̽��ֱ�� of Cambridge - Michelle Oyen

Synthetic organs, nanobots and DNA ‘scissors’: the future of medicine

lw355 — Thu, 12 Oct 2017 08:00:43 +0000

In a new film to coincide with the recent launch of the Cambridge Academy of Therapeutic Sciences, researchers discuss some of the most exciting developments in medical research and set out their vision for the next 50 years.

Professor Jeremy Baumberg from the NanoPhotonics Centre discusses a future in which diagnoses do not have to rely on asking a patient how they are feeling, but rather are carried out by nanomachines that patrol our bodies, looking for and repairing problems. Professor Michelle Oyen from the Department of Engineering talks about using artificial scaffolds to create ‘off-the-shelf’ replacement organs that could help solve the shortage of donated organs. Dr Sanjay Sinha from the Wellcome Trust-MRC Stem Cell Institute sees us using stem cell ‘patches’ to repair damaged hearts and return their function back to normal.

Dr Alasdair Russell from the Cancer Research UK Cambridge Institute describes how recent breakthroughs in the use of CRISPR-Cas9 – a DNA editing tool – will enable us to snip out and replace defective regions of the genome, curing diseases in individual patients; and lawyer Dr Kathy Liddell, from the Cambridge Centre for Law, Medicine and Life Sciences, highlights how research around law and ethics will help to make gene editing safe.

Professor Gillian Griffiths, Director of the Cambridge Institute for Medical Research, envisages us weaponising ‘killer T cells’ – important immune system warriors – to hunt down and destroy even the most evasive of cancer cells.

All of these developments will help transform the field of medicine, says Professor Chris Lowe, Director of the Cambridge Academy of Therapeutic Sciences, who sees this as an exciting time for medicine. New developments have the potential to transform healthcare “right the way from how you handle the patient to actually delivering the final therapeutic product - and that’s the exciting thing”.

Read more about research on future therapeutics in Research Horizons magazine.

Nanobots that patrol our bodies, killer immune cells hunting and destroying cancer cells, biological scissors that cut out defective genes: these are just some of technologies that Cambridge researchers are developing which are set to revolutionise medicine in the future.

̽��ֱ��Future of Medicine

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Bioengineering, embryos and eggshells

cg605 — Wed, 17 May 2017 08:21:18 +0000

In 1999, Dr Michelle Oyen was a bioengineering student, working on a PhD project to measure the stiffness of bone, when the phone rang. It was Dr Steven Calvin, an obstetrician at the local hospital. “I’m trying to understand some issues around miscarriage and premature birth,” he said. “Is there someone there who has a machine that can stretch things, and make measurements of how strong something is?”

Calvin had a specific question: he was performing a procedure aimed at keeping a prematurely opening cervix closed by putting stitches around it. If a cervix opens too soon, it can result in premature birth. During the procedure, antiseptic is painted around the area, including the amniotic sac. He wanted to know if this substance changed the properties of the sac, making it more likely to rupture.

Oyen, now Reader in Bioengineering in Cambridge’s Mechanics and Materials Division and the Biomechanics research group, was fascinated by the idea of applying engineering thinking to this problem. “I was carrying out my experiments in a housekeeping cupboard in the hospital,” she remembers. “I had a rig for strength-testing the amniotic sac. I’d get a call from Dr Calvin that a woman in labour was happy for us to use the sample, I’d grab my rig and set it up in a cupboard down the hall from the delivery room.”

Their first investigation into this question resulted in a paper published in the Journal of Material Science: Materials in Medicine, and sparked what Oyen calls her life’s work: finding out why pregnancies go wrong. “Three per cent of the time, the amniotic sac breaks for no reason that we know,” she says. “That can cause miscarriage, or stillbirth if it’s before viability. Even after that, babies born between 25 and 30 weeks are very premature and so their outcomes are very poor. Even babies born after 30 weeks are still not fully ‘cooked’: you have to get to 37 weeks before we consider you to have made it to the end line. These problems happen in the developed world, even when we have so much technology around us. In the developing world, there’s a whole other set of issues. So when you talk about problems in pregnancy, you’re talking about a big chunk of humanity.”

