Dual 3D printing for vascularized bone tissue regeneration
Dual 3D printing for vascularized bone tissue regeneration
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DOI：
10.1016/j.actbio.2021.01.012
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发表时间：
2021-02-25
影响因子：
9.7
通讯作者：
Zhang, Lijie Grace
中科院分区：
文献类型：
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作者：
Hann, Sung Yun;Cui, Haitao;Zhang, Lijie Grace
足够的血管网络的发展对于成功制造用于再生医学的组织构建体是至关重要的，因为血管化对于执行组织的代谢功能（例如营养物运输和废物去除）是必不可少的。近年来，3D打印血管化骨骼的努力得到了极大的关注，因为骨骼疾病和缺陷对社会的老一代产生了显着影响。然而，传统和以前的3D打印骨骼研究一直受到难以获得重现天然骨骼独特特征所需的纳米级几何精度的困扰。此外，开发真正的仿生血管化骨组织的过程在历史上是复杂的。在这项研究中，使用简单的立体光刻（SLA）和熔融沉积建模（FDM）3D打印系统的组合开发了具有可灌注的内皮化血管通道的仿生纳米骨组织结构。使用FDM打印的聚乙烯醇（PVA）牺牲模板在SLA打印的骨支架内创建可灌注血管通道。在所制造的结构中，骨组织通过人骨髓间充质干细胞（hMSCs）的成骨分化形成，并且在人脐静脉内皮细胞（HUVECs）灌注后，通过内皮化血管通道的血管生成而萌发出独特的毛细血管。此外，在生理学相关的培养条件下评估制造的构建体，以预测植入人体后的组织发育。实验结果显示，定制设计的生物反应器与hMSC-HUVEC共培养系统在长达20天的观察中促进了血管网络的形成和构建体的成骨成熟。重要性声明作为一种新兴的制造新型组织构建体的技术，3D打印由于其出色的可控性，可重复性，和再现性。与先前报道的依赖于传统3D制造技术和传统生物塑料的研究不同，这项工作提出了使用多种新型3D打印系统与生物相容性材料相结合来合成生物墨水以增强血管网络的生长并确保基质生物活性的血管化骨支架的制造和表征。我们还证明，骨生成和血管生成一样，可以促进与使用体内样的流体环境和干细胞和内皮细胞的共培养。(C)2021 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
The development of sufficient vascular networks is crucial for the successful fabrication of tissue constructs for regenerative medicine, as vascularization is essential to perform the metabolic functions of tissues, such as nutrient transportation and waste removal. In recent years, efforts to 3D print vascularized bone have gained substantial attention, as bone disorders and defects have a marked impact on the older generations of society. However, conventional and previous 3D printed bone studies have been plagued by the difficulty in obtaining the nanoscale geometrical precision necessary to recapitulate the distinct characteristics of natural bone. Additionally, the process of developing truly biomimetic vascularized bone tissue has been historically complex. In this study, a biomimetic nano-bone tissue construct with a perfusable, endothelialized vessel channel was developed using a combination of simple stereolithography (SLA) and fused deposition modeling (FDM) 3D printing systems. The perfusable vessel channel was created within the SLA printed bone scaffold using an FDM printed polyvinyl alcohol (PVA) sacrificial template. Within the fabricated constructs, bone tissue was formed through the osteogenic differentiation of human bone marrow mesenchymal stem cells (hMSCs), and distinct capillaries sprouted through the angiogenesis of the endothelialized vessel channel after human umbilical vein endothelial cells (HUVECs) had been perfused throughout. Furthermore, the fabricated constructs were evaluated in physiologically relevant culture conditions to predict tissue development after implantation in the human body. The experimental results revealed that the custom-designed bioreactor with an hMSC-HUVEC co-culture system enhanced the formation of vascular networks and the osteogenic maturation of the constructs for up to 20 days of observation.Statement of significanceAs an emerging technique to fabricate novel tissue construct, 3D printing has been extensively investigated to generate vascularized tissues due to its outstanding controllability, repeatability, and reproducibility. Unlike previously reported studies which have relied on traditional 3D fabrication techniques and conventional bioplastics, this work presents the fabrication and characterization of vascularized bone scaffolds using a combination of multiple novel 3D printing systems with biocompatible materials for the synthesis of bioinks to enhance the growth of vascular networks as well as to ensure matrix bioactivity. We also demonstrate that osteogenesis and angiogenesis alike can be promoted with the use of an in vivo-like fluid environment and the co-culturing of stem cells and endothelial cells. (C) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.