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Introduction: Glioma is known as one of the most malignant brain tumors originated from glial stem cells or progenitor cells [1]. Current therapies to cure glioma cases still seem insufficient [2] due to glioma’s invasiveness and heterogeneous tumor microenvironment [3]. To investigate glioma behavior thoroughly and to develop personalized therapy for tumors is challenging, and various 3D microfluidic platforms were proposed to study glioma tumors [3]. Recently, natural or synthetic polymers have been used for creating the 3D environment for cells. Here, we proposed a microfluidic platform that mimics the glioblastoma tumor microenvironment. We integrated the gelatin-derived hydrogel and microfluidic chips to obtain a more realistic glioma tumor microenvironment.
Methodology: Novel multiplexed microfluidic chips were designed and fabricated via uv&soft lithography. The photomasks were specifically designed and produced to create desired hydrogel geometry within the chips. Prepolymer solution was prepared by adding 5% methacrylated gelatin (GelMA) and 1% Irgacure 2959. Hydrogel contained photoinitator was mixed with U373 glioblastoma cells, and they were transferred into the microfluidic chips by syringe pump. Encapsulation of the glioblastoma cells (U373 human glioblastoma) within the GelMA hydrogel was performed by photocrosslinking under the 365 nm of UV light, and specially designed photomasks was put on the chip during this process. Cell viability, after encapsulation, were analyzed by cell toxicity LIVE/DEAD assay.
Results: Our studies demonstrated that GelMA hydrogel in the microfluidic chip reservoirs demonstrate sufficient structural integrity under the shear stress due to perfusion. High cell viability of encapsulated U373 glioblastoma cells within the GelMA in the chip was observed after several days.
Conclusion: Current therapies for glioma have challenges due to glioma’s invasive character. A depth understanding of its molecular mechanisms is essential to develop personalized treatment. Mimicking tumor microenvironment via microfluidic chips has high potential to create a more realistic in vitro glioma tumor environment, leading to study cell migration, invasion, angiogenesis, and patient-specific treatment [3]. Moreover, in vivo animal studies would be eventually replaced with microfluidic platforms, and these also platforms allow investigating the drug combinations. In this study, we developed microfluidic platforms that offer a high chance of examining glioma tumors and investigating personalized therapies.
[1] Ostrom, Q.T., et al., Neuro-Oncology, 16: p. 1-63. (2014)
[2] Tan, A.C., et al., Ca-Cancer J. Clin., 70, 299–312. (2020)
[3] Ustun, M., et al., Micromachines, 12, 490. (2021)
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