A Microfluidic Device to Fabricate One-Step Cell Bead-Laden Hydrogel Struts for Tissue Engineering
A Microfluidic Device to Fabricate One-Step Cell Bead-Laden Hydrogel Struts for Tissue Engineering
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DOI：
10.1002/smll.202106487
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发表时间：
2021-12-02
期刊：
影响因子：
13.3
通讯作者：
Kim, GeunHyung
中科院分区：
文献类型：
--
作者：
Kim, JuYeon;Lee, Hyeongjin;Kim, GeunHyung
载有细胞的结构广泛应用于各种组织工程应用，包括组织修复。生物打印结构中的细胞与细胞相互作用对于成功的组织修复非常重要，因为细胞-细胞信号传导途径可以调节组织发育和干细胞命运。然而，在常规的载有细胞的生物打印结构中，细胞-细胞相互作用的程度低，这对于这种模式的治疗应用是具有挑战性的。本文中，使用具有载有细胞的甲基丙烯酸酯化明胶（GelMa）生物墨水和作为基质水凝胶的藻酸盐的微流体装置来制造载有细胞聚集的微珠的功能性混合结构。这种方法有效地将细胞与细胞的相互作用程度增加到与细胞球状体相当的水平。混合结构是使用一个步骤的过程中获得的，没有排气过程。它包括细胞珠制造和细胞珠负载结构的挤出过程。适当选择不同的流速以在该过程中为每种水凝胶开发具有均匀分布的细胞珠的载有细胞的支柱。混合支柱表现出比常规藻酸盐/GelMa支柱显著更高的细胞活性，常规藻酸盐/GelMa支柱使用类似的细胞密度和生物墨水制剂进行生物打印。此外，将具有脂肪干细胞的混合支柱植入小鼠体内，与正常生物打印的支柱相比，导致显著更高的肌生成。
Cell-laden structures are widely applied for a variety of tissue engineering applications, including tissue restoration. Cell-to-cell interactions in bioprinted structures are important for successful tissue restoration, because cell-cell signaling pathways can regulate tissue development and stem cell fate. However, the low degree of cell-cell interaction in conventional cell-laden bioprinted structures is challenging for the therapeutic application of this modality. Herein, a microfluidic device with cell-laden methacrylated gelatin (GelMa) bioink and alginate as a matrix hydrogel is used to fabricate a functional hybrid structure laden with cell-aggregated microbeads. This approach effectively increases the degree of cell-to-cell interaction to a level comparable to cell spheroids. The hybrid structure is obtained using a one-step process without the exhausting procedure. It consists of cell bead fabrication and an extrusion process for the cell-bead laden structure. Different flow rates are appropriately selected to develop cell-laden struts with homogeneously distributed cell beads for each hydrogel in the process. The hybrid struts exhibit significantly higher cellular activities than those of conventional alginate/GelMa struts, which are bioprinted using similar cell densities and bioink formulations. Furthermore, hybrid struts with adipose stem cells are implanted into mice, resulting in significantly higher myogenesis in comparison to normally bioprinted struts.