Using body heat to speed healing 07-26

Bioinspired wound dressing contracts in response to body heat. 

Cuts, scrapes, blisters, burns, splinters, and punctures — there are a number of ways our skin can be broken. Most treatments for skin wounds involve simply covering them with a barrier (usually an adhesive gauze bandage) to keep them moist, limit pain, and reduce exposure to infectious microbes, but they do not actively assist in the healing process.

More sophisticated wound dressings that can monitor aspects of healing such as pH and temperature and deliver therapies to a wound site have been developed in recent years, but they are complex to manufacture, expensive, and difficult to customize, limiting their potential for widespread use.

Now, a new, scalable approach to speeding up wound healing has been developed based on heat-responsive hydrogels that are mechanically active, stretchy, tough, highly adhesive, and antimicrobial: active adhesive dressings (AADs). Created by researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University, the Harvard John A. Paulson School for Engineering and Applied Sciences (SEAS), and McGill University, AADs can close wounds

significantly faster than other methods and prevent bacterial growth without the need for any additional apparatus or stimuli. The research is reported in Science Advances.

“This technology has the potential to be used not only for skin injuries, but also for chronic wounds like diabetic ulcers and pressure sores, for drug delivery, and as components of soft robotics-based therapies,” said corresponding author David Mooney, a founding core faculty member of the Wyss Institute and the Robert P. Pinkas Family Professor of Bioengineering at SEAS.

AADs take their inspiration from developing embryos, whose skin is able to heal itself completely, without forming scar tissue. To achieve this, the embryonic skin cells around a wound produce fibers made of the protein actin that contract to draw the wound edges together, like a drawstring bag being pulled closed. Skin cells lose this ability once a fetus develops past a certain age, and any injuries that occur after that point cause inflammation and scarring during the healing process.

To mimic the contractile forces that pull embryonic skin wounds closed, the researchers extended the design of previously developed tough, adhesive hydrogels by adding a thermoresponsive polymer known as PNIPAm, which both repels water and shrinks at around 90 degrees Fahrenheit. The resulting hybrid hydrogel begins to contract when exposed to body heat, and transmits the force of the contracting PNIPAm component to the underlying tissue viastrong bonds between the alginate hydrogel and the tissue. In addition, silver nanoparticles are embedded in the AAD to provide antimicrobial protection.

          

“This technology has the potential to be used not only for skin injuries, but also for chronic wounds like diabetic ulcers and pressure sores, for drug delivery, and as components of soft robotics-based therapies.”

— David Mooney

“The AAD bonded to pig skin with over 10 times the adhesive force of a Band-Aid and prevented bacteria from growing, so this technology is already significantly better than most commonly used wound protection products, even before considering its wound-closing properties,” said Benjamin Freedman, a Graduate School of Arts and Sciences’ postdoctoral fellow in the Mooney lab who is leading the project.

To test how well their AAD closed wounds, the researchers tested it on patches of mouse skin and found that it reduced the size of the wound area by about 45 percent compared to almost no change in area in the untreated samples, and closed wounds faster than treatments including microgels, chitosan, gelatin, and other types of hydrogels. The AAD also did not cause inflammation or immune responses, indicating that it is safe for use in and on living tissues.

Furthermore, the researchers were able to adjust the amount of wound closure performed by the AAD by adding different amounts of acrylamide monomers during the manufacturing process. “This property could be useful when applying the adhesive to wounds on a joint like the elbow, which moves around a lot and would probably benefit from a looser bond, compared to a more static area of the body like the shin,” said co-first author Jianyu Li, a former postdoctoral fellow at the Wyss Institute who is now an assistant professor at McGill University.

The team also created a computer simulation of AAD-assisted wound closure, which predicted that AAD could cause human skin to contract at a rate comparable to that of mouse skin, indicating that it has a higher likelihood of displaying a clinical benefit in human patients.

