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钙及海藻酸钙敷料对巨噬细胞炎症及促进伤口愈合修复特性的体外调节作用

In Vitro Modulation of Macrophage Inflammatory and Pro-Repair Properties Essential for Wound Healing by Calcium and Calcium-Alginate Dressings.

作者信息

Adib Yara, Serror Kevin, Pinzon Jose Amaya, Duciel Laura, Delagrange Marine, Ducos Bertrand, Boccara David, Mimoun Maurice, Chaouat Marc, Bensussan Armand, Samardzic Marina, Bagot Martine, Des Courtils Céline, Michel Laurence

机构信息

Inserm UMRS_1342, Hôpital Saint-Louis, 1 Avenue Claude Vellefaux, 75010 Paris, France.

UFR de Sciences du Vivant, Université Paris Cité, 75006 Paris, France.

出版信息

Cells. 2025 Jun 16;14(12):909. doi: 10.3390/cells14120909.

DOI:10.3390/cells14120909
PMID:40558536
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12190423/
Abstract

Macrophages participate in cutaneous wound healing by adopting M1 pro-inflammatory and M2 immunoregulatory/pro-repair phenotypes. Chronic wounds associated with a deficient macrophage response could benefit from treatments that restore an acute inflammatory response and promote healing. Calcium-alginate dressings release calcium ions, which are potent bioactivators of macrophage function in wounds. Here, the effects of two calcium-alginate dressings, Algosteril (ALG, pure Ca alginate) and Biatain Alginate (BIA, Ca alginate with carboxymethyl cellulose), and a 3 mM CaCl solution were compared in human macrophages polarized to M1 or M2. ALG and CaCl preserved monocyte viability, and BIA reduced it. Both alginates and CaCl reinforced the M1 pro-inflammatory transcriptional profile and phenotype, with significant increases in IL-6 and TNF-α secretion by ALG only. In M2 macrophages, all conditions increased the M1-specific gene expression and reduced M2 markers, suggesting an orientation toward an inflammatory profile. Only ALG significantly increased the secretion of CCL18 and VEGF, suggesting pro-repair activity. All conditions increased M2 phagocytic activity. This work demonstrates the interest in calcium alginates for stimulating macrophage subtypes, which could help restore wound healing, especially in patients with compromised innate immunity. It highlights the differences among the calcium-alginate dressings. The pure alginate shows higher stimulation of macrophage pro-inflammatory and pro-repair functions.

摘要

巨噬细胞通过呈现M1促炎和M2免疫调节/促修复表型参与皮肤伤口愈合。与巨噬细胞反应不足相关的慢性伤口可能受益于恢复急性炎症反应并促进愈合的治疗方法。海藻酸钙敷料会释放钙离子,而钙离子是伤口中巨噬细胞功能的有效生物激活剂。在此,我们比较了两种海藻酸钙敷料Algosteril(ALG,纯海藻酸钙)和Biatain藻酸盐(BIA,含羧甲基纤维素的海藻酸钙)以及3 mM氯化钙溶液对极化至M1或M2的人巨噬细胞的影响。ALG和氯化钙可维持单核细胞活力,而BIA则会降低其活力。两种海藻酸盐和氯化钙均增强了M1促炎转录谱和表型,仅ALG使IL-6和TNF-α分泌显著增加。在M2巨噬细胞中所有条件均增加了M1特异性基因表达并降低了M2标志物,表明趋向于炎症表型。只有ALG显著增加了CCL18和VEGF的分泌,表明具有促修复活性。所有条件均增加了M2吞噬活性。这项研究表明海藻酸钙在刺激巨噬细胞亚型方面具有应用价值,这可能有助于恢复伤口愈合,尤其是对于先天免疫受损患者。它突出了海藻酸钙敷料之间的差异。纯海藻酸盐对巨噬细胞促炎和促修复功能的刺激作用更强。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fd0/12190423/70d595a26e83/cells-14-00909-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fd0/12190423/50719fe710f1/cells-14-00909-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fd0/12190423/8fdc95dd8ec8/cells-14-00909-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fd0/12190423/811319798862/cells-14-00909-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fd0/12190423/a6c00d1dfbd4/cells-14-00909-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fd0/12190423/cfcbb12c455e/cells-14-00909-g004a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fd0/12190423/70d595a26e83/cells-14-00909-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fd0/12190423/50719fe710f1/cells-14-00909-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fd0/12190423/8fdc95dd8ec8/cells-14-00909-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fd0/12190423/811319798862/cells-14-00909-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fd0/12190423/a6c00d1dfbd4/cells-14-00909-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fd0/12190423/cfcbb12c455e/cells-14-00909-g004a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fd0/12190423/70d595a26e83/cells-14-00909-g005.jpg

