Construction of Tissue-Level Cancer-Vascular Model with High-Precision Position Control via In Situ 3D Cell Printing

Area of Science:

• Biotechnology
• Cancer Research
• 3D Bioprinting

Background:

• Tumor size and location significantly impact cancer metastasis by influencing hypoxia and angiogenesis.
• Previous studies lacked flexible techniques to control 3D tumor constructs and their spatial relationship with vasculature.
• Investigating tumor-vascular interactions is crucial for understanding metastasis but is hindered by technological limitations.

Purpose of the Study:

• To present a novel tissue-level platform for studying cancer metastasis using in situ 3D cell printing.
• To enable precise control over the size and spatial positioning of 3D cancer spheroids relative to vasculature.
• To investigate the impact of tumor-vasculature proximity on metastasis-associated changes.

Main Methods:

• Development of a platform combining a metastatic cancer unit (MCU) and a perfusable vascular endothelium system (VES) using in situ 3D cell printing.
• Printing size-tunable (500-1000 µm) and position-controllable 3D cancer spheroids within a bioink bath.
• Establishing self-driven perfusable vascular channels and controlling the distance between MCU and VES to study cancer-vascular interactions.

Main Results:

• A 600 µm diameter MCU exhibited hypoxia, invasion, and pro-angiogenetic signaling.
• Increased proximity between MCU and VES augmented epithelial-mesenchymal transition (EMT) in the cancer unit.
• Close proximity also induced vascular dysfunction and inflammation in the vascular endothelium system.

Conclusions:

• The developed 3D bioprinting platform precisely controls tumor-vasculature interactions, mimicking metastatic progression.
• Tumor proximity to vasculature significantly enhances metastatic potential and associated cellular changes.
• This platform offers a promising tool for precision cancer medicine and personalized treatment strategies.