“We are continuing this research with studies to learn more about how the mechanical cues exerted by AAD impact the biological process of wound healing, and how AAD performs across a range of different temperatures, as body temperature can vary at different locations,” said Freedman. “We hope to pursue additional preclinical studies to demonstrate AAD’s potential as a medical product, and then work toward commercialization.”

Additional authors of the paper include co-first author Serena Blacklow, a former member of the Mooney lab who is now a graduate student at the University of California, San Francisco; Mahdi Zeidi, a graduate student at University of Toronto; and Chao Chen, a former graduate student in SEAS who is now a postdoc at UMass Amherst.

This research was supported by the National Institutes of Health, The Wyss Institute for Biologically Inspired Engineering at Harvard University, the National Sciences and Engineering Research Council of Canada, the Canada Foundation for Innovation, and the Harvard University Materials Research Science and Engineering Center.

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An AI that can predict cell structures 05-12

Fluorescent-labeled cells used to train neural networks. Image: Allen Institute. 


New 3D models of living human cells generated by machine-learning algorithms are allowing scientists to understand the structure and organization of a cell's components from simple microscope images.

Why it matters: The tool developed by the Allen Institute for Cell Science could be used to better understand how cancer and other diseases affect cells or how a cell develops and its structure changes — important information for regenerative medicine.

"Each cells has billions of molecules that, fortunately for us, are organized into dozens of structures and compartments that serve specialized functions that help cells operate," says Allen Institute's Graham Johnson, who helped develop the new model.

What they did: The researchers used gene editing to label the nucleus, mitochondria and other structures inside live human induced pluripotent stem cells (iPSC) with fluorescent tags and took tens of thousands of images of the cells.

They then used those images to train a type of neural network known as Generative Adversarial Networks (GANs). That yielded a model that can predict the most likely shape of the structures and where they are in cells based on just the cell's plasma membrane and nucleus.

Using a different algorithm, they created a model that can take an image of a cell that hasn't been fluorescent-labeled — in which it's difficult to distinguish the cell's components ("it looks like static on an old TV set," Graham Johnson says) — and find the structures.

What they found: When they compare the predicted image to actual labeled ones, the Allen Institute researchers said they are nearly indistinguishable.

The advance: Gene editing and fluorescent dyes often used to study cells only allow a few components to be visualized at once and can be toxic, limiting how long researchers can observe a cell.

Plus, "knowledge gained from more expensive techniques or ones that take a while to do and do well can be inexpensively applied to everyone’s data," says the Allen Institute's Greg Johnson, who also worked on the tool. "This provides an opportunity to democratize science."

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All you need to know about agitated depression 01-2018

Depression is a persistent state of feeling hopeless, sad, or helpless. While there are some common symptoms associated with depression, people can experience depression differently.

One such example is agitated depression. Medical experts may also describe agitated depression as anxious depression or distraught depression.

Though agitated depression is not a distinct type of depression, psychiatric professionals recognize that some people have symptoms of depression as well as agitation.

Fast facts on agitated depression:

Psychiatrists do not define agitated depression as a distinct type of depression.

Agitation can be a common symptom of mood disorders.

Doctors call depression with agitation a "mixed episode" of depression.

Symptoms

Depression with agitation, is known as a "mixed episode" of depression.

Mental health professionals use a manual called the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) to diagnose mental health disorders, including depression.

By using the same criteria, doctors across America can diagnose depressive symptoms in the same way.

For a doctor to diagnose someone with depression, the person must have experienced depressed mood or a loss of interest or pleasure in life (anhedonia) for at least 2 weeks.

Also, a person will also have experienced at least five of the following symptoms:

Feelings of sadness, hopelessness, or irritability on a nearly daily basis.

Lack of interest or pleasure in activities almost every day.

Experiencing significant weight loss or appetite loss that results in weight loss.
Difficulty sleeping or sleeping excessively.

Experiencing psychomotor agitation, restlessness, or feelings of being "slowed down."

Feeling fatigued or having a lack of energy nearly every day.

Feeling worthless or having excessive and unexplained guilt almost every day.

Difficulty thinking clearly, concentrating, or making decisions on a daily basis.

