Nanomedicine – Techso Mogro https://techsomogro.com/ Science, Technology and the Future Fri, 05 May 2023 17:54:40 +0000 en-US hourly 1 https://wordpress.org/?v=6.5.3 Bioprinting at the Molecular Level and Even DNA https://techsomogro.com/bioprinting-molecular-biopolymers-dna-3d-printers/?utm_source=rss&utm_medium=rss&utm_campaign=bioprinting-molecular-biopolymers-dna-3d-printers https://techsomogro.com/bioprinting-molecular-biopolymers-dna-3d-printers/#respond Fri, 05 May 2023 17:54:40 +0000 https://techsomogro.com/?p=34432 Bioprinting today is changing how doctors treat patients by creating replacement parts using biomaterials that replicate bone, blood vessels and the cellular scaffolding upon which joints and ligaments can be regenerated or restored. The ink of 3D bioprinters is living and most often consists of stem cells harvested from the patient.

Researchers, however, are exploring a future where bioprinting will go below the sub-cellular level in constructing living tissue and biopolymers at a nanoscale. States Professor Seung Soo Oh, of Pohang University in South Korea, “The significance of this research lies in proving for the first time the possibility of printing 100% functionally and structurally active biopolymers in ultrafine 3D structures.”

What are biopolymers? They constitute the building blocks of cells. And now, research being done by Professor Oh and others, published recently in Advanced Science, indicates the development of technology to 3D print biopolymers molecule by molecule.

Pohang isn’t the only place where researchers are pushing the technological limits of 3D bioprinting. Back in 2018 scientists at the Lawrence Berkeley National Laboratory and UC Berkeley invented a way to synthesize DNA making DNA printing a future possibility. With the work at Pohang combined with Berkeley, we are a step closer to bioprinting DNA.

For researchers and bioengineers, the ability to 3D-print DNA opens new opportunities that can potentially revolutionize medicine. Imagine a printer that not only can produce living organs and tissues, but also DNA-specific constructs at the sub-cellular level including RNA, proteins, genes, and individual strings of nucleotides.

If unfamiliar with the term nucleotides, these are the fundamental chemical components of nucleic acids. We have named them adenine (A), thymine (T), guanine (G), and cytosine (C). They pair to form chemical bonds with A and G and C combining to form DNA strands. In other words, they are the building blocks of life as we know it here on Earth.

When you start bioprinting nucleotides, personalized medical therapies take on a whole new meaning. It means you can print healthy genes and replace defective ones that cause congenital diseases.

Where CRISPR/Cas9, also developed at UC Berkeley, gives researchers and medical practitioners the ability to cut out individual gene sequences and replace them with healthy ones, now with DNA bioprinting it becomes possible to print an entire chromosome. Imagine what this could mean in cancer treatment and for many other intractable diseases.

The bioprinting dream, however, goes even further. Using the technology will revolutionize agriculture, pharmaceuticals, manufacturing, and even the fuels we make to create energy. Reinforcing this extended capability, Professor Oh states that 3D bioprinting isn’t restricted to just the “bio.” He sees its use with “various materials with diverse optical and electrical properties, including complex materials such as quantum dots and carbon nanotubes.”

Combining the South Korean advancements in nanoscale 3D printing of biopolymers with the work at Berkeley and biomedical engineers may soon see a future where we will print genes, chromosomes, replacement organs and tissue.

This is not Frankenstein’s monster pieced together and made animate, but rather a technological advancement that will allow us to reconstruct our damaged selves from the DNA level and up and even integrate nanomachines and non-biological components.

When Ray Kurzweil first envisioned what he called the Singularity, it involved the merging of human and artificial intelligence, in other words, what Star Trek would call a “mind meld.” I don’t think Kurzweil envisioned integration at the level of DNA.

His prediction of 2045 as the date when humans would become one with our technology is still 22 years in the future. But the evolution of 3D printing of biology with technology capable of adding integrated nanosized circuits puts a new spin on what the Singularity will be and when it might occur.

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AlphaFold AI Revealing the Structure of Every Protein in our Bodies and More https://techsomogro.com/alphafold-ai-reveal-structure-protein-bodies/?utm_source=rss&utm_medium=rss&utm_campaign=alphafold-ai-reveal-structure-protein-bodies https://techsomogro.com/alphafold-ai-reveal-structure-protein-bodies/#respond Sat, 29 Jan 2022 17:03:58 +0000 https://techsomogro.com/?p=31851 A few years ago I wrote about a game created by scientists in the Institute of Protein Design at The University of Washington designed to help them understand the predictability of protein structures and their role in diseases. It was called Foldit. First conceived back in 2008, those who chose to play the game were challenged to unlock protein designs to predict the way they fold. The game is still in play 14 years later.

What is it about proteins that have gamers trying to fold them? It is the natural tendency of proteins to fold as you see from the illustration that appears at the top of this posting. The folds can get pretty intricate. The folding is anything but random because the way a protein configures itself determines how it interacts with the cells in our bodies.

