Synthetic Cell Matrix Devised for Cancer Drug Testing

Scaffold made with electrospun polymer nanofibers in a honeycomb pattern (Smitha Rao, Michigan Tech)

12 Feb. 2020. A bioengineering lab is creating synthetic cell scaffolds that simulate tumor cells and tissue, offering a more reliable way of testing new cancer drugs. Researchers from Michigan Technological University in Houghton describe their process in last month’s issue of the journal IEEE Open Journal of Engineering in Medicine and Biology. The full text is available from the university.

A team led by biomedical engineering professor Smitha Rao is seeking better methods for testing cancer drugs before human clinical trials, to find toxicities or detect other adverse effects, as well as better understand cancer cell growth and migration. Rao’s team, both graduate and undergraduate students, investigated producing simulated cancerous tumor tissue with fine nanoscale polymer fibers, starting with the extracellular matrix or scaffolds, for seeding later with live cancer cells.

“In my lab,” says Rao in a university statement, “the focus has been on standardizing the process and using synthetic materials to keep the same chemical formulation of a scaffold, but change the physical structure of the fibers that are produced.” In the study, the Michigan Tech team altered just one factor, the polymer’s electric field. Otherwise, the researchers maintained the polymer’s nanofiber surface chemistry throughout the study.

The team used a process called electrospinning to create three-dimensional synthetic cell scaffolds.  Electrospinning is a technique that sprays electrically-charged polymer micro- and nanoscale fibers toward a surface, where the fibers form a mat-like structure. The polymer in this case is polycaprolactone or PCL, a bio-compatible and degradable polymer often used in regenerative medicine. In November 2019, Science & Enterprise reported on a portable device that uses electrospinning to spray bio-compatible fibers on simulated wound surfaces to promote healing.

With electrospinning, Rao and colleagues created simulated 3-D tumor tissue scaffolds for different types of breast cancer tumors, using human cancer cell lines. Their tests revealed no one type of scaffold enabled different breast cancer cells to grow into tissue. For example, triple-negative breast cancer cells prefer honeycomb scaffolds, while adenocarcinoma cells, from cancers in mucus-secreting glands, grow better on scaffolds resembling a mesh. And earlier-stage breast tumor cells, before becoming malignant, grow more readily on scaffolds with fibers aligned with each other.

The lab is working with the company DiPole Materials in Baltimore that specializes in electrospinning nanofibers, to scale up the process for industrial and commercial fabrication, such as preclinical drug testing. In the meantime, the Michigan Tech team is exploring ways of applying its cell scaffold process to better understand cancer cell growth and development.

“We can understand in a true 3D system why pre-metastatic cells become metastatic,” notes Rao, “and provide tools to other researchers to study signaling pathways that change between pre-malignant and malignant cells.” Rao tells more about the process in this video.

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