基于光的生物3D打印睾丸类器官作为生殖毒性评估的体外模型。

IF 5.4 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS
Tianyi Feng, Liping Wei, Changhui Zhou, Shenning Li, Yingqi Li, Yali Fang, Wenteng Cui, Xiaohui Li, Lingzhi Bao, Lei Shen, Min Tang, Yan Chang
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引用次数: 0

摘要

类器官可作为体外研究组织发育和毒理学评价的平台。虽然体细胞和生殖细胞的体外成熟已经在类器官中得到证实,但产生可再生的原代睾丸细胞衍生的类器官用于毒性评估仍然具有挑战性。在这项研究中,我们利用基于光的3D生物打印技术在transwell插入物上培育了新生小鼠原代睾丸细胞。根据睾丸组织的细胞外基质组成和力学性能,对生物打印油墨的组成进行了设计和优化。使用优化的培养基培养类器官21天,以支持睾丸细胞的发育和功能。这些生物打印的类器官再现了体内睾丸结构的关键特征,形成了具有细胞组织和基因表达谱的小管状结构,与天然组织相似。暴露于已知的雄性生殖毒性物质雷公藤甲素后,睾丸类器官显示紧密连接蛋白CLAUDIN-11的缺失和体细胞标记物转录水平的改变。每个生物打印睾丸类器官可在1分钟内生成,毒性评估结果可在1个月内获得。这种快速转变使其成为一个有前途的高通量毒理学研究平台,促进了我们对睾丸发育、功能和潜在毒物对男性生殖健康影响的理解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Light-Based 3D Bioprinting of Testicular Organoid as an In Vitro Model for Reproductive Toxicity Assessment.

Organoids can be used as an in vitro platform for studying tissue development and toxicology evaluation. While in vitro maturation of somatic and germ cells has been demonstrated in organoids, generating reproducible primary testicular cell-derived organoids for toxicity evaluation remains challenging. In this study, we developed testicular organoids using light-based 3D bioprinting of neonatal mouse primary testicular cells on transwell inserts. The bioprinting ink composition was specifically designed and optimized based on the extracellular matrix composition and mechanical properties of testicular tissue. The organoids were cultured for 21 days using an optimized medium to support testicular cell development and function. These bioprinted organoids recapitulated key features of the in vivo testicular architecture, forming tubule-like structures with cellular organization and gene expression profiles similar to native tissue. Following exposure to the known male reproductive toxic agent triptolide, testicular organoids showed loss of tight junction protein CLAUDIN-11 and altered transcript levels of somatic markers. Each bioprinted testicular organoid can be generated within 1 min, with toxicity evaluation results available within 1 month. This rapid turnaround makes it a promising high-throughput platform for toxicological studies, advancing our understanding of testicular development, function, and the impact of potential toxicants on male reproductive health.

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来源期刊
ACS Biomaterials Science & Engineering
ACS Biomaterials Science & Engineering Materials Science-Biomaterials
CiteScore
10.30
自引率
3.40%
发文量
413
期刊介绍: ACS Biomaterials Science & Engineering is the leading journal in the field of biomaterials, serving as an international forum for publishing cutting-edge research and innovative ideas on a broad range of topics: Applications and Health – implantable tissues and devices, prosthesis, health risks, toxicology Bio-interactions and Bio-compatibility – material-biology interactions, chemical/morphological/structural communication, mechanobiology, signaling and biological responses, immuno-engineering, calcification, coatings, corrosion and degradation of biomaterials and devices, biophysical regulation of cell functions Characterization, Synthesis, and Modification – new biomaterials, bioinspired and biomimetic approaches to biomaterials, exploiting structural hierarchy and architectural control, combinatorial strategies for biomaterials discovery, genetic biomaterials design, synthetic biology, new composite systems, bionics, polymer synthesis Controlled Release and Delivery Systems – biomaterial-based drug and gene delivery, bio-responsive delivery of regulatory molecules, pharmaceutical engineering Healthcare Advances – clinical translation, regulatory issues, patient safety, emerging trends Imaging and Diagnostics – imaging agents and probes, theranostics, biosensors, monitoring Manufacturing and Technology – 3D printing, inks, organ-on-a-chip, bioreactor/perfusion systems, microdevices, BioMEMS, optics and electronics interfaces with biomaterials, systems integration Modeling and Informatics Tools – scaling methods to guide biomaterial design, predictive algorithms for structure-function, biomechanics, integrating bioinformatics with biomaterials discovery, metabolomics in the context of biomaterials Tissue Engineering and Regenerative Medicine – basic and applied studies, cell therapies, scaffolds, vascularization, bioartificial organs, transplantation and functionality, cellular agriculture
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