Biominerals to bones

Anybody in need of joint replacement surgery will appreciate the options modern medicine provides, but if Kate McGrath has her way, future patients won’t require any screws or other metal parts in their new hips or knees. The director of the MacDiarmid Institute and her research team are borrowing ideas from nature to develop innovative wound-healing and implant technologies. Most joint implants used today are made of metal alloys, which are durable and strong. “But bone is a bit like chalk,” says McGrath. “Imagine a bit of chalk and a metal coin that rub against each other. Which is going to wear out first? That’s what happens in high-impact joints.” Innovations so far have involved roughing the metal surface and coating implants with plastics to achieve better integration and protection of both the implant and bone, but Kate’s team is approaching the problem from a very different angle. Natural materials that need to be strong and hard are invariably made by molecular self-assembly in a process called biomineralisation. Biominerals are everywhere, from the patterned walls enclosing microscopic algae to the massive bones of a whale. Most plants and animals synthesise some form of biomineral material. Plants generally deposit minerals composed of silica, or bioglass, while animals produce materials based on calcium. Marine creatures such as kina and paua use it to grow their shells. Our bones and teeth, and even the tiny otolith in our inner ear, are also biominerals, as are kidney and gall bladder stones. Natural biominerals are often elaborate in detail but lighter, more durable and stronger than manmade ones. To top off the list of desirable attributes, they are also able to regenerate when damaged. “Every single organism undergoes some form of biomineralisation. We’re interested in learning how they do it and in replicating the process in the lab,” says McGrath. The first step was to study the detailed composition of natural biominerals, such as kina spines, and to figure out how they self-assemble into such complex forms. It turns out that the process often involves a soft organic scaffold, made of glycoproteins. It was thought that the organic scaffold acted mostly as a rigid template, but it was McGrath’s work, together with colleague Conrad Lendrum, that demonstrated for the first time that the scaffold and mineral crystals work in tandem, rearranging and assembling simultaneously. The next step was to recreate the process in the lab. “We mimic the process by including an acidic polymer,” says postdoctoral researcher Natasha Evans. “With our materials we’ve worked out that the chemistry of the carbohydrates that we use and the interaction with the acidic polymer can dictate the type of mineral crystal that is formed, so we have very good control of the chemistry of the crystals and are now looking at the physical forms of the materials.” The team started out with thin films, aiming to develop a new, more bio-compatible material that could be used to coat existing implants. Control they have over the process has allowed them to produce spheres and larger components. “There is a diffusion limit,” says McGrath, “because of the process we use for mineralisation we can’t make really thick materials, but by making spheres and compacting them together in a gel you can make large materials.” With the help of 3D-printing, Evans says the team has developed techniques to begin recreating the natural structure of bone. “We can 3D-print a cylinder and infill with chitosan foam, which is mineralised to form our biomimetic material. The porosity inside comes from the size of the bubbles in the foam that we put in.” Mechanical tests have already demonstrated that the material’s tensile strength is comparable to paua shell, and compression tests are underway to see how strong it is. In addition, biological tests have shown that it is compatible with bone cells. “In the first round we used fibroblasts, which are a good model for how cells grow, and in contact with the material they grew normally. We’ve also tested it with human osteoblast, or bone-growing cells and they perform as normal and remain viable.” These results are doubly promising since not only would such a material improve the durability and biological compatibility of implants, it could also help damaged bone heal itself. “Ideally the body would repair itself,” says Evans. “But if you have large breaks, it’s too hard for the bone to grow across the gap, so a lot of regenerative medicine is looking at materials that you can put into place to help the bone to migrate across the gap. This material will slowly degrade as it is replaced by bone.” McGrath originally enrolled in engineering at the University of Canterbury but, inspired by a lecture by Chemist John Blunt, she switched to chemistry. During her PhD at the Australian National University she chose the subject of self-assembly and her research moved closer to physics. Post-doctoral positions in Paris, at L’Université de Pierre et Marie Curie, and at Princeton University followed, where she worked with the pioneers of a research area now known as soft matter physics or biophysics. When she returned to New Zealand, initially to the University of Otago, she made contact with Sir Paul Callaghan, who eventually persuaded her to join The MacDiarmid Institute. As the Institute’s director, she sees herself as a change leader. At about the time she took on the directorship, she also developed and instigated a Masters programme in Advanced Technology Enterprise, which provides students from various disciplines with an opportunity to work together as an actual start-up company and to learn all the “soft skills such as making decisions individually and collectively, market research, and the struggles of the advanced tech space in terms of doing business”. “It’s not just the science we do. The MacDiarmid Institute has the capacity to make a difference, and we actually have the responsibility to do that and to think about it in the context of the innovation sector and outreach, and to dare to do things in different ways.” Listen to Kate McGrath and Natasha Evans speak to Veronika Meduna on Radio New Zealand’s Our Changing World.