Coral genome reveals an alternative pathway for cysteine biosynthesis

Model animals, such as mice and fruit flies, have provided scientists with powerful insights into how cellular biology works. However, model animals are really just a guide, and it can be risky to generalize findings across animals from studying a selection of model organisms.

Cysteine is an important amino acid used in multiple biological processes, including metabolism and protein synthesis. In animals, cysteine biosynthesis was thought to be created exclusively via the transsulfuration pathway, with the cystathionine β-synthase (CBS) enzyme as a key player. However, previous research indicated that the CBS gene had been lost in corals of the genus Acropora. The suggestion was that these corals could not produce cysteine themselves and had to rely on symbiotic relationships with algae to receive it.

“We weren’t searching for possible cysteine biosynthesis in Acropora,” says postdoc Octavio Salazar, who worked on a Center Partnership Fund project with Principal Investigator Manuel Aranda from KAUST and co-workers from the Australian Institute of Marine Science. “We were generating a high-quality genome of the coral Acropora loripes as a valuable genomic resource for future research.”

With the high-resolution genome complete, the team decided to see if they could confirm that the CBS gene was indeed missing. Salazar could find no sign of the gene at the locus where it was meant to be, but he and his colleagues were not convinced that the coral had no other way of synthesizing cysteine.

“I started searching the genome for genes encoding for enzymes that looked similar to those in other known cysteine biosynthesis pathways, such as those found in fungi and bacteria,” says Salazar. “I was quite surprised to find two enzymes in the coral with similarities to a recently identified alternative cysteine biosynthesis pathway in fungi.”

To confirm that the enzymes encoded by these coral genes could synthesize cysteine in vivo, the researchers used yeast mutants with no cysteine biosynthesis capability and gave them the corresponding Acropora genes. The mutants began producing cysteine.

Further, the KAUST team found that both genes were present in the genomes of all animal phyla with the exception of vertebrates, arthropods and nematodes -; the precise three groups that the most common animal model organisms come from.

“This study proves the value of keeping an open mind when it comes to studying living creatures,” says Aranda. “Sometimes knowledge can put you in a box; if you analyze data using only what you think you know, you may well miss something. Our Acropora genome will be hugely valuable for future studies and who knows, it could reveal other unexpected details along the way.”


King Abdullah University of Science & Technology (KAUST)

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DNA nets effectively target the spike protein and detect COVID-19 virus at very low levels

Tiny nets woven from DNA strands can ensnare the spike protein of the virus that causes COVID-19, lighting up the virus for a fast-yet-sensitive diagnostic test – and also impeding the virus from infecting cells, opening a new possible route to antiviral treatment, according to a new study.

Researchers at the University of Illinois Urbana-Champaign and collaborators demonstrated the DNA nets’ ability to detect and impede COVID-19 in human cell cultures in a paper published in the Journal of the American Chemical Society.

“This platform combines the sensitivity of PCR and the speed and low cost of antigen tests,” said study leader Xing Wang, a professor of bioengineering and of chemistry at Illinois. “We need tests like this for a couple of reasons. One is to prepare for the next pandemic. The other reason is to track ongoing viral epidemics – not only coronaviruses, but also other deadly and economically impactful viruses like HIV or influenza.”

DNA is best known for its genetic properties, but it also can be folded into custom nanoscale structures that can perform functions or specifically bind to other structures much like proteins do. The DNA nets the Illinois group developed were designed to bind to the coronavirus spike protein – the structure that sticks out from the surface of the virus and binds to receptors on human cells to infect them. Once bound, the nets give off a fluorescent signal that can be read by an inexpensive handheld device in about 10 minutes.

The researchers demonstrated that their DNA nets effectively targeted the spike protein and were able to detect the virus at very low levels, equivalent to the sensitivity of gold-standard PCR tests that can take a day or more to return results from a clinical lab.

The technique holds several advantages, Wang said. It does not need any special preparation or equipment, and can be performed at room temperature, so all a user would do is mix the sample with the solution and read it. The researchers estimated in their study that the method would cost $1.26 per test.

“Another advantage of this measure is that we can detect the entire virus, which is still infectious, and distinguish it from fragments that may not be infectious anymore,” Wang said. This not only gives patients and physicians better understanding of whether they are infectious, but it could greatly improve community-level modeling and tracking of active outbreaks, such as through wastewater.

