How to Fix Arthritis in Damaged Knee

By stimulating cells to reproduce, electricity has already been shown to help heal soft tissue injuries. Now, an electricity-producing implantable material likewise appears to boost the regrowth of cartilage in compromised joints. In a study conducted at the University of Connecticut, a team led by Asst. Prof. Thanh Nguyen and postdoctoral fellow Yang Liu explored the use of a “tissue scaffold” made out of nanofibers of a biodegradable polymer known as poly-L lactic acid (PLLA). It had previously been used to accelerate the healing of broken bones.

So-called tissue scaffolds take their name from the fact that they have a scaffolding-like three-dimensional internal structure, which acts as a sort of roosting place for adjacent cells to migrate into and reproduce. Eventually, the scaffolding dissolves and is replaced entirely by the cells, resulting in a solid piece of biological tissue.

Unfortunately, according to the scientists, joint cartilage that has been regrown using conventional scaffolds has tended to be weaker than the original cartilage, causing it to quickly break down under regular use. That’s where the PLLA comes in. Along with being biocompatible, it’s also a piezoelectric material, meaning that it produces a small electrical current when mechanically stressed. Therefore, it was believed that if a tissue scaffold made of the material were to be implanted in an arthritic knee joint, it would continuously produce cartilage-boosting electricity as it was squeezed during activities such as walking. In order to test that theory, pieces of the material were placed in the injured knee joints of rabbits, which regularly hopped on a slowly-moving treadmill. It was found that after one to two months, strong, robust cartilage proceeded to grow back within the joints. By contrast, a control group that received non-piezoelectric tissue scaffolding experienced little healing of the damaged cartilage.

Importantly, the material didn’t contain any chemical growth factors, which may cause unwanted side effects. The researchers now want to test the technology on larger, older animals, and to monitor the regrown cartilage for at least a year or two.

Source: https://today.uconn.edu/

New copper surface eliminates bacteria in just two minutes

A new surface that kills bacteria more than 100 times faster and more effectively than standard copper could help combat the growing threat of antibiotic-resistant superbugs. The new copper product is the result of a collaborative research project with RMIT University and Australia’s national science agency, CSIRO, with findings just published in Biomaterials. Copper has long been used to fight different strains of bacteria, including the commonly found golden staph, because the ions released from the metal’s surface are toxic to bacterial cells. But this process is slow when standard copper is used, as RMIT University’s Distinguished Professor Ma Qian explained, and significant efforts are underway by researchers worldwide to speed it up.

The copper magnified 500,000 times under a scanning electron microscope shows the tiny nano-scale pores in the structure

A standard copper surface will kill about 97% of golden staph within four hours,” Qian said. “Incredibly, when we placed golden staph bacteria on our specially-designed copper surface, it destroyed more than 99.99% of the cells in just two minutes.” “So not only is it more effective, it’s 120 times faster.” Importantly, said Qian, these results were achieved without the assistance of any drug. “Our copper structure has shown itself to be remarkably potent for such a common material,” he said.

The team believes there could be a huge range of applications for the new material once further developed, including antimicrobial doorhandles and other touch surfaces in schools, hospitals, homes and public transport, as well as filters in antimicrobial respirators or air ventilation systems, and in face masks. The team is now looking to investigate the enhanced copper’s effectiveness against SARS-COV-2, the virus that causes COVID-19, including assessing 3D-printed samples. Other studies suggest copper may be highly effective against the virus, leading the US Environmental Protection Agency to officially approve copper surfaces for antiviral uses earlier this year.

Source: https://www.rmit.edu.au/news/

Antibody-Drug Delivery System Kills Cancer Cells With Extreme Precision

It sounds like the stuff of science fiction: a man-made crystal that can be attached to antibodies and then supercharge them with potent drugs or imaging agents that can seek out diseased cells with the highest precision, resulting in fewer adverse effects for the patient.

