Biologics offer potential in sports medicine, arthroscopy

Researchers and clinicians could hasten development of biologics for cartilage, ligament and meniscal repair.

Issue: January 2004

Savio Woo, Director of the Musculoskeletal Research Center at the University of Pittsburgh Medical Center, works with the Robotic/UFS Testing System.

COURTESY OF SAVIO WOO

Over the last decade, research into the use of growth factors and other biologic approaches to tissue repair in orthopedics has increased greatly. Food and Drug Administration approval of two bone growth factors in the last few years has heightened interest as well.

But while the use of biologics has begun to have an influence in spinal fusion surgery and long-bone nonunions due to the approval of two bone morphogenetic proteins (BMPs), the impact has been less dramatic in sports medicine and arthroscopy. Despite cutting-edge research being done at research centers across the United States, there is currently only one such biologic in human clinical trials.

A pre-market approval application for the Collagen Meniscus Implant, a scaffold designed to encourage the ingrowth of native meniscal tissue, could be submitted to the FDA late in 2004 or the first quarter of 2005. That is an exception, however, as the great majority of research being done is still at the bench top or animal-model stage.

The potential is clear but much work remains, said Cato T. Laurencin, MD, PhD, chair of the department of orthopedic surgery and professor of biomedical and chemical engineering at the University of Virginia.

“Although clinical applications are still several years away, bone-, cartilage- and ligament-based tissue engineering efforts often benefit from the marriage of materials-oriented and biologically-oriented approaches to effect repair,” Laurencin told Orthopedics Today. “Combining these two approaches will capitalize on the strengths of each while minimizing some of the shortcomings of each as well.”

Barriers

[photo]
The low and high magnifications of a PPHOS nanofiber are shown here.

COURTESY OF CATO T. LAURENRICH

One barrier to bringing the field to fruition is the lack of regular communication and interaction between basic researchers in the lab and clinicians in the operating room. “The close translational research people are too few, in my opinion,” said Savio Woo, PhD, A.B. Ferguson Professor and Director of the Musculoskeletal Research Center at the University of Pittsburgh Medical Center.

Kyriacos Athanasiou, PhD, professor of bioengineering at Rice University and president of the Biomedical Engineering Society, agrees: “There is a general consensus that we are good at performing academic types of research that are clearly the foundation of any subsequent medical products. Where we lack is in the crucial and huge area where some of that work can be translated into a medical application.”

Athanasiou said that in a few years The Wallace H. Coulter Foundation will begin to provide funding to support biomedical engineering research. The main area the foundation would most likely focus on is translational research.

Bridging the gap

Kyriacos Athanasiou, PhD [photo] Kyriacos Athanasiou, PhD, president of the Biomedical Engineering Society.

Woo believes that orthopedic medical societies could help bridge the gap by getting researchers more involved. He said one society that does an outstanding job is the American Society of Shoulder and Elbow Surgeons. They support their PhD members to come to their meetings and ask them to give leadoff talks in each scientific session and to moderate discussions.

One explanation for the divide may be that orthopedic research has changed so much over the years and now focuses heavily on microbiology and biochemistry, especially in the area of biologics. “Before, orthopedic surgeons were working with material scientists and bioengineers on things that they could understand and do. But right now, there are only a few orthopedic surgeons doing that because the science has gotten so sophisticated,” Woo said.

That may be one reason why the number of orthopedic surgeons at the Orthopaedic Research Society’s annual meeting has not kept pace with the increasing overall attendance, he added.

Cost, ease are factors

“Where we lack is in the crucial and huge area where some of that work can be translated into a medical application.”

Kyriacos Athanasiou

In addition to focusing on translational research, scientists and clinicians who are developing new technologies need to try to make them relatively easy to use and inexpensive, said Freddie Fu, MD, chair of the department of orthopedics at the University of Pittsburgh.

“If you make it too complicated and too expensive, health care insurers are going to be very hard on it, and to be honest, these things we are talking about are really lifestyle issues. It’s not like you can’t see or you can’t live.”

Fu said he is interested in simpler approaches like using a patient’s own blood, spinning the growth factors out in the operating room, and injecting them to initiate a healing cascade at the injury site. “To me, that’s exciting. I like the idea that I can do something in the OR in a half hour or an hour and put it back [into the body].”

Whatever tools are used, getting through the FDA’s regulatory channels will not be easy. One of the challenges will be deciding whether these tools should be classified as devices or biologics. That is something that is currently being resolved, said Laurencin, who is a member of the FDA’s Orthopedic and Rehabilitation Devices Advisory Panel.

“The approval of BMPs will herald the use of these materials in a number of off-label applications with both positive and negative consequences. The challenge will be in the successful use of post-market surveillance techniques to identify early trends in both the use and outcomes of these new technologies.”