J Thromb Thrombolysis (2006) 22:55–67 DOI 10.1007/s11239-006-7658-y Host-guest composites for induced hemostasis and therapeutic healing in traumatic injuries Todd A. Ostomel · Peter K. Stoimenov · Patricia A. Holden · Hasan B. Alam · Galen D. Stucky C  Springer Science + Business Media, LLC 2006 Abstract 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 in- duce hemostasis and prevent loss of life from exsanguination. The goals of this work were to identify and implement strate- gies to attenuate a tissue burning side effect associated with the HA, resulting from a large release of heat upon hydra- tion, without adversely affecting the wound healing proper- ties. 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 antibac- terial 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 mod- ified HAs were characterized by TGA, DSC, Thermal Imag- ing, SEM, XRD, XPS, BET, and a Thromboelastograph R  (TEG R  ) was employed to assay the in vitro hemostatic effi- cacy. Antibacterial activity was assayed by measuring the T. A. Ostomel · P. K. Stoimenov · G. D. Stucky () Department of Chemistry and Biochemistry, University of California Santa Barbara, Santa Barbara, California 93106 e-mail: stucky@chem.ucsb.edu P. A. Holden Donald Bren School of Environmental Science and Management, University of California Santa Barbara, Santa Barbara, California 93106 H. B. Alam Department of Surgery, Room A-3021, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 Present address: Massachusetts General Hospital, Division of Trauma, Emergency Surgery and Surgical Critical Care, 165 Cambridge Street, Suite 810 Boston, MA 02114 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 exchang- ing 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 m 2 /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 R  , 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 experi- ments involving animals, and the associated labor and capital costs, necessary to test a new HA. A method for incorporat- ing antibacterial activity against gram negative P. aeruginosa into the Ag-exchanged formulation of zeolite LTA-5A has been described and substantiated. Keywords Hemostatic agent . Thromboelastograph . Zeolites . Traumatic injury . Battlefield injury . Hemorrhage . Swine . Femoral vessels . Groin . Bandages Springer