Skin Substitutes in Reconstruction of Burns RECENT ADVANCES Skin Substitutes in Reconstruction of Burns Dr. S.M. Tahir. Associate Professor Burn Surgery. LUMHS

Epi In USA, 450,000 pts require medical treatment annually. RECENT ADVANCES In USA, 450,000 pts require medical treatment annually. 45,000 admissions to hospitals 3500 deaths. Impact is much greater in developing countries. In India (population over 1 billion) 700,000 cases of burns are hospitalized every year.

Epi: East Mediterranean Region RECENT ADVANCES Systemic review by Kendrick in year 2010. Incidence is 315/100,000. (remarkably in contrast to USA 19/100,000) 50% are young patients. 25% are between age 0-5 years. Hospital mortality is 20-38 % .

Classification ACELLULAR SKIN SUBSTITUTES RECENT ADVANCES6 Classification ACELLULAR SKIN SUBSTITUTES Biobrane® Integra® Alloderm® CELLULAR ALLOGENIC SKIN SUBSTITUTES Transcyte® Dermagraft® Apligraf® (Graftskin®) CELLULAR AUTOLOGOUS SKIN SUBSTITUTES Cultured Epidermal Autograft (CEA) Cultured /Engineered Skin Substitutes (CSS/ESS)

ACELLULAR SKIN SUBSTITUTES Biobrane® RECENT ADVANCES Started in 1970. Now most widely used SS. Made of nylon mesh, which acts as a “dermis” and a silicon membrane which acts as an “epidermis”. Both are embedded in pig collagen. It is mainly used as a temporary coverage for Superficial/mid-dermal burns. Wound. Donor site.

Advantages: Readily availability, low pain, RECENT ADVANCES Advantages: Readily availability, low pain, Shorten hospital admission time, Accelerated wound healing, and Useful adjuvant to Buy time until skin graft material is available.

RECENT ADVANCES Disadvantages: Exudates collected beneath biobrane makes patient prone to infection. Few reported cases of toxic shock. Uses Pig collagen and therefore not accepted in our country .

Biobrane® RECENT ADVANCES

Management of superficial partial thickness burns with Biobrane. (a) An extensively blistered burn wound . (b)meticulously cleaned (c) Biobrane glove has been applied . (d) excellent healing occurs by day 9.

Area to be grafted got Reduced Graft reduction; the superficial burn components heal with Biobrane while the deeper area demarcates allowing accurate grafting with minimal sacrifice of viable tissue.

Elderly Patients Salvage in the elderly; initially appearing superficial, this burn in a 78-year-old struggled to heal spontaneously but resulted in the best outcome.

Temporizing Measure (a) 80% TBSA burn. (b & C )Receives Biobrane initially as a temporizing dressing (d) meshed graft and cultured cell suspension are hold by Biobrane(d) resulting in healing (e).

Acellular skin substitutes Integra® RECENT ADVANCES Pioneered by Yannas and Burke. It is a bi-layered skin , impermeable to water . Epidermal layer is a silicone membrane. The dermal part is made of bovine collagen and shark chondroitin-6-sulphate glycosaminoglycan. After coverage, the wound becomes revascularized within 2-3 weeks. At this stage, the superficial silicone layer is removed and replaced by a very thin split skin graft applied onto the neo-dermis bed.

Advantages: Disadvantages : Immediate availability, RECENT ADVANCES Advantages: Immediate availability, Allowing time for the neo-dermis formation, and Good aesthetic results. Disadvantages : Two-step. Expensive, and Infection (exudate collection underneath).

Application of Integra® Integra is supplied with outer Tyvek pouch. Aluminum foil pouch is opened. INTEGRA® is packaged between 2 polyethylene sheets and an attached center tab. By holding tab, gently peel off one of the polyethylene sheets

Gently peel off the other polyethylene sheet By holding tab, placed into a basin containing the sterile saline solution and carefully remove INTEGRA® from the tab. Rinse INTEGRA®  for 1-2 minutes Integra Can be meshed to 1:1, with non crushing mesher without using instruments.

 INTEGRA® Dermal Regeneration Template is scooped from from the holding basin with gloved hands and place directly onto the wound. The silicone side is facing up and the Collagen-GAG matrix is against the wound bed. The black thread identifies the silicone side.

Alloderm® RECENT ADVANCES This is formed from acellular matrix derived from a cadaveric dermis. The allodermis is processed by salt to remove the epidermis and then extracted with a solution to remove any cellular material. Freeze-dried to render it inert immunologically.  AlloDerm supports tissue regeneration by allowing rapid revascularization, white cell migration and cell population - ultimately being transformed into host tissue for a strong, natural repair.

Basement membrane remains intact but It has no epidermal layer. RECENT ADVANCES Basement membrane remains intact but It has no epidermal layer. Yet this acellular matrix provides a good natural medium for fibroblast and endothelial cells to regenerate from the neo­dermis. Widely used in breast Reconstruction and dental surgery.

Alloderm is usually used as sling to support implant and cover the anterior surface of the implant. The Alloderm is sutured to the body wall posterior to the implant.