In addition, the DNA nets inhibited the virus’s spread in live cell cultures, with the antiviral activity increasing with the size of the DNA net scaffold. This points to DNA structures’ potential as therapeutic agents, Wang said.

“I had this idea at the very beginning of the pandemic to build a platform for testing, but also for inhibition at the same time,” Wang said. “Lots of other groups working on inhibitors are trying to wrap up the entire virus, or the parts of the virus that provide access to antibodies. This is not good, because you want the body to form antibodies. With the hollow DNA net structures, antibodies can still access the virus.”

The DNA net platform can be adapted to other viruses, Wang said, and even multiplexed so that a single test could detect multiple viruses.

“We’re trying to develop a unified technology that can be used as a plug-and-play platform. We want to take advantage of DNA sensors’ high binding affinity, low limit of detection, low cost and rapid preparation,” Wang said.

The National Institutes of Health supported this work through the Rapid Acceleration of Diagnostics program. The researchers will continue to work through the RADx program to explore and accelerate clinical applications for the DNA net platform.

Wang also is affiliated with the Holonyak Micro and Nanotechnology Lab and the Carl R. Woese Institute for Genomic Biology at Illinois.


University of Illinois at Urbana-Champaign

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Novel PTP1B inhibitor drug candidate can prevent lethal lung inflammation in mice

Neutrophils, the most abundant type of white blood cell, are the body’s first line of defense against infection. Foreign pathogens can stress the body and activate neutrophils. When activated, neutrophils employ various weapons to protect the body. But if overactivated, these weapons can damage the body’s own tissues. Lung tissue is saturated with blood vessels, making them very susceptible to neutrophil attacks. If severe enough, acute lung injuries can lead to acute respiratory distress syndrome (ARDS), the leading cause of death due to COVID-19.

Nicholas Tonks, Caryl Boies professor of cancer research at Cold Spring Harbor Laboratory (CSHL), and his team have found a drug candidate that can prevent lethal lung inflammation in mice by inhibiting a protein called PTP1B. Their discovery may help develop better treatments for severe inflammatory conditions like sepsis and COVID-19.

“When you think about COVID-19, acute lung injury and ARDS underlie the fatal aspects of the disease,” Tonks says. “And so, when the pandemic took hold, we were wondering whether there was anything we could do to help, to provide an understanding of this aspect of the disease and suggest ways it could be treated.”

Tonks’ graduate student Dongyan Song investigated whether using a PTP1B inhibitor drug candidate could dampen the lethal consequences of overactive neutrophils in mice. She found that pretreating mice with the PTP1B inhibitor reduced lung tissue damage. When untreated, less than half of the mice survived acute lung injuries and ARDS. But when pretreated, they all survived.

The researchers exploited a natural process, called neutrophil aging, that the body uses to control the immune cell’s lifespan. As they age, neutrophils become less dangerous. Tonks’ team discovered PTP1B inhibition speeds up neutrophil aging. “An aged neutrophil is like a soldier without a weapon,” Song explains. “So regardless of how many neutrophils flood an area, they won’t be able to do serious damage.”

This project was part of a program of COVID-related research at CSHL. Tonks says collaborations with CSHL Professor Mikala Egeblad, postdoc Jose M. Adrover, and CSHL Research Associate Professor Scott Lyons were essential to this discovery. Going forward, he and Song are working to increase the understanding of how PTP1B inhibitors affect the immune system. Tonks hopes his lab’s continued research leads to new treatments and preventative measures for various inflammatory diseases. His lab is currently working with DepYmed, Inc. to take PTP1B inhibitor drug candidates into clinical trials.

Tonks’ lab studies signal transduction, the process that controls how cells respond to signals from their environment. In particular, they focus on the PTP protein family, which Tonks discovered over 30 years ago. Since then, he’s sought to develop small molecule drug candidates that target these proteins, which can provide new approaches for treating major human diseases including cancer and metabolic and neurodegenerative diseases.


Cold Spring Harbor Laboratory

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Viruses exploit ability to sense the environment to maximize their infective yield

New UMBC-led research in Frontiers in Microbiology suggests that viruses are using information from their environment to “decide” when to sit tight inside their hosts and when to multiply and burst out, killing the host cell. The work has implications for antiviral drug development.

