Development of Liver Decellularized Extracellular Matrix Bioink for Three-Dimensional Cell Printing-Based Liver Tissue Engineering
Development of Liver Decellularized Extracellular Matrix Bioink for Three-Dimensional Cell Printing-Based Liver Tissue Engineering
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DOI：
10.1021/acs.biomac.6b01908
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发表时间：
2017-04-01
影响因子：
6.2
通讯作者：
Cho, Dong-Woo
中科院分区：
文献类型：
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作者：
Lee, Hyungseok;Han, Wonil;Cho, Dong-Woo
肝脏是人体的重要器官，在人体中起着重要作用。由于肝功能衰竭和药物性肝损伤后供者缺乏，许多研究集中在开发肝脏替代物和用于移植和药物筛选的体外肝脏模型。虽然已经进行了许多研究，但这些系统不能忠实地模拟肝脏的复杂性。最近，三维(3D)细胞打印技术已经成为可能有助于克服这一限制的许多创新技术之一。然而，在开发针对基于3D细胞打印的肝组织工程优化的生物材料方面，仍有大量的工作要做。因此，在这项工作中，我们开发了一种用于3D细胞打印的肝脏脱细胞外基质(DECM)生物墨水，并对其特性进行了评价。肝脏DECM生物墨水保留了肝脏的主要ECM成分，同时有效地去除了细胞成分，并进一步表现出适合于3D细胞打印的可调节特性。我们进一步研究了肝脏dECM生物墨水的打印参数，以验证打印过程的通用性和保真度。比较了肝DECM生物墨水和市售胶原生物墨水中的干细胞分化和HepG2细胞功能，发现肝DECM生物墨水能诱导干细胞分化，增强HepG2细胞功能。结果表明，所提出的肝脏DECM生物墨水是一种很有前途的基于3D细胞打印的肝脏组织工程生物墨水。
The liver is an important organ and plays major roles in the human body. Because of the lack of liver donors after liver failure and drug-induced liver injury, much research has focused on developing liver alternatives and liver in vitro models for transplantation and drug screening. Although numerous studies have been conducted, these systems cannot faithfully mimic the complexity of the liver. Recently, three-dimensional (3D) cell printing technology has emerged as one of a number of innovative technologies that may help to overcome this limitation. However, a great deal of work in developing biomaterials optimized for 3D cell printing-based liver tissue engineering remains. Therefore, in this work, we developed a liver decellularized extracellular matrix (dECM) bioink for 3D cell printing applications and evaluated its characteristics. The liver dECM bioink retained the major ECM components of the liver while cellular components were effectively removed and further exhibited suitable and adjustable properties for 3D cell printing. We further studied printing parameters with the liver dECM bioink to verify the versatility and fidelity of the printing process. Stem cell differentiation and HepG2 cell functions in the liver dECM bioink in comparison to those of commercial collagen bioink were also evaluated, and the liver dECM bioink was found to induce stem cell differentiation and enhance HepG2 cell function. Consequently, the results demonstrate that the proposed liver dECM bioink is a promising bioink candidate for 3D cell printing based liver tissue engineering.