Glioblastoma-on-a-chip construction and therapeutic applications

Abstract

Glioblastoma (GBM) is the most malignant type of primary intracranial tumor with a median overall survival of only 14 months, a very poor prognosis and a recurrence rate of 90%. It is difficult to reflect the complex structure and function of the GBM microenvironment in vivo using traditional in vitro models. GBM-on-a-chip platforms can integrate biological or chemical functional units of a tumor into a chip, mimicking in vivo functions of GBM cells. This technology has shown great potential for applications in personalized precision medicine and GBM immunotherapy. In recent years, there have been efforts to construct GBM-on-a-chip models based on microfluidics and bioprinting. A number of research teams have begun to use GBM-on-a-chip models for the investigation of GBM progression mechanisms, drug candidates, and therapeutic approaches. This review first briefly discusses the use of microfluidics and bioprinting technologies for GBM-on-a-chip construction. Second, we classify non-surgical treatments for GBM in pre-clinical research into three categories (chemotherapy, immunotherapy and other therapies) and focus on the use of GBM-on-a-chip in research for each category. Last, we demonstrate that organ-on-a-chip technology in therapeutic field is still in its initial stage and provide future perspectives for research directions in the field.

Biophysical Control of the Glioblastoma Immunosuppressive Microenvironment: Opportunities for Immunotherapy

“…Furthermore, when cell culture becomes inaccessible, lab-on-a-chip technology provides a favorable alternative. GBM-on-a-chip platforms provide systems containing the biological and chemical units of a tumor that are involved in suppressing immune cell function [140]. Tumor heterogeneity represents a difficult barrier to bypass in developing effective immunotherapies; however, lab-on-a-chip technology provides a system that can be tailored to easily and accurately generate the heterogeneous regions that can be found in tumors in vivo in terms of their ECM components and characteristic 3D geometry.…”

“…Among these regional characteristics are substrate stiffness, CO 2 concentration, fluid flow, etc. [140]. After using the traditional culture platforms and tunable platforms to assess specific mechanisms, lab-on-a-chip technology can combine multiple parameters to test whether a potential synergy exists and aid in the development of drug screening tools or a deeper study of cancer immunoevasion.…”

“…Interestingly, the development of CAR T technology has recently been applied to macrophages and could be used to bypass the immune reprogramming sequence that converts them into TAMs and instead promote phagocytosis. Moreover, the amount of engulfment correlated with increased target stiffness [140,[156][157][158][159], suggesting a prominent role of biophysics in immune cell processes that have not yet been well studied. The use of bioengineered tools to increase CAR T transfection efficiency and the importance of receptor biophysics on T cell tumoricidal activity support the inclusion of biophysical parameters in the development of next-generation CAR T technologies.…”

Preclinical Models and Technologies in Glioblastoma Research: Evolution, Current State, and Future Avenues

“…For example, a study by Huang et al involved a microfluidic device to study BBB penetration by CAR T cells [289]. The study's results indicate that the microfluidic platform has the potential to comprehend the effects of CAR T therapy on cells located beyond the BBB, also considering concurrent toxicity and the processes of BBB breakdown [290].…”