Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, China.
Lab Chip. 2013 Jun 21;13(12):2350-8. doi: 10.1039/c3lc50183c. Epub 2013 May 3.
The integration of microfabrication and biomaterials enables construction of miniaturized 3D microenvironments with biomimetic micro-architectural and functional features to advance cell-based assays for mechanism investigation of physio/pathology and for prediction of drug responses. However, current biomaterials-assisted constructions of miniaturized 3D cellular microenvironments usually involve cells in the microfabrication process, limiting their wide application in most biomedical labs, where expertise and facilities are not readily available. Here we tackle this challenge by developing off-the-shelf microsponge arrays as pre-formed micro-patterned templates which can separate the microfabrication steps from the cell-handling steps and miniaturize the cell-based assays. The microsponge arrays with tailored microarchitectures (e.g. micropillar/well arrays or bifurcated vascular network) could be stored and delivered to distant locations as ready-to-use chips. The highly porous and microscale sponges enabled automatic and uniform loading of cellular niche components (cells, matrices and soluble factors) by simply pipetting, making it accessible to any lab with basic cell culture setups. Meanwhile, the chips containing miniaturized 3D cellular microenvironments with versatile micro-architectural designs could be integrated (i.e. by autoloading and sandwiching) to enable novel 3D cell-based assays (e.g. discrete gradient-based cytotoxicity test and horizontal 3D invasion assay) in an efficient and parallel manner. The off-the-shelf platform based on microsponge array is expected to be widely applicable across multiple disciplines in cell biology, cell/tissue engineering and pharmacological science.
微制造和生物材料的结合使构建具有仿生微结构和功能特征的小型化 3D 微环境成为可能，从而推进基于细胞的测定方法，以研究生理/病理机制并预测药物反应。然而，当前基于生物材料的小型化 3D 细胞微环境的构建通常涉及微制造过程中的细胞，这限制了它们在大多数缺乏相关专业知识和设备的生物医学实验室中的广泛应用。在这里，我们通过开发即用型微海绵阵列作为预先形成的微图案模板来解决这一挑战，该模板可以将微制造步骤与细胞处理步骤分离，并使基于细胞的测定微型化。具有定制微结构的微海绵阵列（例如微柱/孔阵列或分叉血管网络）可以作为即用型芯片进行存储和运输到遥远的地方。高度多孔和微尺度的海绵可通过简单地移液实现细胞生态位成分（细胞、基质和可溶性因子）的自动和均匀加载，这使得任何具有基本细胞培养设备的实验室都可以使用。同时，包含具有多种微结构设计的小型化 3D 细胞微环境的芯片可以进行集成（即通过自动加载和夹心），从而以高效和并行的方式实现新型 3D 基于细胞的测定（例如离散梯度细胞毒性测试和水平 3D 侵袭测定）。基于微海绵阵列的即用型平台有望在细胞生物学、细胞/组织工程和药理学科学的多个领域得到广泛应用。
