A novel "edgeless" engineered tissue can adapt to any irregular shape, enabling better-looking, more natural-moving hand and face grafts. Alberto Pappalardo felt anxious the morning of the transplant. A group of skin cells had been under his care for a month before they took on their final appearance: a pinkish-white tissue resembling the hind limb of a mouse that could be attached to the animal-like pant legs. If everything went as planned, the mouse's skin would recognize the lab-grown material as its own.
The entire process took less than 10 minutes and 30 seconds to position the new skin. Pappalardo, a physician and postdoctoral fellow at Columbia University Medical Center specializing in dermatology and tissue engineering, remembers that it was a perfect fit. That's significant because it may help address a long-standing problem in treating large wounds, such as burns: how to cover irregular shapes with natural, functional skin.
The "skin construct" developed by Pappalardo is a sheet of human cells that can be implanted on a wound that is too large for a graft from another body part. Growing skin constructs still use flat rectangular or circular patches; the technique has mostly stayed the same for 40 years. According to Hasan Erbil Abaci, an assistant professor of bioengineering and Pappalardo's adviser, these shapes don't match those of body parts like fingers and faces, which is a problem. It takes more patches to cover three-dimensional contours of two dimensions, so the surgery will take longer and require more sutures. Both its aesthetic appeal and its mechanical performance could be better.
Edgeless 3D Graft
The team described how they created an "edgeless" three-dimensional graft, which is shaped to fit a body part and has no seams, in a paper published on January 27 in Science Advances. They started by 3D printing a scaffold that allowed skin cells to develop in the desired shape. To create a dense network of structural molecules, Pappalardo seeded human cells in layers all around the scaffold. He then patiently awaited the development of this network. This engineered skin is more accurate to form and function than before it, and when tested on the mouse, it integrated as if it were native skin.
According to Randolph Sherman, director of plastic surgery at Cedars-Sinai Medical Center, who was not involved in the study, it will not only go on more effectively and take better care, but it will also work better. In the past, Operation Smile's nonprofit Sherman treated patients with severe burns. Even if they recovered after conventional skin grafts, they might stop functioning. Some people had limited neck movement and could not open and close their mouths for their eyes. Sherman is "very optimistic" that this new strategy will resonate with people and advance his industry. He says it might help treat anything from severe dog bites and burns to diabetic ulcers, pressure sores, and diabetic ulcers. He claims better efficiency, take, function, and most likely much better aesthetics. There are four crucial potential game changers.
The skin is a challenging organ to bioengineers because it contains various cell types, takes on complex shapes, and has different mechanical properties depending on location. For example, the skin on your back differs from the skin on your hands or face in both form and function. It doesn't cover your body like Saran Wrap. According to Sherman, it is an active organ that performs numerous tasks. The temperature of the skin is controlled. The skin stores hydration. Wired reported that human skin's nerve endings, which can feel hot, cold, sharp, and dull, serve as the interface with the outside world.
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Improving Lab-Grown Tissues
Bioengineers have significantly improved in replicating that complexity in lab-grown tissues over the previous ten years. For example, they have cultured cells with those precursors to create blood vessels and hair follicles. However, Abaci could not ignore what he perceived as a clear error: the geometry of the skin. Human bodies' skin envelops every curve, and Abaci reasoned that this geometry contributes to the skin's structural integrity. No flat sheet could accomplish this. He found this bothersome as an engineer, he claims.
His group's experiment started with skin grown in an exact cylindrical shape. They printed a porous plastic scaffold for the cells of the inner dermis and outer epidermis of two layers of skin using a 3D scan or digital model. Around the scaffold, Pappalardo cast collagen-coated fibroblasts (dermal cells). He seeded keratinocytes, cells found in the epidermis after that layer had developed for two weeks. The mixture was left to sit for a week with fluid and air on opposite sides, just like our skin. And it was successful. According to Abaci, if they can make a cylinder, they can make any shape.
