Category: Medical Research & Technology

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Research Shows Surgical Simulation Training Improves Performance

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Success with independent surgical simulation training has made it the new normal for students at the Pan Am Clinic.

Traditionally, surgical resident training has been master–apprentice-type relationship, with gradually increasing responsibilities until the trainees can do procedures on their own. Given recent pressures in the health care system, including reduced operating room time, increased difficulty of procedures and working hour restrictions, there is less time for residents to learn using the traditional method.

Surgical simulation, a surprisingly old system, dates back nearly 2500 years, when they were first used to plan innovative procedures while maintaining patient safety. One of the first recorded instances of surgical simulation was the use of leaf and clay models in India around 600 BC to conceptualise nasal reconstruction with a forehead flap

In a recent study, researchers from the University of Manitoba and the Pan Am Clinic recently examined the effectiveness of a mixed reality simulator for the training of arthroscopy novices.

Study author Dr Samuel Larrivée said: “Sports surgeons at our institution noted anecdotally that junior residents had difficulty reaching competency in arthroscopic skills by the end of their three-month rotation, and were not as prepared when starting their senior rotation. There was a need to increase training opportunities outside of the operating room in order to prepare our residents for independent practice.”

Prior to obtaining the ArthroS™ simulator, the University of Manitoba Orthopedic Surgery program occasionally made use of options such as benchtop dry simulators, cadavers and an older generation simulator with active haptics. These largely complemented academic teaching sessions in small groups with some success, and were available for use by residents as needed. But, due to the low fidelity and difficult setup, few residents took advantage of it.

However, medical students readily took to the ArthroS simulator. Alisha Beaudoin, a co-author and medical student, attested to her experience using the ArthroS simulator in her early training. “I found this training to be very helpful during my surgery rotation. Many of my preceptors were impressed by my superior arthroscopic and laparoscopic skills. This training may allow students with an interest in surgery to be more prepared.

“Recently, many Canadian universities have moved to competency-based curriculums where residents must demonstrate competency prior to moving to the next defined practice level. The study noted that this is similar to the training available on VirtaMed ArthroS and that “a user enrolled in the mentoring program is progressed through various levels of training by meeting training targets, essentially providing a proficiency-based progression.”

This paper is the first in what the authors hope is a larger body of work on validating arthroscopy simulators for resident training. There are currently plans to repeat similar studies with the other modules (hip, shoulder, and ankle), with larger sample sizes, and at different levels of training.

Participants were split into three groups: simulator training only, mentor-based training, and a control. After  four weeks, surgical performance improved among both traditional and simulator-based training groups. The study concluded that “simulator training may provide enhanced skills to improve patient safety overall, as residents may become more skilled earlier in their training, leaving more time for the mentor to teach more advanced skills.” Dr Beaudoin further explains: “I believe that simulation training should be introduced into the standardised curriculum because I believe it offers a safe space to hone your skills and improve in a stress-free environment.”

On the strength of the results, the residency programme has made it a requirement in the curriculum that residents in their sports rotation complete the self-learning modules. Dr Larrivée believes this will help residents develop their triangulation skills and memorise the steps ahead of their first surgery, and to consolidate their knowledge.

Source: VirtaMed

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A Step to Towards Electrically Restoring Oral Sensation and Function

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In an effort towards restoring oral functionality lost to nerve or brain damage, researchers at Texas A&M University have determined the minimum electrical stimulation needed to provide sensation in various parts of the mouth.

Sensorimotor feedback loops involve the brain interpreting incoming signals from sensory nerves and then ordering motor nerves to execute a particular movement. Sensorimotor loops play a vital role in voluntary functions, like walking or holding an object, and involuntary movements, like sneezing or blinking.

Within the mouth, both sensory and motor nerves are richly supplied. In particular, sensorimotor nerves in the soft palate and tongue coordinate several intraoral movements related to swallowing, speech and respiration. Damage to either the sensory or motor nerve fibres due to neurotrauma or disease can therefore compromise these essential functions and worsening the quality of life for afflicted individuals.

Electrical nerve stimulation might help jumpstart the nerves into action, much like how a pacemaker can electrically stimulate nerves in the heart, causing the heart muscle to contract. Unlike a pacemaker however, the parameters of the electrical currents needed for proper stimulation of different parts of the mouth have not been investigated.

