Chronic Wounds are wounds that have not healed on their own in a given period of time. They can be managed in different ways, such as specialized dressings, surgery (for example, skin grafts and flaps of the patient's own skin) or the use of bioengineered skin.
The development of bioengineered skin was motivated by the critical need to cover extensive burn injuries in patients with insufficient skin for grafting. Bioengineered skin substitutes have also been widely used for a variety of chronic wounds with the goal of faster and reduced healing infection and better aesthetic appearance.
What is bioengineered skin?
Bioengineered skin consists of an exterior epidermal layer and / or a dermal layer (the layer of skin between the epidermis and the subcutaneous tissue) embedded in an acellular matrix (a supporting structure) forming a biological substitute for the skin.
This "artificial" tissue can be cultured from the patient's own cells or from other "allogenic" (non-proprietary) sources. Most commercial bioengineering skins consist of sheets of cells derived from neonatal foreskin (allogeneic). The neonatal foreskin is chosen because:
- It is a convenient source obtained from healthy babies undergoing circumcision
- has a high epidermal content keratinocytes Mother cells
- cells grow vigorously with high metabolic activity
- allergic reactions against cells are rare.
How does bioengineered skin work?
Bioengineered skin is designed to temporarily take over the functions of the epidermis and / or dermis until the patient's skin barrier is repaired spontaneously or until definitive skin replacement with a skin graft or cultured equivalent is possible.
Bioengineered skin is believed to accelerate wound healing by introducing living cells to restore the conditions necessary for repair, including:
- moist wound environment
- Structural support
- cytokines and growth factors to stimulate the immune response and tissue regeneration.
Important features for a biosynthetic skin substitute include:
- fast and sustained adherence to the wound surface
- waterproofing to the outside bacteria
- allows the transmission of water vapor similar to normal skin
- internal surface structure that allows cell migration /proliferation/ growing new tissue
- flexible and flexible so it can adapt to uneven wound surfaces
- biodegradable
- low cost
- indefinite useful life
- minimum storage requirements
- non-antigenic, so it is not subject to immune rejection by the host
- non-local /systemic toxicity.
How does bioengineered skin compare to skin grafts?
Bioengineered skin substitutes represent artificial alternatives to skin grafts. Its advantages include:
- less pain than skin grafting
- Fewer complications than skin grafting
- always available in any quantity needed
- can be applied in an office environment
- negligible risk of cross infection
- There is no need to harvest grafts or heal wounds at the harvest site.
What is bioengineered skin used for?
Tissue-designed skin substitutes have emerged as a potential alternative to skin grafting in patients with the following conditions:
Leg ulcers because venous insufficiency
- Diabetic foot ulcers
- Ulcers associated with peripheral arterial disease
- Vasculitic ulcers
Pressure ulcers (pressure ulcers).
- Severe burns
- Epidermolysis bullosa (EB)
- Pyoderma gangrenous
- Systemic sclerosis
- Breast reconstruction surgery
- Acute surgical wounds such as those caused by excision fur Cancer.
Commercial bioengineered leather products
Bioengineered leather products that are commercially available in the US and / or Europe are tabulated below.
