Li Zhuqing, Bratlie Kaitlin M
Department of Materials Science & Engineering, Iowa State University, Ames, Iowa 50011, United States.
Department of Chemical & Biological Engineering, Iowa State University, Ames, Iowa 50011, United States.
ACS Appl Bio Mater. 2019 Jan 22;2(1):217-225. doi: 10.1021/acsabm.8b00562. Epub 2018 Dec 19.
In tissue engineering scaffolds, macrophages play a critical role in determining the host response to implanted biomaterials. Macrophage phenotype is dynamic throughout the host response, and a balance of phenotypes is essential for timely progression from injury to proper wound healing. Therefore, it is important to predict how materials will modulate the response of macrophages. In this study, we investigated the effect of methacrylated gellan gum (GG) hydrogels on macrophage phenotype and proliferation with the ultimate goal of improving rational design of biomedical implants. Naïve, along with classically and alternatively activated RAW 264.7 macrophages were seeded on methacrylated gellan gum hydrogels that were fabricated with different thiol-ene ratios and cross-linking mechanisms. Live/dead assays showed that all hydrogels supported cell attachment and proliferation. Stiffer substrates enhanced anti-inflammatory production of nitrites from both naïve and classically activated macrophages compared to the softer substrates. Moreover, arginine and CD206 expression-markers for alternatively activated macrophages-were inhibited by higher thiol content. Introducing ionic cross-links using calcium did not influence the proliferation or polarization for any of the three macrophage phenotypes. Our results suggest that the macrophage phenotype shift from M1 to M2 is controlled by the different cross-linking mechanisms, physical properties, and the chemistry of methacrylated gellan gum hydrogels.
在组织工程支架中，巨噬细胞在决定宿主对植入生物材料的反应方面起着关键作用。巨噬细胞表型在整个宿主反应过程中是动态变化的，表型平衡对于从损伤及时进展到适当的伤口愈合至关重要。因此，预测材料如何调节巨噬细胞的反应很重要。在本研究中，我们研究了甲基丙烯酸化结冷胶（GG）水凝胶对巨噬细胞表型和增殖的影响，最终目标是改进生物医学植入物的合理设计。将未激活的以及经典激活和替代激活的RAW 264.7巨噬细胞接种在以不同硫醇-烯比例和交联机制制备的甲基丙烯酸化结冷胶水凝胶上。活/死检测表明，所有水凝胶都支持细胞附着和增殖。与较软的底物相比，较硬的底物增强了未激活的和经典激活的巨噬细胞产生亚硝酸盐的抗炎能力。此外，较高的硫醇含量抑制了替代激活的巨噬细胞的精氨酸和CD206表达标记。使用钙引入离子交联对三种巨噬细胞表型中的任何一种的增殖或极化都没有影响。我们的结果表明，巨噬细胞从M1到M2表型的转变受甲基丙烯酸化结冷胶水凝胶的不同交联机制、物理性质和化学性质的控制。