If you are not aware as of yet, research on proteins has been front and centre in our battle to defeat COVID-19. So what are they? Proteins in the human body consist of a bundle of amino acids (there are 20 in our species) that fold in multiple ways. The gamers who have been playing Foldit are not only human. Artificial intelligence tools entered the gaming sphere a few years ago and the results have been astonishing.

The most successful Foldit entry has been the British company DeepMind who in 2018 created AlphaFold. When it started playing the game it solved 25 of 43 protein-folding problems fairly easily. The nearest human competitor solved only three.

How does AlphaFold work? It uses two neural networks, the first focused on predicting distances between pairs of specific amino acids, and the second evaluating the possible angles of the chemical bonds between them. AlphaFold has been a success and now its creators are advancing its protein folding capabilities beyond gaming.

A story appearing in MIT Technology Review in the summer of last year described how AlphaFold was being used to predict the shapes of almost every protein in the human body along with hundreds of thousands of proteins found in other animals and plants including yeast, fruit flies and mice. At the time of publication of the MIT article, DeepMind had mapped 350,000 protein structures and predicted it would have over 100 million mapped before the end of 2021. The company is providing its mapping and identification results in a database of protein structures that researchers can download and study.

Meanwhile, in a parallel undertaking, The University of Washington, the creators of Foldit have been working on the Audacious Project to design and test millions of synthetic proteins to help address and solve five major challenges.

  1. The building of better vaccines for pathogens such as influenza and coronaviruses.
  2. Expanding beyond the 20 amino acids limit in designing new proteins borrowing from the more than 500 others found in nature.
  3. The creation of advanced protein containers for targeted drug delivery (adenovirus containers and mRNA colloidal nanoparticle-based vaccine delivery systems represents the outcome of this type of research already yielding results in the new vaccines we have seen developed in the last two years to address the COVID-19 pandemic).
  4. The designing of smart proteins that can identify and help target cancer and other unhealthy cells in our bodies.
  5. And finally, the making of new nanomaterials for manufacturing (a good example where this can be applied is in improving the energy conversion efficiency of solar photovoltaics through the incorporation of nanofabricated new materials and production techniques).

 

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Technology That Restores Our Sense of Touch After a Loss of Limb or Other Injury https://techsomogro.com/technology-restores-sense-touch-loss-limb-injury/?utm_source=rss&utm_medium=rss&utm_campaign=technology-restores-sense-touch-loss-limb-injury https://techsomogro.com/technology-restores-sense-touch-loss-limb-injury/#respond Sat, 24 Jul 2021 15:56:36 +0000 https://techsomogro.com/?p=30784 Researchers at the Department of Biomedical Engineering, Tel Aviv University, along with collaborators from the Sagol School of Neuroscience, the Sackler School of Medicine, and the Sheba Medical Center in Israel, have invented a tiny sensor that is implantable in a damaged limb which can then be connected directly to the nearest healthy nerve to restore the sensation of touch.

Restoring damaged nerves from an injury is difficult. You cannot easily suture broken nerve ends and make them reconnect. I’ll give you an example from personal experience. I broke my legs in a tobogganing accident when I was in university. After multiple surgeries to rebuild the broken weight-bearing bones of my left limb, my nerves from the mid-point below my knee to the ankle no longer worked. This didn’t impede me from walking but I constantly had to pay attention to bumping into things, or accidentally burning or cutting myself on that leg because I couldn’t feel a thing.

That’s the problem this Israeli team of biomedical engineers and medical doctors decided to tackle. They looked at the most recent research into neural prostheses which use sensors to connect severed nerves. But the existing solutions required external power sources. In other words, a battery.

For restoring the sense of touch in a finger, a battery was seen as impractical. So the research team at Tel Aviv University decided to develop a triboelectric nanogenerator, called a TENG. The TENG could be powered by the body’s own movements and nerves. Connecting it directly to a healthy nerve, therefore, would restore sensation.

The TENG is an implantable piezoelectric sensor powered by natural frictional forces. The sensor consists of two tiny plates, each 0.5 centimetres square. When frictional forces cause them to come into contact an electric charge is transmitted to the connected undamaged nerve. If implanted for an injured finger, the frictional tension can vary based on whether the person is using a firm or weak touch.

The TENG can be implanted anywhere in a body to restore tactile sensation. It is built from biocompatible materials so it is well tolerated. So far the team hasn’t used a human subject. But in test animals, they have used the TENG to restore normal walking despite motor nerve damage. In the near future, TENG sensors will be used in a clinical trial with human patients to restore feeling in their fingers.

States Dr. Ben M. Maoz at Tel Aviv University, “Restoring this ability can significantly improve people’s functioning and quality of life, and more importantly, protect them from danger. People lacking tactile sensation cannot feel if their finger is being crushed, burned or frozen.”

