3D printing microporous scaffolds from modular bioinks containing sacrificial, cell-encapsulating microgels.
3D printing microporous scaffolds from modular bioinks containing sacrificial, cell-encapsulating microgels.
复制标题
使用含有牺牲性细胞封装微凝胶的模块化生物墨水 3D 打印微孔支架。
DOI：
10.1039/d3bm00721a
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发表时间：
2023
影响因子：
6.6
通讯作者：
Heilshorn,SarahC
中科院分区：
文献类型：
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作者：
Seymour,AlexisJ;Kilian,David;Navarro,RenatoS;Hull,SarahM;Heilshorn,SarahC
基于微凝胶的生物材料具有固有的孔隙性，并且通常是可挤出的，这使得它们非常适合3D生物打印应用。细胞通常被引入到这些颗粒油墨印刷后使用细胞浸润。然而，由于细胞迁移速度慢，这种策略很难在厚3D打印几何形状中实现与深度无关的细胞分布。为了解决这个问题，我们通过结合两种具有不同功能的微凝胶来利用颗粒墨水模块：(1)由明胶甲基丙烯酰（GelMA）制成的结构，紫外线交联微凝胶和(2)由氧化海藻酸盐（AlgOx）制成的牺牲，细胞负载微凝胶。我们假设，将细胞包裹在牺牲的AlgOx微凝胶中，可以同时引入空隙空间并释放细胞，而这种深度仅通过细胞浸润是无法实现的。以不同的比例混合微凝胶，产生一系列高度可印刷的GelMA: AlgOx微凝胶油墨，其空隙分数范围为0.03至0.35。正如预期的那样，空白部分影响GelMA: AlgOx墨水中人脐静脉内皮细胞（HUVEC）的形态。至关重要的是，孔隙率不会改变3D打印样品中理想的HUVEC分布。这项工作提出了一种制造具有可调孔隙度和与深度无关的细胞分布的结构体的策略，突出了微凝胶基油墨用于3D生物打印的前景。
Microgel-based biomaterials have inherent porosity and are often extrudable, making them well-suited for 3D bioprinting applications. Cells are commonly introduced into these granular inks post-printing using cell infiltration. However, due to slow cell migration speeds, this strategy struggles to achieve depth-independent cell distributions within thick 3D printed geometries. To address this, we leverage granular ink modularity by combining two microgels with distinct functions: (1) structural, UV-crosslinkable microgels made from gelatin methacryloyl (GelMA) and (2) sacrificial, cell-laden microgels made from oxidized alginate (AlgOx). We hypothesize that encapsulating cells within sacrificial AlgOx microgels would enable the simultaneous introduction of void space and release of cells at depths unachievable through cell infiltration alone. Blending the microgels in different ratios produces a family of highly printable GelMA : AlgOx microgel inks with void fractions ranging from 0.03 to 0.35. As expected, void fraction influences the morphology of human umbilical vein endothelial cells (HUVEC) within GelMA : AlgOx inks. Crucially, void fraction does not alter the ideal HUVEC distribution seen throughout the depth of 3D printed samples. This work presents a strategy for fabricating constructs with tunable porosity and depth-independent cell distribution, highlighting the promise of microgel-based inks for 3D bioprinting.