Tag Archives: University of Trento

Regenerate damaged skin, cartilage, and bone with help from silkworms?

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A July 24, 2024 news item on phys.org highlights research into regenerating bone and skin, Note: A link has been removed,

Researchers are exploring new nature-based solutions to stimulate skin and bone repair.

In the cities of Trento and Rovereto in northern Italy and Bangkok in Thailand, scientists are busy rearing silkworms in nurseries. They’re hoping that the caterpillars’ silk can regenerate human tissue. For such a delicate medical procedure, only thoroughbreds will do.

“By changing the silkworm, you can change the chemistry,” said Professor Antonella Motta, a researcher in bioengineering at the University of Trento in Italy. That could, in turn, affect clinical outcomes. “This means the quality control should be very strict.”

Silk has been used in surgical sutures for hundreds of years and is now emerging as a promising nature-based option for triggering human tissue to self-regenerate. Researchers are also studying crab, shrimp and mussel shells and squid skin and bone for methods of restoring skin, bone and cartilage. This is particularly relevant as populations age.

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A July 23, 2024 article by Gareth Willmer for Horizon Magazine, the EU (European Union) research & innovation magazine, which originated the news item, provides more details,

‘Tissue engineering is a new strategy to solve problems caused by pathologies or trauma to the organs, as an alternative to transplants or artificial device implantations,’ said Motta, noting that these interventions can often fail or expire. ‘The idea is to use the natural ability of our bodies to rebuild the tissue.’

The research forms part of the five-year EU-funded SHIFT [Shaping Innovative Designs for Sustainable Tissue Engineering Products] project that Motta coordinates, which includes universities in Europe, as well as partners in Asia and Australia. Running until 2026, the research team aim to scale up methods for regenerating skin, bone and cartilage using bio-based polymers and to get them ready for clinical trials. The goal is to make them capable of repairing larger wounds and tissue damage.

The research builds on work carried out under the earlier REMIX [Regenerative Medicine Innovation Crossing – Research and Innovation Staff Exchange in Regenerative Medicine] project, also funded by the EU, which made important advances in understanding the different ways in which these biomaterials could be used. 

Building a scaffold

Silk, for instance, can be used to form a “scaffold” in damaged tissue that then activates cells to form new tissue and blood vessels. The process could be used to treat conditions such as diabetic ulcers and lower back pain caused by spinal disc degeneration. The SHIFT team have been exploring minimally invasive procedures for treatment, such as hydrogels that can be applied directly to the skin, or injected into bone or cartilage.

The approaches using both silkworms and some of the marine organisms have great potential, said Motta. 

‘We have three or four systems with different materials that are really promising,’ she said. By the end of SHIFT, the goal is to have two or three prototypes that can be developed together with start-up and spin-off companies created in collaboration with the project. 

One of the principles of the SHIFT team has been been exploring how best to harness the concept of a circular economy. For example, they are looking into how waste products from the textile and food industries can be reused in these treatments.

Yet with complicated interactions at a microscale, and the need to prevent the body from rejecting foreign materials, such tissue engineering is a big challenge. 

‘The complexity is high because the nature of biology is not easy,’ said Motta. ‘We cannot change the language of the cells, but instead have to learn to speak the same language as them.’

But she firmly believes the nature-based rather than synthetic approach is the way to go and thinks treatments harnessing SHIFT’s methods could become available in the early 2030s. 

‘I believe in this approach,’ said Motta. ‘Bone designed by nature is the best bone we can have.’

Skin care

Another EU-funded project known as SkinTERM [Skin Tissue Engineering and Regenerative Medicine: From skin repair to regeneration], which runs for almost five years until mid-2025, is also looking at novel ways to get tissue to self-regenerate, focusing on skin. To treat burns and other surface wounds today, a thin layer of skin is sometimes grafted from another part of the body. This can cause the appearance of disfiguring scars and the patient’s mobility may be impacted when the tissue contracts as it heals. Current skin-grafting methods can also be painful.

The SkinTERM team are therefore investigating how inducing the healing process in the networks of cells surrounding a wound might enable skin to repair itself. 

‘We could do much better if we move towards regeneration,’ said Dr Willeke Daamen, who coordinates SkinTERM as a researcher in soft tissue regeneration at Radboud University in Nijmegen, the Netherlands. ‘The ultimate goal would be to get the same situation before and after being wounded.’

Researchers are studying a particular mammal – the spiny mouse – which has a remarkable ability to heal without scarring. It is able to self-repair damage to other tissues like the heart and spinal cord too. This is also true of early foetal skin.

