Robot exercises shoulder cells for better tissue transplants

Host: Benjamin Thompson

Welcome back to the Nature Podcast. This week: the robotic shoulder putting tendons through their paces.

Host: Nick Petrić Howe

And identifying misperceptions that can lead to vaccine hesitancy. I’m Nick Petrić Howe.

Host: Benjamin Thompson

And I’m Benjamin Thompson.

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Host: Benjamin Thompson

On a table in a lab in Oxford sits a very special shoulder joint. It’s robotic and features a plastic humerus bone sitting in a plastic socket. Strings are attached to the bone where the muscles would be and motors can pull on those strings, moving the humerus around. This robotic shoulder has an important job. Inside it are human tendons growing in a small chamber. The idea is that the movement of the shoulder stretches these cells, which could help them to grow into stronger tendon tissue. Here’s reporter Shamini Bundell with more.

Interviewer: Shamini Bundell

Growing cells in a lab is easy enough. They need nutrients, oxygen and something to grow in or on. A petri dish, for example, can often provide a suitable environment. But for some cells, just sitting in a dish isn’t enough.

Interviewee: Pierre Mouthuy

What researchers have shown, for a long time now, is that external mechanical stimulation is really key to mature the tissue properly and to have the cells express the right type of genes and to produce the right extra-cellular matrix.

Interviewer: Shamini Bundell

This is Pierre Mouthuy, a researcher at the Botnar Institute for Musculoskeletal Sciences at the University of Oxford in the UK. Pierre is talking about growing tendons – the tough bits of tissue that connect muscles and bones. He hopes lab-grown tissue could one day be grafted into human bodies to repair tears in shoulder tendons, for example. When they’re growing in a real body, these cells are being constantly stretched and moved around. And it turns out that this constant exercise is really important for the way that they grow, and the kind of extracellular matrix that the cells produce – that’s all the material around the cells that supports them.

Interviewee: Pierre Mouthuy

If you don’t provide that mechanical stimulation then the cells become rounder when they should be elongated. The extracellular matrix is sort of becoming more disorganised, and that really affects the properties of the tissue in the end.

Interviewer: Shamini Bundell

So, researchers have developed systems to make sure the cells get exercised as they develop. They grow the tissue on flexible plastic scaffolds, with fluid providing the oxygen and nutrients, and then they repeatedly stretch and relax them. So far, this has only been done with stretching in a single direction, but that’s pretty different from what tendons would experience in a real shoulder.

Interviewee: Pierre Mouthuy

What the body is providing to native tissues is three-dimensional mechanical stresses being applied in the form of not just tension but also compression and torsion.

Interviewer: Shamini Bundell

So, Pierre’s team developed a new design for a different type of chamber in which to grow cells. It’s flexible enough that it can be pushed, pulled, bent and twisted, just like a real tendon. But Pierre still needed something to do all that pushing, pulling, bending and twisting. What he needed was a robot.

Interviewee: Rafael Hostettler

So, we have been building musculoskeletal robots for a while.

Interviewer: Shamini Bundell

This is Rafael Hostettler, the CEO of robotics company Devanthro. They build an unusual type of robot – human-shaped constructions which they call ‘robodies’.

Interviewee: Rafael Hostettler

And what makes them special is that they have muscles and tendons as we humans do. So, we try to imitate the way the human body works, and we’re doing this because we believe it’s going to help us build robots that are eventually going to move just as natural and graciously as human bodies do. They are being used in research, neuroscience, biomechanics and so on, but eventually they might be used to build better prosthetics and test new implants.

Interviewer: Shamini Bundell

These robots are intended to mimic the shape, the dimensions and the mechanics of the human body.

Interviewee: Rafael Hostettler

And one day I got an email from a certain Pierre Mouthuy in my inbox asking me whether I’d be interested in using robots to grown tendons, and of course I was like hell yeah, that’s exactly in line with where we want to be going eventually.

Interviewer: Shamini Bundell

Pretty soon, Pierre’s lab had their very own robot shoulder. The chamber he and his colleagues developed for growing the tendon cells fits in just as a real tendon would, with one end attached to the humerus and the other end attached to a piece of string which then links to the motor acting as a muscle. The robot can be programmed to move the shoulder joint around, stretching the new tendon tissue as it develops.

