Buckling does the trick

A team of researchers from the University of Amsterdam has now found a way to create materials that are stiff, but still good at absorbing vibrations — and equally importantly, that can be kept very light-weight. David Dykstra, lead author of the publication, explains: “We discovered that the trick was to use materials that buckle, like thin metal sheets. When put together in a clever way, constructions made out of such buckled sheets become great absorbers of vibrations — but at the same time, they preserve a lot of the stiffness of the material they are made out of. Moreover, the sheets do not need to be very thick, and so the material can be kept relatively light.” The image shows an example of a material that uses this buckling of metal sheets to combine all of these desired properties.

A host of applications

The researchers thoroughly investigated the properties of these buckled materials, and found that they all showed this magical combination of stiffness and ability to dissipate vibrations. As known materials do not have this desired combination of properties, the new lab-made materials (or metamaterials) have a very wide range of potential applications, and at a very wide range of scales. Possible uses range from meter-sized (think of aerospace, automotive applications and many other civil designs) to the microscale (applications such as microscopes or nanolithography). Dykstra: “Humans like to build things — small things and big things — and we almost always want these structures to be light. If that can be done with materials that are both stiff and good at shock-absorbing, many existing designs can be improved and many new designs become possible. There really is no end to the possible applications!”

Some patients were more responsive to ropinirole treatment than others, and the researchers were able to predict clinical responsiveness in vitro using motor neurons derived from patient stem cells.

“ALS is totally incurable, and it’s a very difficult disease to treat,” says senior author and physiologist Hideyuki Okano of the Keio University School of Medicine in Tokyo. “We previously identified ropinirole as a potential anti-ALS drug in vitro by iPSC drug discovery, and with this trial, we have shown that it is safe to use in ALS patients and that it potentially has some therapeutic effect, but to confirm its effectiveness we need more studies, and we are now planning a phase 3 trial for the near future.”

To test ropinirole’s safety and effectiveness in patients with sporadic (i.e., non-familial) ALS, the team recruited 20 patients receiving care at Keio University Hospital in Japan. None of the patients carried genes predisposing to the disease, and, on average, they had been living with ALS for 20 months.

The trial was double blinded for the first 24 weeks, meaning that the patients and doctors did not know which patients were receiving ropinirole and which were receiving a placebo. Then, for the following 24 weeks, all patients who wished to continue were knowingly administered ropinirole. Many patients dropped out along the way — partially due to the COVID-19 pandemic — so only 7/13 ropinirole-treated and 1/7 placebo-followed-by-ropinirole-treated patients were monitored for the full year. However, no patients dropped out due to safety reasons.

To determine whether the drug was effective at slowing the progression of ALS, the team monitored a variety of different measures throughout the trial and for 4 weeks after treatment concluded. These included changes in the patients’ self-reported physical activity and ability to eat and drink independently, activity data from wearable devices, and physician-measured changes in mobility, muscle strength, and lung function.

“We found that ropinirole is safe and tolerable for ALS patients and shows therapeutic promise at helping them sustain daily activity and muscle strength,” says first author Satoru Morimoto, a neurologist at the Keio University School of Medicine in Tokyo.

Patients who received ropinirole during both phases of the trial were more physically active than patients in the placebo group. They also showed slower rates of decline in mobility, muscle strength, and lung function, and they were more likely to survive.

The benefits of ropinirole relative to the placebo became increasingly pronounced as the trial progressed. However, placebo group patients who began taking ropinirole halfway through the trial did not experience these improvements, which suggests that ropinirole treatment may only be useful if treatment is started earlier and administered over a longer duration.

Next, the researchers investigated the mechanisms behind ropinirole’s effects and looked for molecular markers of the disease. To do this, they generated induced pluripotent stem cells from the patients’ blood and grew these cells into motor neurons in the lab. Compared to healthy motor neurons, they found that motor neurons from ALS patients showed distinct differences in structure, gene expression, and metabolite concentrations, but ropinirole treatment reduced these differences.

