College of Engineering University of Wisconsin-Madison
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BME MONITOR: The Biomedical Engineering Department Newsletter

 

2007 Newsletter
Featured articles

Experiential learning: BME undergrad design competition stresses real-world challenges

Research may yield improved treatment of diseased lungs

Translational research: Medicine, hand-delivered

Translational research:
Ultrasound waves reflect tissue mechanics

Translational research: 'Balloon' effect:
Blocking aneurysms

Translational research: For ACL repair,
closing the 'gap'

Translational research: Fast, efficient MR imaging

Translational research: Seven new projects launched

Graduate student service award honors Corrine Bahr


Regular Features

Message from the chair

Faculty news:
David Beebe cited as pioneer of miniaturization

In memoriam:
Prof. Paul Bach-y-Rita

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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.


For ACL repair, closing the 'gap'

William Murphy

William Murphy
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Decorative initial cap You 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.

Modified surface of bioresorbable screw.


Modified surface of bioresorbable screw.
(View larger image)


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.



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Copyright 2007 The Board of Regents of the University of Wisconsin System

Date last modified: Monday,30-July-2007 15:43:00 CDT
Date created: 30-July-2007

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