Close to the Bone

EHM talks to the Mayo Clinic’s Daniel Berry, Chair of the Orthopedic Surgery department, and Michael Yaszemski, orthopedic surgeon, who outline the cutting-edge developments in the treatment of musculoskeletal conditions

The very best clinical care

“It's important that the public have an opportunity to understand whether those technological innovations are going to stand the test of time”
-Daniel Berry, Chair of the Orthopedic Surgery department at the Mayo Clinic

Mayo Clinic’s Orthopedic Surgery department has a long history in caring for patients with musculoskeletal tumors of the spine and pelvis. This type of work can require the skills of specialists in many different areas, as orthopedic surgeon Michael Yaszemski explains. “We have a team here at Mayo Clinic that has a special interest in treating these patients. That team includes orthopedic oncology surgeons, orthopedic spinal surgeons, and colleagues from colon-rectal surgery, plastic surgery, urology, vascular surgery, critical care anesthesia, medical oncology, and radiation oncology.”

Over the years, the team has refined techniques to remove these very large tumors and to perform reconstruction of the spine back to the pelvis. These techniques involve everything from removing the tumor and providing critical care to the patient, to reconstruction with the movement of tissues to cover these very large holes that are created.

Coupled with the research side, the department is engaging in regeneration of bone defects, regeneration of cartilage defects, regeneration of nervous system defects (spinal cord and peripheral nerves), and controlled drug delivery to musculoskeletal cancers.

One specific area of concentration is scoliosis, where several novel treatments are currently in the preclinical stage. “We are working on using inducible electromagnets implanted in spines that have scoliosis to be able to modulate their growth from a minimally invasive perspective,” says Yaszemski. “We position electromagnets to one side of the spine or the other. These magnets can either distract across the growing part of the vertebral body, or compress, depending upon whether the magnet is attractive or repulsive. The strength of this attraction or repulsion to encourage the spine to grow in the direction we want it to grow is determined by a wireless connection, much like a cardiology physician would program a pacemaker.

Hip replacement

Yaszemski and his team are working on total joint replacement for hip and knee patients needing reconstruction or prosthetics for amputations. “We are working on a technique called intraosseous transcutaneous amputation prosthesis, which is a technique of having a metal prosthesis put into the residual limb. Typically this is for an above-knee amputation, and then the metal prosthesis will stick out through the skin and have an external component attached to it that would contain both a knee and an ankle. The difficult part of this is the junction between the metal and the skin, and that’s the focus of our investigation at this time.”

“Together with our colleagues in engineering and most importantly, infectious diseases, we are trying to engineer the junction between the metal and the skin so that it will be resistant to infection. We know that this happens in other parts of the body. For example, our oral maxillofacial colleagues and our dental colleagues put metal posts in regularly for people. They integrate into the bone of the mandible or the maxilla – the jawbones – and stick out through the oral mucosa and then they get a prosthetic tooth put on top of them. It can be done. The challenge is to figure out how to do this for a person with an amputation, whether it’s in the leg or the arm.”

Mayo Clinic research is part of the national consortium AFIRM, the Armed Forces Institute of Regenerative Medicine, which involves 23 academic institutions around the country. The consortium encompasses five project areas, with the Mayo Clinic having responsibility for two of those five. “With respect to nerve regeneration, we’re the lead institution,” explains Dr. Yaszemki. “Our collaborators on the nerve project are at Cleveland Clinic, Rutgers and MIT. With respect to the bone regeneration project, I’m the co-principal investigator, together with Cleveland Clinic, and in like fashion we have about five institutions that are contributing to the bone project.

“The goals of the nerve project are to work on the peripheral nervous system, meaning the nerves of the arms, legs and brachial plexus. We at Mayo Clinic are also working on the central nervous system – the spinal cord – with work funded by the National Institutes of Health. We feel that the work that’s being done for AFIRM on the peripheral nervous system will be equally applicable to the central nervous system.”

Nerve work

“Our aim is to treat nerve injuries that have gaps in them that currently don’t have an option for treatment. Typically, for microsurgeons who do peripheral nerve work, gaps of up to about an inch can be handled with local tissues, mobilization of the nerves and grafts from nerves borrowed during surgery from other parts of the body. These are typically sensory nerves that give the patient a bit of a numb spot, but then function to bridge a gap.

“There is no treatment for gaps about one inch or larger, which is why this work will focus on larger gaps of more than two inches as a trial. It involves both allograft nerve tissue, meaning donations from people who have died, and synthetic polymer scaffolds augmented with stem cells. We’re focusing on adult bone marrow stem cells, and the work is progressing well.”

Mayo Clinic’s involvement in the consortium will allow for more individuals to be included in this project. Over the next 12 to 18 months, Dr. Yaszemski’s efforts will focus on segmental defects in bone using polymeric materials fabricated into specific shapes and sizes that are loaded with cells and bioactive molecules.

‘We’re also looking at controlled delivery of novel biomolecules for cancer treatment. The cancer project focuses on musculoskeletal cancers, based upon what we take care of clinically, and we have a number of small molecules that seem to induce the natural death of these cells, while not affecting normal connective tissue cells.

“We’re trying to understand the molecular signaling that goes on to make this effect happen, and then to harness this effect by controlled local delivery to the site of the tumor, so we can get a higher concentration of this treatment where the tumor is, and minimize the concentration to other parts of the body that are cared for, quite appropriately, by systemic chemotherapy that people are getting now. We view this as an adjunct to the existing surgery and systemic chemotherapy by giving additional treatment at the local site of the connective tissue tumor, which is called a sarcoma.”