However, that is precisely what researchers from the Australian Centre for Blood Diseases at Monash University in collaboration with the TU Graz (Austria) have developed: the world’s first metal-organic framework (MOFs) antibody-drug delivery system that has the potential to fast-track potent new therapies for cancer, cardiovascular and autoimmune diseases.

Schematic illustration of the new MOF Antibody crystals and their ability to specifically seek out cancer cells to detect them and deliver highly potent drugs with unprecedented precision

The in vitro study showed that when MOF antibody crystals bind to their target cancer cells and if exposed to the low pH in the cells, they break down, delivering the drugs directly and solely to the desired area.

The metal-organic framework, a mixture of metal (zinc) and carbonate ions, and a small organic molecule (an imidazole, a colourless solid compound that is soluble in water) not only keeps the payload attached to the antibody but can also acts as a reservoir of personalised therapeutics. This is a benefit with the potential to become a new medical tool to target specific diseases with customised drugs and optimised doses.

The findings are now published in the world-leading journal Advanced Materials.

Source: https://www.monash.edu/

Brain Surgery Without a Scalpel

The School of Medicine from the University of Virginia (UVA) researchers have developed a noninvasive way to remove faulty brain circuits that could allow doctors to treat debilitating neurological diseases without the need for conventional brain surgery. The UVA team, together with colleagues at Stanford University, indicate that the approach, if successfully translated to the operating room, could revolutionize the treatment of some of the most challenging and complex neurological diseases, including epilepsy, movement disorders and more. The approach uses low-intensity focused ultrasound waves combined with microbubbles to briefly penetrate the brain’s natural defenses and allow the targeted delivery of a neurotoxin. This neurotoxin kills the culprit brain cells while sparing other healthy cells and preserving the surrounding brain architecture.

A new alternative to brain surgery developed at UVA can wipe out out problematic neurons, a type of brain cell, without causing collateral damage.

This novel surgical strategy has the potential to supplant existing neurosurgical procedures used for the treatment of neurological disorders that don’t respond to medication,” said researcher Kevin S. Lee, PhD, of UVA’s Departments of Neuroscience and Neurosurgery and the Center for Brain Immunology and Glia (BIG). “This unique approach eliminates the diseased brain cells, spares adjacent healthy cells and achieves these outcomes without even having to cut into the scalp.”

The new approach is called PING, and it has already demonstrated exciting potential in laboratory studies. For instance, one of the promising applications for PING could be for the surgical treatment of epilepsies that do not respond to medication. Approximately a third of patients with epilepsy do not respond to anti-seizure drugs, and surgery can reduce or eliminate seizures for some of them. Lee and his team, along with their collaborators at Stanford, have shown that PING can reduce or eliminate seizures in two research models of epilepsy. The findings raise the possibility of treating epilepsy in a carefully-targeted and noninvasive manner without the need for traditional brain surgery.

Another important potential advantage of PING is that it could encourage the surgical treatment of appropriate patients with epilepsy who are reluctant to undergo conventional invasive or ablative surgery. In a scientific paper newly published in the Journal of Neurosurgery, Lee and his collaborators detail the ability of PING to focally eliminate neurons in a brain region, while sparing non-target cells in the same area. In contrast, currently available surgical approaches damage all cells in a treated brain region.

A key advantage of the approach is its incredible precision. PING harnesses the power of magnetic-resonance imaging (MRI) to let scientists peer inside the skull so that they can precisely guide sound waves to open the body’s natural blood-brain barrier exactly where needed. This barrier is designed to keep harmful cells and molecules out of the brain, but it also prevents the delivery of potentially beneficial treatments.

The UVA group’s new paper concludes that PING allows the delivery of a highly targeted neurotoxin, cleanly wiping out problematic neurons, a type of brain cell, without causing collateral damage.

Source: https://newsroom.uvahealth.com/

Bionic Eye Soon Available

A bionic eye being developed by a team of biomedical researchers at the University of Sydney and UNSW has shown to be safe and stable for long-term implantation in a three-month study, paving the way towards human trials.

