Granular synthetic hydrogels are useful bioinks for their compatibility with a variety of chemistries, affording printable, stimuli-responsive scaffolds with programmable structure and function. Additive manufacturing of microscale hydrogels, or microgels, allows for the fabrication of large cellularized constructs with percolating interstitial space, providing a platform for tissue engineering at length scales that are inaccessible by bulk encapsulation where transport of media and other biological factors are limited by scaffold density. Herein, synthetic microgels with varying degrees of degradability are prepared with diameters on the order of hundreds of microns by submerged electrospray and UV photopolymerization. Porous microgel scaffolds are assembled by particle jamming and extrusion printing, and semi-orthogonal chemical cues are utilized to tune the void fraction in printed scaffolds in a logic-gated manner. Scaffolds with different void fractions are easily cellularized post printing and microgels can be directly annealed into cell-laden structures. Finally, high-throughput direct encapsulation of cells within printable microgels is demonstrated, enabling large-scale 3D culture in a macroporous biomaterial. This approach provides unprecedented spatiotemporal control over the properties of printed microporous annealed particle scaffolds for 2.5D and 3D tissue culture.

中文翻译：

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用于多维细胞培养的可挤出和可降解聚乙二醇微凝胶支架的 4D 打印

颗粒状合成水凝胶是有用的生物墨水，因为它们与多种化学物质相容，提供具有可编程结构和功能的可打印、刺激响应支架。微型水凝胶或微凝胶的增材制造允许制造具有渗透间隙空间的大型细胞化结构，为大规模封装无法达到的长度尺度的组织工程提供了平台，其中介质和其他生物因子的运输受到支架密度的限制。在此，通过浸没电喷雾和紫外光聚合制备了具有不同降解程度的合成微凝胶，其直径在数百微米量级。多孔微凝胶支架通过粒子干扰和挤出印刷来组装，并利用半正交化学线索以逻辑门控方式调整印刷支架中的空隙率。具有不同空隙率的支架在打印后很容易细胞化，并且微凝胶可以直接退火成充满细胞的结构。最后，证明了可打印微凝胶中细胞的高通量直接封装，从而能够在大孔生物材料中进行大规模 3D 培养。这种方法为 2.5D 和 3D 组织培养的印刷微孔退火颗粒支架的特性提供了前所未有的时空控制。