Experiencing thoughts of death, thinking of harming one's self, or creating a specific plan for committing suicide.

Agitation is a symptom that can cause a person to experience feelings of uneasiness and anxiety.

Some of the symptoms associated with agitation include:

angry outbursts

clenching fists

disruptive behavior

excessive talking

feeling as if a person cannot sit still or focus
pacing or shuffling feet

tension

wringing of the hands

violent outbursts

A person who has agitated depression experiences feelings of helplessness that can make them feel out of control.

As a result, they can then feel hopeless, which may lead to depressive thoughts. Agitation can cause a person with depression to act impulsively. This could cause a person to hurt themselves or others and engage in harmful behavior.

Depression has many different methods of treatment including self-help. Learn more about the best depression blogs to manage low mood here.

A person with bipolar disorder may experience fluctuating symptoms of depression and mania (an elevated state of being).

Mania is different from agitation because mania causes a person to feel hyper, "high," or overly energetic. A person may only sleep a couple of hours each night and stay awake for extended periods.
Mania does not feel good or euphoric to every person, but it can to some people.

Causes

Depression may be caused by a significant life event, such as the loss of a family member.
Agitation is often a symptom of an underlying mood disorder and is not a condition of its own. The causes of depression itself can be varied and can occur if:

the brain does not regulate mood appropriately

a person has a family history of depression and is more vulnerable to the condition

a person has experienced significant life events that are especially stressful or sad, such as the loss of a family member or divorce

a person has several chronic medical problems

Several of these factors can contribute to depression. However, doctors do not know why a person may experience agitated depression.

A person's temperament that affects their behavior may increase the likelihood that they will experience agitation related to depression.

How is it diagnosed?

Doctors diagnose agitated depression by asking a person to describe the symptoms they are experiencing.

They may ask questions, such as when the symptoms first began, what makes the symptoms better, or what makes the symptoms worse. Sometimes a person's loved ones may also describe the changes they have observed in a person's personality.

A doctor will use the criteria from the DSM-5 to diagnose a person with major depressive disorder, but agitated depression is not diagnosed using DSM-5 criteria. A doctor will also try to rule out other similar conditions, including bipolar disorder.

How is agitated depression treated?

A psychiatrist or other mental health professional may help to treat agitated depression.

Doctors treat agitated depression with a variety of approaches.

In the first instance, a doctor may prescribe medications called sedatives or benzodiazepines.

Examples may include diazepam (Xanax) or lorazepam (Ativan). These medications work quickly to help a person feel calmer and can temporarily relieve agitation.

Additional steps include:

Medications to relieve depression: Doctors may prescribe a variety of drugs to relieve depression, including anti-depressants. If a person does not respond to these medicines, a doctor may add another drug or prescribe a different medication type entirely. Examples can include anti-anxiety medications or mood stabilizers.

Counseling: Seeing a psychiatrist or other mental health professional can help a person identify thoughts and feelings that can signal the start of agitation or depressive symptoms. Therapy can help a person focus on thoughts and behaviors that can help them feel better when they struggle with agitated depression.

Stress-relieving techniques: Relieving stress and depression through physical activity, meditation, deep breathing, and journaling can all help a person cope with feelings agitated depression.
There is no one single solution to treating agitated depression. A doctor must consider a person's unique symptoms.

They will likely take a variety of approaches, including prescribing medications and recommending therapy.

Sometimes it can take several months or even years for a person to find the right combination of medications, therapy, and stress-relieving techniques that help them live better with their agitated depression.

Takeaway

While there is no cure for agitated depression, there are many treatments that can help a person live a healthier, happier life. Although finding the right combination of treatments can take time, help is available.

If a person experiences suicidal thoughts or thoughts of self-harm, they should seek emergency medical attention. Medical professionals can help identify ways to stabilize the person medically, and reduce the risks of them injuring themselves. 

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In pursuit of healthy aging 11-07

Harvard study shows how intermittent fasting and manipulating mitochondrial networks may increase lifespan.