There’s a long and honourable history of collaborations between engineering and medical science, from designing cutting-edge prosthetics to creating technology for robot-assisted surgery. Yet, says Oyen, looking at pregnancy in this way is an area that’s 20 or 30 years behind, say, orthopaedics. “Most of the time, pregnancy kind of works and doctors know how to manage something that goes wrong – but they don’t always understand why it’s happening. It’s something that we fundamentally don’t know about. And that really excites me.”

What makes pregnancy problems so ripe for exploration by engineers? ̽��ֱ��tools, says Oyen – namely, computers. “You can’t do experiments on pregnant women,” she points out. “It is completely unethical. But with computers, we can make a virtual model of the placenta. There’s potential for huge progress there.” One of her team’s recent projects, which gave rise to a paper published in the journal Placenta, is based around images of real placentas taken using a confocal microscope at a very high resolution. These images are then turned into 3D computational models. Oyen and her team can then model how the blood flows through the capillaries of the placenta, bringing oxygen from the mother to the baby. This will aid understanding of why the placenta sometimes malfunctions and fails to bring enough oxygen to the baby, meaning its growth is restricted.

That’s studying the placenta at full term: but its beginnings are also a rich area for research. When a fertilised egg implants into the uterus wall, specialised cells called trophoblasts must migrate in to help form the placenta, a biological process similar to how cancer cells metastasize. In collaboration with the Cambridge Centre for Trophoblast Research, which this year celebrates its tenth anniversary, Oyen’s team is studying how trophoblasts move, a unique cross-departmental group of pregnancy researchers. “ ̽��ֱ��collaboration with others from the Centre has just been amazing,” says Oyen. “That’s the thing about Cambridge. You don’t find such a wealth of expertise anywhere else.”

Pregnancy problems are one of the Oyen Lab’s four main strands of research, the others being more traditional areas of bioengineering, including the creation of synthetic materials using inspiration from the natural world – studying materials such as eggshell and bone to find an equally strong and light material, for example. As any cook knows, Oyen says, an eggshell is actually pretty robust. If you want to break it, you need to hit it hard against your glass bowl. Yet it starts off as a squishy, watery membrane filled with yolk.

Given the right conditions – usually a chicken with average body temperature – it becomes a full egg with a hard shell in about 18 hours. This is a material that is 97per cent ceramic but forms naturally in close to ambient conditions, and therefore is not energy-intensive – unlike concrete, which always involves high temperatures to process. These materials could have medical applications, such as replacing the metal and plastic currently used for new hip and knee joints, or they could even be scaled up to create anything from furniture to buildings: the lab’s current project on eggshell-inspired materials is funded by the US Army Corps of Engineers.

“Materials inspired by bone and eggshell are really good structural materials: why limit them to medicine?” Oyen says. “We can make bone-like material now, but only in lab quantities. It would take a big company to scale it up. Natural materials are really interesting. We build things out of steel and concrete now, but before we started getting the idea to do that, we built things with whatever was around us – wood or stone. People don’t really appreciate what impact this could have on global warming: in 2007, the creation of steel and concrete was responsible for more CO2 emissions than the aviation industry worldwide. We demonise airlines without realising that building a skyscraper also makes a big contribution.”

Looking at the scope of her work, it’s hardly surprising that a glimpse at Oyen’s office bookshelf reveals a dizzying array of interests, from clouds to Russian dictionaries to Cary Grant – not to mention the electronic piano keyboard that stands next to it. “Yes, I have broad interests, which I think is normal for someone in such an interdisciplinary field,” she says. “A lot of my work is synthesising and bringing people together. Most of my students are co-supervised, most of my work is collaborative. I spend very little time sitting in a room, typing on a computer. I get people together. I talk to engineers and medics, I get biologists talking to engineers. I’m the traffic cop in the middle, translating from engineering language to biomedical language.”

Her chosen path is partly personal, she says – Oyen has juvenile arthritis, which began in her teens. Her father worked in an engineering company and had her solving problems from the start. “My motivation is completely selfish,” she says with a grin. “My first degree was in Materials Science and Engineering, and while I was doing that, I twigged that there were medically related engineering applications. I was doing very traditional metallurgy. I had nothing to do with medicine. But when I was having a particularly bad bout with my joints, I started getting interested. I started coming across some of the very traditional approaches to solving medical problems, like total joint replacement, which goes back to the 1950s. You replace living tissue, which is 75 per cent water, with metal and plastic. That’s a very 1950s solution and yet we haven’t come up with anything better.”

