05-Rapid Pressure Hemostatic Drug Delivery and Microsystem Design Based on Battlefield Trauma

PAPER • OPEN ACCESSRapid Pressure Hemostatic Drug Delivery andMicrosystem Design Based on Battlefield TraumaTo cite this article: Wenting Su et al 2023 J. Phys.: Conf. Ser. 2478 122071View the <a href="https://doi.org/10.1088/1742-6596/2478/12/122071">article online</a> for updates and enhancements.You may also like- <a href="https://iopscience.iop.org/article/10.35848/1347-4065/abd1bb">Reviews of low-temperature atmospheric</a> <a href="https://iopscience.iop.org/article/10.35848/1347-4065/abd1bb">pressure plasma for studying hemostasis</a> <a href="https://iopscience.iop.org/article/10.35848/1347-4065/abd1bb">and international standardization</a>Hajime Sakakita, Tetsuji Shimizu and Yuzuru Ikehara- <a href="https://iopscience.iop.org/article/10.1088/1748-605X/aa9b3e">Comparative efficacy of hemorrhage</a><a href="https://iopscience.iop.org/article/10.1088/1748-605X/aa9b3e">control of a novel mesoporous bioactive</a> <a href="https://iopscience.iop.org/article/10.1088/1748-605X/aa9b3e">glass versus two commercial hemostats</a>Sara Pourshahrestani, Nahrizul Adib Kadri, Ehsan Zeimaran et al.- <a href="https://iopscience.iop.org/article/10.1088/1361-6463/aa945e">Benefits of applying low-temperature</a><a href="https://iopscience.iop.org/article/10.1088/1361-6463/aa945e">plasma treatment to wound care and</a><a href="https://iopscience.iop.org/article/10.1088/1361-6463/aa945e">hemostasis from the viewpoints of physics</a> <a href="https://iopscience.iop.org/article/10.1088/1361-6463/aa945e">and pathology</a>Tetsuji Shimizu and Yuzuru Ikehara<img src="/media/202408//1724856370.901381.jpeg" />This content was downloaded from IP address <a href="185.248.186.156">185.248.186.156</a> on 10/01/2024 at 02:35Journal of Physics: Conference Series 2478 (2023) 122071 doi:10.1088/1742-6596/2478/12/122071Rapid Pressure Hemostatic Drug Delivery and Microsystem Design Based on Battlefield TraumaWenting Su1 ，Yi Sun1,2 ，Sining Lv1 ，Bo He1,2and Wenzhong Lou1,2,*1 Beijing Institute of Technology, Beijing, China2 Beijing Institute of Technology Chongqing Innovation Center, Chongqing, ChinaLouwz2020@163.comAbstract. The battlefield rapid pressure hemostatic microsystem maximizes hemostasis efficiency. Battlefield wound has the characteristics of rapid blood loss and irregular surface, which needs to be treated in a very short time. The existing rapid hemostasis method has poor efficiency and no sterilization and disinfection effect. Therefore, we reported a wound pressure hemostatic microsystem based on gas generated by rapid chemical reaction. Before the device is used, the two chemicals in the device are isolated. During hemostasis, the flexible device is applied to the wound surface, and the two chemicals in the device are mixed and chemically reacted. And the large amount of gas generated by the reaction causes the balloon in the device to expand and exert lateral and longitudinal pressure on the surface of the wound, so that the wound quickly closed. At the same time, the drug storage unit in the device is under pressure to release the drug to the wound surface. In addition, the chemical reaction of the device has an endothermic effect, which can rapidly cool the wound surface. The lateral and longitudinal pressures of the flexible microsystem in the process of hemostasis were analyzed by numerical simulation. In the experiment, the maximum longitudinal pressure reached 270mmHg , meeting the requirements of surface wound hemostasis.1. IntroductionHaemorrhage is the leading cause of preventable combat deaths on the battlefield. Massive hemorrhage has always been an important cause of Combat Casualty in conventional wars, accounting for about 30%~50% of all Combat casualties. Massive hemorrhage and the resulting hypovolemic shock are one of the key points of Combat wound treatment. Therefore, Tactical Combat Casualty Care (Tactical Combat Casualty Care) in the United States TCCC) put hemostasis in the first place of battle wound control [1-5]. According to the literature review analysis, in the Korean War, among the 1136 soldiers killed in battle, 32.4% died due to bleeding, second only to the major organ injury; Massive bleeding was also one of the leading causes of death on the southwest frontier, accounting for about 50 per