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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

作     者:Anne-Charlotte Ponsen Richard Proust Sabrina Soave Françoise Mercier-Nom´e Isabelle Garcin Laurent Combettes Jean-Jacques Lataillade Georges Uzan 

作者机构:INSERM UMRS-MD 1197Universit´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-SaclayINSERMInflammationMicrobiome and ImmunosurveillanceClamartFrance INSERM UMRS 1174Universit´e Paris-SaclayOrsayFrance Centre de Transfusion Sanguine des Arm´eesClamartFrance 

出 版 物:《Bioactive Materials》 (生物活性材料(英文))

年 卷 期:2022年第7卷第12期

页      面:368-382页

核心收录:

学科分类:0831[工学-生物医学工程(可授工学、理学、医学学位)] 08[工学] 0805[工学-材料科学与工程(可授工学、理学学位)] 

基  金:We are very grateful to Dr.Florence Armstrong for her scientific advice and for participating in supervision of A-C.P.’s PhD research.We also express our gratitude to Dr.C´eline Revenu for her help in writing the article.We thank Dr.Claude Boucheix for his scientific advice and for proofreading of the paper.We are grateful to the UMS-44(ex UMS-33)for providing access to its many platforms,and especially to Denis Clay,who runs the Cytometry platform,as well as the whole team at the animal house.We warmly thank Aurore Devocelle,Antonietta Messina,Nassima Benzoubir,and Marwa Hussein for their help with experiments performed to help answer the reviewers’questions.Finally,we would like to thank the Direction G´en´erale de l’Armement(DGA)which partially financed A-C.P.’s PhD in the context of a CIFRE-D´efense thesis(n◦10/2014/DGA) in particular Dr.Emmanuelle Guillot-Combe,who is responsible for the follow-up of the PhD students. 

主  题:Hemostatic agent Alginate Surgery Hemostasis Endothelial cells Tissue repair 

摘      要: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.

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