Continuous microfluidic encapsulation of single mesenchymal stem cells using alginate microgels as injectable fillers for bone regeneration
Continuous microfluidic encapsulation of single mesenchymal stem cells using alginate microgels as injectable fillers for bone regeneration
复制标题
使用藻酸盐微凝胶作为骨再生的可注射填充剂对单个间充质干细胞进行连续微流体封装
DOI：
10.1016/j.actbio.2020.05.024
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发表时间：
2020-07-15
影响因子：
9.7
通讯作者：
Wang, Huanan
中科院分区：
文献类型：
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作者：
An, Chuanfeng;Liu, Weijian;Wang, Huanan
将细胞包封在微尺度水凝胶中可以提供三维（3D）微环境的模拟，以支持细胞活力和功能，并保护细胞免受环境应激，其已广泛用于组织再生和细胞治疗。在这里，开发了一种基于微流体的方法，用于使用藻酸盐微凝胶在单细胞水平上连续包封间充质干细胞（MSC）。这种微流体技术将芯片上封装、凝胶化和去乳化集成到一步制造过程中，这使得可扩展的细胞封装成为可能，同时保留加载细胞的活力和功能。值得注意的是，我们观察到在单细胞水平上包封在藻酸钙微凝胶中的MSC显示出显著增强的骨生成和微凝胶的加速矿化，这仅在诱导7天后发生。此外，在大鼠胫骨消融模型中，与MSC与微凝胶和脱细胞微凝胶混合相比，装载在藻酸盐微凝胶中的MSC显示出显著增强的骨形成。总之，目前的微流控技术代表了连续单细胞封装，制造和纯化的重要一步。这些微凝胶可以通过为包封的MSC提供可控的成骨微环境来促进骨再生，并以微创的方式促进干细胞治疗骨缺损。在这里，我们报道了一种基于微流体的方法，通过将芯片上封装、凝胶化和去乳化集成到一步制造过程中，连续封装具有高活力和功能性的单个MSC。更重要的是，在单细胞水平上，包封在藻酸盐微凝胶中的MSC显示出显著增强的成骨作用，显著加速体外矿化和体内成骨能力。因此，这种单细胞包封技术可以促进用于骨再生的干细胞治疗，并有可能用于各种组织工程应用。(C)2020 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
The encapsulation of cells in microscale hydrogels can provide a mimic of a three-dimensional (3D) microenvironment to support cell viability and functions and to protect cells from the environmental stress, which have been widely used in tissue regeneration and cell therapies. Here, a microfluidics-based approach is developed for continuous encapsulation of mesenchymal stem cells (MSCs) at the single-cell level using alginate microgels. This microfluidic technique integrated on-chip encapsulation, gelation, and de-emulsification into a one-step fabrication process, which enables scalable cell encapsulation while retaining the viability and functionality of loaded cells. Remarkably, we observed MSCs encapsulated in Ca-alginate microgels at the single-cell level showed significantly enhanced osteogenesis and accelerated mineralization of the microgels which occurred only after 7 days of induction. Furthermore, MSCs laden in alginate microgels displayed significantly enhanced bone formation compared to MSCs mixed with microgels and acellular microgels in a rat tibial ablation model. To conclude, the current microfluidic technique represents a significant step toward continuous single cell encapsulation, fabrication, and purification. These microgels can boost bone regeneration by providing a controlled osteogenic microenvironment for encapsulated MSCs and facilitate stem cell therapy in the treatment of bone defects in a minimally invasive delivery way.Statement of SignificanceThe biological functions and therapeutic activities of single cells laden in microgels for tissue engineering remains less investigated. Here, we reported a microfluidic-based method for continuous encapsulation of single MSCs with high viability and functionality by integrating on-chip encapsulation, gelation, and de-emulsification into a one-step fabrication process. More importantly, MSCs encapsulated in alginate microgels at the single-cell level showed significantly enhanced osteogenesis, remarkably accelerated mineralization in vitro and bone formation capacity in vivo. Therefore, this single-cell encapsulation technique can facilitate stem cell therapy for bone regeneration and be potentially used in a variety of tissue engineering applications. (C) 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.