The team are examining these systems to learn more about how they work and the processes occurring in the area around cells, known as the extracellular matrix. They hope to identify factors that might have a role in the regenerative process, and test how it might be induced in humans. 

Kick-start

‘We’ve been trying to learn from those systems on how to kick-start such processes,’ said Daamen. ‘We’ve made progress in what kinds of compounds seem at least in part to be responsible for a regenerative response.’

Many lines of research are being carried out among a new generation of multidisciplinary scientists being trained in this area, and a lot has already been achieved, said Daamen.

They have managed to create scaffolds using different components related to skin regeneration, such as the proteins collagen and elastin. They have also collected a vast amount of data on genes and proteins with potential roles in regeneration. Their role will be further tested by using them on scar-prone cells cultured on collagen scaffolds.

‘The mechanisms are complex,’ said Dr Bouke Boekema, a senior researcher at the Association of Dutch Burn Centres in Beverwijk, the Netherlands, and vice-coordinator of SkinTERM. 

‘If you find a mechanism, the idea is that maybe you can tune it so that you can stimulate it. But there’s not necessarily one magic bullet.’

By the end of the project next year, Boekema hopes the research could result in some medical biomaterial options to test for clinical use. ‘It would be nice if several prototypes were available for testing to see if they improve outcomes in patients.’

Research in this article was funded by the Marie Skłodowska-Curie Actions (MSCA). The views of the interviewees don’t necessarily reflect those of the European Commission. If you liked this article, please consider sharing it on social media.

Interesting. Over these last few months, I’ve been stumbling across more than my usual number of regenerative medicine stories.

Submersible dandelions and the materials they could inspire

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Before launching into the news item and if you’re as ignorant about the term as I was, here’s what it means to be a dandelion clock, from the dandelion clock definition on Wiktionary [Note: Links have been removed]),

A single stem of a dandelion in its post-flowering state with the downy covering of its head intact. The term is applied when the flower is used, or is thought of as suitable for use, in a children’s pastime by which the number of puffs needed to blow the filamentous achenes from a dandelion is supposed to tell the time.

A March 3, 2021 news item on phys.org announces dandelion research (Note: A link has been removed),

Fields are covered with dandelions in spring, a very common plant with yellow-gold flowers and toothed leaves. When they wither, the flowers turn into fluffy white seed heads that, like tiny parachutes, are scattered around by the wind. Taraxacum officinale—its scientific name—inspired legends and poems and has been used for centuries as a natural remedy for many ailments.

Now, thanks to a study conducted at the University of Trento [Università di Trento], dandelions will inspire new engineered materials. The air trapping capacity of dandelion clocks [emphasis mine] submerged in water has been measured in the lab for the first time. The discovery paves the way for the development of new and advanced devices and technologies that could be used in a broad range of applications, for example, to create devices or materials that retain air bubbles under water.

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I found the dandelion squeezing sequence to be quite fascinating.

A March 3, 2021 Università di Trento press release (also on EurekAlert), which originated the news item, provides more detail,

The study was coordinated by Nicola Pugno, professor of the University of Trento and coordinator of the Laboratory of Bio-inspired, Bionic, Nano, Meta Materials & Mechanics at the Department of Civil, Environmental and Mechanical Engineering.
The discovery was given international prominence by “Materials Today Bio”, a multidisciplinary journal focused on the interface between biology and materials science, chemistry, physics, engineering, and medicine.

Nicola Pugno outlined how the research unfolded: “Diego Misseroni and I started to work on a discovery that my daughter made, in her first year in high school. She noticed that dandelion clocks, when submerged by water, turn silvery because they trap air. We have quantified this discovery. For the first time, we have measured the air trapping capacity of dandelion clocks in a laboratory setting. This paper demonstrated that kids and young adults can make significant discoveries by observing nature”.

When submerged in water, the research team observed, the soft seed heads turn silver in color, become thinner and take on a rhombus-like shape. The team then developed an analytical model to measure the mechanical properties of the flower, in order to mimic them and create re-engineered dandelion-like materials.

Bioinspired engineering can explore different opportunities thanks to this discovery, such as miniaturized parachute-like elements to develop innovative devices and advanced, light and low-cost technological solutions to trap and transport air bubbles underwater. These materials could be used, for example, in underwater operations.

It’s been a while (see my Nov. 21, 2018 posting ‘Regenerating tooth enamel’) since I’ve featured research from Nicola Pugno here.

