Micro- and Nanopatterned Topographical Cues for Regulating Macrophage Cell Shape and Phenotype.
Micro- and Nanopatterned Topographical Cues for Regulating Macrophage Cell Shape and Phenotype.
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DOI：
10.1021/acsami.5b10589
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发表时间：
2015-12-30
影响因子：
9.5
通讯作者：
Liu WF
中科院分区：
文献类型：
--
作者：
Luu TU;Gott SC;Woo BW;Rao MP;Liu WF
控制巨噬细胞和生物材料之间的相互作用对于调节对植入物的反应至关重要。虽然长期以来人们一直认为生物材料的表面化学调节免疫反应，但最近的研究表明，材料的几何形状实际上可能占主导地位。我们之前的研究表明，巨噬细胞的伸长调节其向促进愈合表型的极化。在这项工作中，我们阐明了如何利用表面拓扑来改变巨噬细胞的形态和极化状态。使用深度蚀刻技术，我们制造了含有微和纳米图案凹槽的钛表面，这些凹槽先前已被证明可以促进细胞伸长。分析了小鼠骨髓源性巨噬细胞在不同凹槽宽度下的形态、表型标记和细胞因子分泌情况。结果表明，微和纳米图案的凹槽影响巨噬细胞的延伸，在400-500 nm宽的基质上达到峰值。表面凹槽不影响炎症激活，但驱使巨噬细胞向抗炎、促愈合表型发展。尽管巨噬细胞在所有条件下的tnf - α分泌水平都很低，但与其他Ti表面的细胞相比，巨噬细胞在中间凹槽宽度上分泌的抗炎细胞因子IL-10水平明显较高。我们的研究结果强调了利用表面形貌来调节巨噬细胞功能的潜力，从而控制伤口愈合和组织修复对生物材料的反应。
Controlling the interactions between macrophages and biomaterials is critical for modulating the response to implants. While it has long been thought that biomaterial surface chemistry regulates the immune response, recent studies have suggested that material geometry may in fact dominate. Our previous work demonstrated that elongation of macrophages regulates their polarization towards a pro-healing phenotype. In this work, we elucidate how surface topology might be leveraged to alter macrophage cell morphology and polarization state. Using a deep etch technique, we fabricated titanium surfaces containing micro and nano-patterned grooves, which have been previously shown to promote cell elongation. Morphology, phenotypic markers, and cytokine secretion of murine bone marrow derived macrophages on different groove widths were analyzed. The results suggest that micro and nano-patterned grooves influenced macrophage elongation, which peaked on substrates with 400-500 nm wide grooves. Surface grooves did not affect inflammatory activation, but drove macrophages towards an anti-inflammatory, pro-healing phenotype. While secretion of TNF-alpha remained low in macrophages across all conditions, macrophages secreted significantly higher levels of anti-inflammatory cytokine, IL-10, on intermediate groove widths compared to cells on other Ti surfaces. Our findings highlight the potential of using surface topography to regulate macrophage function, and thus control the wound healing and tissue repair response to biomaterials.