Response to Excessive Blood Loss The human body's response to blood loss can vary based on the amount of lost blood. When an excessive amount of blood is lost (15% or more of circulating blood volume), the body goes into a state known as hypovolemic, or hemorrhagic, shock [5]. During hypovolemic shock, the heart is unable to pump enough blood to compensate for the amount lost [4]. Over 40% blood loss results in the extreme slowing of heartbeat, organ failure, and low blood pressure [5]. As more and more blood is lost, cells do not get the nutrients and oxygen needed for survival. As a result, vital organs start to shut down because their cells are rapidly dying [5]. During combat, many soldiers go into hypovolemic shock because field medics are unable to quickly transport these wounded soldiers to a medical facility. This is also the case for civilians who are delayed proper medical care. According to trauma surgeon Col. Brian J. Eastridge [6], the leading cause of deaths in the Army from combat in Iraq and Afghanistan was uncontrolled blood loss. He believes that hemorrhage control needs to be one of the top priorities of military medical research [6]. New Biotechnologies Recently, advances in biotechnology have been specific to controlling blood loss. These new methods involve biomedical technologies that react hand-in-hand with the body. Currently, four new biotechnologies show a promising future for military use in preventing blood loss. The technologies include injectable polymer foam, biological film layers, chemical coatings, and high intensity ultrasounds. Each of these technologies will be explored in depth below. 1: DARPA Injectable Foam New injectable foam by Arsenal Medicals has a promising future in field medicine. As seen in Figure 1, The Defense Advanced Research Projects Agency (DARPA) funds polyurethane foam that molds to the abdomen and stops excessive blood loss [7]. Once the patient is taken to a medical facility, the hardened foam can be surgically removed in order to assess the damage. According to Arsenal Medicals [7], the foam should reduce blood loss six-fold. The chemistry behind this injectable foam is simple. The foam is made up of two compounds: polyol and isocyantes [8]. Polyol is a type of alcohol, and isocyantes are highly reactive chemicals commonly used in making foams [9]. These two liquids are injected together into the body. Once inside the body, the foam expands to about 30 times the original size as it blankets the abdomen [7]. As shown in Figure 1, the foam creates a tight and secure holding of the ab2 Anu Rajendran Warford Wed 2pm WRIT 340 Illumin Article dominal organs. Ali Mejaddam et al. [10] tested the polyurethane foam on swine. They created a massive abdominal injury in each of the swine. The control group received standard battlefield resuscitation, and the experimental group received the resuscitation and the polyurethane foam injection [10]. In the control group, there was only an 8% survival rate in a span of 3 hours after injury [10]. However, in the experimental group, the survival rate was around 72% in the same time span [10]. Figure 1: The polyurethane foam is injects through the belly button region. Once two liquids create a foam that exapnds to the entire abdominal region [7]. Although this injectable foam is a promising technology, it is still in research and may not be widely in use anytime soon. The side effects of this foam in humans are also not known because it has only been tested on swine. More research and review need to be completed before medics can use them on their patients. 2: Nanoscale Biological Coating Researchers at the Massachusetts Institute of Technology have created a biological coating for bandages that can stop hemorrhaging (bleeding). By using a porcine (pig) spleen injury model, researchers tested the biological coating by spraying their hemostatic film onto a gelatin sponge [11]. The hemostatic film is made from thrombin and tannic acid by using a layer-bylayer (LbL) technique [11]. Thrombin (Figure 2) is a natural clotting factor that plays an important role in hemostasis [12]. Hemostasis is a process that causes bleeding to stop. Thrombin is degradable, and therefore cannot be used as a coating alone [11]. Tannic acid, which is found in black tea, is able to successfully create hydrogen bonds with thrombin [6]. The pairing of throm3 Anu Rajendran Warford Wed 2pm WRIT 340 Illumin Article bin and tannic acid creates a film that promotes rapid hemostasis [9]. Figure 2: Thrombin Molecule. Thrombin and Tannic Acid used together to create biological coating [9]. The advantage of the LbL technique is that it allows a large amount of thrombin to be stored in the sponges [11]. Previously developed biological coatings could not store a dense amount of hemostatic material. These newly coated sponges can also be stored for months before use [11]. This could improve the survival rate of soldiers and civilians during battle because of how easily these coated sponges can be transported and stored. Similar to the injectable foam, this film coating has not been tested on human subjects. The side effects or success rate of this foam on the human body is currently unknown. However, the results from the study using porcine show a positive future for this coating. 3: Smart Bandages Using the idea behind the strength of glass fiber, Chirag Gajjar [13] from North Carolina State University is on a mission to create bandages with similar properties. Glass fiber can effectively slow down blood flow because of the material’s hydrophilicity (capability of hydrogen bonding) and highly negative surface charge [14]. However, glass is obviously not safe in the body. Gajjar’s research team has discovered a chemical called tetraethyl orthosilicate (TEOS) [13]. TEOS has similar properties to glass fibers. By coating common textile wound dressing materials with TEOS, the treatment of human blood plasma resulted in an increase in production of a blood clot [13], [15]. The time for clotting to form decreased by 25% to 30% with these coated dressings compared to the non-coated dressings [13]-[15]. TEOS coated the materials 4 Anu Rajendran Warford Wed 2pm WRIT 340 Illumin Article with a glass-like surface, but did not have any of the same side effects as glass fibers [14]. The cotton wound dressing seemed to be the best at slowing down blood flow when coated with TEOS. The goal of this research is to eventually create a bandage that can stop blood flow twice as fast as a regular bandage [13]. 