Manipulating mitochondrial networks inside cells — either by dietary restriction or by genetic manipulation that mimics it — may increase lifespan and promote health, according to new research from Harvard T.H. Chan School of Public Health.

The study, published Oct. 26 online in Cell Metabolism, sheds light on the basic biology involved in cells’ declining ability to process energy over time, which leads to aging and age-related disease, and how interventions such as periods of fasting might promote healthy aging.

Mitochondria — the energy-producing structures in cells — exist in networks that dynamically change shape according to energy demand. Their capacity to do so declines with age, but the impact this has on metabolism and cellular function was previously unclear. In this study, the researchers showed a causal link between dynamic changes in the shapes of mitochondrial networks and longevity.

The scientists used C. elegans (nematode worms), which live just two weeks and thus enable the study of aging in real time in the lab. Mitochondrial networks inside cells typically toggle between fused and fragmented states. The researchers found that restricting the worms’ diet, or mimicking dietary restriction through genetic manipulation of an energy-sensing protein called AMP-activated protein kinase (AMPK), maintained the mitochondrial networks in a fused or “youthful” state. In addition, they found that these youthful networks increased lifespan by communicating with organelles called peroxisomes to modulate fat metabolism.

“Low-energy conditions such as dietary restriction and intermittent fasting have previously been shown to promote healthy aging. Understanding why this is the case is a crucial step toward being able to harness the benefits therapeutically,” said Heather Weir, lead author of the study, who conducted the research while at Harvard Chan School and is now a research associate at Astex Pharmaceuticals. “Our findings open up new avenues in the search for therapeutic strategies that will reduce our likelihood of developing age-related diseases as we get older.”

“Although previous work has shown how intermittent fasting can slow aging, we are only beginning to understand the underlying biology,” said William Mair, associate professor of genetics and complex diseases at Harvard Chan School and senior author of the study. “Our work shows how crucial the plasticity of mitochondria networks is for the benefits of fasting. If we lock mitochondria in one state, we completely block the effects of fasting or dietary restriction on longevity.”

Next steps for the researchers including testing the role mitochondrial networks have in the effect of fasting in mammals, and whether defects in mitochondrial flexibility might explain the association between obesity and increased risk for age-related diseases.

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The Fight Against Antibiotic-Resistant Bacteria Might Start With Vaccines 09-04

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It seems like a major part of keeping kids healthy these days is managing their microbial exposure. On the one hand, we’re told that letting our kids get dirty and tempering our use of hand sanitizer can help cultivate a healthy population of good microbes in and on the body, which is associated with lower rates of chronic maladies like asthma and allergies. On the other hand, we know that among all the benign and beneficial bacteria in the world lurk some that are deadly, causing diseases such as whooping cough, pneumonia and meningitis.

To treat these diseases, we need antibiotics, but the downside is that antibiotics indiscriminately kill bacteria in the body, including the ones that contribute to our health. Meanwhile, every course of antibiotics gives bacteria that are resistant to the drugs a chance to grow and thrive. That makes for more antibiotic-resistant infections, all of which are harder to treat and some of which can’t be treated at all.

Ideally, we want to protect our kids from deadly bacteria without disturbing the good ones or worsening the trend of antibiotic resistance. And this is exactly what vaccines do. They give us exposure to the pathogen — be it bacterial or viral — in a weakened, killed or partial form so that we can develop immunity to it without getting the full-blown illness. If we’re exposed to the real thing later, our bodies have antibodies specific to that pathogen ready to fight back. No antibiotics needed, and our friendly microbes can continue to live in peace. But when parents choose not to vaccinate their kids, they’re increasing the kids’ chances of not only becoming seriously ill, but also of needing antibiotic treatment and other medical interventions down the road.

