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Nano-particle mediated M2 macrophage polarization enhances bone formation and MSC osteogenesis in an IL-10 dependent manner.
Biomaterials ( IF 12.8 ) Pub Date : 2020-01-31 , DOI: 10.1016/j.biomaterials.2020.119833 Olwyn R Mahon 1 , David C Browe 2 , Tomas Gonzalez-Fernandez 3 , Pierluca Pitacco 2 , Ian T Whelan 4 , Stanislas Von Euw 2 , Christopher Hobbs 5 , Valeria Nicolosi 5 , Kyle T Cunningham 6 , Kingston H G Mills 6 , Daniel J Kelly 7 , Aisling Dunne 8
Biomaterials ( IF 12.8 ) Pub Date : 2020-01-31 , DOI: 10.1016/j.biomaterials.2020.119833 Olwyn R Mahon 1 , David C Browe 2 , Tomas Gonzalez-Fernandez 3 , Pierluca Pitacco 2 , Ian T Whelan 4 , Stanislas Von Euw 2 , Christopher Hobbs 5 , Valeria Nicolosi 5 , Kyle T Cunningham 6 , Kingston H G Mills 6 , Daniel J Kelly 7 , Aisling Dunne 8
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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.
中文翻译：
纳米粒子介导的M2巨噬细胞极化以IL-10依赖性方式增强骨形成和MSC成骨作用。
在支架植入后进行前再生免疫应答是功能组织再生不可或缺的部分。对植入的生物材料的免疫反应取决于多种因素，包括生物物理线索，例如材料硬度，形貌和粒径。在这项研究中，我们开发了一种用于骨缺损愈合的免疫调节支架，其中包含模拟骨的纳米羟基磷灰石颗粒（BMnP）。我们首先证明，与市售的微米级羟基磷灰石颗粒相反，内部产生的BMnP优先将人类巨噬细胞极化为M2型，激活转录因子cMaf并特别增强抗炎细胞因子IL-10的产生。此外，纳米颗粒处理的巨噬细胞在体外增强间充质干细胞（MSC）的成骨作用，并且这种作用以IL-10依赖性的方式发生，这表明该细胞因子具有直接的促成骨作用。BMnP还能够在人类巨噬细胞和HUVEC中驱动促血管生成反应。将功能化支架整合到大鼠股骨缺损模型中后，免疫细胞亚群的表征显示出相似的特征，微米大小的羟基磷灰石功能化支架引发促炎性反应，其特征是与BMnP功能化支架相比，T细胞浸润且M1巨噬细胞标记物表达升高。促进M2巨噬细胞极化，组织血管形成和增加骨量。
更新日期：2020-01-31
中文翻译：
纳米粒子介导的M2巨噬细胞极化以IL-10依赖性方式增强骨形成和MSC成骨作用。
在支架植入后进行前再生免疫应答是功能组织再生不可或缺的部分。对植入的生物材料的免疫反应取决于多种因素，包括生物物理线索，例如材料硬度，形貌和粒径。在这项研究中，我们开发了一种用于骨缺损愈合的免疫调节支架，其中包含模拟骨的纳米羟基磷灰石颗粒（BMnP）。我们首先证明，与市售的微米级羟基磷灰石颗粒相反，内部产生的BMnP优先将人类巨噬细胞极化为M2型，激活转录因子cMaf并特别增强抗炎细胞因子IL-10的产生。此外，纳米颗粒处理的巨噬细胞在体外增强间充质干细胞（MSC）的成骨作用，并且这种作用以IL-10依赖性的方式发生，这表明该细胞因子具有直接的促成骨作用。BMnP还能够在人类巨噬细胞和HUVEC中驱动促血管生成反应。将功能化支架整合到大鼠股骨缺损模型中后，免疫细胞亚群的表征显示出相似的特征，微米大小的羟基磷灰石功能化支架引发促炎性反应，其特征是与BMnP功能化支架相比，T细胞浸润且M1巨噬细胞标记物表达升高。促进M2巨噬细胞极化，组织血管形成和增加骨量。
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