Self-propelled particles that transport cargo through flowing blood and halt hemorrhage

Baylis, James R.; Yeon, Ju Hun; Thomson, Max H.; Kazerooni, Amir; Wang, Xu; John, Alexander E. St.; Lim, Esther B.; Chien, Diana; Anna, Lee; Zhang, Jesse Q.; Piret, James M.; Machan, Lindsay; Burke, Thomas F.; White, Nathan J.; Kastrup, Christian J.

doi:10.1126/sciadv.1500379

Cited by 173 publications

(188 citation statements)

References 36 publications

(48 reference statements)

Supporting

Mentioning

182

Contrasting

Order By: Relevance

“…Previously, we developed a self-propelling particle system that foams and reacts when placed in water or blood. (15) The particles are composed of calcium carbonate (CaCO 3 ) with adsorbed thrombin. The particles are physically mixed with solid protonated tranexamic acid, which causes them to release carbon dioxide gas when placed in an aqueous solution, such as blood (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…However a combat-relevant large animal model is required to mimic the hemorrhage volumes and pressures seen in humans after combat injury. (15) That publication included a pilot study, in which these self-propelled, thrombin-loaded particles were loaded onto gauze and increased survival following femoral artery injury and hemorrhage in a small cohort of swine. Here, we extended this study to a larger cohort, measured additional clinical parameters, and tested against the kaolin-based QuikClot Combat Gauze® (KG) bandage (Z-Medica, Wallingford, CT) currently approved by the Committee on Tactical Combat Casualty Care for battlefield use.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Self-Propelled Dressings Containing Thrombin and Tranexamic Acid Improve Short-Term Survival in a Swine Model of Lethal Junctional Hemorrhage

Baylis

John

Wang

et al. 2016

Shock

Self Cite

View full text Add to dashboard Cite

Hemorrhage is the leading cause of preventable death in trauma, and hemorrhage from noncompressible junctional anatomic sites is particularly difficult to control. The current standard is QuikClot Combat Gauze packing, which requires 3 min of compression. We have created a novel dressing with calcium carbonate microparticles that can disperse and self-propel upstream against flowing blood. We loaded these microparticles with thrombin and tranexamic acid and tested their efficacy in a swine arterial bleeding model without wound compression. Anesthetized immature female swine received 5 mm femoral arteriotomies to induce severe junctional hemorrhage. Wounds were packed with kaolin-based QuikClot Combat Gauze (KG), propelled thrombin-microparticles with protonated tranexamic acid (PTG), or a non-propelling formulation of the same thrombin-microparticles with non-protonated tranexamic acid (NPTG). Wounds were not compressed after packing. Each animal then received one 15 mL/kg bolus of hydroxyethyl starch solution followed by Lactated Ringer’s as needed for hypotension (maximum: 100 mL/kg) for up to 3 hours. Survival was improved with PTG (3-hr survival: 8/8, 100%) compared to KG (3/8, 37.5%) and NPTG (2/8, 25%) (p<0.01). PTG animals maintained lower serum lactate and higher hemoglobin concentrations than NPTG (p<0.05) suggesting PTG decreased severity of subsequent hemorrhagic shock. However, total blood loss, Lactated Ringer’s infusion volumes, and mean arterial pressures of surviving animals were not different between groups (p>0.05). Thus, in this swine model of junctional arterial hemorrhage, gauze with self-propelled, pro-thrombotic microparticles improved survival and two indicators of hemorrhagic shock when applied without compression, suggesting this capability may enable better treatment of non-compressible junctional wounds.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Self-Propelled Dressings Containing Thrombin and Tranexamic Acid Improve Short-Term Survival in a Swine Model of Lethal Junctional Hemorrhage

Baylis

John

Wang

et al. 2016

Shock

Self Cite

View full text Add to dashboard Cite

show abstract

“…The TXA‐HCl was prepared as previously described, with modifications; concentrated HCl was added to 0.5 mol/L TXA (Chem‐Impex, Wood Dale, IL) and the solution was lyophilized to yield solid TXA‐HCl. To make spTXA, CaCO 3 microparticles (3 μm; American Elements, Los Angeles, CA), TXA‐HCl, and Na 2 CO 3 (Thermo Fisher Scientific, Waltham, MA) were mechanically mixed together in a 6:3.3:1 mass ratio.…”

