Alternatives

 

What skin substitutes are available and how do they work?
Apligraf vs. other substitutes
Apligraf vs. standard of care for diabetic ulcers
Risks of Apligraf vs. other treatments
More Skin Substitutes
Other types of wound treatments

 

Skin substitutes currently Available:

Epidermal:

Epidermal skin grafts involve the cultivation of large quantities of keratinocytes in vitro and tissue technology to develop a thin sheet of subculture epidermal cells.  The only epidermal autograft available today and approved by the FDA is Epicel (Genzyme Tissue Repair Corporation, Cambridge, MA)  This product has been available since 1988 for burn wound repair.  The advantages of an epidermal autograft are that they cover large wound areas.  They provide permanent coverage with autologous cells of the patient.  They have very acceptable cosmetic results and they act as a stimulus to wound healing through eventual regeneration of the dermis.  The disadvantages of epidermal grafts is that they require a new injury to the patient to harvest a biopsy speciment.  They also require a two to three week wait for the cultivation of the epithelium. The epidermal grafts lack a dermal bed and are also relatively thin and fragile in comparison to other graft substitutes.

Dermal:

Dermal grafts include donor cadaver allograft skin used for temporary wound coverage on burn patients.  The antigenic donor epithelium with a split-thickness skin graft has resulted in very good graft take to patients with little rejection.  Yet safety and availability concerns do limit the use of this graft for wound therapy. 

The donor skin is chemically treated after it is harvested to remove all antigenic epidermal cellular components.  Alloderm (LifeCell Corporation, Woodlands, TX)  has created a product that leaves immunologically inert acellular dermal matrix and an intact basement membrane complex for application to burn wound sites.  This product has been used in hospitals alone, and with cultured autograft skin sites with good results.  Although this therapy seems prominent, there have been no studies comparing the use of living and non-living dermis substitutes.

Two dermal products:

    1.  Integra (Integra LifeSciences Corporation, Plainsboro, NJ.)

    2. Dermagraft (Advanced tissue Sciences inc. La Jolla, CA.)

Composite:

There are numerous products today that are under trial in the composite graft category.  Composite grafts are made of bi-laminate membranes combining a silastic outer covering that is bonded to a collagen based dermal analog (usually bovine and collagen chondroitin sulfate).       A list of these products is provided.  Although several exist, there is not one that outweighs another in regard to clinical use or patient preference.

Two composite products:

    1.   Composite Culture Skin - CCS (Ortec International Inc., New York NY.)

           

           

    2.   Apligraf (Organogenesis, Canton, MA.)

          

 

Apligraf vs. other skin substitutes:

Apligraf Advantages:

Disadvantages:

 

Apligraf vs. standard of care for diabetic ulcers

 

Risks of Apligraf vs. other treatments

Autologous Skin Graft:  injury and scarring of harvest site.

  Engineered Skin Substitutes:

Compression Therapy Risks:

 

More Skin Substitutes.

Epicel (Genzyme Tissue Repair Corp, Cambridge Mass.) Consists of cultured autologous keratinocyte sheets used for patients with burns.  Cost is $790 for a 50 cm piece.  An average of 100 pieces are used per patient.

Transcyte (Advanced Tissue Sciences, La Jolla, CA) temporary coverage of burns.  Allogeneic fibroblasts are grown on a nylon mesh and the cost is approximately $675 for a 5x7 in. Per piece.  The product is approved for treatment of diabetic foot ulcers in Australia, England, Canada, Denmark, Finland, Norway, the Netherlands, and New Zealand.  FDA is still requiring an ongoing trial since 1998 which has not yet been completed.  Current average cost in Canada is $440 for a 2x3 in piece.  This product is instructed to be applied once a week for up to eight weeks. 

Alloderm (LifeCell Corp, Woodland, Tex) This product involves processing human cadaver skin to remove antigenic cellular components.  This leaves an immunologically inert acellular dermal matrix with an intact basement membrane complex.  Although not recommended for large coverage, this dermal matrix has several uses from smaller scale surgical wounds, small burns, and scar revision.  This product has a smaller selling price of $180 for each 200 cm package. 

VivoDerm (ER Squibb & Sons Inc, Princeton, NJ)  This product has been approved for use in Germany, Italy, and the United Kingdom but is unavailable in the U.S.  This company produces a sheet of culture autologous keratinocytes from a patient biopsy that are grown on a hyaluronic acid membrane.  Small manufactures pores allow the keratinocytes to migrate through the membrane to the direct surface of the wound.  This product although unregulated, has been successful in treating burns, and chronic venous ulcers. 

 

Other types of wound treatments:

Standard Compression therapy has remained the “gold standard” of treatment of venous ulcers.  Of all dressings and topical products on the market, none have proven significantly more effective than standard compression therapy.

