Department of Obstetrics and Gynecology, University Hospital Augsburg, Stenglinstrasse 2, Augsburg 86156, Germany.
Department of Pathology, University Hospital Augsburg, Stenglinstrasse 2, Augsburg 86156, Germany.
Acta Biomater. 2023 Oct 1;169:363-371. doi: 10.1016/j.actbio.2023.08.018. Epub 2023 Aug 13.
It is well known that pelvic organ prolapse (POP) significantly reduces the quality of life of affected women and in many cases requires corrective surgery. Aim of the study was to compare the immune response against titanized versus non-titanized meshes, especially macrophage polarization and immune checkpoint association. For this, we analyzed 644 POP surgeries, which were performed between 2017 and 2022, in our department. Four of them needed revision surgery caused by erosion. We analyzed the influx of CD68 & CD163 positive macrophages and the expression of immune checkpoint molecules PD-L1 and PD1 in these 4 patients. We identified a large number of CD68 and CD163 positive macrophages and additionally a PD-L1 expression of these cells. Based on the in-vivo results, we isolated monocytes and co-cultivated monocytes with different mesh material covered with or without fibroblasts. We identified a significantly enhanced macrophage activation and PD-L1 expression in macrophages surrounding non-titanized polypropylene mesh material. Encapsulation of the material by fibroblasts was crucial for that. Specifically, CD68-positive macrophages are upregulated (p < 0.001), co-expressing PD-L1 (p < 0.001) in monocytes co-cultivated with non-titanized polypropylene meshes. Monocytes co-cultivated with titanized polypropylene meshes showed significantly lower expression of CD163 (p = 0.027) and PD-L1 (p = 0.022). In conclusion, our in vitro data suggest that the titanium coating leads to a decreased polarization of macrophages and to a decreased immune response compared to non-titanized meshes. This could be an indication for the increased incidence of erosion of the non-titanized meshes, which is a severe complication of this procedure and requires revision surgery. STATEMENT OF SIGNIFICANCE: Pelvic organ prolapse is a well-known problem for women and often requires corrective surgery. Polypropylene meshes are often used, which differ in their coating (titanized vs. non-titanized). A severe side effect of these surgeries is mesh erosion, due to onset of inflammation, which requires revision surgery. We examined all erosion cases (4 of 644 patients) with implanted nontitanium-coated meshes by immunohistochemistry and found upregulation of macrophage polarization (as markers CD68 and CD163) and increased expression of the immune checkpoint molecules PD-L1 and PD1. This suggests inflammatory processes and an enhanced immune response. In addition, we set up an in vitro experiment to investigate whether coating plays a role. Here, we demonstrated that the non-titanized meshes elicited a significantly higher immune response in comparison to titanized meshes, which could lead to the higher erosion rate of the non-titanized meshes. Our results highlight the benefit of titanized meshes, which should lead to a lower revision surgery rate and thus improved patient outcome.
众所周知，盆腔器官脱垂（POP）显著降低了受影响女性的生活质量，在许多情况下需要进行矫正手术。本研究旨在比较钛化与非钛化网片的免疫反应，特别是巨噬细胞极化和免疫检查点关联。为此，我们分析了我们科室在 2017 年至 2022 年间进行的 644 例 POP 手术，其中 4 例因侵蚀而需要进行翻修手术。我们分析了这 4 名患者中 CD68 和 CD163 阳性巨噬细胞的流入以及免疫检查点分子 PD-L1 和 PD1 的表达。我们发现大量 CD68 和 CD163 阳性巨噬细胞，并且这些细胞的 PD-L1 表达增加。基于体内结果，我们分离了单核细胞，并将单核细胞与不同的网片材料共培养，这些网片材料覆盖有或没有成纤维细胞。我们发现非钛化聚丙烯网片材料周围的巨噬细胞的激活和 PD-L1 表达明显增强。成纤维细胞对材料的包裹至关重要。具体来说，与非钛化聚丙烯网片共培养的单核细胞中 CD68 阳性巨噬细胞的表达上调（p<0.001），并共表达 PD-L1（p<0.001）。与钛化聚丙烯网片共培养的单核细胞中 CD163（p=0.027）和 PD-L1（p=0.022）的表达明显降低。总之，我们的体外数据表明，与非钛化网片相比，钛涂层导致巨噬细胞极化减少和免疫反应降低。这可能表明非钛化网片的侵蚀发生率增加，这是该手术的严重并发症，需要进行翻修手术。 意义声明：盆腔器官脱垂是女性的一个已知问题，通常需要进行矫正手术。聚丙烯网片经常被使用，它们的涂层不同（钛化与非钛化）。这些手术的一个严重副作用是由于炎症引起的网片侵蚀，这需要进行翻修手术。我们通过免疫组织化学检查了所有植入非钛化网片的侵蚀病例（644 例患者中的 4 例），发现巨噬细胞极化（作为标记物 CD68 和 CD163）上调和免疫检查点分子 PD-L1 和 PD1 的表达增加。这表明存在炎症过程和增强的免疫反应。此外，我们进行了一项体外实验来研究涂层是否起作用。在这里，我们证明与钛化网片相比，非钛化网片引起的免疫反应明显更高，这可能导致非钛化网片的侵蚀率更高。我们的结果强调了钛化网片的优势，这应该会降低翻修手术率，从而改善患者的预后。
