Artificial skin

Artificial skin is a collagen scaffold that induces regeneration of skin in mammals such as humans. The term was used in the late 1970s and early 1980s to describe a new treatment for massive burns. It was later discovered that treatment of deep skin wounds in adult animals and humans with this scaffold induces regeneration of the dermis. It has been developed commercially under the name IntegraTM and is used in massively burned patients, during plastic surgery of the skin, and in treatment of chronic skin wounds. Artificial skin is a collagen scaffold that induces regeneration of skin in mammals such as humans. The term was used in the late 1970s and early 1980s to describe a new treatment for massive burns. It was later discovered that treatment of deep skin wounds in adult animals and humans with this scaffold induces regeneration of the dermis. It has been developed commercially under the name IntegraTM and is used in massively burned patients, during plastic surgery of the skin, and in treatment of chronic skin wounds. Alternatively, the term “artificial skin” sometimes is used to refer to skin-like tissue grown in a laboratory, although this technology is still quite a way away from being viable for use in the medical field. 'Artificial skin' can also refer to flexible semiconductor materials that can sense touch for those with prosthetic limbs, (also experimental). The skin is the largest organ in the human body. Skin is made up of three layers, the epidermis, dermis and the fat layer, also called the hypodermis. The epidermis is the outer layer of skin that keeps vital fluids in and harmful bacteria out of the body. The dermis is the inner layer of skin that contains blood vessels, nerves, hair follicles, oil, and sweat glands. Severe damage to large areas of skin exposes the human organism to dehydration and infections that can result in death. Traditional ways of dealing with large losses of skin have been to use skin grafts from the patient (autografts) or from an unrelated donor or a cadaver. The former approach has the disadvantage that there may not be enough skin available, while the latter suffers from the possibility of rejection or infection. Until the late twentieth century, skin grafts were constructed from the patient's own skin. This became a problem when skin had been damaged extensively, making it impossible to treat severely injured patients entirely with autografts. A process for inducing regeneration in skin was invented by Dr. Ioannis V. Yannas (then an assistant professor in the Fibers and Polymers Division, Department of Mechanical Engineering, at Massachusetts Institute of Technology) and Dr. John F. Burke (then chief of staff at Shriners Burns Institute in Boston, Massachusetts). Their initial objective was to discover a wound cover that would protect severe skin wounds from infection by accelerating wound closure. Several kinds of grafts made of synthetic and natural polymers were prepared and tested in a guinea pig animal model. By the late 1970s it was evident that the original objective was not reached. Instead, these experimental grafts typically did not affect the speed of wound closure. In one case, however, a particular type of collagen graft led to significant delay of wound closure. Careful study of histology samples revealed that grafts that delayed wound closure induced the synthesis of new dermis de novo at the injury site, instead of forming scar, which is the normal outcome of the spontaneous wound healing response. This was the first demonstration of regeneration of a tissue (dermis) that does not regenerate by itself in the adult mammal. After the initial discovery, further research led to the composition and fabrication of grafts that were evaluated in clinical trials. These grafts were synthesized as a graft copolymer of microfibrillar type I collagen and a glycosaminoglycan, chondroitin-6-sulfate, fabricated into porous sheets by freeze-drying, and then cross-linked by dehydrothermal treatment. Control of the structural features of the collagen scaffold (average pore size, degradation rate and surface chemistry) was eventually found to be a critical prerequisite for its unusual biological activity. In 1981 Burke and Yannas proved that their artificial skin worked on patients with 50 to 90 percent burns, vastly improving the chances of recovery and improvised quality of life. John F. Burke also claimed, in 1981, ' is soft and pliable, not stiff and hard, unlike other substances used to cover burned-off skin.' Several patents were granted to MIT for the creation of collagen-based grafts that can induce dermis regeneration. U.S. Pat. 4,418,691 (December 6, 1983) was cited by the National Inventors Hall of Fame as the key patent describing the invention of a process for regenerated skin (Inductees Natl Inventors Hall of Fame, 2015). These patents were translated later into a commercial product (IntegraTM) by Integra LifeSciences Corp., a company founded in 1993. IntegraTM grafts received FDA approval in 1996 and since then are being applied worldwide to treat patients who are in need of new skin to treat massive burns, those undergoing plastic surgery of the skin, and patients with chronic skin wounds as well as others who suffer from certain forms of skin cancer.In clinical practice, a thin graft sheet manufactured from the active collagen scaffold is placed on the injury site, which is then covered with a thin sheet of silicone elastomer that protects the wound site from bacterial infection and dehydration. The graft can be seeded with autologous cells (keratinocytes) in order to accelerate wound closure, however the presence of these cells is not required for regenerating the dermis. Grafting skin wounds with IntegraTM leads to the synthesis of normal vascularized and innervated dermis de novo, followed by re-epithelization and formation of epidermis. Although early versions of the scaffold were not capable of regenerating hair follicles and sweat glands, later developments by S.T Boyce and coworkers led to solution of this problem. The mechanism of regeneration using an active collagen scaffold has been largely clarified. The scaffold retains regenerative activity provided that it has been prepared with appropriate levels of the specific surface (pore size in range 20-125 µm), degradation rate (degradation half-life 14 ± 7 days) and surface chemical features (ligand densities for integrins α1β1 and α2β1 must exceed approximately 200 μΜ α1β1 and α2β1 ligands). It has been hypothesized that specific binding of a sufficient number of contractile cells (myofibroblasts) on the scaffold surface, occurring within a narrow time window, is required for induction of skin regeneration in the presence of this scaffold. Studies with skin wounds have been extended to transected peripheral nerves, and the combined evidence supports a common regeneration mechanism for skin and peripheral nerves using this scaffold. Research is continually being done on artificial skin. Newer technologies, such as an autologous spray-on skin produced by Avita Medical, are being tested in efforts to accelerate healing and minimize scarring. The Fraunhofer Institute for Interfacial Engineering and Biotechnology is working towards a fully automated process for producing artificial skin. Their goal is a simple two-layer skin without blood vessels that can be used to study how skin interacts with consumer products, such as creams and medicines. They hope to eventually produce more complex skin that can be used in transplants.