cent of deaths in regimented aid stations. According to the data of us Vietnam War attrition, in the analysis of the causes of death of the wounded, about 9% were severe trauma and massive bleeding. Of the 4596 casualties who died in Afghanistan and Iraq from 2001 to 2011, 24.3% were considered to be survivable (n=976), and 90.9% of the preventable causes of death were massive bleeding. In terms of time distribution, massive hemorrhage and hemorrhagic shock were the important causes of early death. The more blood a casualty loses, the faster shock sets in. According to the analysis of 464 cases of landmine casualties in the former Soviet war in Afghanistan, the statistical<img src="/media/202408//1724856370.959415.png" />Content from this work may be used under the terms of the Creative Commons Attribution 3.0 licence. Any further distribution of this work must maintain attribution to the author(s) and the title of the work, journal citation and DOI.Published under licence by IOP Publishing Ltd 1Journal of Physics: Conference Series 2478 (2023) 122071 doi:10.1088/1742-6596/2478/12/122071results showed that the main causes of death in the early stage were vital organ damage, massive hemorrhage, brain injury with intracranial hypertension and shock, accounting for 49.57% of the total deaths. 20.43% died within 10~30 min, 21.50% died within 30~60 min, 73. 11% died within 4~6 h.At present, the main hemostatic methods are divided into physical hemostasis and chemical hemostasis :(1) new-type tourniquet and combat readiness forceps, which are used for inguinal artery hemorrhage, have good hemostasis effect [6]-[8], but cannot be applied to deep cavity wounds. Genevieve R. Mueller et al. from Oregon Biomedical Engineering Institute developed a new syringe-like medical device named &quot;XStat&quot; for the treatment of borderline injuries caused by incompressible bleeding [9]. Li Meng from Qian Xuesen Space Technology Laboratory proposed a rapid hemostatic device for battlefield penetrating wounds [10]. The elastic expansion support hemostatic material of the unfolded structure was used to fill the penetrating wounds to achieve the effect of compression hemostasis, but the physical method could not effectively identify the wounds, and it was easy to cause infection. Graphene-based sponge is a kind of emerging materials for hemostasis of trauma, with multistage pore structure, rapid liquid absorption capacity, easy surface functionalization and other characteristics, showing good effects in hemostasis of trauma [7]. (2) Chemical hemostasis mainly includes fibrin, chitosan or polyacetylglucosamine, etc., which can accelerate clotting by activating platelets and clotting factors [11-13]. Cryopreservation is a new minimally invasive surgical technique, low temperature has the characteristics of tissue buffering, low probability of adverse reactions occurred in hemostasis sterilization. Deng Zhongshan et al. [13-15] studied the influence of blood vessels in the freezing process. However, cryogenic refrigeration is faced with the problem of large equipment and high power consumption, which cannot be used in emergency environment. High-temperature hemostasis, as a traditional hemostasis method, was already adopted in the Eastern Han Dynasty of China more than 2000 years ago [17]. The application of new technology in high-temperature hemostasis field spawned a new method of electrocoagulation and blood stasis. In 2014, Mark R. Brinton et al. [18]-[21] from the United States proposed a miniature electromotive hemostasis system. Through the experiment of electric stimulation, it was shown that the miniature electromotive pulse electromotive vascular system could shrink the femoral artery in a few seconds, but the system was large in volume and required high driving energy.The traditional physical and chemical hemostasis method has large wound surface, long time, low hemostasis efficiency and difficult to give consideration to the function of elimination. Traditional high temperature hemostatic method can produce calcination, the organization and collateral damage, such as secondary wound, in this paper, based on chemical reactions (react with sodium bicarbonate solid aluminium sulfate solution) rapid pressure big wound rapid hemostatic xiaosha technology, using chemical reaction principle of non-fertilization have