Mechanical Engineering Graduate Program, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Institute of Science and Technology, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Diamantina, Brazil.
PLoS One. 2020 Dec 11;15(12):e0243840. doi: 10.1371/journal.pone.0243840. eCollection 2020.
Bone marrow (BM) is an organ responsible for crucial processes in living organs, e. g., hematopoiesis. In recent years, Organ-on-a-Chip (OoC) devices have been used to satisfy the need for in vitro systems that better mimic the phenomena occurring in the BM microenvironment. Given the growing interest in these systems and the diversity of developed devices, an integrative systematic literature review is required. We have performed this review, following the PRISMA method aiming to identify the main characteristics and assess the effectiveness of the devices that were developed to represent the BM. A search was performed in the Scopus, PubMed, Web of Science and Science Direct databases using the keywords (("bone marrow" OR "hematopoietic stem cells" OR "haematopoietic stem cells") AND ("organ in a" OR "lab on a chip" OR "microfluidic" OR "microfluidic*" OR ("bioreactor" AND "microfluidic*"))). Original research articles published between 2009 and 2020 were included in the review, giving a total of 21 papers. The analysis of these papers showed that their main purpose was to study BM cells biology, mimic BM niches, model pathological BM, and run drug assays. Regarding the fabrication protocols, we have observed that polydimethylsiloxane (PDMS) material and soft lithography method were the most commonly used. To reproduce the microenvironment of BM, most devices used the type I collagen and alginate. Peristaltic and syringe pumps were mostly used for device perfusion. Regarding the advantages compared to conventional methods, there were identified three groups of OoC devices: perfused 3D BM; co-cultured 3D BM; and perfused co-cultured 3D BM. Cellular behavior and mimicking their processes and responses were the mostly commonly studied parameters. The results have demonstrated the effectiveness of OoC devices for research purposes compared to conventional cell cultures. Furthermore, the devices have a wide range of applicability and the potential to be explored.
骨髓（BM）是一个负责生命器官中关键过程的器官，例如造血。近年来，器官芯片（OoC）设备已被用于满足体外系统的需求，这些系统更好地模拟了 BM 微环境中发生的现象。鉴于人们对这些系统的兴趣日益浓厚，以及开发的设备种类繁多，需要进行综合的系统文献综述。我们按照 PRISMA 方法进行了这项综述，旨在确定旨在代表 BM 的设备的主要特点并评估其有效性。在 Scopus、PubMed、Web of Science 和 Science Direct 数据库中使用关键词（("bone marrow" OR "hematopoietic stem cells" OR "haematopoietic stem cells") AND ("organ in a" OR "lab on a chip" OR "microfluidic" OR "microfluidic*" OR ("bioreactor" AND "microfluidic*"))）进行了搜索。纳入了 2009 年至 2020 年期间发表的原始研究文章，综述共包括 21 篇论文。对这些论文的分析表明，它们的主要目的是研究 BM 细胞生物学、模拟 BM 生态位、建立 BM 病理模型和进行药物检测。关于制造方案，我们观察到聚二甲基硅氧烷（PDMS）材料和软光刻法是最常用的。为了再现 BM 的微环境，大多数设备使用 I 型胶原蛋白和藻酸盐。蠕动泵和注射器泵主要用于设备灌注。与传统方法相比，OoC 设备具有三个优势：灌注 3D BM；共培养 3D BM；和灌注共培养 3D BM。细胞行为及其过程和反应的模拟是最常用的研究参数。结果表明，与传统细胞培养相比，OoC 设备在研究目的方面具有有效性。此外，这些设备具有广泛的适用性和探索潜力。
