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publicado em 16/08/2011 às 20h42:00
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Tiny particles mimics biological complexity of normal cells

New MIT technology can lead to a better distribution of drugs and artificial tissues that mimic natural tissue

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Tiny particles made of polymers hold great promise for the construction of artificial tissues, the distribution of drugs. However, current production methods for such microparticles produces a limited set of forms and can only be made with certain materials, limiting their usefulness. In an advance that could vastly expand the possible applications of such particles, the MIT engineers have developed a way of making microparticles of almost all forms, using a small mold that changes shape in response to temperature. They can also just put the drugs in different compartments of the particles, making it easier to control the timing of drug release, or arrange for different layers of cells to create tissue that mimics the structure of natural fabrics.

The new technique, described in an article published online on July 18 in the Journal of the American Chemical Society, also allow researchers to create microparticles from the most diverse materials, said graduate student, Halil Tekin, the MIT in electrical engineering and computer science and lead author of the paper. Currently, most of the distribution of drug particles and cells encapsulated in microgels is created using photolithography, which includes ultraviolet light to turn liquid polymers in a solid gel. However, this technique can be used only with certain materials such as polyethylene glycol (PEG), and ultraviolet light can damage cells. Another way to create tiny microparticles is to fill a 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 the creation of multiple layers.

The MIT research team led by Professor Ali Khademhosseini, associated with the Harvard-MIT Division of Health Sciences and Technology, and Professor Robert Langer, David H. Koch Institute, overcame this obstacle by building micromoldes a temperature sensitive material that shrinks when heated. The mold is first filled with a liquid gel that contains a cell type or drug. After the gel solidifies, the mold is heated and the walls around the solid gel to shrink away from the gel and creating extra space to be added a second layer. The system can also be modified to incorporate additional layers, Tekin said. "The method is very creative. It offers the opportunity to make multilayer microstructures. The next step is to figure out what you can do with two layers of these structures.", Says Professor Michael Sefton, University of Toronto Institute of Biomaterials and Biomedical Engineering, which was not involved in this project.

So far, the researchers created cylindrical and cubic particles, and particles long, striped, and many other forms should be possible, Tekin said. His starting material was a gel made of agarose, a type of sugar. The long and striped particles could be particularly useful for elongated tissues such as heart tissue, skeletal muscle or neural tissue. In this study, the researchers created particles with a striped first layer of fibroblasts (cells found in connective tissue), surrounding a layer of endothelial cells that form blood vessels. The researchers also created cubic and cylindrical particles, in which liver cells were encapsulated in the first layer, surrounding a layer of endothelial cells. This arrangement can accurately replicate the liver tissue. Gels can also be embedded with proteins that help guide cells into 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 most of the structural body tissues, including cartilage. Eventually, researchers hope to use this technique to build tissues and organs, and even large integers. some tissues in the laboratory can be used to test potential new drugs. "If we can create 3-D tissues, which are actually functional and mimic the native tissue, they will give the right answers to drugs," Tekin said. This could accelerate the drug discovery process and reduce costs because it would take a few experiences with animals, he says.

   Palavras-chave:   Microparticles    Polymers    Cell shapes    Gel    Mold    Drugs    Halil Tekin    MIT    Journal of the American Chemical Society   
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