Skin Graft Procedure:  This procedure is performed on patients with severe burns or chronic, deep venous ulcers.  The surgery consists of choosing a donor site, cleaning the burned area, and harvesting (where the healthy skin is shaved and prepared to be donated).  During hospitalization, an area of skin 10/1000 of an inch thick is shaved off a donor with an instrument called a Dermatome  Skin can be harvested from either a cadaver (a homograft, allograft, or cadaver skin) and is placed onto the effected burn area that has been cleaned and sterilized.  A compression wrap secures the donor skin to the patient while vascularization of the donor skin secures the two tissues together during a period of immobilization for approximately 5 days. 

With temporary skin graft treatments, Cadaver skin is used as a temporary covering for cleaned wound surfaces before an autograft is placed.  An unmeshed cadaver tissue is put over the excised wound and stapled into place.  Post-operatively, the cadaver skin is covered with a dressing that is removed prior to the permanent autografting.

Selozinc: a Zinc past bandage that is applied to surface wound areas.  This product is a ready-prepared bandage made or rich, thick, anti-inflammatory zinc past.  This paste is spread over the wound by a saturated rolled gauze.  This product favors muscle and connective tissue movements because it remains supple after application.  It is used for healing venous ulcers, phlebothombosis, sequelae, and varices.  It’s advantages over normal compression wraps is that it provides a semi-rigid compression bandage with the stimulating growth factors of zinc.  The price of a roll of this product is relatively inexpensive at $11.08 for a 4” x 10 yds piece.  The product is also available by the case that includes ten rolls for $301.16.  Because of the affordability and simplicity of this therapy, it is a common option for the treatment of varicose ulcerations.  There are several similar zinc paste products on the market that are used as dressings in several skin therapies.

Wound Coverage with Amniotic Membrane:  Cellular or acellular dermal component alternative would be human amniotic membrane.  These are obtained from the human placenta after delivery and are in large supply at major hospitals.  They are prepared rather inexpensively and possess most of the characteristics of an ideal skin substitute.  They adhere to the wound excellently, there is low immunogeneicity, decrease of pain, bacterial control, and stimulation of healing.  Another advantage is that they are transparent and allow the inspection of the wound.  They are used to cover meshed autografts and are very effective in sterilizing contaminated wounds and cleaning burns of bacteria in 3 to 5 days.  Amniotic membranes must be change daily and covered with gauze.  They do not allow long-term coverage and can be dissolved by the wound very early.  They must be kept refrigerated for up to 6 hours and they can also be frozen for storage or banking. 

Xenogeneic Grafts: Animal grafts achieve only temporary wound coverage, but the unlimited availability under well-controlled conditions make animal skin a good skin substitute.  Porcine skin is the most common source of a xeno-graft because it is very similar to human skin.  Ionizing radiation is used to guarantee sterility for application and freeze-drying has been used to decrease the antigenic properties and increase it potential to inhibit bacterial growth. 

Most common as a temporary dressing for coverage of second-degree burns.  Especially after early excising and promotes scar free healing with an average application duration of approximately 10 days.  Disadvantages of porcine grafts include expensive irradiation and free-drying.  Therefore an alternative technique using glycerin for storage has been developed.  To prevent rejection of xenogeneic tissues, efforts have been made to make non-immunogeneic artificial dermal matrices.  These dermal components must cover the largest wounds, control fluid loss, and prevent infections. 

Only a few of these products are commercially available.  One, (SkinTemp: Biocore Medical Technologies, Topeka, KS.) Uses a type 1 Bovine matrix and is applied after Mohs micro graphic surgery in a minority of patients in whom immediate reconstruction is contraindicated and a patient needs a long-term biological dressing that stimulates wound healing.  This product proved to heal epithelialized wounds three weeks faster than conventionally treated historical controls. 

Also, (SYNTACOLL AG, Herisau, Switzerland) uses a type 1 bovine Achilles tendon derived collagen membrane has been used to promote healing of acute and chronic wounds and leg ulcers. 

Autograft: A sheet of tissue taken from the person who was wounded that is used to permanently cover the wounds.  This is essentially an organ transplant.  An autograft is surgically removed by a Dermatome that shaves off the top layer of skin from an inconspicuous area on the body.  The site will heal on its own.  There are two forms of grafts for permanent wound coverage.

  Sheet Grafts:  A piece of donor skin is harvest from the body that is the same size as the burn area.  The new tissue sheet is then laid over the wound and stapled into place.  The donor skin is not stretch but adequately covers the burned area.  When the body surface of the burn is large, sheet grafts are used for the most visible parts of the body to prevent scarring.  The disadvantages include small areas of graft might be lost from a build up of fluid under the sheet after surgery.  These also create other wound areas where the tissue is harvested but are very durable and tend to prevent scarring.

