Sacrificial microgel-laden bioink-enabled 3D bioprinting of mesoscale pore networks
Sacrificial microgel-laden bioink-enabled 3D bioprinting of mesoscale pore networks
复制标题
含有牺牲微凝胶的生物墨水支持的中尺度孔隙网络 3D 生物打印
DOI：
10.1007/s42242-020-00062-y
复制
发表时间：
2020-02-01
影响因子：
7.9
通讯作者：
He, Yong
中科院分区：
文献类型：
--
作者：
Shao, Lei;Gao, Qing;He, Yong
三维（3D）生物打印是一种强大的方法，能够制造保留复杂生物功能的3D组织结构。然而，生物墨水凝胶化后形成的致密水凝胶网络往往限制了包封细胞的迁移和增殖。本文中，设计了一种牺牲性载有微凝胶的生物墨水策略，用于直接生物打印具有介观孔网络（MPN）的构建体，以增强营养物递送和细胞生长。含有细胞/明胶甲基丙烯酰基（GelMA）混合物和凝胶化明胶微凝胶的载有牺牲微凝胶的生物墨水首先热交联以通过挤出生物打印到冷平台上来制造临时的预先设计的载有细胞的构造。然后，通过GelMA的光交联使构建体永久稳定。在明胶微凝胶随后溶解后形成打印的构建体内部的MPN。这些MPN允许有效的氧/营养扩散，促进生物活性组织的产生。具体而言，包封在具有MPN的生物打印大规模构建体（≥ 1 cm）中的成骨细胞和人脐静脉内皮细胞在培养期间显示出增强的生物活性。基于牺牲性载有微凝胶的生物墨水的3D生物打印策略提供了一种简便的方法来促进具有MPN的复杂组织构建体的形成，并为未来基于MPN的组织构建体的优化以及在组织工程的不同领域中的应用奠定了基础。
Three-dimensional (3D) bioprinting is a powerful approach that enables the fabrication of 3D tissue constructs that retain complex biological functions. However, the dense hydrogel networks that form after the gelation of bioinks often restrict the migration and proliferation of encapsulated cells. Herein, a sacrificial microgel-laden bioink strategy was designed for directly bioprinting constructs with mesoscale pore networks (MPNs) for enhancing nutrient delivery and cell growth. The sacrificial microgel-laden bioink, which contains cell/gelatin methacryloyl (GelMA) mixture and gelled gelatin microgel, is first thermo-crosslinked to fabricate temporary predesigned cell-laden constructs by extrusion bioprinting onto a cold platform. Then, the construct is permanently stabilized through photo-crosslinking of GelMA. The MPNs inside the printed constructs are formed after subsequent dissolution of the gelatin microgel. These MPNs allowed for effective oxygen/nutrient diffusion, facilitating the generation of bioactive tissues. Specifically, osteoblast and human umbilical vein endothelial cells encapsulated in the bioprinted large-scale constructs (≥ 1 cm) with MPNs showed enhanced bioactivity during culture. The 3D bioprinting strategy based on the sacrificial microgel-laden bioink provided a facile method to facilitate formation of complex tissue constructs with MPNs and set a foundation for future optimization of MPN-based tissue constructs with applications in diverse areas of tissue engineering.