Biocompatibility Research Of A Hemostatic Agent-ZSM-5 Zeolite

Uncontrolled bleeding is the leading cause of death during the prehospital period in both military combat and civilian trauma cases, and effective control of hemorrhage after injury could improve outcome. However, for a long time, there are no significantly improvements on first aid hemorrhage control during the prehospital period. Although traditional hemorrhage control methods such as direct pressure or, the application of a tourniquet can control bleeding from extremity injuries, presently can do little to control bleeding from complex wounds, and could cause severe complications when applied improperly. It will have potentiality in developing a new type of hemostatic agent which can control hemorrhage effectively under the condition of wars, natural disasters and rescues in the future.Our department has paid close attention to the development of first aid hemostatic agent in foreign armies and has discussed the feasibility of using ZSM-5 zeolite as first aid hemostatic agent firstly in China. This experiment demonstrated that in a model of lethal groin injury, hemorrhage control with ZSM-5 zeolite could significantly reduce the mortality from 100% to 0%. Exothermic reaction was observed when zeolite powder was poured on the wound and it demonstrated that confined thermal injuries occured around the wounds site. Our country abounds in zeolite resources and there are solid research foundations and experiences about zeolite as catalyst and ion exchanger. It provides sufficient condition to develop zeolite as hemostatic agent. This experiment aims to make further study on the biocompatibility on ZSM-5 zeollite hemostatic agent made in China. According to Chinese evaluation standards on medical devices(GB/T 16886),We studied as follows in two parts:1. Cytotoxicity test portion: We used the methods of methyl- thiazolyl- tetrazolium (MTT) assay and direct contact cell culture to evaluate cytotoxicity of ZSM-5 zeolite. The morphology of the cells was observed by light microscope and electronmicroscope. Results: The property of ZSM-5 zeolite was stable and the toxic levels ranged from 0 to 1 degree. There was no sign of cytotoxicity induced by ZSM-5 zeolite, the morphology of the cells close to the samples was normal.2. Animal test portion: The acute toxicity of system, hemolysis test, pyrogen test, intracutaneous stimulation, sensitization and micronucleus test were studied on ZSM-5 zeolite. In order to find out the side-effect of the zeolite granules'remains left in the wounds to body, muscle implantation test was also studied. Results: There were no obvious acute toxicity, hemolysis reaction , pyrogen reaction, intracutaneous stimulation, sensitization and potential mutagenesis in the micronucleus test were observed. These were all consistent with the Chinese biological evaluation of medical devices. Obvious inflammatory reaction was observed when ZSM-5 zeolite was implanted in muscle for 12 weeks. Conclusion: The ZSM-5 zeolite has reliable biocompatibility, which has accorded with the request of the primary detection of biosecurity and the experiment before clinical application. This study provides an important reference for clinical application in future. But muscle implantation test showed that zeolite could cause inflammatory reaction when it remained in wound surface for long term. This suggests that the zeolite granulas must be debrided up when suture the wounds.