Skin substitutes are wound coverage materials that aid in wound closure and replace the functions of the skin, either temporarily or permanently, depending on the product characteristics.
Skin represents approximately 16% of the total body weight. Skin has main functions of protection of inner structures, important role in protein and vitamin D metabolism.
Restoration of a skin barrier is of critical importance and may be achieved in numerous ways. Conventionally, autologous split or full-thickness skin graft have been recognized as the best definitive for wound coverage. But the limitation and morbidity of donor side is major handicap.
Skin substitutes are considered as reasonable alternatives. These provide rapid wound coverage, require less vascularised wound bed, increase the dermal component of wound and reduce inhibitory factors.
The decrease in inflammatory response reduces subsequent scarring.
Skin substitutes generally have higher cost, expertise and experience.
The skin is made up of two distinct layers, the epidermis and the dermis. Cultured or artificial dressings, therefore, may be used as a substitute for the epidermal layer, the dermal layer, or both.
Characteristics of a Skin Substitute
Ideally, a skin substitute should provide immediate replacement of both the lost dermis and epidermis, with permanent wound coverage
It should be able to resist infection, prevent water loss and able to withstand the shear forces. At the same time it should be inexpensive, widely available and have long shelf life.
It should not be antigenic, flexible in thickness, conforming to irregular wound surface and durable. It should be easy to apply and secure.
There is no single substitute that fulfills the above mentioned criteria.
Classification of Skin Substitutes
Composition based Classification
Class I: Temporary impervious dressing materials
Single layer materials
- Biological – amniotic membrane, potato peel
- Synthetic – Polymer sheet or foam
Bi-layered Tissue Engineered Materials
Class II: Single layer durable skin substitutes
- Epidermal substitutes – Cultured epithelial autograft
- Dermal substuitutes
- Bovine collagen shhet
- Porcine collagen sheet [Kollagen®]
- Bovine dermal matrix, e.g. Matriderm®
- Human dermal matrix, e.g. Alloderm®
Class III: Composite skin substitutes
- Skin graft
- Tissue engineered skin
- Dermal regeneration template – e.g. Integra®
Temporary and Permanent Skin substitutes
Temporary skin substitutes provide temporary physiologic wound closure. It protects the wound from mechanical trauma and creates physical barrier to bacteria. It also forms moist wound environment.
The common uses are
- Donor site dressing to facilitate epithelialisation and pain control,
- Dressing clean superficial wounds until epithelialisation
- Temporary physiological closure of deep dermal and full thickness wounds while awaiting autografting,
- As sandwich graft technique over the widely meshed autografts and
- As a test graft where the wound bed is doubtful.
The permanent skin substitutes have the roles of permanently achieving wound closure, replacing the skin components and providing a higher quality skin replacement than the thin autogolous skin graft.
Biological and Synthetic
These skin substitutes which act temporarily like skin, have the advantages of being relatively abundant in supply and not expensive. While the synthetic skin substitutes can be synthesised on demand and can be modulated for specific purposes with increased control over scaffold composition, the biological skin substitutes have a more intact and native ECM structure which may allow the construction of a more natural new dermis. They also allow excellent re-epithelialisation characteristics due to the presence of a basement membrane. However, natural constructs can exhibit problems with slow vascularisation of the material. The most widely used biological substitute worldwide are cadaveric skin allograft, porcine skin xenograft and amnion.
Xenograft, allograft and amnion are examples of bilologic skin graft whereas Dermagraft and Matriderm are examples of commercially available skin coverages.
Biological Skin Substitutes
Allografts and xenografts
Allografts, or homografts are transplanted from one individual to another within the same species and typically taken from cadevers.
Xenografts are grafts from different species. These are also called heterografts and most commonly taken from pig or bovine skin.
Both allografts and xenografts are biologic dressings only, are ultimately rejected by the patient’s immune system, and need to be removed prior to definitive wound treatment or skin grafting.
Xenografts are rejected before undergoing revascularization. Allografts initially undergo revascularization but are typically rejected after approximately 10 days. Immunocompromised patients [severe burn] may tolerate them longer.
Xenografts can be used as a temporary dressing for clean partial-thickness wounds, such as are incurred with toxic epidermal necrolysis.
Commerically available products modifications to extend the lifespan and microbial resistance of the graft.
The amnion is a thin semi-transparent tissue forming the innermost layer of the fetal membrane. The amnion has been used as biological dressings since early part of twentieth century.
Because there is a risk of contamination and disease transmission, therefore amnion is collected from placentae of selected and screened donors.
Various methods for preservation cryopreservation in liquid nitrogen, preservation in silver nitrate, storage in antibiotics solution, glycerol-preserved sheets, dried sheets and gamma-irradiated sheets.
It is an effective biological skin substitutes for use in burn wounds. It has advantages that it maintains low bacterial count, reducing loss of protein, fluid and electrolytes. It also decreases pain and accelerates wound healing.
It has good handling properties.
It is particularly useful for superficial partial-thickness facial burns.It is also used for temporary coverage in wound bed preparation and sandwich grafting technique.
Cultured epithelial autografts
A large surface area of keratinocytes can be obtained from the relatively small biopsy of healthy skin from the patient. The autologous keratinocytes are isolated, cultured and expanded into sheets over periods of 3–5 weeks.
