Mimicking Biological Complexity, İn A Tiny Particle

Tiny particles made of polymers hold great promise for targeted delivery of drugs and as structural scaffolds for building artificial tissues. However, current production methods for such microparticles yield a limited array of shapes and can only be made with certain materials, restricting their usefulness. In an advance that could broadly expand the possible applications for such particles, MIT engineers have developed a way to make microparticles of nearly any shape, using a micromold that changes shape in response to temperature. They can also precisely place drugs into different compartments of the particles, making it easier to control the timing of drug release, or arrange different cells into layers to create tissue that closely mimics the structure of natural tissues.

The new technique, described in a paper published online July 18 in the Journal of the American Chemical Society, also allows researchers to create microparticles from a much more diverse range of materials, says Halil Tekin, an MIT graduate student in electrical engineering and computer science and lead author of the paper.

Currently, most drug-delivering particles and cell-encapsulating microgels are created using photolithography, which relies on ultraviolet light to transform liquid polymers into a solid gel. However, this technique can be used only with certain materials, such as polyethylene glycol (PEG), and the ultraviolet light may harm cells.

Another way to create microparticles is to fill a tiny mold with a liquid gel carrying drug molecules or cells, then cool it until it sets into the desired shape. However, this does not allow for creation of multiple layers.

The MIT research team, led by Ali Khademhosseini, associate professor in the MIT-Harvard Division of Health Sciences and Technology, and Robert Langer, the David H. Koch Institute Professor, overcame that obstacle by building micromolds out of a temperature-sensitive material that shrinks when heated.

The mold is first filled with a liquid gel that contains one kind of cell or drug. After the gel has solidified, the mold is heated so the walls surrounding the solid gel shrink, pulling away from the gel and creating extra space for a second layer to be added. The system could also be modified to incorporate additional layers, Tekin says.