Tag Archives: cartilage

Humans could have salamander-like ability to regrow cartilage

Despite not being able to regrow a limb like a salamander, humans have some capacity to restore cartilage in their joints, a study showed. This opens the door to new treatments for joint injuries and diseases like osteoarthritis.

Credit Wikimedia Commons.

The findings, published in Science Advances, run counter to a widely held belief. Because the cartilage cushioning the joints lacks its own blood supply, the body can’t repair damage from an injury or the wear-and-tear of aging.

And that, in part, is why so many people eventually develop osteoarthritis, where broken-down cartilage causes pain and stiffness in the joints. But that lack of blood supply does not mean there’s no regenerative capacity in the cartilage, according to the study.

“Cartilage in human joints can repair itself through a process similar to that used by creatures such as salamanders and zebrafish to regenerate limbs,” according to Duke Health, which helped lead the research.

Salamanders and other animals with regenerative abilities have a type of molecule called microRNA, which helps regulate joint tissue repair. Humans have microRNA too, but the mechanism for cartilage repair is stronger in some parts of the body, the study found. For example, the microRNA molecules are more active in our ankles, and less active in our knees and hips.

“We were excited to learn that the regulators of regeneration in the salamander limb appear to also be the controllers of joint tissue repair in the human limb,” said Duke professor and researcher Ming-Feng Hsueh. “We call it our ‘inner salamander’ capacity.”

The “age” of cartilage, meaning whether proteins have changed the structure or undergone amino acid conversions, depends on its location in the body, the study found. Cartilage is “young” in the ankles, “middle-aged” in the knees, and “old” in the hips. This correlation lines up with how animals regenerate fastest at the furthest tips of their bodies, like tails or the ends of legs.

For years, scientists have known humans do have some regenerative capabilities — when children’s fingertips are amputated, the tip can regenerate when treated correctly. But it was widely believed that these capabilities were limited and that humans were “unable to counteract cumulative damage” to their joints.

The findings could have huge implications for athletes or people with joint injuries. MicroRNA could be injected into joints or developed into medicines that prevent or reverse arthritis, the study said. In the more distant future, it could even “establish a basis for human limb regeneration.”

The next step is to figure out what regulators humans lack that salamanders have — and then see if it’s possible to “add the missing components back,” said Duke professor Virginia Byers Kraus, one of the lead authors of the study. Once those missing components are identified, they could be combined with microRNA to create a “molecular cocktail” aimed at regenerating entire limbs.

“We believe that an understanding of this ‘salamander-like’ regenerative capacity in humans, and the critically missing components of this regulatory circuit, could provide the foundation for new approaches to repair joint tissues and possibly whole human limbs,” Kraus said.

Fluorescent 3d-printed tissue.

New 3D-printing process creates ligaments, tendons for transplant — paves the way for replacement organs

New research is merging 3D printing with human stem cells to provide on-demand tissues such as ligaments and tendons for transplant.

Fluorescent 3d-printed tissue.

Fluorescent cells the team printed to showcase their new process.
Image credits Robby Bowles / University of Utah College of Engineering.

It’s a tough life, and sometimes, our bodies pay the price. Such tolls, however, needn’t be permanent — and, new research from the University of Utah is making it easier than ever before to repair the damage. The team’s efforts pave the way to 3D-printed human tissues such as ligaments and tendons that can be used from transplant.

Break a leg! We can fix it later

“This is a technique in a very controlled manner to create a pattern and organizations of cells that you couldn’t create with previous technologies,” says University of Utah biomedical engineering assistant professor and paper co-author Robby Bowles.

“It allows us to very specifically put cells where we want them.”

Patients that require replacement tissues currently also need to supply it themselves from another part of the body or receive it from a cadaver. Such procedures carry their own risks, involve quite a lot of discomfort on the part of the patient, and (especially in the case of cadaver-sourced tissues) may be very off-putting for certain people. There’s also the risk that replacement tissue is of poor quality, either due to wear and tear or complications in the material’s retrieval from the body.

In an effort to work around these issues and reduce the total number of surgeries a potential patient would have to go through to receive a replacement, Bowles’ team worked on developing a 3D-printing method which can produce viable biological tissues.