A virus’s ability to sense its environment, including elements produced by its host, adds “another layer of complexity to the viral-host interaction,” says Ivan Erill, professor of biological sciences and senior author on the new paper. Right now, viruses are exploiting that ability to their benefit. But in the future, he says, “we could exploit it to their detriment.”

Not a coincidence

The new study focused on bacteriophages-;viruses that infect bacteria, often referred to simply as “phages.” The phages in the study can only infect their hosts when the bacterial cells have special appendages, called pili and flagella, that help the bacteria move and mate. The bacteria produce a protein called CtrA that controls when they generate these appendages. The new paper shows that many appendage-dependent phages have patterns in their DNA where the CtrA protein can attach, called binding sites. A phage having a binding site for a protein produced by its host is unusual, Erill says.

Even more surprising, Erill and the paper’s first author Elia Mascolo, a Ph.D. student in Erill’s lab, found through detailed genomic analysis that these binding sites were not unique to a single phage, or even a single group of phages. Many different types of phages had CtrA binding sites-;but they all required their hosts to have pili and/or flagella to infect them. It couldn’t be a coincidence, they decided.

The ability to monitor CtrA levels “has been invented multiple times throughout evolution by different phages that infect different bacteria,” Erill says. When distantly related species demonstrate a similar trait, it’s called convergent evolution-;and it indicates that the trait is definitely useful.

Timing is everything

Another wrinkle in the story: The first phage in which the research team identified CtrA binding sites infects a particular group of bacteria called Caulobacterales. Caulobacterales are an especially well-studied group of bacteria, because they exist in two forms: a “swarmer” form that swims around freely, and a “stalked” form that attaches to a surface. The swarmers have pili/flagella, and the stalks do not. In these bacteria, CtrA also regulates the cell cycle, determining whether a cell will divide evenly into two more of the same cell type, or divide asymmetrically to produce one swarmer and one stalk cell.

Because the phages can only infect swarmer cells, it’s in their best interest only to burst out of their host when there are many swarmer cells available to infect. Generally, Caulobacterales live in nutrient-poor environments, and they are very spread out. “But when they find a good pocket of microhabitat, they become stalked cells and proliferate,” Erill says, eventually producing large quantities of swarmer cells.

So, “We hypothesize the phages are monitoring CtrA levels, which go up and down during the life cycle of the cells, to figure out when the swarmer cell is becoming a stalk cell and becoming a factory of swarmers,” Erill says, “and at that point, they burst the cell, because there are going to be many swarmers nearby to infect.”

Listening in

Unfortunately, the method to prove this hypothesis is labor-intensive and extremely difficult, so that wasn’t part of this latest paper-;although Erill and colleagues hope to tackle that question in the future. However, the research team sees no other plausible explanation for the proliferation of CtrA binding sites on so many different phages, all of which require pili/flagella to infect their hosts. Even more interesting, they note, are the implications for viruses that infect other organisms-;even humans.

“Everything that we know about phages, every single evolutionary strategy they have developed, has been shown to translate to viruses that infect plants and animals,” he says. “It’s almost a given. So if phages are listening in on their hosts, the viruses that affect humans are bound to be doing the same.”

There are a few other documented examples of phages monitoring their environment in interesting ways, but none include so many different phages employing the same strategy against so many bacterial hosts.

This new research is the “first broad scope demonstration that phages are listening in on what’s going on in the cell, in this case, in terms of cell development,” Erill says. But more examples are on the way, he predicts. Already, members of his lab have started looking for receptors for other bacterial regulatory molecules in phages, he says-;and they’re finding them.

New therapeutic avenues

The key takeaway from this research is that “the virus is using cellular intel to make decisions,” Erill says, “and if it’s happening in bacteria, it’s almost certainly happening in plants and animals, because if it’s an evolutionary strategy that makes sense, evolution will discover it and exploit it.”

For example, to optimize its strategy for survival and replication, an animal virus might want to know what kind of tissue it is in, or how robust the host’s immune response is to its infection. While it might be unsettling to think about all the information viruses could gather and possibly use to make us sicker, these discoveries also open up avenues for new therapies.

