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[生物制造:组织再生的新方法]

[Biofabrication: new approaches for tissue regeneration].

作者信息

Horch Raymund E, Weigand Annika, Wajant Harald, Groll Jürgen, Boccaccini Aldo R, Arkudas Andreas

机构信息

Universitätsklinikum Erlangen, Plastische und Handchirurgische Klinik.

Abteilung für Molekulare Innere Medizin Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg.

出版信息

Handchir Mikrochir Plast Chir. 2018 Apr;50(2):93-100. doi: 10.1055/s-0043-124674. Epub 2018 Jan 29.

Abstract

BACKGROUND

The advent of Tissue Engineering (TE) in the early 1990ies was fostered by the increasing need for functional tissue and organ replacement. Classical TE was based on the combination of carrier matrices, cells and growth factors to reconstitute lost or damaged tissue and organs. Despite considerable results in vitro and in experimental settings the lack of early vascularization has hampered its translation into daily clinical practice so far. A new field of research, called "biofabrication" utilizing latest 3D printing technologies aims at hierarchically and spatially incorporating different cells, biomaterials and molecules into a matrix to alleviate a directed maturation of artificial tissue.

MATERIALS AND METHODS

A literature research of the relevant publications regarding biofabrication and bioprinting was performed using the PubMed data base. Relevant papers were selected and evaluated with secondary analysis of specific citations on the bioprinting techniques.

RESULTS

180 relevant papers containing the key words were identified and evaluated. Basic principles into the developing field of bioprinting technology could be discerned. Key elements comprise the high-throughput assembly of cells and the fabrication of complex and functional hierarchically organized tissue constructs. Five relevant technological principles for bioprinting were identified, such as stereolithography, extrusion-based printing, laser-assisted printing, inkjet-based printing and nano-bioprinting. The different technical methods of 3D printing were found to be associated with various positive but also negative effects on cells and proteins during the printing process. Research efforts in this field obviously aim towards the development of optimizing the so called bioinks and the printing technologies.

CONCLUSION

This review details the evolution of the classical methods of TE in Regenerative Medicine into the evolving field of biofabrication by bioprinting. The advantages of 3D bioprinting over traditional tissue engineering techniques are based on the assembling of cells, biomaterials and biomolecules in a spatially controlled manner to reproduce native tissue macro-, micro- and nanoarchitectures, that can be utilized not only to potentially produce functional replacement tissues or organs but also to serve as new models for basic research. Mimicking the stromal microenvironment of tumor cells to study the process of tumor formation and progression, metastasis, angiogenesis and modulation of the associated processes is one of these applications under research. To this end a close collaboration of specialists from the fields of engineering, biomaterial science, cell biology and reconstructive microsurgery will be necessary to develop future strategies that can overcome current limitations of tissue generation.

摘要

背景

20世纪90年代初组织工程(TE)的出现,是由于对功能性组织和器官替代的需求不断增加。传统的组织工程基于载体基质、细胞和生长因子的组合,以重建受损或缺失的组织和器官。尽管在体外和实验环境中取得了相当大的成果,但早期血管化的缺乏至今阻碍了其转化为日常临床实践。一个名为“生物制造”的新研究领域,利用最新的3D打印技术,旨在将不同的细胞、生物材料和分子分层且空间性地整合到一个基质中,以促进人工组织的定向成熟。

材料与方法

使用PubMed数据库对有关生物制造和生物打印的相关出版物进行文献研究。选择相关论文,并通过对生物打印技术的特定引用进行二次分析来评估。

结果

识别并评估了180篇包含关键词的相关论文。可以看出生物打印技术发展领域的基本原理。关键要素包括细胞的高通量组装以及复杂且功能分层组织的组织构建体的制造。确定了生物打印的五个相关技术原理,如立体光刻、挤出式打印、激光辅助打印、喷墨式打印和纳米生物打印。发现3D打印的不同技术方法在打印过程中对细胞和蛋白质有各种积极和消极影响。该领域的研究工作显然旨在开发优化所谓生物墨水和打印技术。

结论

本综述详细介绍了再生医学中传统组织工程方法向通过生物打印发展的生物制造领域的演变。3D生物打印相对于传统组织工程技术的优势在于,能够以空间可控的方式组装细胞、生物材料和生物分子,以重现天然组织的宏观、微观和纳米结构,这不仅可用于潜在地生产功能性替代组织或器官,还可作为基础研究的新模型。模拟肿瘤细胞的基质微环境以研究肿瘤形成和进展、转移、血管生成以及相关过程的调节,是正在研究的这些应用之一。为此,工程、生物材料科学、细胞生物学和重建显微外科领域的专家密切合作,对于制定能够克服当前组织生成限制的未来策略将是必要的。

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