间充质干细胞
巨噬细胞极化
免疫系统
材料科学
细胞因子
细胞生物学
脚手架
再生(生物学)
巨噬细胞
组织工程
体外
骨愈合
生物医学工程
免疫学
化学
生物
医学
解剖
生物化学
作者
Olwyn R. Mahon,David C. Browe,Tomas Gonzalez‐Fernandez,Pierluca Pitacco,I. Whelan,Stanislas Von Euw,Christopher Hobbs,Valeria Nicolosi,Kyle T. Cunningham,Kingston H. G. Mills,Daniel J. Kelly,Aisling Dunne
出处
期刊:Biomaterials
[Elsevier]
日期:2020-05-01
卷期号:239: 119833-119833
被引量:239
标识
DOI:10.1016/j.biomaterials.2020.119833
摘要
Engineering a pro-regenerative immune response following scaffold implantation is integral to functional tissue regeneration. The immune response to implanted biomaterials is determined by multiple factors, including biophysical cues such as material stiffness, topography and particle size. In this study we developed an immune modulating scaffold for bone defect healing containing bone mimetic nano hydroxyapatite particles (BMnP). We first demonstrate that, in contrast to commercially available micron-sized hydroxyapatite particles, in-house generated BMnP preferentially polarize human macrophages towards an M2 phenotype, activate the transcription factor cMaf and specifically enhance production of the anti-inflammatory cytokine, IL-10. Furthermore, nano-particle treated macrophages enhance mesenchymal stem cell (MSC) osteogenesis in vitro and this occurs in an IL-10 dependent manner, demonstrating a direct pro-osteogenic role for this cytokine. BMnPs were also capable of driving pro-angiogenic responses in human macrophages and HUVECs. Characterization of immune cell subsets following incorporation of functionalized scaffolds into a rat femoral defect model revealed a similar profile, with micron-sized hydroxyapatite functionalized scaffolds eliciting pro-inflammatory responses characterized by infiltrating T cells and elevated expression of M1 macrophages markers compared to BMnP functionalized scaffolds which promoted M2 macrophage polarization, tissue vascularization and increased bone volume. Taken together these results demonstrate that nano-sized Hydroxyapatite has immunomodulatory potential and is capable of directing anti-inflammatory innate immune-mediated responses that are associated with tissue repair and regeneration.
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