The future weaver

Biomedical engineer Melissa Knothe Tate is harnessing the ancient art of the loom to push the boundaries of regenerative medicine. 

Melissa Knothe Tate

Photo: Paul Henderson Kelly

Tucked away in a small room in UNSW’s Graduate School of Biomedical Engineering sits a 19th century–era weaver’s wooden loom. Operated by punch cards and hooks, the machine was the first rudimentary computer when it was unveiled in 1801.

While on the surface it looks like a standard Jacquard loom, it has been enhanced with motherboards integrated into each of the loom’s five hook modules and connected to a computer. This state-of-the-art technology means complex algorithms control each of the 5,000 feed-in fibres with incredible precision.

That capacity means the loom can weave with an extraordinary variety of substances, from glass and titanium to rayon and silk, a development that has attracted industry attention around the world.

The interest lies in the natural advantage woven materials have over other manufactured substances. Instead of manipulating material to create new shades or hues as in traditional weaving, the fabrics’ mechanical properties can be modulated, to be stiff at one end, for example, and more flexible at the other.

“Instead of a pattern of colours we get a pattern of mechanical properties,” says Melissa Knothe Tate, UNSW’s Paul Trainor Chair of Biomedical Engineering. “Think of a rope; it’s uniquely good in tension and in bending. Weaving is naturally strong in that way.”

While the loom’s materials have countless potential manufacturing applications – one tyremaker believes a titanium weave could spawn a new generation of thinner, stronger and safer steel-belt radials – Professor Knothe Tate is more interested in the machine’s human potential.

Meliisa Knothe Tate loom

Melissa Knothe Tate with the Jacquard loom. Photo: Paul Henderson Kelly

She believes it is possible, for example, to weave biological tissues – essentially human body parts – in the lab to replace and repair our failing joints. What’s more, she is convinced that one day those same parts will be woven inside the body.

“It’s always been a dream of mine to teach cells to weave their own repair,” Knothe Tate says. It would be a “living loom” and the ultimate disruptive technology, “but we’re not there yet, so we want to learn from the cells and begin the process in the lab”.

“Weaving is an ancient art but if you bring the newest technology to it, I think some pretty exciting things can happen.”

Biomedical “sweet spot”

Even in a discipline where the name is derived from the Latin ingenium, meaning “cleverness” and ingeniare, meaning “to contrive or devise”, UNSW’s biomedical engineers are pushing boundaries. Down the hall from Knothe Tate’s office atop the Gordon Samuels Building, a team led by Scientia Professor Nigel Lovell and Professor Gregg Suaning is designing a bionic eye.

Nearby Dr Lauren Kark is engineering a new generation of prosthetic limbs, while other researchers are developing biomimetic-inspired materials to regenerate tissue.

And in UNSW’s Wainwright Analytical Centre and the Biomedical Imaging Facility are some of the world’s most advanced microscopes, capable of capturing the inner workings of a single living cell.

Knothe Tate believes biomedical engineering is on the cusp of enormous advances. “I always talk about being in the sweet spot. It’s like there’s a wave and biomed is at the forefront,” she says.

The interface of mechanics and physiology is the focus of Knothe Tate’s work. In March, she travelled to the United States to present another aspect of her work at a meeting of the international Orthopedic Research Society in Las Vegas. That project – which has been dubbed “Google Maps for the body” – explores the interaction between cells and their environment in osteoporosis and other degenerative musculoskeletal conditions such as osteoarthritis.

Using previously top-secret semiconductor technology developed by optics giant Zeiss, and the same approach used by Google Maps to locate users with pinpoint accuracy, Knothe Tate and her team have created “zoomable” anatomical maps from the scale of a human joint down to a single cell.

Biomedical engineer Professor Melissa Knothe Tate and her team are zooming in and out of the human body right down to single cells. Starting with the knee joint, the researchers can figure out how cells interact and impact on conditions like osteoarthritis.

She has also spearheaded a groundbreaking partnership that includes the Cleveland Clinic, and Brown and Stanford universities to help crunch terabytes of data gathered from human hip studies – all processed with the Google technology. Analysis that once took 25 years can now be done in a matter  of weeks, bringing researchers ever closer to a set of laws that govern biological behaviour.

Her vision was a key reason for UNSW and the Paul Trainor Foundation bringing Knothe Tate to Australia to take up the inaugural Paul Trainor Chair in Biomedical Engineering, named after the father  of Australia’s medical devices, who died in 2006.

“Paul Trainor was the veritable founder of the biomedical industry in Australia. He was responsible for developing and championing the cochlear implant and cardiac pacemakers, among other technologies, and a big part of my position here at UNSW is to reinvigorate the industry he helped create, and to build on it even more,” Knothe Tate says.

Head of School, Professor John Whitelock, says the future of biomedical engineering relies on innovative academics like Knothe Tate crossing boundaries and commercialising their discoveries. “Just two years into her role, Melissa is pushing boundaries and has already patented several new technologies. She’s more than proved she is the right person to continue Paul Trainor’s legacy,” he says.

