Reconstruction of Tumor Educated Vascular Network on Gelatin Methacrylate Microfluidic Chips

Vascular network of tumor microenvironment plays an important role in the scenario of tumor development. Anti-angiogenic strategies that have recently emerged, are a new generation of anticancer drugs that function based on... [ view full abstract ]

Vascular network of tumor microenvironment plays an important role in the scenario of tumor development. Anti-angiogenic strategies that have recently emerged, are a new generation of anticancer drugs that function based on regulating the structure of tumor vasculature for increasing the amount of drug delivered all through the tumor. Considering the intricate signaling networks in tumor microenvironment and the presence of a wide spectrum of angio-regulatory agents, how exactly these therapies work and why patients respond differently to these drugs and how to tailor these therapies with chemotherapeutics or molecularly targeted agents to increase survival rates are the main questions of this area that have remained unanswered due to the paucity of preclinical vascular models currently available.
In the current study, we have developed a novel Gelatin Methacrylate (GelMa) microfluidic chip with a 3 dimensional network of capillaries ranging from 25 to 100 micrometer in size, distributed at variable distances all around a tumor chamber. Endothelial cells lining the channels with different widths and distances (a network of capillaries mimicking pathologic conditions) from the tumor have the opportunity to start sprouting towards the tumor, through the GelMa matrix that is mechanically matched to the extracellular matrix in vivo, and represent the details of angiogenesis process during tumor development.
This platform can depict the dynamic nature of tumor vasculature and provide novel insights for the evaluation of structural, molecular and cellular biomarkers correlated with action mechanism of candidate drugs and their final efficiency.