Dermal equivalent

The dermal equivalent, also known as dermal replacement or neodermis, is an in vitro model of the dermal layer of skin. There is no specific way of forming a dermal equivalent, however the first dermal equivalent was constructed by seeding dermal fibroblasts into a collagen gel. This gel may then be allowed to contract as a model of wound contraction. This collagen gel contraction assay may be used to screen for treatments which promote or inhibit contraction and thus affect the development of a scar. Other cell types may be incorporated into the dermal equivalent to increase the complexity of the model. For example, keratinocytes may be seeded on the surface to create a skin equivalent, or macrophages may be incorporated to model the inflammatory phase of wound healing.[1]

A number of commercial dermal equivalents with different compositions and development methods are available. These include Integra, AlloDerm, and Dermagraft, among others.

Purpose

Autotransplantation has been common practice for treating individuals who have a need for skin transplants. However, there is the issue of needing repeated grafts or transplants for patients with serious injuries such as burn victims, leading to numerous problems including lack of supply of the skin, preservation, and the possibility if disease transmission.[2] Thus, this prompted for the development of various techniques to create artificial skin, including dermal equivalents.

Now, the use of dermal equivalents has expanded from burn wounds to other areas such as various reconstructive surgeries and treatment of chronic wounds.

Risks

There are potential risks when it comes to the application of any dermal equivalent, as there is with any skin grafting or skin substitution technique. These concerns include but are not limited to a negative immune response, possible infection, slow healing, pain, and scarring.[3]

History

The development of artificial skin and dermis began in the 20th century.[4] It was prompted by the discovery of the ability to isolate and culture cells in vitro, which was in 1907 by American embryologist Ross Granville Harrison when he was able to isolate and grow embryonic tissues from frogs in his laboratory.[4] In 1975, keratinocytes, which are cells that account for the majority epidermal skin cells,[5] were first isolated and successfully cultured in vitro by James G. Rheinwald and Howard Green.[6] Afterwards, in 1981, bilayer artificial skin or dermal graft was developed by John F. Burke, Ioannis Yannas, and other researchers, which was successful in covering “physiologically close to 60% of the body surface.”[7]

Burke’s dermal graft was one of the earliest developments of the dermal equivalent, or “neodermis”.[7] Years later, Integra artificial skin, which is now called Integra Dermal Regeneration Template (IDRT) by Integra LifeSciences, was developed from Burke et al.'s innovation.[8] It became the first commercial product approved by the FDA for dermal replacements and listed as one of the "Significant Medical Device Breakthroughs" in 1996.[9]

Commercial products and applications

There are a variety of dermal equivalents from how they are developed and what they are used for. The following three are some of the most commonly reviewed and assessed dermal equivalents.[10][11]

Integra

The initial research of dermal equivalent leading to the Integra product resulted in a bilayer structure consisting of a dermal portion and epidermal portion. The dermal portion is composed of bovine hide collagen and chondroitin 6-sulfate that is crosslinked with glutaraldehyde.[7] The epidermal portion is composed of Silastic covering the dermis.[7] For application, the bilayer structure is placed on the wound after removal of the eschar and left for several days.[7] Then, the epidermal layer is removed and replaced with artificial epidermis.[7] The dermal equivalent, or neodermis layer, is not removed as it is suitable for growth of cells and vessels.[7] The two layer process, however, may potentially lead to an infection due to any unwanted accumulation between the layers.[3] The main and primary use of Integra was for burn victims who required skin grafts.[2][7]

Integra Dermal Regeneration Template

Formerly known as Integra artificial skin, Integra Dermal Regeneration Template, or IDRT, was the first FDA approved product for dermal replacements. The Integra Dermal Regeneration Template’s bilayer structure is composed of bovine tendon collagen and chondroitin-6-sulfate for the dermal layer, and polysiloxane for the epidermal layer.[12] The polysiloxane epidermal layer is semipermeable, allowing for the controlled water vapor loss, flexible anti-bacterial support of the wound, and mechanical strength for the dermal equivalent.[11] The dermal layer scaffold promotes vascularization and generation of a neodermis.[11] Similar to its predecessor, the method of application is the same. IDRT has low risks of immunogenic response, as well as low disease transmission.[11]

AlloDerm

AlloDerm is the first type of acellular dermal matrix (ADM) derived from the skin of cadavers from the collagen fiber network after the removal of the epidermal layer of the cadaveric skin.[13][14] It is widely used in dental surgeries for gingival grafting,[15] abdominal hernia repair,[13] oculoplastic and orbital surgeries,[14] and breast surgeries.[16] Due to its acellular structure, there is no immunogenic response caused from the application of AlloDerm.[11]

Dermagraft

Dermagraft is a human fibroblast–derived dermal replacement.[17] It is derived from neonatal dermal fibroblasts implanted into a bioabsorbable polyglactin mesh scaffold along with extracellular matrix proteins that are secreted by the fibroblasts.[17] It can promote re-epithelization, however, there is a potential for antigenic response.[11] Dermagraft is mainly used for the treatment of chronic wounds such as various ulcers including diabetic foot ulcers and venous foot ulcers.[17] It received premarket approval from the FDA in 2001 for the treatment of diabetic foot ulcers.[18][19]

