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Elegance in Spine: Extracavitary Approaches
The delicate task of dealing with spinal problems is getting a bit less complex, says Dr. Francis Shen. Orthopedists can now remove a section of rib and approach the front of the vertebrae from the back in an oblique direction.

Endotec Beats FDA, Strikes Blow for Innovation
Endotec has struck a blow for every orthopedic surgeon who wants to develop a better device. See how the company’s founders took on the FDA and got a federal judge to charge the agency with “stymieing progress and technological advancement.” How did they do it? Read on.

From Obesity to Osteoarthritis, the Carpal Tunnel Connection
It’s certainly no surprise that Carpal Tunnel Syndrome (CTS) is an exceedingly common orthopedic malady. But, as PearlDiver’s data show, the linkage between obesity, osteoarthritis and other conditions to CTS is most surprising. Check it out.

Using DNA to Predict Scoliosis
Six million people (estimate from the National Scoliosis Foundation) have scoliosis in one form or another. The primary age for onset of idiopathic scoliosis is 10-15 years old. Finally, there is a test which can reliably predict scoliosis. Fewer X-rays. Lower cost. Better outcomes.

New Capital, New Science for Cartilage Repair
$36 million invested in the last couple of months. TiGenix has more than that in the bank to fund market penetration. Then a new paper last week finds molecular cause of OA. Cartilage repair momentum is building.

Should I Become a Physician-Employee?
Large healthcare institutions are increasingly purchasing orthopedic practices. What does this mean for patient referrals? How beneficial can it be for orthopedists? The upside is more stability, among other things…and one of the downsides is loss of freedom.

Outrageous Whistleblower Lawsuit Challenged
Spine surgeons sued by whistleblowers in Boston are fighting back. Their lawyer is outraged and says the claimants are just shopping an old and settled case to another judge. Is this the proverbial lipstick on a pig? Find out.

Medical Education Under the Microscope – Is It Up to Today’s Challenges?
Where is the line drawn between what medical schools, residencies, and professors should provide to students and what doctors-in-training should reach for themselves? Here are the results of interviews with three senior surgeons, who opine on things such as attitudes, how people learn, and the possible effects on the field.

The Underlying Meaning of Zimmer’s Purchase of Abbott Spine
From the price paid to the timing, this transaction held an underlying meaning for the entire spinal implant industry. Zimmer, the $4.2 billion (revenue) diversified orthopedic company is now #5 in spine. More to come?

Resurging Lumbar and Cervical Total Disc Replacement Markets! New PearlDiver Estimates
Rumors of the TDA market’s demise were premature. Increasingly positive long term patient data is at the core of a resurging lumbar and cervical TDR market. Senior analyst Matt Menze tackles the TDA market and interviews one of the fathers of TDR, Dr. Scott Blumenthal from the Texas Back Institute. Where is this market actually heading? We think to the $2 billion range by 2015. All details here.

Six Days in June – Biomet and Zimmer Battle for Distributors in Kentucky
Documents filed recently in a Kentucky lawsuit pull the curtain back on an epic battle between Biomet and Zimmer. For six fevered days in June 2007, Biomet CEO Jeff Binder and founder Dane Miller went into the trenches to save one of their own. For all the details, read on.

Multicenter Clinical Trials: Do They Get the Respect They Deserve?
They’re not fast or sexy, but they are critical…large trials, that is. With multiple sites and principal investigators who donate their time, large trials are more complex—and normally yield more actionable data—than smaller, quicker studies. But large trials don’t always get the respect they deserve. And, says at least one physician-researcher, this could affect the future of the field.

Patent Wars: Medtronic Attacks NuVasive
MSD’s lawsuit came amid a period of declining spinal implant market share – from a peak of 60% in late 1998 (just prior to being acquired by Medtronic) to, we estimate, 36% currently – and a growing sense that MSD’s reign as the king of spine was coming to a close. What’s really behind Medtronic’s attack on its former senior exec? Read on.

Those interested in regenerative medicine might want to train their eyes on the Buckeye state. Hard at work to push the field of tissue engineering into the future are David Butler, Ph.D., a Professor of Biomedical Engineering, and his colleagues at the University of Cincinnati.

Commenting on yesteryear, Dr. Butler explains, “The history of tissue engineering involved a shotgun approach à la ‘Let’s mix this with that and hope we get something that works.’ My colleagues and I have been trying to be more strategic in finding faster and more efficient ways to repair orthopedic injuries. As was the traditional approach, we had been putting in cells or materials and, if they didn’t work, trying something else. Instead, we began asking, ‘What is the environment in which we are placing the tissue engineered construct?’ We set out to determine how much force a given tissue was experiencing and what the patterns of those forces were. The answers would then represent design criteria for new products.”

Theoretically beautiful…but how are they making it a reality? Dr. Butler: “We are using animal studies to measure the in vivo forces transmitted by the tendon during activities of daily living. This will ultimately mean that when we go to the lab to tissue engineer something we might be able to make something that will, when it repairs, be able to match the forces and patterns of force occurring in the live animal, even accounting for a safety factor. It’s obviously a backwards approach, but it makes sense.”