“Electrical stimulation can modulate nerve currents or action potentials, which are the mode of communication to and from the brain,” said Hangue Park, assistant professor in the Department of Electrical and Computer Engineering. “And so, electrical stimulation should be carefully applied, because if not, then it might cause undesirable effects, or it might not stimulate anything at all.”

To investigate the minimum stimulation currents needed, Park and his team place tiny metal electrodes in a standard dental retainer. These electrodes were positioned in subjects’ mouths to stimulate either their soft palate or the side and tip of the tongue, which are dense in sensory nerves. The researchers slowly changed the amplitude of the stimulation current, keeping the frequency fixed. Subjects reported when they began feeling a sensation and when the sensation was uncomfortable, and the same experiment was repeated with a higher frequency of current.

After compiling their data, the team determined the average perception and discomfort thresholds for the tongue and soft palate. In addition, they produced an equivalent circuit of the intraoral cavity to duplicate the electrical properties of that area. This circuit, the researchers said, can help to further study the effects of electrical stimulation offline without requiring human subjects.

The researchers noted that their next steps would be to electrically stimulate the intraoral region and investigate how these simulations change chewing, swallowing and other behaviours.

“Sensorimotor systems can be extremely vulnerable to damage due to neural defects, aging and neurodegenerative diseases,” Park said. “In this study, we have begun to lay the groundwork for electrically stimulating parts of the mouth that control involuntary and voluntary movements. Our work is a seminal study and it is important so that we can, in the near future, help people that face enormous challenges doing everyday tasks that we take for granted.”

Source: Texas A&M University

Journal information: Park, B., et al. (2021) Electrical Characterization of the Tongue and the Soft Palate using Lumped-Element Model for Intraoral Neuromodulation. IEEE Transactions on Biomedical Engineering. doi.org/10.1109/TBME.2021.3070867.

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New Machine Learning Tools Could Save Teeth

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Machine learning tools could help identify those at greatest risk for tooth loss and refer them for further dental assessment for early interventions to avert or delay the conditions.

The study by researchers at the Harvard School of Dental Medicine compared five different algorithms using various combinations of variables to screen for risk. The results showed those that factored medical characteristics and socioeconomic variables, including race, education, arthritis, and diabetes, outperformed algorithms that relied on dental clinical indicators alone.

“Our analysis showed that while all machine-learning models can be useful predictors of risk, those that incorporate socioeconomic variables can be especially powerful screening tools to identify those at heightened risk for tooth loss,” said study lead investigator Hawazin Elani, assistant professor of oral health policy and epidemiology at HSDM.

The approach could be used to screen people globally and in a variety of health care settings even by non-dental professionals, she added. This approach could be applied around the world, even allowing non-dental professionals to screen patients.

Tooth loss can affect quality of life, well-being, nutrition, and social interactions. It is also associated with dementia. If the earliest signs of dental disease are identified, then the process can be delayed or averted with prompt treatment. However, many people with dental disease may not see a dentist until the process is too far gone. This is where screening tools could help identify those at highest risk and refer them for further assessment, the team said.

For the study, the researchers used data on nearly 12 000 adults from the National Health and Nutrition Examination Survey to design and test five machine-learning algorithms and assess their predictions for both complete and incremental tooth loss among adults based on socioeconomic, health, and medical characteristics.

A key point is that algorithms were designed to assess risk without a dental exam, though anyone at risk for tooth loss would still need one. The study’s findings point to the importance of socioeconomic factors.

“Our findings suggest that the machine-learning algorithm models incorporating socioeconomic characteristics were better at predicting tooth loss than those relying on routine clinical dental indicators alone,” Elani said. “This work highlights the importance of social determinants of health. Knowing the patient’s education level, employment status, and income is just as relevant for predicting tooth loss as assessing their clinical dental status.”

Low socioeconomic status populations have long been known to have greater rates of tooth loss, likely due to lack of regular access to dental care, among other reasons, the team said.

“As oral health professionals, we know how critical early identification and prompt care are in preventing tooth loss, and these new findings point to an important new tool in achieving that,” said Jane Barrow, associate dean for global and community health and executive director of the Initiative to Integrate Oral Health and Medicine at HSDM. “Dr. Elani and her research team shed new light on how we can most effectively target our prevention efforts and improve quality of life for our patients.”

