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用于生成具有复杂几何形状的高分辨率和保真度工程组织的载干细胞水凝胶生物墨水。

Stem cell-laden hydrogel bioink for generation of high resolution and fidelity engineered tissues with complex geometries.

作者信息

Jeon Oju, Lee Yu Bin, Lee Sang Jin, Guliyeva Nazilya, Lee Joanna, Alsberg Eben

机构信息

Department of Biomedical Engineering, University of Illinois at Chicago, Chicago, IL, 60607, USA.

Department of Chemistry, University of Illinois at Chicago, Chicago, IL, 60607, USA.

出版信息

Bioact Mater. 2021 Dec 22;15:185-193. doi: 10.1016/j.bioactmat.2021.11.025. eCollection 2022 Sep.

Abstract

Recently, 3D bioprinting has been explored as a promising technology for biomedical applications with the potential to create complex structures with precise features. Cell encapsulated hydrogels composed of materials such as gelatin, collagen, hyaluronic acid, alginate and polyethylene glycol have been widely used as bioinks for 3D bioprinting. However, since most hydrogel-based bioinks may not allow rapid stabilization immediately after 3D bioprinting, achieving high resolution and fidelity to the intended architecture is a common challenge in 3D bioprinting of hydrogels. In this study, we have utilized shear-thinning and self-healing ionically crosslinked oxidized and methacrylated alginates (OMAs) as a bioink, which can be rapidly gelled by its self-healing property after bioprinting and further stabilized via secondary crosslinking. It was successfully demonstrated that stem cell-laden calcium-crosslinked OMA hydrogels can be bioprinted into complicated 3D tissue structures with both high resolution and fidelity. Additional photocrosslinking enables long-term culture of 3D bioprinted constructs for formation of functional tissue by differentiation of encapsulated human mesenchymal stem cells.

摘要

最近,3D生物打印作为一种有前景的生物医学应用技术被广泛探索,它有潜力制造出具有精确特征的复杂结构。由明胶、胶原蛋白、透明质酸、藻酸盐和聚乙二醇等材料组成的细胞封装水凝胶已被广泛用作3D生物打印的生物墨水。然而,由于大多数基于水凝胶的生物墨水在3D生物打印后可能无法立即快速稳定,因此在水凝胶的3D生物打印中,实现高分辨率和与预期结构的保真度是一个常见的挑战。在本研究中,我们使用了具有剪切变稀和自愈合特性的离子交联氧化和甲基丙烯酸化藻酸盐(OMA)作为生物墨水,其在生物打印后可通过自愈合特性快速凝胶化,并通过二次交联进一步稳定。成功证明了负载干细胞的钙交联OMA水凝胶可以被生物打印成具有高分辨率和保真度的复杂3D组织结构。额外的光交联能够对3D生物打印构建体进行长期培养,通过封装的人间充质干细胞的分化形成功能性组织。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0556/8940765/3e57f2c923cc/ga1.jpg

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