The research and invention are described in a journal article that appeared on June 17, 2021, in ACS Nano. The article is entitled, “Restoring Tactile Sensation Using a Triboelectric Nanogenerator.”

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Is Aging a Pandemic Equivalent to COVID-19? Not Really While Researchers Show Us 100 May be the “New 60” https://techsomogro.com/is-aging-a-pandemic-equivalent-to-covid-19/?utm_source=rss&utm_medium=rss&utm_campaign=is-aging-a-pandemic-equivalent-to-covid-19 https://techsomogro.com/is-aging-a-pandemic-equivalent-to-covid-19/#respond Thu, 11 Jun 2020 15:34:55 +0000 https://techsomogro.com/?p=29536

June 11, 2020 – About a week ago I received an e-mail blast from Peter Diamandis, of X-Prize fame, in which he stated that the world is facing two pandemics: the first COVID-19, the second, aging. Aging has been with us as a species from the moment humans emerged from the tree of life. Calling it a pandemic seems facile. It’s like calling erectile dysfunction a disease in men rather than a sign of aging. But nonetheless, the biopharmaceutical industry and scientific community are tackling aging as if it were a disease.

In Peter’s e-mail he reviewed the technologies on the cutting edge that could add 20 to 30 healthy years to the lifespan of the average human. He describes 100 as the new 60 in the coming decades.

On this planet today live 7.8 billion humans of which 9% are over the age of 65. That’s approximately 720 million of us who have reached a point where the accumulations of our life’s journey has piled up leaving us with chronic health problems like heart and respiratory diseases, cancer, arthritis, dementia, and other conditions. These problems don’t start the day we turn 65. They are acquired over a lifetime and some believe they are symptoms of larger condition called aging. Peter argues that science and medicine is only now beginning to recognize the spectrum of conditions as being within the overall disease called aging.

Should we accept the natural limits of our species? And if we do, just what are these limits? Is it 90, 100, 110, or more? Many species on this planet outlive us. Bowhead whales can live for 200 years, and Greenland Sharks,  Sea Turtles, and some land tortoises can make it to 400 years or more. And then there are trees that can live thousands of years. What is innate in them that is not in us? Peter asks if this is a hardware or software problem, and if so, don’t we already have sufficient knowledge and the tools necessary to repair both?

On this blog site we write about some of these tools such as CRISPR, stem cells, gene drives, and more. Dr. David Sinclair of Harvard Medical School, in his book Lifespan, believes the technologies we have or are in the process of maturing will allow people born today to live to 120 in good health, and even make it to 150 or more. These tools include:

  1. CRISPR & Gene Therapy
  2. Stem Cell Therapy
  3. Wnt Pathway Manipulation
  4. Senolytic Medicines

CRISPR & Gene Therapy

Aging happens because our normal cell functions over a lifetime begin to destabilize. When cells no longer have the capacity to thrive they experience apoptosis, cell death. But in using gene therapy tools there is no reason for specific cells in our bodies to die. And with CRISPR-Cas9, we can go into our DNA and edit it inside the cell to provide a repair kit for almost any problem.

Today we can re-engineer our DNA instructions by target specific areas of the genome, snipping out bad code, and inserting a healthy bit of replacement instructions. CRISPR is cheap, fast, and getting easier to use. Recently, scientists at the Broad Institute associated with MIT and Harvard University, unveiled CRISPR 2.0, a next-generation editor that’s extremely precise capable of changing a single nucleobase of which there are four strung out along the double helix that is the basis for life on this planet.

David Liu, a Harvard chemical biologist states, “Of more than 50,000 genetic changes currently known to be associated with disease in humans … 32,000 of those are caused by the simple swap of one base pair for another.”

Stem Cell Therapy

We are made up of more than 30 trillion cells. All of them were derived from the embryo defined as pluripotent stem cells. Our bodies contain millions of stem cells which can replace damaged tissue. As we age the number of stem cells decline.

But what if we could restore our stem cell population? What if we could take stem cells from harvested placentas and augment our stem cell population? Celularity is a company doing just this to extend life using placenta-derived stem cells.

Wnt Pathway Manipulation

A San Diego-based company, Samumed, is targeting the signaling pathways that regulate adult stem cell self-renewal and differentiation through a pathway known as “Wnt” which stands for Wingless and Int-1, pathways to allow proteins that engage the surface receptors on the cell wall to pass signals to the cell’s inner workings. Proteins are critical to executing DNA and RNA instructions and Samumed is using this normal cellular process to deliver instructions through nine new drugs to regrow cartilage, heal tendons, remove wrinkles, stop a multitude of cancers, and reverse Alzheimer’s.

Senolytic Medicines

Our body’s cells have a limited shelf life. They can divide approximately 50 times before dying, a condition called apoptosis. But what if we could end programmed cellular death without unintended consequences?

In our body today a small fraction of our cells are senescent cells that don’t go through an end of life with damaging consequences for our bodies. These cells secrete molecules that trigger inflammatory responses and change the behaviour of nearby cells. They are associated with many of the symptoms of aging including fibrosis, blood vessel calcification, osteoarthritis, and diminished organ function.