Not your average engineer

The daughter of an electrical engineer who led the US Navy’s nuclear program in EMP, the electromagnetic pulse aftermath of nuclear blasts, Knothe Tate had an itinerant childhood, following her father as he moved between postings.

Like her dad, she was fascinated with science and technology from an early age. Curious about temperature’s effects on growth, the 12-year-old Knothe Tate asked for an incubator and cleared space in the family fridge to experiment with chicken embryos.

She spent her spare high school hours shadowing doctors  and penned curious adolescent letters to surgeons about the ethical dilemmas of breast augmentation and cosmetic surgery. “I thought I was going to be a reconstructive surgeon for children with congenital malformations, but I just don’t like hospitals,” she admits.

While hospitals proved a no-go zone, Knothe Tate still held a love for medicine’s impact on human life. Moulding her own biomedical engineering degree long before the discipline existed, Knothe Tate enrolled at Stanford in separate degrees in biology and mechanical engineering, working three jobs for financial support.

Though majoring in science, Knothe Tate was also passionate about philosophy and art, with a particular interest in German language and culture. Drawn to Europe, she packed up and headed to the Swiss Federal Institute of Technology – ETH Zurich – to complete her doctoral studies. It would be a seminal experience, opening her world to new opportunities and ways of thinking – as well  as bringing husband, Ulf Knothe, with whom she’s had a daughter, into her life.

Knothe Tate keeps a picture of her Swiss graduating class on her desk. It features just  two women: “One is the secretary of the school and one is me.”

Today, half of Knothe Tate’s research team is women, a ratio reflected in the Graduate School of Biomedical Engineering as a whole. “It’s a huge change, and it’s one of the things that’s most encouraging,” she says.

From Zurich, Knothe Tate and Ulf, an orthopaedic surgeon who collaborates with  his wife on many of her studies, were recruited to the Cleveland Clinic. Colleagues thought she was crazy to turn down a plum Swiss post – a Gemachtesbett or “made bed” in terms of academia – for the north-eastern US. “I always pick the challenge, I think it’s sort of hardwired. I just needed to find my own path, a new path,” she says.

It was a formative time that brought her out of the lab and into contact with patients. “You see all the families, it’s so present,” she says of her clinical role. “As an engineer I had the feeling that what we were doing was really important and we’d better make sure it’s relevant for patients. It had  a huge impact on my future research directions.”

Weaving the future

In her UNSW office, Knothe Tate’s desk is surrounded by bones. The walls, too, are filled with framed images of the inner workings of muscles, joints and ligaments. Captured by some of the world’s most sophisticated fluorescence and electron microscopes, the multicoloured architecture is scattered on black backgrounds like constellations.

On her computer screen, a research paper displays a cross-section of a sheep’s femur, together with second harmonic and multiphoton images that capture the distribution of the section’s structural proteins. “What you see is the weave of the cells that inhabit our bodies,” Knothe Tate says, pointing to the fluorescent green, yellow and orange interplay of fibres between bone and muscle.

Our bones, she explains, are super strong, able to bear incredible weight because they contain the protein collagen (without it they would be  brittle like chalk). They are covered by a sleeve  of protective tissue called the periosteum.

One of periosteum’s unique qualities is its toughness. Another protein, elastin, makes it, “stretchy like a rubber band”. But due to the collagen, “it’s a rubber band that doesn’t break”. “It’s only 500 microns thick; so it’s fascinating  to think this soft fabric – our body’s fabric – imbues our bones with such super strength,” Knothe Tate says.

As a composite structure, periosteum has emergent properties – its strength lies in more than the sum of its parts. These “smart” properties are what Knothe Tate is reproducing on her loom.

Melissa Knothe Tate cross section

A cross section of a sheep's femur, showing the periosteum bounded by skeletal muscle and bone. Image: supplied

“What we do with the loom algorithms is  a scale-up process. It’s mimicking the patterns we find in nature,” she explains. “That could be in periosteum or tree bark or a whole host of other things that you then apply to medical products or in other industries.”

Those other industies could end up being particularly lucrative. On a recent flight between Frankfurt and Singapore, Knothe Tate got talking to two steel executives. “When they heard about the loom, they could see it had enormous potential for designing and weaving new and improved steel belts in their tyres, an area that’s seen little innovation in the past 20 years,” says Knothe Tate. She promised them she would be in touch.

Meanwhile, work has begun on the loom’s first medical pilot project: weaving the prototype of  a custom compression sleeve for women suffering lymphoedema after breast cancer surgery. The painful, disfiguring condition is caused by an accumulation of fluid in the limbs after draining nodes, or after glands are removed from the armpit. Not all women who undergo lumpectomy or mastectomy develop lymphoedema but for those who do, Knothe Tate says, it can be “almost as bad or worse than the cancer diagnosis itself”.

Treatments currently focus on using a one-size-fits-all static pressure cuff that compresses the limb to prevent fluid build-up. As well as being uncomfortable and ugly, Knothe Tate says it’s possible the cuff exacerbates the condition over time by shutting down the lymphatic system’s natural pumping action.

