Additive manufacturing of hierarchical injectable scaffolds for tissue engineering
Additive manufacturing of hierarchical injectable scaffolds for tissue engineering
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DOI：
10.1016/j.actbio.2018.05.056
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发表时间：
2018-08-01
影响因子：
9.7
通讯作者：
Braschler, T.
中科院分区：
文献类型：
--
作者：
Beduer, A.;Piacentini, N.;Braschler, T.
我们提出了一种3D打印技术，允许自由形式制造厘米级的可注射结构，用于微创输送。它们是由低温基底上的3D打印和基于羧甲基纤维素的冷冻凝胶墨水的优化相结合而产生的。所得的高度多孔和弹性的冷冻凝胶是生物相容的，并且允许在注射压缩期间保护细胞活力。植入小鼠皮下空间后，它们被松散的纤维血管组织定殖，炎症迹象最小，并在3个月时保持无炎症。最后，我们通过控制低温打印过程中的基板温度来改变局部孔径。这使得能够控制体外局部细胞接种密度和体内无细胞支架中的血管化密度。总之，我们解决了大的，但可注射和高度生物相容性的支架的3D生物打印的需要，并通过控制局部孔径显示局部反应的调制。重要性声明这项工作结合了3D增材制造的力量与临床上有利的微创输送。我们通过优化低温3D打印工艺获得多孔、高度可压缩和机械坚固的结构。只需要一台基本的商用3D打印机和对反应速率和冷冻的基本控制。所获得的多孔水凝胶能够承受通过比其最大线性尺寸小多达50倍的毛细管的递送，这是迄今为止前所未有的压缩比。接种到水凝胶上的细胞在压缩期间受到保护。水凝胶结构在皮下注射到小鼠中后3个月进一步表现出优异的生物相容性。我们最后证明，局部调节孔径赠款控制血管密度在体内。这提供了原理证明，可以在3D打印过程中编码有意义的生物信息，在微创植入后发挥其作用。(C)2018 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
We present a 3D-printing technology allowing free-form fabrication of centimetre-scale injectable structures for minimally invasive delivery. They result from the combination of 3D printing onto a cryogenic substrate and optimisation of carboxymethylcellulose-based cryogel inks. The resulting highly porous and elastic cryogels are biocompatible, and allow for protection of cell viability during compression for injection. Implanted into the murine subcutaneous space, they are colonized with a loose fibrovascular tissue with minimal signs of inflammation and remain encapsulation-free at three months. Finally, we vary local pore size through control of the substrate temperature during cryogenic printing. This enables control over local cell seeding density in vitro and over vascularization density in cell-free scaffolds in vivo. In sum, we address the need for 3D-bioprinting of large, yet injectable and highly biocompatible scaffolds and show modulation of the local response through control over local pore size.Statement of SignificanceThis work combines the power of 3D additive manufacturing with clinically advantageous minimally invasive delivery. We obtain porous, highly compressible and mechanically rugged structures by optimizing a cryogenic 3D printing process. Only a basic commercial 3D printer and elementary control over reaction rate and freezing are required. The porous hydrogels obtained are capable of withstanding delivery through capillaries up to 50 times smaller than their largest linear dimension, an as yet unprecedented compression ratio. Cells seeded onto the hydrogels are protected during compression. The hydrogel structures further exhibit excellent biocompatibility 3 months after subcutaneous injection into mice. We finally demonstrate that local modulation of pore size grants control over vascularization density in vivo. This provides proof-of-principle that meaningful biological information can be encoded during the 3D printing process, deploying its effect after minimally invasive implantation. (C) 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.