| Product | Description | Indications approved by the US FDA. | Unapproved uses | Competitive advantages | Disadvantages |
|---|---|---|---|---|---|
| Alloderm® [LifeCell Inc. Woodlands, Texas, USA] | Skin tissue donated from cadavers to make an acellular dermal matrix that was lyophilized after processing. It is used to serve as a scaffold for normal tissue remodeling. the collagen The frame provides strength to the skin and contains no cells that can cause rejection or irritation. Duration of permanent contact. Available in Australia on a case-by-case basis. | Full thickness burns / wounds | Other formulations (Cymetra ™, Repliform ™) have been used to fill Soft fabric defects in plastic, gynecological, dental and urological surgery | Not rejected without cases of viral transmission after> 100,000 product applications; 2 year shelf life | Lack cellular components |
| Apligraf® [[Organogenesis Inc. Canton, Massachusetts USA] | Is a culturederived from equivalent human skin. Like human skin, it has 2 layers. The upper epidermal layer is made of living human beings. keratinocytes. The lower dermal layer consists of human fibroblasts combined with bovine collagen to produce a protein matrix. This living skin construction is similar in cell proliferation to human skin. Duration of permanent contact. Available in Australia for clinical trials only. | Venous / diabetic ulcers | Epidermolysis bullosa; anecdotal reports, case studies, and pilot trials in many other conditions, such as recurrent hernia repair, reconstruction of the major abdominal cavity, burns and pressure ulcers | It mimics the function of the dermis; cryopreserved product | 5 days shelf life; awkward logistics of ordering and use |
| Celaderm ™ [Celadon Science LLC, Brookline, MassachusettsUSA] | It is an allograft containing active keratinocytes made from epithelial neonatal foreskin cells. Although metabolically active, they are not capable of proliferating. | (None) | Partial and full thickness burns, venous wounds | > 6 months shelf life; relatively cheap; good results in many pilot studies | Not FDA approved |
| Dermagraft® [Smith and Nephew Inc. Largo, Florida, USA] | It is a single layer biosynthetic dermal substitute made from human fibroblasts obtained from the neonatal foreskin and cultured on a bioabsorbable polyglactin mesh for several weeks. Matrix proteins are secreted during the culture period and include human dermal collagens and soluble factors that create a three-dimensional matrix that is used as a dermal replacement or temporary skin substitute. Duration of permanent contact. Available in UK and Canada. | Diabetic foot ulcers; ulcers secondary to epidermolysis bullosa | (None) | It mimics the function of the dermis; cryopreserved product | Difficult order and application logistics; short shelf life (unless cryopreserved) |
| Epicel® [Genzyme Biosurgery, Cambridge, Massachusetts USA] | Autologous keratinocytes from a patient's healthy skin tissue are cultured to form cultured epidermal autografts. Autografts are processed into sheets that are attached to a Vaseline gauze backing using stainless steel surgical clips. Duration of permanent contact. | Deep partial and full thickness burns; congenital naevi | (None) | Autologous cells; no rejection, high incidence catchment | Fragile; personalized preparation one day of shelf life; lower cosmesis in many patients |
| Endoform® Dermal Insole [Aroa Biosurgery, New Zealand, marketed by Hollister Inc.] | A xenograft the extracellular matrix (ECM) composed of a complex mix of biological products molecules. Provides structure, substrates and signs for regenerative healing. Restores cell-ECM interactions, aids cell migration, encourages new blood vessel formation and neutralizes enzymes. Patient cells migrate to the scaffold. Usually, patients are treated once a week for 6 to 12 weeks. | Diabetic, venous, arterial and pressure ulcers. Surgical, partial and full thickness wounds, trauma, drainage, tunneled / undercut wounds | (None) | Matrix metalloproteinase inhibition; economic fast cure; fixing is not required; accessible at all wound care treatment sites; 3 year shelf life | Should not be applied if there is an uncontrolled, acute infection inflammationexcessive exudate or bleeding not indicated for third degree burns |
| EZ Derm ™ [Brennen Medical Inc. Saint Paul, Minnesota, USA] | It is a porcine (pig) (non-human skin graft) derived xenograft from collagen that has been chemically crosslinked with aldehyde to provide strength and durability. | Partial thickness burns, venous ulcers, diabetic ulcers, pressure ulcers. | (None) | Relatively long lifespan | Possible immune response and / or disease transmission |
