Medical Technologies

Researchers at the Terasaki Institute in Los Angeles have developed a new method to create 3D printed muscle constructs with enhanced muscle cell alignment and maturation. The technique involves creating microparticles loaded with insulin-like growth factor (IGF) using a microfluidic platform. Then, these particles are included in a bioink that also incorporates myoblast cells and a gelatin-based hydrogel. Once 3D printed, the resulting constructs show enhanced cell growth, elongation, and alignment, and in some cases even began to spontaneously contract after a ten day incubation. The Terasaki researchers hope that their innovation will help pave the way for fully functional, lab-created muscle transplants for human patients.

Skeletal muscle is clearly crucial for movement and basic activity. If such muscle becomes injured or has to be removed because of injury or disease, then a patient’s quality of life can change significantly as their ability to move and perform daily activities is affected. Moreover, other closely associated tissues, such as lymph or blood vessels, may also be affected, leading to additional complications. At present, the main treatment option is to remove healthy muscle from elsewhere in the body and transplant it to the region where it is required.  

However, this is not ideal. Not only is this strategy highly invasive, damaging healthy tissue to repair an injury elsewhere, but it can have mixed results, with issues such as incomplete innervation affecting the transplant performance and limiting the activity of the transplanted muscle. These issues have prompted scientists to attempt to create lab-grown alternatives using biomaterials.

3D bioprinting represents a very useful technique in this context, allowing researchers to print constructs in various shapes and sizes very rapidly. These researchers used this approach, but enhanced it with the judicious inclusion of slow-release growth factors to influence cell activity within the construct.

They included microparticles in the bioink that release IGF slowly within the construct over a period of days, helping to steer the included myoblasts cells towards a skeletal muscle phenotype. So far, the method appears to help in encouraging the cells to elongate and align, just like the real thing, and some constructs even demonstrated muscle contractions.   

“The sustained release of IGF-1 facilitates the maturation and alignment of muscle cells, which is a crucial step in muscle tissue repair and regeneration,” said Ali Khademhosseini, a researcher involved in the study. “There is great potential for using this strategy for the therapeutic creation of functional, contractile muscle tissue.”

Study in journal Macromolecular Bioscience: Enhanced Maturation of 3D Bioprinted Skeletal Muscle Tissue Constructs Encapsulating Soluble Factor‐Releasing Microparticles

Via: Terasaki Institute

Researchers at RMIT in Australia have developed a drug-free approach to kill bacteria and fungi that can infect surfaces on medical implants. Such pathogens can cause serious and difficult-to-treat infections around medical implants, sometimes requiring the removal of the implant. In addition, many microbes are increasingly resistant to common antibiotics, highlighting the need for drug-free approaches. This new technique is inspired by the nanopillars present on dragonfly wings, which can skewer microbial cells, killing them. The researchers used a relatively simple plasma etching technique to create such nanopillars on titanium surfaces, and tested their ability to kill multi-drug resistant Candida cells, a fungal pathogen behind many medical device infections.      

Medical implants can rectify many unfortunate clinical situations, but they can also harbor microbes that can colonize the surfaces of the device after implantation. This typically leads to a nasty infection, which is often complicated by biofilm formation, and may require the eventual removal of the implant. Antimicrobial drug resistance is a further complication, and this has inspired these researchers to create a drug-free surface modification that can kill microbes indiscriminately.

They used a plasma etching technique to create tiny pillars on titanium, which is used in many medical implants. The tiny spikes are approximately the height of a bacterial cell, and when a cell settles on the surface, the spikes can lead to perforations in the cell that can cause its death. In studies so far, the researchers have shown that if the cell does not die outright, it will still perish a little later because of the damage it sustained.

“The fact that cells died after initial contact with the surface — some by being ruptured and others by programmed cell death soon after — suggests that resistance to these surfaces will not be developed,” said Elena Ivanova, a researcher involved in the study. “This is a significant finding and also suggests that the way we measure the effectiveness of antimicrobial surfaces may need to be rethought. This latest study suggests that it may not be entirely necessary for all surfaces to eliminate all pathogens immediately upon contact if we can show that the surfaces are causing programmed cell death in the surviving cells, meaning they die regardless.”

An intact Candida cell on polished titanium surface (left), and a ruptured Candida cell on the micro-spiked titanium surface (right).

