Depositing Drug-Release Coatings on Orthopedic Implants a Layer at a Time

Author: 
Bob Michaels
Images show a bare substrate (left) and a substrate coated using MIT researchers’ layer-by-layer technology (right).

Despite progress in technologies for combating biofilm formation, approximately 1% of hip implants, 4% of knee implants, and more than 15% of implants associated with orthopedic trauma still fail as a result of implant-induced infection, according to the Stevens Institute of Technology (Hoboken, NJ). Contributing to the effort to further reduce infection rates, researchers at the Massachusetts Institute of Technology (MIT; Cambridge, MA) have designed a coating technique that relies on a layer-by-layer deposition method and tunable drug loading. Their goal is to create a coating that will provide long-term protection against biofilm formation on orthopedic implants.

“Our layer-by-layer technique is a versatile approach to the formation of conformal thin films on surfaces with various geometries, including materials commonly used for implantable devices such as pins, sutures, and prosthetic bones,” explains Jessie (Sze Yinn) Wong, a PhD candidate in the department of chemical engineering at MIT. “Using the layer-by-layer technique, films that are very thin and have tunable antibiotic or anti-inflammatory drug-loading capability can be applied onto surfaces of orthopedic implants.”

The MIT team’s layer-by-layer approach is based on the alternating adsorption of materials containing complementary charged or functional groups, leading to the formation of nanostructured thin films. Most often, according to Wong, this method is used to alternately deposit oppositely charged polyelectrolytes to build up a polymeric film, the composition of which can be tuned on the nanometer-length scale by changing their assembly or postassembly conditions. “Because we are building up the films a monolayer at a time, we are able to control the drug loading as well as the architecture of the film,” Wong says. “In this work, we combine a permanent microbicidal film with a hydrolytically degradable top film, offering controlled and localized delivery of therapeutics.”

Designed to prevent biofilm formation, the technology contains a permanent antimicrobial coating that kills bacteria on contact. Built on top of this film, a second completely degradable film incorporating a therapeutic agent is designed to slowly degrade under physiological conditions, releasing drugs into the local environment. “For example, the top degradable film can be made to load an antibiotic that will be released and take out any infection present at the implant site,” Wong remarks. “When the top degradable film is completely gone, the permanent antimicrobial film is left behind for long-term prevention of biofilm formation.”

In addition to its ability to deposit a permanent antimicrobial film, the MIT researchers’ layering process is cost-effective because it requires only minute quantities of polymer material, according to Wong. At the same time, the film is so thin that it does not alter the original functionality of orthopedic implants. “High drug-loading capacity is achieved,” Wong states, “even though the film is very thin.”

Another advantage of this layer-by-layer technology is that it can be used to tune drug loading simply by changing the number of layers that are deposited, Wong notes. The degradation rate can also be tuned by using polymers with different degradation kinetics.

An in vivo model has shown that the drug-releasing film does not raise biocompatibility issues, while in vitro studies indicate that mammalian cells adhere and proliferate well on the surface of the permanent antimicrobial film. The researchers’ next step, Wong notes, is to build an in vivo model for testing both the drug-releasing and the permanent antimicrobial films.