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一种使用前成骨细胞和人脂肪干细胞制造基于胶原蛋白/细胞外基质的生物墨水的新方法。

A New Approach for Fabricating Collagen/ECM-Based Bioinks Using Preosteoblasts and Human Adipose Stem Cells.

机构信息

Department of Biomechatronic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University (SKKU), Suwon, South Korea.

Department of Surgery, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, South Korea.

出版信息

Adv Healthc Mater. 2015 Jun 24;4(9):1359-68. doi: 10.1002/adhm.201500193. Epub 2015 Apr 15.

DOI:10.1002/adhm.201500193
PMID:25874573
Abstract

Cell-printing methods have been used widely in tissue regeneration because they enable fabricating biomimetic 3D structures laden with various cells. To achieve a cell-matrix block, various natural hydrogels that are nontoxic, biocompatible, and printable have been combined to obtain "bioinks." Unfortunately, most bioinks, including those with alginates, show low cell-activating properties. Here, a strategy for obtaining highly bioactive ink, which consisted of collagen/extracellular matrix (ECM) and alginate, for printing 3D porous cell blocks is developed. An in vitro assessment of the 3D porous structures laden with preosteoblasts and human adipose stem cells (hASCs) demonstrates that the cells in the bioinks are viable. Osteogenic activities with the designed bioinks show much higher levels than with the "conventional" alginate-based bioink. Furthermore, the hepatogenic differentiation ability of hASCs with the bioink is evaluated using the liver-specific genes, albumin, and TDO2, under hepatogenic differentiation conditions. The genes are activated within the 3D cell block fabricated using the new bioink. These results demonstrate that the 3D cell-laden structure fabricated using collagen/ECM-based bioinks can provide a novel platform for various tissue engineering applications.

摘要

细胞打印方法已广泛应用于组织再生领域,因为它们能够制造含有各种细胞的仿生 3D 结构。为了获得细胞-基质块,已经将各种无毒、生物相容且可打印的天然水凝胶结合起来以获得“生物墨水”。不幸的是,包括藻酸盐在内的大多数生物墨水的细胞激活性能都较低。在这里,开发了一种用于打印 3D 多孔细胞块的策略,该策略获得了由胶原/细胞外基质 (ECM) 和藻酸盐组成的高生物活性墨水。体外评估了负载原代成骨细胞和人脂肪干细胞 (hASC) 的 3D 多孔结构,结果表明生物墨水中的细胞是存活的。与“传统”基于藻酸盐的生物墨水相比,设计的生物墨水显示出更高水平的成骨活性。此外,在肝向分化条件下,使用肝特异性基因白蛋白和 TDO2 评估了生物墨水中 hASC 的肝向分化能力。在使用新生物墨水制造的 3D 细胞块中激活了这些基因。这些结果表明,使用基于胶原/ECM 的生物墨水制造的 3D 细胞负载结构可为各种组织工程应用提供新平台。

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