A Photopolymerizable Hyaluronic Acid-Collagen Model of the Invasive Glioma Microenvironment with Interstitial Flow

Our work investigates how the tumor microenvironment drives invasion of tumor cells in glioblastoma, the deadliest form of brain cancer. Specifically, we're interested in how interstitial fluid flow driven by increased intratumoral pressures causes tumor cells to invade into the surrounding brain parenchyma. We currently use these 3D hyaluronic acid collagen system mass models combined with MII imaging and a computational analysis to study glioma invasion driven by interstitial fluid flow.

For the individual approaches, fluid flow is generated by applying pressure on the top of the TME model, mimicking interstitial fluid flow in the brain. Providing the right physical cues to replicate the tissue microenvironment is a continual challenge. Our three-dimensional model uses hyaluronic acid and collagen, both found in the brain matrix, and sustained interstitial fluid flow.

Together, these factors provide key physical signals to healthy and cancerous cells. Our recent work indicates that resident brain cells influence how glioma cells respond to interstitial flow. However, this response depends on patient-specific factors.

To study the influence of these factors on glioma invasion, we developed a patient-informed model of the glioma invasive front that mimics native brain tissue. The patient tumor model allows for a highly controlled in vitro experiment that still represents tissue-level factors that influence glioma invasion. Further, this model is accessible compared to similar models of glioma invasion and interstitial flow because it does not require tubing or pumps, and it uses commercially available materials.