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The dermal equivalent, also known as dermal replacement or neodermis, is an ''
in vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology and ...
'' 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
fibroblast
A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells of ...
s into a
collagen gel. This gel may then be allowed to contract as a model of
wound contraction
Wound healing refers to a living organism's replacement of destroyed or damaged tissue by newly produced tissue.
In undamaged skin, the epidermis (surface, epithelial layer) and dermis (deeper, connective layer) form a protective barrier again ...
. 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
A scar (or scar tissue) is an area of fibrous tissue that replaces normal skin after an injury. Scars result from the biological process of wound repair in the skin, as well as in other organs, and tissues of the body. Thus, scarring is a n ...
. Other cell types may be incorporated into the dermal equivalent to increase the complexity of the model. For example,
keratinocytes
Keratinocytes are the primary type of cell found in the epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells.
Basal cells in the basal layer (''stratum basale'') of the skin are sometimes referre ...
may be seeded on the surface to create a
skin equivalent, or
macrophages
Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...
may be incorporated to model the inflammatory phase of
wound healing
Wound healing refers to a living organism's replacement of destroyed or damaged tissue by newly produced tissue.
In undamaged skin, the epidermis (surface, epithelial layer) and dermis (deeper, connective layer) form a protective barrier aga ...
.
A number of commercial dermal equivalents with different compositions and development methods are available. These include Integra, AlloDerm, and Dermagraft, among others.
Purpose
Autotransplantation
Autotransplantation is the organ transplantation, transplantation of Organ (anatomy), organs, Biological tissue, tissues, or even particular proteins from one part of the body to another in the same person (''wikt:auto-, auto-'' meaning "self" ...
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.
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.
History
The development of artificial skin and dermis began in the 20th century.
It was prompted by the discovery of the ability to isolate and culture cells ''
in vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology and ...
'', 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.
In 1975, keratinocytes, which are cells that account for the majority epidermal skin cells, were first isolated and successfully cultured in vitro by James G. Rheinwald and Howard Green. Afterwards, in 1981, bilayer artificial skin or dermal graft was developed by
John F. Burke
John F. Burke (July 22, 1922 – 2011) was an American medical researcher at Harvard University widely known for his co-invention of synthetic skin in 1981, together with Dr. Ioannis V. Yannas.
, Ioannis V. Yannas">ttp://articles.latimes.com/2011/nov/14/health/la ...
, Ioannis V. Yannas, and other researchers, which was successful in covering “physiologically close to 60% of the body surface.”
Burke’s dermal graft was one of the earliest developments of the dermal equivalent, or “neodermis”.
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. 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.
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.
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.
The epidermal portion is composed of
Silastic covering the dermis.
For application, the bilayer structure is placed on the wound after removal of the
eschar and left for several days.
Then, the epidermal layer is removed and replaced with artificial epidermis.
The dermal equivalent, or neodermis layer, is not removed as it is suitable for growth of cells and vessels.
The two layer process, however, may potentially lead to an infection due to any unwanted accumulation between the layers.
The main and primary use of Integra was for burn victims who required skin grafts.
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. 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.
The dermal layer scaffold promotes vascularization and generation of a neodermis.
Similar to its predecessor, the method of application is the same. IDRT has low risks of immunogenic response, as well as low disease transmission.
AlloDerm
AlloDerm is the first type of
acellular dermal matrix
Non-cellular life, or acellular life is life that exists without a cellular structure for at least part of its life cycle. Historically, most (descriptive) definitions of life postulated that an organism must be composed of one or more cells, b ...
(ADM) derived from the skin of
cadavers from the collagen fiber network after the removal of the epidermal layer of the cadaveric skin.
It is widely used in dental surgeries for
gingival grafting, abdominal hernia repair,
oculoplastic and orbital surgeries,
and breast surgeries. Due to its acellular structure, there is no immunogenic response caused from the application of AlloDerm.
Dermagraft
Dermagraft is a human
fibroblast
A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells of ...
–derived dermal replacement.
It is derived from neonatal
dermal fibroblast
Dermal fibroblasts are Cell (biology), cells within the dermis layer of skin which are responsible for generating connective tissue and allowing the skin to recover from injury. Using organelles (particularly the rough endoplasmic reticulum), derma ...
s implanted into a bioabsorbable
polyglactin
Vicryl (polyglactin 910) is an absorbable, synthetic, usually braided suture, manufactured by Ethicon Inc., a subsidiary of Johnson and Johnson. A monofilament version is also made for use in ophthalmic practice. It is indicated for soft tissue ...
mesh scaffold along with
extracellular matrix proteins that are secreted by the fibroblasts.
It can promote re-epithelization, however, there is a potential for antigenic response.
Dermagraft is mainly used for the treatment of chronic wounds such as various ulcers including
diabetic foot ulcers and venous foot ulcers.
It received premarket approval from the FDA in 2001 for the treatment of diabetic foot ulcers.
See also
*
Tissue engineering
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 biologi ...
*
Artificial skin
*
Regenerative medicine
Regenerative medicine deals with the "process of replacing, engineering or regenerating human or animal cells, tissues or organs to restore or establish normal function". This field holds the promise of engineering damaged tissues and organs by st ...
*
Regeneration in humans
References
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External links
IntegraAlloDermDermagraft
{{DEFAULTSORT:Dermal Equivalent
Skin physiology