In the Musculoskeletal Research Laboratory of Mount Sinai’s new Centre for Regenerative Medicine, Dr. Tom Willett—a Scientific Associate in the lab of Dr. Marc Grynpas and Associate Scientist in the Division of Orthopaedic Surgery—is testing the biomechanical properties of bone and determining new means to maintain the toughness of bone grafts produced by tissue banks and used in orthopaedic reconstructive surgeries. His latest project is one of several collaborative initiatives between the Grynpas lab and members of the Department of Orthopaedics at Mount Sinai Hospital.
“The orthopaedic team as a whole has been extremely engaged with and interested in our work,” says Dr. Grynpas, a Senior Investigator at the Hospital’s Samuel Lunenfeld Research Institute. “In turn, their clinical expertise has given us new insight to validate and apply our findings.”
Dr. Willett is also working with orthopaedic surgeon Dr. Paul Kuzyk on biomechanical evaluation of reconstructive techniques to repair fractures occurring after knee replacement surgery (i.e., periprosthetic distal femur fracture around total knee replacements). The incidence of these fractures is increasing, and they are challenging to repair and slow to heal, especially among a typically elderly patient population where osteoporosis is common.
With Dr. Willett’s background in mechanical engineering and with support from a new Young Investigator Grant from the Orthopaedic Research and Education Foundation awarded last month to Dr. Kuzyk, the team is testing the biomechanical performance of various methods used to fix these fractures, including metal intramedullary nails, as well as metal plates with or without bone allografts.
Using a state-of-the-art mechanical testing machine, the team is measuring how much force can be endured by each reconstruction type.
“It’s difficult to conduct a clinical study in this area and therefore ideal to have a biomechanical model to test this work,” says Dr. Kuzyk. “Tom has been an instrumental collaborator in this project because of his background in engineering.”
Dr. Kuzyk, who joined Mount Sinai’s Division of Orthopaedic Surgery last November, says that “I couldn’t imagine a more perfect scenario for a researcher-surgeon. Access to the expertise at the Lunenfeld has been instrumental to this project.”
In a separate study, researchers in the Grynpas lab are working with Dr. Peter Ferguson, an orthopaedic oncologist in Mount Sinai Hospital’s Sarcoma Program. Their work is aimed at reducing the risk of fractures in patients with soft tissue sarcomas who receive radiation treatment.
Radiation is important in treating soft tissue sarcoma but has been linked to an increased risk of bone fracture.
Approximately 80 to 90 per cent of femur fractures sustained following radiation treatment for sarcoma will not heal, leading to what is termed a “non union.” These fractures may require the implantation of a large metal implant, or lead to limb amputation. To study the biological effects of irradiating the bone and to develop possible new strategies to prevent these fractures, the Grynpas lab—in collaboration with Dr. Ferguson—have developed a rat model to assess fractures and determine the potential of the OP-1 protein to promote healing of fractures following radiation.
Preliminary results have shown that prior irradiation does indeed inhibit fracture healing. The team is now studying the revascularization and marrow development surrounding areas of irradiation to determine the factors that lead to impaired bone healing.
“We have been fortunate to be able to combine our clinical experience with the tremendous expertise available in the Grynpas lab in an effort to overcome this very serious complication of cancer treatment,” says Dr. Ferguson.
“It is very motivating to know that patients will benefit from our research,” adds Dr. Willett.
The Grynpas lab is also working with Dr. Rita Kandel, clinician-scientist and Chief of Pathology and Laboratory Medicine at Mount Sinai Hospital, on news means to build improved joint replacements. A grant from the U.S. Army in 2010 kick-started their project to create leading-edge biological replacements for damaged joints and further their research in joint regeneration.
The project is a multidisciplinary effort involving bioengineers, orthopaedic surgeons, veterinary surgeons, bone biologists and stem cell biologists, and includes researchers at the University of Toronto (in Dr. Robert Pilliar’s lab), University of Waterloo, McMaster University and the Ontario Veterinary College.
Drs. Kandel and Grynpas, with additional expertise from Lunenfeld scientist Dr. Andras Nagy’s lab will study the use of stem cells for biological joint replacements in animal models, before beginning clinical studies in humans within approximately five years.
“This is the first time in Canada that stem cells have been used for joint regeneration,” said Dr. Kandel. “We are very excited to begin this research endeavour, and anticipate that this will put us at the forefront of orthopaedic and regenerative medicine in North America.”
Joint replacements, such as artificial knees and hips, are increasingly common. They're a boon for people with failing joints, but the replacement parts aren't as durable as the originals. Usually made of metal and plastic that may be cemented to bone, they can deteriorate and loosen, and usually need replacing after 10 to 20 years.
But what if implants were made from materials that would actually allow bone and cartilage to grow into them and eventually replace them? This theory was the starting point for Drs. Kandel and Grynpas.
“The idea is to use a patient’s own cells and a biodegradable material to avoid the complications of current metal or plastic joint replacements,” said Dr. Kandel. “We anticipate that biological replacements will overcome many of the current limitations of traditional replacements.” The ‘bio replacements’ could be used to repair joint tissues damaged by disease or injury, or as ligament, intervertebral disc, or bone replacements.