The bone builder

Professor Melissa Knothe Tate

Armed with ingenuity and a sewing machine, Melissa Knothe Tate has created a ‘sleeve’ that mimics the regenerative capabilities of bones. By Myles Gough. 

For anyone who has suffered a traumatic bone break, the long road to a full recovery is usually fraught with multiple surgeries and a great deal of pain.

High-impact car crashes or explosions, or the removal of cancerous tumours, can leave bones with missing pieces even after the fracture itself is repaired.

‘Standard of care’ techniques to fill in those missing parts exist, but treatment times are long, patients experience significant discomfort and are subjected to rigorous compliance schedules, and there’s no guarantee of success.

The methods also require invasive grafting, where segments of bone are taken from elsewhere in the body, or from animals, and ground into a mixture to be packed into the empty space.

But a more patient friendly option involving one procedure and no grafts has several companies eager for clinical trials with the new technology.

Professor Melissa Knothe Tate, recently appointed the Paul M. Trainor Chair in Biomedical Engineering, has designed an implantable device that mimics the regenerative capabilities of periosteum – an elastic membrane covering the surface of our bones.

The sleeve-like device is sutured to healthy tissue like a patch over the bone and provides a network of channels for stem cells and bone-forming material to take hold.

Based at the Graduate School of Biomedical Engineering at UNSW, Knothe Tate is keen to use her position to bring some of the newest and oldest technologies together. She hopes to establish outreach programs for Indigenous communities and encourage innovation by getting Indigenous youth to observe their environment and explore ways nature has engineered itself to maximise adaptation and survival.

Knothe Tate says translational research and challenging existing dogma are two hallmarks of her work. These traits are evident in her breakthroughs in bone repair, work that began a decade ago at Case Western Reserve University and the Cleveland Clinic in Ohio, with a team that included her orthopaedic surgeon husband, Ulf Knothe.

In operations on sheep, a piece of intact periosteum was patched over a missing section of bone. The results were startlingly effective: in less than two weeks, gaps about 2.5cm long had filled with new bone.

“We were quite surprised and delighted,” she recalls.

But there was a problem. The procedure depended on the presence of the layer of periosteum, which after a traumatic injury is rarely left intact.

“As an engineer, I immediately started thinking, ‘What’s the most basic way we can replace the periosteum?’ So I got out my old sewing machine.

“We know what periosteum is made of – it’s essentially a combination of elastin … and collagen, which is a very tough protein that helps hold your skin together. And we know there are periosteum-derived stem cells, which are natural bone builders.”

Using surgical sutures, Knothe Tate sewed together two elastic sheets, which are used in reconstructive surgery. The outside layer was kept intact, the inside layer was perforated with small holes.

The stitching created pockets into which collagen sponges were tucked. And onto their surfaces, she seeded stem cells from the periosteum.

“It seemed so simple, but it worked beautifully,” she says.

The results were published in the journal PLOS ONE in 2011. Not only did they show the device was able to hasten bone growth in their animal model, but importantly no grafting was required.

“Orthopaedic surgeons thought this was heresy,” says Knothe Tate. “But we have to be open to surprises. You don’t need the graft – in fact, the graft impaired the ingression of these stem cells into the defect where they do their work.”

She has patented the innovation, which she says blurs the line between an implant and a delivery device. 

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