Unity Biotechnology is a Brisbane, California company focused on developing senolytic therapies with a goal to eliminate senescent cells associated with osteoarthritis, pulmonary diseases, and other aging conditions. They have under development a number of senolytic medications aimed at musculoskeletal, ophthalmology, pulmonary, neurology, and multiple organ aging challenges.

One of their drugs under development, UBX0101, is being evaluated for the treatment of osteoarthritis of the knee. That got me interested. ApparentlyUBX0101 is a small molecule inhibitor of the MDM2/p53 protein to trigger the elimination of senescent cells. In Phase 1 clinical trial, with patients suffering from moderate to severe osteoarthritis of the knee, initial results announced in June of last year showed promising improvements in pain and function. That’s not a cure, but for someone suffering from osteoarthritis of the knee, those two improvements would be a welcome relief.

 

 

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Advances in Pharmacology Show How AI, New Ways to do Protein Folding and Nanotechnology Are Game Breakers https://techsomogro.com/advances-pharmacology-show-ai-nanotechnology-game-breakers/?utm_source=rss&utm_medium=rss&utm_campaign=advances-pharmacology-show-ai-nanotechnology-game-breakers https://techsomogro.com/advances-pharmacology-show-ai-nanotechnology-game-breakers/#respond Thu, 19 Dec 2019 16:54:22 +0000 https://techsomogro.com/?p=28659 December 19, 2019 – The following posting is inspired by a recent Peter Diamandis e-mail blast in which he discusses the changes happening in biopharmacology because of the proliferation of information in the form of massive amounts of data and new technologies. Among these innovations were new ways of applying artificial intelligence (AI) to the development of new pharmaceuticals and our uncovering of new nanoscience and a better understanding of the role of proteins in finding cures for many of the most intractable diseases. So without further ado, I will use some of Peter’s words along with some additions from me to explain.


GANs and New Pharmaceuticals

Around 2012, a computer scientist-turned-biophysicist, Alex Zhavoronkov, noticed that AI was getting better at image, voice, and text recognition. He knew that all three tasks shared a critical commonality, massive datasets available to use to train the AI. By 2014, Zhavoronkov was using the technology for discovering new drugs.

Zhavoronkov had heard about a new AI technique known as generative adversarial networks (GANs). How does it work? By pitting two neural networks against each other, with minimal instructions the technology could produce novel outcomes. Before this researchers were using GANs to do things like design new objects or create one-of-a-kind, fake human faces. It was Zhavoronkov who saw pharmacological possibilities. He figured GANs would allow researchers to verbally describe drug attributes in terms such as “The compound should inhibit protein X at concentration Y with minimal side effects in humans,” and then let the AI construct an appropriate molecule from scratch.

Zhavoronkov set up Insilico Medicine on the campus of Johns Hopkins University in Baltimore, Maryland, and over three years using GANs was able to develop a drug discovery engine that sifts through millions of data samples and determines the biological signature and characteristics of specific diseases. It can then identify the most promising treatment targets and generate molecules perfectly suited for them. States Zhavoronkov, “The result is an explosion in potential drug targets and a much more efficient testing process … AI allows us to do with fifty people what a typical drug company does with five thousand.”

Right now, the GANS is being used to find new drugs for cancer, aging, fibrosis, Parkinson’s, Alzheimer’s, ALS, diabetes, and many others. The first drug coming to market is a treatment for hair loss slated to start Phase I trials in 2020.

Insilico is also in the early stages of using its tools to predict the outcomes of clinical trials in advance. If successful, the technique will enable researchers to shorten the time and money spent in the traditional testing process.

Applying AI to Protein Folding

For those of you unfamiliar with the role proteins play in our bodies I refer you to an article posted on this site back in 2013 and a game called FoldIt, created by researchers at the University of Washington, which uses the collective effort of crowdsourcing to develop new protein folds. And you may not be aware that CRISPR/Cas9, the gene-editing tool taking genetic engineering mainstream, is in fact, a tool that uses a protein to excise bad genes and replace them with healthy ones. So proteins are a hot subject in the world of pharmacology today and scientists are using AI to identify new drug targets that bind with them.

Proteins consist of amino acids that fold in different ways to take on different functions. A protein containing a hundred amino acids, rather small by body standards, produces a googol-cubed-worth of potential shapes. (That’s a one followed by three hundred zeroes.)

Back in 1994, a biannual protein-folding competition was created with little success until 2018 when the creators of DeepMind turned neural networks loose on the problem. DeepMind took on the task of determining the most likely distance between a protein’s base pairs and the angles of their chemical bonds. They called their end-product, AlphaFold. In its first entry into the competition, it solved 25 of 43 protein-folding problems compared to the second-place finisher with only three.