There is a word in bioengineering – bioinspiration – which, within the context of the discipline, means a method of solving engineering problems using natural approaches. A bioengineer will systematically study how nature has solved problems and then try to map that method on to a current problem. Perhaps it’s not too much of a stretch to say that a kind of bioinspiration is at the root of everything Oyen does: taking both nature’s design flaws and extraordinary abilities – to regrow, renew and create life – as a starting point for making things work better, from carrying a child to creating a city.

“There is so much potential in all our work, but in the pregnancy work, I feel like it’s really just getting started,” she says. “High risk, high reward – and the reward is better outcomes for mothers and babies. It’s what engineering is all about: problem-solving. It’s creative. After all, the root of the word engineer is not engine, but ingenuity.”

Dr Oyen is a Fellow at Homerton College.

Article by Lucy Jolin. This article first appeared in CAM - the Cambridge Alumni Magazine, edition 80. Find out more about Dr Oyen's work.

Homerton Fellow Dr Michelle Oyen explains why she has dedicated her working life to investigating why pregnancies go wrong.

I spend very little time sitting in a room, typing on a computer. I get people together. I talk to engineers and medics, I get biologists talking to engineers. I’m the traffic cop in the middle

Dr Michelle Oyen

Anna Huix

Michelle Oyen

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Would you live in a city made of bone?

sc604 — Thu, 23 Jun 2016 13:47:51 +0000

Between them, concrete and steel are responsible for as much as a tenth of worldwide carbon emissions. Before they ever reach a construction site, both steel and concrete must be processed at very high temperatures – which takes a lot of energy. And yet, our cities are completely dependent on these two unsustainable materials.

“I fly back and forth a lot between the UK and the US, and I’d been harbouring a lot of guilt about the effect that had on my carbon footprint – I’d always assumed, as many of us do, that air travel is a huge contributor to carbon emissions,” says bioengineer Dr Michelle Oyen of Cambridge’s Department of Engineering. “But the truth is, while the emissions caused by air travel are significant, far more are caused by the production of concrete and steel, which of course is what most cities are built from.”

So what does that mean for cities of the future, as more and more of us live in urban areas? How can we continue to build while reducing carbon emissions?

Whereas some researchers are investigating ways of producing steel and concrete in more energy-efficient ways, or finding ways of using less, Oyen would rather turn the tables completely, and create new building materials that are strong, sustainable and take their inspiration from nature.

“What we’re trying to do is to rethink the way that we make things,” says Oyen. “Engineers tend to throw energy at problems, whereas nature throws information at problems – they fundamentally do things differently.”

Oyen works in the field of biomimetics – literally ‘copying life’. In her lab, with funding support from the US Army Corps of Engineers, she constructs small samples of artificial bone and eggshell, which could be used as medical implants, or even be scaled up and used as low-carbon building materials.

Like the real things, artificial bone and eggshell are composites of proteins and minerals. In bone, the proportions of protein and mineral are roughly equal – the mineral gives bone stiffness and hardness, while the protein gives it toughness or resistance to fracture. While bones can break, it is relatively rare, and they have the benefit of being self-healing – another feature that engineers are trying to bring to biomimetic materials.

In eggshell, the ratios are different: about 95% mineral to 5% protein, but even this small amount of protein makes eggshell remarkably tough considering how thin it is.

When making the artificial bone and eggshell, the mineral components are ‘templated’ directly onto collagen, which is the most abundant protein in the animal world. “One of the interesting things is that the minerals that make up bone deposit along the collagen, and eggshell deposits outwards from the collagen, perpendicular to it,” says Oyen. “So it might even be the case that these two composites could be combined to make a lattice-type structure, which would be even stronger – there’s some interesting science there that we’d like to look into.”

In her lab, Oyen and her team have been making samples of artificial eggshell and bone via a process that could be easily scaled up – and since the process takes place at room temperature, the samples take very little energy to produce. But it may be some time before we’re living in bone and eggshell houses.

For one, the collagen that Oyen needs to make these materials comes from natural (meaning animal) sources. One of the things she’s currently investigating is whether a non-animal-derived or even synthetic protein or polymer could be used instead of natural collagen.

