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Carl R. Woese Institute for Genomic Biology

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Slow and steady: A drug delivery implant that folds – and paces – itself

Researchers who seek to improve drug delivery systems encounter a principle that evokes the fabled race between the tortoise and the hare: many of the chemicals produced naturally by the body to promote growth or healing are released in a steady, controlled manner.  Although intuition suggests that more medicine means a faster cure, drug delivery devices meant to reproduce this type of signaling are actually less effective if they release (and run out of) drug too quickly.  Finding better ways to sustain this type of biological signaling over a desired treatment period is important to a variety of medical advances, including tissue regeneration, but creating materials that mimic this controlled release has proved technically challenging.

Associate Professor of Chemical and Biomolecular Engineering and Institute for Genomic Biology member Hyunjoon Kong and collaborators have developed an ingenious solution; an easily synthesized substance that, when implanted in tissue or placed in a water-based solution, folds itself into a shape that controls and directs the release of hormones or other embedded drugs.

Hydrogels, water-absorbing solid materials that resemble a sturdier version of Jell-O, have been used previously for controlled biomolecule delivery.  Hydrogels can be chemically modified to bond directly to the drug or chemical of interest, and gradually release the drug as the chemical bonds degrade.  This approach has several difficulties: the chemical modifications used can negatively affect both the drug and the hydrogel, the process of modifying the gel is usually expensive, and it is difficult to synthesize the gel in shapes that allow the released drug to infiltrate nearby tissue.

To address these difficulties, Kong, Materials Science and Engineering graduate student Kwanghyun Baek, and their fellow researchers created a hydrogel with two layers comprising the same type of material, but made to differ in how each layer expands when exposed to water.  These differences are what produce their hydrogel’s ability to fold itself into a multi-layered tube.

The way this folding occurs may seem familiar to anyone who has ever curled decorative ribbon with a pair of scissors.  As the ribbon is pulled over a sharp edge, the outside surface of the ribbon is stretched more than the inside surface.  Since the outside surface is now longer than the inside surface, the ribbon must compensate by curling, with the now-shorter inner surface always taking the inside track.

The two layers of the hydrogel designed by Kong and others behave in a similar way: when placed in solution, the outer layer becomes longer relative to the inner layer.  The formerly flat gel rolls up into a tube, one that coils more tightly or more loosely according to what structural properties are selected for each layer of the gel.

One advantage of this tubular shape is that it can be used to physically limit the release of biomolecules of interest.  If a drug is loaded into the inner layer of the bilayer hydrogel, the drug-laden surface area that is exposed in the folded shape is very limited; no chemical modifications are necessary to slow and prolong the diffusion of the drug from the gel. The drug will also be forced to diffuse mainly from the two ends of the tube, allowing the release to be directed toward a particular area or tissue.

Baek, Kong and colleagues examined the efficacy of their hydrogel in promoting blood vessel growth when this inner layer was loaded with growth factor; tissue implanted with the self-folding gel showed more vessel growth than tissue implanted with gel strips, rings or discs containing the same initial quantity of growth factor.  Because it is relatively easy to produce and control the structural properties of similar self-folding hydrogels and load them with any of a variety of biomolecules, this innovation has a broad range of potential therapeutic applications.

Kong was the principal investigator and Baek the first author on a recent communication in Advanced Materials that reported these and related findings.  Other authors of the study were postdoctoral researcher Jae Hyun Jeong, graduate student Artem Shkumatov, and Bioengineering/Electrical and Computer Engineering Professor and Institute for Genomic Biology affiliate Rashid Bashir.  The work was reported in the October 18, 2013 issue of Advanced Materials (DOI: 10.1002/adma.201300951).

Image: Baek K, Jeong JH, Shkumatov A, Bashir R, Kong H. In situ self-folding assembly of a multi-walled hydrogel tube for uniaxial sustained molecular release. [Supporting information] Adv Mater. 2013;25(39):5568-5573.

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Regenerative Biology and Tissue Engineering
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