The Phoenix99 Bionic Eye is an implantable system, designed to restore a form of vision to patients living with severe vision impairment and blindness caused by degenerative diseases, such as retinitis pigmentosa. The device has two main components which need to be implanted: a stimulator attached to the eye and a communication module positioned under the skin behind the ear.

Publishing in Biomaterials, the researchers used a sheep model to observe how the body responds and heals when implanted with the device, with the results allowing for further refinement of the surgical procedure. The biomedical research team is now confident the device could be trialed in human patients.

The Phoenix99 Bionic Eye works by stimulating the retina—a thin stack of neurones lining the back of the eye. In healthy eyes, the cells in one of the layers turn incoming light into electrical messages which are sent to the brain. In some retinal diseases, the cells responsible for this crucial conversion degenerate, causing vision impairment. The system bypasses these malfunctioning cells by stimulating the remaining cells directly, effectively tricking the brain into believing that light was sensed.

Importantly, we found the device has a very low impact on the neurons required to ‘trick’ the brain. There were no unexpected reactions from the tissue around the device and we expect it could safely remain in place for many years,” said Mr Samuel Eggenberger, a biomedical engineer who is completing his doctorate with Head of School of Biomedical Engineering Professor Gregg Suaning.

Our team is thrilled by this extraordinary result, which gives us confidence to push on towards human trials of the device. We hope that through this technology, people living with profound vision loss from degenerative retinal disorders may be able to regain a useful sense of vision,” added Mr Eggenberger.

Source: https://neurosciencenews.com/

 

Microrobot Fish Swims Through the Body to Vomit Drugs on cancer

Delivering chemotherapy drugs directly to cancers could help reduce side effects, and soon that job could be done by tiny 3D-printed robotic animals. These microrobots are steered by magnets, and only release their drug payload when they encounter the acidic environment around a tumor.

A new microrobot fish could one day swim through the body with a mouthful of drugs, and automatically spit them up when it encounters cancer cells

The new microrobots are made of hydrogel 3D printed into the shape of different animals, like a fish, a crab and a butterfly, with voids that can carry particles. The team adjusted the printing density in specific areas, like the edges of the crab’s claws or the fish’s mouth, so that they can open or close in response to changes in acidity. Finally, the microrobots were placed in a solution containing iron oxide nanoparticles to make them magnetic.

The end result was microrobots that could be loaded up with drug nanoparticles and steered towards a target location using magnets, where they would release their payload automatically due to changes in pH levels.

In lab tests, the researchers used magnets to guide a fish microrobot through simulated blood vessels, towards a cluster of cancer cells at one end. In that area, the team made the solution slightly more acidic and the fish opened its mouth and spat out the drugs on cue, killing the cancer cells. In other tests, crab microrobots could be made to clasp drug nanoparticles with their claws, scuttle to a target location, and release them.

Source: https://newatlas.com/

How to Repair Severe Spinal Cord Injuries

Northwestern University researchers have developed a new injectable therapy that harnessesdancing molecules” to reverse paralysis and repair tissue after severe spinal cord injuries. In a new study, researchers administered a single injection to tissues surrounding the spinal cords of paralyzed mice. Just four weeks later, the animals regained the ability to walk.

By sending bioactive signals to trigger cells to repair and regenerate, the breakthrough therapy dramatically improved severely injured spinal cords in five key ways: (1) The severed extensions of neurons, called axons, regenerated; (2) scar tissue, which can create a physical barrier to regeneration and repair, significantly diminished; (3) myelin, the insulating layer of axons that is important in transmitting electrical signals efficiently, reformed around cells; (4) functional blood vessels formed to deliver nutrients to cells at the injury site; and (5) more motor neurons survived. After the therapy performs its function, the materials biodegrade into nutrients for the cells within 12 weeks and then completely disappear from the body without noticeable side effects.