See also

References
  1. Newton PM, Watson JA, Wolowacz RG, Wood EJ (August 2004). "Macrophages restrain contraction of an in vitro wound healing model". Inflammation. 28 (4): 207–214. doi:10.1023/B:IFLA.0000049045.41784.59. PMID 15673162. S2CID 9612298.
  2. Greenfield E, Jordan B (June 1996). "Advances in burn wound care". Critical Care Nursing Clinics of North America. Wound Care. 8 (2): 203–215. doi:10.1016/S0899-5885(18)30336-8. PMID 8716388.
  3. Alrubaiy L, Al-Rubaiy KK (January 2009). "Skin substitutes: a brief review of types and clinical applications". Oman Medical Journal. 24 (1): 4–6. doi:10.5001/omj.2009.2. PMC 3269619. PMID 22303500.
  4. Pickerill HP (October 1951). "On the possibility of establishing skin banks". British Journal of Plastic Surgery. 4 (3): 157–165. doi:10.1016/s0007-1226(51)80028-6. PMID 14886567.
  5. McGrath JA (2004). Anatomy and Organization of Human Skin. Rook's Textbook of Dermatology. John Wiley & Sons, Ltd. pp. 45–128. doi:10.1002/9780470750520.ch3. ISBN 978-0-470-75052-0.
  6. Rheinwald JG, Green H (November 1975). "Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinizing colonies from single cells". Cell. 6 (3): 331–343. doi:10.1016/s0092-8674(75)80001-8. PMID 1052771. S2CID 53294766.
  7. Burke JF, Yannas IV, Quinby WC, Bondoc CC, Jung WK (October 1981). "Successful use of a physiologically acceptable artificial skin in the treatment of extensive burn injury". Annals of Surgery. 194 (4): 413–428. doi:10.1097/00000658-198110000-00005. PMC 1345315. PMID 6792993.
  8. "Artificial Skin: The Innovation That Changed Complex Burn Wound Care Forever". ITT Blog | Integra LifeSciences. 2021-04-23. Retrieved 2021-10-27.
  9. Office of Device Evaluation (2009-01-20). "Annual Report Fiscal Year 1996 (October 1, 1995 - September 30, 1996)" (PDF). Food and Drug Administration. Archived from the original (PDF) on 2009-01-20. Retrieved 2021-10-27.
  10. Kirsner RS, Falanga V, Eaglstein WH (June 1998). "The development of bioengineered skin". Trends in Biotechnology. 16 (6): 246–249. doi:10.1016/S0167-7799(98)01196-2. PMID 9652135.
  11. Savoji H, Godau B, Hassani MS, Akbari M (2018). "Skin Tissue Substitutes and Biomaterial Risk Assessment and Testing". Frontiers in Bioengineering and Biotechnology. 6: 86. doi:10.3389/fbioe.2018.00086. PMC 6070628. PMID 30094235.
  12. "Integra® Dermal Regeneration Template" (PDF). Archived (PDF) from the original on 2021-03-25.
  13. Buinewicz B, Rosen B (February 2004). "Acellular cadaveric dermis (AlloDerm): a new alternative for abdominal hernia repair". Annals of Plastic Surgery. 52 (2): 188–194. doi:10.1097/01.sap.0000100895.41198.27. PMID 14745271. S2CID 46170403.
  14. Park SJ, Kim Y, Jang SY (January 2018). "The application of an acellular dermal allograft (AlloDerm) for patients with insufficient conjunctiva during evisceration and implantation surgery". Eye. 32 (1): 136–141. doi:10.1038/eye.2017.161. PMC 5770710. PMID 28799557.
  15. Shaikh MS, Lone MA, Matabdin H, Lone MA, Soomro AH, Zafar MS (February 2021). "Regenerative Potential of Enamel Matrix Protein Derivative and Acellular Dermal Matrix for Gingival Recession: A Systematic Review and Meta-Analysis". Proteomes. 9 (1): 11. doi:10.3390/proteomes9010011. PMC 8005981. PMID 33668721.
  16. Macadam SA, Lennox PA (2012-05-01). "Acellular dermal matrices: Use in reconstructive and aesthetic breast surgery". The Canadian Journal of Plastic Surgery. 20 (2): 75–89. doi:10.1177/229255031202000201. PMC 3383551. PMID 23730154.
  17. Hart CE, Loewen-Rodriguez A, Lessem J (June 2012). "Dermagraft: Use in the Treatment of Chronic Wounds". Advances in Wound Care. 1 (3): 138–141. doi:10.1089/wound.2011.0282. PMC 3623576. PMID 24527294.
  18. Zhang Z, Michniak-Kohn BB (January 2012). "Tissue engineered human skin equivalents". Pharmaceutics. 4 (1): 26–41. doi:10.3390/pharmaceutics4010026. PMC 3834903. PMID 24300178.
  19. "Summary of Safety and Effectiveness Data" (PDF). Food and Drug Administration. September 2001. Archived (PDF) from the original on 2017-01-27.
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