3D‐Bioprinted Mini‐Brain: A Glioblastoma Model to Study Cellular Interactions and Therapeutics

Abstract

Glioblastoma-associated macrophages (GAMs) play a crucial role in the progression and invasiveness of glioblastoma multiforme (GBM); however, the exact crosstalk between GAMs and glioblastoma cells is not fully understood. Furthermore, there is a lack of relevant in vitro models to mimic their interactions. Here, novel 3D-bioprinted mini-brains consisting of glioblastoma cells and macrophages are presented as tool to study the interactions between these two cell types and to test therapeutics that target this interaction. It is demonstrated that in the mini-brains, glioblastoma cells actively recruit macrophages and polarize them into a GAM-specific phenotype, showing clinical relevance to transcriptomic and patient survival data. Furthermore, it is shown that macrophages induce glioblastoma cell progression and invasiveness in the mini-brains. Finally, it is demonstrated how therapeutics can inhibit the interaction between GAMs and tumor cells resulting in reduced tumor growth and more sensitivity to chemotherapy. It is envisioned that this 3D-bioprinted tumor model is used to improve the understanding of tumor biology and for evaluating novel cancer therapeutics.

The Construction and Application of Three‐Dimensional Biomaterials

“…A variety of approaches have been proposed to prepare 3D biomaterials, such as electro‐jetting/‐spinning, micro‐molding, microfluidics, and 3D bio‐printing . By using these methods, biomaterials with 3D, biomimetic, and desired structures can be achieved . Meanwhile, different polymerization techniques, including ionic crosslinking, solvent exchange, and photo‐polymerization, are applied to fabricate cured 3D biomaterials .…”

Additive Manufacturing of Precision Biomaterials

“…Bottom right: Crosstalk between macrophages and glioblastoma cells, enabling the study of phenotypic alterations of both cell populations. Adapted with permission . Copyright 2019, Wiley‐VCH.…”

“…At higher throughput, robotic dispensing has also been applied to model muscle and tendon tissues for improved drug screening and disease modeling . Recently, bioprinting has been adapted to model glioblastoma development, immune cell interactions, and therapy in miniaturized brain models (Figure b) . Laser assisted bioprinting is an additional technology that provides control over the spatial location of cells and materials for microscale tissue fabrication …”

“…[183] Recently, bioprinting has been adapted to model glioblastoma development, immune cell interactions, and therapy in miniaturized brain models (Figure 4b). [173,184] Laser assisted bioprinting is an additional technology that provides control over the spatial location of cells and materials for microscale tissue fabrication. [185] In all cases, the general principle has been to use AM to define the organization and material properties of the 3D Adv.…”

Fabricating Mechanically Robust Binder‐Free Structured Zeolites by 3D Printing Coupled with Zeolite Soldering: A Superior Configuration for CO2 Capture

“…[13,14] Self-supporting is the other strategy through freeze casting, [15] sacrificial templating, [16] quasi-solid gel crystallization, [17] pulsed current processing, [18] which is an effective approach to enhance the volume efficiency of the fixed bed reactor. [20][21][22][23] Various porous materials including porous ceramics, [24] porous polymers, [25] metalorganic frameworks, [26] and covalent organic frameworks [27] with complex self-supporting architectures have been successfully fabricated by 3D printing, particularly, 3D printing has proven to be an attractive strategy to tailor monolithic zeolite adsorbents and catalysts with hierarchical structures that are favorable for diffusions. [13,18,19] Recently, the unique capabilities of computer-aided additive manufacturing, also known as 3D printing, for accurate fabrication of geometries with customization, flexibility, and complexity, drive a revolution in the fields of biomedical engineering, energy, catalysis, and environment.…”