How to Generate Cartilage Cells

 As any weekend warrior understands, cartilage injuries to joints such as knees, shoulders, and hips can prove extremely painful and debilitating. In addition, conditions that cause cartilage degeneration, like arthritis and temporomandibular joint disorder (TMJ), affect 350 million people in the world and cost the US public health system more than $303 billion every year. Patients suffering from these conditions experience increased pain and discomfort over time.

However, an exciting study led by faculty at The Forsyth Institute suggests new strategies for making cartilage cells with huge implications in regenerative medicine for future cartilage injuries and degeneration treatments. In a paper, entitled “GATA3 mediates nonclassical β-catenin signaling in skeletal cell fate determination and ectopic chondrogenesis,” co-first authors Takamitsu Maruyama and Daigaku Hasegawa, and senior author Wei Hsu, describe two breakthrough discoveries, including a new understanding of a multifaced protein called β-catenin. Dr. Hsu is a senior scientist at the Forsyth Insitute and a Professor of Developmental Biology at Harvard University. He is also an affiliate faculty member of the Harvard Stem Cell Institute.

The goal of this study,” said Dr. Maruyama of Forsyth, “was to figure out how to regenerate cartilage. We wanted to determine how to control cell fate, to cause the somatic cell to become cartilage instead of bone.

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New Bandage Could Seal Hole in the Heart

A Band-Aid® adhesive bandage is an effective treatment for stopping external bleeding from skin wounds, but an equally viable option for internal bleeding does not yet exist. Surgical glues are often used inside the body instead of traditional wound closure techniques like stitches, staples, and clips because they reduce the patient’s time in the hospital and lower the risk of secondary injury/damage at the wound site. An effective surgical glue needs to be strong, flexible, non-toxic, and able to accommodate movement, yet there are no adhesives currently available that have all of those properties. Researchers at the Wyss Institute (Harvard University) have developed a new super-strong hydrogel adhesive inspired by the glue secreted by a common slug that is biocompatible, flexible, and can stick to dynamically moving tissues even in the presence of blood.

The hydrogel itself is a hybrid of two different types of polymers: a seaweed extract called alginate that is used to thicken food, and polyacrylamide, which is the main material in soft contact lenses. When these relatively weak polymers become entangled with each other, they create a molecular network that demonstrates unprecedented toughness and resilience for hydrogel materials – on par with the body’s natural cartilage. When combined with an adhesive layer containing positively-charged polymer molecules (chitosan), the resulting hybrid material is able to bind to tissues stronger than any other available adhesive, stretch up to 20 times its initial length, and attach to wet tissue surfaces undergoing dynamic movement (e.g., a beating heart).

Studies of the hydrogel adhesive demonstrated that it is capable of withstanding three times the amount of tension that disrupts the best current medical adhesives, maintaining its stability and adhesion when implanted into rats for two weeks, and sealing a hole in a pig heart that was subjected to tens of thousands of cycles of pumping. Additionally, it caused no tissue damage or adhesions to surrounding tissues when applied to a liver hemorrhage in mice.

The hydrogel adhesive has numerous potential applications in the medical field, either as a patch that can be cut to desired sizes and applied to many tissues including bone, cartilage, tendon, or pleura, or as an injectable solution for deeper injuries. It can also be used to attach medical devices to their target structures, such as an actuator to support heart function. While the current iteration is designed to be a permanent structure, it could be made to biodegrade over time as the body heals from injury.

Source: https://wyss.harvard.edu/

New Lab-Made Cartilage to Rebuild Your Knees Efficiently

Over-the-counter pain relievers, physical therapy, steroid injections — some people have tried it all and are still dealing with knee pain. Often knee pain comes from the progressive wear and tear of cartilage known as osteoarthritis, which affects nearly one in six adults — 867 million people — worldwide. For those who want to avoid replacing the entire knee joint, there may soon be another option that could help patients get back on their feet fast, pain-free, and stay that way.

Writing in the journal Advanced Functional Materials, a Duke University-led team says they have created the first gel-based cartilage substitute that is even stronger and more durable than the real thing. Mechanical testing reveals that the Duke team’s hydrogel — a material made of water-absorbing polymers — can be pressed and pulled with more force than natural cartilage, and is three times more resistant to wear and tearImplants made of the material are currently being developed by Sparta Biomedical and tested in sheep. Researchers are gearing up to begin clinical trials in humans next year.

Duke researchers have developed a gel-based cartilage substitute to relieve achy knees that’s even stronger and more durable than the real thing. Clinical trials to start next year

If everything goes according to plan, the clinical trial should start as soon as April 2023,” said Duke chemistry professor Benjamin Wiley, who led the research along with Duke mechanical engineering and materials science professor Ken Gall.

To make this material, the Duke team took thin sheets of cellulose fibers and infused them with a polymer called polyvinyl alcohol — a viscous goo consisting of stringy chains of repeating molecules — to form a gel. The cellulose fibers act like the collagen fibers in natural cartilage, Wiley said — they give the gel strength when stretched. The polyvinyl alcohol helps it return to its original shape. The result is a Jello-like material, 60% water, which is supple yet surprisingly strong.