Section: Methodsmentioning

confidence: 99%

“…Delivering TXA directly to the wound would decrease the time to treatment and would enable delivery of TXA both locally and systemically. However, topical delivery of hemostatic agents, such as TXA, is complicated in severe bleeding by the brisk outward flow of blood, which prevents therapeutics from reaching the damaged vasculature . A delivery vehicle that transports topical TXA against blood flow deep into wounds could improve its ability to inhibit fibrinolysis and stop bleeding.…”

Section: Introductionmentioning

confidence: 99%

“…We have developed self‐propelling particles that transport against flow to deliver therapeutic cargoes. Formulations of self‐propelling particles that contained thrombin and TXA increased thrombin's efficacy and reduced bleeding times and improved survival in several animal models, including endoscopic sinus surgery in sheep and junctional hemorrhage without compression in swine . These self‐propelling particles are composed of calcium carbonate (CaCO 3 ) mechanically mixed with protonated TXA (TXA‐HCl).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Topical tranexamic acid inhibits fibrinolysis more effectively when formulated with self‐propelling particles

Baylis

Lee

John

et al. 2019

Journal of Thrombosis and Haemostasis

Self Cite

View full text Add to dashboard Cite

Background Endogenous fibrinolytic activation contributes to coagulopathy and mortality after trauma. Administering tranexamic acid (TXA), an antifibrinolytic agent, is one strategy to reduce bleeding; however, it must be given soon after injury to be effective and minimize adverse effects. Administering TXA topically to a wound site would decrease the time to treatment and could enable both local and systemic delivery if a suitable formulation existed to deliver the drug deep into wounds adequately. Objectives To determine whether self‐propelling particles could increase the efficacy of TXA. Methods Using previously developed self‐propelling particles, which consist of calcium carbonate and generate CO2 gas, TXA was formulated to disperse in blood and wounds. The antifibrinolytic properties were assessed in vitro and in a murine tail bleeding assay. Self‐propelled TXA was also tested in a swine model of junctional hemorrhage consisting of femoral arteriotomy without compression. Results Self‐propelled TXA was more effective than non‐propelled formulations in stabilizing clots from lysis in vitro and reducing blood loss in mice. It was well tolerated when administered subcutaneously in mice up to 300 to 1000 mg/kg. When it was incorporated in gauze, four of six pigs treated after a femoral arteriotomy and without compression survived, and systemic concentrations of TXA reached approximately 6 mg/L within the first hour. Conclusions A formulation of TXA that disperses the drug in blood and wounds was effective in several models. It may have several advantages, including supporting local clot stabilization, reducing blood loss from wounds, and providing systemic delivery of TXA. This approach could both improve and simplify prehospital trauma care for penetrating injury.

show abstract

Micro/Nanomachines and Living Biosystems: From Simple Interactions to Microcyborgs

Hong

Pumera

2018

Adv Funct Materials

110

View full text Add to dashboard Cite

Miniaturization of machines into the micro/nanoscale is an essential ingredient toward better understanding and control of the microscopic world. As an emerging research area, micro/nanomachines have attracted substantial efforts of researchers from multiple disciplines. Mimicking the biological machines in nature, artificial micro/nanomachines are becoming increasingly sophisticated so that they can serve as useful tools to address problems encountered in the intricate biosystems. This review highlights the recent efforts for and toward application of micro/nanomachines in living biosystems, including microorganisms, biological cells, and human body. With progressive steps toward translating micro/nanomachines research into practice, using these tiny machines to tackle thorny problems in biosystems may not only exist in the Hollywood science fiction film.

show abstract

Self-propelled particles that transport cargo through flowing blood and halt hemorrhage

Abstract: Simple, water-reactive particles can carry enzymes upstream through aqueous solutions and into wounds to halt severe bleeding.

Cited by 173 publications

References 36 publications

Self-Propelled Dressings Containing Thrombin and Tranexamic Acid Improve Short-Term Survival in a Swine Model of Lethal Junctional Hemorrhage

Self-Propelled Dressings Containing Thrombin and Tranexamic Acid Improve Short-Term Survival in a Swine Model of Lethal Junctional Hemorrhage

Topical tranexamic acid inhibits fibrinolysis more effectively when formulated with self‐propelling particles

Micro/Nanomachines and Living Biosystems: From Simple Interactions to Microcyborgs

Contact Info

Product

Resources

About