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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

引用

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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