While it is easy to visualize the antimicrobial activity as a simple skewering action, it is more like a stretching action, as the cells are pulled by different pillars. “It’s like stretching a latex glove,” said Ivanova. “As it slowly stretches, the weakest point in the latex will become thinner and eventually tear. This new surface modification technique could have potential applications in medical devices but could also be easily tweaked for dental applications or for other materials like stainless steel benches used in food production and agriculture.”     

Study in journal Advanced Materials Interfaces: Apoptosis of Multi‐Drug Resistant Candida Species on Microstructured Titanium Surfaces

Via: RMIT

Researchers at ETH Zurich have developed an insulin delivery system that relies on music as a trigger. The unusual technology is based on calcium ion channels that typically reside in the cell membrane. Such channels are sensitive to mechanical deformation and these researchers discovered that sound waves will activate the channels. When insulin-producing cells are genetically modified to express this channel, they will experience an influx in calcium ions when music is played close by, prompting them to release insulin. The concept could be useful as a treatment for diabetes, whereby such cells, housed in a specialized capsule, are implanted in patients who can then use music externally to trigger insulin release when required.

Researchers are developing an array of advanced implantable technologies that could remove the constant struggle of those living with diabetes. While an artificial pancreas sounds cool, what about just blasting “We Will Rock You” by Queen into your belly at full volume every time you need an insulin pick-me-up?

The idea sounds bizarre, but these researchers have discovered that their sound-responsive cells are highly attuned to specific pieces of music, with the winning piece, thankfully, being the aforementioned hit by Queen. The technology is still in its infancy, but may represent an alternative route to new treatments for diabetes.

The calcium ion channel in question derives from E. coli bacteria, and is highly responsive to mechanical deformation, in this case provided by the voice of Freddie Mercury. Once opened, the channel allows calcium ions to rush into the cell, which in turn causes insulin-filled vesicles to fuse with the cell membrane and release their contents into the external environment.

So far, so good, but what if a patient with such implanted cells is exposed to “We Will Rock You” or other loud noise while going about their everyday business? Thankfully, the system requires a speaker to be placed right over the location of the cell implant, and ambient noise is highly unlikely to trigger insulin release.

In tests so far, “We Will Rock You” triggered about 70% of the onboard insulin to be released within 15 minutes, whereas other tested music produced a more modest release. The technique still requires a lot of refinement before it is likely to see use in patients, but could represent a less complex and minimally invasive way to produce on-demand insulin release.  

Study in journal The Lancet Diabetes & Endocrinology: Tuning of cellular insulin release by music for real-time diabetes control

Via: ETH Zurich

Researchers at the University of Colorado Anschutz Medical Campus have developed a technique that may spot the very early signs of Alzheimer’s disease, years before symptoms arise. The method may alert patients and clinicians to an increased risk of the disease, potentially allowing them to take steps to slow the disease progression. The method involves using a simple EEG headband while sleeping. The researchers have identified EEG signatures in aging adults that may indicate early Alzheimer’s pathology. These EEG phenomena relate to memory reactivation that occurs during sleep, and may reveal aspects of early-stage Alzheimer’s disease such as amyloid positivity and cognitive decline.

Alzheimer’s disease has significant consequences for those who experience it and those who care for them. Moreover, with our aging population, levels of Alzheimer’s disease are likely to significantly increase. Identifying the disease early is tricky, and many people are diagnosed when symptoms such as memory loss have already manifested. However, identifying the early stages of the disease may allow someone to take steps to slow its progression, and with the advent of new Alzheimer’s treatments in the future it may even be possible to avoid the disease altogether.

This latest technological development may provide such an early warning system for Alzheimer’s and has the bonus of being completely non-invasive. The system is based on simple EEG measurements that are taken during sleep, using a simple soft headband. These researchers have studied over two hundred aging adults, and correlated aspects of Alzheimer’s disease with EEG phenomena.  

“This digital biomarker essentially enables any simple EEG headband device to be used as a fitness tracker for brain health,” said Brice McConnell, MD, PhD, a researcher involved in the study. “Demonstrating how we can assess digital biomarkers for early indications of disease using accessible and scalable headband devices in a home setting is a huge advancement in catching and mitigating Alzheimer’s disease at the earliest stages.”

The EEG headband picks up phenomena during memory reactivation during sleep, which the researchers have correlated with aspects of Alzheimer’s disease. For instance, the University of Colorado team identified a relationship between slow wave-theta bursts and slow wave-sleep spindles found in EEG data with cognitive impairment, the presence of amyloid proteins and protein biomarkers of Alzheimer’s disease that are found in the cerebrospinal fluid.  

