Interdisciplinary Nanoscience Center, Aarhus University, 8000 Aarhus C, Denmark.
Sino-Danish College (SDC), University of Chinese Academy of Sciences, Beijing 101400, China.
ACS Appl Mater Interfaces. 2021 May 19;13(19):22142-22149. doi: 10.1021/acsami.1c00798. Epub 2021 May 7.
Constructing artificial lymph vessels, which play a key role in the immune response, can provide new insights into immunology and disease pathologies. An immune tissue is a highly complex network that consists of lymph vessels, with a "beads-on-a-string" knotted structure. Herein, we present the facile and rapid fabrication of beads-on-a-string knotted cell-laden fibers using coaxial spinning of alginate by exploiting the Plateau-Rayleigh instability. It is shown how alterations in the flow rate and alginate concentration greatly affect the beads-on-a-string structure, rooted in the Plateau-Rayleigh instability theory. Biocompatibility was confirmed by the lactate dehydrogenase (LDH) assay and live/dead staining of the encapsulated human white blood cells. Finally, the encapsulated white blood cells were still functional as indicated by their anti-CD3 activation to secrete interleukin 2. The rapid fabrication of a cell-laden beads-on-a-string three-dimensional (3D) culture platform enables a crude mimicry of the lymph vessel structure. With joint expertise in immunology, microfluidics, and bioreactors, the technology may contribute to the mechanistic assay of human immune response in vitro and functional replacement.
构建在免疫反应中起着关键作用的人工淋巴管，可以为免疫学和疾病病理学提供新的见解。免疫组织是一个高度复杂的网络，由淋巴管组成，具有“串珠”状的打结结构。在此，我们通过利用海藻酸钠的同轴纺丝，在不外加任何试剂的情况下，利用瑞利不稳定性（Plateau-Rayleigh instability），简便快速地制备出串珠状的细胞填充纤维。实验表明，通过改变流速和海藻酸钠浓度，可以极大地影响串珠状结构，这与瑞利不稳定性理论有关。通过乳酸脱氢酶（lactate dehydrogenase，LDH）检测和包封的人白细胞的死活染色，证实了其生物相容性。最后，包封的白细胞仍然具有功能，因为它们可以通过抗 CD3 激活来分泌白细胞介素 2。该细胞填充的串珠状三维（3D）培养平台的快速制造，可以粗略模拟淋巴管结构。通过免疫学、微流控和生物反应器方面的专业知识，该技术可能有助于体外人类免疫反应的机制分析和功能替代。