Source: Harvard Medical School

Journal information: Hawazin W. Elani et al, Predictors of tooth loss: A machine learning approach, PLOS ONE (2021). DOI: 10.1371/journal.pone.0252873

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India Tests Out Drones for Medical Deliveries

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An aviation firm has carried out the first tests in India of drone deliveries at long ranges, in a step towards one day delivering medicines as well as COVID vaccines to remote areas.

India, with a population of 1.3 billion people spread across some 3.2 million square kilometres is the world’s seventh-largest country by land mass. Experts say that widespread use of drones could be a game-changer for medical services in the South Asian nation’s hard-to-reach rural areas with often poor roads and lack of healthcare infrastructure.

Drones are a cost-effective alternative to road transport in difficult terrains. They can be used in the transport of blood from the blood bank to the place of surgery and that of specimens from hard-to-reach areas to the labs in nearby towns. They can deliver essential medicines like anti-venom for snake bite and dog bite and prevent deaths.

Throttle Aerospace Systems is among 20 organisations granted permits by the government since May to conduct experimental flights beyond the current limit of 450 metres.

Two drones were tested in the southern state of Karnataka: one that can carry up to one kilogramme for 20 kilometres for nearly an hour, and another that can lift two kilogrammes for 15 kilometres.

“Medicines was the payload here and… 2.5 kilometres were covered in seven minutes and it delivered the medicines at the designated point and the drone returned,” Throttle’s co-founder, Sebastian Anto, told AFP at the test site.

This month the Indian government also invited bids from drone operators to help set up a pilot project for the delivering of medical supplies as it seeks to bolster its flagging COVID vaccination drive.

Samiran Panda,  epidemiology chief of the Indian Council of Medical Research, told The Hindu daily newspaper that the technology could help innoculate priority groups in hard-to-reach places.

“We need smart vaccination instead of mass vaccination to stem an epidemic,” Panda told the newspaper last week.

However, India lags behind many other nations when it comes to drones both in terms of their uses and the regulatory framework.Under current regulations, they have to be flown in full view, or within 450 metres, of their operators on the ground.

In Germany, it is reported that researchers are testing drone prototypes that can track down disaster victims by their screams. In Australia, drones using artificial intelligence algorithms are being used to spot crocodiles and count koalas in rugged terrain.

“Drone technology would have a huge impact in those areas where emergency medicines and vaccines could be supplied,” co-founder of lobby group the Drone Federation of India, Vipul Singh, told AFP.

“Where it takes a few hours to travel 20-30 kilometres by road, whereas a drone can actually travel that distance in 10 to 15 minutes,” said Singh, also the co-founder of Bangalore-based Aarav Unmanned Systems.

Source: Medical Xpress

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‘Windscreen Wiper’ Tool for Laparoscopes Allows Uninterrupted View

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A Brigham Young University student has developed a ‘windscreen wiper’ tool for laparoscopes that continuously keeps the camera end clean.

The laparoscope, a slender rod with a camera tip, allows doctors to see inside a body during surgery. Laparoscopes have made surgery less invasive and easier for surgeons and patients, but the device does have a problematic drawback: it must be removed, cleaned, and reinserted multiple times during surgery.

Engineering graduate student Jacob Sheffield has developed a tiny origami-based device that serves as a miniature windshield wiper for laparoscope camera lenses. When installed, the device eliminates the need to remove and reinsert laparoscopes every five or so minutes during surgery, which would allow surgeons to focus on the patient without disruptions.

“It’s like driving the car in the rain,” Sheffield explained. “If you can focus on driving and not on reaching out the window to wipe off the windshield with your hand, you can keep your focus on what’s important.”

His technology, developed with mentoring from BYU professor Larry Howell in the Compliant Mechanisms Research Lab and help from ME undergrad Amanda Lytle, is called LaparoVision. The disposable mechanism snaps on to existing laparoscopes and features a one-piece curved wiper that conforms to the cylindrical walls of the medical tool. The wiper, which is so small it can rest on the end of a finger, is actuated by a trigger outside of the body.