How does AlphaFold work? It uses two neural networks, one focused on predicting distances between pairs of specific amino acids, and a second evaluating the possible angles of the chemical bonds between them. The two return a score estimating likely structures that match a compilation of known protein fragments, and the generation of completely new protein structures.

The potential implications of AI-accelerated protein folding for new pharma cannot be underestimated and what it could mean for treating patients with Huntington’s, ALS, myotonic dystrophy, and other diseases.

Targeted Drug Delivery Using Gene-Editors and Nanobots

Another theatre of war for improved drugs is in the realm of drug delivery. Converging exponential technologies are paving the way for massive implications in both human health and industry shifts. The aforementioned CRISPR stands to revolutionize synthetic biology and the treatment of genetically-linked diseases. Researchers are now demonstrating how this gene-editing tool can be applied to create materials that shape-shift on command. Think of the potential of materials that can dissolve instantaneously when stimulated, releasing a specified drug in a highly targeted location.

Then there are nanobots, micro-machines capable of providing targeted drug delivery. In a recent review of medical micro- and nanorobotics, the lead authors from the University of Texas at Austin and the University of California, San Diego found numerous successful tests of in vivo operations using medical micro- and nanorobots.

Drugs From The Future

Inefficient, slow-to-innovate, and risk-averse industries will be disrupted in the years ahead and Big Pharma is an area worth watching right now. Two areas, in particular, are getting headlines, advances in addressing longevity, and in disease prevention. The aforementioned Insilico is one of the companies leading the way.

The convergence of massive datasets, growing computational power, the rise of quantum computing, and innovations in AI, are bringing us closer to a world in which personalized drugs delivered directly to specified targets will become the standard of care. Rejuvenation biotechnology will be commercially available sooner than you think.

Zhavoronkov sees the timeline at “maybe 20 years … a reasonable horizon for tangible rejuvenational biotechnology.”

How might any of us use an extra 20 or more healthy years in our lives? What impact would that have on the world?

 

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Nanotechnology and the Future of Medicine https://techsomogro.com/nanotechnology-future-medicine/?utm_source=rss&utm_medium=rss&utm_campaign=nanotechnology-future-medicine https://techsomogro.com/nanotechnology-future-medicine/#respond Sat, 19 Oct 2019 19:06:31 +0000 https://techsomogro.com/?p=28411 October 19, 2019 – What is nanotechnology? It is technology built with parts a mere fraction of the width of a human hair, and it holds great promise for use in a wide number of fields including medicine where it seems to be catching on very quickly creating less invasive ways to diagnose and treat disease.

One of these nanotechnology breakthroughs is a category called smart pills. This technology is being used to detect cancer, diagnose Crohn’s and other inflammatory bowel diseases, detect enlarged veins that restrict the esophagus, and deliver or monitor critically needed medications. Here are just a few examples of this growing field.

The PillCam has fostered an entirely new approach to endoscopy of the small intestine. Using tiny wireless cameras no bigger than a vitamin capsule, doctors receive thousands of pictures of an area of the small intestine that traditional endoscopy procedures can’t easily reach using a tube with an enclosed video camera lens and feed inserted through the rectum or down the throat. With the PillCam, you swallow, it travels through your gut and eventually comes out with a bowel movement and can be flushed away. There is a small risk the capsule could lodge somewhere in the lining of the bowel, but the risks are far less than what can occur in traditional endoscopies.

The Vibrant Capsule is swallowed to treat chronic constipation without the use of chemicals or drugs. It provides mechanical stimulation inducing normal contractions of the large bowel.

Dose tracking pills like the Abilify Mycite can be used to record drug ingestion to ensure a patient is taking critically important medicine.

The Atmo Gas Capsule when swallowed senses oxygen, hydrogen, and carbon dioxide levels in the body’s gut in real time, and provides doctors with an invaluable tool for assessing the microbiome of the intestine.

From doing biopsies, to performing microsurgery, to tiny bots that deliver drugs to a site in the body, or seek out and destroy proteins associated with the spread of some types of cancers, these powerful and tiny tools that can enter our bodies represent a remarkable advance in medical practice.

But that’s not all. Nanotechnology is being used to turn your smartphone into a microscope capable of detecting virus particles in blood samples. And nano patches containing thousands of microneedles are being used to deliver smaller vaccine doses, causing fewer immune reactions. And nanofiber infused hydrogel bandages are being applied to stop bleeding, detect infection, and release antibiotics if needed.

The biggest remaining challenge is to get both medical professional and public acceptance of these nano-inventions. Fortunately, infographics like the one depicted below provide easily digestible information with links for those readers who want to learn more.

 

 

Is Nanotechnology the Future of Medicine?
Source: Best Health Degrees

 

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Can Nanoparticle Injections Prevent Spinal Cord Injury Paralysis? https://techsomogro.com/nanoparticle-injections-prevent-spinal-cord-injury-paralysis/?utm_source=rss&utm_medium=rss&utm_campaign=nanoparticle-injections-prevent-spinal-cord-injury-paralysis https://techsomogro.com/nanoparticle-injections-prevent-spinal-cord-injury-paralysis/#respond Wed, 17 Jul 2019 15:20:34 +0000 https://techsomogro.com/?p=27924 July 17, 2019 – Co-opting the immune response as a therapeutic approach to a traumatic injury to the spine is seen by researchers at the University of Michigan as an “EpiPen” for the central nervous system, and brain.

