title: Engineering a Brain Cancer Chip for High-throughput Drug Screening.
abstract: 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.
authors.affiliation: Department of Biomedical Engineering, University of Houston, 3605 Cullen Blvd, Room 2027, Houston, TX, USA.
authors.forename: Yantao
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Biomedical Engineering, University of Houston, 3605 Cullen Blvd, Room 2027, Houston, TX, USA.
authors.forename: Duong Thanh
authors.initials: DT
authors.lastname: Nguyen
authors.affiliation: Department of Biomedical Engineering, University of Houston, 3605 Cullen Blvd, Room 2027, Houston, TX, USA.
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Akay
authors.affiliation: Bioinspired Engineering and Biomechanics Center, Xi'an Jiaotong University, Xi'an 710049, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Biomedical Engineering, University of Houston, 3605 Cullen Blvd, Room 2027, Houston, TX, USA.
authors.forename: Metin
authors.initials: M
authors.lastname: Akay
mesh_terms: D000970:Antineoplastic Agents / Q000302:isolation & purification*; D001932:Brain Neoplasms / Q000188:drug therapy*; D018929:Cell Culture Techniques / Q000379:methods*; D045744:Cell Line, Tumor; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D057166:High-Throughput Screening Assays; D006801:Humans; D015203:Reproducibility of Results; D018874:Spheroids, Cellular
chemical_list: D000970:Antineoplastic Agents