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A new hemostatic agent composed of Zn^(2+)-enriched Ca^(2+)alginate activates vascular endothelial cells in vitro and promotes tissue repair in vivo

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Bioactive Materials 2022年第12期7卷 368-382页

作者： Anne-Charlotte Ponsen Richard Proust Sabrina Soave Françoise Mercier-Nom´e Isabelle Garcin Laurent Combettes Jean-Jacques Lataillade Georges Uzan INSERM UMRS-MD 1197 Universit´e Paris-SaclayInstitut Andr´e LwoffHˆopital Paul BrousseVillejuifFrance Plateforme d’Histologie Immunopathologie de Clamart(PHIC) Universit´e Paris-SaclayINSERMCNRSInstitut Paris Saclay d’Innovation Th´erapeutiqueChˆatenay-MalabryFrance Universit´e Paris-Saclay INSERMInflammationMicrobiome and ImmunosurveillanceClamartFrance INSERM UMRS 1174 Universit´e Paris-SaclayOrsayFrance Centre de Transfusion Sanguine des Arm´ees ClamartFrance

To control capillary bleeding, surgeons may use absorbable hemostatic agents, such as Surgicel® and TachoSil®. Due to their slow resorption, their persistence in situ can have a negative impact on tissue repair in the resected organ. To avoid complications and obtain a hemostatic agent that promotes tissue repair, a zinc-supplemented calcium alginate compress was developed: HEMO-IONIC®. This compress is non-absorbable and is therefore removed once hemostasis has been achieved. After demonstrating the hemostatic efficacy and stability of the blood clot obtained with HEMO-IONIC, the impact of Surgicel, TachoSil, and HEMO-IONIC on cell activation and tissue repair were compared (i) in vitro on endothelial cells, which are essential to tissue repair, and (ii) in vivo in a mouse skin excision model. In vitro, only HEMO-IONIC maintained the phenotypic and functional properties of endothelial cells and induced their migration. In comparison, Surgicel was found to be highly cytotoxic, and TachoSil inhibited endothelial cell migration. In vivo, only HEMO-IONIC increased angiogenesis, the recruitment of cells essential to tissue repair (macrophages, fibroblasts, and epithelial cells), and accelerated maturation of the extracellular matrix. These results demonstrate that a zinc-supplemented calcium alginate, HEMO-IONIC, applied for 10 min at the end of surgery and then removed has a long-term positive effect on all phases of tissue repair.

关键词： hemostatic agent Alginate Surgery Hemostasis Endothelial cells Tissue repair

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hemostatic agents for prehospital hemorrhage control: a narrative review

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Military Medical Research 2020年第4期7卷 444-463页

作者： Henry T.Peng Defence Research and Development Canada Toronto Research Centre1133 Sheppard Avenue WestTorontoON M3K 2C9Canada

Hemorrhage is the leading cause of preventable death in combat trauma and the secondary cause of death in civilian trauma.A significant number of deaths due to hemorrhage occur before and in the first hour after hospital arrival.A literature search was performed through PubMed,Scopus,and Institute of Scientific Information databases for English language articles using terms relating to hemostatic agents,prehospital,battlefield or combat dressings,and prehospital hemostatic resuscitation,followed by cross-reference searching.Abstracts were screened to determine relevance and whether appropriate further review of the original articles was warranted.Based on these findings,this paper provides a review of a variety of hemostatic agents ranging from clinically approved products for human use to newly developed concepts with great potential for use in prehospital settings.These hemostatic agents can be administered either systemically or locally to stop bleeding through different mechanisms of action.Comparisons of current hemostatic products and further directions for prehospital hemorrhage control are also discussed.

关键词： hemostatic agent Hemorrhage control Trauma

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CoolClot,a novel hemostatic agent for controlling life-threatening arterial bleeding

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World Journal of Emergency Medicine 2013年第2期4卷 123-127页

作者： SMJ Mortazavi A Tavasoli M Atefi N Tanide N Radpey P Roshan-shomal H Moradi S Taeb Radiology Department School of Allied Medical SciencesShiraz University of Medical SciencesShirazIran The Centre for Radiological Research Shiraz University of Medical SciencesShirazIran Shiraz Blood Transfusion Organization ShirazIran The Centre for Research on Stem Cell Shiraz University of Medical SciencesIran

BACKGROUND:Uncontrolled bleeding is the first leading cause of preventable death in the battlefield and the 2nd cause of mortality in civil accidents.Incompressible hemorrhage control is among the interventions that drastically increase the survival rate in wound individuals.We have previously shown that a certain mixture of bentonite and zeolite minerals can significantly decrease the bleeding in rats.METHODS:In this study,nine healthy hybrid dogs were selected and after induction of anesthesia with ether,either arterial puncture by a needle or arteriotomy was performed on both groin regions of the dogs.For control arteries(either the right or left femoral artery),only pressure by sterilized gauze was performed,while for the femoral arteries of the opposite side,our invented hemostatic agent,namely CoolClot,was topically used before applying the pressure.In the second stage of the study,to assess the coagulation time,blood samples were collected from 10 volunteer students.RESULTS:CoolClot significantly decreased the bleeding time in animals whose femoral arteries were cut or punctured.In the human phase of the study,the mean coagulation time in control blood samples was 253.4+44.1 seconds,whereas it was 149.5+50.0,162.3±74.6 and 143.4±114.6seconds,respectively in blood samples treated with bentonite,zeolite and CoolClot(P<0.05).CONCLUSIONS:As controlling bleeding after a life-threatening arterial damage is critical for increasing the chance of survival,the results obtained in this study indicate the significant efficacy of CoolClot in shortening the bleeding time.Our experiments also indicate that CoolClot can significantly reduce the clotting time in human blood samples.

关键词： Bleeding hemostatic agent CoolClot Bentonite and zeolite

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A Novel Tissue Adhesive Composed of Modified Gelatin and Polysaccharides

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材料科学与工程学报 2000年第Z2期20卷 781-785页

作者： Xiumei MO Institute for Frontier Medical Science Kyoto University 53 Kawahara-cho Sakyo-ku Kyoto Japan Institute of Materials Science East China University of Science and TechnologyShanghai 200237 China Institute for Frontier Medical Science Kyoto University 53 Kawahara-cho Sakyo-ku Kyoto Japan

A two-component adhesive glue was prepared from gelatin and polysaccharides. Gelatin was modified with ethylenediamine (ED) in the presence of water soluble carbodiimine (WSC) to introduce more amino groups into the original gelatin, while dextran and hydroxyethyl-starch (HES) were oxidized by sodium periodate to convert neighbouring hydroxyl groups into dialdehyde groups. Upon mixing the two polymer components in aqueous solution, Schiff's base reaction occurred between the amino groups in the modified gelatin and the aldehyde groups in the modified polysaccharides to give intermolecular crosslinking and gel formation. This new glue showed a capability to stop bleeding and seal tissues when a cut liver of rat was used for hemostatic experiments. It could also form a gel much faster than fibrin glue in in-vitro experiments. The fastest gel formation took place within 2 sec and the bonding strength to porcine skin was about 225gf/cm2 when an amino-gelatin (55% amino) and an aldehyde-HES (>84% dialdehyde) was mixed. In contrast, the gelation time and bonding strength of fibrin gluewere 5 seconds and 120gf/cm2, respectively. The effective adhesive properties have also been identified by the animal experiments of rat.

关键词： hemostatic agent Gelatin Polysaccharides Gel Dextran: Hydroxyethyl starch Schiff's base: adhesive

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