Hydroxyapatite nanoparticles are incorporated into multilayer coatings for faster bone tissue growth. Image courtesy of the Hammond Lab |
Every
year, more than a million Americans receive an artificial hip or knee
prosthesis. Such implants are designed to last many years, but in about
17% of patients who receive a total joint replacement, the implant
eventually loosens and has to be replaced early, which can cause
dangerous complications for elderly patients.
To
help minimize these burdensome operations, a team of MIT chemical
engineers has developed a new coating for implants that could help them
better adhere to the patient’s bone, preventing premature failure.
“This
would allow the implant to last much longer, to its natural lifetime,
with lower risk of failure or infection,” says Paula Hammond, the David
H. Koch Professor in Engineering at MIT and senior author of a paper on
the work appearing in the journal Advanced Materials.
The
coating, which induces the body’s own cells to produce bone that fixes
the implant in place, could also be used to help heal fractures and to
improve dental implants, according to Hammond and lead author Nisarg
Shah, a graduate student in Hammond’s lab.
An alternative to bone cement
Artificial
hips consist of a metal ball on a stem, connecting the pelvis and
femur. The ball rotates within a plastic cup attached to the inside of
the hip socket. Similarly, artificial knees consist of plates and a stem
that enable movement of the femur and tibia. To secure the implant,
surgeons use bone cement, a polymer that resembles glass when hardened.
In some cases, this cement ends up cracking and the implant detaches
from the bone, causing chronic pain and loss of mobility for the
patient.
“Typically,
in such a case, the implant is removed and replaced, which causes
tremendous secondary tissue loss in the patient that wouldn’t have
happened if the implant hadn’t failed,” Shah says. “Our idea is to
prevent failure by coating these implants with materials that can induce
native bone that is generated within the body. That bone grows into the
implant and helps fix it in place.”
The
new coating consists of a very thin film, ranging from 100 nm to one
micron, composed of layers of materials that help promote rapid bone
growth. One of the materials, hydroxyapatite, is a natural component of
bone, made of calcium and phosphate. This material attracts mesenchymal
stem cells from the bone marrow and provides an interface for the
formation of new bone. The other layer releases a growth factor that
stimulates mesenchymal stem cells to transform into bone-producing cells
called osteoblasts.
Once
the osteoblasts form, they start producing new bone to fill in the
spaces surrounding the implant, securing it to the existing bone and
eliminating the need for bone cement. Having healthy tissue in that
space creates a stronger bond and greatly reduces the risk of bacterial
infection around the implant.
“When
bone cement is used, dead space is created between the existing bone
and implant stem, where there are no blood vessels. If bacteria colonize
this space they would keep proliferating, as the immune system is
unable to reach and destroy them. Such a coating would be helpful in
preventing that from occurring,” Shah says.
It
takes at least two or three weeks for the bone to fill in and
completely stabilize the implant, but a patient would still be able to
walk and do physical therapy during this time, according to the
researchers.
Tunable control
There
have been previous efforts to coat orthopedic implants with
hydroxyapatite, but the films end up being quite thick and unstable, and
tend to break away from the implant, Shah says. Other researchers have
experimented with injecting the growth factor or depositing it directly
on the implant, but most of it ends up draining away from the implant
site, leaving too little behind to have any effect.
The
MIT team can control the thickness of its film and the amount of growth
factor released by using a method called layer-by-layer assembly, in
which the desired components are laid down one layer at a time until the
desired thickness and drug composition are achieved.
“This
is a significant advantage because other systems so far have really not
been able to control the amount of growth factor that you need. A lot
of devices typically must use quantities that may be orders of magnitude
more than you need, which can lead to unwanted side effects,” Shah
says.
The
researchers are now performing animal studies that have shown promising
results: The coatings lead to rapid bone formation, locking the
implants in place.
This
coating could be used not only for joint replacements, but also for
fixation plates and screws used to set bone fractures. “It is very
versatile. You can apply it to any geometry and have uniform coating all
around,” Shah says.
Another
possible application is in dental implants. Conventionally, implanting
an artificial tooth is a two-step process. First, a threaded screw is
embedded in the jaw; this screw has to stabilize by integrating with the
surrounding bone tissue for several months before the patient returns
to the clinic to have the new crown attached to the screw. This could be
reduced to a one-step process in which the patient receives the entire
implant using a version of these coatings.
This
research was funded by the National Institutes of Health’s National
Institute on Aging and conducted at the David H. Koch Institute for
Integrative Cancer Research with support from the Institute for Soldier
Nanotechnologies at MIT.
Osteophilic Multilayer Coatings for Accelerated Bone Tissue Growth