| Integra® [Integra LifeSciences Corp. Plains-boro, NJ, USA] | It is a bilayer membrane system (two layers) made of a porous matrix of fibers that crosslink bovine tendon collagen and glycosaminoglycan. The epidermal replacement layer is made of a thin layer of poly silicone to control humidity. Duration of permanent contact. Product available in Australia. | Deep partial and full thickness burns | (None) | Two layers; good barrier function; used in more than 10,000 patients; moderate shelf life | Operational removal of the silicone layer is required |
| Laserskin® [Fidia Advanced Biopolymers, Italy] | This product is based on a biodegradable matrix composed of a benzyl esterified hyaluronic acid derivative with order To bePerforated microholes for the growth and proliferation of autologous keratinocytes. Autologous keratinocytes are isolated from a skin. biopsy and grown directly in the womb. The graft can be removed from the culture without altering the arrangement of the basement membrane proteins. Duration of permanent contact. This product is currently commercially available only in Europe. | (None) | Partial thickness burns, chronic venous and pressure ulcers, vitiligo | Autologous cells; without rejection; high incidence of permanent intake | Two-day shelf life; fragile custom grooming |
| Oasis® [Healthpoint, USA] | It is a substitute for acellular skin made from the porcine (pig) small intestine. The matrix is composed of acellular collagen and acts as a covering for the wound. It accommodates the remodeling of host tissue by providing an acellular dermal scaffold for tissue growth. | Partial / total pressure, venous and diabetic wounds / burns | (None) | 1.5 year shelf life | Potential immune response |
| OrCel® [Ortec International Inc. New York, New York, USA] | Formally known as composite cultured skin, it is an equivalent live skin. This bilayer cell matrix is made from human dermal cells. [containing neonatal foreskin-derived cultured keratinocytes and fibroblasts] cultured in bovine collagen sponge. Duration of permanent contact. | Reconstruction surgery of the hand in patients suffering from recessive dystrophic epidermolysis bullosa and for the healing of autograft donor sites in patients with burns. | Venous and diabetic wounds. | Imitates cytokine skin healing expression; Shelf life of 9 months; cryopreserved | Requires cryopreserved storage |
| TransCyte® [Smith and Nephew Inc. Florida, USA; Advanced Tissue Sciences Inc. La Jolla, California, USA] | It is a bilaminate skin substitute made from human fibroblasts grown in a silicone-coated nylon mesh and combined with a synthetic epidermal layer. Duration of temporary contact. Product available in Australia. | Full and partial thickness burns | (None) | 1.5 years frozen shelf life | The silicone membrane must be removed. |
Cost considerations
Although the initial capital cost of bioengineered skin substitute is higher than standard wound dressings, the cost-effectiveness analysis has shown that the total cost of using bioengineered skin may be less than standard care due to the earliest wound resolution and the shortest time in hospital / assisted care.
Ethical considerations
The following ethical and / or religious concerns associated with the use of skin substitutes should be considered in the treatment of patients with chronic wounds.
- The use of donor organs or animal tissue in the preparation of bioengineered skin can pose problems for ethnic or religious groups, vegans, vegetarians, and animal rights activists.
- Transmission of viral and prion diseases and use of material neonates.
Patients should be informed about the product. constituents in bioengineered leather to guarantee your informed consent.
Safety
Bioengineered skin substitutes are considered at least as safe as standard therapies for burns and wound care, based on evidence from randomized controlled trials.
Contraindications
Apligraf® is contraindicated to use in the following situations:
- infected wounds
- known allergy to bovine collagen
- known hypersensitivity to components in the product agarose delivery medium.
Dermagraft® is contraindicated for use in the following situations:
- ulcers that have signs of clinical infection
- ulcers that have breast treaties
- patients with known hypersensitivity to bovine products.
Challenges and future directions
Technological improvements may result in better bioengineered skin products in the future.
The controversies and unanswered questions associated with the design of bioengineered skin products include:
- Does adding dermal tissue improve results compared to applying sheets of cultured epidermal keratinocytes alone?
- Does the addition of keratinocytes improve the results obtained using a culture fibroblasts-contain matrix alone?
- Does freezing, thawing, and rinsing cells damage or remove potentially beneficial growth factors necessary for wound healing?
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