Dr. Joel Amundson, a pediatrician in Portland, Oregon, finds himself frequently talking about vaccines and antibiotics in the same breath. Oregon has one of the lowest immunization rates in the nation, and Amundson said many of the parents he counsels want to keep their kids “all-natural” and see vaccines as an unnecessary medical intervention. But when he explains that vaccines are a tool for decreasing medical interventions, including antibiotic use, that often changes their perspective. “That’s a huge benefit to my families,” he said, “It definitely has them more interested in doing vaccines when they understand that.”

Some parents who are reluctant to vaccinate worry about side effects, and though some kids will experience short-lived, minor reactions such as swelling at the injection site, serious side effects are extremely rare. Side effects from antibiotics, including diarrhea, rashes and allergic reactions, are generally more common and severe, Amundson said. “I see far more harm from antibiotics than I do from vaccines, by a huge margin. It’s not subtle,” he said.

Of course, when a person has a serious bacterial infection, the benefits of antibiotics far outweigh those risks, because these diseases can be deadly. “When we need them, we really need them,” said Janet Gilsdorf, professor emerita of pediatric infectious diseases at the University of Michigan. But in a world where antibiotic-resistant infections are thought to kill 50,000 people each year in the U.S. and Europe alone, a problem that the United Nations has called “the greatest and most urgent global risk,” reducing our use of antibiotics helps preserve their value. “The fewer infections we have, the fewer antibiotics we need to use, and we know that the use of antibiotics is what drives antibiotic resistance,” Gilsdorf said.

Vaccines have prevented millions of illnesses

Estimated number of infections prevented by vaccines over the lifespan of children born in the U.S. in 2009

INFECTIOUS DISEASE	CAUSED BY		CASES PREVENTED
Varicella	Virus	3,942,546	–
Measles	Virus	3,835,825	–
Pertussis	Bacteria	2,950,836	–
Pneumococcus-related diseases	Bacteria	2,323,952	–
Mumps	Virus	2,312,275	–
Rubella	Virus	1,981,066	–
Rotavirus	Virus	1,582,940	–
Diphtheria	Bacteria	275,028	–
HepB	Virus	239,993	–
HepA	Virus	153,164	–
Polio	Virus	67,463	–
Hib	Bacteria	19,606	–
Congenital rubella syndrome	Virus	632	–
Tetanus	Bacteria	169	–

Source: Pediatrics

We don’t yet have research on whether emphasizing this benefit of vaccines might encourage parents to immunize their kids. While the vast majority of parents vaccinate their kids on schedule, the number of parents who are reluctant to do so does seems to be increasing in the U.S., despite a mountain of evidence supporting the efficacy and safety of vaccines. Reasons for parents’ concerns about vaccines are varied, and each type of concern will likely need to be addressed differently to improve vaccination rates. But there’s some evidence that parents are becoming more aware of the problem of antibiotic resistance, and a study of Austrian adults found that those with more knowledge about antibiotics were more likely to get the flu vaccine.

There’s no question that vaccines have dramatically reduced the burden of disease. A study published in 2014 estimated that among U.S. children born in 2009, following the recommended childhood vaccine schedule (not including the flu vaccine) would prevent 20 million cases of disease across their lifespans, and about 30 percent of these are bacterial diseases that would likely require antibiotic treatment. These are diseases like diphtheria and pertussis, both of which were major causes of childhood illness and death before their vaccines were developed in the first half of the 20th century.

More recently, the vaccine for Haemophilus influenzae type b (Hib), which the Food and Drug Administration approved for use in toddlers starting in 1985 and infants in 1990, nearly eliminated the dangerous blood and brain infections caused by this bacteria.

Pneumococcal vaccines have also reduced our dependence on antibiotics. The first was recommended in the U.S. for infants and young children in 2000, followed in 2010 by an updated version covering more strains of the bug. Like Hib, pneumococcus bacteria can cause pneumonia and invasive blood and brain infections, but it’s also a major cause of ear infections, which are one of the biggest reasons that children are prescribed antibiotics. Before the vaccine was added to the infant immunization schedule, up to 40 percent of invasive pneumococcal infections — meaning infections that spread to parts of the body, such as the bloodstream, that are normally germ-free — were resistant to at least one antibiotic, making them more difficult and costly to treat. The first pneumococcus vaccine decreased antibiotic-resistant invasive pneumococcal infections in young children by 81 percent, and the second vaccine caused an additional 61 percent drop. (These studies looked at different age groups, however; the first included only children younger than 2, and the second looked at children up to age 4.)

