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.[1] It has been developed commercially under the name Integra and is used in massively burned patients, during plastic surgery of the skin, and in treatment of chronic skin wounds.[2]

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).

Background

The skin is the largest organ in the human body.[3] 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.[4] 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 with autografts only.[5]

Regenerated skin: discovery and clinical use

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.[6] 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.[7][8][9][10][11][12] After the initial discovery, further research led to the composition and fabrication of grafts that were evaluated in clinical trials.[11][13] 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.[14] 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 improved quality of life.[15][16] John F. Burke also claimed, in 1981, "[The Artificial skin] is soft and pliable, not stiff and hard, unlike other substances used to cover burned-off skin."[17]

Several patents were granted to MIT for the creation of collagen-based grafts that can induce dermis regeneration. U.S. Patent 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[18]). These patents were later translated into a commercial product by Integra LifeSciences Corp., a company founded in 1989.[19] Integra Dermal Regeneration Template received FDA approval in 1996, and the FDA listed it as a "Significant Medical Device Breakthrough" in the same year.[20] Since then, it has been applied worldwide to treat patients who are in need of new skin to treat massive burns[21] and traumatic skin wounds,[22] those undergoing plastic surgery of the skin,[23] as well as others who suffer from certain forms of skin cancer.[24]

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.[10] Grafting skin wounds with Integra 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.[25]

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).[26] 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.[27] 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.[28]

Further research

Research is continually being done on artificial skin. Newer technologies, such as an autologous spray-on skin produced by Avita Medical,[29] 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.[30]

Hanna Wendt, and a team of her colleagues in the Department of Plastic, Hand and Reconstructive Surgery at Medical School Hannover Germany, have found a method for creating artificial skin using spider silk. Before this, however, artificial skin was grown using materials like collagen. These materials did not seem strong enough. Instead, Wendt and her team turned to spider silk, which is known to be 5 times stronger than Kevlar. The silk is harvested by “milking” the silk glands of golden orb web spiders. The silk was spooled as it was harvested, and then it was woven into a rectangular steel frame. The steel frame was 0.7 mm thick, and the resulting weave was easy to handle or sterilize. Human skin cells were added to the meshwork silk and were found to flourish under an environment providing nutrients, warmth and air. However at this time, using spider silk to grow artificial skin in mass quantities is not practical because of the tedious process of harvesting spider silk.[31]

Australian researchers are currently searching for a new, innovative way to produce artificial skin. This would produce artificial skin more quickly and in a more efficient way. The skin produced would only be 1 millimeter thick and would only be used to rebuild the epidermis. They can also make the skin 1.5 millimetres thick, which would allow the dermis to repair itself if needed. This would require bone marrow from a donation or from the patient's body. The bone marrow would be used as a “seed," and would be placed in the grafts to mimic the dermis. This has been tested on animals and has been proven to work with animal skin. Professor Maitz said, “In Australia, someone with a full-thickness burn to up to 80 per cent of their body surface area has every prospect of surviving the injury... However their quality of life remains questionable as we're unable, at present, to replace the burned skin with normal skin…We're committed to ensuring the pain of survival is worth it, by developing a living skin equivalent.”[32]

Synthetic skin

Another form of “artificial skin” has been created out of flexible semiconductor materials that can sense touch for those with prosthetic limbs.[33][34] The artificial skin is anticipated to augment robotics in conducting rudimentary jobs that would be considered delicate and require sensitive “touch”.[33][35] Scientists found that by applying a layer of rubber with two parallel electrodes that stored electrical charges inside of the artificial skin, tiny amounts of pressure could be detected. When pressure is exerted, the electrical charge in the rubber is changed and the change is detected by the electrodes. However, the film is so small that when pressure is applied to the skin, the molecules have nowhere to move and become entangled. The molecules also fail to return to their original shape when the pressure is removed.[36] A recent development in the synthetic skin technique has been made by imparting the color changing properties to the thin layer of silicon with the help of artificial ridges which reflect a very specific wavelength of light. By tuning the spaces between these ridges, color to be reflected by the skin can be controlled.[37] This technology can be used in color-shifting camouflages and sensors that can detect otherwise imperceptible defects in buildings, bridges, and aircraft.

