Host-guest composites for induced hemostasis and therapeutic healing in traumatic injuries

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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 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.

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