The Advances in Glioblastoma On-a-Chip for Therapy Approaches.

Abstract

Simple SummaryThis systematic review showed different therapeutic approaches to glioblastoma on-a-chip with varying levels of complexity, answering, from the simplest question to the most sophisticated questions, in a biological system integrated in an efficient way. With advances in manufacturing protocols, soft lithography in PDMS material was the most used in the studies, applying different strategy geometrics in device construction. The microenvironment showed the relevant elaborations in co-culture between mainly human tumor cells and support cells involved in the collagen type I matrix; remaining an adequate way to assess the therapeutic approach. The most complex devices showed efficient intersection between different systems, allowing in vitro studies with major human genetic similarity, reproducibility, and low cost, on a highly customizable platform.This systematic review aimed to verify the use of microfluidic devices in the process of implementing and evaluating the effectiveness of therapeutic approaches in glioblastoma on-a-chip, providing a broad view of advances to date in the use of this technology and their perspectives. We searched studies with the variations of the keywords “Glioblastoma”, “microfluidic devices”, “organ-on-a-chip” and “therapy” of the last ten years in PubMed and Scopus databases. Of 446 articles identified, only 22 articles were selected for analysis according to the inclusion and exclusion criteria. The microfluidic devices were mainly produced by soft lithography technology, using the PDMS material (72%). In the microenvironment, the main extracellular matrix used was collagen type I. Most studies used U87-MG glioblastoma cells from humans and 31.8% were co-cultivated with HUVEC, hCMEC/D3, and astrocytes. Chemotherapy was the majority of therapeutic approaches, assessing mainly the cellular viability and proliferation. Furthermore, some alternative therapies were reported in a few studies (22.6%). This study identified a diversity of glioblastoma on-a-chip to assess therapeutic approaches, often using intermediate levels of complexity. The most advanced level implemented the intersection between different biological systems (liver–brain or intestine–liver–brain), BBB model, allowing in vitro studies with greater human genetic similarity, reproducibility, and low cost, in a highly customizable platform.