A new hemostatic agent composed of Zn<sup>2+</sup>-enriched Ca<sup>2+</sup> alginate activates vascular endothelial cells <i>in vitro</i> and promotes tissue repair <i>in</i> <i>vivo</i>.

Ponsen, Anne-Charlotte; Proust, Richard; Soave, Sabrina; Mercier-Nomé, Françoise; Garcin, Isabelle; Combettes, Laurent; Lataillade, Jean-Jacques; Uzan, Georges · Bioact Mater · 2022

basic_science · Level V

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Abstract

To control capillary bleeding, surgeons may use absorbable hemostatic agents, such as Surgicel® and TachoSil®. Due to their slow resorption, their persistence <i>in situ</i> 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) <i>in vitro</i> on endothelial cells, which are essential to tissue repair, and (ii) <i>in vivo</i> in a mouse skin excision model. <i>In vitro</i>, 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. <i>In vivo</i>, 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.