Specifically, motor neurons grown from ALS patients had shorter neurites compared to healthy motor neurons, but these axons grew to a more normal length when the cells were treated with ropinirole. The team also identified 29 genes related to cholesterol synthesis that tended to be upregulated in motor neurons from ALS patients, but ropinirole treatment suppressed their gene expressions over time. They also identified lipid peroxide as a good surrogate marker for estimating the effect of ropinirole both in vitro and clinically.

“We found a very striking correlation between a patient’s clinical response and the response of their motor neurons in vitro,” says Morimoto. “Patients whose motor neurons responded robustly to ropinirole in vitro had a much slower clinical disease progression with ropinirole treatment, while suboptimal responders showed much more rapid disease progression despite taking ropinirole.”

The researchers say that this suggests that this method — of growing and testing motor neurons from patient-derived induced pluripotent stem cells — could be used clinically to predict how effective the drug would be for a given patient. It’s unclear why some patients are more responsive to ropinirole than others, but the researchers think that it’s probably due to genetic differences that they hope to pinpoint in future studies.

House-owners the world over consider ‘knocking through’ walls to achieve more open-plan living or changing layouts to accommodate new arrivals or circumstances. The results may be impressive, but they come at a sizeable financial and environmental cost. But what if it wasn’t necessary to demolish internal brick and/or plaster walls and build new ones?

Researchers at Cambridge’s Centre for Natural Material Innovation and partners PLP Architecture have just unveiled Ephemeral, an innovative alternative using engineered wood, at the London Design Biennale at London’s Somerset House (1st — 25th June 2023).

The project, led by Cambridge researcher Ana Gatóo, invites visitors to step into a home constructed around principles of affordability, sustainability, flexibility and adaptation. The flexible wooden partition walls — developed by Gatóo as part of her Cambridge PhD research — are made using kerfing, which allows wood to bend without breaking, the same technique employed in the construction of guitars and other stringed instruments.

The resulting wooden walls are simple, resilient, foldable and movable, meaning they can respond to the changing needs of residents, for instance, as children are born or leave the nest; as age or mobility bring changing requirements; or as homeworking patterns change.

Gatóo says: “Self-assembly and modular furniture have improved so many people’s lives. We’ve developed something similar but for walls so people can take total control of their interior spaces.”

“If you have lots of money, you can hire a designer and alter the interiors of your house, but if you don’t, you’re stuck with very rigid systems that could be decades out-of-date. You might be stuck with more rooms than you need, or too few. We want to empower people to make their spaces their own.”

The team’s ‘rooms of requirement’ provide elegant, affordable solutions which can be built into the fabric of the building from its first design, or seamlessly retrofitted — avoiding the mountains of carbon associated with demolition and reconstruction.

Gatóo says: “We’re using engineered timber, which is affordable and sustainable. It’s a natural material which stores carbon, and when you don’t need it anymore, you can make something else with it. So you are creating minimal waste.”

Gatóo and her colleagues are based in the University of Cambridge’s Centre for Natural Material Innovation, a world leader in research into innovative and sustainable uses of timber in construction.

The team emphasises that their system could be used anywhere in the world, in workplaces as well as in homes, and the researchers have already had encouraging conversations with industry, including with affordable housing developers in India.

Gatóo says: “I’ve worked in development and post-disaster housing with NGOs in many countries around the world, always using sustainable materials. When I started my PhD, I wanted to merge making housing more affordable and social with technical innovation and sustainability. This is what our cities of the future need — caring for people and the environment at the same time.”

Implemented at scale, this innovation could change the construction industry for the better, empowering people to adapt their spaces to their needs while slashing housing costs and overcoming some of the hurdles which the construction industry must tackle to be part of a sustainable future.

Working with Cambridge Enterprise, the research team is seeking industry and policy partners to further advance product feasibility for industry-wide adoption.

The project is supported by PLP Architecture, The Laudes Foundation, the Future Observatory and the AHRC Design Accelerator.