Look to nature for inspiration22 January 2020
Throughout his 20-year career, Professor William Murphy of the University of Wisconsin-Madison has looked to nature for inspiration. He has designed ‘bio-inspired’ materials for a host of medical applications, ranging from brain-on-a-chip techniques to materials that deliver messenger RNA for tissue regeneration. But how is his pure research being translated into real-world settings? Abi Miller investigates.
William Murphy, a professor of biomedical engineering and orthopaedics at the University of Wisconsin-Madison, is a prolific inventor. Over the course of his career, he has designed a vast array of materials, ranging from 3D-printed implants for bone regeneration to materials that control the micro-environment of stem cells.
With 21 patents to his name and 29 others pending, Murphy was named to the National Academy of Inventors class of fellows in 2018. This is the highest professional distinction accorded to academic inventors.
However, despite the diversity of his output, there is a common underlying theme. Murphy’s lab focuses on ‘bio-inspired’ materials – in other words, materials that take their cues from nature itself.
“The types of properties that our materials have typically mimic some aspect of nature’s materials,” he explains. “For example, the way we synthesise some of our mineral-based materials is inspired by the way that minerals in nature are synthesised. And there are materials in nature that have properties that would be difficult for us to design de novo.”
For an academic who started out in fundamental physics, this was perhaps an unlikely route to take. Murphy came to biomaterials via material science – more specifically an interest in superconductivity. As a physics major at Illinois Wesleyan University, his biology training did not extend much further than a course in Biology 101. However, by the time he reached graduate school, he had moved beyond pure research and was starting to deliberate the real-world applications of material science.
“I very much wanted to use material science to help people, and so I got interested in biomedical materials, or biomaterials, for that reason,” he recalls. “While I was interested in all aspects of material science, this was the area I felt has the greatest impact on society.”
Let’s get physical
With a physicist’s eye view on biology – appreciating materials first and biological processes second – he was able to gain a foothold in what is a highly multidisciplinary field. Bio-inspiration is a fastemerging discipline that calls for integrative and original thinking. It requires the ability to look at natural materials – or even living matter – and understand how their structure or function might be mimicked synthetically. Sources of inspiration run the gamut from seashells to human organs to plants.
“Plant-derived materials are particularly good at fluid transport and in some cases they have particular physical or mechanical properties that would be very difficult to manufacture,” says Murphy. “We’ve created approaches that allow us to take plant-derived materials and process them so they can be used as biomedical materials.”
Surveying his work to date, it is easy to get bogged down by its sheer variety. Murphy has used plant leaves as scaffolding to grow human cells. He has created a mineral coating that mimics bone and appears to keep proteins stable. He has created replacement tissue from stem cells and addressed bottlenecks across many aspects of biomedicine.
However, there are a few categories of research that he thinks have the greatest potential for longterm impact. One is a screening method for materials, which is similar to the techniques used in drug discovery.
“When people are trying to screen for an individual drug, they might start with hundreds or thousands of candidates of drugs and then ultimately zero in on the candidates that are most likely to have efficacy,” he explains. “We’ve applied that model to materials identification, meaning we can look at hundreds or thousands of different material compositions and observe their biological effects very efficiently.
That allows us to identify materials with unique characteristics that do something a typical biomedical material would not.” Clearly, this paves the way for many new inventions and novel material compositions. But it’s the platform technology itself that Murphy considers to be his most salient invention. It might be used, for example, within medical device coatings, homing in on the ones that promote desired outcomes without causing infection or inflammation.
Murphy has also explored materials that deliver messenger RNA, to more effectively activate genes in target cells. Already, this technique has shown promise in animal models, within skin wound healing and spinal cord injury repair.
“In most cases, what we’re focused on is leveraging the gene product so it remains active for an extended period of time,” Murphy says. “Messenger RNA delivery has lots of advantages as a way of treating patients with disease, but one of its really big drawbacks is that it doesn’t last very long and its gene products don’t get expressed for very long – in many cases minutes to hours. We’d like to use messenger RNA delivery to effect healing processes that take weeks to months, so we’ve been using materials to prolong its biological impact.”
He has also been working on a new tissue-on-achip technique, which involves growing human brain and liver organoids from stem cells. These tissues can be used for disease modeling and drug discovery, and over time could eliminate the need for animal testing.
“Probably the simplest future application that we’re working on is looking at cancer growth in the brain,” says Murphy. “We can add tumour-derived cells from a patient into these kinds of brain tissues on a chip, and we can evaluate whether the cells will take root and grow. By doing so we can understand more about how metastatic brain cancer develops or how cancers might metastasise to the brain, and we can identify new drugs that might block its growth. Ultimately, we think this could lead to personalised treatments for cancer.”
Given his focus on real-world applicability, it is no wonder that Murphy’s lab has developed four spin-off companies. The most notable of these is maybe Stem Pharm, which creates a jelly-like material designed to support the development of stem cells. More broadly, his team works closely with biologists and clinicians with a view to translating materials from concepts to clinics. Unfortunately, it is not always easy to convert pure research into viable medical applications. As Murphy explains, one of the critical obstacles lies in understanding whether there is a real opportunity to apply a technology.
“We as academic researchers often at times assume that because there’s an unmet need in the clinic, there’s clearly an opportunity to develop a new biomaterial or a new type of treatment,” he says. “That doesn’t take into account the additional hurdles along the path of technological development, including an understanding of the business case and the regulatory environment, or even whether there’s truly an unmet need in the clinic.”
Insofar as his team has overcome these hurdles, it has been through speaking to other people outside the university setting. “It’s been by learning what the potential applications are for a technology and being humble in our assertions about its likely applicability,” says Murphy.
Since last September, Murphy has chaired the nascent Forward BIO Initiative, a collaboration between the University of Wisconsin-Madison, the state of Wisconsin and the biomanufacturing industry. Geared towards making Wisconsin a recognised centre of excellence for biomanufacturing, the initiative will offer resources to translate innovations into commercial products. It includes an institute at the university, which Murphy directs, as well as an incubator facility for new spin-off companies.
“The Forward BIO Initiative aims to create new ways of translating technologies out of the university and into the private sector so that they can impact society,” says Murphy. “We’re identifying technologies that have potential for societal impact, and then we’re putting them on a path for achieving that impact, including understanding the clinical and regulatory environment, and the business opportunity. In some cases we’ll work towards generating new start-up companies that can take the handout from the university and develop a technology further.”
According to [University of Wisconsin-Madison] chancellor Rebecca Blank, the initiative “leverages one of our key long-term strengths at UW, which is working at the crossroads where multiple disciplines connect”. It goes without saying that Murphy’s own work serves as a prime example.
Within his own lab, Murphy will be continuing with the many projects already under way, and harnessing the approaches that have been used to date to create whole new classes of biomaterial. But the important part will be turning the discovery into something with the potential to make a difference.
“We really need to listen to the clinicians that are going to be using these technologies and the businesspeople that are going to need to further develop our technologies after they leave the university,” Murphy points out “Those conversations with clinicians, with business folks, with regulatory experts, have been really very important.”