Generation of a Perfusable 3D Lung Cancer Model by Digital Light Processing

Area of Science:

• Biotechnology
• Oncology
• Drug Discovery

Background:

• Lung cancer remains a leading cause of cancer mortality globally, necessitating novel therapeutic strategies.
• Current drug development relies on accurate human cancer models to assess treatment efficacy.
• Existing models often lack the complexity of the tumor microenvironment, limiting their predictive power.

Purpose of the Study:

• To develop and validate a novel 3D bioprinted non-small cell lung cancer model incorporating a perfusion system for drug screening.
• To evaluate the impact of dynamic cultivation via perfusion on drug efficacy and cellular response compared to static 2D and 3D cultures.
• To establish a reproducible and accessible model for initial assessment of anticancer drug cytotoxicity.

Main Methods:

• Generation of a 3D non-small cell lung cancer model using digital light processing (DLP) bioprinting with simulated vasculature.
• Cultivation of the 3D model under static and dynamic (perfusion) conditions.
• Assessment of gemcitabine efficacy by determining IC50 values and evaluating cell viability, apoptosis markers (caspase-3, PARP-1) in 2D and 3D cultures.

Main Results:

• The 3D bioprinted model with perfusion demonstrated significantly increased cell viability (~60%) under dynamic cultivation compared to static conditions.
• Gemcitabine efficacy was enhanced in the perfusion system, with increased cytotoxicity, apoptosis (4x caspase-3, 6x PARP-1), and a higher IC50 value in 3D constructs compared to 2D cultures.
• The drug penetration into the hydrogel matrix resulted in an IC50 value three orders of magnitude higher in 3D models than in 2D cultures.

Conclusions:

• The developed 3D bioprinted lung cancer model with perfusion offers a promising platform for initial drug screening and cytotoxicity testing.
• Dynamic cultivation significantly improves the physiological relevance of the model, enhancing drug response and mimicking in vivo conditions more closely.
• Further refinements, including multi-cell types and endothelialization, are needed for advanced drug characterization.