Abstract：
Hematopoietic stem cells (HSCs) are the apical cells of the hematopoietic system, giving rise to cells of the blood and lymph lineages. HSCs reside primarily within bone marrow niches that contain matrix and cell-derived signals that help inform stem cell fate. Aspects of the bone marrow microenvironment have been captured in vitro by encapsulating cells within hydrogel matrices that mimic native mechanical and biochemical properties. Hydrogel microparticles, or microgels, are increasingly being used to assemble granular biomaterials for cell culture and noninvasive delivery applications. Here, we report the optimization of a gelatin maleimide hydrogel system to create monodisperse gelatin microgels via a flow-focusing microfluidic process. We report characteristic hydrogel stiffness, stability, and swelling characteristics as well as encapsulation of murine hematopoietic stem and progenitor cells, and mesenchymal stem cells within microgels. Microgels support cell viability, confirming compatibility of the microfluidic encapsulation process with these sensitive bone marrow cell populations. Overall, this work presents a microgel-based gelatin maleimide hydrogel as a foundation for future development of a multicellular artificial bone marrow culture system.
摘要：
造血干细胞（HSC）是造血系统的顶端细胞，产生血液和淋巴谱系的细胞。HSC主要存在于骨髓壁龛内,其包含有助于告知干细胞命运的基质和细胞衍生信号。通过将细胞封装在模拟天然机械和生化特性的水凝胶基质中,已经在体外捕获了骨髓微环境的方面。水凝胶微粒，或者微凝胶，越来越多地用于组装用于细胞培养和非侵入性递送应用的颗粒状生物材料。这里,我们报告了明胶马来酰亚胺水凝胶系统的优化，以通过流动聚焦微流体过程产生单分散明胶微凝胶。我们报告了特征水凝胶刚度，稳定性,和肿胀特征以及小鼠造血干细胞和祖细胞的封装，和微凝胶内的间充质干细胞。微凝胶支持细胞活力，确认微流体封装过程与这些敏感的骨髓细胞群体的相容性。总的来说,这项工作提出了一种基于微凝胶的明胶马来酰亚胺水凝胶，作为未来开发多细胞人工骨髓培养系统的基础。
