The effect of osteoimmunomodulation on the osteogenic effects of cobalt incorporated β-tricalcium phosphate
The effect of osteoimmunomodulation on the osteogenic effects of cobalt incorporated β-tricalcium phosphate
复制标题
骨免疫调节对钴掺入的β-磷酸三钙的成骨作用的影响
DOI：
10.1016/j.biomaterials.2015.04.044
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发表时间：
2015-08-01
期刊：
影响因子：
14
通讯作者：
Xiao, Yin
中科院分区：
文献类型：
--
作者：
Chen, Zetao;Yuen, Jones;Xiao, Yin
成骨细胞系是成骨的直接效应器，因此，通常用于评估骨替代材料的体外成骨能力。这种方法在测试新型骨生物材料时已经达到了它的目的；然而，体外和体内研究结果不一致，表明控制材料介导成骨能力的机制尚不清楚。骨免疫学和免疫调节这一新兴领域已经使我们对骨生物材料的看法发生了范式转变，从惰性材料转变为骨免疫调节材料，突出了免疫细胞在材料介导的成骨过程中的重要性。在这一过程中忽视免疫反应的重要性是目前评估方案的一个主要缺点。在这项研究中，我们评估了一种潜在的血管生成骨替代材料钴结合β -磷酸三钙（CCP），比较了传统的“一种细胞类型”方法和“多细胞类型”方法来评估成骨，后者包括使用免疫细胞。我们发现CCP提取物本身足以促进骨髓干细胞（BMSCs）的成骨分化，而当巨噬细胞参与时，这种作用被抵消。在CCP的反应中，巨噬细胞表型切换到M1极端，释放促炎细胞因子和骨分解代谢因子。当CCP材料植入大鼠股骨髁缺损模型时，炎症标志物和骨破坏明显增加，并伴有纤维包封，而不是新骨形成。这些发现表明，在体外评估中纳入免疫细胞（巨噬细胞）与体内组织反应相匹配，并且该方法在体外评估材料刺激成骨时更准确地表明免疫细胞的重要作用。(C) 2015 Elsevier Ltd.版权所有。
Osteoblast lineage cells are direct effectors of osteogenesis and are, therefore, commonly used to evaluate the in vitro osteogenic capacity of bone substitute materials. This method has served its purposes when testing novel bone biomaterials; however, inconsistent results between in vitro and in vivo studies suggest the mechanisms that govern a material's capacity to mediate osteogenesis are not well understood. The emerging field of osteoimmunology and immunomodulation has informed a paradigm shift in our view of bone biomaterials from one of an inert to an osteoimmunomodulatory material highlighting the importance of immune cells in materials-mediated osteogenesis. Neglecting the importance of the immune response during this process is a major shortcoming of the current evaluation protocol. In this study we evaluated a potential angiogenic bone substitute material cobalt incorporated with beta-tricalcium phosphate (CCP), comparing the traditional "one cell type" approach with a "multiple cell types" approach to assess osteogenesis, the latter including the use of immune cells. We found that CCP extract by itself was sufficient to enhance osteogenic differentiation of bone marrow stem cells (BMSCs), whereas this effect was cancelled out when macrophages were involved. In response to CCP, the macrophage phenotype switched to the M1 extreme, releasing pro-inflammatory cytokines and bone catabolic factors. When the CCP materials were implanted into a rat femur condyle defect model, there was a significant increase of inflammatory markers and bone destruction, coupled with fibrous encapsulation rather than new bone formation. These findings demonstrated that the inclusion of immune cells (macrophages) in the in vitro assessment matched the in vivo tissue response, and that this method provides a more accurate indication of the essential role of immune cells when assessing materials-stimulated osteogenesis in vitro. (C) 2015 Elsevier Ltd. All rights reserved.