Mimicking biological complexity, in a tiny particle

August 16, 2011 by Anne Trafton, MIT News
Using a temperature-responsive micromold, MIT engineers created two-layer gel microparticles (the red and green areas represent separate layers). Photo: Halil Tekin

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 , 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 , which relies on to transform liquid polymers into a solid gel. However, this technique can be used only with certain materials, such as (PEG), and the ultraviolet light may harm cells.

Another way to create microparticles is to fill a tiny mold with a liquid gel carrying 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.

"The method is quite creative," says Michael Sefton, professor at the University of Toronto Institute of Biomaterials and Biomedical Engineering, who was not involved in this project. "It offers the opportunity to make multilayer microstructures. The next step is figuring out what you can do with these two-layer structures."

Artificial tissue

So far, the researchers have created cylindrical and cubic particles, as well as long striped particles, and many other shapes should be possible, Tekin says. Their starting material was a gel made of agarose, a type of sugar.

The long striped particles would be particularly useful for engineering elongated tissues such as cardiac tissue, skeletal muscle or neural tissue. In this study, the researchers created striped particles with a first layer of fibroblasts (cells found in connective tissue), surrounded by a layer of endothelial cells, which form blood vessels. Researchers also created cubic and cylindrical particles in which liver cells were encapsulated in the first layer, surrounded by a layer of endothelial cells. This arrangement could accurately replicate liver tissue.

Such gels could also be embedded with proteins that help the cells orient themselves in a desired structure, such as a tube that could form a capillary. The researchers are also planning to create particles that contain collagen, which constitutes much of the body's structural tissues, including cartilage.

Eventually, the researchers hope to use this technique to build large tissues and even entire organs. Such tissues could be used in the laboratory to test potential new drugs. "If you can create 3-D tissues which are functional and really mimicking the native tissue, they are going to give the right responses to drugs," Tekin says.

This could speed up the drug discovery process and decrease the costs, because fewer animal experiments would be needed, he says.

This story is republished courtesy of MIT News (web.mit.edu/newsoffice/), a popular site that covers news about MIT research, innovation and teaching.

Explore further: Building organs block by block: Tissue engineers create a new way to assemble artificial tissues

Related Stories

MIT method allows 3-D study of cells

April 24, 2006

MIT bioengineers have devised a new technique that makes it possible to learn more about how cells are organized in tissues and potentially even to regrow cells for repairing areas of the body damaged by disease, accidents ...

Coming Soon: Blood Vessels from a Test Tube?

June 4, 2007

Our tissues and organs consist of a complex, closely balanced assembly of different types of cells, extracellular matrix, and special signal-carrying molecules. The growth of such structures in the laboratory, perhaps for ...

New nanoparticles could improve cancer treatment

October 5, 2010

In recent years, studies have shown that for many types of cancer, combination drug therapy is more effective than single drugs. However, it is usually difficult to get the right amount of each drug to the tumor. Now researchers ...

Recommended for you

Scientists develop new theory of molecular evolution

October 23, 2017

Researchers from the University of Colorado Anschutz Medical Campus and the University College London have developed a new theory of molecular evolution, offering insights into how genes function, how the rates of evolutionary ...

Austrian researchers facilitate lipid data analysis

October 23, 2017

No lipids, no life. In all organisms, lipids form cell walls, store energy and release it when necessary, and play an important role in cell signalling. It has been proved that changes in the composition of lipids play a ...

Close up view of growing polymer chain show jump steps

October 20, 2017

(Phys.org)—A team of researchers at Cornell University has devised a means for watching as a polymer chain grows after application of a catalyst. In their paper published in the journal Science, the team explains how they ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

1 / 5 (1) Aug 16, 2011
Artificial organs.

Should probably start on the pancrease first, since it's one of those things that you just can't live without...

Keep it up guys, Borg technology is what we all want.

I wonder how high average human life span can be stretched if you can just clone more and more organs in perfect health to be transplanted?

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.