3D bioprinted tumor model with extracellular matrix enhanced bioinks for nanoparticle evaluation

Area of Science:

• Biotechnology
• Biomaterials Science
• Cancer Research

Background:

• Traditional 2D cell cultures and animal models inadequately represent the human tumor microenvironment (TME).
• This limitation hinders the accurate evaluation of nanoparticle (NP) transport and the clinical translation of nano-drug formulations.
• A need exists for more physiologically relevant models to study NP-TME interactions.

Purpose of the Study:

• To develop and validate a 3D bioprinted tumor model using adipose-derived decellularized extracellular matrix (ECM) enhanced hybrid bioink.
• To compare the biological relevance and NP interaction characteristics of the 3D model against traditional 2D cell cultures.
• To assess the utility of this 3D model for evaluating NP delivery and drug resistance within a TME context.

Main Methods:

• Fabrication of a 3D tumor model using 3D bioprinting with an ECM-enhanced hybrid bioink.
• Formation of multicellular spheroids within the 3D printed structure.
• In vitro and in vivo characterization of the 3D model, including protein and gene expression analysis, and tumorigenicity assessment.
• Evaluation of NP cellular uptake efficiency and drug resistance in both 2D and 3D models.
• Simultaneous tracking of ECM remodeling and epithelial-mesenchymal transition in the 3D model.

Main Results:

• The 3D bioprinted tumor model exhibited enhanced similarity to the native TME in terms of protein/gene expression and tumorigenicity compared to 2D cultures.
• Multicellular spheroids formed in the 3D model, closely mimicking in vivo tumor structures.
• Cellular uptake of NPs was significantly lower in the 3D model due to the ECM barrier, indicating reduced NP permeability.
• Increased drug resistance was observed in the 3D model compared to 2D cultures, highlighting the influence of the TME.
• The model successfully tracked key TME characteristics like ECM remodeling and epithelial-mesenchymal transition.

Conclusions:

• The 3D bioprinted tumor model effectively replicates critical aspects of the TME, including ECM remodeling and multicellular organization.
• This model provides a more accurate platform for assessing NP behavior, such as cellular uptake and drug resistance, compared to 2D systems.
• The developed 3D model holds significant potential for improving the preclinical evaluation of nano-drug formulations, facilitating their translation to clinical applications.