Acta Biomaterialia ( IF 9.4 ) Pub Date : 2020-05-23 , DOI: 10.1016/j.actbio.2020.05.024 Chuanfeng An 1 , Weijian Liu 2 , Yang Zhang 3 , Bo Pang 4 , Hui Liu 4 , Yujie Zhang 1 , Haoyue Zhang 1 , Liyuan Zhang 5 , Hongbing Liao 4 , Changle Ren 2 , Huanan Wang 1
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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 Significance
The 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.
中文翻译：
使用藻酸盐微凝胶作为用于骨骼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。
将细胞封装在微尺度水凝胶中可提供三维（3D）微环境的模拟物，以支持细胞生存力和功能并保护细胞免受环境压力，这已广泛用于组织再生和细胞疗法中。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封装间充质干细胞（MSC）。这种微流体技术将芯片上的封装，凝胶化和去乳化功能集成到了一个一步的制造过程中，该过程可实现可扩展的细胞封装，同时保留负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封装在海藻酸钙微凝胶中的MSCs显着增强了成骨作用，并加速了微凝胶的矿化作用，仅在诱导7天后发生。此外，与在大鼠胫骨消融模型中混合有微凝胶和无细胞微凝胶的MSC相比，藻酸盐微凝胶中载有MSC的骨形成显着增强。总而言之，当前的微流体技术代表了朝着连续单细胞封装，制造和纯化迈出的重要一步。这些微凝胶可通过为封装的MSC提供受控的成骨微环境来促进骨骼再生，并以微创递送方式促进干细胞治疗骨缺损的治疗。与在大鼠胫骨消融模型中混合有微凝胶和无细胞微凝胶的MSC相比，藻酸盐微凝胶中载有MSC的骨形成显着增强。总而言之，当前的微流体技术代表了朝着连续单细胞封装，制造和纯化迈出的重要一步。这些微凝胶可通过为封装的MSC提供受控的成骨微环境来促进骨骼再生，并以微创递送方式促进干细胞治疗骨缺损的治疗。与在大鼠胫骨消融模型中混合有微凝胶和无细胞微凝胶的MSC相比，藻酸盐微凝胶中载有MSC的骨形成显着增强。总而言之，当前的微流体技术代表了朝着连续单细胞封装，制造和纯化迈出的重要一步。这些微凝胶可通过为封装的MSC提供受控的成骨微环境来促进骨骼再生，并以微创递送方式促进干细胞治疗骨缺损的治疗。和净化。这些微凝胶可通过为封装的MSC提供受控的成骨微环境来促进骨骼再生，并以微创递送方式促进干细胞治疗骨缺损的治疗。和净化。这些微凝胶可通过为封装的MSC提供受控的成骨微环境来促进骨骼再生，并以微创递送方式促进干细胞治疗骨缺损的治疗。
重要声明
载于微凝胶中用于组织工程的单细胞的生物学功能和治疗活性的研究仍较少。在这里，我们报告了一种基于微流体的方法，通过将片上封装，凝胶化和去乳化集成到一个步骤的制造过程中，来连续封装具有高活力和功能性的单个MSC。更重要的是，囊封在藻酸盐微凝胶中的单细胞水平的MSCs显着增强了成骨作用，显着加速了体外矿化和体内骨形成能力。因此，这种单细胞包封技术可以促进干细胞治疗以促进骨骼再生，并有可能在各种组织工程应用中使用。
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