Controlled M1-to-M2 transition of aged macrophages by calcium phosphate coatings.

Controlled M1-to-M2 transition of aged macrophages by calcium phosphate coatings.
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DOI:
10.1016/j.biomaterials.2018.07.012
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发表时间:
2019-03
期刊:
影响因子:
14
通讯作者:
Kuhn LT
Kuhn LT
中科院分区:
工程技术1区
文献类型:
--
作者:
Alhamdi JR;Peng T;Al-Naggar IM;Hawley KL;Spiller KL;Kuhn LT

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由于骨细胞和免疫系统的年龄相关变化,老年人的骨愈合能力减弱和延迟。鉴于免疫系统和骨骼细胞之间的相互作用,需要解决骨骼和免疫系统缺陷的疗法来有效治疗老年患者的骨损伤。在健康组织修复中观察到的巨噬细胞活化的顺序涉及从促炎状态到促修复状态的转变。在老年患者中,炎症消退较慢并阻碍愈合。本研究的目的是设计一种新型的药物输送系统,用于使用骨移植材料对巨噬细胞极化进行时间引导。仿生磷酸钙涂层(bCaP)在物理和时间上将促炎刺激干扰素-γ(IFNγ)与促修复刺激辛伐他汀(SIMV)分开。使用人单核细胞系(THP-1)鉴定有效剂量,并使用从老年小鼠获得的骨髓巨噬细胞进行测试。使用两种细胞类型实现了M1至M2的顺序活化。这些结果表明,这种新型的免疫调节药物递送系统具有控制老年患者骨骼中巨噬细胞活化的潜力。
Older adults suffer from weakened and delayed bone healing due to age-related alterations in bone cells and in the immune system. Given the interaction between the immune system and skeletal cells, therapies that address deficiencies in both the skeletal and the immune system are required to effectively treat bone injuries of older patients. The sequence of macrophage activation observed in healthy tissue repair involves a transition from a pro-inflammatory state followed by a pro-reparative state. In older patients, inflammation is slower to resolve and impedes healing. The goal of this study was to design a novel drug delivery system for temporal guidance of the polarization of macrophages using bone grafting materials. A biomimetic calcium phosphate coating (bCaP) physically and temporally separated the pro-inflammatory stimulus interferon-gamma (IFNγ) from the pro-reparative stimulus simvastatin (SIMV). Effective doses were identified using a human monocyte line (THP-1) and testing culminated with bone marrow macrophages obtained from old mice. Sequential M1-to-M2 activation was achieved with both cell types. These results suggest that this novel immunomodulatory drug delivery system holds potential for controlling macrophage activation in bones of older patients.
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