Creating artificial nanostructures to house living cells

Important for artificially growing biotissue, finding new drugs, and stem cell research
February 6, 2013

A three-dimensional grid can keep cells in place (credit: Aleksandr Ovsianikov et al./Vienna University of Technology)

Using lasers, a research team at the Vienna University of Technology is developing microstructures for embedding living cells.

The process allows living cells to be incorporated into intricate custom structures, similar to biological tissue, in which cells are surrounded by the cell’s normal extracellular matrix.

This technology is particularly important for artificially growing biotissue, for finding new drugs, or for stem cell research.

Developing 3D structures for biomedical research

“Growing cells on a flat surface is easy, but such cell cultures often behave differently from the cells in a real three-dimensional tissue,” says research team leader Aleksandr Ovsianikov.

In two dimensions, conventional Petri dishes are used; no standard system has yet been available for three dimensional cell cultures. Such a 3D-matrix needs to be porous, so that the cells can be supplied with all the necessary nutrients.

Furthermore, it is important that the geometry, and the chemical and mechanical parameters of this matrix can be precisely adjusted to study and induce necessary cell responses, the researchers say. The structure should also be produced quickly and in large quantities, because biological experiments usually have to be carried out in many cell cultures at the same time to yield reliable data.

A laser hardens the liquid material exactly at the focal point (credit: Aleksandr Ovsianikov et al./Vienna University of Technology)

To meet these requirements, the interdisciplinary Additive Manufacturing Technologies research group at the Vienna University of Technology is developing technologies to create three dimensional structures with sub-micron (under a millionth of a meter) precision.

“We want to develop a universal method, which can serve as a standard for three-dimensional cell cultures and which can be adapted for different kinds of tissue and different kinds of cells,” says Ovsianikov.

A laser-generated cell structure

Here’s the recipe:

  1. Suspend cells in a liquid (mostly water).
  2. Add cell-friendly molecules. The focused laser beam breaks up double bonds at exactly the right places. A chemical chain reaction then causes the molecules to bond and create a polymer. (This reaction is only triggered when two laser photons are absorbed at the same time. Only within the focal point of the laser beam is the density of photons high enough for that. Material outside the focal point is not affected by the laser. “That is how we can define, with unprecedented accuracy, at which points the molecules are supposed to bond and create a solid scaffold,” explains Ovsianikov.)
  3. Guide the focus of the laser beam through the liquid, creating a solid structure in which living cells are incorporated.
  4. Wash away the the surplus molecules.

This process allows a hydrogel structure to be built that is similar to the extracellular matrix that  surrounds our own cells in living tissue. This biomimetic approach plays an increasingly important role, especially in materials science. Ovsianikov is confident that in many cases, this technology will render animal testing unnecessary and yield much quicker and more significant results.

Turning Stem Cells into Tissue

Stem cell research is a particularly interesting field of application for the new technology. “It is known that stem cells can turn into different kinds of tissue, depending on their environment.” says Aleksandr Ovsianikov. “On top of a hard surface, they tend to develop into bone cells; on a soft substrate they may turn into neurons.” In the laser-generated 3D structure, the rigidity of the substrate can be tuned so that different types of tissue can be created.

Ovsianikov has been awarded the ERC Starting Grant from the European Research Council (ERC) of approximately 1.5 million Euros.

It will be interesting to see if this technology can be combined with the 3D printing process for stem cells developed by Heriot-Watt University. — Editor