“What we found is these abnormal levels of proteins are related to sleep memory reactivations, which we could identify in people’s brainwave patterns before they experienced any symptoms,” said McConnell. “Identifying these early biomarkers for Alzheimer’s disease in asymptomatic adults can help patients develop preventative or mitigation strategies before the disease advances.”

Study in journal Alzheimer’s & Dementia: Mapping sleep’s oscillatory events as a biomarker of Alzheimer’s disease

Via: University of Colorado

Researchers at Nanyang Technological University in Singapore have developed a tiny, flexible battery that is intended for use in smart contact lenses. The device is as thin as the human cornea and can be charged by a saline solution, which is particularly useful in the eye, as it is full of salty tears. When the battery-equipped smart lens is not in use, such as at night, then it can be stored in a saline solution, helping to further recharge the battery. The device avoids materials that could cause damage to the eye, such as metal electrodes, and works through a glucose oxidase coating that generates current when it reacts with ions in tears, such as sodium and potassium.

Smart contact lenses that monitor our health and even treat disease could be just around the corner. However, without a reliable and safe power source, such lenses are not likely to see much use. The problem is that these lenses must be very thin, and it is also preferable to avoid materials that could cause damage to the eye if they became exposed to its naked surface. These factors put bulky, conventional batteries out of the picture.

To address this, these researchers have created a very thin battery that does not contain metal electrodes and which can actually harvest power from the eye itself, or at least the salty tears that bathe it. “The most common battery charging system for smart contact lenses requires metal electrodes in the lens, which are harmful if they are exposed to the naked human eye,” said Yun Jeonghun, one of the lead developers of the new battery. “Meanwhile, another mode of powering lenses, induction charging, requires a coil to be in the lens to transmit power, much like wireless charging pad for a smartphone. Our tear-based battery eliminates the two potential concerns that these two methods pose, while also freeing up space for further innovation in the development of smart contact lenses.”

The researchers have tested the device using a simulated human eye. So far, they have shown that the device can produce 45 microamperes in current with a maximum power of 201 microwatts, with the potential for up to 200 charge/discharge cycles.

“This research began with a simple question: could contact lens batteries be recharged with our tears?” said Lee Seok Woo, another researcher involved in the study. “There were similar examples for self-charging batteries, such as those for wearable technology that are powered by human perspiration. However, previous techniques for lens batteries were not perfect as one side of the battery electrode was charged and the other was not. Our approach can charge both electrodes of a battery through a unique combination of enzymatic reaction and self-reduction reaction. Besides the charging mechanism, it relies on just glucose and water to generate electricity, both of which are safe to humans and would be less harmful to the environment when disposed, compared to conventional batteries.”

Study in journal Nano Energy: A tear-based battery charged by biofuel for smart contact lenses

Via: Nanyang Technological University

Researchers at the Harvard Wyss Institute have developed a technique that lets clinicians to characterize and monitor melanoma. The system involves using a microneedle patch that can draw deep interstitial fluid into itself through a series of penetrating hyaluronic acid needles. The needles can later be dissolved to release the biomarkers into a test tube before analysis, using a highly sensitive technique called Simoa, to detect individual biomarker protein molecules. The Simoa method involves capturing these molecules using an antibody attached to a magnetic bead, which allows the researchers to use magnets to separate and isolate the molecules for ultimate detection. The approach could permit clinicians to easily identify which melanoma patients are more likely to respond favorably to treatments such as immunotherapies, and also monitor how treatment is progressing.     

Melanoma is a highly aggressive cancer, but has one clinical advantage of being easily accessible on the skin. This means that largely skin-specific technologies, such as microneedle patches, could be useful here. This latest research leverages this to create a microneedle patch that can assist in measuring levels of important biomarkers within melanoma lesions.

While some melanoma patients respond well to certain immunotherapies, approximately 50% do not, and even amongst those that do, treatment resistance can later emerge. Assessing which patients are likely to respond, and determining if treatment is going as planned, may require the analysis of tumor biomarkers. However, it can be difficult to extract such biomarkers from deeper layers of the skin and repeated invasive biopsies to monitor treatment progress is not desirable.

Hence, this latest microneedle patch, which can sample interstitial fluid from within a superficial tumor minimally invasively. “Rapid readout of the responses to melanoma therapy using microneedles may enable effective drug screening and patient stratification to maximize therapeutic benefits,” said Natalie Artzi, a researcher involved in the study.

