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纤维涂层聚丙烯网片负载基质金属蛋白酶抑制剂GM6001对伤口愈合的影响:对疝修补术的启示

Influence of MMP inhibitor GM6001 loading of fibre coated polypropylene meshes on wound healing: Implications for hernia repair.

作者信息

Böhm Gabriele, Groll Jürgen, Heffels Karl-Heinz, Heussen Nicole, Ink Peter, Alizai Hamid Patrick, Neumann Ulf Peter, Schnabel Reinhild, Mirastschijski Ursula

机构信息

1 Department of General and Visceral Surgery, 62546 Klinikum Bremen-Ost , Bremen, Germany.

2 Department of General-, Visceral- and Transplant Surgery, University Hospital, Technical University of Aachen (RWTH), Germany.

出版信息

J Biomater Appl. 2018 May;32(10):1343-1359. doi: 10.1177/0885328218759043. Epub 2018 Feb 21.


DOI:10.1177/0885328218759043
PMID:29466900
Abstract

Polypropylene meshes are standard for hernia repair. Matrix metalloproteinases play a central role in inflammation. To reduce the inflammatory response and improve remodelling with an associated reduction of hernia recurrence, we modified polypropylene meshes by nanofibre coating and saturation with the broad-spectrum matrix metalloproteinase inhibitor GM6001. The aim was to modulate the inflammatory reaction, increase collagen deposition and improve mesh biointegration. Polypropylene meshes were surface-modified with star-configured NCO-sP(EO -stat-PO) and covered with electrospun nanofibres (polypropylene-nano) and GM6001 (polypropylene-nano-GM). In a hernia model, defects were reconstructed with one of the meshes. Inflammation, neovascularization, bio-integration, proliferation and apoptosis were assessed histologically, collagen content and gelatinases biochemically. Mesh surface modification resulted in higher inflammatory response compared to polypropylene. Pro-inflammatory matrix metalloproteinase-9 paralleled findings while GM6001 reduced matrix metalloproteinase-9 significantly. Significantly increased matrix metalloproteinase-2 beneficial for remodelling was noted with polypropylene-nano-meshes. Increased vascular endothelial growth factor, neo-vascularization and collagen content were measured in polypropylene-nano-meshes compared to polypropylene. GM6001 significantly reduced myofibroblasts. This effect ended after d14 due to engineering limitations with release of maximal GM6001 loading. Nanofibre-coating of polypropylene-meshes confers better tissue vascularization to the cost of increased inflammation. This phenomenon can be only partially compensated by GM6001. Future research will enable higher GM6001 uptake in nano-coated meshes and may alter mesh biointegration in a more pronounced way.

摘要

聚丙烯网片是疝气修补的标准材料。基质金属蛋白酶在炎症中起核心作用。为了减少炎症反应并改善重塑过程,同时降低疝气复发率,我们通过纳米纤维涂层和用广谱基质金属蛋白酶抑制剂GM6001进行饱和处理来对聚丙烯网片进行改性。目的是调节炎症反应,增加胶原蛋白沉积并改善网片的生物整合。聚丙烯网片用星形配置的NCO-sP(EO -stat-PO)进行表面改性,并用静电纺丝纳米纤维(聚丙烯-纳米)和GM6001(聚丙烯-纳米-GM)覆盖。在疝气模型中,用其中一种网片修复缺损。通过组织学评估炎症、新血管形成、生物整合、增殖和凋亡,通过生化方法评估胶原蛋白含量和明胶酶。与聚丙烯相比,网片表面改性导致更高的炎症反应。促炎基质金属蛋白酶-9的情况与之相似,而GM6001显著降低了基质金属蛋白酶-9。在用聚丙烯-纳米网片时,发现对重塑有益的基质金属蛋白酶-2显著增加。与聚丙烯相比,聚丙烯-纳米网片中测量到血管内皮生长因子增加、新血管形成和胶原蛋白含量增加。GM6001显著减少了肌成纤维细胞。由于工程限制,最大GM6001负载量释放后,这种效果在第14天结束。聚丙烯网片的纳米纤维涂层以增加炎症为代价赋予更好的组织血管化。这种现象只能通过GM6001部分得到补偿。未来的研究将使纳米涂层网片中GM6001的摄取量更高,并可能以更显著的方式改变网片的生物整合。

相似文献

[1]
Influence of MMP inhibitor GM6001 loading of fibre coated polypropylene meshes on wound healing: Implications for hernia repair.

J Biomater Appl. 2018-5

[2]
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[3]
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[4]
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J Biomed Mater Res B Appl Biomater. 2017-10-10

[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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引用本文的文献

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[3]
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[4]
Development of nanotechnology for advancement and application in wound healing: a review.

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[5]
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