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3D 生物打印全包容型生物分析平台用于细胞研究。

3D-bioprinted all-inclusive bioanalytical platforms for cell studies.

机构信息

Medical School, Stanford University, Palo Alto, CA, USA.

Department of Electrical Engineering, University of California, Irvine, CA, USA.

出版信息

Sci Rep. 2020 Sep 4;10(1):14669. doi: 10.1038/s41598-020-71452-6.

Abstract

Innovative drug screening platforms should improve the discovery of novel and personalized cancer treatment. Common models such as animals and 2D cell cultures lack the proper recapitulation of organ structure and environment. Thus, a new generation of platforms must consist of cell models that accurately mimic the cells' microenvironment, along with flexibly prototyped cell handling structures that represent the human environment. Here, we adapted the 3D-bioprinting technology to develop multiple all-inclusive high throughputs and customized organ-on-a-chip-like platforms along with printed 3D-cell structures. Such platforms are potentially capable of performing 3D cell model analysis and cell-therapeutic response studies. We illustrated spherical and rectangular geometries of bio-printed 3D human colon cancer cell constructs. We also demonstrated the utility of directly 3D-bioprinting and rapidly prototyping of PDMS-based microfluidic cell handling arrays in different geometries. Besides, we successfully monitored the post-viability of the 3D-cell constructs for seven days. Furthermore, to mimic the human environment more closely, we integrated a 3D-bioprinted perfused drug screening microfluidics platform. Platform's channels subject cell constructs to physiological fluid flow, while its concave well array hold and perfused 3D-cell constructs. The bio-applicability of PDMS-based arrays was also demonstrated by performing cancer cell-therapeutic response studies.

摘要

创新的药物筛选平台应该能够提高新型和个性化癌症治疗的发现率。常见的模型,如动物和 2D 细胞培养,缺乏对器官结构和环境的适当重现。因此,新一代的平台必须包含能够准确模拟细胞微环境的细胞模型,以及灵活的原型化细胞处理结构,以代表人体环境。在这里,我们采用了 3D 生物打印技术,开发了多种高通量的、定制的类器官芯片平台,以及打印的 3D 细胞结构。这些平台有可能进行 3D 细胞模型分析和细胞治疗反应研究。我们展示了生物打印的 3D 人类结肠癌细胞结构的球形和矩形几何形状。我们还演示了直接 3D 生物打印和快速原型制作基于 PDMS 的微流控细胞处理阵列在不同几何形状中的应用。此外,我们成功地监测了 3D 细胞结构 7 天的存活情况。此外,为了更紧密地模拟人体环境,我们集成了一个 3D 生物打印的灌流药物筛选微流控平台。平台的通道使细胞结构经受生理流体流动,而其凹形井阵列容纳和灌流 3D 细胞结构。基于 PDMS 的阵列的生物适用性也通过进行癌症细胞治疗反应研究得到了证明。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c67/7474064/356a1e3508fa/41598_2020_71452_Fig1_HTML.jpg

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