So far, the researchers have tested the patch in a mouse model of melanoma, and treated the tumors using focused ultrasound and a nanoparticle-based immunotherapy. They were able to detect the rise and fall of biomarkers involved in inflammation that correlated with mouse survival.

“Merely a few microliters of interstitial fluid obtained with microneedles provide a wealth of biomarker information as normal skin cells, local immune cells, and cancer cells constantly secrete diverse signaling molecules and metabolites,” said Daniel Dahis, another researcher involved in the study. “After the microneedles are retrieved, their tips can be simply dissolved to release the captured molecules into a test tube for us to start the biomarker analysis.”

Study in journal Advanced Functional Materials: Monitoring Melanoma Responses to STING Agonism and Focused Ultrasound Thermal Ablation Using Microneedles and Ultrasensitive Single Molecule Arrays

Via: Wyss Institute

Researchers at the National University of Singapore have developed a highly sensitive pressure sensor that can provide haptic feedback for surgeons using laparoscopic tools or for use in robotic grippers as part of robotic surgical systems. The technology is inspired by the surface of the lotus leaf, which is extremely sensitive to the pressure exerted by tiny drops of water and will repel them. This sensor is also highly sensitive, using an incorporated layer of air to detect tiny pressure changes, and a surface coating inside to reduce friction. Called “eAir”, the devices can also be highly miniaturized to just a few millimeters in size, making them well suited for inclusion in laparoscopic devices.

“Conducting surgeries with graspers presents its unique challenges,” said Benjamin Tee, a researcher involved in the study. “Precise control and accurate perception of the forces applied are critical, but traditional tools can sometimes fall short, making surgeons rely heavily on experience, and even intuition. The introduction of soft and readily integrable eAir sensors, however, could be a game-changer.”

These researchers were inspired to develop a new pressure sensor for use in minimally invasive surgery and also potentially to monitor intracranial pressure. Conventional pressure sensors tend to be bulky, inconsistent in their measurements and they are often made using stiff materials that inhibit their sensitivity.  

“When surgeons perform minimally-invasive surgery such as laparoscopic or robotic surgery, we can control the jaws of the graspers, but we are unable to feel what the end-effectors are grasping,” Kaan Hung Leng, a surgeon who is familiar with the research. “Hence, surgeons have to rely on our sense of sight and years of experience to make a judgement call about critical information that our sense of touch could otherwise provide.”

The Singapore team were inspired by the sensitivity of lotus leaves to tiny falling water droplets, whereby the leaves repel the droplets quickly. “The sensor, akin to a miniature ‘capacity meter’, can detect minute pressure changes — mirroring the sensitivity of a lotus leaf to the extremely light touch of a water droplet,” said Tee.

“The haptic or tactile feedback provided by smart pressure sensors has the potential to revolutionize the field of minimally-invasive surgery,” said Hung Leng. “For example, information about whether a tissue that is being grasped is hard, firm or soft provides an additional and important source of information to aid surgeons in making prudent decisions during a surgery. Ultimately, these intra-operative benefits have the potential to translate into improved surgical and patient outcomes.”

Study in journal Nature Materials: Frictionless multiphasic interface for near-ideal aero-elastic pressure sensing

Via: National University of Singapore

Researchers at the University of California San Francisco have developed a brain computer interface that can lets someone with severe paralysis communicate with both speech and facial expressions, in the form of a digital avatar. The breakthrough advances what has been possible, with previous brain computer interface systems providing speech only, and allows people to communicate more completely, encompassing facial expressions, which are an important aspect of natural communication. The system includes electrodes that intercept brain signals that are intended for the muscles of the face, essentially decoding complex facial expressions.

Brain computer interfaces have provided a window into the minds of those with severe paralysis who may otherwise struggle to communicate, or who may not be able to communicate at all. Controlling motorized wheelchairs and other robotic assistance devices is one aspect of such technologies, but communication remains one of the most important.

Despite this, to date, brain computer interfaces have focused on offering basic speech capabilities. However, human communication is more sophisticated than basic speech, and includes a myriad of complex facial expressions and other body language. In this latest development, these researchers have pioneered the use of a digital avatar as a means for a severely paralyzed woman to communicate using a repertoire of facial expressions that accompany speech.

