Better, faster biomaterials design with high throughput technology
by Angela C.H. McDonald
In the body, cells receive instructive signals from their niche, but how do researchers direct stem cells to perform a specific function? Researchers supply cues to cells in the form of growth factors, small molecules, cell culture density, culture surface and biomaterial design. Cells respond to these cues by altering cellular processes such as cytoskeletal organization, proliferation, adhesion, migration, secretory behaviour and differentiation.
Of particular interest to materials scientists is the cell's response to surfaces it sits on. A growing body of research is focused on enhancing biomaterial function by manipulating a number of material design parameters including the surface or topography of the materials themselves (reviewed here).
In regenerative medicine, biomaterials can function as support for cells and tissue transplanted into the body, templates for tissue regeneration and substrates for delivery and release of biological substances such as growth factors or cells into the body. The intended function of a biomaterial will inform biomaterial design strategies to elicit a specific cellular response.
A number of studies in the spinal cord injury field have experimented with material surface topography to enhance cell adhesion to scaffolds, cell migration along scaffolds and cellular differentiation. For example, altering topographic properties of materials to enhance neural regeneration results in increased neurite outgrowth and organization along nerve guidance channels.
Until recently, materials scientists have tested relatively few topographical patterns for biomaterial design. However, last month a paper published in the Proceedings of the National Academy of Sciences described a high-throughput topography screening system that will now allow researchers to screen thousands of topographical patterns at once.
Using a mathematical algorithm, researchers built distinct surface topographies using three shapes (circles, isosceles triangles and rectangles) that can be used to create different patterns. For example, triangles were used to generate angles and smooth areas were created using circles. For screening, researchers randomly selected 2176 of 154,320,600 distinct surface topographies to create the TopoChip.
To test the bioactivity of surface topographies, human mesenchymal stromal cells were grown on TopoChips. Multiple surface topographies induced a range of cellular responses including cell spreading, elongation and rounding. Using high-content imaging in combination with computer algorithms, researchers identified topographical parameters that enhance cell proliferation and differentiation.
While the ability to identify optimal topographical patterns could enhance biomaterial function, other design parameters including surface stiffness, chemistry and release of growth factors will likely provide an additive affect. Interestingly, the current issue of Nature Methods describes a high throughput artificial microarray system that allows researchers to manipulate multiple biochemical and biophysical properties in the same screening assay. The result was the creation of an artificial niche that supports the culture of mouse neural stem cells.
Materials scientists hope that the availability of high throughput screening tools for the optimization of biomaterial design will enhance our ability to direct cells to perform specific tasks. If scientists can successfully communicate instructions to cells, we will greatly improve regenerative medicine strategies.