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胶原蛋白作为用于3D打印的生物墨水:综述

Collagen as a bio-ink for 3D printing: a critical review.

作者信息

Debnath Souvik, Agrawal Akhilesh, Jain Nipun, Chatterjee Kaushik, Player Darren J

机构信息

Department of Materials Engineering, Indian Institute of Science, C.V. Raman Avenue, Bangalore 560012, India.

Department of Bioengineering, Indian Institute of Science, C.V. Raman Avenue, Bangalore 560012, India.

出版信息

J Mater Chem B. 2025 Feb 5;13(6):1890-1919. doi: 10.1039/d4tb01060d.

DOI:10.1039/d4tb01060d
PMID:39775500
Abstract

The significance of three-dimensional (3D) bioprinting in the domain of regenerative medicine and tissue engineering is readily apparent. To create a multi-functional bioinspired structure, 3D bioprinting requires high-performance bioinks. Bio-inks refer to substances that encapsulate viable cells and are employed in the printing procedure to construct 3D objects progressive through successive layers. For a bio-ink to be considered high-performance, it must meet several critical criteria: printability, gelation kinetics, structural integrity, elasticity and strength, cell adhesion and differentiation, mimicking the native ECM, cell viability and proliferation. As an exemplar application, tissue grafting is used to repair and replace severely injured tissues. The primary considerations in this case include compatibility, availability, advanced surgical techniques, and potential complications after the operation. 3D printing has emerged as an advancement in 3D culture for its use as a regenerative medicine approach. Thus, additive technologies such as 3D bioprinting may offer safe, compatible, and fast-healing tissue engineering options. Multiple methods have been developed for hard and soft tissue engineering during the past few decades, however there are many limitations. Despite significant advances in 3D cell culture, 3D printing, and material creation, a gold standard strategy for designing and rebuilding bone, cartilage, skin, and other tissues has not yet been achieved. Owing to its abundance in the human body and its critical role in protecting and supporting human tissues, soft and hard collagen-based bioinks is an attractive proposition for 3D bioprinting. Collagen, offers a good combination of biocompatibility, controllability, and cell loading. Collagen made of triple helical collagen subunit is a protein-based organic polymer present in almost every extracellular matrix of tissues. Collagen-based bioinks, which create bioinspired scaffolds with multiple functionalities and uses them in various applications, is a represent a breakthrough in the regenerative medicine and biomedical engineering fields. This protein can be blended with a variety of polymers and inorganic fillers to improve the physical and biological performance of the scaffolds. To date, there has not been a comprehensive review appraising the existing literature surround the use of collagen-based bioink applications in 'soft' or 'hard' tissue applications. The uses of the target region in soft tissues include the skin, nerve, and cartilage, whereas in the hard tissues, it specifically refers to bone. For soft tissue healing, collagen-based bioinks must meet greater functional criteria, whereas hard tissue restoration requires superior mechanical qualities. Herein, we summarise collagen-based bioink's features and highlight the most essential ones for diverse healing situations. We conclude with the primary challenges and difficulties of using collagen-based bioinks and suggest future research objectives.

摘要

三维(3D)生物打印在再生医学和组织工程领域的重要性显而易见。为了创建多功能的仿生结构,3D生物打印需要高性能的生物墨水。生物墨水是指包裹有活细胞的物质,在打印过程中用于通过连续的层逐步构建3D物体。要使生物墨水被认为是高性能的,它必须满足几个关键标准:可打印性、凝胶化动力学、结构完整性、弹性和强度、细胞粘附和分化、模仿天然细胞外基质、细胞活力和增殖。作为一个典型应用,组织移植用于修复和替换严重受损的组织。在这种情况下的主要考虑因素包括兼容性、可用性、先进的手术技术以及术后的潜在并发症。3D打印作为一种再生医学方法,已成为3D培养的一项进步。因此,诸如3D生物打印之类的增材技术可能会提供安全、兼容且愈合快的组织工程选择。在过去几十年中,已经为硬组织和软组织工程开发了多种方法,然而仍有许多局限性。尽管在3D细胞培养、3D打印和材料制造方面取得了重大进展,但设计和重建骨骼、软骨、皮肤及其他组织的金标准策略尚未实现。由于胶原蛋白在人体中含量丰富且在保护和支撑人体组织方面起着关键作用,基于软质和硬质胶原蛋白的生物墨水对于3D生物打印来说是一个有吸引力的选择。胶原蛋白具有良好的生物相容性、可控性和细胞负载能力。由三螺旋胶原亚基组成的胶原蛋白是一种基于蛋白质的有机聚合物,几乎存在于每个组织的细胞外基质中。基于胶原蛋白的生物墨水能够创建具有多种功能的仿生支架并将其用于各种应用,这代表了再生医学和生物医学工程领域的一项突破。这种蛋白质可以与多种聚合物和无机填料混合,以改善支架的物理和生物学性能。迄今为止,尚未有一篇全面的综述来评估围绕基于胶原蛋白的生物墨水在“软”或“硬”组织应用方面的现有文献。目标区域在软组织中的用途包括皮肤、神经和软骨,而在硬组织中,它具体指骨骼。对于软组织愈合,基于胶原蛋白的生物墨水必须满足更高的功能标准,而硬组织修复则需要卓越的机械性能。在此,我们总结了基于胶原蛋白的生物墨水的特性,并突出了针对不同愈合情况最重要的特性。我们最后阐述了使用基于胶原蛋白的生物墨水的主要挑战和困难,并提出了未来的研究目标。

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