 Meshed Skin Grafts:  These grafts are used on very large burn wound areas when enough donor skin is unavailable.  This procedure involves enlarging the donor skin available.  In the process, donor skin is passed through a machine that inserts small slits into the skin that allow expansion similar to “netting”.  Most donor skin is enlarged at 1:1 or a 1:2 ratio.  This procedure causes the skin graft to be much more fragile than a sheet graft and involves more permanent scarring.  The small islets in the skin graft allow epithelial growth and allows blood and body fluid to drain from under the skin grafts, and it allows donor skin to cover a greater area.  Donor skin thickness is approximately .014 inches thick. 

 “Warm Up” Therapy: This procedure involves an external device that is used to physically warm the area of the wound.  The concept involves the wound’s inability to maintain a temperature of 37 degrees Celsius as a result of tissue loss.  By “warming up” the damaged area healing is promoted by increasing localized blood flow to the wound. 

 Growth Factor Treatment:  The use of Regranex (Ortho-McNeil) and a serum of growth factors produced from platelets.  This therapy has proven very expensive and is used more in Europe than the U.S. Some exciting new clinical trials are underway involving PDGF AA and AB isoforms that are in phase III trials for pressure ulcers.  Fibrostat (Procyon Biopharma) a growth factor of collagen is in trial for use in follow up surgery of serious burns to prevent scarring.  Several companies such as Celtrix, Genzme, Human Genome Sciences, Daewoong, Johnson & Johnson, Ethicon, Chiron, all have various pharmaceutical growth factors involved in clinical trials at the moment.  Taken together, there is hope that this will be the new approach that will provide a simpler, more effective treatment for patients with chronic ulcers.

Disease Treatment: The treatment of the underlying disease in addition to stimulation of the wound healing process by physical stimuli or the application of exogenous growth factors will greatly reduce the cost of venous ulcer treatment  and skin replacement.  By curing diabetes, the Health care costs applied to diabetic foot ulcers is eliminated. 

Physical Devices:  Several physical devices have been utilized to heal wounds of patients.  This category ranges from compression bandages, laser treatment, and electrical stimulation.  For the past 60 years, physicians have found the application of a low-dose direct current could promote wound healing.  A study found that a low pulsed direct current reduced a wound area 45% for skin ulcer patients after 4 weeks of treatment.  Since then, this investigations have documented the treatment of burn wounds, diabetic ulcers, keloids, and skin infections with a low-dose electrical stimulation.  The Dermapulse (Staodyn Inc, Longmont, CO) instrument is battery powered and is made from silver ink applied to carbon filled vinyl with carbon-filled silicone rubber sheets connected to two dispersion electrodes.  The study resulted in patients with chronic venous ulcers found a reduction of the wound pain within the first few days.  Some patient's ulcers reduced in size 36.5% after a period of 38 days.  The Oxygen level in the skin at the ulcer margin also improved by 80% promoting healing.  The use of Dermapulse (Staodyn Inc, Longmont, CO) as a growth factor and alternate therapy to skin substitutes is currently under investigation.  Although this seems a probable solution to the surgical injury that is most often used to heal burn wounds, physical treatment has not taken hold of the medical world as a prominent solution for chronic ulcer therapy.  Physicians and patients are looking for a more visible, immediate solution for their pain.

Synthetic Dressings:  The most popular of all treatment therapy for major burn wound patients.  This is because it is readily available, relatively simple procedure, and has proven effectiveness.  During this procedure, the material must be neutral, adhere to the wound area, be flexible, protect the wound from external bacteria, allow fluid escape, and are relatively low cost.  Many products on the market today prevent the formation of crusts and favor spontaneous healing by forming an impermeable isolated environment that is ideal for healing.  Most dressings are made of hydrocolloid, polyurethane films, and membranes made from a synthetic polypeptide.  Hydrocolloid dressings are most often used on burns and take approximately 7 to 15 days to create a healing environment on the wound. 

An example of a synthetic dressing:

DuoDerm (ConvaTec) is an extremely popular wound healing for pressure ulcers and leg ulcers.  This product interacts with the wound to produce a soft mass allowing removal of the dressing without damaging newly formed tissue.  At $55.00 a piece, this therapy is relatively inexpensive and simple to perform.  The product is used to prevent friction to fragile skin and does not require any additional adhesive.  The dressing may be left in place for close to 7 days or until the wound is healed.  A risk of this product involves the chance of a local infection during the use of the dressing.  Too frequent dressing changes can remove newly formed skin tissue and strip the wound area.  The product is available in several sizes as well as in gel form.

The product is painless and easy to apply but requires sterile surfaces.  The hydrocolloid surface interacts with secretions forming an absorbing gel that has a pressure effect.  The synthetic dressings are relatively easy to use, cause no harmful side effects, and are tolerated by relatively all patients causing favor over other treatment therapies.