Biomaterials and 3D Bioprinting Strategies to Model Glioblastoma and the Blood–Brain Barrier

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.

Three-dimensional (3D) scaffolds as powerful weapons for tumor immunotherapy

“…They could prompt encapsulation of immune cells for further immunocyte functionalization which lays a solid foundation to build up in vitro 3D experimental models [ 52 ]. Compared to in vivo animal models and in vitro 2D models, 3D frameworks not only possess structurally and functionally physiological environment-mimic matrixes but also permit hierarchical control of biological processes in multidimensions which is extremely required in the explanation of immunomodulatory molecular and cellular mechanisms [ [53] , [54] , [55] ]. Moreover, suitable scaffolds can serve as cell harbour or the entrepot for co-delivering other chemical agents and biologic factors to support engineered cell cultivation [ 45 , 56 , 57 ].…”

A Novel Hydroxamic Acid-Based Curcumin Derivative as Potent Histone Deacetylase Inhibitor for the Treatment of Glioblastoma

“…In addition, DMC-HA displayed acceptable oral bioavailability (40.2%). Discovery of drugs for the treatment of GBM encounters formidable challenges to their ability to cross the blood-brain barrier (BBB) (31). Thus, we further investigated the distribution of DMC-HA to identify whether it has the ability to cross the BBB.…”

Using Spheroids as Building Blocks Towards 3D Bioprinting of Tumor Microenvironment

“…3D bioprinting possesses superior flexibility and controllability on the spatial arrangement of biomaterials and cells, which has been expansively applied to tumor-related studies including TME mimicking, tumor angiogenesis, tumor metastasis, and antitumor drug screening using individual cells and miscellaneous biomaterials[ 18 - 21 ]. Nevertheless, individually dispersed cells within the hydrogel matrix are insufficient in faithfully recapitulating specific disease states either indicating fibrosis or tumor propagation[ 22 ]. In contrast, spheroids could be a perfect alternative and implementable approach.…”