Macrophage phenotype switch by sequential action of immunomodulatory cytokines from hydrogel layers on titania nanotubes
Macrophage phenotype switch by sequential action of immunomodulatory cytokines from hydrogel layers on titania nanotubes
复制标题
通过二氧化钛纳米管上水凝胶层的免疫调节细胞因子的连续作用来改变巨噬细胞表型
DOI：
10.1016/j.colsurfb.2018.01.007
复制
发表时间：
2018-03-01
影响因子：
5.8
通讯作者：
Feng, Bo
中科院分区：
文献类型：
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作者：
Chen, Junhong;Li, Mengting;Feng, Bo
植入后组织与植入物之间发生的炎症反应可引起局部组织坏死，甚至导致植入物失效，因此受到越来越多的关注。巨噬细胞在炎症的各个阶段都起着关键作用。促炎（M1）和抗炎（M2）巨噬细胞包括两种主要表型，并且在特定时间点从M1到M2的转换对于伤口愈合和组织再生是重要的。因此，我们假设能够促进巨噬细胞表型转换的生物材料系统应该能够减轻炎症并促进愈合。为此，在二氧化钛纳米管（TNT）上制备双水凝胶层系统作为储库以调节白细胞介素-4（IL-4）和干扰素-γ（IFN-γ）的释放。在该系统中，IL-4（一种抗炎细胞因子）被装载在TNT中，IFN-γ（一种促炎细胞因子）位于壳聚糖/β-甘油磷酸二钠和羧甲基壳聚糖/京尼平的两个水凝胶层之间。IFN-γ在3天内快速释放，而IL-4表现出持续释放曲线。在与间充质干细胞和巨噬细胞的培养中，该系统显示出良好的细胞相容性，并显着促进细胞增殖。用ELISA、流式细胞仪和PCR检测巨噬细胞表型转换。结果表明，从系统释放的IFN-γ在3天内刺激巨噬细胞向M1转换，而持续释放的IL-4在4天后使巨噬细胞向M2极化。该系统可通过两种细胞因子的顺序作用调节巨噬细胞表型从M1向M2的转换，可用于研究组织与植入物之间的免疫反应。本研究也为功能性生物材料的设计提供了新的思路。(C)2018 Elsevier B. V.版权所有。
Inflammatory response occurring between tissues and implants after implantation has attracted increasing attention because it can cause local tissue necrosis and even implant failure. Macrophages play a key role in all stages ofinflammation. Pro-inflammatory (M1) and anti-inflammatory (M2) macrophages comprise two main phenotypes and the switch from M1 to M2 at specific time points is important for wound healing and tissue regeneration. Therefore, we hypothesized that biotnaterial systems capable of facilitating macrophage phenotype switching should attenuate inflammation and enhance healing. To this end, a system of double hydrogel layers on titania nanotubes (TNT) was prepared as reservoir to modulate the release of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma). In this system, IL-4, an anti-inflammatory cytokine, was loaded in TNT and IFN-gamma, a pro-inflammatory cytokine, was located between two hydrogel layers of chitosan/beta-glycerophosphate disodium and carboxymethyl chitosan/genipin. IFN-gamma released rapidly in 3 days, whereas IL-4 exhibited a sustained release profile. In culture with mesenchymal stem cells and macrophages, this system displayed good cytocompatibility and significantly promoted cell proliferation. Macrophage phenotype switch was determined by ELISA, FACS and PCR. The results manifested that IFN-gamma released from the system stimulated switching of macrophages to M1 in 3 days, whereas sustained release of IL-4 polarized macrophages to M2 after 4 days. This system can modulate macrophage phenotype switching from M1 to M2 by sequential action of the two cytokines, and might be used to research immune response between tissues and implants. The present study also provided a novel strategy for designing functional biomaterials. (C) 2018 Elsevier B.V. All rights reserved.