How to Grow Fully Functioning Hair Follicles

We can add functional mouse hair follicles to body parts that scientists have successfully grown in the lab, outside the body. Using cells obtained from embryonic mice, for the first time researchers were able to produce hair follicle organoidssmall, simple versions of an organ – that grew hair.

Moreover, they were able to influence the pigmentation of the hair; and, when the follicles were transplanted into living hairless mice, they continued to function across multiple hair growth cycles. This research, the team says, could help aid efforts to treat hair loss, as well as provide alternative models to animal testing and drug screening.

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Sticker on the Skin Provides Clear Image of Heart, Lungs

Ultrasound imaging is a safe and noninvasive window into the body’s workings, providing clinicians with live images of a patient’s internal organs. To capture these images, trained technicians manipulate ultrasound wands and probes to direct sound waves into the body. These waves reflect back out to produce high-resolution images of a patient’s heart, lungs, and other deep organs.

Currently, ultrasound imaging requires bulky and specialized equipment available only in hospitals and doctor’s offices. But a new design by MIT engineers might make the technology as wearable and accessible as buying Band-Aids at the pharmacy. In a paper appearing today in Science, the engineers present the design for a new ultrasound sticker — a stamp-sized device that sticks to skin and can provide continuous ultrasound imaging of internal organs for 48 hours.

The researchers applied the stickers to volunteers and showed the devices produced live, high-resolution images of major blood vessels and deeper organs such as the heart, lungs, and stomach. The stickers maintained a strong adhesion and captured changes in underlying organs as volunteers performed various activities, including sitting, standing, jogging, and biking. The current design requires connecting the stickers to instruments that translate the reflected sound waves into images. The researchers point out that even in their current form, the stickers could have immediate applications: For instance, the devices could be applied to patients in the hospital, similar to heart-monitoring EKG stickers, and could continuously image internal organs without requiring a technician to hold a probe in place for long periods of time.

If the devices can be made to operate wirelessly — a goal the team is currently working toward — the ultrasound stickers could be made into wearable imaging products that patients could take home from a doctor’s office or even buy at a pharmacy.

We envision a few patches adhered to different locations on the body, and the patches would communicate with your cellphone, where AI algorithms would analyze the images on demand,” says the study’s senior author, Xuanhe Zhao, professor of mechanical engineering and civil at MIT. “We believe we’ve opened a new era of wearable imaging: With a few patches on your body, you could see your internal organs.

The study also includes lead authors Chonghe Wang and Xiaoyu Chen, and co-authors Liu Wang, Mitsutoshi Makihata, and Tao Zhao at MIT, along with Hsiao-Chuan Liu of the Mayo Clinic in Rochester, Minnesota.

Source: https://news.mit.edu/

Biosynthetic Cornea Implant Restores Vision

A cornea implant made out of collagen gathered from pig skin has restored the vision of 20 volunteers in a landmark pilot study. Pending further testing, the novel bioengineered implant is hoped to improve the vision of millions around the world awaiting difficult and costly cornea transplant surgeries. More than one million people worldwide are diagnosed blind every year due to damaged or diseased corneas. A person’s vision can be easily disrupted when this thin outer layer of tissue surrounding the eye degenerates. A person suffering corneal blindness can have their vision restored by receiving a corneal transplant from a human donor. However, a lack of cornea donors means barely one in 70 people with corneal blindness will ever be able to access a transplant. Plus, the surgical procedure can be complex, amplifying the lack of access to this vision-restoring procedure for people in low– and middle-income countries.

This new research first looked to develop cornea implants that didn’t rely on human donor tissue. Over a decade ago the researchers first demonstrated biosynthetic corneas were effective replacements for donor corneas. But those earlier studies still relied on complex lab-grown human collagen, molded into the shape of corneas. This new study demonstrates the same biosynthetic cornea can be effectively produced using medical-grade collagen sourced from pig skin. Not only is this a cheap and sustainable source of collagen, but improved engineering techniques mean these bioengineered corneas can be safely stored for almost two years, unlike donated human corneas which must be used within two weeks of harvesting.

A pilot study saw bioengineered implants restore the vision of 14 volunteers who were completely blind before the experimental procedure

The results show that it is possible to develop a biomaterial that meets all the criteria for being used as human implants, which can be mass-produced and stored up to two years and thereby reach even more people with vision problems,” explained Neil Lagali, one of the researchers working on the project. “This gets us around the problem of shortage of donated corneal tissue and access to other treatments for eye diseases.

The other innovation demonstrated in the study is a new surgical approach for implanting the bioengineered cornea. Instead of needing to surgically remove a patient’s pre-existing cornea, as would be done when transplanting a donor cornea, the new method leaves that tissue intact. Only a small suture is necessary to insert the novel implant.

