In vitro response of macrophages to ceramic scaffolds used for bone regeneration
In vitro response of macrophages to ceramic scaffolds used for bone regeneration
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DOI：
10.1098/rsif.2016.0346
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发表时间：
2016-07-01
影响因子：
3.9
通讯作者：
Spiller, Kara L.
中科院分区：
文献类型：
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作者：
Graney, Pamela L.;Roohani-Esfahani, Seyed-Iman;Spiller, Kara L.
巨噬细胞是炎症反应的主要细胞，是愈合的主要调节因子，并介导骨折愈合和对植入生物材料的炎症反应。然而，它们对生物材料介导的骨修复的表型贡献还不完全清楚。因此，我们使用基因表达和蛋白质分泌分析，以调查之间的相互作用，在体外原代人单核细胞衍生的巨噬细胞和陶瓷支架，已被证明有不同程度的成功，在体内促进骨再生。具体而言，选择钙锆石（Ca 3 ZrSi 2 O 9）和锶硬硅钙石锌尖晶石（SrCa 2 ZnSi 2 O 7-ZnAl 2 O 4）支架作为两种材料，与临床使用的磷酸三钙羟基磷灰石（TCP HA）相比，在负载下在体内大缺损中增强骨再生。主成分分析显示，支架差异调节巨噬细胞表型。基因表达的时间变化包括促炎M1、抗炎M2 a和促重塑M2 c巨噬细胞表型标志物的变化。值得注意的是，TCP HA支架促进了许多M1相关基因的上调和许多M2 a和M2 c相关基因的下调。支架对巨噬细胞的影响主要归因于直接的细胞支架相互作用，因为在transwell培养中仅观察到微小的变化。最终，阐明巨噬细胞生物材料的相互作用将有助于设计用于骨修复的免疫调节生物材料。
Macrophages, the primary cells of the inflammatory response, are major regulators of healing, and mediate both bone fracture healing and the inflammatory response to implanted biomaterials. However, their phenotypic contributions to biomaterial-mediated bone repair are incompletely understood. Therefore, we used gene expression and protein secretion analysis to investigate the interactions in vitro between primary human monocyte-derived macrophages and ceramic scaffolds that have been shown to have varying degrees of success in promoting bone regeneration in vivo. Specifically, baghdadite (Ca3ZrSi2O9) and strontium hardystonite gahnite (Sr Ca2ZnSi2O7-ZnAl2O4) scaffolds were chosen as two materials that enhanced bone regeneration in vivo in large defects under load compared with clinically used tricalcium phosphate hydroxyapatite (TCP HA). Principal component analysis revealed that the scaffolds differentially regulated macrophage phenotype. Temporal changes in gene expression included shifts in markers of pro-inflammatory M1, anti-inflammatory M2a and pro-remodelling M2c macrophage phenotypes. Of note, TCP HA scaffolds promoted upregulation of many M1-related genes and downregulation of many M2a- and M2c-related genes. Effects of the scaffolds on macrophages were attributed primarily to direct cell scaffold interactions because of only minor changes observed in transwell culture. Ultimately, elucidating macrophage biomaterial interactions will facilitate the design of immunomodulatory biomaterials for bone repair.