“We’re interested in more gentle sleeves that also enable active pumping, and that’s the whole idea of this technology; you harness the movement of the patient,” she says of the patented sleeve, which is designed using super-resolution imaging to map the tensile properties of an individual’s arm, the special fluorescence channels highlighting the sleeve’s elastin and collagen weave. Collaborators on the project are Stan Rockson at Stanford, Sydney University’s Sharon Kilbreath and Helen Mackie of Mount Wilga Private Hospital.

Also on board is UNSW Art & Design’s Liz Williamson, an internationally acclaimed textile artist. Williamson’s role will be to provide artistic and technical advice on the intricacies of the weaving process (see breakout story below).

“The project’s been a lot of fun,” says Knothe Tate, who travelled to Chico in northern California for weaving lessons with the loom-maker before she got started. She also keeps  two antique Bernina sewing machines in her office to sew new research prototypes. “They’re old machines but they’re so tough. They can handle almost any material – even leather.”

The ultimate weave

A “smarter” lymphoedema sleeve that reduces harm is no small achievement, but Knothe Tate has her sights set far higher.

Her next step is to use the loom technology to weave biodegradable tissues for joint replacements and repairs, replacing high-tech metals and plastics with biological polymers that can be absorbed and recycled by the body. The inspiration for these came after a sickening mountain bike accident in the US in 2012 that shattered her shoulder.

“The first titanium implant the surgeons used to reconstruct my AC joint failed before I even recovered from surgery. And I thought if this  is the best they can do, it’s not very good,” Knothe Tate says. So she invented a new technology, to address the problem, creating solutions for tissue repair in the process.

Also in the pipeline is a second loom-related product – artificial periosteum, which can be implanted in the body to speed up the repair  of bone fractures, damaged cartilage, and other sports injuries. “It’s a prototype of a surgical membrane that’s been made on the sewing machine. We are weaving them now, and we’ll be testing them soon in a live animal model,” Knothe Tate says.

However, the periosteum prototype is made from silicone, which, like titanium doesn’t integrate well with the body. The ideal would be to weave implants out of a patient’s own biological material. This too is on the horizon.

In 2013, along with a colleague from San Sebastian in Spain, Knothe Tate proved a “biological weave” could be done on a micro scale, publishing a paper in which the team described successfully “programming” stem  cells to weave tissue on a silicone substrate in the lab. The cells essentially became a living loom.

“Cells are already expert weavers,” Knothe Tate explains. “If you can provide them with a pattern, or architecture, in the form of adhesional proteins, the cells will just do what they naturally do.”

Ultimately, Knothe Tate wants to teach these stem cells to weave their own repairs inside the body. That may seem like the outer limits of science fiction, but Knothe Tate believes it will happen within a decade. “These kinds of disruptive technologies move things forward exponentially,” she says. “When it happens it will be a huge step forward at once.”

Knothe Tate believes the calibre of biomedical engineering research underway at UNSW, combined with “unbelieveable infrastructure  and imaging capacity” means the University will be at the vanguard of this leap forward.

“We have these Ferrari microscopes – where you can see right down to the ruffled membrane of a cell and the cell’s own skeleton – you can go down and down. We have that capacity here, which is pretty phenomenal.”

Knothe Tate says she is thriving in Australia. Importantly, she says, there’s an “entrepreneurial spirit” here that has dwindled in the US following the global financial crisis. The loom and its associated patents are testament to that. “Life’s too short, we’ve got to try it all. There’s too  much fun to be had.”

Biomedical engineering projects to watch

  • The bionic eye
  • Pre-suicidal speech recognition
  • Sugar polymers for tissue regeneration
  • Human haptics and touch-enabled computer applications for surgical simulations and rehabilitation robotics
  • Next-generation lower-limb prosthetics
  • Bio-engineered heparin for better and longer blood storage
  • Flexible conducting polymers for future medical devices.

Crafting the body

Though they approach weaving from radically different perspectives, creative partner Liz Williamson sees an elegant synergy in her collaboration with Knothe Tate.

Williamson, an associate professor at UNSW Art & Design, is an internationally renowned textiles artist and weaver celebrated as one of Australia’s Living Treasures.

She is a key partner in Knothe Tate’s lymphoedema project – the pair has jointly applied for an NHMRC Development Grant to finalise the research and Williamson will provide technical and creative guidance.

It’s an unusual collaboration, but Williamson says art and science go hand in hand, particularly weaving and medicine.

Liz Williamson

Liz Williamson. Photo: Susan Trent/Gasbag Studios

“Where I weave structures that relate and respond to the body, Melissa [Knothe Tate] creates architectures that harness the body’s movement. We are coming from different directions but we are both responding to  the body,” she says.

“There’s a wonderful flow and counterbalance with Melissa’s engineering work. It’s exciting to be challenged by her vision.”

Beyond the biomedical realm, Knothe Tate envisages a suite of creative applications for the loom, including art installations and woven sculpture.

Williamson is thrilled to have a world-class Jacquard loom at UNSW – an instrument  she describes as “state-of-the-art in terms  of its scale and quality” – and says the sky’s the limit when it comes to potential uses.