VerveTimes stated after the discovery. There was a debate over what to do next. One group wanted to grow a face, but the group that wanted to try something new won. They pictured a five-finger structure that could be cut open at the wrist, slid on like a glove, and stitched. According to Abaci, the surgery involves applying bandages to the wrist region.
To test how well the "edgeless" construct held up compared to conventional grafts, the lab printed a five-fingered scaffold the size of a sugar packet, prepared the cells as usual, and then tested it. Edgeless constructs outperformed flat patches by up to 400% in a mechanical strain test. The extracellular matrix-a network of proteins and molecules that gives tissue structure-was seen in microscope images as healthy and more regular. Hyaluronic acid was one of the more abundant molecules in this matrix, and the arrangement of the cells was more natural. Abaci was both delighted and surprised by how the cells responded to the simple change in geometry. Nothing else. Because it allows the cells to grow naturally and enclosed, he believes that this approach is better at producing a skin substitute that is more similar to the original.
A new kind of “edgeless” engineered tissue can fit any irregular shape, paving the way for hand and face grafts that look and move better.
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Pappalardo Hair Experience
Pappalardo's mouse experiment, which he performed 11 times, raises the question of whether a skin graft like this could survive. He attempted the mouse's hindlimb because the area's geometry was intricate; the same surgery couldn't be performed with flat grafts. The skin replacement fully merged with the mouse's surrounding skin four weeks later. The process by which they could make this work was quite exciting, according to Carnegie Mellon biomedical engineer Adam Feinberg. These technologies will soon be more widely accessible. In another ten years or so, it will ultimately change how professionals can treat illness and injury in the human body.
He is particularly curious about how they might vascularize the skin by encouraging the growth of blood vessels in it. That might be of great assistance to those who have diabetic ulcers. Feinberg asserts that poor blood circulation is one of the causes of diabetic ulcers in people and that vascularization is what keeps tissue alive. If engineers could make the tissue more vascular, treating those patients might be more straightforward.
Sashank Reddy, a plastic surgeon and tissue engineer at Johns Hopkins University, noted that the team could grow these structures from tiny biopsies rather than transplanting a significant amount of tissue from another part of the patient's body. Reddy explains that to resurface someone's forearm, a significant amount of skin must be removed from their back or thigh. That tissue's "donor site," from which it was removed, develops a defect. He continues, "The geometry of this approach is also lovely, but it also spares the donor site defect."
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Sherman points out that a transplant that can be completed in an hour significantly improves current graft operations, which can take between 4 and 11 hours and necessitate extensive anesthesia for a vulnerable patient. It might be a significant step forward, according to Sherman. Before being used by surgeons, the new constructs must still overcome several obstacles, such as clinical trials, according to Reddy. Businesses have yet to test the use of engineered tissue in patients widely. A human ear was made from cells and transplanted last year by 3DBio.
Furthermore, Reddy observes that this tissue lacks many skin-related elements, including sweat glands and hair follicles. Some may consider these "nice to haves", " but according to him, they play a significant role in securing the skin. To match skin tone, it's also essential to include skin pigments. However, he is upbeat that these additions will be possible and points out that surgical demonstrations in mice translate to humans more readily than drug trials in mice. It's less of a leap to say that it will reproduce, he claims, though there are always surprises in biology. The problem is less one of fundamental discovery and more one of engineering.
Abaci believes there is potential for using this engineered skin to test medications and cosmetics and to investigate the skin's basic biology. But his primary interest is developing transplants, ideally, ones that can be worn as a single piece and may be engineered with assistance from other research teams concentrating on fat, muscle, or cartilage.
In the interim, his team has been working on creating more critical constructs, like an adult male hand. (They believe that a 4-millimeter biopsy would be sufficient to obtain the 45 million fibroblasts and 18 million keratinocytes required for a culture that size. The scaffold will be eliminated, and actual tissue will begin to be printed instead. That would eradicate some steps and give them more control over the skin's functionality and consistency in various areas. Tissue engineers are optimistic that new methods like this will become clinically viable. Feinberg remarks it is no longer a matter of if but when this will be available.
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