The innovative concept was impressive enough to earn Sheffield the title of 2021 Student Innovator of the Year at BYU, an award which also provides kickstarter money to develop a project.

“It’s extremely helpful to get that funding through BYU awards programs and the feedback you get from judges is invaluable,” Sheffield said. “My advice for future applicants is even if you don’t win or get money out of it, use the deadline of the competitions to drive progress for your idea.”

For Sheffield, the idea came about when he was meeting with surgeons across the country on other medical technologies being tested in the CMR lab. The issue of laparoscope removal and cleaning kept coming up in their conversations. The tool is used in 5 million surgeries every year in the US alone, and in roughly 90% of those procedures, the device must be removed.

Sheffield said that, according to many surgeons and studies, every five to eight minutes the device has to be pulled out and the lens wiped clean. With operating rooms costing $62 a minute, those fairly regular removals prove costly and frustrating. However, even more importantly, withdrawal of the scope at a critical time can cause serious risks for the patient.

“There is a high correlation in keeping the scope clean, maintaining surgical focus and ensuring timely and safe patient outcomes,” Sheffield said. “But it’s not just about improving efficiency during surgery; every time you lose vision it could be a critical part in the surgery where you make an incision and get blood on the lens and you can’t see what’s going on.”

Sheffield is currently in talks to license the technology and has now formed a startup (Bloom Surgical) to bring the device to market. Currently he is focusing on showing that the device is reliable and sage, and working towards getting FDA clearance for the tool.

Source: Brigham Young University

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New Printable Biosensor Could Guide Surgery

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Surgeons may soon be able to pinpoint critical regions in tissues during surgery without interruption thanks to a new, 3D-printable biosensor.

Associate Professor Chi Hwan Lee created the biosensor, which enables both recording and imaging of tissues and organs during a surgical operation. Research on the biosensor was published in Nature Communications.

Prof Lee explained the benefits of such devices: “Simultaneous recording and imaging could be useful during heart surgery in localising critical regions and guiding surgical interventions such as a procedure for restoring normal heart rhythm.”

Existing methods to simultaneously record and image tissues and organs have proven challenging because other sensors used for recording typically interrupt the imaging process.

“To this end, we have developed an ultra-soft, thin and stretchable biosensor that is capable of seamlessly interfacing with the curvilinear surface of organs; for example the heart, even under large mechanical deformations, for example cardiac cycles,” Prof Lee said. “This unique feature enables the simultaneous recording and imaging, which allows us to accurately indicate the origin of disease conditions: in this example, real-time observations on the propagation of myocardial infarction in 3D.”

The biosensors are made of soft bio-inks and are rapid-prototyped to a custom-fit design, fitting a variety of sizes and shapes of an organ. The bio-inks used are softer than tissue, and can stretch without experiencing sensor degradation but also have reliable natural adhesion to the wet surface of organs without needing extra adhesives. The formulation and synthesis of the bio-inks was thanks to Kwan-Soo Lee’s research group in Los Alamos National Laboratory.

The researchers have produced a number of prototype biosensors using different shapes, sizes and configurations. Craig Goergen, the Leslie A Geddes Associate Professor of Biomedical Engineering in Purdue’s Weldon School of Biomedical Engineering, and his laboratory group have tested the prototypes in mice and pigs in vivo.

“Professor Goergen and his team were successfully able to identify the exact location of myocardial infarctions over time using the prototype biosensors,” Prof Lee said. “In addition to these tests, they also evaluated the biocompatibility and anti-biofouling properties of the biosensors, as well as the effects of the biosensors on cardiac function. They have shown no significant adverse effects.”

Source: Purdue University

Journal information: Kim, B., et al. (2021) Rapid custom prototyping of soft poroelastic biosensor for simultaneous epicardial recording and imaging. Nature Communications. doi.org/10.1038/s41467-021-23959-3.

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Device Uses Body to Charge Wearable Tech

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A team from the National University of Singapore (NUS) has devised an innovative way to charge wearable devices such as medical monitors — by transmitting power through the body to other devices.

Advancements in wearable technology are reshaping the way we live, work and play, and also how healthcare is delivered and received. Wearable devices include wristbands, smartwatches, wearable mobile sensors, and other mobile hub medical devices that collect a large range of data from blood sugar and exercise routines to sleep and mood. 

