Artificial skin

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Artificial skin made by Integra composed of an outer silicone film and inner matrix of cross linked fibers. Integra skin.webp
Artificial skin made by Integra composed of an outer silicone film and inner matrix of cross linked fibers.

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]

Contents

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 Ioannis V. Yannas (then an assistant professor in the Fibers and Polymers Division, Department of Mechanical Engineering, at Massachusetts Institute of Technology) and 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 have 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]

Design considerations

Fabricating artificial skin has the difficulty of mimicking living tissue with similar biological and mechanical performance. As outlined by Integra founders Yannas and Burke, there are three key factors to consider in the creation of artificial skin: material, bio/physiochemical properties, and mechanical properties. [7]

Material

Material selection is the most important part for designing artificial skin. It needs to be biocompatible with the body while having adequate properties for adequate function. Human skin is made of type I collagen, elastin, and glycosaminoglycan. [29] The artificial skin by Integra is made of a copolymer composed of collagen and glycosaminoglycan. [7] Collagen is a hydrophilic polymer whose degradation and stiffness can controlled by the degree of cross linking. However, it can be brittle and susceptible to breakdown by the enzyme collagenase. In order to make the material tougher and more resistant, a copolymer is formed with glycosaminoglycan (GAG). GAGs are long polysaccharides that act as shock absorbers. Collagen-GAG (CG) matrices have a higher modulus of elasticity and energy needed to fracture than collagen alone, making it a more ideal material. [7] An outer layer of silicone is normally applied to the matrix in order to serve as a protective layer. [30] Another material that can be used in synthetic skin is elastin. [31] Elastin has a similar effect to GAG as it reduces the tensile strength and compressive modulus of the material while increasing its toughness. [31]

Mechanical properties

Not only does the material have to be biocompatible and conducive to proliferation, it also has to have mechanical properties similar to that of real skin in order to serve as an adequate substitute. Skin is the first line of defense for the body, so it is subject to lots of chemical and mechanical assaults. As such, the artificial skin needs to be strong and tear resistant from stretching that occurs in everyday activity. It also needs to be strong enough to resist sutures from surgery. Stiffness can be controlled in several ways. As previously mentioned, crosslinking through chemical or biophysical methods. [32] Chemical methods produce stronger materials, but biophysical methods are more conducive to cell proliferation. [32] Furthermore, it has been noted that skin is viscoelastic and undergoes hysteresis- it has a time dependent stress relaxation factor and goes through a separate path during unloading.

Another important consideration is the wettability of the material. This is the ability of a liquid to maintain contact with a solid surface. If the CG matrix membrane does not wet the woundbed substrate properly, air pockets can form which will lead to infection. [7] The membrane must not be too stiff so it can drape over the surface. Furthermore, shear (lateral) or peeling (normal) forces can displace the membrane such that air pockets can reform. This can be mitigated by adding an adhesive bond like eschar or scab between the two surfaces. Although the mechanical properties of the synthetic skin do not need to be exactly the same as human, the main ones that should be similar include modulus of elasticity, tear strength, and fracture energy. [7]

Biophysical and physiochemical properties

Ultimately, the goal of the synthetic skin is to close the wound and regrow new skin. This means it first adheres to the wound and creates an airtight seal where neodermal growth can occur. During this time, the synthetic skin must degrade such that there is space for the newly grown skin. Thus, biocompatibility and degradability are also under consideration for design. [7]

Further research

Research is continually being done on artificial skin. Newer technologies, such as an autologous spray-on skin produced by Avita Medical, [33] 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. [34]

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. [35]

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." [36]

Synthetic skin

Another form of "artificial skin" has been created out of flexible semiconductor materials that can sense touch for those with prosthetic limbs. [3] [37] The artificial skin is anticipated to augment robotics in conducting rudimentary jobs that would be considered delicate and require sensitive "touch". [3] [38] 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. [39] 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. [40] 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. [41]

Related Research Articles

<span class="mw-page-title-main">Biopolymer</span> Polymer produced by a living organism

Biopolymers are natural polymers produced by the cells of living organisms. Like other polymers, biopolymers consist of monomeric units that are covalently bonded in chains to form larger molecules. There are three main classes of biopolymers, classified according to the monomers used and the structure of the biopolymer formed: polynucleotides, polypeptides, and polysaccharides. The Polynucleotides, RNA and DNA, are long polymers of nucleotides. Polypeptides include proteins and shorter polymers of amino acids; some major examples include collagen, actin, and fibrin. Polysaccharides are linear or branched chains of sugar carbohydrates; examples include starch, cellulose, and alginate. Other examples of biopolymers include natural rubbers, suberin and lignin, cutin and cutan, melanin, and polyhydroxyalkanoates (PHAs).

<span class="mw-page-title-main">Collagen</span> Most abundant structural protein in animals

Collagen is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole-body protein content. Collagen consists of amino acids bound together to form a triple helix of elongated fibril known as a collagen helix. It is mostly found in connective tissue such as cartilage, bones, tendons, ligaments, and skin. Vitamin C is vital for collagen synthesis, and Vitamin E improves the production of collagen.

<span class="mw-page-title-main">Tissue engineering</span> Biomedical engineering discipline

Tissue engineering is a biomedical engineering discipline that uses a combination of cells, engineering, materials methods, and suitable biochemical and physicochemical factors to restore, maintain, improve, or replace different types of biological tissues. Tissue engineering often involves the use of cells placed on tissue scaffolds in the formation of new viable tissue for a medical purpose, but is not limited to applications involving cells and tissue scaffolds. While it was once categorized as a sub-field of biomaterials, having grown in scope and importance, it can is considered as a field of its own.

