Fan Yantao, Nguyen Duong Thanh, Akay Yasemin, Xu Feng, Akay Metin
Department of Biomedical Engineering, University of Houston, 3605 Cullen Blvd, Room 2027, Houston, TX, USA.
Bioinspired Engineering and Biomechanics Center, Xi'an Jiaotong University, Xi'an 710049, China.
Sci Rep. 2016 May 6;6:25062. doi: 10.1038/srep25062.
Glioblastoma multiforme (GBM) is the most common and malignant of all human primary brain cancers, in which drug treatment is still one of the most effective treatments. However, existing drug discovery and development methods rely on the use of conventional two-dimensional (2D) cell cultures, which have been proven to be poor representatives of native physiology. Here, we developed a novel three-dimensional (3D) brain cancer chip composed of photo-polymerizable poly(ethylene) glycol diacrylate (PEGDA) hydrogel for drug screening. This chip can be produced after a few seconds of photolithography and requires no silicon wafer, replica molding, and plasma bonding like microfluidic devices made of poly(dimethylsiloxane) (PDMS). We then cultured glioblastoma cells (U87), which formed 3D brain cancer tissues on the chip, and used the GBM chip to perform combinatorial treatment of Pitavastatin and Irinotecan. The results indicate that this chip is capable of high-throughput GBM cancer spheroids formation, multiple-simultaneous drug administration, and a massive parallel testing of drug response. Our approach is easily reproducible, and this chip has the potential to be a powerful platform in cases such as high-throughput drug screening and prolonged drug release. The chip is also commercially promising for other clinical applications, including 3D cell culture and micro-scale tissue engineering.
多形性胶质母细胞瘤(GBM)是所有人类原发性脑癌中最常见且恶性程度最高的,药物治疗仍是最有效的治疗方法之一。然而,现有的药物发现和开发方法依赖于传统的二维(2D)细胞培养,而这种培养方式已被证明不能很好地代表天然生理状态。在此,我们开发了一种新型的三维(3D)脑癌芯片,其由可光聚合的聚(乙二醇)二丙烯酸酯(PEGDA)水凝胶组成,用于药物筛选。该芯片经过几秒钟的光刻即可制备,不像由聚二甲基硅氧烷(PDMS)制成的微流控装置那样需要硅片、复制模塑和等离子体键合。然后,我们培养了胶质母细胞瘤细胞(U87),这些细胞在芯片上形成了3D脑癌组织,并使用GBM芯片对匹伐他汀和伊立替康进行联合治疗。结果表明,该芯片能够实现高通量的GBM癌球体形成、多种药物同时给药以及对药物反应进行大规模并行测试。我们的方法易于重复,并且这种芯片有潜力成为高通量药物筛选和延长药物释放等情况下的强大平台。该芯片在包括3D细胞培养和微尺度组织工程在内的其他临床应用方面也具有商业前景。