Here’s a link to and a citation for Pugno’s dandelion-ispired work

Air-encapsulating elastic mechanism of submerged Taraxacum blowballs by M.C.Pugno, D.Misseroni, N.M.Pugno. Materials Today Bio Volume 9, January 2021, 100095 DOI: 10.1016/j.mtbio.2021.100095

This paper is open access.

Felted carbon nanotubes

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Parachute (sculpted felt lantern). Artist and artisan felter: Chantal Cardinal. Studio: FELT à la main with LOVE

Scientists from Kiel University (Christian-Albrechts-Universität zu Kiel; Germany) and the University of Trento (Italy) claim to have developed a new method for integrating carbon nanotubes (CNTs) into new materials in a technique they describe as similar to felting according to a November 21, 2017 news item on Nanowerk,

Extremely lightweight, electrically highly conductive, and more stable than steel: due to their unique properties, carbon nanotubes would be ideal for numerous applications, from ultra-lightweight batteries to high-performance plastics, right through to medical implants. However, to date it has been difficult for science and industry to transfer the extraordinary characteristics at the nanoscale into a functional industrial application. The carbon nanotubes either cannot be combined adequately with other materials, or if they can be combined, they then lose their beneficial properties.

Scientists from the Functional Nanomaterials working group at Kiel University (CAU) and the University of Trento have now developed an alternative method, with which the tiny tubes can be combined with other materials, so that they retain their characteristic properties. As such, they “felt” the thread-like tubes into a stable 3D network that is able to withstand extreme forces.

In contrast to the ‘felted’ image which opened this posting, here’s an image of the ‘felted’ carbon nanotubes,

In this new process, the tiny, thread-like carbon nanotubes (CNTs) arrange themselves – almost like felting – to form a stable, tear-resistant layer. Photo/Copyright: Fabian Schütt Courtesy: Kiel University

A November 21, 2017 Kiel University press release (also on EurekAlert), which originated the news item, expands on the theme and adds another analogy,

Industry and science have been intensively researching the significantly less than one hundred nanometre wide carbon tubes (carbon nanotubes, CNTs), in order to make use of the extraordinary properties of rolled graphene. Yet much still remains just theory. “Although carbon nanotubes are flexible like fibre strands, they are also very sensitive to changes,” explained Professor Rainer Adelung, head of the Functional Nanomaterials working group at the CAU. “With previous attempts to chemically connect them with other materials, their molecular structure also changed. This, however, made their properties deteriorate – mostly drastically.”

In contrast, the approach of the research team from Kiel and Trento is based on a simple wet chemical infiltration process. The CNTs are mixed with water and dripped into an extremely porous ceramic material made of zinc oxide, which absorbs the liquid like a sponge. The dripped thread-like CNTs attach themselves to the ceramic scaffolding, and automatically form a stable layer together, similar to a felt. The ceramic scaffolding is coated with nanotubes, so to speak. This has fascinating effects, both for the scaffolding as well as for the coating of nanotubes.

On the one hand, the stability of the ceramic scaffold increases so massively that it can bear 100,000 times its own weight. “With the CNT coating, the ceramic material can hold around 7.5kg, and without it just 50g – as if we had fitted it with a close-fitting pullover made of carbon nanotubes, which provide mechanical support,” summarised first author Fabian Schütt. “The pressure on the material is absorbed by the tensile strength of the CNT felt. Compressive forces are transformed into tensile forces.”

The principle behind this is comparable with bamboo buildings [emphasis mine], such as those widespread in Asia. Here, bamboo stems are bound so tightly with a simple rope that the lightweight material can form extremely stable scaffolding, and even entire buildings. “We do the same at the nano-scale with the CNT threads, which wrap themselves around the ceramic material – only much, much smaller,” said Helge Krüger, co-author of the publication.

The materials scientists were able to demonstrate another major advantage of their process. In a second step, they dissolved the ceramic scaffolding by using a chemical etching process. All that remains is a fine 3D network of tubes, each of which consists of a layer of tiny CNT tubes. In this way, the researchers were able to greatly increase the felt surface, and thus create more opportunities for reactions. “We basically pack the surface of an entire beach volleyball field into a one centimetre cube,” explained Schütt. The huge hollow spaces inside the three-dimensional structure can then be filled with a polymer. As such, CNTs can be connected mechanically with plastics, without their molecular structure – and thus their properties – being modified. “We can specifically arrange the CNTs and manufacture an electrically conductive composite material. To do so only requires a fraction of the usual quantity of CNTs, in order to achieve the same conductivity,” said Schütt.

