Three-dimensional bioprinted glioblastoma microenvironments model cellular dependencies and immune interactions

Area of Science:

• Biomedical Engineering
• Cancer Biology
• Neuro-oncology

Background:

• Brain tumors, particularly glioblastoma, are complex ecosystems.
• Macrophages/microglia play a significant role in recurrent glioblastoma.
• Existing models lack the complexity to fully represent the tumor microenvironment.

Purpose of the Study:

• To develop a reproducible and scalable 3D bioprinting method for brain tumor models.
• To investigate the role of macrophages in glioblastoma stem cell (GSC) behavior within a 3D microenvironment.
• To identify novel therapeutic targets using advanced biomimetic models.

Main Methods:

• Developed a rapid 3D bioprinting technique using hyaluronic acid-rich hydrogels.
• Co-cultured glioblastoma stem cells (GSCs) with astrocytes and neural precursor cells, with and without macrophages.
• Utilized whole-genome CRISPR screening in bioprinted multicellular systems.

Main Results:

• Bioprinted constructs with macrophages mimicked patient-derived transcriptional profiles linked to survival, stemness, invasion, and drug resistance.
• Identified unique molecular dependencies in GSCs within the 3D bioprinted model compared to traditional sphere cultures.
• Demonstrated the ability of the model to recapitulate key aspects of glioblastoma pathophysiology.

Conclusions:

• 3D bioprinting provides a scalable and physiologically relevant platform for studying brain tumors.
• Macrophage integration is critical for accurately modeling glioblastoma behavior and drug response.
• This platform enables interrogation of cellular crosstalk, invasion, and immunologic interactions in brain tumors.