Such devices can help patients and providers manage chronic conditions such as diabetes, heart conditions, and chronic pain. According to the Pew Research Center, 60% of US adults reported tracking their weight, diet, or exercise routine; 33% of US adults track health symptoms or indicators such as blood pressure, blood sugar, or sleep patterns; and 8% of adults specifically use medical devices, such as glucose meters.

One major obstacle of using wearables is keeping these devices properly and conveniently powered. The more wearable devices are worn, the more often there is the need to charge multiple batteries. Many users find it cumbersome to charge numerous devices every day, and inconvenient service disruptions occur when batteries run out.

A research team, led by Associate Professor Jerald Yoo from the Department of Electrical and Computer Engineering and the N.1 Institute for Health at NUS, has come up with an innovative solution to these problems. Their technology utilises the human body as a medium for power transmission, enabling a single device, such as a mobile phone placed in the pocket, to wirelessly power other wearable devices on a user’s body. The team’s novel system has an added advantage – it can harvest unused energy from electronics in a typical home or office environment to power the wearables.

Their achievement was first published in the journal Nature Electronics on 10 June 2021. It is the first of its kind to be established among existing literature on electronic wearables.

Power transmission through the body

To extend the battery life of wearable devices, power transmission and energy harvesting approaches are required. However, current approaches for powering up body area wearables are hampered by short distances, intervening obstacles and unstable power delivery. As such, none of the current methods are suitable for the sustainable provision of power to wearables placed around the entire human body.

The NUS approach turned the obstacle of the human body into an advantage by designing a receiver and transmitter system that uses the human body as a medium for power transmission and energy harvesting. Each receiver and transmitter contains a chip that is used as a springboard to extend coverage over the entire body.

The power transmitter need only be on a single power source, such as a smart watch, while multiple power receivers can be placed anywhere on the person’s body. The system then harnesses energy from the source to power multiple wearables on the user’s body via a process termed as body-coupled power transmission. In this way, only one device needs to be charged, and the rest of the wearable devices can be powered from that source. The team’s experiments showed that a single, fully-charged power source to power up to 10 wearable devices on the body, for a duration of over 10 hours.

The researchers also found that typical office and home environments have parasitic electromagnetic (EM) waves that people are constantly exposed to from sources such as running computers. To tap this energy, their novel receiver scavenges the EM waves from the environment, and through a process referred to as body-coupled powering, the human body is able to harvest this energy to power the wearable devices.

Smaller wearables without batteries

On the benefits of his team’s method, Assoc Prof Yoo said, “Batteries are among the most expensive components in wearable devices, and they add bulk to the design. Our unique system has the potential to omit the need for batteries, thereby enabling manufacturers to miniaturise the gadgets while reducing production cost significantly. More excitingly, without the constraints of batteries, our development can enable the next generation wearable applications, such as ECG patches, gaming accessories, and remote diagnostics.”

The NUS team will continue to improve the efficiency of their transmitter/receiver system, so that hopefully any given power-transmitting device such as a smartphone can extend the battery life of other wearable technologies, some of which, like medical monitors, can be quite important.

Source: National University of Singapore

Journal reference: Li, J., et al. (2021) Body-coupled power transmission and energy harvesting. Nature Electronics. doi.org/10.1038/s41928-021-00592-y. 

Categories : COVID Medical Research & TechnologyTags :

A COVID Vaccine Without the Jab

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University of Queensland scientists used a ‘patch’ to deliver a US-developed COVID vaccine without the jab, and successfully protected mice from the virus.

The vaccine candidate from University of Texas Hexapro was delivered via the high-density microarray patch (HD-MAP) and provided protection against COVID disease with a single, painless ‘click’ from a handheld applicator.

Dr David Muller, from UQ’s School of Chemistry and Molecular Biosciences, said the vaccine patch produced strong immune responses that were shown to be effective when the mice were exposed to SARS-CoV-2.

“When the Hexapro vaccine is delivered via HD-MAP applicator – rather than a needle – it produces better and faster immune responses,” Dr Muller said.

“It also neutralises multiple variants, including the UK and South Africa variants.