Interviewee: Pierre Mouthuy

What we have been able to show so far with this system is that it is feasible to use robots as a way to mechanically stimulate cells that are being grown in these little flexible chambers. We’ve also shown that the mechanical stimulation that we provide is important and that it has an effect on the gene expression profile of the cells and the viability of those cells. Now, what we haven’t really shown yet and what remains to be done is to see how this new platform is comparing to the traditional systems.

Interviewer: Shamini Bundell

The new system stimulates the tissues in a much more complex and realistic way than the previous single-directional stretches. If this new setup leads to a big improvement in the tissues themselves, Pierre hopes that it could be used to improve treatments for tears in rotator cuff tendons – that’s the shoulder tendons that the robot is replicating.

Interviewee: Pierre Mouthuy

At the moment, it’s about 25% of the population above the age of 60 that has some rotator cuff tendon tear problem, and many people need to go into surgery. The problem that we have is that the fail rate of these surgical repairs is at around 40%.

Interviewer: Shamini Bundell

In the future, grafting in new tissue might be a better way of repairing torn tendons, and the lab-grown tissues would have to be suitably strong. Growing cells in a robotic body has other possible applications too.

Interviewee: Pierre Mouthuy

There are other disciplines that this could be useful for as well. For example, to look at improving rehabilitation exercises by looking at how the cells are being affected by a particular exercise. Or it could also be used in translational research to screen through biomaterials to ensure that they are mechanically suitable for humans.

Interviewer: Shamini Bundell

But Pierre says that all of this is a long way off.

Interviewee: Pierre Mouthuy

So, this has been years of work already and obviously now we’ve demonstrated that it is feasible to use this approach. And I think the fun only starts now because we can explore the different possibilities that they can do and look into whether it can really help to improve the quality of the grafts, by providing these more physiologically relevant mechanical stresses.

Host: Benjamin Thompson

That was Pierre Mouthuy from the University of Oxford in the UK. You also heard from Rafael Hostettler of Devanthro, Germany. We’ll link to their paper in the show notes as well as to a video made by Shamini in which you can see the shoulder in action.

Host: Nick Petrić Howe

Coming up: how correcting misperceptions increased COVID vaccine uptake in the Czech Republic. Before then, it’s time for this week’s Research Highlights, read by Dan Fox.

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Dan Fox

A new robotic device that can operate inside of a medical scanner could pave the way for MRI-guided robotic surgery. Magnetic resonance imaging is used to reveal soft tissue, offering a valuable view inside the body. But surgeons can't operate inside of MRI scanners, and robotic devices with magnetic components could become dangerous projectiles inside the powerful magnetic field. But now, researchers have developed an MRI-compatible motor whose speed can be precisely controlled. The new motor actually uses the MRI machine’s own magnetic field to function. The team built a prototype device featuring this motor and a large needle and, using real time MRI, the researchers guided the device's needle to a target location in a cut of pork loin and performed a mock biopsy. They hope that their device could also be used for non-surgical applications, such as MRI-guided ultrasound therapy. Have a scan of that research in Communications Engineering.

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Dan Fox

A man's skeleton has yielded the first ancient human genome from Pompeii, the city destroyed by the eruption of Vesuvius in 79 AD. Previously, only limited genetic data has been collected from humans and animals found in the city. So, to obtain more complete genomes, researchers extracted and sequenced DNA from the inner ear bones of two individuals recovered from a building known as Casa del Fabbro, or House of the Craftsmen. One of the individuals was a 35-40-year-old man from whom a partial genome sequence was produced. The man's DNA broadly resembles that of people in present-day central Italy and Sardinia. Yet it showed some differences from previously published genetic data from people who lived in Italy during the Roman imperial age, hinting at relatively high genetic diversity during this period. Further ancient genomes from Pompeii could help to reconstruct the genetic history of an ancient Roman city frozen in time. Read that research in full in Scientific Reports.

