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载有缓释大麻二酚清漆的聚乙醇酸910网片抑制生物膜形成和巨噬细胞细胞因子分泌:一项体外研究。

Polyglactin 910 Meshes Coated with Sustained-Release Cannabigerol Varnish Inhibit Biofilm Formation and Macrophage Cytokine Secretion: An In Vitro Study.

作者信息

Abudalu Mustafa, Aqawi Muna, Sionov Ronit Vogt, Friedman Michael, Gati Irith, Munz Yaron, Ohana Gil, Steinberg Doron

机构信息

The Biofilm Research Laboratory, The Institute of Biomedical and Oral Research (IBOR), The Faculty of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel.

Department of General Surgery, Barzilai Medical Center, Ashkelon 7830604, Israel.

出版信息

Pharmaceuticals (Basel). 2023 May 13;16(5):745. doi: 10.3390/ph16050745.

Abstract

Synthetic surgical meshes are commonly used in abdominal wall reconstruction surgeries to strengthen a weak abdominal wall. Common mesh-related complications include local infection and inflammatory processes. Because cannabigerol (CBG) has both antibacterial and anti-inflammatory properties, we proposed that coating VICRYL (polyglactin 910) mesh with a sustained-release varnish (SRV) containing CBG would prevent these complications. We used an in vitro infection model with and an in vitro inflammation model of lipopolysaccharide (LPS)-stimulated macrophages. Meshes coated with either SRV-placebo or SRV-CBG were exposed daily to in tryptic soy medium (TSB) or macrophage Dulbecco's modified eagle medium (DMEM). Bacterial growth and biofilm formation in the environment and on the meshes were assessed by changes in optical density, bacterial ATP content, metabolic activity, crystal violet staining, spinning disk confocal microscopy (SDCM), and high-resolution scanning electron microscopy (HR-SEM). The anti-inflammatory effect of the culture medium that was exposed daily to the coated meshes was analyzed by measuring the release of the cytokines IL-6 and IL-10 from LPS-stimulated RAW 264.7 macrophages with appropriate ELISA kits. Additionally, a cytotoxicity assay was performed on Vero epithelial cell lines. We observed that compared with SRV-placebo, the segments coated with SRV-CBG inhibited the bacterial growth of in the mesh environment for 9 days by 86 ± 4% and prevented biofilm formation and metabolic activity in the surroundings for 9 days, with respective 70 ± 2% and 95 ± 0.2% reductions. The culture medium that was incubated with the SRV-CBG-coated mesh inhibited LPS-induced secretion of IL-6 and IL-10 from the RAW 264.7 macrophages for up to 6 days without affecting macrophage viability. A partial anti-inflammatory effect was also observed with SRV-placebo. The conditioned culture medium was not toxic to Vero epithelial cells, which had an IC of 25 µg/mL for CBG. In conclusion, our data indicate a potential role of coating VICRYL mesh with SRV-CBG in preventing infection and inflammation in the initial period after surgery.

摘要

合成外科补片常用于腹壁重建手术,以加固薄弱的腹壁。常见的与补片相关的并发症包括局部感染和炎症反应。由于大麻二酚(CBG)具有抗菌和抗炎特性,我们提出用含CBG的缓释清漆(SRV)涂覆薇乔(聚乙醇酸910)补片可预防这些并发症。我们使用了体外感染模型以及脂多糖(LPS)刺激巨噬细胞的体外炎症模型。将涂有SRV安慰剂或SRV-CBG的补片每天置于胰蛋白胨大豆培养基(TSB)或巨噬细胞杜尔贝科改良伊格尔培养基(DMEM)中。通过光密度变化、细菌ATP含量、代谢活性、结晶紫染色、转盘共聚焦显微镜(SDCM)和高分辨率扫描电子显微镜(HR-SEM)评估环境和补片上的细菌生长及生物膜形成。通过使用合适的ELISA试剂盒测量LPS刺激的RAW 264.7巨噬细胞中细胞因子IL-6和IL-10的释放,分析每天暴露于涂覆补片的培养基的抗炎作用。此外,对Vero上皮细胞系进行了细胞毒性试验。我们观察到,与SRV安慰剂相比,涂有SRV-CBG的部分在补片环境中对金黄色葡萄球菌的细菌生长抑制9天,抑制率为86±4%,并在9天内防止周围环境中的生物膜形成和代谢活性,分别降低70±2%和95±0.2%。与涂有SRV-CBG补片一起孵育的培养基在长达6天的时间内抑制RAW 264.7巨噬细胞中LPS诱导的IL-6和IL-10分泌,而不影响巨噬细胞活力。SRV安慰剂也观察到部分抗炎作用。条件培养基对Vero上皮细胞无毒,CBG对其半数抑制浓度为25μg/mL。总之,我们的数据表明用SRV-CBG涂覆薇乔补片在预防术后初期感染和炎症方面具有潜在作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/498e/10221007/251c6ea0f535/pharmaceuticals-16-00745-g001.jpg

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