4: Deep Bleeder Acoustic Coagulation The Deep Bleeder Acoustic Coagulation (DBAC) program, sponsored by DARPA, is an ultrasound device that could potentially prevent soldiers from losing too much blood [16]. The goal of the DBAC program is to create a portable and noninvasive system to stop internal bleeding [16]. As shown in Figure 3, DARPA’s plan is to create an arm cuff that goes through three main steps using high-intensity focused ultrasound (HIFU) [16]. The first step uses low-intensity ultrasound waves to scan and detect the area of excessive blood loss. Then, the HIFU will locate the area of bleed. Once it locates the area, the DBAC will create a 3D model of the damaged blood vessel [17]. The final step is to coagulate (clot) the area of bleeding by firing HIFU at the affected vessel [16]. The goal is to create a device that does all of these things autonomously. The DBAC program is still in its early stages of design and review. It could be a few years before any results using coagulated blood samples can be obtained. Nonetheless, this technology could be used in emergency situations outside of combat. Figure 3: DBAC Cuff and the process behind the high frequency ultrasound coagulation [18]. 5 Anu Rajendran Warford Wed 2pm WRIT 340 Illumin Article Conclusion: The Future of Biotechnology Every two seconds, someone in the United States is saved. More than 38,000 blood donations are no longer needed every day. These statistics may become true one day thanks to the use of biomedical technologies. The four recent blood loss-controlling technologies discussed only scratch the surface of trauma care. A sea of research is already underway for hemorrhagic control. Old techniques, such as tourniquets and bandages, are being improved, while new techniques, such as chemical sealants, are being implemented. Though these biotechnologies have been developed for military purposes, paramedics and civilians everywhere can use them. Countries lacking adequate medical facilities can use these technologies to help rural patients until they can be transported for treatment. Unfortunately, this may not happen for many years. Many of these technologies are in the beginning stages of testing. Still, results from research have been hopeful and positive. Biotechnology for controlling blood loss can only continue to open a wide variety of opportunities. Blood is one of the most important aspects of the human body, and finding ways to successfully prevent blood loss can help save many lives. References: [1] "American Red Cross," American Red Cross, 2012. [Online]. Available: http://www.redcrossblood.org/learn-about-blood/blood-facts-and-statistics. [Accessed 12 February 2013]. [2] L. Kobayashi, "Surgical Critical Care Hypovolemic Shock Resuscitation," Surgical Clinics of North America, vol. 92, no. 6, pp. 1403-1423, 2012. [3] P. Kime, "Study: 25% of war deaths medically preventable," Army Times, 28 June 2012. [4] E. K. L. Lerner and B. W. Lerner, "Circulatory System," in The Gale Encyclopedia of Science, Detroit, Gale, Cengage Learning, 2008, pp. 945-950. [5] C. L. Conley, "Encyclopædia Britannica Academic Edition," Encyclopædia Britannica Inc, 2013. [Online]. Available: http://www.britannica.com.libproxy.usc.edu/EBchecked/topic/69685/blood. [Accessed 10 February 2013]. [6] B. J. Eastridge, A. Starr, J. P. Minei and G. E. O'Keefe, "The Importance of Fracture Pattern in Guiding Therapeutic Decision-Making in Patients with Hemorrhagic Shock and Pelvic Ring Disruptions," Journal of Trauma-Injury Infection & Critical Care, vol. 53, no. 3, pp. 446-451, 2002. 6 Anu Rajendran Warford Wed 2pm WRIT 340 Illumin Article [7] S. Young, "Injectable Foam Expands in the Belly, Stops the Bleeding," MIT Technology Review, 22 January 2013. [8] J. Eischeid, "Injectable Foam Blocks Internal Bleeding on the Battlefield," Scientific American, 4 February 2013. [9] A. Trafton, "New way to stop the bleeding," MIT news, 10 January 2012. [10] A. Mejaddam, M. Duggan and U. Sharma, In Situ Self-Expanding Polyurethane Polymer Foam Improves Survival In A Model Of Noncompressible Massive Abdominal Hemorrhage, Watertown: Arsenal Medical, 2012. [11] A. Shukla, J. C. Fang, S. Puranam, F. R. Jensen and P. T. Hammond, "Hemostatic Multilayer Coatings," Advanced Materials, vol. 24, no. 4, pp. 492-496, 2012. [12] M. W. King, "Introduction to Blood Coagulation," The Medical Biochemistry Page, 6 February 2013. [Online]. Available: http://serpins.med.unc.edu/~fcc/ResearchPicts2006/Thrombin.html. [Accessed 10 February 2013]. [13] C. R. Gajjar, "Improving the Hemostatic Property of Common Textile Fibers," North Carolina State University, Raleigh, 2011. [14] M. B. Gorber and M. V. Sefton, "Biomaterial-associated thrombosis: roles of coagulation factors, complement, platelets and leukocytes," Biomaterials, vol. 25, no. 26, pp. 56815703, 2004. [15] S. Fecht, "Smart Bandages Could Staunch Blood Flow From Wounds," Popular Mechanics, 25 October 2012. [16] T. Tether, "Defense Advanced Research Projects Agency," 13 March 2008. [Online]. Available: www.darpa.mil/WorkArea/DownloadAsset.aspx?id=1664. [Accessed 9 February 2013]. [17] E. Sofge, "Top 4 New Breakthrough Medical Devices: Live @ DARPATech," Popular Mechanics, 1 October 2009. [18] E. Sofge, "6 Future Mods for Our Minds and Bodies," Popular Mechanics, 1 October 2009. 7