Three-dimensional (3D) bioprinting is an emerging tissue engineering technology, already with several remarkable accomplishments and with more promises to fulfill. Besides the enduring goal of making tissues for implantation, it could also become an essential tool in the worldwide trend to replace animal experimentation with improved in vitro models for disease mechanism studies, or with new high-throughput pharmacological and toxicology assays. All these require the speed, reproducibility, and standardization that bioprinting could easily provide. However, originating from additive manufacturing with its top-down approach of “filling” a virtual volume with a semifluid (hydrogel) material, the finer internal anatomic structure of the tissues, as well as vascularization and innervation, has remained difficult to implement. Thus, the next frontier in bioprinting is the generation of more anatomically realistic models, needed for ascending to the functionality of living tissues. In this study, I discuss the conceptual and practical barriers still hampering the attainment of this goal and suggest solutions to overcome them. In this regard, I introduce two workflows that combine existing methods in new operational sequences: (1) bioprinting guided by images of histological sections assembled in 3D constructs and (2) bioprinting of bidimensional vascular patterns implemented among stackable cellular layers. While more sophisticated methods to capture the tissue structure in 3D constructs certainly exist, I contend that extrusion bioprinting may still offer a simple, practical, and affordable option.

中文翻译：

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用于疾病建模和药物测试的解剖学真实组织结构的三维生物打印

三维 (3D) 生物打印是一种新兴的组织工程技术，已经取得了多项非凡的成就，并有望实现。除了制造用于植入的组织的持久目标外，它还可能成为全球趋势中的重要工具，以改进的体外实验取代动物实验。疾病机制研究模型，或新的高通量药理学和毒理学分析。所有这些都需要生物打印可以轻松提供的速度、可重复性和标准化。然而，源自增材制造及其自上而下的用半流体（水凝胶）材料“填充”虚拟体积的方法，组织更精细的内部解剖结构以及血管化和神经支配仍然难以实现。因此，生物打印的下一个前沿是生成更逼真的解剖模型，这是提升活组织功能所需的。在这项研究中，我讨论了仍然阻碍实现这一目标的概念和实践障碍，并提出了克服这些障碍的解决方案。在这方面，我介绍了两个将现有方法结合到新操作序列中的工作流程：（1）由组装在 3D 结构中的组织切片图像引导的生物打印和（2）在可堆叠细胞层之间实现的二维血管图案的生物打印。虽然在 3D 结构中捕获组织结构的更复杂的方法肯定存在，但我认为挤出生物打印可能仍然提供一个简单、实用且负担得起的选择。