3D printers

Universidad Carlos III de Madrid, Center for Energy, Environmental and Technological Research, Hospital General Universitario Gregorio Marañón and BioDan Group created a 3D bioprinter capable of creating human skin that functions exactly as real skin does.[38]

References

  1. ↑ Garfein, E. (2009-01-01), Orgill, Dennis; Blanco, Carlos (eds.), "2 - Skin replacement products and markets", Biomaterials for Treating Skin Loss, Woodhead Publishing Series in Biomaterials, Woodhead Publishing, pp. 9–17, ISBN 9781845693633, retrieved 2019-10-23
  2. ↑ Winfrey, M. E.; Cochran, M.; Hegarty, M. T. (January 1999). "A new technology in burn therapy: INTEGRA artificial skin". Dimensions of Critical Care Nursing. 18 (1): 14–20. doi:10.1097/00003465-199901000-00003. ISSN 0730-4625. PMID 10639995.
  3. ↑ Dahiya, R. S. (2012). Robotic Tactile Sensing. Springer. p. 265. ISBN 978-94-007-0578-4.
  4. ↑ "Artificial Skin - used, first, blood, body, produced, Burke and Yannas Create Synthetic Skin, Graftskin".
  5. ↑ "How is artificial skin made?: Information from". Answers.com. Retrieved 2013-10-17.
  6. ↑ I.V. Yannas (1981). Dineen (ed.). "Use of artificial skin in wound management". The Surgical Wound: 170–191.
  7. ↑ I.V. Yannas; J.F. Burke (1980). "Design of an artificial skin I. Basic design principles". J. Biomed. Mater. Res. 14 (1): 65–81. doi:10.1002/jbm.820140108. PMID 6987234.
  8. ↑ I.V. Yannas; J.F. Burke; M. Warpehoski; P. Stasikelis; E.M. Skrabut; D. Orgill; D.J. Giard (1981). "Prompt, long-term functional replacement of skin". Trans. Am. Soc. Artif. Intern. Organs. 27: 19–22. PMID 7036496.
  9. ↑ I.V. Yannas; J.F. Burke; D.P. Orgill; E.M. Skrabut (1982). "Wound tissue can utilize a polymeric template to synthesize a functional extension of skin". Science. 215 (4529): 174–176. Bibcode:1982Sci...215..174Y. doi:10.1126/science.7031899. PMID 7031899.
  10. 1 2 I.V. Yannas E. Lee; D.P. Orgill; E.M. Skrabut; G.F. Murphy (1989). "Synthesis and characterization of a model extracellular matrix which induces partial regeneration of adult mammalian skin". Proc. Natl. Acad. Sci. USA. 86 (3): 933–937. doi:10.1073/pnas.86.3.933. PMC 286593. PMID 2915988.
  11. 1 2 J.F. Burke; I.V. Yannas; W.C.Q. Jr.; C.C. Bondoc; W.K. Jung (1981). "Successful use of a physiologically acceptable artificial skin in the treatment of extensive burn injury". Ann. Surg. 194 (4): 413–428. doi:10.1097/00000658-198110000-00005. PMC 1345315. PMID 6792993.
  12. ↑ G.F. Murphy; D.P. Orgill; I.V. Yannas (1990). "Partial dermal regeneration is induced by biodegradable collagen-glycosaminoglycan grafts". Lab. Invest. 62 (3): 305–313. PMID 2314050.
  13. ↑ D.A. Heimbach; A. Luterman; J. Burke; A. Cram; D. Herndon; J. Hunt; M. Jordan; W. McManus; L. Solem; G. Warden; et al. (1988). "Artificial dermis for major burns". Ann. Surg. 208 (3): 313–320. doi:10.1097/00000658-198809000-00008. PMC 1493652. PMID 3048216.
  14. ↑ I.V. Yannas; J.F. Burke; P.L. Gordon; C. Huang; R.H. Rubinstein (1980). "Design of an artificial skin II: Control of chemical composition". J. Biomed. Mater. Res. 14 (2): 107–131. doi:10.1002/jbm.820140203. PMID 7358747.
  15. ↑ Vitello, Paul. "Dr. John F. Burke, Dies at 89; Created Synthetic Skin". Retrieved 2018-07-30.
  16. ↑ Singh, Rajat (2015-07-27). "adventures: artifical [sic] skin". adventures. Retrieved 2018-07-30.
  17. ↑ Altman, Lawrence K. "ARTIFICIAL SKIN FOR BURN VICTIMS IS REPORTED DEVELOPED IN BOSTON". Retrieved 2018-07-30.
  18. ↑ "Ioannis Yannas to be inducted into the National Inventors Hall of Fame".
  19. ↑ Times, David Karas/The (2012-01-09). "Plainsboro's Integra LifeSciences opens Asia office". nj. Retrieved 2021-09-21.
