Better Ways to Rebuild
Badly Injured Bones


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Engineers at Georgia Institute of Technology, each focused on different disciplines, are together developing a new technology that will help the body repair traumatic bone injuries more effectively and at lower cost than current methods.

The technology involves using a new system to deliver proteins, called growth factors, to the damaged bone. The most widely used growth factor, bone morphogenetic protein-2 (BMP-2), is typically delivered using a collagen sponge that releases large amounts of the drug initially and thus requires large amounts of the growth factor for subsequent delivery. This treatment is costly because a lot of growth factor is required, and there is also the risk of excess growth factor flowing into nearby areas and creating bone formations where it’s not wanted.

The new delivery system binds BMP-2 with microparticles of the drug heparin, a widely used anticoagulant, and researchers found that the BMP-2 stayed tightly bound to the heparin and was released slowly over time.

“We can control things a lot of better,” says Dr. Todd McDevitt, a professor of biomedical engineering at Georgia Tech and Emory University with joint appointment in the George W. Woodruff School of Mechanical Engineering. “[The new delivery system] does two very important things. We can keep BMP-2 in a bone defect site more stably. It doesn’t lose activity, and by doing that we can get away with using a lot less.” That also means there isn’t as much excess growth factor that can float away and build unwanted formations.

McDevitt believes the collaboration of his lab with two others has resulted in the work coming together better and more quickly than if the three had not been interacting.

“If you want to try something big, you had better start looking beyond just yourself. You can’t do it all. It’s more fun and usually more productive. That’s certainly been the case here,” he says.

Researchers bound the most clinically used growth factor, BMP-2, with microparticles of the drug heparin. Source: Georgia Tech

One initial challenge was figuring out how much growth factor binding capacity the materials had. “As far as we could tell from the reported literature, people either tried to saturate it or they just didn’t get as much binding. We, meanwhile, got a really high amount of growth factor binding to the materials, more than 100 times we could find in other places. That means we could add more if we need to but it also means maybe we don’t add so much to get a biological response,” McDevitt says.

If all the binding space on the material is not used, there will be room to add in more of other important factors for regeneration of different cells, improving, for example, vascularization, he says.

“The nice thing is that many times with biomaterials you have to come up with more sophisticated chemistry changes to your materials to enable something like that. Here we don’t have that problem because there is a class of materials that can combine a lot of different growth factors. So we are starting to look at what are some of the co-molecules that we can deliver with BMP-2 to make it even more potent,” he explains. “It was a very pleasant surprise.”

McDevitt’s lab is focused mainly on stem cell engineering, particularly how to control stem cells. “One of the big things we have been interested in is what do stem cells make in terms of regenerative types of therapy,” he says. A neighboring lab of Dr. Johnna S. Temenoff has been working with delivery systems for biomaterials, and the two colleagues began talking about what materials might be better to combine with growth factors, like BMP-2, for better delivery to cells. The third lab of Dr. Robert Guldberg focuses on bone repair strategies and has done a lot of work with the delivery of BMP-2 with other types of materials.

Moving forward, the team plans to test its work in an in vivo setting that Guldberg’s lab has used. “We have to do a lot of dosing and safety well before clinical studies. If that yields the success we hope, then we will go to one large animal type of study before going to clinical trials,” McDevitt says.

The BMP market for use in orthopedics is well over $1 billion, according to McDevitt. “If you can have even a slight improvement in a form that could be easily injectable or mixed or integrated with current delivery platforms, then major impact is very real,” he says.

Nancy S. Giges is an independent writer.

One of the big things we have been interested in is what do stem cells make in terms of regenerative types of therapy.

Dr. Todd McDevitt, Georgia Tech and Emory University

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November 2014

by Nancy S. Giges, ASME.org