Research Program
Basic Science
New, collaborative Approaches in Orthopaedic Research Give Hope to a Myriad of
Patients Infinite applications. Limitless possibilities. The University of
Tennessee-Campbell Clinic Department of Orthopaedic Surgery is poised at the
threshold of new treatments and preventive medicine due to pioneering research
supported by Campbell Foundation. Key collaborations in research are propelling
the department forward.
"We
have scientist, bioengineers, and clinicians working side by side accelerating
the 'bench to bedside' approach" said
Karen Hasty, PhD, chief researcher for the
department and George Thomas Wilhelm, MD Endowed Professor in Orthopaedics.
"The clinician evaluates an orthopaedic problem in the
context of his individual patient with respect to age, health status, and
available therapies. The cell biologist focuses on the same problem as a
malfunction of cellular interactions. A biomedical engineer might consider this
problem as a defect in the skeletal structure and investigate mechanical failure
of the skeletal structure as well as replacement biomaterials. "What
is the correct approach? All of the above! The relationship between these
investigators represents the "3-D" view that is vital for developing
innovative therapies.
Dr. S. Terry Canale, President, Campbell Foundation, and recently appointed
Chair of the UT-Campbell Clinic Department of Orthopaedics, is enthusiastic
about this collaboration of basic scientists and clinicians. "We are on the verge
of the orthopaedic scientist being able to isolate specialized living cells in
the test tube, multiply them in culture, and ultimately create living,
structural body parts such as knees and hip joints that can then be implanted
into the human body by orthopaedic surgeons." Dr. Hasty adds, "Every year, there
is new information and new technology, enabling us to examine questions we
couldn't explore before."
Large-scale studies usually require funding from large institutions such as
the National Institutes of Health (NIH). Corporate partnerships also provide
resources for larger research projects, but that is not enough. These
organizations will not fund untested hypotheses, so Campbell Foundation helps
fill this critical gap. "The Foundation provides seed money for pilot studies to
extract preliminary data, backing up proposals for larger grants. A surgical
resident and surgeon at the bedside may propose an alternate method of
treatment, but how do you test this? Patients need conservative, tested
therapies. Pilot studies allow us to test the feasibility of new ideas and pave
the way for acquiring research grants to conduct large scale testing," Hasty
said. The department currently collaborates with businesses such as Medtronic
Sofamor Danek, Smith & Nephew, and Wright Medical Technology. An example of just
one of these projects is a study of a Smith & Nephew product called Jax, a bone
graft substitute. Scientist Richard Smith, PhD
is
working closely with the company on this project, the results of which have just
been accepted for presentation at the National Orthopaedic Research Society
meeting. The breadth of orthopaedic research projects in the Department of
Orthopaedics can also benefit other fields of medicine from neurology to tissue
engineering to oncology. Growing and reimplanting an individual's own stem cells
to regenerate tissue is the goal of one study, "The Use of Mesenchymal Stem
Cells for Repairing Growth Plate Defects." Everyone has mesenchymal stem cells (MSCs)
in his or her bone marrow that function to aid healing of damaged tissues.
However, they are normally present in very small numbers. Harvesting MSCs,
growing them in culture to large numbers, and reimplanting them where needed - a field know as tissue
engineering - could have limitless applications. One of the researchers working on
this project, Jae Ahn, MD, PhD, is specifically concentrating on the cells'
role in growth plate repair. Growth plates, found at the ends of the body's
long bones, cause the bones to lengthen during childhood. This area of bone
grows rapidly in children, so it is weak and vulnerable to fracture. Trauma
to the growth plate can cause a discrepancy in limb lengths. Dr. Ahn has
been testing the use of MSCs in growth plate repair in young rabbits and has
had his work accepted for presentation at the national meeting of the
Pediatric Orthopaedic Society of North America.
Principles learned in this study could benefit many other disciplines. For
example, neurology could use tenets of tissue engineering to replace diseased
dopamine cells in the brains of Parkinson's Disease patients. And
Dr. Robert
Heck, orthopaedic oncologist with Campbell Clinic, already has direct
applications in mind for regenerating bone tissue in pediatric cancer patients
at St. Jude.
Another project is a melding of the basic science of growing tissue in
culture with the clinical application of surgically implanting this tissue.
"Growing Chondrocytes in Culture for Tissue Transplantation" is a collaborative
study of the Department of Orthopaedics with Jae Rho, PhD and Kwidoek Park, PhD,
of the University of Memphis, and
Frederick Azar, MD
of Campbell Clinic. They are growing cartilage cells in culture for
transplantation into cartilage defects in pigs and will also examine the role of
mechanical stress on cartilage degeneration.
"Cartilage is a tissue that requires mechanical stress
to be healthy, but clearly, wear and tear play a major role in joint
degeneration. So, what are the critical elements that shift the balance? What
role does aging play in this shift?" Dr. Hasty said.
Understanding why cartilage breaks down in osteoarthritis and
autoimmune diseases such as rheumatoid arthritis is the chief research area of
Dr. Hasty in the Department of Orthopaedics. This
research involves identifying the enzymes that break down cartilage,
understanding how they work and finding what causes their production or inhibits
them. Funded by the VA and NIH grants, this study was the subject for the
Department of Orthopaedics' presentation at the American College of
Rheumatology.
A recent study by the Centers for Disease Control and
Prevention asserts that arthritis now affects one in three adults in the United
States. This would account for 69.9 million arthritis sufferers.
"We are an aging population in this country. The collaborative
work we are doing now has the potential to help older people heal faster and
live longer, more active lives," says Dr. Hasty.
Current research projects and sheer momentum in the Department
of Orthopaedic Surgery offer great hope to patients of all ages suffering from a
broad spectrum of maladies - from bone cancer to congenital musculoskeletal
disorders, from arthritis to Parkinson's Disease, from diseases of aging to
sports injuries, just to name a few. The collaborative team approach of the
researchers puts these findings on the fast track to help all of our patients
much sooner. "I really believe in this," said Dr. Hasty. "These partnerships are
the wave of the future."
Research to Lengthen Life of Joint Implants
Committed to optimizing quality of life for all current and
future joint replacement patients, Campbell researchers are involved in
breakthrough research on joint implant loosening. An estimated 15 percent of all
replacement patients will need revision surgery at some point due to loosening.
With funding from Smith & Nephew, Inc., the University of Tennessee-Campbell
Clinic Department of Orthopaedic Surgery is working to find the cause of
osteolysis, a resorption of bone around implants, wearing bone away until the
implant loosens enough to fail. Of patients needing revision surgery, 40 percent
are caused by osteolysis. Applications of research findings are aimed at
lengthening the life of implants and lessening the need for later revision
surgery. "Revision is very hard on the patients," said Richard A. Smith, PhD,
the project's principal investigator and Assistant Professor in the Department
of Orthopaedic Surgery. "There is less bone to work with than in the primary
replacement, and the lifespan of the revised hip is much shorter than with the
first surgery." Smith, in orthopaedic research for over 17 years, explained
previous research has linked joint implant loosening to wear debris generated by
the implant. The studies beg more questions. "In biology, each question answered
brings a whole new set of questions," said Smith. "The questions of wear
particles and their role is not answered. We are trying to understand the
biological mechanisms involved in osteolysis; Does it have anything to do with
materials used in the hip replacement? Is is exacerbated by drugs the patient
takes to combat their disease? It gets pretty complicated, but we're getting
closer," Smith said.
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