Not familiar with the EpiPen? Carried by tens of thousands who may experience anaphylaxis in response to an allergy, these injectors save lives. But who would have thought that you could use such a device, albeit not containing epinephrine, to deal with spinal cord injury?

University of Michigan researchers replaced the normal contents of the EpiPen with injectable nanoparticles to stop immune cells from reaching the site of a spinal cord injury. The particles, about the size of cell debris, and negatively charged, are non-pharmaceutical and therefore produce no side effects. By blocking immune cells from a trauma site, the researchers were trying to stop the natural process of inflammation, often a consequence of these cells when they arrive. The researchers found that their nanoparticles didn’t block all immune cells, just most of the ones that were inflammatory, letting ones that support tissue regrowth to get through.

The research results appear in the July 8, 2019 issue of PNAS, Proceedings of the National Academy of Sciences of the United States of America. The authors describe the administration of lactide-co-glycolide nanoparticles by site injection and the results which show a reduction in the number of pro-inflammatory immune cells. The outcome showed a 4-fold decline in immune cell infiltration and a 3-fold reduction in gliotic scarring. The nanoparticle injections increased the number of regenerating axons and myelination by up to 40% helping to restore locomotor function.

For the 250,000 to 500,000 people who each year suffer a spinal cord injury, this EpiPen approach could dramatically improve outcomes.

According to the World Health Organization, people who suffer a spinal cord injury are two to five times more likely to suffer a premature death. And such injuries carry substantial individual and societal costs. Those most at risk are young males between ages 20 and 29 with the ratio of male-to-female at least 2:1 among adults.

Treating spinal cord injury, however, has a checkered history with most patients experiencing paralysis in either the lower limbs, paraplegia or in all four, quadriplegia. And steroidal treatments at the time of the injury and after have produced complications such as sepsis, gastrointestinal bleeding, and blood clots.

Immune response complications are a known problem in medicine. In spinal cord injury as well as for chronic inflammatory responses the most common treatments have failed to deliver a long-term positive outcome. As one who suffers from osteoarthritis, a chronic inflammatory disease, I have periodically received cortisone injections to help reduce pain and inflammation. And today I use cannabis in the form of CBD oil to mitigate the pain associated with the condition.

But what about this nanoparticle EpiPen approach to treat my inflammatory disease, not just spinal cord trauma?

Diseases are known to present inflammation. Not just osteoarthritis, but rheumatoid arthritis, lupus, multiple sclerosis, and many others cause white blood cells, antibodies, cytokines, and other immunological chemicals to respond to the area of the body where the condition occurs. The problem for medical researchers is that there are dozens of immunological and inflammatory molecules and pathways throughout our bodies through which these protective agents interact with an injury site or disease presence. The loops and feedbacks of these pathways mean inflammation can turn on and off in any number of ways. For chronic inflammatory diseases, the response, however, doesn’t switch off and the swelling and pain remain a constant. Inflammatory responses include hives, itching, swelling, pain, and even anaphylaxis.

It will be interesting to follow this early research into nanoparticle injections. If they should prove effective in human trials, could this become a treatment standard for chronic inflammatory response as well as traumatic spinal cord or even brain injury? If so, this research at the University of Michigan could prove to be a significant treatment breakthrough.

 

This illustration shows the lower spine with the highlighted area indicating a location where spinal trauma could occur leading to lower-limb paralysis. (Image credit: Michigan Engineering)

 

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Is Regenerative and Personalized Treatment the Future of Medicine? https://techsomogro.com/regenerative-personalized-treatment-future-medicine/?utm_source=rss&utm_medium=rss&utm_campaign=regenerative-personalized-treatment-future-medicine https://techsomogro.com/regenerative-personalized-treatment-future-medicine/#respond Wed, 10 Jul 2019 20:54:37 +0000 https://techsomogro.com/?p=27892 July 10, 2019 – This submission comes from Josh Wardini. It is his fifth contribution to this blog site and includes some interesting content on where regenerative medicine is headed in the 21st century. 


The concept of rejuvenating our bodies through the use of stem cells is no longer a foreign idea. It comes with a degree of controversy as clinics offering stem cell treatment are popping up across the world making promises to cure diseases, restore joints, ease arthritis, and cure cancer. That promise remains tantalizing because the idea to be able to regenerate any damaged tissue in you using cells from you seems fantastic.

Why is the promise of stem cells possible?

The human body is unbelievably smart. It can recognize foreign cells and organ rejection can occur even in cases when a donor is considered to be a near-perfect match to the patient. But grow an identical heart derived from the patient’s own cells, and the results may be different. So in a world where technology is evolving to accommodate anything’s possible, why not tissue regeneration.

