Knee pain – it's familiar to runners, skiers, and almost anyone over a certain age. Yet doctors often urge patients to postpone knee replacement surgery as long as possible because the artificial joint may not last long.
Now, a collaborative research project that began at the University of Toronto’s Institute of Biomaterials & Biomedical Engineering (IBBME) is using a new "biological 3-D printing" process to move researchers one step closer to revolutionizing the treatment and care of those suffering from osteoarthritis, joint diseases or injuries through the use of biological joint replacements.
Approximately 60 per cent of people older than 50 suffer from some degree of arthritis, where cartilage – the material of the body that cushions the joints – erodes, damaging the bone and causing pain and mobility issues. Yet current replacement materials – metal, ceramic and plastic – offer only short-term solutions to long-term care.
“In 20 to 30 years these materials will ultimately fail,” explains Dr. Rita Kandel, chief of pathology at Mount Sinai, and a professor in the Department of Laboratory Medicine & Pathobiology and the Institute of Biomaterials & Biomedical Engineering, as well as director of the Collaborative Program in Musculoskeletal Science at the University of Toronto.
“The current materials used can’t withstand the prolonged application of forces. Wear and fatigue can set in, resulting in failure through aggravated allergic responses or outright fracture. Synthetic implant materials can’t heal if there’s a fracture."
Bob Pilliar, professor emeritus in the Faculty of Dentistry and IBBME, was one of three researchers – along with Kandel and Professor Marc Grynpas – who set out in the 1990s to discover a biological material to replace joints.
Pilliar and his team developed a structure made from calcium polyphosphate – consisting of calcium and phosphate, the same mineral components found in human bone – that, when manufactured in a particular way, provides a porous, biodegradable bone substitute that can also serve as a “template” for new bone formation to a desired form.
Human bone grows into and through the porous calcium polyphosphate – anchoring it in place in the area in need of repair – while allowing bone to develop and biologically bond to maturing cartilage cells layered on top. Over time, the calcium polyphosphate template degrades, safely and naturally flushing out of the body, leaving behind a newly generated natural joint structure.
But discovering a bone template was only the first major hurdle; the second was to create cartilage in quantities sufficient to cover large surfaces in need of repair.
Cartilage is an incredibly difficult part of the body to repair. “Once the cartilage is damaged, that’s it – the body does not have the ability to create more or repair it,” explains David Lee, a PhD candidate in Kandel’s lab involved in the tissue engineering aspects of the project.
Thus far, tissue engineering strategies for repairing damaged cartilage have proven elusive, since cells extracted from the tissue and grown to numbers large enough to work with tend to lose their cartilage characteristics. So the team developed a strategy that draws on other types of cells, such as stem cells extracted from bone marrow. These cells are grown in large numbers and reprogrammed into immature cartilage cells, which are then layered and grown on and into the top part of the porous calcium polyphosphate construct.
So far the team has proven that the biological resurfacing has been successful for repair and regeneration of small cartilage defect areas. “Now we’re looking to see if a larger joint replacement can survive,” explains Pilliar of their latest study: a large femoral knee replacement.
Since the researchers’ early days, the project has morphed into a multi-disciplinary collaboration between numerous universities, namely Waterloo, Guelph, McMaster and Queen’s.
The bone substitutes are manufactured at Waterloo University, for instance, where biological 3D printing technology is being utilized to make each joint template “to measure”. Meanwhile, a collaborator at Queen’s University is developing a new surgical guidance system that will help surgeons make cuts that precisely match the individual’s intended replacement bone and cartilage during surgery.
While Kandel estimates that clinical trials are up to five years away, this new, biological joint technology represents the ultimate promise of personalized medicine – a means for the body’s own materials to grow back whole joints.