“If you are developing an antiviral drug, and you know the virus is listening in on a particular signal, then maybe you can fool the virus,” Erill says. That’s several steps away, however. For now, “We are just starting to realize how actively viruses have eyes on us-;how they are monitoring what’s going on around them and making decisions based on that,” Erill says. “It’s fascinating.”


University of Maryland Baltimore County

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Asexuals form connections that may be similar to non-asexuals’ romantic relationships

Many asexual individuals, those with little to no sexual attraction, are in long-term satisfying romantic relationships, but there has been little study on how and why they last and thrive. New research from Michigan State University found that, despite asexuals’ lack of or dislike for sexual attraction, the ingredients that make for a successful relationship among asexual individuals are virtually the same as those in any other relationship.

“Although asexuals don’t have the desire for sexual relationships, they nevertheless form romantic relationships and those connections look at least somewhat similar to non-asexuals’ romantic relationships,” said William Chopik, associate professor in MSU’s psychology department and coauthor of the study.

The study, published in Frontiers in Psychology, is among the largest studies of asexual individuals’ relationships ever conducted and the only one to examine what predicts commitment and longevity in their relationships. The study looked at a sample of 485 people who self-identified as on the asexual spectrum and are currently in a romantic relationship. This is one of the only published studies that allowed people to self-identify with any asexual spectrum label, in addition to allowing them to use any other sexual or romantic labels that fit.

“I sincerely hope that this study will more widely show the diversity of the asexual community, shed light on their experiences and show that being on the asexual spectrum does not preclude one from successful romantic relationships or love,” said coauthor and research associate Alexandra Brozowski.

The long-standing theory about what predicts who breaks up and who stays in relationships, called the Investment Model, says that people stay in relationships if they are happy and satisfied, if they have invested time and energy into the relationship and if they don’t have any other options. Many theories say that sex is a central part of romantic relationships, which doesn’t leave room for asexual relationships.

“We found that the same ingredients predict success in these relationships, so they’re not weird, bizarre, worse than or much different at all from non-asexual people’s relationships.” Chopik said. “The hope is that this destigmatizes asexual people’s relationships as just as satisfied and common as non-asexual people’s relationships.”


Michigan State University

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An AI Message Decoder Based On Bacterial Growth Patterns

From a box of Cracker Jack to The Da Vinci Code, everybody enjoys deciphering secret messages. But biomedical engineers at Duke University have taken the decoder ring to place it’s never been before—the patterns created by bacterial colonies.

Depending on the initial conditions used, such as nutrient levels and space constraints, bacteria tend to grow in specific ways. The researchers created a virtual bacterial colony and then controlled growth conditions and the numbers and sizes of simulated bacterial dots to create an entire alphabet based on how the colonies would look after they fill a virtual Petri dish. They call this encoding scheme emorfi.

The encoding is not one-to-one, as the final simulated pattern corresponding to each letter is not exactly the same every time. However, the researchers discovered that a machine learning program could learn to distinguish between them to recognize the letter intended.

“A friend may see many images of me over the course of time, but none of them will be exactly the same,” explained Lingchong You, professor of biomedical engineering at Duke. “But if the images are all consistently reinforcing what I generally look like, the friend will be able to recognize me even if they’re shown a picture of me they’ve never seen before.”

To encrypt real messages, the encoder ends up creating a movie of a series of patterns, each correlating to a different letter. While they may look similar to the untrained eye, the computer algorithm can distinguish between them. So long as the receiver knows the set of initial conditions that led to their creation, an interloper should not be able to crack the code without a powerful AI of their own.

Give the cypher a try yourself. You can type in anything from your name to the Gettysburg Address, or even the Christmas classic, “Be sure to drink your Ovaltine.”


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Tools And Education Can Reduce Sugary Drink Consumption For Low-Income Latino Families

As the White House prepares for the first conference on hunger, nutrition and health in more than 50 years, public health officials point out that providing access to safe potable drinking water must be part of the national conversation. Low income and minority populations in the US are less likely to drink plain water and also have negative perceptions about tap water, which has been associated with consuming high sugar beverages. This can lead to health issues ranging from cavities to having a higher Body Mass Index and risks factors for diabetes.