And the findings thus far? “We have determined that different tissues experience different levels of force. Ligaments like the ACL in the knee have time periods when the tissue has no force on it; then there are times when the forces increase quickly. For example, during the swing phase of gait the forces are very small or zero, but once the foot makes contact, the forces rise quickly. So when we design a tissue engineered tendon repair, we’re going to be able to say ‘xyz’ is our goal. Regarding the maximum or failure force on the tissue, we have found that under normal conditions ligaments experience only about 7%-10% of the failure force of that tissue. Tendons work differently, however, and even when someone is quietly standing, the tendon could be carrying 8%-10% of its failure force because it is connected in series to the muscle. Not only is the tendon always carrying force, but forces can rise during activity to as high as 40% of failure. This means that as a tissue engineer, I don’t want to design a ligament the same way I design a tendon because the demands on the tendon are higher than the demands on the ligament. This applies not only to tissue engineering but to whatever procedures orthopedic surgeons elect to perform. If they know the force environment for a particular set of activities, they can make better decisions about patient care.”

“The next step,” says Dr. Butler, “is to say, ‘Given that I know the environment, what if I use stem cells from the patient, direct these cells into biological scaffolds, and then mechanically stimulate the resulting tissue engineered construct in culture?’ Could we create something that would meet the in vivo demands I’ve already recorded? Over the last eight to 10 years we’ve engineered things outside the body that, after we implant them and allow them to repair for 12 weeks, match the behavior of normal tendons. We’ve been able to match the normal tissue forces and deformations up to the threshold of in vivo forces that we’ve recorded and 50% beyond that. By contrast, if we had just created defect injuries in a tendon and allowed them to heal naturally, that repair doesn’t come close to being able to carry the in vivo forces of a normal tendon. We are essentially preconditioning these constructs to the environment they’ll be experiencing for different in vivo activities.”

And the orthopedic community is watching. “In 2007 we were honored with the Kappa Delta award from the American Academy of Orthopaedic Surgeons,” states Dr. Butler. Our team of engineers (Drs. Natalia Juncosa-Melvin, Jason Shearn and Hani Awad), surgeons, pathologists (Drs. Marc Galloway and Greg Boivin), and a cell culture expert (Cynthia Gooch) worked closely together for nearly a decade. For example, my surgical colleague, Dr. Marc Galloway, has been involved in all the surgeries that have led to these advances. But we also realize that our work is not patient-ready because we don’t have something surgeons can easily handle—it’s not anything that comes off the shelf. At the same time, we are pleased that surgeons see that what we are doing is something that can be repeated for ligaments, menisci, and cartilage, but this process requires that we know the in vivo loading environment tolerated by each of these structures.”

And to ensure sufficient surgeon input, Dr. Butler created a venue for their participation. “I put together a consortium of four orthopedic surgeons in Cincinnati to meet monthly and discuss our tendon research and how to improve the study design. Drs. Samer Hasan, Keith Kenter, and Michael Greiwe joined Dr. Galloway in order to provide valuable clinical information that could be translated to the lab. They are involved in all of our animal surgeries, and they have significantly increased the value and repeatability of our studies.”

To further his understanding of the field, Dr. Butler sometimes must look to the nursery. “To a great extent NIH and leaders in tissue engineering are driving the tissue engineering train. They have suggested that one way the field might improve at a faster rate is if we could understand something about how tissues normally develop from birth. To this end, I am working on animal studies with Dr. Christopher Wylie, a developmental biologist at Cincinnati Children’s Hospital. We are studying how tendons form at birth to see what the patterns are and if we may be able to stimulate the tissue engineered constructs in culture with some of same signals being used when the tendon is normally formed. Thus far we have learned that certain genes get turned on early; we can see which ones are turned on where and we are looking at what growth factors and signals we must use to stimulate appropriate gene expression. The signaling is critical. With the collagen 1 gene we can see bright yellow turning on in cells in a certain location. When turned on, the collagen 2 gene is blue. We are trying to find those signals in the cells that cause the gene to increase its expression. If we can identify those signals we know what factors to deliver in culture to improve repairs.”

Such grand undertakings require the contribution of grand entities. “In April 2007, Drs. Jack Lewis, Cy Frank and I co-chaired a conference sponsored by the Orthopaedic Research and Education Foundation, the Orthopaedic Research Society, NIH, and seven companies. For three days orthopedists, biologists, engineers, and people with expertise in material sciences pored over ways to start developing a master plan of how to more effectively solve these tissue engineering problems. The idea was that, unlike when we just tried to mix this and that, the most important thing now is to carefully define the clinical problem we want to solve. Using example problems and with surgeon input, we said, ‘Given those problems, what animal and tissue models would we then use to study those issues?’ We recognize the advantages and limitations of the models, but by knowing how their performance compares to how patients function, we could then go ahead and do tissue engineering in the lab with models that were good predictors of clinical outcome. Those of us in this field have been preaching this approach to the orthopedic community…and it seems to be working.”

Of course, Dr. Butler understands that there is much work to be done. “It is clear that we’re going to need special kinds of biomaterials that can serve as scaffolds for cells. These scaffolds have to be compatible with cells so they don’t change the way cells function. And they must be stiff enough for the surgeon to handle them, put them in, and not have them fall apart. Also on the horizon is the translation of these cell-based therapies for orthopedic repair. Obtaining approval for cell-based therapies from the FDA has been a slow process. It’s very new and people are leery of it. Overall, the leaders of orthopedic companies recognize that biological repairs will be the future of the industry. Those of us serving on review panels like the NIH Musculoskeletal Tissue Engineering study section see good grants come in all the time. Unfortunately, we lack the necessary level of funding to support all of this novel and important research. That could change, however, if orthopedic surgeons see the value of tissue engineering and jump on the bandwagon. Together, we can ultimately influence Congress and improve the environment for the field and, eventually, for patients as well.”