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本文引用的文献

1
Reprogram to heal: Macrophage phenotypes as living therapeutics.重编程以实现治愈:巨噬细胞表型作为活体疗法。
Life Sci. 2025 Jun 15;371:123601. doi: 10.1016/j.lfs.2025.123601. Epub 2025 Apr 4.
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A novel calcium alginate hydrogel formulation to enhance monocyte/macrophage anti-inflammatory activity.一种新型海藻酸钙水凝胶制剂,用于增强单核细胞/巨噬细胞的抗炎活性。
Int J Biol Macromol. 2025 May;306(Pt 1):141251. doi: 10.1016/j.ijbiomac.2025.141251. Epub 2025 Feb 20.
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Are All Alginate Dressings Equivalent?所有藻酸盐敷料都等效吗?
J Biomed Mater Res B Appl Biomater. 2025 Mar;113(3):e35557. doi: 10.1002/jbm.b.35557.
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Immunomodulatory hydrogel orchestrates pro-regenerative response of macrophages and angiogenesis for chronic wound healing.免疫调节水凝胶调控巨噬细胞的促再生反应和血管生成,实现慢性伤口愈合。
Biomaterials. 2025 Mar;314:122848. doi: 10.1016/j.biomaterials.2024.122848. Epub 2024 Sep 24.
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In vitro effects of wound-dressings on key wound healing properties of dermal fibroblasts.体外敷料对真皮成纤维细胞关键伤口愈合特性的影响。
Exp Dermatol. 2024 May;33(5):e15098. doi: 10.1111/exd.15098.
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Calreticulin: a multifunctional protein with potential therapeutic applications for chronic wounds.钙网蛋白:一种对慢性伤口具有潜在治疗应用价值的多功能蛋白质。
Front Med (Lausanne). 2023 Aug 24;10:1207538. doi: 10.3389/fmed.2023.1207538. eCollection 2023.
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Transglutaminase 2 Facilitates Murine Wound Healing in a Strain-Dependent Manner.转谷氨酰胺酶 2 以应变依赖的方式促进小鼠伤口愈合。
Int J Mol Sci. 2023 Jul 14;24(14):11475. doi: 10.3390/ijms241411475.
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Cutaneous changes in diabetic patients: Primed for aberrant healing?糖尿病患者的皮肤变化:是否有利于异常愈合?
Wound Repair Regen. 2023 Sep-Oct;31(5):700-712. doi: 10.1111/wrr.13108. Epub 2023 Jul 19.
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Modulation of NK cell activation by exogenous calcium from alginate dressings .藻酸盐敷料中外源钙对 NK 细胞活化的调节作用。
Front Immunol. 2023 Apr 6;14:1141047. doi: 10.3389/fimmu.2023.1141047. eCollection 2023.
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Fine-Tuning the Endcap Chemistry of Acrylated Poly(Ethylene Glycol)-Based Hydrogels for Efficient Burn Wound Exudate Management.微调基于丙烯酸化聚乙二醇的水凝胶的端盖化学性质以实现高效烧伤创面渗出液管理
Macromol Biosci. 2023 Mar;23(3):e2200341. doi: 10.1002/mabi.202200341. Epub 2022 Dec 7.