When did we take the first regenerative medicine steps?

It first started in 1954 with the first kidney transplant. And today, according to the Alliance for Regenerative Medicine, there are 1,060 clinical trials and 900 companies globally focused on this field. Here’s an idea of what financing for the industry currently looks like:

 

 

Are Regenerative and Personalized Medicine One in the Same? 

Not quite. Regenerative is a subset of personalized medicine, an approach that attempts to tailor-fit treatment to an individual. It is a departure from the current practice by physicians and biomedical companies of “one-size-fits-all” medicine. It could mean tailoring or developing a unique drug treatment to match a person’s DNA. With regenerative medicine the treatment is designed to allow the body to repair itself through cell, tissue, and organ replacement. The treatments are hyper-customized using a patient’s own stem cells. As you can imagine, getting this type of treatment to scale is proving to be pretty expensive. But its promise has lured close to one thousand companies to work in the field as can be seen in the graphic displayed below.

 

 

Treatments Made Possible by Regenerative and Personalized Medicine

The Alliance for Regenerative Medicine has compiled the clinical trials by medical category. The largest number are devoted to oncology followed by heart and circulatory diseases, diseases of the central nervous system, and musculoskeletal diseases. A visual breakdown of trials can be seen in the image below:

 

 

Treatments currently on the leading edge include:

  1. Reprogramming cells to fight disease. Through cellular immunotherapy, doctors are capable of altering white blood cells to attack and kill a patient’s cancer cells. Done by reprogramming cellular DNA, the treatment is succeeding with patients experiencing 100% recovery. As of 2019, this field of gene and gene-modified therapy is enjoying financing to the tune of $2.1 billion with funds for 374 ongoing clinical trials worldwide.
  2. Disease-modeling and treatment personalization. Research at Harvard’s Stem Cell Institute has reached the point where researchers are using stem cells to create tissues or organs identical to those of a patient. The ability to grow complex cultures called organoids is allowing scientists to observe disease onset and test treatments. They are examining the effects on organoids to tailor-fit treatment to the patient. The research and clinical trials are showing promise but to date, only 46 clinical trials are ongoing globally with financing capped at $14 million as of 2019.
  3. Regenerative surgery. Tissue engineering using stem cells and artificially made scaffolds is allowing scientists to maintain or restore damaged tissues and even entire organs. A great example of this is being deployed to repair damaged cartilage in knees and in treating degenerative diseases such as osteoarthritis. As of 2019, this branch of regenerative medicine has grown into an $823 million industry with 268 clinical trials currently ongoing around the world, the majority of them already in Phase II.

Regenerative is just getting started

As exciting as this burgeoning field is, the high cost involved and the cutting-edge nature of the technology is holding the field back. But the data shows that things are looking up. Research and Markets predicts a staggering 23.35% compound annual growth by 2022 compared to 2016 numbers. And experts forecast growth to $66 billion annually.

Why not? Lowered risks, minimally invasive procedures, and more efficient disease treatment and prevention should eventually guarantee lower costs and higher recovery and cure rates. Just what insurers, hospitals, and doctors want.

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Injectable Hydrogel Sustains Stem Cells for Long-Term Survival in Regenerative Therapy https://techsomogro.com/injectable-hydrogel-sustains-stem-cells-long-term-survival-regenerative-therapy/?utm_source=rss&utm_medium=rss&utm_campaign=injectable-hydrogel-sustains-stem-cells-long-term-survival-regenerative-therapy https://techsomogro.com/injectable-hydrogel-sustains-stem-cells-long-term-survival-regenerative-therapy/#respond Sat, 08 Jun 2019 19:28:54 +0000 https://techsomogro.com/?p=27782 June 8, 2019 – Dr. Deepa Ghosh and a team of researchers from the Institute of Nano Science and Technology in Mohali, Punjab, published a paper in April of this year in the journal ACS Applied BioMaterials, where they described the invention of a hydrogel designed to provide long-term survival of mesenchymal stem cells (MSC), adult stem cells that can be harvested from a patient, and used in a growing number of medical treatments.

I have a personal interest in MSC for use in treating osteoarthritis, something I have suffered from for more than 45 years. I have always been concerned about the viability of stem cell injections particularly in terms of rates of survival once transplanted into an injury site. One reason for concern is how the cells will defend themselves from the body’s natural immune system. MSC implants could be subject to attack from T-cells and other white cells that would treat their arrival as a foreign substance.

But what Ghosh and her colleagues have created is a protective transporting hydrogel shell that contains the MSC supporting the viability of the cells for as much as a month after injection. The hydrogel is a concoction of cellulose-like material and chitosan, a derivative of chitin which forms the exoskeleton of crustaceans like shrimp.