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Host: Nick Petrić Howe

As we’ve covered many times on Coronapod, a significant breakthrough in the fight against COVID-19 was the development of safe, effective vaccines. Of course, these vaccines still aren’t available to everyone, but in places where they are, there remains a significant hurdle to their uptake: vaccine hesitancy. This week in Nature, a new paper is looking at a way to help overcome this issue. It focuses on the Czech Republic, and how providing people with accurate information about doctors’ vaccine beliefs affected uptake rates. Reporter Lorna Stewart spoke to paper author Vojtěch Bartoš, an economist from the University of Milan, to find out more about the study, which began with a large-scale survey of what doctors in the Czech Republic really thought about the COVID-19 vaccines when they started to become available. The reality was that more than 90% trusted the vaccines and intended to be vaccinated, if they hadn’t been already. However, this doesn’t really match up with the public’s perception of what doctors thought, as Vojta explains.

Interviewee: Vojtěch Bartoš

The most common response was that about 50% of the doctors would be supporting it. The average was about 60%. So, huge underestimation of the actual true views of doctors.

Interviewer: Lorna Stewart

So, it's a massive mismatch. 90% of doctors are intending to get vaccinated, but the public perception is that only 50-60% of doctors would be wanting to get vaccinated. The public really thought doctors were on the fence, in effect. What did you decide to do about that mismatch?

Interviewee: Vojtěch Bartoš

So, the simplest thing that we can do is to provide people with information, right, and let them act upon this information. So, what we did, we provided half of our sample of the general public with compressed information about the results of the survey among doctors. And this intervention happened at the very onset of the vaccination campaign in March 2021.

Interviewer: Lorna Stewart

So, let’s start with just intentions. What did you find? Was giving accurate information about doctors’ beliefs enough to alter vaccine intentions?

Interviewee: Vojtěch Bartoš

Yeah, so what we see pretty much immediately after this intervention is, first of all, correction in beliefs about doctors’ views. So, this is reassuring that people really understood this information. And then we see an immediate effect also on the intentions to get vaccinated among the group that received this information about the doctors’ views.

Interviewer: Lorna Stewart

And what I love in the research is that you then you took it one step further. You didn't just look at intentions but you looked at who actually had the vaccine in your sample.

Interviewee: Vojtěch Bartoš

So, that's correct. In the beginning, right after the intervention, we do not see any effects, and that's understandable because there was the time when the eligibility was really restricted to several groups. There were some restrictions based on age. There were restrictions based on occupation. And once the eligibility criteria became more lax, that was in summer 2021, so three months approximately after the information intervention, and then we actually see also the significant uptake in vaccination.

Interviewer: Lorna Stewart

How much is that significant uptake?

Interviewee: Vojtěch Bartoš

So, that significant uptake is about 4 percentage points. So, it seems that some people were thinking about it for a longer time perhaps and then once their eligibility came, they were more willing to get vaccinated than those people who did not receive the information from us.

Interviewer: Lorna Stewart

And did that surprise you?

Interviewee: Vojtěch Bartoš

To be honest, as an economist, that should not surprise me because these people have received a very strong informational signal based on which they could learn 90% of doctors are in support of vaccines or willing to get vaccinated themselves. And since we understand that doctors are a fairly trusted group of experts, especially in the domain of health, right, which is natural, then this should not actually be surprising. What was surprising was the magnitude. And what was surprising was also how lasting the effect is. So, really, three months after the intervention, we are still seeing the effect. And then when we move on – so our study runs actually until end of November 2021 so this is nine months after the initial intervention – we still see that the effect is persistence. So, it doesn't seem that our intervention would only speed up the vaccination process. It actually convinced some people who were initially not willing to get vaccinated to take the vaccine up just after hearing this simple message.

Interviewer: Lorna Stewart

It's really interesting to me that you say doctors are so trusted and especially for health information. What about people who don't trust doctors? We know that vaccine hesitancy is a broad church and there are lots of different reasons why people might be reluctant to have the vaccine. Surely those who don't trust doctors are unlikely to be swayed by knowing what the doctors’ opinions are of the vaccine? Who do you think your intervention is convincing, and who is not being convinced?

Interviewee: Vojtěch Bartoš

We don't think that we are convincing everybody, right. We are convincing those people for whom the information is relevant, right. And imagine that there is a whole spectrum of individuals, some who are already convinced, some who cannot be convinced, but then there is a vast majority of the population that is somewhere in between, that has their doubts, that has their fears that has their uncertainties, that is being exposed to all of these media interviews with sceptical doctors that may kind of reinforce the fear. So, it is precisely this group somewhere in the middle that benefits from this information. For them, this information is useful and can actually change their behaviour.

