Patterned Gels Direct Stem Cell Growth

Mesenchymal stem cells are found in bone marrow and can differentiate into fat, cartilage, muscle or bone. Such cells have potential application in tissue regeneration, implantation and transplantation. For this type of regenerative medicine, it is important to be able to control the behaviour of mesenchymal stem cells so they can achieve the desired outcomes.

Stem cells grow effectively on gel-phase materials that mimic the extracellular matrix and can provide cues for effective cell growth. However, achieving precise spatial and temporal control of mesenchymal stem cells is an important target and encouraging them to differentiate specifically with such control remains challenging.

Professor David Smith’s research group have considerable experience in working with supramolecular gels, self-assembled from simple low-molecular-weight building blocks into nanoscale materials. As a part of previous research, they had demonstrated that such materials could support mesenchymal stem cells and gained an understanding of how additives, such as gold nanoparticles, could promote cell growth.

Working in Professor Smith’s team, PhD student Chayanan Tangsombun developed an innovative approach for patterning such materials that would potentially enable them to control stem cells with spatial resolution. She soaked paper stamps, cut into various shapes, in a solution of gold chloride, and then placed them on top of the gel. The gold salt diffused from the stamp into the gel, where the chemistry of the gelator itself reduced the gold and caused it to assemble into gold nanoparticles. These bright purple nanoparticles were formed with spatial resolution imposed by the pattern (see figure).

When mesenchymal stem cells were grown on the patterned gel in the lab of Professor Paul Genever, they proliferated very well on the patterned domain, where they differentiated into bone cells (so-called osteogenesis), but outside of the patterned region they did not grow so effectively. The patterned gel therefore directed the mesenchymal stem cells to turn into bone cells with well-defined spatial resolution. There was also a degree of temporal control depending on the precise gel composition.

Reflecting on the work Professor Smith said: "It’s remarkable to see such a simple approach, using a paper stamp to print chemical patterns into a gel, providing such effective control over the fate of mesenchymal stem cells, it always makes me smile when we can use chemistry to instruct biology what to do!

"In the future, we hope to use this kind of technology, alongside other methods for printing, shaping and patterning gels, in order to create highly functional structured materials capable of sophisticated cell growth outcomes suitable for application in regenerative medicine."