Cultured epithelial autografts are limited by the fragility and difficulty of handling. The take rate is unpredictable take rate and there is high cost involved.
Epicel is one such example.
But this type of skin substitute have been associated with high rates of infection and graft loss, due to lack of dermal layer.
Cultured skin substitute (CSS) is composed of a CEA combined with a cultured autologous dermal layer and provides a more biologically similar material for skin replacement.
Replicating the complexity of the dermal structure has been quite challenging.
Acellular dermal allografts, such as AlloDerm, Matriderm are composed of cadaveric dermis that serves as a scaffold for the ingrowth of recipient tissue. These processed to remove cells while preserving the essential biological components and structure of the dermal matrix to support regeneration.
AlloDerm has also been used in combination with a split-thickness skin graft for single-stage soft tissue defect reconstruction.
Strattice (LifeCell), SurgiMend (TEI Biosciences), GraftJacket (Wright Medical Technologies), NeoForm (Mentor Corporation), and DermaMatrix (Synthes) are other examples.
They are used for coverage of partial and full-thickness defects. These can be permanently incorporated into the patient’s new skin layers without being rejected by the patient’s immune system.
Immediate availability and reduction of risk due to acellular nature are advantages.
Thinner split-thickness skin grafts can be used and improve overall split-thickness skin graft incorporation.
Synthetic Skin Substitutes
An ideal synthetic skin dressings or substiture should be stable, immunocompatible, biodegradable and provide an adequate environment for the regeneration of tissue.
It is desirable that it maintains its three-dimensional structure for at least 3 weeks to allow ingrowths of blood vessels, fibroblast and coverage by epithelial cells. Biodegradation should preferably take place after this period.
Foreign body reaction should be minimal as it could lead to scarring.
Important synthetic skin substitutes available in the market are discussed
Biobrane (Smith-Nephew) consists of an inner layer of nylon mesh that allows fibrovascular ingrowth and an outer layer of silastic that serves as barrier to water loss and bacteria.
It is composed of a silicone membrane (the epidermal layer) coated on one side with porcine collagen and embedded with nylon mesh (the dermal layer). When used to cover partial-thickness wounds, the mesh adheres to the wound until healing occurs below.
When used to cover partial-thickness wounds, the mesh adheres to the wound until healing occurs beneath. Biobrane needs to be removed prior to skin grafting.
There is good evidence that supports the use of Biobrane
It has been found to reduce pain in the management of burns, particularly in partial-thickness burns in children.
Patient treated with Biobrane were found to have lesser pain, there was reduction in duration of hospital stay and wound healing time.
However, Biobrane has been associated with permanent scarring in partial-thickness scald wounds.
Biobrane is used in burn wounds, chronic wounds, or following skin resurfacing.
Dermagraft and Transcyte
Dermagraft is a bioabsorbable polyglactin mesh seeded with allogenic neonatal fibroblast.
It is used in burn wounds, chronic wounds and diabetic ulcers.
It can be used as a temporary or permanent covering.
Dermagraft is claimed to produce results as good as allograft. its removal is considered easier than allograft. No adverse reactions have been repeorted.
TransCyte is a nylon mesh incubated with human fibroblasts that provides a partial dermal matrix with an outer silicone layer as a temporary epidermis. It is indicated for use in deep partial or excised full-thickness wounds prior to autogenous skin graft placement. It must be removed or excised prior to grafting full-thickness wounds.
Integra (Integra LifeSciences Corp) is a dermal regeneration template consisting of bovine collagen, chondroitin-6-sulphate and a silastic membrane.
It is used in deep partial-thickness and full-thickness burn wounds and full-thickness skin defects of other etiologies,
he bovine collagen dermal analogue integrates with the patient’s own cells and the temporary epidermal silicone is peeled away as the dermis regenerates followed by a very thin autograft.
Apligraft [composite allograft] is a bilayered living skin equivalent, composed of type I bovine collagen and allogenic keratinocyte and neonatal fibroblast
It is used in partial to full thickness burns, skin graft donor sites, chronic wounds, diabetic ulcers and epidermolysis bullosa.
As it has shelf life of just 5 days, it is applied fresh.
It has been shown to accelerate wound closure. When it is combined with autograft has produced better results than autograft only.
Matriderm(Skin and Health Care AG, Billerbeck, Germany) is a structurally intact matrix of bovine type I collagen with elastin. It is utilised for dermal regeneration in full thickness or deep dermal burn wounds and chronic wounds. The matrix serves as a support structure for the ingrowth of cells and vessels.
The elastin component improves the stability and elasticity of the regenerating tissue.
During wound healing fibroblast lays down the extracellular matrix and the Matriderm is resorbed.
The indications are similar to Integra.
OrCel is a bilayered cellular matrix in which normal human allogeneic neonatial epidermal keratinocytes and dermal fibroblasts are cultured in two separate layers into a type I bovine collagen sponge.
It is indicated in the treatment of chronic wounds and skin graft donor sites. OrCel has also been used as an overlay dressing on split-thickness skin grafts to improve function and cosmesis.
Hyalomatrix (Fidia Advanced Biopolymers) is a bilayer hyaluronan base scaffold with autologous fibroblast with outer silicone membrane. The scaffold delivers hyaluronan to the wound bed. The silicone membrane acts as a temporary epidermal barrier.
It is indicated in burn wounds and chronic wounds.
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