From Lake Wobegon Country – a Unique Ortho Research and Skills Lab

The identifying sign on the three-story, 55, 000 square foot brick building on 10th Avenue in Minneapolis reads “Life Science Building.” To find the entrance a visitor has to walk around to the back near the loading dock. There a half flight of stairs leads to a small atrium where, on a bench, rests a life-size bronze statue of Mark Twain.

Though graced with an English department icon, the building houses an extraordinary combination of high level orthopedic device testing, surgical training and biomedical research. A battery of machines in the basement, called the Biomechanics lab, test all manner of implants and devices for their own researchers and for companies on a contract basis. Spine-related testing represents up to 70% of the lab’s work.

Courtesy of Excelen Center for Bone & Joint Research and Education (excelen.org)

The enterprise is housed in a building that had once been a residence hall for nurses. Now a warren of narrow hallways and utilitarian dropped ceilings, the building retains, hidden away, its crown molding, fine plaster work, artisan crafted woodwork, even a fireplace sealed off somewhere behind a wall. A swimming pool in the basement was filled in and now houses the 2, 000 square foot skills lab with its operating room lighting, basic instrument set up and specialized power drills and saws that provide surgeons hands-on cadaveric training.

When founded in 1978 by Dr. Ramon Gustilo, an orthopedic surgeon who wanted more space to tinker with improvements to surgical instruments, it was called the Midwest Orthopedic Research Foundation.  The organization remained under that name until the Internet age when the group discovered that the letters MORF were not available as a “.org” so he and colleagues changed the name to Excelen Center for Bone & Joint Research and Education (excelen.org).

In the 1980s Richard Kyle, M.D, later a president of the American Academy of Orthopaedic Surgeons and chairman of the department of orthopaedic surgery at the Hennepin County Medical Center, joined Gustilo in the Biomechanics lab. Gustilo startled his wife when he came home one day and told her he had spent their pension money on an MTS Model 810 load frame, an expensive piece of mechanical testing equipment for the organization. Though Excelen now owns three of MTS systems’ massive testing machines, the one Gustile bought is still in use. More recently, Kyle, with colleagues and investors, bought the building and later donated it to Excelen.

Gustilo was interested in infections in open fractures and in the 1970s he came up with a classification system that is still in use. Recently, when research papers were ranked on the number of times they were citied in orthopedics research, Gustilo’s ranked fourth.

Excelen remains focused on bone healing with co-morbidities such as bone infections, particularly those related to implants. Fractures that have been fixed with metal plates or rods can become infected by bacteria that live in a biofilm on the surface of the implant making the healing of infected bones a major challenge. Joan Bechtold, Ph.D., director of the Orthopaedic Biomechanics Lab, the Minneapolis Medical Research Foundation and Professor, Department of Orthopaedic Surgery, Mechanical and Biomedical Engineering, University of Minnesota, is working on various methods for the control of infections using a variety of techniques, including the testing of coatings, such as silver and antibiotics, on implants.

“Hip and knee infections are hard to treat because the implant itself carries the infectious agents, ” Bechtold said, “Until you get the implant out you really cannot treat it.” She said that bugs, from whatever source, land on the implant and coat it with the slime-like material that prevents antibiotics from getting to it. Her present research, working with rats, is aimed at finding a solution to this problem.

Joan Bechtold, Ph.D.A further complication occurs when, in the process of loosening, an implant such as a hip implant gets walled off from the bone and the body creates a kind of shell around it. “Surgeons talk about a white dense cavity. What we have done is break through that cavity bringing in the blood supply, the marrow and other elements to the site, which has been about as successful as some of the other coating treatments, ” Bechtold said.

Bechtold is attacking the problem from three perspectives: with coatings, with bone grafts and with bone-graft substitutes such as allografts and ceramic and collagen-based materials. She and Kjeld Soballe, M.D., Ph.D., and other colleagues of the University of Arhus, Denmark, recently examined periosteum, the thin lining of cells on the surface of bone. Mixed in with the little pieces of periosteum they found formations of cells that are associated with fracture healing. “We think there is some promise there so we are going to look into optimizing it further, ” she said.

Much of their research is immediately applicable, Bechtold noted. An example is the use of hydroxyapatite coated implants which, when used in experimental revision surgery, give surgeons a fixation that is on a par with the primary implant or various bone graft studies evaluating antibiotic inclusion and bioburden reduction. Bechtold is working with the Cleveland Clinic, the University of Minnesota Veterinary School and the Institute for Surgical Research on a severe soft tissue and bone defect study using goats as models.

Working with Twin Star Medical, located next door, the laboratory has assisted in the development of a solution to what is called “compartment syndrome” that affects soldiers injured by improvised explosive devices. As Andrew Schmidt, M.D., explained, “When you break a bone in the leg the whole leg bleeds and swells. If the pressure gets so high that blood stops flowing through the muscle, the leg muscle dies. It’s not easy to diagnose this condition and there is no way to prevent it.

“If an injured soldier’s leg starts swelling during the eight-hour transport to Germany for treatment, he could arrive with permanent damage. Currently, the only way to try and save the leg muscle is to perform a fasciotomy, slitting the skin from one end to the other to allow the muscle to bulge out and relieve the pressure. This leaves large wounds that must remain open for several days until the swelling goes down, which may save the limb but further complicate the management of these patients.”

This solution is the development of a skinny 1-millimeter soaker-hose-like catheter that can be inserted into the tissue and, when suction is applied, will draw out fluid from the muscle. It is now being studied in large multicenter studies around the country. Schmidt believes that with the device, “we’ll reduce unnecessary fasciotomies and we may even be able to prevent some patients from needing them in the first place.”

A study of smoking as it relates to fracture healing, conducted by Excelen, had an unexpected outcome. As Kyle explained, “Even one cigarette a day affects the bone’s ability to heal and increases the possible rate of nonunion by as much as 30 percent compared to a nonunion rate of 2 percent to 3 percent for nonsmokers.  This is huge.”

So, in cooperation with researchers at the Minneapolis Medical Research Foundation and the University of Minnesota’s NCI Translational Tobacco Use and Research Center, Excelen undertook a study of the effect of tobacco, with and without nicotine, on the healing of broken bones in rats.

Bechtold was one of the investigators on the study. She found that while an extract of tobacco containing nicotine did impair the mechanical strength of the healing fractures on the subject rats, nicotine, by itself, did not. The denicotinized tobacco was not the problem.

Somewhat to their surprise, the investigators discovered that some of the other 3, 500 ingredients in tobacco had to be the culprit.

“Another complex mechanical process we examine is how well a fixation device at a fracture site holds up when you apply torsion or bending, ” Bechtold said. “With a national team of researchers our engineering team did a torsion test with seven different combinations of locking and non-locking screws.  Surgeons used our results to minimize the number of locking screws required, which are more expensive and more difficult to remove .The results also helped identify which screw patterns are most effective.”

Though this outcome was not originally intended, Excelen has become an incubator for medical-technology companies. Several, including DGIMed Ortho, Inc., Zyga Technology and Twin Star Medical got their start utilizing the research and testing facilities available at Excelen. One now has 40 employees. More than 100 clinical fellows from the United States, Asia and Europe have trained there, participating in research in areas from orthopedic trauma to infection to joint replacement.

As life expectancy lengthens, the need increases for improved, cost-effective treatment for orthopedic injuries and diseases. While many orthopedic departments have testing and research laboratories, the nonprofit Excelen is in a class by itself. The leaders of Excelen plan to keep the organization’s focus on its role as a unique consolidated resource for orthopedic scientists, engineers, physicians and students.