By building up coatings one molecular layer at a time, MIT researchers have made a new class of materials that can release drugs, and even genes, in an exact sequence and at a predetermined rate. The method could be widely applicable for designing novel multilayered materials to improve the safety of medical implants and to serve as elaborate scaffolding in the tissue engineering of cells to make bones, blood vessels, muscles, and livers in the lab.
The multilayered materials initially could be used to coat medical implants, such as hip replacements, cutting down on infections and promoting healing. Animal trials could start as early as next year for that purpose.
“The technology itself is much bigger than the applications we’re talking about starting with,” says Paula Hammond, professor of chemical engineering at MIT, who directed the research to develop the materials. “The idea that we can deliver drugs and genes from a surface in a controlled sequence is something that can ultimately have an impact in cancer, and it can have an impact in tissue engineering, which is another area we’re beginning to look at.”
To make the coatings – reported online this week in the Proceedings of the National Academies of Science – researchers began with a well-known process, called layer-by-layer electrostatic assembly, that gives molecular control over the components of the coating. Such coatings, which alternate between positively and negatively charged particles and polymers, break down in the body, releasing their contents in a controlled manner.*
The researchers hoped it would be possible to combine different drugs into separate layers of the single coating. “We set about to build something with multiple components,” says Kris Wood, a graduate student at MIT in charge of the project. It turned out to be much more complex than they’d anticipated, however. In their first attempts, components added in successive layers ended up mixing together, causing them to be released all at once, rather than sequentially. Eventually, the researchers discovered that heating a layer between different components, so that polymers formed covalent bonds, would create a “net or meshwork,” Wood says, that kept the components from mixing.
This method can be used to combine any components that have different electrical charges, holding the coating together electrostatically. These could include various polymers and drugs, nanostructures, such as highly branched dendrimers that can assist with drug delivery, and particles of metals such as silver, known to have antimicrobial properties.
*Clarification: Hammond developed the first such coatings that break down in the body. Most other electrostatic, layer-by-layer coatings do not break down in the body.
Because the method does not require harsh chemicals or extensive heating, it could also be used to incorporate proteins and nucleic acids, which Hammond says have been very difficult to deliver safely in the body for treatments. She says their coating could deliver these biological molecules both safely and specifically to where they’re needed, cutting down on the overall cost.
For orthopedic implants, one layer of the coating would release antibiotics starting right after the surgery, combined with anti-inflammatory drugs. Later, with infection defeated by this powerful, localized treatment, another layer of the coating would release a protein-like growth factor to stimulate the growth of bone in order to secure the implant in place. Many such layers and a wide variety of molecules can be incorporated into the coatings, which could also provide a transparent coating for replacement lenses used in cataract surgery.
For tissue engineering, the coatings could be used for “evolvable materials scaffolds onto which cells can grow and have growth factors introduced over time, or have specific genes introduced over time that program them to become what we want them to become,” Hammond says.
Hammond is already in contact with orthopedics researchers and surgeons who say her coatings could be helpful. Myron Spector, director of orthopedic research at the Brigham and Women’s Hospital, who works with Hammonds, says that, although infections affect only a few percent of the hundreds of thousands of patients who receive hip and knee replacements in the United States, preventing such infections is important. “It’s not a high percentage…but it’s devastating when it occurs, and can be life-threatening.”
Mitchel Harris, an orthopedic surgeon at Brigham and Women’s Hospital in Boston, says the technology seems promising, but also notes, “Unless it is inexpensive, it’s going to face an uphill battle [to introduce the coatings], because the reimbursement for implants is going down. If the implant continues to take up more and more of the reimbursement amount, then hospitalization won’t be covered. It makes it difficult.”*
Hammond says that if animal trials go well, it will still be three years before the coatings can be tried out in humans. Spector says the work is “very clever” and that in addition to improving current treatments, it could suggest new ones.
*Clarification: The cost of the coatings is yet to be determined. The process for making them is very cheap, Hammond says, and most of the cost will come from the drugs used. In some cases, the coatings would eliminate the need for a second surgery and long hospitalizations, she says, so saving money.