emergency environment effect the technical features of the time is short, fast hemostasis, The efficiency of hemostasis and elimination is expected to be greatly improved, and the large wound surface can be cooled based on the chemical endothermic reaction principle of sodium bicarbonate and aluminum sulfate. The rapid hemostasis and elimination microsystem can realize directional contact precise hemostasis on the wound surface, and the tissue temperature around the wound surface is normal temperature, which greatly reduces the secondary damage around the wound.2. Mechanism study and model design of rapid pressure hemostasis2.1. Study on wound surface pressure hemostasisPressure hemostasis micro system designed in this paper mainly from two aspects: (1) the hemostasia through expanding gas produces chemical reaction, because of the system were applied on the surface of the skin, can be produced on the surface of the wound from becoming bigger pressure, (2) the use of direct pressure and release of aluminum sulfate and carbonate reaction endothermic effect, reduce the temperature of the surface of the wound from becoming cool down on the wound. In order to obtain the deformation law of the vascular tissue on the wound surface, the cross section of the external endothermic source was made round, and the cross section of the endothermic source was inJournal of Physics: Conference Series 2478 (2023) 122071 doi:10.1088/1742-6596/2478/12/122071contact with the vascular wound surface. Arterial vessels are composed of three layers. As the innermost intima is composed of very thin elastin and its thickness is negligible, the arterial vessels designed by the model are double-layer. The outer layer is collagen fiber layer composed of collagen fiber bundles, and the inner layer is elastic fiber layer, which is easier to stretch. In clinical practice, it is difficult to obtain the data of thermal deformation of vascular tissues through in vivo experiments, but the relationship between thermal effect of biological tissues and critical temperature given by Niemz [22] can be used as the basis for thermal deformation of vascular tissues.The biological heat conduction equation of vascular wound under the action of external boundary temperature is:Pc(∂T / ∂t) = ▽(k.▽T) + Qb + Qnet (1) 	P is vascular tissue density, c is heat capacity, k is thermal conductivity of vascular tissue, Qb is blood perfusion term and Qnet is metabolic heat production term. Due to the short time ofhemostatic effect of high-temperature suture, metabolic thermogenesis was not considered. In addition, Qb , as a blood perfusion term, represents heat dissipation in the heat transfer process, which can be achieved by applying a boundary heat flux, namely:Qb =hl (Text — T) (2)Where, hl stands for different heat dissipation coefficients, and hl values are also different due to the different depths of arterial vessels in the body. Text stands for room temperature, while T stands for external temperature source.The pressure hemostasis of blood vessels on wound surface under external endothermic environment was analyzed by multi-physical field simulation. During the study, the physical parameters of vascular tissue, such as density, heat capacity and thermal conductivity, changed with the change of water content, organic matter and temperature in the tissue. The inner membrane is mainly composed of elastic fibers with a small Young's modulus of (3 ~ 6) ×106 dyn/cm2 . We take 6 ×106 dyn/cm2 , i.e. 0.6mpa. The outer membrane is mainly composed of collagen fibers, with Young's modulus up to 4.3×1010 dyn/cm2 , i.e. 4.3GPa. Poisson's ratio V of biological tissues is 0.4.The data is shown in Table 1.Table 1. Material parameters of inner and outer vascular membranes at room temperature.<table><tr><td></td><td>Unit</td><td>Inner layer</td></tr><tr><td>Density (ρ)</td><td>kg/m3</td><td>1050</td></tr><tr><td>Young's modulus (E)</td><td>MPa</td><td>0.6</td></tr><tr><td>Poisson's ratio (v)</td><td></td><td>0.4</td></tr><tr><td>Thermal conductivity (k)</td><td>W/(m. ℃)</td><td>0.48</td></tr><tr><td>Heat capacity (c)</td><td>J/(kg.