Interviewer: Lorna Stewart

So, now the data were collected in the Czech Republic. Do you have any sense of how these findings might translate to other parts of the world?

Interviewee: Vojtěch Bartoš

So, we've already talked about trust, right, as one of the potential key components, that this information would be only accepted by the general public if they actually trust the source of the information. And when we look at where the Czech Republic stands in terms of trust and doctors, we had a look at a paper that is documenting survey data from about 29 countries, then the Czech Republic stands somewhere at the median. So, there are 50% of countries from this survey where the trust is somewhat higher. There is about 50% where the trust is somewhat lower. So, I guess there is a vast range of settings where our information intervention could actually be applicable.

Interviewer: Lorna Stewart

I'm really interested in sort of vaccine hesitancy more generally. Do you think this sort of intervention is powerful enough to counteract the damage that we've seen done generally to vaccine confidence?

Interviewee: Vojtěch Bartoš

I believe that our intervention can at least help. It will definitely not resolve it. We were talking about that earlier, that there is some group of people who are just so convinced and who are so distrustful of the system that this type of intervention won't sway their opinion towards being in favour of vaccines. However, there is still this middle group, and this is the group that is most susceptible to actually being affected by these campaigns from the vaccine deniers. And if these people are provided with a simple and credible source of information from a group of experts who they can rely on then I guess it could work, and it could prevent more people kind of falling into this group of those extreme deniers.

Host: Nick Petrić Howe

That was Vojtěch Bartoš. To find out more about this research, look out for a link to the paper in the show notes.

Host: Benjamin Thompson

Finally on the show, it's time for the Briefing chat, where we discuss some of the articles that have been featured in the Nature Briefing. And Nick, I'm going to go first this week, and I've got a story that I read about in Nature and it's based on a paper in the journal Nature Sustainability and it's looking at metals. Now, metals are, of course, a very important part of the modern economy, right? Have a look around. A lot of the stuff you can buy has metal in it. But research has shown that these metals might not have the longest lifespan in terms of their use.

Host: Nick Petrić Howe

Right, okay, and why might they not have that long of a lifespan? And where are these metals, I guess, going?

Host: Benjamin Thompson

Well, what I’ll say is billions of tonnes of metals, I learned, are dug up each year, right? And metal production accounts for about 8% of global greenhouse emissions, and so recycling and reusing metals could really help lower metal’s environmental impacts, as you might imagine. But maybe learning where these metals are being lost is important too. Now, losses do occur in many stages of a metal’s lifespan. So, for example, some metals are dug up as part of mining and never turned into like a product, and so are lost there. Others are lost when a machine breaks and you throw it away. And some are turned into things like fertilisers and sprayed on the ground and lost that way. But what this work has shown is that cumulatively, 84% of global losses occur during the waste management and recycling phases, so when metals end their lives in landfills or recycling plants. So, a huge amount.

Host: Nick Petrić Howe

So, all this metal is just sort of going there and then never been used again. Is that right?

Host: Benjamin Thompson

Well, I think what they've looked at here is the lifespan of different metals. So, specifically, they've looked at the economic lifetimes of 61 commercially used metals, and it shows that most are disposed or lost, rather than recycled or reused. But it's not the same for every sort of metal. So gold, for example, stays in use for a couple of centuries, and it can be repurposed many times. There are other examples too – lead, for example. Whereas other metals, including some that have been designated as critically important in the European Union and the US, look to have really high rates of loss and really low rates of recycling. And these are things like cobalt, which is used in lithium-ion batteries, and gallium, which is used in semiconductor production, for example. And some of these metals have an estimated lifetime of only a year or so, which is obviously vastly different.

Host: Nick Petrić Howe

Do the authors of the paper suggest anything that we can sort of do about this? Because obviously, lots of metal is being used and I don't think that's going to slow down anytime soon.

Host: Benjamin Thompson

Yeah, I mean, I think you’re right. And what was suggested in this article is that maybe mandates could be put in place to make sure that metals are reused. And the example they've got here is that the EU is considering requiring that some types of battery use recycled lithium and nickel and cobalt and so forth to up the recycling levels. But that's not necessarily an easy process, as we've talked about on the podcast before.

Host: Nick Petrić Howe

Well, maybe give me a little bit of a refresher then. Like, why is it a difficult process?