The new study, published in Nature Biotechnology, describes the results of a pilot trial that tested the implant in 20 volunteers, 14 of whom were completely blind before the experimental procedure. At the two-year follow-up the study reports all 20 volunteers had completely regained their vision and experienced no adverse effects from the surgery.

Source: https://newatlas.com/

Stretchy Brain-mimicking AI BioSensor Tracks Continuously Your Health

It’s a brainy Band-Aid, a smart watch without the watch, and a leap forward for wearable health technologies. Researchers at the University of Chicago’s Pritzker School of Molecular Engineering (PME) have developed a flexible, stretchable computing chip that processes information by mimicking the human brain. The device, described in the journal Matter, aims to change the way health data is processed.

With this work we’ve bridged wearable technology with artificial intelligence and machine learning to create a powerful device which can analyze health data right on our own bodies,” said Sihong Wang, a materials scientist and Assistant Professor of Molecular Engineering.

Today, getting an in-depth profile about your health requires a visit to a hospital or clinic. In the future, Wang said, people’s health could be tracked continuously by wearable electronics that can detect disease even before symptoms appear. Unobtrusive, wearable computing devices are one step toward making this vision a reality.

The future of healthcare that Wang—and many others—envision includes wearable biosensors to track complex indicators of health including levels of oxygen, sugar, metabolites and immune molecules in people’s blood. One of the keys to making these sensors feasible is their ability to conform to the skin. As such skin-like wearable biosensors emerge and begin collecting more and more information in real-time, the analysis becomes exponentially more complex. A single piece of data must be put into the broader perspective of a patient’s history and other health parameters.

Source: https://pme.uchicago.edu/

How to ‘Time Jump’ Skin Cells

Research from the Babraham Institute has developed a method to “time jump” human skin cells by 30 years, turning back the aging clock for cells without losing their specialized function. Work by researchers in the Institute’s Epigenetics research program has been able to partly restore the function of older cells, as well as rejuvenating the molecular measures of biological age. The research is published today in the journal eLife, and while this topic is still at an early stage of exploration, it could revolutionize regenerative medicine.

As we age, our cells‘ ability to function declines and the  accumulates marks of aging. Regenerative biology aims to repair or replace cells including old ones. One of the most important tools in regenerative biology is our ability to createinducedstem cells. The process is a result of several steps, each erasing some of the marks that make cells specialized. In theory, these stem cells have the potential to become any cell type, but scientists aren’t yet able to reliably recreate the conditions to re-differentiate stem cells into all cell types.

The new method, based on the Nobel Prize-winning technique scientists use to make stem cells, overcomes the problem of entirely erasing cell identity by halting reprogramming part of the way through the process. This allowed researchers to find the precise balance between reprogramming cells, making them biologically younger, while still being able to regain their specialized cell function.

In 2007, Shinya Yamanaka was the first scientist to turn normal cells, which have a specific function, into  which have the special ability to develop into any cell type. The full process of stem cell reprogramming takes around 50 days using four key molecules called the Yamanaka factors. The new method, called “maturation phase transient reprogramming,” exposes cells to Yamanaka factors for just 13 days. At this point, age-related changes are removed and the cells have temporarily lost their identity. The partly reprogrammed cells were given time to grow under normal conditions, to observe whether their specific skin cell function returned. Genome analysis showed that cells had regained markers characteristic of  (fibroblasts), and this was confirmed by observing collagen production in the reprogrammed cells.

Young fibroblasts in the first image, the two are after 10 days, on the right with treatment, the last two are after 13 days, right with treatment. Red shows collagen production which has been restored

To show that the cells had been rejuvenated, the researchers looked for changes in the hallmarks of aging. As explained by Dr. Diljeet Gill, a postdoc in Wolf Reik’s lab at the Institute who conducted the work as a Ph.D. student, “Our understanding of aging on a molecular level has progressed over the last decade, giving rise to techniques that allow researchers to measure age-related biological changes in human cells. We were able to apply this to our experiment to determine the extent of reprogramming our new method achieved.”

Source: https://phys.org/

A Forest-based Yard Im­proved the Im­mune Sys­tem of Day­care Chil­dren in Only a Month

Playing through the greenery and litter of a mini forest‘s undergrowth for just one month may be enough to change a child’s immune system, according to an experiment in Finland. When daycare workers rolled out a lawn, planted forest undergrowth (such as dwarf heather and blueberries), and allowed children to care for crops in planter boxes, the diversity of microbes in the guts and on the skin of young kids appeared healthier in a very short space of time.

Compared to other city kids who play in standard urban daycares with yards of pavement, tile and gravel, 3-, 4-, and 5-year-olds at these greened-up daycare centers in Finland showed increased T-cells and other important immune markers in their blood within 28 days.