<span class="mw-page-title-main">Wound healing</span> Series of events that restore integrity to damaged tissue after an injury

Wound healing refers to a living organism's replacement of destroyed or damaged tissue by newly produced tissue.

<span class="mw-page-title-main">Skin grafting</span> Surgical transplantation of skin

Skin grafting, a type of graft surgery, involves the transplantation of skin. The transplanted tissue is called a skin graft.

<span class="mw-page-title-main">Biomaterial</span> Any substance that has been engineered to interact with biological systems for a medical purpose

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<span class="mw-page-title-main">Integra LifeSciences</span> Device manufacturing company

Integra LifeSciences is a global medical device manufacturing company headquartered in Princeton, New Jersey. Founded in 1989, the company manufactures products for skin regeneration, neurosurgery, reconstructive and general surgery. Integra artificial skin became the first commercially reproducible skin tissue used to treat severe burns and other skin wounds.

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References

  1. ↑ Garfein, E. (2009). "2 - Skin replacement products and markets". In Orgill, Dennis; Blanco, Carlos (eds.). Biomaterials for Treating Skin Loss. Woodhead Publishing Series in Biomaterials. Woodhead Publishing. pp. 9–17. doi:10.1533/9781845695545.1.9. ISBN   9781845693633.
  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. 1 2 3 Dahiya, Ravinder S.; Valle, Maurizio (2013). Robotic Tactile Sensing. Springer. p. 265. doi:10.1007/978-94-007-0579-1. 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. 1 2 3 4 5 6 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 (27 July 2015). "Artificial Skin (1981)". 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 (9 January 2012). "Plainsboro's Integra LifeSciences opens Asia office". nj. Retrieved 2021-09-21.
  20. ↑ "Office of Device Evaluation – Annual Report – Fiscal Year 1996 (October 1, 1995 - September 30, 1996)" (PDF). Food and Drug Administration . 20 January 2009. 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. (30 June 2013). "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. ↑ Thinda S, Wright HV, Mawn LA (February 2012). "Integra Bilayer Matrix Wound Dressing Closure of Large Periorbital Traumatic Wound". Arch Ophthalmol. 130 (2): 217–219. doi:10.1001/archopthalmol.2011.1178.
  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 (2nd 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. ↑ Yang, Wen; Sherman, Vincent R.; Gludovatz, Bernd; Schaible, Eric; Stewart, Polite; Ritchie, Robert O.; Meyers, Marc A. (27 March 2015). "On the tear resistance of skin". Nature Communications. 6 (1): 6649. doi: 10.1038/ncomms7649 . ISSN   2041-1723. PMC   4389263 . PMID   25812485.
  30. ↑ Fritz, Jason R.; Phillips, Brett T.; Conkling, Nicole; Fourman, Mitchell; Melendez, Mark M.; Bhatnagar, Divya; Simon, Marcia; Rafailovich, Miriam; Dagum, Alexander B. (October 2012). "Comparison of Native Porcine Skin and a Dermal Substitute Using Tensiometry and Digital Image Speckle Correlation". Annals of Plastic Surgery. 69 (4): 462. doi:10.1097/SAP.0b013e31824a43b0. ISSN   0148-7043.
  31. 1 2 Ryan, Alan J.; O'Brien, Fergal J. (1 December 2015). "Insoluble elastin reduces collagen scaffold stiffness, improves viscoelastic properties, and induces a contractile phenotype in smooth muscle cells". Biomaterials. 73: 296–307. doi:10.1016/j.biomaterials.2015.09.003. ISSN   0142-9612.
  32. 1 2 Haugh, Matthew G.; Murphy, Ciara M.; McKiernan, Ross C.; Altenbuchner, Cornelia; O'Brien, Fergal J. (May 2011). "Crosslinking and Mechanical Properties Significantly Influence Cell Attachment, Proliferation, and Migration Within Collagen Glycosaminoglycan Scaffolds". Tissue Engineering Part A. 17 (9–10): 1201–1208. doi:10.1089/ten.tea.2010.0590. hdl: 2262/55329 . ISSN   1937-3341.
  33. ↑ Gravitz, Lauren (5 November 2009). "Spraying on Skin Cells to Heal Burns". Technology Review . Retrieved 2010-02-15.
  34. ↑ Fraunhofer-Gesellschaft (19 May 2009). "Artificial Skin Manufactured In Fully Automated Process". Science Daily . Retrieved 2010-02-15.
  35. ↑ "Artificial Skin Made From Spider Silk : Discovery News". News.discovery.com. 10 August 2011. Retrieved 2013-10-17.
  36. ↑ "New form of artificial human skin". News-medical.net. 14 June 2010. Retrieved 2013-10-17.
  37. ↑ Steenhuysen, Julie (12 September 2010). "Artificial "skin" materials can sense pressure". Yahoo News. Reuters. Archived from the original on 2010-09-16. Retrieved 2010-10-14.
  38. ↑ 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.
  39. ↑ "New artificial skin could make prosthetic limbs and robots more sensitive". e! Science News. 13 September 2010. Retrieved 2013-10-17.
  40. ↑ L. Zhu; J. Kapraun; J. Ferrara; C.J. Chang-Hasnain (March 2015). "Flexible photonic metastructures for tunable coloration" (PDF). Optica. 2 (3): 255–258. Bibcode:2015Optic...2..255Z. doi: 10.1364/OPTICA.2.000255 .
  41. ↑ "3-D bioprinter to print human skin". ScienceDaily. 23 January 2017.
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