  20. ↑ "Wayback Machine" (PDF). Food and Drug Administration. 2009-01-20. Archived from the original (PDF) on 2009-01-20. Retrieved 2021-09-21.
  21. ↑ González Alaña, I.; Torrero López, J.V.; Martín Playá, P.; Gabilondo Zubizarreta, F.J. (2013-06-30). "Combined use of negative pressure wound therapy and Integra® to treat complex defects in lower extremities after burns". Annals of Burns and Fire Disasters. 26 (2): 90–93. ISSN 1592-9558. PMC 3793885. PMID 24133403.
  22. ↑ "Validate User". jamanetwork.com. Retrieved 2021-09-21.
  23. ↑ Chang, Daniel K.; Louis, Matthew R.; Gimenez, Alejandro; Reece, Edward M. (August 2019). "The Basics of Integra Dermal Regeneration Template and its Expanding Clinical Applications". Seminars in Plastic Surgery. 33 (3): 185–189. doi:10.1055/s-0039-1693401. ISSN 1535-2188. PMC 6680073. PMID 31384234.
  24. ↑ Chalmers, R. L.; Smock, E.; Geh, J. L. C. (December 2010). "Experience of Integra(®) in cancer reconstructive surgery". Journal of Plastic, Reconstructive & Aesthetic Surgery: JPRAS. 63 (12): 2081–2090. doi:10.1016/j.bjps.2010.02.025. ISSN 1878-0539. PMID 20335086.
  25. ↑ P. Sriwiriyanont; K.A. Lynch; K.L. McFarland; D.M. Supp; S.T. Boyce (2013). "Characterization of hair follicle development in engineered skin substitutes". PLOS ONE. 8 (6): 65664. Bibcode:2013PLoSO...865664S. doi:10.1371/journal.pone.0065664. PMC 3684595. PMID 23799033.
  26. ↑ D.S. Tzeranis; Soller E.C.; Buydash M.C.; So P.T.C.; Yannas I.V. (2015). "C In Situ Quantification of Surface Chemistry in Porous Collagen Biomaterials". Annals of Biomedical Engineering. 44 (3): 803–815. doi:10.1007/s10439-015-1445-x. PMC 4791220. PMID 26369635.
  27. ↑ Yannas, Ioannis. Yannas I.V. Tissue and Organ Regeneration in Adults (second ed.). New York: Springer.
  28. ↑ E.C. Soller; D.S. Tzeranis; K. Miu; P.T. So & I.V. Yannas (2012). "Common features of optimal collagen scaffolds that disrupt wound contraction and enhance regeneration both in peripheral nerves and in skin". Biomaterials. 33 (19): 4783–91. doi:10.1016/j.biomaterials.2012.03.068. PMID 22483241.
  29. ↑ Gravitz, Lauren (November 5, 2009). "Spraying on Skin Cells to Heal Burns". Technology Review. Retrieved February 15, 2010.
  30. ↑ Fraunhofer-Gesellschaft (May 19, 2009). "Artificial Skin Manufactured In Fully Automated Process". Science Daily. Retrieved February 15, 2010.
  31. ↑ "Artificial Skin Made From Spider Silk : Discovery News". News.discovery.com. 2011-08-10. Retrieved 2013-10-17.
  32. ↑ "New form of artificial human skin". News-medical.net. 14 June 2010. Retrieved 2013-10-17.
  33. 1 2 Dahiya, Ravinder S.; Valle, Maurizio (13 March 2019). Robotic Tactile Sensing: Technologies and System. Springer Netherlands. doi:10.1007/978-94-007-0579-1. ISBN 978-94-007-0578-4 – via www.springer.com.
  34. ↑ Steenhuysen, Julie (12 September 2010). "Artificial "skin" materials can sense pressure". Yahoo News. Reuters. Archived from the original on 16 September 2010. Retrieved 14 September 2010.
  35. ↑ Dahiya, Ravinder; Monica Gori (14 April 2010). "Probing with and into Fingerprints". Journal of Neurophysiology. 104 (1): 1–3. doi:10.1152/jn.01007.2009. PMID 20393056.
  36. ↑ "New artificial skin could make prosthetic limbs and robots more sensitive". e! Science News. 2010-09-13. Retrieved 2013-10-17.
  37. ↑ L. Zhu; J. Kapraun; J. Ferrara; C.J. Chang-Hasnain (March 2015). "Flexible photonic metastructures for tunable coloration". Optica. 2 (3): 255–8. Bibcode:2015Optic...2..255Z. doi:10.1364/OPTICA.2.000255.
  38. ↑ "3-D bioprinter to print human skin". ScienceDaily.
This article is issued from Offline. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.