Host-guest composites for induced hemostasis and therapeutic healing in traumatic injuries
Introduction: The United States military currently outfits our soldiers with a zeolite-based hemostatic agent (HA) that is applied directly onto a traumatic wound to induce hemostasis and prevent loss of life from exsanguination. The goals of this work were to identify and implement strategies to attenuate a tissue burning side effect associated with the HA, resulting from a large release of heat upon hydration, without adversely affecting the wound healing properties. Five ion exchanged derivatives of the parent HA were prepared and characterized with regard to their material and thermal properties, in vitro hemostatic efficacy, and antibacterial activity.
Methods: The five host-guest high-surface-area HAs were prepared by ion exchanging the zeolite linde type 5A with aqueous salt solutions under controlled conditions. The modified HAs were characterized by TGA, DSC, Thermal Imaging, SEM, XRD, XPS, BET, and a Thromboelastograph® (TEG®) was employed to assay the in vitro hemostatic efficacy. Antibacterial activity was assayed by measuring the zone of no growth of Pseudomonas aeruginosa biofilms growing in contact with the ion exchanged HAs.
Results: The heat released during application of the HA can be minimized from 680 J/g to 420 J/g by ion exchanging the calcium ions in zeolite linde type 5A with cations of a reduced hydration enthalpy. Zeolite-based HAs that demonstrate in vitro clot induction time of R ≤ 1.8 min, and with surfaces areas ≥ 634 m2/g, correlate with 75% in vivo swine survivability of a universally lethal groin injury. Silver exchanged HA maintained a zone of no growth of P. aeruginosa with a surface area twice the geometrical surface area of an HA pressed pellet for 24 hours in an LB Agar assay.
Conclusions: Two strategies for reducing the large amount of heat released by a zeolite-based HA during application have been described and quantified: (1) ion exchange and (2) prehydration. Five ion-exchanged derivatives of the original HA have been prepared and assayed for hemostatic efficacy both in vitro, by TEG®, and in vivo, by clinical swine trials. Contact activation coagulation rates, α, were found to increase with the amount of heat released by the HA. In Vitro clot induction time, R, and HA surface area have been identified as predictors of in vivo hemostatic performance. A proposed rationale for selecting hemostatic materials based on these parameters will likely reduce the quantity of experiments involving animals, and the associated labor and capital costs, necessary to test a new HA. A method for incorporating antibacterial activity against gram negative P. aeruginosa into the Ag-exchanged formulation of zeolite LTA-5A has been described and substantiated.
KeywordsHemostatic agent Thromboelastograph Zeolites Traumatic injury Battlefield injury Hemorrhage Swine Femoral vessels Groin Bandages
Unable to display preview. Download preview PDF.
- 1.Ryan KL, Kheirabad B, Klemke HG, Martini W, Delgado AV, Pusateri AE (2003) Overview of the hemostasis research program: advances and future directions. Army Medical Department Journal PB-8-03-7/8/9:12–25Google Scholar
- 4.Hursey FX, Dechene FJ (1989) inventors; Method of Treating Wounds. United States of America patent #4,822,349Google Scholar
- 5.Z-Medica I. www.z-medica.com. In: Newington, CT.
- 6.Wright James K, Kalns J, Wolf Edward A, et al (2004) Thermal injury resulting from application of a granular mineral hemostatic agent. J TRAUM 57(2):224–30Google Scholar
- 7.Ostomel TA, Stoimenov PK, Holden PA, Stucky GD, (2005) inventors; Porous Inorganic Materials for Therapeutic Wound Healing. United States patent application #60/668,022Google Scholar
- 8.Breck DW (1974) Zeolite molecular sieves, John Wiley & Sons, Inc.Google Scholar
- 9.Barrer RM (1978) Zeolites and clay minerals as sorbents and molecular sieves. Academic Press, New YorkGoogle Scholar
- 17.Glidden PF, Malaska C, Herring SW (2000) Thromboelastograph assay for measuring the mechanical strength of fibrin sealant clots. Clin Appl Thromb-Hem 6(4):226–233Google Scholar
- 21.Alam Hasan B (2005) Zeolite hemostatic dressing: battlefield use. In: Advanced technology applications for combat casualty care (ATACCC0); 2005 August 15–17; St. Petersburg, FLGoogle Scholar
- 23.Alam HB, Kheirabadi BS (2005) Hemostatic efficacy of two advanced dressings in an aortic hemorrhage model in swine—Discussion. J TRAUMA 59(1):34–35Google Scholar
- 31.Helfferich F (1962) Ion exchange. McGraw-Hill Book Company, Inc., New YorkGoogle Scholar
- 35.Morishita M, Miyagi M, Yamasaki Y, Tsuruda K, Kawahara K, Iwamoto Y (1998) Effect of silver zeolite on plaque formation. J Dent Res 77:845–845Google Scholar