PDF(Pubmed)
Abstract：
Analogous of pixels to two-dimensional pictures, voxels-in the form of either small cubes or spheres-are the basic building blocks of three-dimensional objects. However, precise manipulation of viscoelastic bio-ink voxels in three-dimensional space represents a grand challenge in both soft matter science and biomanufacturing. Here, we present a voxelated bioprinting technology that enables the digital assembly of interpenetrating double-network hydrogel droplets made of polyacrylamide/alginate-based or hyaluronic acid/alginate-based polymers. The hydrogels are crosslinked via additive-free and biofriendly click reaction between a pair of stoichiometrically matched polymers carrying norbornene and tetrazine groups, respectively. We develop theoretical frameworks to describe the crosslinking kinetics and stiffness of the hydrogels, and construct a diagram-of-state to delineate their mechanical properties. Multi-channel print nozzles are developed to allow on-demand mixing of highly viscoelastic bio-inks without significantly impairing cell viability. Further, we showcase the distinctive capability of voxelated bioprinting by creating highly complex three-dimensional structures such as a hollow sphere composed of interconnected yet distinguishable hydrogel particles. Finally, we validate the cytocompatibility and in vivo stability of the printed double-network scaffolds through cell encapsulation and animal transplantation.
摘要：
类似于二维图片的像素，体素-以小立方体或球体的形式-是三维物体的基本构建块。然而,粘弹性生物墨水体素在三维空间中的精确操纵代表了软物质科学和生物制造的巨大挑战。这里,我们提出了一种体素生物打印技术,该技术能够数字组装由聚丙烯酰胺/藻酸盐基或透明质酸/藻酸盐基聚合物制成的互穿双网络水凝胶液滴.水凝胶通过一对带有降冰片烯和四嗪基团的化学计量匹配的聚合物之间的无添加剂和生物耦合点击反应交联，分别。我们开发了理论框架来描述水凝胶的交联动力学和刚度，并构造状态图来描绘它们的机械性能。多通道打印喷嘴被开发以允许高粘弹性生物墨水的按需混合而不会显著损害细胞活力。Further,我们通过创建高度复杂的三维结构，例如由互连但可区分的水凝胶颗粒组成的空心球，展示了体素生物打印的独特能力。最后,我们通过细胞封装和动物移植验证了打印的双网络支架的细胞相容性和体内稳定性。
