Controlling cellular organization is crucial in the biofabrication of tissue-engineered scaffolds, as it affects cell behavior as well as the functionality of mature tissue. Thus far, incorporation of physiochemical cues with cell-size resolution in three-dimensional (3D) scaffolds has proven to be a challenging strategy to direct the desired cellular organization. In this work, a rapid, simple, and cost-effective approach is developed for continuous printing of multicompartmental hydrogel fibers with intrinsic 3D microfilaments to control cellular orientation. A static mixer integrated into a coaxial microfluidic device is utilized to print alginate/gelatin-methacryloyl (GelMA) hydrogel fibers with patterned internal microtopographies. In the engineered microstructure, GelMA compartments provide a cell-favorable environment, while alginate compartments offer morphological and mechanical cues that direct the cellular orientation. It is demonstrated that the organization of the microtopographies, and consequently the cellular alignment, can be tailored by controlling flow parameters in the printing process. Despite the large diameter of the fibers, the precisely tuned internal microtopographies induce excellent cell spreading and alignment, which facilitate rapid cell proliferation and differentiation toward mature biofabricated constructs. This strategy can advance the engineering of functional tissues.

中文翻译：

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通过设计的 3D 微隔室化控制生物打印中的细胞组织

控制细胞组织在组织工程支架的生物制造中至关重要，因为它影响细胞行为以及成熟组织的功能。到目前为止，在三维 (3D) 支架中加入具有细胞大小分辨率的物理化学线索已被证明是指导所需细胞组织的一项具有挑战性的策略。在这项工作中，开发了一种快速、简单且具有成本效益的方法，用于连续打印具有内在 3D 微丝的多室水凝胶纤维，以控制细胞取向。使用集成到同轴微流体装置中的静态混合器来打印具有图案化内部微拓扑结构的藻酸盐/明胶-甲基丙烯酰 (GelMA) 水凝胶纤维。在工程化的微结构中，GelMA 隔室提供了一个有利于细胞的环境，而藻酸盐隔室提供指导细胞方向的形态和机械线索。结果表明，可以通过控制打印过程中的流量参数来定制微拓扑结构的组织，从而调整细胞排列。尽管纤维的直径很大，但精确调整的内部微拓扑结构可诱导出色的细胞扩散和排列，从而促进细胞快速增殖和向成熟的生物制造结构分化。这种策略可以推进功能组织的工程化。尽管纤维的直径很大，但精确调整的内部微拓扑结构可诱导出色的细胞扩散和排列，从而促进细胞快速增殖和向成熟的生物制造结构分化。这种策略可以推进功能组织的工程化。尽管纤维的直径很大，但精确调整的内部微拓扑结构可诱导出色的细胞扩散和排列，从而促进细胞快速增殖和向成熟的生物制造结构分化。这种策略可以推进功能组织的工程化。