“And it’s much more user-friendly than a needle – you simply ‘click’ an applicator on the skin, and 5000 microscopic projections almost-imperceptibly deliver vaccine into the skin.

“The UQ team, together with Vaxxas, hope to take the technology to the world and are looking for funding opportunities to accelerate to clinical trials as soon as possible.”
Dr Muller said that Hexapro, delivered by the high-density microarray patch, could dramatically assist global vaccine rollout effort, particularly for billions of vulnerable people in low- and middle-income countries.

“We’ve shown this vaccine, when dry-coated on a patch, is stable for at least 30 days at 25 degrees Celsius and one week at 40 degrees, so it doesn’t have the cold chain requirements of some of the current options.”

High-density microarray patch (HD-MAP)

Vaxxas was founded in 2011 with the help of University of Queensland. The company’s president and CEO, David L Hoey, said he was extremely excited about the findings.

“These results are extremely clear – vaccination by HD-MAP produces much stronger and more protective immune responses against COVID-19 in model systems than via needle or syringe,” he said.

“We thank and recognise our incredible research collaborators at UQ for these important findings.

“The prospect of having a single-dose vaccine, that could be easily distributed and self-administered, would greatly improve global pandemic vaccination capabilities,” said Hoey

The research is currently undergoing peer review and has been published in BioRxiv (DOI: 10.1101/2021.05.30.446357).

Source: The University of Queensland

Categories : Medical Research & Technology Neurodegenerative DiseasesTags :

Precise Ultrasound Heating of Neurons Could Treat Neurological Disorders

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A multidisciplinary team at Washington University in St. Louis has developed a new brain stimulation technique using focused ultrasound that is able to turn specific types of neurons in the brain on and off and precisely control motor activity without surgical device implantation.

Being able to turn neurons on and off can treat certain neurological disorders such as Parkinson’s disease and epilepsy. Used for over six decades, deep brain stimulation techniques have had some treatment success in neurological disorders, but those require surgical device implantation. 

The team, led by Hong Chen, assistant professor of biomedical engineering in the McKelvey School of Engineering and of radiation oncology at the School of Medicine, is the first to provide direct evidence showing noninvasive activation of specific neuron types in mammalian brains by combining an ultrasound-induced heating effect and genetics, which they have named sonothermogenetics. It is also the first work to show that the ultrasound- genetics combination can robustly control behaviour by stimulating a specific target deep in the brain.

The results of the three years of research were published online in Brain Stimulation. 

“Our work provided evidence that sonothermogenetics evokes behavioural responses in freely moving mice while targeting a deep brain site,” Chen said. “Sonothermogenetics has the potential to transform our approaches for neuroscience research and uncover new methods to understand and treat human brain disorders.”

Chen and colleagues delivered a viral construct containing TRPV1 ion channels to genetically-selected neurons in a mouse model. Then, they delivered small pulses of heat generated by low-intensity focused ultrasound to the selected neurons in the brain via a wearable device. The heat, only a few degrees warmer than body temperature, activated the TRPV1 ion channel, which then acted as a switch to turn the neurons on or off.

“We can move the ultrasound device worn on the head of free-moving mice around to target different locations in the whole brain,” said Yaoheng Yang, first author of the paper and a graduate student in biomedical engineering. “Because it is noninvasive, this technique has the potential to be scaled up to large animals and potentially humans in the future.”

Building on prior research from his lab, professor of biomedical engineering Jianmin Cui and his team found for the first time that ion channel activity can be influenced by ultrasound alone, possibly leading to new and noninvasive ways to control the activity of specific cells. They discovered that focused ultrasound modulated the currents flowing through the ion channels on average by up to 23%, depending on channel and stimulus intensity. Following this work, researchers found close to 10 ion channels with this capability, but all of them are mechanosensitive, not thermosensitive.

The work also builds on the concept of optogenetics, the combination of the targeted expression of light-sensitive ion channels and the precise delivery of light to stimulate neurons deep in the brain. While optogenetics has increased discovery of new neural circuits, it has limited penetration depth due to light scattering, requiring surgical implantation of optical fibres to reach deeper into the brain.

Sonothermogenetics has the promise to target any location in the mouse brain with millimetre-scale resolution without causing any damage to the brain, Chen said. She and her team are further refining the technique and validating their work.