Natural cartilage can withstand a whopping 5,800 to 8,500 pounds per inch of tugging and squishing, respectively, before reaching its breaking point. Their lab-made version is the first hydrogel that can handle even more. It is 26% stronger than natural cartilage in tension, something like suspending seven grand pianos from a key ring, and 66% stronger in compression — which would be like parking a car on a postage stamp. “It’s really off the charts in terms of hydrogel strength,” Wiley said.

The team has already made hydrogels with remarkable propertiesIn 2020, they reported that they had created the first hydrogel strong enough for knees, which feel the force of two to three times body weight with each step.

Source: https://today.duke.edu/
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https://www.spartabiomedical.com/

Woman Gets 3D Printed Ear Transplant Made of Her Own Cells

In what the company is calling a “groundbreaking reconstructive procedure,” 3DBio Therapeutics has transplanted a 3D-printed ear made of living cells. The reconstruction is the first in-human phase of the clinical trial for the implant, called AuriNovo, and appears to be the first 3D-printed implant made of living tissues.

The implant is specifically for patients with microtia, a rare congenital ailment where the outer ear is either underdeveloped or doesn’t exist at all. According to the Centers for Disease Control and Prevention, it’s hard to estimate just how many people are impacted because of the range of the ailment varies, but estimates show that the birth defect impacts about 1 in every 2,000 to 10,000 in the U.S. The cause, in most cases, is unknown, although some cases are caused by genetic changes or the use of isotretinoin, or Accutane medication, during pregnancy.

The patient who received the transplant is a 20-year-old woman from Mexico whose right ear is impacted by the ailment. She received the surgery in March, and will continue to be monitored for five years, a spokesperson for 3DBio said.

Dr. Arturo Bonilla, a pediatric surgeon at the Congenital Ear Institute, the largest pediatric microtia center in North America, led the transplant. In a statement, he said that he’s “inspired” by what the advancement could mean for microtia patients.

Traditionally, doctors have to harvest rib cartilage or use porous polyethylene (PPE) implants to do this kind of transplant, both of which come with a set of challenges. Using rib cartilage, for example, requires a substantial harvest from at least three ribs and typically must be done in at least two separate hours-long procedures. It could result in a chest deformity, and the implants are rigid and can cause discomfort. PPE implants typically requires taking a large section of skin from a patient’s scalp, and because the implant is not made of biological material, there is early risk for infection and later risk of implant changes, discomfort and even a risk of the implant shattering.

Using a patient’s own cartilage cells is less invasive, and according to Bonilla, will allow for a more flexible ear. He also said that for those who have microtia, getting such a surgery can drastically help with their self-esteem. While it is not believed to impact hearing, it does offer an aesthetic relief.

This image shows what the 20-year-old patient’s ear looked like both before and after she received the 3D-bioprinted transplant. 

“An issue that becomes more prominent is bullying or teasing. Children don’t understand that they’re hurting somebody else’s feelings, but it really does affect them in a major way. And that’s usually when they start coming to my office, so that I can start taking care of them and helping them and advising them as far as what are the next options,” Bonilla said. “…The new technology with AuriNovo is exciting. I’ve actually been waiting for this my whole career.”

To create the new appendage, doctors conducted a biopsy on the ear of the patient that was impacted and extracted chondrocytes, the cells that create cartilage. Those cells were then expanded and mixed with what the company calls ColVivo collagen-based bio-ink before being molded with a 3D bioprinter into the size and shape of the patient’s opposite ear.

Source: https://www.cbsnews.com/

How to Fix Arthritis in Damaged Knee

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

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

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

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

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

Have Kneecap Pain? Exercise Your Hips!

The body is always interesting. For decades some physical therapists have treated knee pain by having their patients perform knee exercises. However, more recently physical therapists have figured out that most kneecap pain is actually coming from a hip problem. Let’s dig in.

The knee cap has to track evenly in the groove or it can become painful and wear away the cartilage on one side or the other. Since the most common way the knee cap is shifted is toward the outside (lateral) and there is a muscle that can pull it toward the inside (the VMO or vastus medialis obliqus), for decades physical therapists would give patients exercises for that muscle. However, there’s another reason the knee cap can track toward the outside. That has to do with the leg bone itself moving inward. That moves the groove for the knee cap, which is controlled at the hip. So which is it? Do you need to exercise the knee muscles? The hip muscles? Or both?

The hip muscles do all sorts of things and one of them is to hold your hips externally rotated. When these muscles get weak, the body caves inward, much like we see in our modern computer and phone-centric worlds (see above). When that happens, the knee cap groove at the end of the femur moves inward. Hence, much of hip physical therapy for patellofemoral problems is working on the hip external rotators. Meaning exercises where you rotate the feet or hip outward, for example, clamshell exercises.

This new research is a meta-analysis of 13 studies on exercises to help patellofemoral pain. The authors broke the studies how into hip+knee, hip-only, and knee-only exercises. They found that hip+knee and hip-only exercises worked about as well as each other to get rid of PF pain, but that knee-only exercises were inferior. This fits with what we know about how this problem develops.

The upshot? If you want to get rid of knee cap pain, the answer lies in strengthening your weak hip muscles! So make sure you get your clamshells and glute bridges in today.

Source: https://stem-cells.in-the.news/