“Another issue is the construction industry is a very conservative one,” Oyen says. “All of our existing building standards have been designed with concrete and steel in mind. Constructing buildings out of entirely new materials would mean completely rethinking the whole industry. But if you want to do something really transformative to bring down carbon emissions, then I think that’s what we have to do. If we’re going to make a real change, a major rethink is what has to happen.”

Dr Michael Ramage from the Department of Architecture is another Cambridge researcher who believes we need to expand our use of natural materials in buildings. Ramage has several ongoing research projects that are looking into the use of wood – one of the oldest building materials we have – for tall buildings.

Working with PLP Architecture and engineers Smith and Wallwork, Ramage recently delivered plans for an 80-storey, 300 m high, timber skyscraper to the Mayor of London. ̽��ֱ��proposals currently being developed would create more than 1,000 residential units in a 1 million square-foot, mixed-use tower and mid-rise terraces, integrated into the Barbican in central London.

Like other natural materials, the primary benefit of using wood as a building material is that it is a renewable resource, unlike concrete and steel. Ramage’s research is also investigating other potential benefits of using wood for tall buildings, such as reduced costs and improved construction timescales, increased fire resistance and a significant reduction in the overall weight of buildings.

“If London is going to survive an increasing population, it needs to densify,” says Ramage. “One way is taller buildings. We believe people have a greater affinity for taller buildings in natural materials rather than steel and concrete towers. ̽��ֱ��fundamental premise is that timber and other natural materials are vastly underused and we don’t give them nearly enough credit. Nearly every historic building, from King’s College Chapel to Westminster Hall, has made extensive use of timber.”

̽��ֱ��tallest timber building in the world at the moment is a 14-storey apartment block in Bergen, Norway, but Ramage foresees future cities where timber skyscrapers sit alongside those made of concrete and steel.

“Future cities may not look a whole lot different – you may not know immediately if you are in a timber, steel or concrete building,” says Ramage. “But cities might be a whole lot quieter, as most timber buildings are built off site, and then just assembled on site, and use roughly a fifth as much truck traffic as equivalent concrete buildings. In other words, what needs to be delivered in five trucks for a concrete building can be delivered in one truck for a timber building. That’s an incredible advantage, for cost, for environment, for traffic and for cyclists.”

“ ̽��ֱ��material properties of bone and wood are very similar,” says Oyen. “Just because we can make all of our buildings out of concrete and steel doesn’t mean we should. But it will require big change.”

̽��ֱ��cities of today are built with concrete and steel – but some Cambridge researchers think that the cities of the future need to go back to nature if they are to support an ever-expanding population, while keeping carbon emissions under control.

Just because we can make all of our buildings out of concrete and steel doesn’t mean we should. But it will require big change

Michelle Oyen

Abdul Rahman

City

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Opinion: Dreaming big with biomimetics: could future buildings be made with bone and eggshells?

Anonymous — Wed, 09 Mar 2016 12:41:18 +0000

As the world grapples with climate change, we urgently need to find ways of reducing our CO₂ emissions. Sectors which rely heavily on fossil fuels, such as energy and aviation, are commonly held to be the worst offenders. But what most people don’t realise is that there’s another culprit, hiding in plain sight; on the streets of our cities, and in the buildings where we live and work.

In 2007 alone, steel and concrete were each responsible for more CO₂ emissions than the entire global aviation industry. Before reaching the construction site, both steel and cement must be processed at very high temperatures – and this takes a lot of energy. So how can we reduce our dependence on these “dirty” materials, when they play such a crucial role in construction?

One option is to use natural materials, such as wood. Humans have been building with wood for thousands of years, and wooden structures are currently experiencing a minor resurgence – partly because it’s a cheap and sustainable material.

But there are some disadvantages to building with wood; the material can warp in humid conditions, and is susceptible to attack by pests such as termites. And while natural materials, such as wood, are appealing from an environmental perspective, they can be unsatisfying for engineers who might wish to make components in a specific shape or size.

Copying life

So what if, instead of using natural materials as we find them, we make new materials that are inspired by nature? This idea started to gain traction in the research community in the 1970s and really exploded in the 1990s, with the development of nanotechnology and nanofabrication methods. Today, it forms the basis of a new field of scientific research: namely, “biomimetics” – literally “copying life”.