Source: Sci Tech Daily

Journal information: Yaoheng Yang et al, Sonothermogenetics for noninvasive and cell-type specific deep brain neuromodulation, Brain Stimulation (2021). DOI: 10.1016/j.brs.2021.04.021

Categories : Medical Research & Technology Skeletal SystemTags :

New Biomaterial Produced from Frog Skin and Fish Scales

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Researchers at Nanyang Technological University, Singapore (NTU Singapore) have developed a new biomaterial made entirely from discarded bullfrog skin and fish scales that could help in bone repair.

The porous biomaterial, which contains the same compounds that are predominant in bones, acts as a scaffold for osteoblasts, or bone-forming cells, to adhere to and multiply, leading to new bone formation. Bone-forming cells successfully latched onto the biomaterial and started growing, and it was found to have a low inflammatory risk.

This kind of scaffold could help regenerate bone tissue lost to disease or injury, such as jaw defects from trauma or cancer surgery. It could also assist bone growth around surgical implants such as dental implants.

The current standard practice of using a patient’s own tissues means extra surgery is needed for bone extraction. The biomaterial used, frog skin and fish scales, are a significant waste stream produced by Singapore’s aquaculture industry and using them helps repurpose this waste.

‘Waste-to-resource’

“We took the ‘waste-to-resource’ approach in our study and turned discards into a high-value material with biomedical applications, closing the waste loop in the process,” said Dalton Tay, Assistant Professor, Nanyang Technological University. “Our lab studies showed that the biomaterial we have engineered could be a promising option that helps with bone repair. The potential for this biomaterial is very broad, ranging from repairing bone defects due to injury or ageing, to dental applications for aesthetics. Our research builds on NTU’s body of work in the area of sustainability and is in line with Singapore’s circular economy approach towards a zero-waste nation.”

To make the biomaterial, the team first extracted Type 1 tropocollagen (many molecules of which form collagen fibres) from the discarded skins of the American bullfrog and hydroxyapatite (a calcium-phosphate compound) from the scales of snakehead fish, commonly known as the Toman fish.

Collagen and hydroxyapatite (HA) are two predominant components found in bones, thus conferring on the biomaterial a structure, composition, and ability to promote cell attachment similar to bone, as well as toughness.

The scientists removed all impurities from the bullfrog skin, then blended it to form a thick collagenous paste that is diluted with water, from which collagen was extracted. “Using this approach, we were able to obtain the highest ever reported yield of collagen of approximately 70 per cent from frog skin, thus making this approach commercially viable,” said Asst Prof Tay, who is also from the NTU School of Biological Sciences (SBS).

HA was harvested from discarded fish scales through calcination – a purification process that requires high heat – to remove the organic matter, and then air-dried.

The biomaterial was synthesised by adding HA powder to the extracted collagen, then cast into a mould to make a 3D porous scaffold — a two-week process which the team believes can be shortened.

Testing the biomaterial

To assess the biological performance of the porous biomaterial scaffold for bone repair, the scientists seeded bone-forming cells onto the scaffold.

The cells proliferated, and after a week, the cells were uniformly distributed across the scaffold – an indicator that the scaffold could promote proper cellular activities and eventually lead to tissue formation. The scientists also found that the presence of HA in the biomaterial significantly enhanced bone formation.

The biomaterial was also tested for its tendency to cause an inflammatory response, which is common after a biomaterial is implanted in the body.

Using real-time polymerase chain reaction, the scientists found that the expression of pro-inflammatory genes in human immune cells exposed to the biomaterial stayed “relatively modest” compared to a control exposed to endotoxins, a compound known to stimulate immune response, said Asst Prof Tay.

For instance, the expression of the gene IL6 in the biomaterial group was negligible and at least 50 times lower than that of the endotoxins-exposed immune cells. This suggests that the risk of the NTU-developed biomaterial to trigger an excessive acute inflammatory response is low.

The team is now further evaluating the long-term safety and efficacy of the biomaterial as dental products. Further research would involve studying how the body responds to this biomaterial in the long term, as well its use in other applications such as skin wounds, along with further development of the waste-to-resource pipeline.

A preprint copy of the article is available as a PDF for download.

Source: Nanyang Technical University