Development of the process took two years to complete, the team reports. It relies on stem cells harvested from a patient’s body fat, which are printed on a hydrogel layer to form a tendon or ligament. These cells are grown in vitro (in the lab) in a culture and then implanted. According to the team, the technique can be used to create replacements for connective tissue such as ligaments, tendons, or cartilage — even complex structures such as spinal disks. Such disks are very complex structures that include bony interfaces (transitional areas), and must be reconstructed completely for a successful transplant, they add.

“[The 3D-printing process] will allow patients to receive replacement tissues without additional surgeries and without having to harvest tissue from other sites, which has its own source of problems,” says Bowles.

Much of the research went exactly into tackling complex structures such as spinal disks. Connective tissue is never ‘pure’ — it always includes multiple and complex patterns of interweaving cells. The tendons that flank your muscles, for example, must have transition zones to gradually shift into and attach to adjacent tissues, be them bone or muscle.

Bowles and his co-author David Ede, a former biomedical engineering master’s student at Utah, teamed up with Salt Lake City-based company, Carterra, Inc., which develops microfluidic devices for medicine. They developed their printer starting from a piece of hardware that Carterra typically uses to print antibodies for cancer screening applications. Bowles’ team developed a new printhead for the device that can lay down human cells with a high degree of control. The printhead, Bowles adds, could be adapted for any kind of 3-D printer.

As a proof of concept, the duo printed genetically-modified, fluorescent cells, so they could analyze the structure of the final tissue.

Bowles, with a background in musculoskeletal research, said the technology currently is designed for creating ligaments, tendons and spinal discs. However, he excitedly adds that “it literally could be used for any type of tissue engineering application”. Eventually, the team hopes their technique can be used to print out whole organs, which would be a major breakthrough for patients on transplant waiting lists the world over.

The paper “Microfluidic Flow Cell Array for Controlled Cell Deposition in Engineered Musculoskeletal Tissues” has been published in the journal Tissue Engineering Part C: Methods.

Scientists create 3D tissue printer that prints cartilage

Researchers from the US have developed a hybrid printer that is able to print cartilage which might one day be implanted into injured patients to help them re-grow lost cartilage in vulnerable areas, such as joints.

The innovative 3D printer is a mix of a mix of a traditional ink jet printer and an electrospinning machine; the concept was presented in a study published in the journal Biofabrication by the Institute of Physics.

“This is a proof of concept study and illustrates that a combination of materials and fabrication methods generates durable implantable constructs,” said Dr. James Yoo, a professor at the Wake Forest Institute for Regenerative Medicine, and an author on the study.

The matter of creating cartilage is still a field under development, with many options being studied (ie robotic systems). The key here, however, is the electrospinning machine.

Electrospinning machines use an electrical charge to draw very fine (typically on the micro or nano scale) fibres from a liquid or polymer; the polymers can be easily controlled and made porous which is extremely important in creating cartilage in the surrounding tissue.

The technique was used on mice, and after eight weeks it had developed the structures and properties of real cartilage, proving it could have extreme utility in humans/

System To Build Transplant Tissue Created

 

cartilage

Organ transplants are no longer a novelty,  but transplants could help save a lot of lives of people who need certain tissues to live. There is probably going to be a day when laboratories could be able to grow synthetically engineered tissues such as muscle or cartilage needed for transplants [later edit: Scientists create 3D tissue printer that prints cartilage]. A big step forward has been made by Cornell engineers who describe in the journal Nature Materials a microvascular system they have created – it can nourish growing tissues, and this is probably bigger than most people think, meaning that the system could accommodate many kinds of tissue. They have created tiny channels within a water-based gel that mimic a vascular system at the cellular scale and can supply oxygen, essential nutrients and growth factors to feed individual cells.

“A significant impediment to building engineered tissues is that you can’t feed the core,” said Abraham Stroock, Cornell assistant professor of chemical and biomolecular engineering and one of the paper’s senior authors. “Simply embedding this mimic of a microvascular system allows you to maintain the core of the tissue during culture.” Gel scaffolds, he said, “are the culture flasks of the future.”.

Researchers are able to provide just the right nutrients and proteins to certain parts of the growing tissue to make it grow different on one side than the other. Like a bone on one side and cartilage on the other.

This gives solutions to the physical engineering aspects of growing tissues synthetically. But the biological problems remain and they are very hard to solve; scientists have not found a a source of cells which could be grown without changing the cell’s characteristics.