Pneumococcal vaccines have also reduced our dependence on antibiotics. The first was recommended in the U.S. for infants and young children in 2000, followed in 2010 by an updated version covering more strains of the bug. Like Hib, pneumococcus bacteria can cause pneumonia and invasive blood and brain infections, but it’s also a major cause of ear infections, which are one of the biggest reasons that children are prescribed antibiotics. Before the vaccine was added to the infant immunization schedule, up to 40 percent of invasive pneumococcal infections — meaning infections that spread to parts of the body, such as the bloodstream, that are normally germ-free — were resistant to at least one antibiotic, making them more difficult and costly to treat. The first pneumococcus vaccine decreased antibiotic-resistant invasive pneumococcal infections in young children by 81 percent, and the second vaccine caused an additional 61 percent drop. (These studies looked at different age groups, however; the first included only children younger than 2, and the second looked at children up to age 4.)

The U.S., Israel and the U.K. have also observed big drops in kids’ ear infections coinciding with the introduction of pneumococcal vaccines. (Other factors, such as increased breastfeeding and tightened diagnostic criteria for ear infections, have likely contributed to these improvements, but researchers believe that the vaccines have played an important role.) In a paper published last year, researchers estimated that making the pneumococcal vaccine universally available to children in the 75 countries they looked at could not only prevent disease but also avert 11.4 million days of antibiotic treatment each year, a 47 percent drop in current antibiotic use for pneumonia.

Less obviously, vaccines that protect against illnesses caused by viruses rather than bacteria can also help cut antibiotic use. For example, influenza is viral, but flu season always brings an uptick in antibiotic prescriptions. In many cases, the antibiotics are being inappropriately prescribed, but some are necessary treatments for secondary bacterial infections, like pneumonia and ear infections, that can move in when a person’s immune system is busy fighting the virus. When Ontario, Canada, started offering free flu vaccines, the province’s rate of antibiotic prescriptions associated with the flu dropped by 64 percent.

The vaccine against measles, another viral infection, also probably decreases antibiotic use. A 2015 paper showed that a measles infection weakens a person’s immune system for two to three years, which explains why the measles vaccine reduces childhood mortality by 30 percent to 50 percent in poor countries, which can’t be explained by measles prevention alone. “Not having measles is a really good thing for your immune system in terms of preventing other infections,” said Marc Lipsitch, professor of epidemiology at Harvard T.H. Chan School of Public Health.

In a paper published last year, Lipsitch argued that development of new vaccines should be considered an important strategy in the fight against antibiotic-resistant bacteria. He believes that it would be most useful to have vaccines against certain bacterial strains that patients tend to pick up in hospitals — those strains are often resistant to multiple antibiotics. A more effective flu vaccine and a vaccine for respiratory syncytial virus, known as RSV, which sends more than 57,000 young children and 177,000 elderly people in the U.S. to the hospital each year, could also reduce antibiotic use. Potential vaccines for a number of these diseases are in various stages of clinical trials.

Lipsitch envisions vaccines that go even further. “I actually think one of the most interesting ideas I’ve had is the idea of using vaccines directly to target [antibiotic] resistant bacteria, not just all bacteria, but directly aiming at the targets that are the resistant genes.” This type of vaccine would be especially helpful for bacteria like pneumococcus and Staphylococcus aureus, which are so ubiquitous that they’re unlikely to be eliminated; keeping drug resistance at bay would help us coexist with them more peacefully. “The idea of these resistance-targeted vaccines is to try to make life extra hard for the resistant organisms,” Lipsitch said.