Two new studies from the George Washington University’s Milken Institute School of Public Health now suggest that providing low-income families with a low cost water filter pitcher to use at home increases their water consumption and decreases their consumption of sugary drinks.

“These findings are the first to confirm, in an intervention study, that providing access to affordable, safe, palatable tap water in the US can significantly reduce sugary drink intake among low income families,” Uriyoán Colón-Ramos, associate professor at the George Washington University Milken Institute School of Public Health and senior author on both papers, said. “We already know that drinking water is good for you, but these findings now suggest that water security is a major factor when considering healthy lifestyle interventions for lower income and minority populations.”

In the first study,  Colón-Ramos and her colleagues studied 92 parents of infants/toddlers who participated in Early Head Start programs that serve predominantly Hispanic low-income communities in the Washington DC metro area. The team found that when given a water filter, even with no other interventions, families were more likely to begin drinking more water and significantly lowered their consumption of sugary drinks. Families that received a water filter plus a 12 week educational and motivational intervention to replace sugary drinks and fruit juice with filtered tap water, also significantly reduced their sugary drink intake and their consumption of fruit juice.

In the second study, Colón-Ramos and her colleagues focused on explaining how the low-cost water filter pitcher helped parents reduce their consumption of sugar sweetened beverages and increase their water intake. The team conducted in-depth interviews and found that using the water filter improved the flavor of water from the tap and increased parents’ perceptions of water safety. With safe and palatable drinking water at home parents did not feel they had to buy bottled water and ration water consumption as before. The increase in water consumption replaced the intake of other beverages, such as sugary drinks, fruit juice and sports drinks.

“We already knew that drinking potable water is good for you. The United Nations says that access to sufficient, safe, acceptable, physically accessible, and affordable water is a basic human right. What we did not know is that when that human right is violated or when access to it is inconsistent, which can happen and is happening in communities in the US, this can significantly contribute to individuals choosing to drink sugary beverages.” Colón-Ramos explained.

“This research demonstrates that nutritional status and dietary behaviors can significantly improve family health habits –and these early life nutritional practices may have a profound lifetime effect on children,” William Dietz, Chair of the Redstone Global Center for Prevention and Wellness, which helped fund the studies, said. “Public health practitioners always seek affordable and accessible interventions to improve health outcomes, and these studies provide us with insights that can be more broadly applied to reduce sugary drink intake.”


George Washington University

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The Leopoldina Annual Assembly Looks At Ways Of Achieving Global Health And Equity

Cooperation among many disciplines is required to improve the health situation and equity of all people worldwide. At its two-day Annual Assembly 2022, which will begin today in Halle (Saale)/Germany, the German National Academy of Sciences Leopoldina addresses “Global Health: From Health Services to Climate Change and to Social Justice” and thus focuses on a broad spectrum of global health issues. In the morning, WHO Director General Dr. Tedros Adhanom Ghebreyesus, German Federal Minister of Education and Research Bettina Stark-Watzinger, and Minister President of Saxony-Anhalt Dr. Reiner Haseloff will all give welcome addresses. The Annual Assembly lectures are all being livestreamed.

“Global Health is an interdisciplinary field of work that aims to improve the health of everyone worldwide and to promote health equity. Health impact must be taken into account in all areas of policymaking, an approach known as ‘Health in all policies'”, expert in veterinary medicine and microbiology Prof. Dr. Lothar H. Wieler says. The President of the Robert Koch Institute has been a member of the Leopoldina since 2010. As Acting Senator of the Section Global Health, he is part of the Annual Assembly’s Organising Committee, alongside the Leopoldina members Prof. Dr. Susanne Hartmann, biologist and infection immunologist, and molecular biologist and virologist Prof. Dr. Thomas C. Mettenleiter. In his Inaugural Address today at 12.15 p.m., Wieler will discuss the lessons of the COVID-19 pandemic for global health.

Social scientist Prof. Dr. Johanna Hanefeld will speak about “International Health Protection and Health Equity” in today’s evening lecture at 8.15 p.m. The Head of the Centre for International Health Protection at the Robert Koch Institute in Berlin/Germany will discuss issues such as the significance of globally connected and more robust public health systems.

