自愈水凝胶
细胞外基质
离子霉素
材料科学
三维细胞培养
细胞培养
基质(化学分析)
3D生物打印
细胞生物学
生物物理学
T细胞
组织工程
生物医学工程
细胞
化学
免疫系统
免疫学
细胞内
生物
医学
生物化学
遗传学
高分子化学
复合材料
作者
Joel P. Joseph,Sriram Bharath Gugulothu,Dipankar Nandi,Kaushik Chatterjee
出处
期刊:ACS Macro Letters
[American Chemical Society]
日期:2023-07-19
卷期号:12 (8): 1085-1093
被引量:10
标识
DOI:10.1021/acsmacrolett.3c00271
摘要
T cells play a critical role in the adaptive immune response of the body, especially against intracellular pathogens and cancer. In vitro, T cell activation studies typically employ planar (two-dimensional, 2D) culture systems that do not mimic native cell-to-extracellular matrix (ECM) interactions, which influence activation. The goal of this work was to study T cell responses in a cell line (EL4) and primary mouse T cells in three-dimensional (3D) bioprinted matrices of varied stiffness. Cell-laden hydrogels were 3D bioprinted from gelatin methacryloyl (GelMA) using a digital light processing (DLP)-based 3D bioprinter operated with visible light (405 nm). Mechanical characterization revealed that the hydrogels had pathophysiologically relevant stiffnesses for a lymph node-mimetic tissue construct. EL4, a mouse T cell lymphoma line, or primary mouse T cells were 3D bioprinted and activated using a combination of 10 ng/mL of phorbol myristate acetate (PMA) and 0.1 μM of ionomycin. Cellular responses revealed differences between 2D and 3D cultures and that the biomechanical properties of the 3D bioprinted hydrogel influence T cell activation. Cellular responses of the 2D and 3D cultures in a soft matrix (19.83 ± 2.36 kPa) were comparable; however, they differed in a stiff matrix (52.95 ± 1.36 kPa). The fraction of viable EL4 cells was 1.3-fold higher in the soft matrix than in the stiff matrix. Furthermore, primary mouse T cells activated with PMA and ionomycin showed 1.35-fold higher viable cells in the soft matrix than in the stiff matrix. T cells bioprinted in a soft matrix and a stiff matrix released 7.4-fold and 5.9-fold higher amounts of interleukin-2 (IL-2) than 2D cultured cells, respectively. Overall, the study demonstrates the changes in the response of T cells in 3D bioprinted scaffolds toward engineering an ex vivo lymphoid tissue-mimetic system that can faithfully recapitulate T cell activation and unravel pathophysiological characteristics of T cells in infectious biology, autoimmunity, and cancers.
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