 

A new injectable therapy forms nanofibers with two different bioactive signals (green and orange) that communicate with cells to initiate repair of the injured spinal cord.

Our research aims to find a therapy that can prevent individuals from becoming paralyzed after major trauma or disease,” said Northwestern’s Samuel I. Stupp, who led the study. “For decades, this has remained a major challenge for scientists because our body’s central nervous system, which includes the brain and spinal cord, does not have any significant capacity to repair itself after injury or after the onset of a degenerative disease. We are going straight to the FDA to start the process of getting this new therapy approved for use in human patients, who currently have very few treatment options.”

Stupp is Board of Trustees Professor of Materials Science and Engineering, Chemistry, Medicine and Biomedical Engineering at Northwestern, where he is founding director of the Simpson Querrey Institute for BioNanotechnology (SQI) and its affiliated research center, the Center for Regenerative Nanomedicine.

The research has been published in the journal Science. The study is now available online.

Source: https://news.northwestern.edu/

New Tesla Battery With 4680 Cells

Tesla has unveiled its latest structural battery pack with 4680 cells during a Gigafactory Berlin tour ahead of Model Y production at the new factory. The start of production at Gigafactory Berlin is not just significant for Tesla’s growth in Europe, but it will also mark the launch of an important new version of the Model Y. Tesla plans to build the new Model Y at Gigafactory Berlin on a whole new platform with its structural battery pack.

At its Battery Day event last year, Tesla not only unveiled its new 4680 battery cell but also a new battery architecture built around the new cellInspired by the aerospace innovation of building airplane wings as fuel tanks instead of building the fuel tanks inside the wings, Tesla decided to build a battery pack that acts as a body structure, linking the front and rear underbody partsCurrently, Tesla builds battery packs by combining cells into modules, which are put together to form a battery pack. That battery pack is installed into the vehicle platform.

The difference with this new concept is that Tesla is not using modules, and is instead building the entire battery pack as the structural platform of the vehicle, with the battery cells helping to solidify the platform as one big unit. Using its expertise in giant casting parts, Tesla can connect a big single-piece rear and front underbody to this structural battery pack.

This new design reduces the number of parts, the total mass of the battery pack, and therefore enables Tesla to improve efficiency and ultimately the range of its electric vehicles (412 Miles or 663 km).

Source: https://electrek.co/

DNA Is Not the Only Mode of Biological Inheritance

A little over a decade ago, a clutch of scientific studies was published that seemed to show that survivors of atrocities or disasters such as the Holocaust and the Dutch famine of 1944-45 had passed on the biological scars of those traumatic experiences to their children.

The studies caused a sensation, earning their own BBC Horizon documentary and the cover of Time – and no wonder. The mind-blowing implications were that DNA wasn’t the only mode of biological inheritance, and that traits acquired by a person in their lifetime could be heritable. Since we receive our full complement of genes at conception and it remains essentially unchanged until our death, this information was thought to be transmitted via chemical tags on genes called “epigenetic marks” that dial those genes’ output up or down. The phenomenon, known as transgenerational epigenetic inheritance, caught the public imagination, in part because it seemed to release us from the tyranny of DNA. Genetic determinism was dead.

A model of DNA methylation – the process that modulates genes. The influence of environment or lifestyle on this process is being studied

A decade on, the case for transgenerational epigenetic inheritance in humans has crumbled. Scientists know that it happens in plants, and – weakly – in some mammals. They can’t rule it out in people, because it’s difficult to rule anything out in science, but there is no convincing evidence for it to date and no known physiological mechanism by which it could work. One well documented finding alone seems to present a towering obstacle to it: except in very rare genetic disorders, all epigenetic marks are erased from the genetic material of a human egg and sperm soon after their nuclei fuse during fertilisation. “The [epigenetic] patterns are established anew in each generation,” says geneticist Bernhard Horsthemke of the University of Duisburg-Essen in Germany.

