Science

MIT microparticle-making technique opens up biomedical possibilities

Using a temperature-responsive micromold, MIT engineers created two-layer gel microparticles (the red and green areas represent separate layers)
(Photo: Halil Tekin)
Using a temperature-responsive micromold, MIT engineers created two-layer gel microparticles (the red and green areas represent separate layers)
(Photo: Halil Tekin)

Whether you want to deliver medication to specific cells or create scaffolds for building artificial tissues, currently one of the best media for doing so are polymer microparticles filled with drugs or cells. Traditionally, it has only been possible to make such particles in a few shapes, out of a few materials, and/or with only one layer of "cargo" inside. A new technique developed at the Massachusetts Institute of Technology (MIT), however, could see multilayered microparticles being made in many shapes, from a wider variety of materials.

As things presently stand, photolithography is one of the most common methods used for creating drug-delivering or cell-encapsulating microparticles. The ultraviolet light that is required to transform the liquid polymers into a solid gel can harm the cells, however, plus the technique can only be used with materials such as polyethylene glycol.

Another approach involves filling a mold with a liquid gel carrying drug molecules or cells, then letting it cool until it sets. This method still doesn't allow for multiple layers, however.

MIT's new technique starts the same way, in that a liquid drug- or cell-containing gel is inserted into a tiny mold. Once the gel has set, the mold is heated, which causes its walls to shrink back away from the sides of the molded gel. A second layer of gel, containing a different type of drug or cell, can then be added in the extra space that the shrinkage has opened up. The process could theoretically be repeated several times, to create a microparticle containing several layers.

That multilayered particle could then be used for the timed release of several types of drugs, or to more closely emulate the structure of a certain type of natural tissue.

Starting with an agarose (sugar) gel, the MIT researchers have so far used the technique to create cylindrical, cubic, and long striped microparticles, although they state that many other shapes and materials should be possible. The striped particles contained a layer of fibroblasts, which are cells that make up connective tissue, surrounded by a layer of endothelial cells, which form blood vessels. That composition could make them ideal for the engineering of elongated tissues such as skeletal muscle, or cardiac or neural tissue.

The cylindrical and cubic particles contained liver cells surrounded by a layer of endothelial cells, and could be used to replicate liver tissue. Conceivably, gels could also be used that contained proteins to help cells orient themselves within a specific structure, or that contained collagen, to rebuild structural tissues such as cartilage.

Farther down the road, MIT would like to use the technology to build larger tissues or even complete organs, in order to more accurately and efficiently test drug responses in a laboratory setting.

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