In the morning, the Leopoldina honours the materials scientist and biomedical engineer Prof. Dr. Francesca Santoro with the “Leopoldina Early Career Award”. The award, funded by the Commerzbank Foundation, is valued at 30,000 euros. In her lecture the award winner will discuss her work in the field of bioelectronics, where she is developing new materials capable of interacting with the skin and the brain.

Yesterday, Thursday 22 September, the Leopoldina Senate elected the geologist Prof. Dr. Onno Oncken as member of the Academy’s Presidium. He succeeds engineering expert Prof. Dr. Sigmar Wittig, who as Secretary of Class I ‒ Mathematics, Natural Sciences and Engineering, has been a member of the Academy’s Presidium since 2012. The Senate also elected Vice President Prof. Regina Riphahn Ph.D. for another term. The economist, a member of the Leopoldina since 2007, is Professor of Statistics and Empirical Economic Research at Friedrich-Alexander-Universität Erlangen-Nürnberg.

This year also sees more than 35 highly talented pupils from throughout Germany attend the Annual Assembly. They will listen to the lectures at the event and have the chance to speak to the researchers. The pupils’ programme is funded by the “Friends of the Leopoldina” association.

The Annual Assembly is being livestreamed on the Leopoldina’s YouTube channel: The livestream is available until 6.30 p.m. today, and again for the evening lecture at 8.15 p.m. and on Saturday from 8.30 a.m. Lectures are held in English and German and simultaneously interpreted. You can find the full programme of the Annual Assembly and further information on the Leopoldina website:

A Review On Mobile Sensing In The COVID-19 Era

Mobile sensing has shown its power in the pervasive and effective monitoring of COVID-19 in varying population scales and time duration, according to a study published in Health Data Science, a Science Partner Journal.

Behind this work are the researchers at the Sensing System for Health Lab led by Dr. Laura Barnes at the University of Virginia. They have been working on promoting health and well-being using mobile sensing and data analytics techniques.

Mobile sensing, a digital surveillance tool, leverages embedded sensors in mobile devices such as smartphones and wearables. As mobile sensing has become a promising way to monitor the trajectories of the pandemic by collecting the data on individual, community, and global scales, this paper investigated the study designs, expected health outcomes, and existing limitations of such mobile-based human-subject work to guide future practice. As such, this paper stands out among a panoply of articles on the use of mobile devices for COVID-19 response.

“We reviewed existing work’s 1) aims and designs, 2) sensing duration and population coverage, 3) outcomes and limitations, to better taxonomize and understand this topic.” says Zhiyuan Wang, PhD student with Sensing Systems for Health Lab.

“Existing work has demonstrated the capacity of mobile sensing to not only 1) remotely detect infectious status, but to also 2) longitudinally track disease progression for personalized medicine, 3) to passively trace exposures and 4) broadly observe the influence of the pandemic on population health”, shares Professor Laura Barnes, the lab director.

However, technical and societal limitations still exist, including data availability and system adoption challenges, clinical and application issues, and privacy and ethical concerns. These limitations have hindered further actions of computer scientists, clinicians, and epidemiologists in leveraging mobile sensing for human health.

Current or emerging technologies may provide a solution to these constraints. For example, advances in data analytics and machine learning methods may help improve data quality because of their ability to process sparse, heterogenous and multimodal mobile sensing data streams. Also, mobile sensing at even larger scales, particularly in clinical settings, could be carried out leveraging the next generation of sensors and sensing platforms.

Other stakeholders can also make an impact on how mobile sensing can yield clinical and social benefits. Such efforts can include mitigating potential threats to privacy, equity and health disparities; promoting technological and health literacy in all communities; and making trust-based and shared decisions that properly balance risks and benefits.

Barnes and her team wish to see more works where computer scientists, clinicians, and epidemiologists design and implement the study collaboratively with experts in social science and public policy to enable more effective, scalable, and socially equal mobile health systems for infectious disease.


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Advanced Robotics To Address The Translational Gap In Tendon Engineering

A review paper by scientists at the University of Oxford discussed possible benefits of using humanoid musculoskeletal robots and soft robotic systems as bioreactor platforms in producing clinically useful tendon constructs.

