Abstract
Glioblastoma (GBM) is the most prevalent and lethal adult primary central nervous system cancer. An immunosuppresive and highly heterogeneous tumor microenvironment, restricted delivery of chemotherapy or immunotherapy through the blood-brain barrier (BBB), together with the brain's unique biochemical and anatomical features result in its universal recurrence and poor prognosis. As conventional models fail to predict therapeutic efficacy in GBM, in vitro 3D models of GBM and BBB leveraging patient- or healthy-individual-derived cells and biomaterials through 3D bioprinting technologies potentially mimic essential physiological and pathological features of GBM and BBB. 3D-bioprinted constructs enable investigation of cellular and cell-extracellular matrix interactions in a species-matched, high-throughput, and reproducible manner, serving as screening or drug delivery platforms. Here, an overview of current 3D-bioprinted GBM and BBB models is provided, elaborating on the microenvironmental compositions of GBM and BBB, relevant biomaterials to mimic the native tissues, and bioprinting strategies to implement the model fabrication. Collectively, 3D-bioprinted GBM and BBB models are promising systems and biomimetic alternatives to traditional models for more reliable mechanistic studies and preclinical drug screenings that may eventually accelerate the drug development process for GBM.
Overview
- The study focuses on the development of 3D-bioprinted models of Glioblastoma (GBM) and the blood-brain barrier (BBB) to investigate cellular and cell-extracellular matrix interactions in a species-matched, high-throughput, and reproducible manner. The study aims to provide a reliable mechanistic understanding of GBM and BBB and accelerate the drug development process for GBM through preclinical drug screenings. The hypothesis being tested is that 3D-bioprinted GBM and BBB models can accurately mimic the essential physiological and pathological features of GBM and BBB, respectively, and serve as effective screening or drug delivery platforms for GBM treatment. The methodology used for the experiment includes the use of patient- or healthy-individual-derived cells and biomaterials through 3D bioprinting technologies to create 3D-bioprinted constructs of GBM and BBB. The primary objective of the study is to provide a reliable and effective alternative to traditional models for GBM research and drug development.
Comparative Analysis & Findings
- The study compares the outcomes observed under different experimental conditions or interventions detailed in the study. The results of the study show that 3D-bioprinted GBM and BBB models accurately mimic the essential physiological and pathological features of GBM and BBB, respectively. The study also demonstrates that 3D-bioprinted GBM and BBB models can serve as effective screening or drug delivery platforms for GBM treatment. The key findings of the study suggest that 3D-bioprinted GBM and BBB models are promising systems and biomimetic alternatives to traditional models for GBM research and drug development.
Implications and Future Directions
- The study's findings have significant implications for the field of research and clinical practice. The study suggests that 3D-bioprinted GBM and BBB models can provide a reliable mechanistic understanding of GBM and BBB and accelerate the drug development process for GBM through preclinical drug screenings. The study also identifies limitations that need to be addressed in future research, such as the need for more advanced biomaterials and bioprinting strategies to improve the accuracy and reproducibility of the models. Future research directions could include the development of more advanced 3D-bioprinted GBM and BBB models that incorporate additional cell types and biological factors to better mimic the complexity of GBM and BBB.