Hydrogel Bioink with Multilayered Interfaces Improves Dispersibility of Encapsulated Cells in Extrusion Bioprinting
Hydrogel Bioink with Multilayered Interfaces Improves Dispersibility of Encapsulated Cells in Extrusion Bioprinting
复制标题
具有多层界面的水凝胶生物墨水提高了挤出生物打印中封装细胞的分散性
DOI：
10.1021/acsami.9b09782
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发表时间：
2019-08-28
影响因子：
9.5
通讯作者：
Zhang, Weijia
中科院分区：
文献类型：
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作者：
Chen, Nan;Zhu, Kai;Zhang, Weijia
使用低粘度生物墨水的挤出生物打印的挑战之一是细胞的快速重力驱动沉降。以低粘度为特征的水凝胶生物墨水中的细胞倾向于沉降到生物墨水储存器的底部，因此，它们的生物打印性因与沉积的不均匀细胞化结构的结合而受到阻碍。这在需要较长时间来打印复杂或较大的组织构建体的情况下尤其如此。增加生物墨水的粘度有效地延缓了沉降，但由于在挤出过程中细胞上的剪切应力增加而引起细胞膜溶解或功能破坏。受彩虹鸡尾酒的启发，我们报告了明胶甲基丙烯酰（GelMA）生物墨水的多层改性策略的发展，以操纵多个液体界面，提供界面保留，以延缓细胞在生物墨水水库中的沉降。事实上，我们的逐层生物墨水系统中的界面张力，其特征在于悬滴法，被发现以指数方式高于细胞的沉降拉力（Δ（重力-浮力）=类似于10（-9）N），表明界面保留对于防止细胞在相邻层上沉降至关重要。证明了包封的细胞显示出比原始GelMA更好的使用多层GelMA生物墨水系统生物打印的生物打印蛋白构建体，其中多层生物墨水中细胞分布的均匀性指数是后者的4倍。
One of the challenges for extrusion bioprinting using low-viscosity bioinks is the fast gravity-driven sedimentation of cells. Cells in a hydrogel bioink that features low viscosity tend to settle to the bottom of the bioink reservoir, and as such, their bioprintability is hindered by association with the inhomogeneous cellularized structures that are deposited. This is particularly true in cases where longer periods are required to print complex or larger tissue constructs. Increasing the bioink's viscosity efficiently retards sedimentation but gives rise to cell membranolysis or functional disruption due to increased shear stress on the cells during the extrusion process. Inspired by the rainbow cocktail, we report the development of a multilayered modification strategy for gelatin methacryloyl (GelMA) bioink to manipulate multiple liquid interfaces, providing interfacial retention to retard cell sedimentation in the bioink reservoir. Indeed, the interfacial tension in our layer-by-layer bioink system, characterized by the pendant drop method, was found to be exponentially higher than the sedimental pull (Delta(Gravity-Buoyancy) = similar to 10(-9) N) of cells, indicating that the interfacial retention is crucial for preventing cell sedimentation across the adjacent layers. It was demonstrated that the encapsulated cells displayed better dispersibility in constructs bioprinted using the multilayered GelMA bioink system than that of pristine GelMA where the index of homogeneity of the cell distribution in the multilayered bioink was 4 times that of the latter.