Improving cell cultures in 2.5 dimensions

Regenerative medicine could eventually produce tissues and organs to replace organ donation, develop new cancer therapies, and create lab-grown meat alternatives to reduce climate impact.

To enable these applications, one of the questions that needs to be addressed is determining how stem cells’ growth substrates affect their ability to expand into useful cell types.

The traditional two-dimensional surfaces that cell cultures are grown on lack the signals needed for complex structures to develop. Alternatively, three-dimensional cell growth has its own problems — namely, spheroid cultures tend to struggle with diffusing nutrients to their center, and their density makes them hard to image.

Gilmour et al. pointed to 2.5-dimensional approaches as the next step for expanding the applications of in vitro cell growth.

“2.5D combines the best of both worlds — 3D culture giving the biophysical and architectural signals needed to push stem cells into mature cell types, but also an engineered, stable interface with the surface allowing for attachment and spreading of these mature cells for imaging and measurement,” said author Stuart Fraser.

With bombarding ions, plasmas can further improve this method. Plasmas can modify the surfaces of culture environments to create signals similar to those that occur in vivo by enabling reagent-free, covalent bonding with biomolecules and hydrogels.

“This form of bonding is strong and ensures that the bound species are stable in solution over the long periods desired for cell culture studies,” said author Marcela Bilek. “This approach is a convenient way to provide biochemical, mechanical, and topographical signals on the culture surfaces to control cell behaviors.”

The researchers emphasized the need for interdisciplinary collaboration between biologists, physicists, and materials scientists to develop better interfaces between cells and their substrates to expand in vitro cell growth techniques.

Source: “Plasma processes for the creation of customizable bio-instructive surfaces and interfaces,” by Aaron D. Gilmour, Jameel Sardharwalla, Stuart T. Fraser, Xuege Feng, Sophia C. Franklin, Clara T. H. Tran, and Marcela M. M. Bilek, Applied Physics Letters (2026). The article can be accessed at https://doi.org/10.1063/5.0301610 .