Microfluidic Modulation of Microvasculature in Microdissected Tumors

Area of Science:

• Oncology
• Biomedical Engineering
• Vascular Biology

Background:

• The tumor microenvironment's (TME) microvasculature is crucial for cancer signaling, but its ex vivo modeling is challenging.
• Engineered tissues often use non-native components, potentially affecting drug efficacy studies.
• Microdissected tumors preserve the TME but are difficult to perfuse.

Purpose of the Study:

• To develop a microfluidic platform for perfusing microdissected tumor microvasculature.
• To assess the impact of microfluidic perfusion on microvascular structure and function.
• To investigate the effects of nitric oxide pathway drugs on endothelial cells within perfused tumors.

Main Methods:

• Development of a novel microfluidic platform for perfusing microdissected tumors.
• Comparison of microfluidic perfusion versus diffusive transport in maintaining microvasculature.
• 3D imaging analysis of microvascular structures and CD31 expression.
• Exploration of nitric oxide pathway drug effects on endothelial cells under shear stress.

Main Results:

• Microfluidic perfusion resulted in larger, longer microvascular structures compared to diffusive transport.
• Enhanced expression of CD31 (endothelial cell marker) was observed in microfluidically perfused tissues.
• Nitric oxide pathway drugs demonstrated effects on endothelial cells sensitive to shear stress.

Conclusions:

• Controlled microfluidic perfusion is critical for preserving tumor microvasculature in ex vivo models.
• This platform enables better biomimicry in cancer models, bridging research and clinical applications.
• Findings offer insights into optimizing cancer treatments through vascular modulation.