Applications for use range from battery and filter technology as a filling material for conductive plastics, implants for regenerative medicine, right through to sensors and electronic components at the nano-scale. The good electrical conductivity of the tear-resistant material could in future also be interesting for flexible electronics applications, in functional clothing or in the field of medical technology, for example. “Creating a plastic which, for example, stimulates bone or heart cells to grow is conceivable,” said Adelung. Due to its simplicity, the scientists agree that the process could also be transferred to network structures made of other nanomaterials – which will further expand the range of possible applications.

So, we have ‘felting’ and bamboo buildings. I can appreciate the temptation to use multiple analogies especially since I’ve given into it, on occasion.  But, it’s never considered good style, not even when I do it.

Getting back to the work at hand, here’s a link to and a citation for the paper,

Hierarchical self-entangled carbon nanotube tube networks by Fabian Schütt, Stefano Signetti, Helge Krüger, Sarah Röder, Daria Smazna, Sören Kaps, Stanislav N. Gorb, Yogendra Kumar Mishra, Nicola M. Pugno, & Rainer Adelung. Nature Communications 8, Article number: 1215 (2017) doi:10.1038/s41467-017-01324-7 Published online: 31 October 2017

This is an open access paper.

One final comment, I notice that one of the authors is Nicola Pugno who was last mentioned here in an August 30, 2017 posting titled: Making spider silk stronger by feeding graphene and carbon nanotubes to spiders.

Making spider silk stronger by feeding graphene and carbon nanotubes to spiders

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Spider silk is already considered a strong and tough material but now scientists have found a way to enhance those properties. From an August 15, 2017 Institute of Physics Publishing press release (also on EurekAlert),

…  researchers in Italy and the UK have found a way to make Spidey’s silk a lot stronger, using various different spider species and carbon nanotubes or graphene.

The research team, led by Professor Nicola Pugno at the University of Trento, Italy, succeeded in having their spiders produce silk with up to three times the strength and ten times the toughness of the regular material.

Their discovery, published today in the journal 2D Materials, could pave the way for a new class of bionicomposites, with a wide variety of uses.

Professor Pugno said: “Humans have used silkworm silks widely for thousands of years, but recently research has focussed on spider silk, as it has extremely promising mechanical properties. It is among the best spun polymer fibres in terms of tensile strength, ultimate strain, and especially toughness, even when compared to synthetic fibres such as Kevlar.

“We already know that there are biominerals present in in the protein matrices and hard tissues of insects, which gives them high strength and hardness in their jaws, mandibles and teeth, for example. So our study looked at whether spider silk’s properties could be ‘enhanced’ by artificially incorporating various different nanomaterials into the silk’s biological protein structures.”

To do this, the team exposed three different spider species to water dispersions containing carbon nanotubes or graphene.

After collecting the spiders’ silk, the team tested its tensile strength and toughness.

Professor Pugno said: “We found that the strongest silk the spiders spun had a fracture strength up to 5.4 gigapascals (GPa), and a toughness modulus up to 1,570 joules per gram (J/g). Normal spider silk, by comparison, has a fracture strength of around 1.5 GPa and a toughness modulus of around 150 J/g.

“This is the highest fibre toughness discovered to date, and a strength comparable to that of the strongest carbon fibres or limpet teeth. These are still early days, but our results are a proof of concept that paves the way to exploiting the naturally efficient spider spinning process to produce reinforced bionic silk fibres, thus further improving one of the most promising strong materials.

“These silks’ high toughness and resistance to ultimate strain could have applications such as parachutes.”

“Furthermore, this process of the natural integration of reinforcements in biological structural materials could also be applied to other animals and plants, leading to a new class of “bionicomposites” for innovative applications.”

Remember this? “You are what you eat.” If you’ve ever had doubts about that saying, these spiders should be laying them to rest.

Sadly, this news release doesn’t explain much about the decision to feed the spiders graphene or carbon nanotubes, which are identical other than in their respective shapes (sheet vs tube)  and whether those shapes did or did not affect the strength of the silk.

Here’s a link to and a citation for the paper,

Spider silk reinforced by graphene or carbon nanotubes by Emiliano Lepore, Federico Bosia, Francesco Bonaccorso, Matteo Bruna, Simone Taioli, Giovanni Garberoglio, Andrea C Ferrari, and Nicola Maria Pugno. 2D Materials, Volume 4, Number 3 DOI: https://doi.org/10.1088/2053-1583/aa7cd3 Published 14 August 2017

© 2017 IOP Publishing Ltd

This paper is behind a paywall.

Pugno was most recently mentioned here in a May 29, 2015 posting where he was listed as an author for a paper on synthesizing spider silk. Prior to 2015 I was familiar with Pugno’s name due to his work on adhesiveness in geckos.