In an article appearing in yesterday’s The Hindu Business Line, Ghosh is quoted stating, “the hydrogel addresses the issue of the long- term survival of adult stem cells in simulated cultures that mimic the actual body tissue. We observed that cells survive and multiply for a period of one month, which is sufficient time for tissue regrowth.” In other words, the hydrogel doesn’t interfere with the capability of the MSC to interact with neighbouring cells and stimulate division.

Ghosh’s hydrogel, following implantation, supports normal functioning of the MSC contained within it. Subsequently the MSC secrete a growth factor called paracrine which signals nearby non-stem cells to alter behaviours. MSC injected into a knee joint protected by the Ghosh hydrogel would, as a result, in no way inhibit signaling to chondrocytes, cartilage cells, or osteocytes, bone cells, to begin to multiply. It is interesting that the two cells tested by Ghosh and her team were chondrocytes, and fibroblasts, the latter skin cells, and showed no inhibiting factors. The next step will be to apply what they have learned in the laboratory to animal studies. And if those are successful we should see human clinical trials in the near future.

The potential of the hydrogel-MSC composite injection serving as scaffolding for reconstructing knee cartilage or repairing wounds and damaged organs cannot be underestimated. The injectable’s ability to take the required shape within an injection site and provide adhesion to the surrounding tissue is a significant breakthrough that if replicable in animal and subsequent human patients, could change the way osteoarthritic joints and other injuries get treated in the near future.

 

The above illustration which appears in the journal article shows mesenchymal stem cells combined with hydrogel being injected into a wound site. The protective gel conforms to the wound and allows the stem cells to communicate with surrounding cells and begin the process of differentiation and replication. (Source: Polysaccharide-based Hybrid Self-healing Hydrogel Supports Paracrine Response of Mesenchymal Stem Cells)
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Gizmos & Gadgets: Wake Forest Researchers Build Skin Bioprinter https://techsomogro.com/wake-forest-researchers-build-skin-bioprinter/?utm_source=rss&utm_medium=rss&utm_campaign=wake-forest-researchers-build-skin-bioprinter https://techsomogro.com/wake-forest-researchers-build-skin-bioprinter/#respond Sun, 03 Mar 2019 20:43:54 +0000 https://techsomogro.com/?p=27219 March 3, 2019 – Scientists at the Wake Forest Institute for Regenerative Medicine have invented a mobile system for bio-printing skin to do on-site treatments of wounds. The technology mixes skin cells with a hydrogel for the printer’s ink and then applying the mixture to a wound providing a boost to natural healing.

In a Scientific Reports paper published on February 12th of this year entitled “In Situ Bioprinting of Autologous Skin Cells Accelerates Wound Healing of Extensive Excisional Full-Thickness Wounds,” the authors at the Wake Forest School of Medicine describe how over 7 million patients in the United States experience chronic and episodic wounds leading to $25 billion in annual expenses. Chronic wounds include diabetic, venous, and pressure ulcers. Episodic wounds come from burns and other external non-disease sources. They note that “full thickness” skin injuries are a major source of morbidity and mortality. More than 500,000 Americans annually suffer from burns requiring in-hospital treatment including skin grafts, and for the U.S. military, between 10 and 30% of combat casualties are a result of burn injuries.

The earlier skin wounds get treated leads to greater survivability from burn-related injuries. Currently, skin grafts are the gold standard but getting healthy donor grafts is fraught with potential challenges both in availability and in terms of immune rejection risks. Synthetic materials represent a substitute for grafts but they are costly and cosmetically produce less than desirable results.

A number of other types of technologies have been attempted to heal wounds and accelerate healing. These include spraying or applying liquids with skin cell tissue on wound sites to seed the healing process. The bioprinter takes the above processes several steps further.

How so?
  1. It is portable and can easily be transported.
  2. It can be used with a wide range of wound types and sizes.
  3. It can deliver multiple skin cell types precisely where needed.
  4. It is easily sterilized.
  5. It is easy to operate.
  6. It is relatively low cost.
The bioprinter consists of a handheld 3D scanner and print head with 8 nozzles each driven by its own dispensing motor. Its full reach extends to 127 centimeters (more than 4 feet) which makes it flexible to cover the entire torso of a patient. At the same time, the bioprinter form factor is small enough to easily be transported to almost any site. You can maneuver through doorframes easily. And once in position, it can be locked in place on an operating table to deliver bioprinting with high accuracy. To ensure the skin constructed is an exact fit with a patient’s wound, the bioprinter uses a real-time 3D laser scanner.
In initial comparisons with cell spraying and liquid application therapies, the bioprinter results show more rapid wound closure, reduced skin contraction, and faster healing. Human clinical trials are planned in the near future.

 

The five images seen here show the 3D bioprinter in schematics and in operation. Image (A) shows a schematic of the system. (B) breaks down the main components. (C) shows how the wounds are first scanned to obtain a topography. (D) shows the actual skin bioprinting process. And (E) shows the scanning, facilitating, and depositing of the multiple cell types delivered to the wound site. (Image credit: Wake Forest Institute for Regenerative Medicine)
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