Now a team of engineers has developed a three-dimensional hydrogel that more closely mimics conditions in the brain. In a paper in the journal Biomaterials, the researchers describe the new material and their approach, which allows them to selectively tune up or down the malignancy of the cancer cells they study.
Hyaluronic acid (HA) is a key component of the extracellular matrix that provides structural and chemical support to cells throughout the body. HA contributes to cell proliferation and cell migration, and local changes in HA levels have been implicated in tumor growth.
In the new study, Pedron observed how glioma cells behaved in two different hydrogels – one based on methacrylated gelatin (GelMA) and the other using a more conventional polyethylene glycol (PEG) biomaterial. These two materials vary in one important trait: GelMA is a naturally derived material that contains adhesive sites that allow cells to latch onto it; synthetic PEG does not.
“The purpose of having these two systems was to isolate the effect of HA on glioma cells,” Pedron said. If changing HA levels produced different effects in different gels, that would indicate that the gels were contributing to those effects, she said.
Instead, Harley and Pedron found that additions of HA to glioma cells had “very similar” effects in both materials. Adding too little or too much HA led to reduced malignancy, while incorporating just enough HA led to significantly enhanced malignancy. This held true for multiple types of glioblastoma multiforme cells. This suggests that “it’s the HA itself that is likely the cause for this malignant change,” Harley said.
“If you have a material that allows you to selectively tune up or down malignancy, that will allow you to ask lots of questions about treatment methods for more malignant or less malignant forms of glioma. It also will allow scientists to try to get a response that’s closer to what you see in the body,” he said.
“If you talk to pathologists, they’ll say a biomaterial will never allow you to grow a full brain tumor, which is probably true,” Harley said. “But it’s realistic to think that a well-designed biomaterial will allow you to study aspects of glioma growth and treatment in a way that’s much richer than simply looking in a petri dish and much more accessible than trying to study tumor development within the brain itself.”The U. of I. department of chemical and biomolecular engineering, the Institute for Genomic Biology and the Campus Research Board supported this research.
The paper, “Regulation of Glioma Cell Phenotype in 3D Matrices by Hyaluronic Acid,” is available online.
Diana Yates | University of Illinois
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