Biological cells are often referred to as “the building blocks of life”, because they are the smallest units of living matter. But to create a multi-cellular organism like you or me, cells must clump together with a support structure to form the biological materials we’re made of, tissues such as bone, cartilage, and muscle. It’s materials like these, which scientists interested in biomimetics have turned to for inspiration.

In order to make biomimetic materials, we need to have a deep understanding of how natural materials work. We know that natural materials are also “composites”: they are made of multiple different base materials, each with different properties. Composite materials are often lighter than single component materials, such as metals, while still having desirable properties such as stiffness, strength and toughness.

Making biomimetic materials

Materials engineers have spent decades measuring the composition, structure and properties of natural materials such as bone and eggshell, so we now have a good understanding of their characteristics.

For instance, we know that bone is composed of hydrated protein and mineral, in almost equal proportions. ̽��ֱ��mineral confers stiffness and hardness, while the protein confers toughness and resistance to fracture. Although bones can break, it is relatively rare, and they have the benefit of being self-healing – another feature that engineers are trying to bring to biomimetic materials.

Like bone, eggshell is a composite material, but it is around 95% mineral and only 5% hydrated protein. Yet even that small amount of protein is enough to make eggshell very tough, considering its thinness – as most breakfast cooks will have noticed. ̽��ֱ��next challenge is to turn this knowledge into something solid.

There are two ways to mimic natural materials. Either you can mimic the composition of the material itself, or you can copy the process by which the material was made. Since natural materials are made by living creatures, there are no high temperatures involved in either of these methods. As such, biomimetic materials – let’s call them “neo-bone” and “neo-eggshell” – take much less energy to produce than steel or concrete.

In the laboratory, we have succeeded in making centimetre-scale samples of neo-bone. We do this by preparing different solutions of protein with the components that make bone mineral. A composite neo-bone material is then deposited from these solutions in a biomimetic manner at body temperature. There is no reason that this process – or an improved, faster version of it – couldn’t be scaled up to an industrial level.

Of course, steel and concrete are everywhere, so the way we design and construct buildings is optimised for these materials. To begin using biomimetic materials on a large scale, we’d need to completely rethink our building codes and standards for construction materials. But then, if we want to build future cities in a sustainable way, perhaps a major rethink is exactly what’s needed. ̽��ֱ��science is still in its infancy, but that doesn’t mean we can’t dream big about the future.

Michelle Oyen, Reader in Bioengineering, ̽��ֱ�� of Cambridge

This article was originally published on ̽��ֱ��Conversation. Read the original article.

̽��ֱ��opinions expressed in this article are those of the individual author(s) and do not represent the views of the ̽��ֱ�� of Cambridge.

Michelle Oyen (Department of Engineering) discusses how we could reduce our dependence on "dirty" materials like steel and concrete.

James Royal-Lawson

A tray of eggs up close

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Collagen mechanics: learning from nature

bjb42 — Mon, 01 Sep 2008 15:37:11 +0000

Mention the word ‘biology’ and most people think immediately about cells. However, large portions of the human body are non-cellular and are made instead from an extracellular matrix (ECM) that provides much of the structural support around cells. This supportive function of the ECM is especially evident in the connective tissues of the body. Many load-bearing structures such as bones, teeth and ligaments are connective tissues and these have been the focus of recent bioengineering research in Cambridge.

Dr Michelle Oyen, Lecturer in the new Engineering for Life Sciences programme in the Department of Engineering, is studying the mechanical functions of connective tissues. Her research ranges from fundamental science and engineering projects through to collaborative projects with clinicians for developing mechanics-based tools for use in medical practice. ̽��ֱ��unifying theme of this research lies with the primary component of many connective tissues: the structural protein collagen.

Building blocks of natural materials

Collagen is ubiquitous; this triple-helical protein makes up a quarter of all proteins in the body. It self-assembles from the molecular scale up to large fibre-like structures, creating a hierarchical material with remarkable physical properties. Collagen combines with other ECM components – mainly water, non-collagenous proteins and sugars – and, in mineralised tissues, with bioceramics analogous to earth minerals. These non-living, but cell-derived, materials combine with cells to form living yet mechanically robust tissues.

