Natural extracellular matrix governs cells providing biomechanical and biofunctional outstanding properties, despite being porous and mostly made of soft materials. Among organs, specific tissues present specialized macro-architectures. For instance, hepatic lobules present radial organization, while vascular sinusoids are branched from vertical veins, providing specific biofunctional features. Therefore, it is imperative to mimic such structures while modeling tissues. So far, there is limited capability of coupling oriented macro-structures with interconnected micro-channels in programmable long-range vertical and radial sequential orientations. Herein, a three-directional ice crystal elongation (3DICE) system is presented to code geometries in cryogels. Using 3DICE, guided ice crystals growth templates vertical and radial pores through bulky cryogels. Translucent isotropic and anisotropic architectures of radial or vertical pores are fabricated with tunable mechanical response. Furthermore, 3D combinations of vertical and radial pore orientations are coded at the centimeter scale. Cell morphological response to macro-architectures is demonstrated. The formation of endothelial segments, CYP450 activity, and osteopontin expression, as liver fibrosis biomarkers, present direct response and specific cellular organization within radial, linear, and random architectures. These results unlock the potential of ice-templating demonstrating the relevance of macro-architectures to model tissues, and broad possibilities for drug testing, tissue engineering, and regenerative medicine.

天然细胞外基质控制细胞，提供生物力学和生物功能的优异特性，尽管它是多孔的并且主要由软材料制成。在器官中，特定组织呈现专门的宏观结构。例如，肝小叶呈放射状组织，而血管窦从垂直静脉分支，提供特定的生物功能特征。因此，在对组织进行建模时模拟此类结构势在必行。到目前为止，在可编程远程垂直和径向顺序定向中将定向宏观结构与互连微通道耦合的能力有限。在此，提出了一种三向冰晶伸长 (3DICE) 系统来对冷冻凝胶中的几何形状进行编码. 使用 3DICE，引导冰晶生长模板通过庞大的冷冻凝胶垂直和径向孔。径向或垂直孔的半透明各向同性和各向异性结构采用可调机械响应制造。此外，垂直和径向孔隙方向的 3D 组合以厘米尺度编码。证明了对宏观结构的细胞形态学反应。内皮片段的形成、 CYP450活性和骨桥蛋白作为肝纤维化生物标志物的表达，在径向、线性和随机结构内呈现直接反应和特定细胞组织。这些结果揭示了冰模板的潜力，展示了宏观架构与模型组织的相关性，以及药物测试、组织工程和再生医学的广泛可能性。