But would it be tough to sell people on more vaccines for both kids and adults when some people are refusing to get the vaccines we already have? “I think it ought to be a pretty easy sell, actually,” said David Salisbury, associate fellow at the Chatham House Centre on Global Health Security in London and former director of immunization at the U.K. Department of Health. “Imagine if an ear infection, which happens so commonly in children, became untreatable. You can fantasize about false risks of the vaccines, but they turn to nothing when you compare them with untreatable infections. Would you seriously prefer your child not to have a vaccine and risk an infection to which there was no treatment?”

A global challenge as big as antibiotic resistance will require multiple solutions, including reducing the use of antibiotics in agriculture and developing new antibiotics, but Salisbury says that vaccines deserve more attention and investment. Gilsdorf is on board with that. “What we need is more good science, which means we need more funding for the National Institutes of Health, the National Science Foundation, and these federal agencies that support scientists to learn the nitty-gritty of these bacteria,” she said.

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Using Stem Cells to Heal Broken Bones 06-08

A promising new method for regenerating bones using the body's own stem cells may possibly eliminate the need for bone grafts.

When a fracture will not heal, people are typically left with two options.
One is bone grafting, the other is surgery.

A new treatment that uses gene and stem cell therapies could promise success with a less-invasive procedure.

Researchers led by a team from Cedars-Sinai Medical Center in Los Angeles, tested the therapy on laboratory animals and found that it triggered bones to regrow their own tissue.

If it is found safe in humans, the process could replace bone grafting as the gold standard treatment.

“We are just at the beginning of a revolution in orthopedics,” Dan Gazit, co-director of the Skeletal Regeneration and Stem Cell Therapy Program in the Department of Surgery and the Cedars-Sinai Board of Governors Regenerative Medicine Institute, said in a statement.

The study was published in the journal Science Translational Medicine.

Bone grafts can result in gaps between fracture edges, and often require surgery to relocate bone from other places in the body to fill in the spaces.

Bone can come from the patient or a cadaver.

But healthy bone isn’t always available, and surgeries can lead to other complications.

A stem cell solution

The new method involves implanting a collagen matrix made up of bone-inducing genes into stem cells.

It is inserted into the gap over a two-week span. An ultrasound pulse and microbubbles help the matrix get into the cells.

“Our method relies on the body’s own repair cells [stem cells],” Gadi Pelled, senior author, and an assistant professor of surgery at Cedars-Sinai, told Healthline. “We recruit them to the injury site and then activate them to regenerate bone in an efficient way.”

“The uniqueness of our method is that it is injectable and minimally invasive,” Pelled said.

Researchers found that the fractures were healed eight weeks after the procedure. The bone that grew into the empty space was as strong as surgical bone grafts.

“We showed that our method was equivalent, in terms of fracture healing, to the use of an autograft [bone graft obtained from the patient’s own body], which is the gold standard today,” Gazit said. “Our method does not require the harvest of bone, which often leads to prolonged pain and hospitalization and risk of infection, and that is our advantage.”

Stem cell concerns?

Because the process uses stem cells from the patient’s body without external manipulation, it may not face many of the hurdles that other stem cell treatments come up against.

“But obviously we will need to show that our method is not toxic and is safe to use in people before it is approved for use in the clinic,” added Zulma Gazit, PhD, co-director of the Skeletal Regeneration and Stem Cell Therapy Program in the Department of Surgery and the Cedars-Sinai Board of Governors Regenerative Medicine Institute.

Moving forward

In cases where there are large gaps or fractures unable to heal, the method can be repeated to grow more bone.

That’s something that will need to be reproduced in additional studies, but the latest study is the first to show that this ultrasound-mediated gene delivery can be used to treat nonhealing bone fractures, Pelled added.

David Forsh, an assistant professor of orthopedics at the Icahn School of Medicine at Mount Sinai, and chief of orthopedic trauma at Mount Sinai St. Luke’s, said the breakthrough needs to be reproduced before it goes mainstream.

Similar research has been conducted in the past, but the way this was done is something new, according to his knowledge.

“It sounds good,” Forsh told Healthline. “It’s very promising that they were able to achieve this.”

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