DURING THE STUDY, FOREST UNDERGROWTH, LAWN TURF AND PLANTER BOXES, IN WHICH CHILDREN PLANTED AND TENDED CROPS, WERE ADDED TO PAVED, TILED AND GRAVEL-COATED YARD AREAS AT DAYCARE CENTRES

We also found that the intestinal microbiota of children who received greenery was similar to the intestinal microbiota of children visiting the forest every day,” explained environmental scientist Marja Roslund from the University of Helsinki in 2020, when the research was published.

Prior research has shown early exposure to green space is somehow linked to a well-functioning immune system, but it’s still not clear whether that relationship is causal or not.

The experiment in Finland is the first to explicitly manipulate a child’s urban environment and then test for changes in their microbiome and, in turn, a child’s immune system.

Source: https://www2.helsinki.fi/

Google Launches a Dermatology AI App in EU

Billions of times each year, people turn to Google’s web search box for help figuring out what’s wrong with their skin. Now, Google is preparing to launch an app that uses image recognition algorithms to provide more expert and personalized help. A brief demo at the company’s developer conference last month showed the service suggesting several possible skin conditions based on uploaded photos.

Machines have matched or outperformed expert dermatologists in studies in which algorithms and doctors scrutinize images from past patients. But there’s little evidence from clinical trials deploying such technology, and no AI image analysis tools are approved for dermatologists to use in the US, says Roxana Daneshjou, a Stanford dermatologist and researcher in machine learning and health.

Many don’t pan out in the real world setting,” she says.

Google’s new app isn’t clinically validated yet either, but the company’s AI prowess and recent buildup of its health care division make its AI dermatology app notable. Still, the skin service will start small—and far from its home turf and largest market in the US. The service is not likely to analyze American skin blemishes any time soon.

At the developer conference, Google’s chief health officer, Karen DeSalvo, said the company aims to launch what it calls a dermatology assist tool in the European Union as soon as the end of this year. A video of the app suggesting that a mark on someone’s arm could be a mole featured a caption saying it was an approved medical device in the EU. The same note added a caveat: “Not available in the US.”

Google says its skin app has been approved “CE marked as a Class I medical device in the EU,” meaning it can be sold in the bloc and other countries recognizing that standard. The company would have faced relatively few hurdles to secure that clearance, says Hugh Harvey, managing director at Hardian Health, a digital health consultancy in the UK. “You essentially fill in a form and self-certify,” he says. Google’s conference last month took place a week before tighter EU rules took effect that Harvey says require many health apps, likely including Google’s, to show that an app is effective, among other things. Preexisting apps have until 2025 to comply with the new rules.

Source: https://www.wired.com/

Skin and Bones Repaired by Bioprinting

Fixing traumatic injuries to the skin and bones of the face and skull is difficult because of the many layers of different types of tissues involved, but now, researchers have repaired such defects in a rat model using bioprinting during surgery, and their work may lead to faster and better methods of healing skin and bones.

Schematic of the skin and bone bioprinting process. After scanning, the bone and then skin layers are bioprinted creating a layered repair with bone, a barrier layer, and dermis and epidermis

This work is clinically significant,” said Ibrahim T. Ozbolat, Associate Professor of Biomedical Engineering and Neurosurgery, Penn State. “Dealing with composite defects, fixing hard and soft tissues at once, is difficult. And for the craniofacial area, the results have to be esthetically pleasing.

Currently, fixing a hole in the skull involving both bone and soft tissue requires  using bone from another part of the patient’s body or a cadaver. The bone must be covered by soft tissue with blood flow, also harvested from somewhere else, or the bone will die. Then surgeons need to repair the soft tissue and skin. Ozbolat and his team used extrusion bioprinting and droplet bioprinting of mixtures of cells and carrier materials to print both bone and soft tissueThere is no surgical method for repairing soft and hard tissue at once,” said Ozbolat. “This is why we aimed to demonstrate a technology where we can reconstruct the whole defect — bone to epidermis — at once.”

The researchers attacked the problem of bone replacement first, beginning in the laboratory and moving to an animal model. They needed something that was printable and nontoxic and could repair a 5-millimeter hole in the skull. The “hard tissue ink” consisted of collagen, chitosan, nano-hydroxyapatite and other compounds and mesenchymal stem cells — multipotent cells found in bone marrow that create bone, cartilage and bone marrow fat. The hard tissue ink extrudes at room temperature but heats up to body temperature when applied. This creates physical cross-linkage of the collagen and other portions of the ink without any chemical changes or the necessity of a crosslinker additive.