CELLULAR ALLOGENIC SKIN SUBSTITUTES Transcyte® RECENT ADVANCES The Transcyte® tissue engineered skin substitute is made from a nylon mesh and a silastic semi permissible layer. Allogenic fibroblasts from neonatal foreskin are embedded in the mesh and allowed to grow for 3-6 weeks to produce a cellular matrix of collagen and growth factors which may enhance wound healing.  It is left in place until either spontaneous separation occurs which indicates wound bed healing or the wound is dealt with surgically. It has been licensed by the FDA for use in burns.

TransCyte is a temporary cover made from artificial skin, which promotes faster healing in burn patients without the pain and complexity involved in current treatment programs.

Dermagraft® RECENT ADVANCES The Dermagraft® skin substitute is similar to Transcyte® but It lacks the silicone layer and Contains viable fibroblasts. It is produced by mixing living neonatal foreskin fibroblasts with a polyglycolic acid mesh (Dexon or Vicryl).

The polyglycolic acid mesh is absorbed within 3-4 weeks. RECENT ADVANCES The fibroblasts are cryopreserved at -80°C to maintain viability and when implanted to the wound, start to proliferate and produce a variety of growth factors and extracellular collagen matrix components.  The polyglycolic acid mesh is absorbed within 3-4 weeks. It has been used effectively in Diabetic foot

Diagnosis: DFU of 6 months duration Ulcer healed in 8 weeks after adding 8 applications of Dermagraft to conventional therapy RECENT ADVANCES

Apligraf®(Graftskin®) RECENT ADVANCES The FDA approved it for clinical use in 1998 for the treatment of venous ulcers or neuropathic diabetic ulcers. It has both living dermis and epidermis and therefore example of “skin equivalent’ or “organo-typical skin substitute” .

Apligraf RECENT ADVANCES It is prepared by mixing living fibroblasts from neonatal foreskin with bovine collagen type I and left for 2 weeks to allow formation of new collagen and matrix resulting in dense fibrous network. A suspension of living neonatal foreskin keratinocytes (from the same or different neonatal donor) is seeded on the surface of the dermal fibrous matrix and left for 4 days to proliferate and differentiate.

Apligraf Licensed indication are (not responding to other measures) RECENT ADVANCES Licensed indication are (not responding to other measures) Diabetic and Venous ulcer It is also used to manage wounds in Epidermolysis bullosa, Donor sites, Surgical excision of skin cancer and Burns.

Apligraft as supplied Apligraft is being Remove from package

PERFORATING APLIGRAFT FENESTRATE MESH

Apligraft is being applied to the wound

Apligraft can be fixed to wound by using any of the following Staple Steri Strip Skin glue.

CELLULAR AUTOLOGOUS SKIN SUBSTITUTES Cultured Epidermal Autograft (CEA) RECENT ADVANCES The technique of cells culture was originally developed by Rheinwald and Green The use of these substitutes is useful when we need permanent skin coverage by cultured autologous keratinocytes.

Cultured Epidermal Autograft (CEA) EPICEL RECENT ADVANCES Skin biopsy is taken from the patient. Dermis and subcutaneous tissue are removed. The remaining epidermis is minced with mice fibroblast which is already lethally irradiated using 3T3. Allow to grow 4-5 weeks using culture medium containing essential elements including epidermal growth factors

RECENT ADVANCES Cultured keratinocytes are difficult to handle and therefore they need a delivery system or a supporting dressing. Commercially available CEA vary in delivery system and supporting dressing.

Application of Cultured Epidermal Autografts Cultured Epidermal Autografts Applied to the Hand and Arm

RECENT ADVANCES Clinically problem associated with use of Keratinocytes are due to poorly developed dermoepidemal junction and include. Blisters formation following small amounts of friction since the dermal epidermal junction is not completely developed. Scarring, contracture and Hyperkeratosis. 

However it is unpredictable ranges from 0% to 100%. RECENT ADVANCES Take rate is usually 30-80%. However it is unpredictable ranges from 0% to 100%. CEA is susceptible to digestion by collagenase enzymes present in the wound bed.

Cultured Skin Substitutes (CSS) Engineered Skin Substitutes(ESS) It has both epidermal and dermal components. It is an autologous graft so there is minimal risk of infection transmission. It provides permanent coverage. Several types were developed recently with different dermal biosynthetic scaffolds. The most commonly used type is a hyaluronic acid derived substitute.

RECENT ADVANCES Hyaluronic acid (Hyaluronan) is a naturally occurring polymer within the skin and it has been found to be pro-angiogenic thus stimulating blood vessel growth. It was found first in the vitreous humor of the eye in 1934 and subsequently synthesized in vitro in 1964.

Hyaluronic acid facilitates the RECENT ADVANCES Hyaluronic acid facilitates the Growth and movement of fibroblasts, Controls matrix hydration and Osmoregulation. It is also a free radical scavenger and an inflammatory regulator.

Flow Chart for ESS RECENT ADVANCES

Selective Culture of Skin

Example Case

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