℃)</td><td>3850</td></tr><tr><td>Thermal expansion coefficient (α)</td><td>℃-1</td><td>1×10-5</td></tr><tr><td>Moisture content (ωn/ωw)</td><td></td><td>0.8</td></tr></table>The second step is to establish the wound surface pressure hemostasis model and carry out multi-physical field simulation. In comsol multi-physical field simulation analysis software, the augmented Lagrange method was used to calculate surface contact and perform simulation analysis ofthe pressure hemostasis system, as shown in Figure 1(a) and (b). It was obtained that when the pressure in the airbag reached 1. 1atm the downforce on the skin was 12.5kpa, meeting the minimumJournal of Physics: Conference Series 2478 (2023) 122071 doi:10.1088/1742-6596/2478/12/122071hemostatic pressure requirement of 10kPa. At the same time, the application exerts tangential tightening pressure on the traumatized surface, as shown in Figure 1(d)(e).<img src="/media/202408//1724856371.3444061.png" />Figure 1. (a)(b) Simulation model structure (c) Pressure simulation diagram of the microsystem expanding in the central airbag(d)(e) Simulation diagram of tangential pressure on traumatic surfaceThe third step is to establish the wound model and conduct the simulation analysis of pressure hemostasis in the wound modelSince the diameter of blood vessels in different parts of the human body is different, and the convective heat transfer coefficient is also different, and the thickness of the inner and outer layers of various blood vessels is basically the same, these key factors need to be taken into account in clinical trials of pressure hemostasis. The convective heat transfer coefficient of blood in the human body is generally 0.5W/m2*K. Through numerical simulation, we found that with the increase of blood vessel diameter, the first &quot;closing&quot; time of blood vessel wound under pressure was longer, which may be because the increase of blood vessel circumference led to the longer compression deformation time and thus the longer wound healing time. At the same time, we can also find that the convection heat transfer coefficient of blood, that is, the influence of heat dissipation conditions on pressureJournal of Physics: Conference Series 2478 (2023) 122071 doi:10.1088/1742-6596/2478/12/122071hemostasis almost does not exist. Table 2 shows the relevant parameters for establishing the wound surface vascular rupture model, and the model is shown in figure 2.Table 2. Parameters related to vascular and wound models.<table><tr><td>Name</td><td>Value</td><td>Description</td></tr><tr><td>S_l (mm)</td><td>0.5</td><td>Wound width</td></tr><tr><td>S_h (mm)</td><td>4</td><td>Wound length</td></tr><tr><td>S_z (mm)</td><td>0</td><td>Temperature source location</td></tr><tr><td>T_b (degC)</td><td>37</td><td>Temperature</td></tr><tr><td>h_l (W/m2*K)</td><td>5</td><td>Coefficient of heat dissipation</td></tr><tr><td>ωn</td><td>0.8</td><td>Moisture content of inner layer</td></tr><tr><td>ωw</td><td>0.5</td><td>Moisture content of outer layer</td></tr><tr><td>D (mm)</td><td>6</td><td>Blood vessel diameter</td></tr><tr><td>Thickness_w (mm)</td><td>1</td><td>Thickness of outer layer</td></tr></table><img src="/media/202408//1724856371.444569.jpeg" />Figure 2. Effect of length and width of vascular wound on wound pressure &quot;suture&quot; hemostasisIn pressure hemostasis, it is also crucial to analyze the influence of wound shape on &quot;suture&quot; hemostasis of vascular wound by setting pressure at 100mmHg. Since vascular wound presents flat olive shape, we respectively analyze the influence of changes in wound length S_l and width S_h on wound &quot;suture&quot; speed at high temperature at 37 ℃ . When the wound width S_h = 0.5mm, parameterized scan was performed on the wound length S_l, and when the wound length S_l = 4mm, parameterized scan was performed on the wound width S_h, as shown in figure 2. From the information in figure 2, we can see that as the length and width of the wound increase, the woundJournal of Physics: Conference Series 2478 (2023) 122071 doi:10.1088/1742-6596/2478/12/122071&quot;suturing&quot; time becomes longer under pressure. At the same time, we also found that with the increase of the same amplitude, the change of length S_l has a greater influence on the hemostasis of vascular wound &quot;suture&quot; than width S_h. Therefore, when the length of the wound changes greatly, it is necessary to change the temperature or the cross-section size of the temperature source or even the position of the temperature source. However, when the width of the wound changes, it can not be changed according to the actual situation.2.2. System structure designIn the design of pressure hemostatic microsystem, the surface microsystem is mainly composed of three parts: pressure generating device, drug delivery device and detection feedback device. The action mechanism of the microsystem is shown in Figure 3.