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June 4, 2020

Synthetic scaffolds shake up cell culture status quo

Written By: Tom Ziemer


When researchers across the biomedical sciences want to culture cells, they often turn to Matrigel to help them do it.

The gel, drawn from cancer cells in mice, mimics the body’s own extracellular matrix, a supportive network of molecules that aids cellular function and processes. The widely available and versatile gel allows scientists to grow and differentiate stem cells, create organoids for drug testing, probe the development of blood vessels and more.

 William Murphy
William Murphy

“Matrigel is a material that’s been used by biologists for decades,” says Bill Murphy, a professor of biomedical engineering, orthopedics and rehabilitation at the University of Wisconsin-Madison. “But it’s not a material that biologists particularly like to use.”

Murphy and Elizabeth Aisenbrey, a postdoctoral researcher in Murphy’s Bioinspired Materials Laboratory, examined the drawbacks of Matrigel and the rise of synthetic alternatives in a paper published in Nature Reviews Materials in May 2020.

“It’s been the only thing that’s worked for many applications—up until recently,” says Murphy, the Harvey D. Spangler Professor and H.I. Romnes Faculty Fellow. “Really, over the last five or 10 years, there has been a lot more progress in trying to create synthetic materials that can do what Matrigel does but don’t suffer from the same limitations that Matrigel intrinsically has.”

Those limitations include variability in the material’s makeup that have hindered researchers’ attempts to reliably reproduce results from prior studies, a resistance to physical and biochemical alterations to better suit specific applications, and the potential for contaminants stemming from its animal origin. The latter is of particular concern when thinking about creating and manufacturing cell therapies for use in humans.

Like Matrigel, synthetic scaffolds made of polymers promote cell growth and tissue formation. But researchers can also tailor them to a given purpose—differentiating stem cells or assembling organoids, for example—by manipulating their properties. But biomedical engineers like Murphy and a growing number of startup companies are also increasingly creating synthetic scaffolds that offer the versatility to rival Matrigel.

“What we’re finding is if we do enough material discovery and, particularly, high-throughput material discovery, we can identify some materials that are ‘one-size-fits-many’ rather than ‘one-size-fits-one,’” says Murphy. “Matrigel, I would argue, is ‘one-size-sort-of-fits-many.’ But it doesn’t really fit any.”

Murphy and his research group have developed array-based screening methods that allow them to test human cells’ responses to thousands of materials at a time. In a 2017 paper in Nature Biomedical Engineering, he and collaborators identified a synthetic polymer hydrogel that was more effective than Matrigel for use in blood vessel development assays.

More recently, they screened about 1,000 materials to identify three that proved highly effective in culturing human mesenchymal stem cells, patient-derived adult stem cells that can be used in cell therapies.

In their paper, Murphy and Aisenbrey note the cost of creating synthetic scaffolds has been a barrier to widespread adoption. But Murphy says that is changing.

“We now have a number of startup companies that are developing these materials and demonstrating that they are as effective or even more effective than Matrigel,” he says. “And maybe more importantly, they’re demonstrating this in high-value applications.”

Those applications include drug discovery and biomanufacturing. Synthetic scaffolds could allow for personalized drug screenings on cells taken from a patient. In biomanufacturing, which Murphy says could be a game changer for synthetics, such materials could offer the safety and level of control that’s essential when producing human cells for therapies.

To realize that potential, though, Murphy stresses the importance of ongoing dialogue among researchers developing synthetic materials, companies that can commercialize them, and clinicians and industry scientists who will use them. As director of the Forward BIO Institute at UW-Madison and chair of the Forward BIO Initiative, a public-private partnership, those are the sorts of conversations he aims to facilitate.

“The reality is we could invent a wonderfully effective new material,” he says, “but if it doesn’t fit into the workflows that are used in industry, then it’s just a science project.”