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Volumetric Bioprinting of Complex Living-Tissue Constructs within Seconds

机译：在几秒钟内完成复杂的活组织构建体的体积生物打印

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Biofabrication technologies, including stereolithography and extrusion-based printing, are revolutionizing the creation of complex engineered tissues. The current paradigm in bioprinting relies on the additive layer-by-layer deposition and assembly of repetitive building blocks, typically cell-laden hydrogel fibers or voxels, single cells, or cellular aggregates. The scalability of these additive manufacturing technologies is limited by their printing velocity, as lengthy biofabrication processes impair cell functionality. Overcoming such limitations, the volumetric bioprinting of clinically relevant sized, anatomically shaped constructs, in a time frame ranging from seconds to tens of seconds is described. An optical-tomography-inspired printing approach, based on visible light projection, is developed to generate cell-laden tissue constructs with high viability (>85%) from gelatin-based photoresponsive hydrogels. Free-form architectures, difficult to reproduce with conventional printing, are obtained, including anatomically correct trabecular bone models with embedded angiogenic sprouts and meniscal grafts. The latter undergoes maturation in vitro as the bioprinted chondroprogenitor cells synthesize neo-fibrocartilage matrix. Moreover, free-floating structures are generated, as demonstrated by printing functional hydrogel-based ball-and-cage fluidic valves. Volumetric bioprinting permits the creation of geometrically complex, centimeter-scale constructs at an unprecedented printing velocity, opening new avenues for upscaling the production of hydrogel-based constructs and for their application in tissue engineering, regenerative medicine, and soft robotics.
机译：生物制造技术，包括立体平版印刷术和基于挤出的印刷，正在彻底改变复杂工程组织的创建。生物打印的当前范例依赖于重复构建块（通常是充满细胞的水凝胶纤维或体素，单个细胞或细胞聚集体）的逐层附加沉积和组装。这些增材制造技术的可扩展性受到其印刷速度的限制，因为冗长的生物制造过程会损害电池功能。克服了这些限制，描述了临床相关尺寸，解剖学形状的构建体在数秒至数十秒的时间范围内的体积生物打印。基于可见光投影的光学层析启发印刷方法已被开发出来，可从基于明胶的光敏水凝胶中产生具有高生存力（> 85％）的细胞组织结构。获得了自由形式的结构，这些结构很难用常规印刷来复制，包括解剖学上正确的小梁骨模型，其中包括嵌入的血管生成芽和半月板移植物。后者在体外进行成熟，因为生物打印的软骨生成细胞可以合成新的纤维软骨基质。而且，产生自由浮动的结构，如通过印刷功能性的基于水凝胶的球笼式流体阀所证明的。体积生物打印允许以前所未有的打印速度创建几何复杂，厘米级的构建体，为扩大基于水凝胶的构建体的生产及其在组织工程，再生医学和软机器人中的应用开辟了新途径。

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