Moreover, the new system can decode these brain signals at a speed of 80 words per minute, which is a marked improvement in speed over pre-existing commercial technologies. The researchers attached electrodes to areas of the participant’s brain that are involved in speech and facial expressions, and trained the system over time to recognize the signals that corresponded to certain words and facial expressions.

“The accuracy, speed and vocabulary are crucial,” said Sean Metzger, a researcher involved in the study. “It’s what gives a user the potential, in time, to communicate almost as fast as we do, and to have much more naturalistic and normal conversations.”

Here’s a video from UCSF about the technology:

Study in journal Nature: A high-performance neuroprosthesis for speech decoding and avatar control

Via: UCSF

Researchers at the University of Edinburgh have developed a new method to create multilayered tubes from cells. The technique could be very useful for recreating multilayered tubular constructs that are found in the body, such as the intestines and blood vessels. Accurately modeling such complex structures in the lab could open new doors in terms of medical research and may even pave the way for bioengineered intestinal or vascular constructs that are suitable for implantation in human patients.

The method is called rotational internal flow layer engineering (RIFLE), and is low-cost, rapid and can be used to create constructs on a small scale. In essence, the technique involves delivering cells in a liquid suspension to a tube that is spinning at high speed (9000 rpm). The resulting centrifugal force causes the cell suspension to spread over the internal surface of the tube, where the cells can settle and form a monolayer, with additional cell layers being added iteratively.

Our bodies are full of complex structures that are set to keep scientists busy over the following decades as they seek to recreate them in the lab. While this is a challenge, creating transplantable organs on the lab bench is a worthwhile goal, given the shortage of available transplants, and should also make medical research easier and avoid the need to use experimental animals to find new treatments.

This is the goal of RIFLE, which aims to recreate the layered, tubular structures within our bodies, such as the intestine or blood vessels. The technology uses a spinning tube to distribute a cell suspension all over its internal surface, creating a cell layer that is just one cell thick. Then, a new layer can be added on top, allowing the researchers to create multilayered constructs.  

“With the RIFLE technology, we can create, in the laboratory, the high-resolutions that we observe in human layered tubular tissue, such as blood vessels,” said Ian Holland, a researcher involved in the study. “Crucially, this uses the same materials and cells we find in our own bodies. This level of accuracy is essential for researchers who want to develop new medicines and investigate diseases — ultimately reducing the need for experiments involving animals.”

Study in journal Biofabrication: Stratified tissue biofabrication by rotational internal flow layer engineering

Via: University of Edinburgh

Researchers at Stanford University have developed a new type of cancer therapy. The technology targets mucins, sugar-coated proteins that help cancer cells to metastasize and avoid the immune system. In particular, mucins enable cancer cells to survive free-floating as they travel through the blood during metastasis and can also trick immune cells into assuming that the cancer cell is not a threat. The new treatment involves combining an enzyme called mucinase with a cancer-specific nanobody that can bind to the cell surface, allowing the mucinase to destroy any mucins present. In tests with mice with simulated breast and lung cancer, the treatment significantly reduced tumor growth and enhanced survival.     

Cancer cells employ a variety of tricks to ensure their survival and growth. One involves mucins, a common sugar-coated protein that is found on the surface of many cell types. “Mucins play important roles throughout the body, such as forming mucus in our gut and lungs, and protecting us from pathogens,” said Gabrielle Tender, a researcher involved in the study. “Cancers dial this natural process up to 11, hijacking the functions of mucins to protect themselves and spread throughout the body.”

In cancer cells, mucins assist in allowing the cell to live as it floats freely through the blood vessels and finds a new site to create a metastatic tumor. Ordinarily, cells from solid tumors are more accustomed to surviving within a solid tissue mass, so this role for mucins is crucial in metastasis. Mucins also act as camouflage against the immune system, helping cancer cells to evade destruction.

Mucins are ubiquitous within the body, and so don’t represent a good drug target on their own. However, by combining a bacterially derived mucinase, an enzyme that can cleave mucins off the cell surface, with a cancer-targeting nanobody, the researchers ensured that their treatment would not target healthy cells.

So far, in tests with mice with simulated lung and breast cancer, the treatment successfully slowed tumor growth and enhanced mouse survival. “We have decades of evidence from cancer patients and experiments that mucins are important in cancer, but there was not that much that we could previously do to get rid of these mucins,” said Tender. “We were inspired that we finally have an approach to degrade mucins on cancer cells.”    

Study in journal Nature Biotechnology: Design of a mucin-selective protease for targeted degradation of cancer-associated mucins

Via: Stanford University