Different people define epigenetics differently, which is another reason why the field is misunderstood. Some define it as modifications to chromatin, the package that contains DNA inside the nuclei of human cells, while others include modifications to RNA. DNA is modified by the addition of chemical groups. Methylation, when a methyl group is added, is the form of DNA modification that has been studied  most, but DNA can also be tagged with hydroxymethyl groups, and proteins in the chromatin complex can be modified too.

Researchers can generate genome-wide maps of DNA methylation and use these to track biological ageing, which as everyone knows is not the same as chronological ageing. The first such “epigenetic clocks” were established for blood, and showed strong associations with other measures of blood ageing such as blood pressure and lipid levels. But the epigenetic signature of ageing is different in different tissues, so these couldn’t tell you much about, say, brain or liver. The past five years have seen the description of many more tissue-specific epigenetic clocks.

Mill’s group is working on a brain clock, for example, that he hopes will correlate with other indicators of ageing in the cortex. He has already identified what he believes to be an epigenetic signature of neurodegenerative disease. “We’re able to show robust differences in DNA methylation between individuals with and without dementia, that are very strongly related to the amount of pathology they have in their brains,” Mill says. It’s not yet possible to say whether those differences are a cause or consequence of the pathology, but they provide information about the mechanisms and genes that are disrupted in the disease process, that could guide the development of novel diagnostic tests and treatments. If a signal could be found in the blood, say, that correlated with the brain signal they’ve detected, it could form the basis of a predictive blood test for dementia.

Source: https://www.theguardian.com/

How to Replace the Neurons that Die off in Parkinson’s Disease

When disease or old age ravage the body, it would be great to turn back the clock by swapping out the damaged cells, replacing them with new ones, like for like. Pluripotent stem cells (PSCs) self-replicate and have the potential in the human body to develop into almost any cell type. As such, they have long held potential in the development of regenerative medicines. But obtaining a steady supply of PSCs proved challenging for a number of reasons.

In 2006, researchers introduced a method to reprogram adult cells into a pluripotent state. These induced pluripotent stem cells (iPSCs) could then be coaxed to differentiate into different cell types. Fifteen years on, iPSC technology has become the basis for many drug development efforts, and it could one day change the outlook for millions of people.

iPSC-based therapies could replace, for example, the neurons that die off in Parkinson’s disease or the retinal tissue damaged by macular degeneration. Or perhaps they could obviate the need for a heart transplant. The technology is a marked change for big pharma.

Neurons, derived from stem cells, have potential to replace those lost to Parkinson’s disease. But delivering the cells, and ensuring they survive and integrate, are still big challenges

This is a completely different way of looking at medicine—replacing diseased cells rather than drugging them. And we’re right on that precipice,” says Seth Ettenberg, Chief Executive Officer of BlueRock Therapeutics, a biotechnology company headquartered in Cambridge, MA, and a Bayer subsidiary. “It’s an incredibly exciting time for the field.

Using tools such as gene-editing, researchers are seeking to make iPSC-based treatments more effective. The past few years have seen significant progress in the development of treatments.

Parkinson’s disease (PD) is a neurodegenerative disorder that affects more than ten million people worldwide, characterized by the progressive loss of dopamine-producing midbrain neurons, which causes tremors and other motor and neurological symptoms. Mainstay treatments can alleviate symptoms, but do not halt disease progression.

Researchers hope that iPSC-based therapies could replace the neurons killed as Parkinson’s disease progresses. Dopamine-producing neurons derived from iPSCs have been shown to improve behaviour in a rat model of PD. In one patient, dopamine cells from autologous iPSCs seemed to stabilize or even slightly improve motor symptoms 18-24 months after transplantation.

The brain is a difficult organ to access, however. “Cells will be administered to the midbrain via neurosurgery using devices designed to ensure cells are not damaged during delivery,” says Stefan Frank, associate director of Bayer’s iPSC platform strategy. “The cells then need to stay there, survive and integrate.”

Source: https://www.nature.com/