The new review paper, published on 15 Sep 2022 in the journal Cyborg and Bionic Systems, summarizes current trends in tendon tissue engineering and discusses how conventional bioreactors are unable to provide physiologically relevant mechanical stimulation given that they largely rely on uniaxial tensile stages. The paper then highlights musculoskeletal humanoid robots and soft robotic systems as platforms for providing physiologically relevant mechanical stimulation that could overcome this translational gap.

Tendon and soft tissue injuries are a growing social and economic problem, with the tendon repair market in the United States being estimated at $ 1.5 billion USD. Tendon repair surgeries have high rates of revision, with upwards of 40% of rotator cuff repairs failing post-operatively. Production of engineered tendon grafts for clinical use is a potential solution for this challenge. Conventional tendon bioreactors mainly provide uniaxial tensile stimulation. The lack of systems which recapitulate in vivo tendon loading is a major translational gap.

“The human body provides tendons with three-dimensional mechanical stress in the form of tension, compression, torsion, and shear. Current research suggests that healthy native tendon tissue requires multiple types and directions of stress. Advanced robotic systems such as musculoskeletal humanoids and soft robotics promising platforms that may be able to mimic in vivo tendon loading” explained author Iain Sander, a researcher at the University of Oxford with the Soft Tissue Engineering Research Group.

Musculoskeletal humanoid robots were initially designed for applications such as crash test dummies, prostheses, and athletic enhancement. They attempt to imitate human anatomy by having similar body proportions, skeletal structure, muscle arrangement, and joint structure. Musculoskeletal humanoids such as Roboy and Kenshiro use tendon-driven systems with myorobotic actuators that mimic human neuromuscular tissue. Myorobotic units consist of a brushless dc motor which generates tension like human muscles, attachment cables which act as the tendon unit, and a motor driver board with a spring encoder, which act as the neurologic system by sensing variables including tension, compression, muscle length, and temperature. Proposed advantages of musculoskeletal humanoids include the ability to provide multiaxial loading, potential for loading in consideration of human movement patterns, and provision of loading magnitudes comparable to in vivo forces. One recent study has demonstrated the feasibility of growing human tissue on a musculoskeletal humanoid robot for tendon engineering.

Biohybrid soft robotics is focused on developing biomimetic, compliant robotic systems which permit adaptive, flexible interactions with unpredictable environments. These robotic systems are actuated through a number of modalities, including temperature, pneumatic and hydraulic pressure, and light. They are made of soft materials including hydrogels, rubber, and even human musculoskeletal tissue. These systems are already being used to provide mechanical stimulation to smooth muscle tissue constructs and have been implemented in vivo in a porcine model. These systems are attractive for tendon tissue engineering given that: i) their flexible, compliant properties allow them wrap around anatomic structures, mimicking the configuration of native tendon ii) they are capable of providing multiaxial actuation and iii) a number of the techniques used in soft robotics overlap with current tendon tissue engineering practices.Looking forward, the team envision advanced robotic systems as platforms which will provide physiologically relevant mechanical stimulus to tendon grafts prior to clinical use. There are a number of challenges to consider as advanced robotic systems are implemented. Firstly, it will be important for future experiments to compare technologies proposed in this review to conventional bioreactors. With development of systems capable of providing multiaxial loading, it will be important to find methods for quantifying strain in 3D. Finally, advanced robotic systems will need to be more affordable and accessible for widespread implementation.

“An increasing number of research groups are showing that it is feasible to use advanced robotics in combination with living cells and tissues for tissue engineering and bioactuation applications. We are now at an exciting stage where we can explore the different possibilities of incorporating these technologies in tendon tissue engineering and examine whether they can really help improve the quality of engineered tendon grafts”, said Pierre-Alexis Mouthuy, the review article’s senior author. In the long term, these technologies have potential to improve quality of life for individuals, by decreasing pain and risk of tendon repair failure, for healthcare systems, by reducing the number of revision surgeries, and for the economy, by improving workplace productivity and lowering healthcare costs.

Authors of the paper include Iain Sander, Nicole Dvorak, Julie Stebbins, Andrew J Carr, Pierre-Alexis Mouthuy.

This work has been completed with the financial support of the United 16 Kingdom’s Engineering and Physical Sciences Research Council (project number: 17 P/S003509/1), and the Rhodes Trust.


Beijing Institute of Technology Press Co., Ltd

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