<img src="/media/202408//1724856371.480213.jpeg" />Figure 3. Schematic diagram of rapid pressure hemostasis microsystemThe principle of the pressure generating device is to use sodium bicarbonate solid and aluminum sulfate solution to produce chemical reaction, the reaction formula is as follows:NaHCO3 + Al2 (SO4 )3 == 3Na2SO4 + 2Al(OH)3 ↓ +6CO2 ↑ (3) 	Carbon dioxide gas produced by chemical reaction, pneumatic compression of air pressure produced by the bleeding to stop bleeding, at the same time, the surface large trauma quick pressure hemostatic medicine drugs in a unit of storage in monitoring system through the pressure relief to the wound surface for hemostasis and disinfection sterilization, system structure diagram as shown infigure 4 (a), the system principle diagram as shown in figure 4 (b).Journal of Physics: Conference Series 2478 (2023) 122071 doi:10.1088/1742-6596/2478/12/122071<img src="/media/202408//1724856371.52916.png" />Figure 4. (a)System structure diagram (b)System principle diagram2.3. Study on drug delivery technologyAt the same time that the pressure stops the bleeding, the drug storage unit is located on the surface of the balloon and wound, and the drug is released to the wound site under the pressure. The deformation of different drug storage units under the same pressure was studied in figure. 5. After analysis, the deformation of the convex drug storage unit was the largest, reaching 1.35mm, meeting therequirements of releasing drugs onto the wound surface.<img src="/media/202408//1724856371.621013.png" />Figure 5. Deformation analysis of boss, quadrilateral, hexagon and hemispherical3. ResultsThrough the research on surface type trauma Pressure hemostasis, the designed hemostasis microsystem is processed and manufactured, and the key device &quot;Pressure Air Bags&quot; is produced by 3D printing, as shown in Figure 6.Journal of Physics: Conference Series 2478 (2023) 122071 doi:10.1088/1742-6596/2478/12/122071<img src="/media/202408//1724856371.703087.png" />Figure 6. Pressure air bagsThe principle and structure of the rapid pressure hemostasis microsystem are described in figure 4, and the hardware-in-the-loop simulation experiment is carried out. The theoretical prototype is shown in figure 7:<img src="/media/202408//1724856371.966311.png" />Figure 7. (a) Principle prototype (b) Pressure detection 1 minute after reactionAfter the simulation analysis of the principle prototype, the pressure reaches 270mmHg, which meets the requirements of wound surface pressure hemostasis.4. ConclusionInnovation points of this paper: (1) By studying the vascular rupture model on the wound surface, the law of vascular deformation under pressure was studied. (2) In view of the collateral damage problems such as burning and secondary wounds caused by traditional high-temperature hemostasis methods, the principle of chemical endothermic reaction of sodium bicarbonate and aluminum sulfate was designed to achieve the cooling of large wounds. Rapid hemostatic xiaosha micro system which can realize the orientation of the trauma surface contact precision hemostatic, surface temperature of surrounding tissue trauma under normal temperature, sharply reduced to wound around the secondaryJournal of Physics: Conference Series 2478 (2023) 122071 doi:10.1088/1742-6596/2478/12/122071injury (3) the principle prototype experiments, has been reached 270 mmHg in surface radial stress, meet the requirement of pressure hemostasis, and can meet the demand of deformation of pressure vessels.References[1] J. F. Kragh, M. L. Littrel, J. A. Jones, T. J. Walters, D. G. Baer, “Battle casualty survival with emergency tourniquet use to stop limb bleeding,” J. Emerg. Med., vol. 41, no. 6, pp. 590–597, 2011.[2] J. F. Kelly, A. E. Ritenour, D. F. McLaughlin, K. A. Bagg, A. N. Apodaca, C. T. Mallak, L. Pearse, M. M. Lawnick, , “Injury severity and causes of death from operation iraqi freedom and operation enduring freedom: 2003–2004 versus 2006,” J. 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