Formulation Development Forum: Microscale Hydrogels

Microscale hydrogels are used in targeted drug delivery and tissue engineering. The spatial organization of biological entities or chemical compounds within hydrogel microstructures is important. Sequentially patterned microgels can spatially organize either living materials to mimic biological complexity or multiple chemicals to design functional microparticles for drug delivery (1). Current methods for producing such microparticles, however, restrict the type of shapes that can be generated and the kinds of the materials that can be used to produce the microparticles, thereby limiting their usefulness. Researchers at the Massachusetts of Technology (MIT) and Harvard University recently reported on new methods that address the challenges in producing microscale hydrogels, according to an Aug. 16, 2011, MIT press release (2).

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. This technique has certain limitations. It can be used only with certain materials, such as polyethylene glycol, and the ultraviolet light may harm cells. In another approach, microparticles also can be used to fill a mold with a liquid gel carrying drug molecules or cells. The gel is cooled until it sets into the desired shape. This approach, however, does not allow for creation of multiple layers (1).

The researchers' approach sought to address these two issues: the restriction of using photocrosslinkable polymers as the materials to pattern hydrogels and the limitation in the shapes that can be generated using static molds as a micromolding approach. Specifically, they reported on a dynamic micromolding technique to fabricate sequentially patterned hydrogel microstructures through the thermoresponsiveness of poly(N-isopropylacrylamide)-based micromolds. The researchers reported that these micromolds were responsive and exhibited shape changes under temperature variations, which facilitated the sequential molding of microgels at two different temperatures. They fabricated multicompartmental striped, cylindrical, and cubic microgels that encapsulated fluorescent polymer microspheres or different cell types. These researchers asserted that these "responsive" micromolds can be used to immobilize living materials or chemicals into sequentially patterned hydrogel microstructures (1, 2).

In addition to being used in drug delivery, the various particle sizes also have potential for tissue-engineering applications. For example, the long, striped particles may be useful for engineering elongated tissues, such as cardiac tissue, skeletal muscle, or neural tissue. In their study, the researchers created striped particles with a first layer of fibroblasts surrounded by a layer of endothelial cells. They also created cubic and cylindrical particles in which liver cells were encapsulated in the first layer surrounded by a layer of endothelial cells, an arrangement for potentially replicating liver tissue (1).

Such gels also could 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 also are planning to create particles that contain collagen for building large tissues and entire organs as vehicles for laboratory testing of potential new drugs. "If you can create 3D tissues which are functional and really mimic the native tissue, they are going to give the right responses to drugs," said Halil Tekin, an MIT graduate student and lead author of a recent article detailing his team's research, in the MIT release (2). Such an advance would offer the potential of accelerating the drug discovery and development processes.

Sources

1. H. Tekin, J. Am. Chem. Soc. 133 (33), pp 12944–12947 (2011).

2. MIT, "Mimicking Biological Complexity in a Tiny Particle," Press Release (Cambridge, MA, Aug. 16, 2011).