The researchers used droplet printing to create the soft tissue with thinner layers than the bone. They used collagen and fibrinogen in alternating layers with crosslinking and growth enhancing compounds. Each layer of skin including the epidermis and dermis differs, so the bioprinted soft tissue layers differed in composition. Experiments repairing 6 mm holes in full thickness skin proved successful. Once the team understood skin and bone separately, they moved on to repairing both during the same surgical procedure. “This approach was an extremely challenging process and we actually spent a lot of time finding the right material for bone, skin and the right bioprinting techniques,” said Ozbolat.

The scientists have reported their results in Advanced Functional Materials.

Source: https://news.psu.edu/

How To Reverse Diabetes

Using induced pluripotent stem cells produced from the skin of a patient with a rare, genetic form of insulin-dependent diabetes called Wolfram syndrome, researchers transformed the human stem cells into insulin-producing cells and used the gene-editing tool CRISPR-Cas9 to correct a genetic defect that had caused the syndrome. They then implanted the cells into lab mice and cured the unrelenting diabetes in those mice.

The findings, from researchers at Washington University School of Medicine in St. Louis, suggest the CRISPR-Cas9 technique may hold promise as a treatment for diabetes, particularly the forms caused by a single gene mutation, and it also may be useful one day in some patients with the more common forms of diabetes, such as type 1 and type 2.

Wolfram syndrome is caused by mutations to a single gene, providing the researchers an opportunity to determine whether combining stem cell technology with CRISPR to correct the genetic error also might correct the diabetes caused by the mutation. Patients with Wolfram syndrome develop diabetes during childhood or adolescence and quickly require insulin-replacement therapy, requiring insulin injections multiple times each day. Most go on to develop problems with vision and balance, as well as other issues, and in many patients, the syndrome contributes to an early death.

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Researchers at Washington University School of Medicine in St. Louis have transformed stem cells into insulin-producing cells. They used the CRISPR gene-editing tool to correct a defect that caused a form of diabetes, and implanted the cells into mice to reverse diabetes in the animals. Shown is a microscopic image of insulin-secreting beta cells (insulin is green) that were made from stem cells produced from the skin of a patient with Wolfram syndrome.

This is the first time CRISPR has been used to fix a patient’s diabetes-causing genetic defect and successfully reverse diabetes,” said co-senior investigator Jeffrey R. Millman, PhD, an assistant professor of medicine and of biomedical engineering at Washington University. “For this study, we used cells from a patient with Wolfram syndrome because, conceptually, we knew it would be easier to correct a defect caused by a single gene. But we see this as a stepping stone toward applying gene therapy to a broader population of patients with diabetes.

The study is published online in the journal Science Translational Medicine.

Source: https://medicine.wustl.edu/

Electrified Tattoos and Personalized Biosensors

Electrical engineers at Duke University have devised a fully print-in-place technique for electronics that is gentle enough to work on delicate surfaces including paper and human skin. The advance could enable technologies such as high-adhesion, embedded electronic tattoos and bandages tricked out with patient-specific biosensors.

Two electronically active leads directly printed along the underside of Duke graduate student Nick Williams’s pinky successfully light up an LED when a voltage is applied

When people hear the term ‘printed electronics,’ the expectation is that a person loads a substrate and the designs for an electronic circuit into a printer and, some reasonable time later, removes a fully functional electronic circuit,” said Aaron Franklin, Associate Professor at Duke.

“Over the years there have been a slew of research papers promising these kinds of ‘fully printed electronics,’ but the reality is that the process actually involves taking the sample out multiple times to bake it, wash it or spin-coat materials onto it,” Franklin said. “Ours is the first where the reality matches the public perception.

The concept of so-called electronic tattoos were first developed in the late 2000s at the University of Illinois by John A. Rogers, who is now Professor of Materials Science and Engineering at Northwestern University. Rather than a true tattoo that is injected permanently into the skin, Rogers’s electronic tattoos are thin, flexible patches of rubber that contain equally flexible electrical components.

The thin film sticks to skin much like a temporary tattoo, and early versions of the flexible electronics were made to contain heart and brain activity monitors and muscle stimulators. While these types of devices are on their way to commercialization and large-scale manufacturing, there are some arenas in which they’re not well suited, such as when direct modification of a surface by adding custom electronics is needed. “For direct or additive printing to ever really be useful, you’re going to need to be able to print the entirety of whatever you’re printing in one step,” said Franklin. “Some of the more exotic applications include intimately connected electronic tattoos that could be used for biological tagging or unique detection mechanisms, rapid prototyping for on-the-fly custom electronics, and paper-based diagnostics that could be integrated readily into customized bandages.”

The techniques are described in a series of papers published in the journal Nanoscale and in the journal ACS Nano.

Source: https://pratt.duke.edu/