Biofabrication of Modular Spheroids as Tumor-Scale Microenvironments for Drug Screening.

Area of Science:

• Biomaterials Engineering
• Cancer Biology
• Drug Discovery

Background:

• Preclinical tumor models are crucial for drug discovery but often fail to replicate native tumor complexity, impacting clinical trial success.
• Existing microscale tumor models are limited by cell-line dependency, time requirements, and lack of improved clinical outcomes.

Purpose of the Study:

• To compare hydrogel microspheres and cell-dense spheroids for generating 3D tumor microenvironments.
• To bioassemble these modules into 3D printed scaffolds for automated, tumor-scale model fabrication.
• To characterize fabrication efficiency, cell architecture, and drug response in these novel constructs.

Main Methods:

• Fabrication of cell-encapsulated Gel-MA microspheres and traditional spheroids using SKOV3 and HFF cells (monocultures and cocultures).
• Automated bioassembly of modules into 3D printed thermoplastic scaffolds to create tumor-scale models.
• Characterization of fabrication efficiency, cell architecture, and chemosensitivity assays (doxorubicin).

Main Results:

• Gel-MA microspheres showed high reproducibility and suitable dimensions for bioassembly across cell types.
• Only cocultured spheroids formed compact modules appropriate for bioassembly.
• Cocultured cells in 3D bioassembled constructs exhibited a five-fold increase in doxorubicin resistance compared to 2D monolayers.

Conclusions:

• The developed bioassembly system efficiently creates tailorable, tumor-scale models from various modules.
• These 3D tumor models demonstrate enhanced drug resistance, offering a more predictive preclinical platform.
• This approach has the potential to modernize drug discovery pipelines and improve tumorigenesis studies.