TRANSLATIONAL RESEARCH:
Engineer-clinician collaborations yield innovative,
applied solutions
Funded via the W.H. Coulter
Translational Research Partnership in Biomedical Engineering,
these research projects recently concluded in year one of the
partnership. This partnership fosters early-stage collaborations
between University of Wisconsin biomedical engineering researchers
and practicing physicians that will enable researchers to deliver
their advances more quickly to patients.
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For ACL repair, closing the 'gap'
ou might be sprinting hard down the basketball
court or climbing carefully down a ladder. Suddenly, your knee twists
and buckles and you fall to the floor in pure agony.
In less than a second, you “popped” the
anterior cruciate ligament, or ACL. Now, most likely, you’ll spend
the next year of your life fully recovering from this common knee injury.
You’re not alone. Nearly 40,000 patients annually
undergo surgery and six months or more of physical therapy to reconstruct
and rehabilitate a torn ACL, says Assistant Professor William
Murphy.
In reconstructive ACL surgery, doctors drill a tunnel
in the femur and another tunnel in the tibia. They thread a tendon graft—usually
a piece of hamstring or patellar tendon—through the tunnels and
fix it in place at the ends with either a permanent metal screw or a
bioresorbable screw, which eventually dissolves into the body.
As many as 4,000 patients a year require repeat ACL
surgery—in part, says Murphy, because tendon-to-bone healing proceeds
poorly and the leg-bone tunnels expand considerably
over time. “There’s a 60 percent increase in tunnel area
at three years without fixation—and in some studies, when you
fix the tendon with a screw you actually get an even larger increase
in the tunnel area,” he says. “So this is a significant
problem. It really decreases the stability of the bone here and slows
healing.”
With one elegantly designed screw, Murphy and Associate
Professor Ben
Graf (also surgery) and Professor Mark
Markel (also veterinary medicine) believe they not only can alleviate
that problem, but promote bone tendon and bone healing in the process.
The group drew inspiration from recent studies in
which researchers packed a growth-factor-infused “sponge”
into the leg-bone tunnels to promote bone in-growth. “They’ve
seen quite good healing,” says Murphy.
However, rather than packing in a sponge material,
his group’s solution addresses the problem by modifying the surface
of standard bioresorbable screws. The researchers began with a growth
factor known as bone morphogenetic protein 2, or BMP2. Using a room-temperature
incubation process, they grew a thin calcium-phosphate-based coating
(a hydroxyapatite), which included the full-length BMP2 protein, on
bioresorbable screws from their partner, Smith & Nephew. Viewed
under a microscope, the coating looks similar in structure and composition
to bone.
In initial tests, the three found that the BMP2 growth
factor releases gradually—in a linear fashion—over time,
which was the result they hoped to see. And when bone stem cells are
exposed to the BMP2 incorporated into the coatings, they exhibit a hallmark
of bone differentiation. Murphy, Graf and Markel now are studying whether
their coated screws drive new bone growth and tendon-to-bone healing
in sheep models of an ACL reconstruction, which are similar in size
to human implants.
Expanding upon this research, the group also is studying
how to use the incubation process to incorporate virtually anything
biological into a coating. “The key here is that it’s a
room-temperature process, so we can incorporate biologics without blowing
them apart,” says Murphy. “Typically, when you make a coating—particularly
a ceramic coating on an orthopedic implant—it’s done at
very high temperatures that would really deactivate anything biological.”
In a single molecule, the researchers’ latest
coating includes a combination of a novel protein “tag”
that is designed to bind to hydroxyapatite minerals, and a growth factor
portion derived from BMP2. Remarkably, says Murphy, the group engineered
a molecule that binds so tightly that it’s essentially linked
to a surface.
He believes the coating could be useful in orthopedics,
where doctors could dip or paint it onto the many orthopedic implants
that contain hydroxyapatite, potentially adding healing properties to
those implants. “The molecule we engineered to bind to the surface
remains active, so it remains able to promote healing of bone and potentially
other tissue types as well,” he says.