Collagen takes on different roles in different parts of the body. In structural tissues, like bones and ligaments, it’s found in rope-like fibres that provide resistance to stretching and tearing forces. In cartilage, which is mostly loaded in compression, collagen has more of a ‘holding’ function, with the fibres arranged rather like a basket, retaining other hydrated proteins and sugars. In the lens of the eye, collagen is crystalline, organised precisely for optical transparency. In fact, there are over 20 different types of collagen in the body, and it is not even known precisely what functions they all fulfil.

Mechanics in medicine

̽��ֱ��study of the biomechanical properties of collagen and ECM is a particularly exciting and fast-growing field in reproductive medicine. One aspect of Dr Oyen’s research has been to examine the physical properties of the ECM in the amniotic sac, the membrane that ruptures (the ‘breaking of waters’), signalling imminent birth.

Rupture occurring before full-term gestation results in approximately a third of all premature births. Following the first-ever set of rigorous bioengineering studies on placental membranes, Dr Oyen and clinical colleagues at the ̽��ֱ�� of Minnesota concluded that the phenomenon is due to localised damage, not widespread overall membrane deterioration, and that diagnostic techniques may be developed to detect localised thinning and ECM damage for intervention into premature birth.

This project is taking a new direction since Dr Oyen’s arrival in Cambridge. By teaming up with researchers at the newly opened Centre for Trophoblast Research (www.trophoblast.cam.ac.uk), she will be able to examine placental development from an engineering and mechanics perspective.

Mimicking nature

Nature clearly creates dynamic, mechanically functional tissues that are different from anything engineers have made. As an example, cartilage, which forms the gliding surface that permits joint movement, is approximately 75% water and only 25% collagen, sugar and other proteins, and yet its stiffness and shock-absorbing capability make it comparable to solid rubber. Moreover, the cartilage-on-cartilage sliding interface has lower friction than ice sliding on ice.

In fact, when engineers design materials, uniformity and simplicity are often prized. Engineering materials do not always feature the multi-level hierarchical organisations found in protein-based materials, nor do they exemplify the dramatic spatial non-uniformity that has been found to strengthen natural materials. So, by learning from nature, novel engineering systems might be developed that utilise the principles found in natural materials – a field of technology that has been termed biomimetics.

In some instances, biomimetics takes the form of direct imitation, as in the case of a nanocomposite of mineral and proteins similar to natural bone. For cases of major bone defects, such as occurs through trauma or cancer, a bone-like material that is biocompatible can be seeded with cells to form a ‘tissue-engineered’ construct and implanted within the body. However, if you consider just how lightweight, yet stiff, strong and tough, a bone-like material is, why not use it for other structural applications such as architecture? This is a challenge that Dr Oyen is investigating.

To do this, you need to go back to first principles – how the material forms. With funding from the Royal Society, Dr Oyen is examining biomineralisation and the formation of mechanically robust bone-like materials. ̽��ֱ��work differs from tissue-engineering approaches in that there is no cellular component and the end applications are viewed as being remote from medicine. Although a large number of groups have considered the synthesis of biomimetic materials, far fewer have taken a primary angle associated with the measurement of mechanical properties. Dr Oyen views the materials as successful when they replicate both bone composition and mechanical behaviour.

Inspirational materials

It is also possible to abstract ideas from nature without directly imitating the materials themselves. As examples, key concepts that could guide the formation of ‘bone-inspired’ materials include: composite materials with a very large stiffness mismatch between the phases; materials that form from room-temperature deposition of a ceramic onto a self-assembled polymer; materials with up to seven different levels of hierarchical organisation; and materials that are self-healing. Each of these concepts could be applied to a system that is not protein based, and ongoing research both at Cambridge and across the world is incorporating these types of principles for materials development.

Compared with many branches of engineering, biomimetic engineering is comparatively new. In this rapidly expanding field, the lessons learnt from the physical and mechanical properties of natural materials such as collagen and bone offer great promise within an engineering framework. Not only is this sure to make a difference to 21st-century healthcare, but there are also ways in which engineering will itself benefit from the abstraction of ideas from nature.

For more information, please contact the author Dr Michelle Oyen (mlo29@cam.ac.uk)

at the Department of Engineering.

Because of their unique structure, biological tissues exhibit physical and mechanical properties that are unlike anything in the world of engineering.

So, by learning from nature, novel engineering systems might be developed that utilise the principles found in natural materials – a field of technology that has been termed biomimetics.

Dr Jon Heras, Equinox Graphics

collagen

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