Host: Benjamin Thompson

Well, there are a bunch of reasons. And in the article, they talk about one in particular, like alloys that are made up of two or more metals can be technologically and economically very difficult to kind of tease apart. But one of the scientists in the article says it's really important to give metals a second, third or even fourth life, if we're going to try and build sustainable economies in the future.

Host: Nick Petrić Howe

I'll think about this next time I'm doing my recycling, Ben. Thanks for bringing that one to the Briefing chat. For my story this week, I've been reading a story in The New York Times, and it's about the sort of unusual story of how humans have affected cockroach sex.

Host: Benjamin Thompson

I mean, I'm kind of speechless, Nick. I don't really know where to take this one whatsoever. Go on then, tell me what's going on.

Host: Nick Petrić Howe

I didn't put that in the most sensical way. So, what we need to understand here is a little bit about cockroach sex and a little bit about pesticides. So, when you want to control an animal, say a cockroach, and you want to give them something that's not great for them, say a pesticide, how might you do that?

Host: Benjamin Thompson

Well, I'm imagining that you want to tempt them in with something that they would want, right?

Host: Nick Petrić Howe

Exactamundo. So, what people have done is they have poisoned things like glucose, which cockroaches really like. But what's happened because of that is cockroaches are now starting to avoid glucose. There's a big selection pressure because if they take it, they die. So, they've evolved to sort of not do that. But what's interesting is glucose also forms a part of cockroach mating. So, what happens when a male wants a female to mate with them is they sort of tempt them in with a sweet treat. So, they have a mixture of lipids and sugars that come out of a gland on their back, and they show it to the female to be like, ‘Hey, come and get some of this.’ The female takes it and then mating sort of happens. Insects have all sorts of weird mating ways. But the problem for the cockroaches is that this sugary treat from the male's backside turns to glucose in the female’s mouth, and they've started to avoid glucose, and so this then puts them off it. So, researchers have been looking into this sort of strange phenomenon to work out what exactly is happening here.

Host: Benjamin Thompson

I mean, I have so many questions here, Nick. I mean, I'm guessing then that this is quite a neat thing because I guess it's evolved quite fast, right? Humans have only been putting cockroach pesticide down for a while. So, you've got that selection pressure, as you say, but there's also another selection pressure on not breeding, and I don't really know how to square that circle.

Host: Nick Petrić Howe

Yeah, because what you might be thinking is, ‘Great, that means they'll breed less and we'll have less pests, so it's sort of controlling it, even if they're not taking the poison.’ But that's not actually the case. So, these researchers have been looking into the cockroach mating, and what they’ve found is that in the males that avoid glucose and also the females avoid glucose. When they mate, the males are just super quick. So, there's a moment where the females are just starting to eat and, in their mouths, this sugary thing has not turned into glucose, and they use that time as an opportunity to begin the mating process. Whereas males that haven't developed this aversion to sweet glucose, they don't do this. So, there's a sort of bit of push and pull coming on in sort of the evolution but, as you say, it's a really interesting example of a very quick, rapid evolution. But those sorts of like extreme selection pressures will do that, especially to a species like a cockroach that breeds very quickly.

Host: Benjamin Thompson

I mean, this is all kind of weird, but that does make sense. I mean, obviously, cockroach control is a big deal, is big business, right? Is there some way that humanity could take advantage of this for our own ends?

Host: Nick Petrić Howe

Yeah, so understanding this and understanding the sort of responses of the cockroaches to pesticides will enable pesticide producers in the future to make better pesticides. But as we've seen throughout history, it’s always a little bit of this back and forth, so we may develop one thing and then they'll develop something else and onwards goes evolution. As the famous quote goes, life finds a way.

Host: Benjamin Thompson

Well, yes, it does. Shall we leave it there, I think, for this week’s Briefing chat? I think that’s probably a sensible move, isn’t it? Now, if you'd like to read more about these stories, we'll put links to them in the show notes, and a link to where you can sign up for the Nature Briefing to have even more science news delivered directly to your inbox.

Host: Nick Petrić Howe

And that's all we've got time for this week. But don't forget, you can always reach out to us on Twitter – we're @NaturePodcast. Or you can send us an email to podcast@nature.com. I’m Nick Petrić Howe.

Host: Benjamin Thompson

And I’m Benjamin Thompson. See you next time.