巨噬细胞在疏水修饰的水凝胶上的粘附和表型转移

Zihao Xu, Dohgyu Hwang, Michael D. Bartlett, Shan Jiang, K. Bratlie
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引用次数: 0

摘要

巨噬细胞表型的平衡是成功植入的必要条件。因此,应精心设计生物材料,以更好地调节巨噬细胞的反应。我们证明巨噬细胞粘附和表型转移可以通过疏水修饰的水凝胶进行调节。本研究提出了利用底物疏水性控制细胞粘附和分化的基本概念。以甲基丙烯酸结冷胶(MGG)为原料,通过光引发的巯基烯原位聚合交联制备凝胶。通过将不同长度的疏水分支连接到MGG上来控制其疏水程度。仔细控制附着,使水凝胶压缩模量不受疏水改性的影响。与未改性的MGG相比,改性后的MGG水凝胶的水接触角增大,溶胀率降低。随后将幼稚和活化的巨噬细胞播种在具有不同表面润湿性的水凝胶上。细胞的增殖和扩散随着表面疏水性的增加而增加。水凝胶表面与疏水探针的粘附量随底物疏水性的增加而增加。这表明疏水表面可能会增加蛋白质的吸附,从而增加细胞的扩散。底物疏水性也改变了M1和M2巨噬细胞的细胞因子分泌。亚硝酸盐产量(M1的标志)和尿素产量(M2的标志)都随着底物疏水性的增加而增加,其中硝酸盐产量更为明显。在这些底物上接种的巨噬细胞随着底物疏水性的增加而转向更亲炎的表型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Macrophage Adhesion and Phenotypic Shifts on Hydrophobically Modified Hydrogels
A balance of macrophage phenotypes is essential in successful implantation. Therefore, biomaterials should be carefully designed to better regulate the response of macrophages. We demonstrate macrophage adhesion and phenotypic shifts can be modulated with hydrophobically modified hydrogels. This study represents a fundamental concept in controlling cell adhesion and differentiation with substrate hydrophobicity. Gel synthesis was carried out using methacrylated gellan gum (MGG), which was polymerized and crosslinked through a photo-initiated thiol-ene reaction in situ. The degree of hydrophobicity was controlled by attaching hydrophobic branches of different lengths to the MGG. The attachment was carefully controlled so that the hydrogel compressive modulus was not affected by the hydrophobic modification. Compared to unmodified MGG, the water contact angle increased and the swelling ratio decreased for modified MGG hydrogels. Naive and activated macrophages were subsequently seeded on the hydrogels with different surface wettability. Cell proliferation and spreading increased with increasing surface hydrophobicity. Hydrogel surface adhesion to a hydrophobic probe was quantified and showed an increasing trend with increasing substrate hydrophobicity. This suggests that the hydrophobic surface may increase protein adsorption, which, in turn, increases cell spreading. Cytokine secretion by M1 and M2 macrophages were also altered by substrate hydrophobicity. Both nitrite production, a marker of M1, and urea production, a marker of M2, increased with substrate hydrophobicity, with nitrate production being more pronounced. RAW 264.7 macrophages seeded on these substrates shifted to a more pro-inflammatory phenotype with increasing substrate hydrophobicity.
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