Mimicking Embedded Vasculature Structure for 3D Cancer on a Chip Approaches through Micromilling

Area of Science:

• Biomedical Engineering
• Cell Biology
• Tissue Engineering

Background:

• Cellular responses, including motility, are significantly influenced by their three-dimensional (3D) microenvironment and nutrient/oxygen supply via vascular structures.
• Traditional 2D cell culture methods and 3D systems with rectangular channels inadequately replicate the complex, physiologically relevant vascular architecture found in vivo.

Purpose of the Study:

• To develop and validate a novel cell-on-a-chip system that more accurately mimics the 3D cellular microenvironment and vascular supply.
• To enable more physiologically relevant studies of cell motility and response to chemical stimuli within a 3D extracellular matrix (ECM).

Main Methods:

• Engineered perfusable microfluidic channels with curved cross-sections embedded within a 3D collagen matrix.
• Utilized sacrificial circular gelatin templates for channel fabrication, removed via temperature control.
• Incorporated motile breast cancer cells within the collagen matrix and applied chemical stimulation from the microfluidic channels.

Main Results:

• The developed system successfully created a 3D cellular environment with anatomically relevant vascular structures.
• Breast cancer cells demonstrated directed migration towards the chemical stimulus supplied by the artificial vasculature.
• The system provides a more accurate simulation of cell behavior in response to vascular cues compared to 2D or rectangular channel 3D systems.

Conclusions:

• This innovative 3D extracellular matrix (ECM) system with artificial vasculature offers a more physiologically relevant platform for studying cellular dynamics.
• The system holds potential for gaining novel insights into multidirectional chemokineses and chemotaxis relevant to cancer and other diseases.
• It advances the simulation of cell-matrix and cell-vasculature interactions in a 3D context.