ACELLULAR DERMAL MATRIX AND AUTOGENOUS MICROSKIN

CO-GRAFT OF ACELLULAR DERMAL MATRIX AND AUTOGENOUS MICROSKIN IN A CHILD WITH EXTENSIVE BURNS

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SUMMARY. A 6-yr-old boy was the victim of a burns accident in a public bathhouse. The burns involved the face, neck, upper and lower extremities, anterior and posterior trunk, and both buttocks, covering 72% of the total body surface area (TBSA). The lesions in the lower extremities and parts of the right upper extremity were deep partial-thickness, comprising 40% TBSA. On day 5 post-burn, the lesions in both lower extremities were excised to the extent of the fascia under general anaesthesia. Meshed J1 Jayya Acellular Dermis®, a kind of acellular allodermal (ADM) matrix, was then placed on the left knee joint. The right knee joint served as control. The wounds in both lower extremities were then overlaid with microskin autografting. At 19 days post-application, the lesions in both lower extremities had almost completely resurfaced. Follow-up at six months revealed well-healed and stable skin of acellular ADM and microskin autografts on the left knee. However, the skin of the right knee was unstable and there was a chronic residual ulcer. Both legs showed some significant hypertrophic scars. The left knee joint (acellular ADM grafted site) showed mild contractures, while the right knee joint developed a significant contracture. The “skin” of the co-graft covered site appeared thicker and more elastic. The movement range of the left knee joint was much larger than that of the right knee joint. These results suggest that co-graft of acellular dermal matrix and autogenous microskin may be an effective way to repair this functional site in children with extensive burns and to improve the functional and cosmetic results.

Introduction

Microskin grafting has proved to be an effective method for the treatment of extensive burns in which the area of available donor skin is inadequate.1 In this method, a piece of thin split-thickness autogenous skin (0.15-0.30 mm in thickness) is harvested and minced into tiny particles for grafting. Owing to the lack of dermis, the healed wound always has a poor functional and cosmetic result.2 A chronic ulcer and a severe hypertrophic scar often develop. In the joint area, contracture of the scar always confines movement. To improve the overall cosmetic and functional outcome of microskin autograft, a co-graft of allodermal matrix (ADM) and autogenous microskin was utilized both in animals and in adult patients.2-4 The co-graft skins had a very elastic and smooth texture compared with traditional microskin autografts, showing less cicatrization and ulceration.3 Here we report on a successful application of co-graft of acellular ADM and autogenous microskin in a 6-yr-old child with extensive burns.

Case report

A 6-yr-old boy was the victim of an accident that occurred in a public bathhouse on 31 January 2005, when he fell into the boiling-water pool as he walked along the edge of the pool. The patient sustained burns due to boiling water. After being removed from the source of his injury, the patient was transported to a local medical unit 15 min post-burn. Topical moist exposed burn ointment (MEBO) was applied. After a period of 8 h, the patient was transferred to our burns centre. During transit, the patient was resuscitated with 625 ml liquid, including 300 ml Ringer’s lactated fluid, 125 ml sodium bicarbonate, and 200 ml low molecular weight dextran. Besides the intravenous fluid, he drank a total of 500 ml plain boiled water.
On admission, the patient was found to be in a state of hypovolaemic shock: he was thirsty, his skin was cool and white, his pulse weak, and capillary refill was delayed. The burns involved the face, neck, upper and lower extremities, anterior and posterior trunk, and both buttocks, covering 72% of his total body surface area (TBSA) (Fig. 1).

Fig. 1 - Six-yr-old boy with 72% TBSA burn caused by boiling water.

The wounds in both lower extremities and parts of the right upper extremity were deep partial-thickness, comprising 40% TBSA (Fig. 2); the rest of the wounds were superficial partial-thickness. Prompt venotomy was performed to establish intravenous access. Resuscitation with Ringer’s lactated fluid and plasma was given and adjusted to a maintenance level of adequate urine output and haemodynamics. Haemodynamic stability was achieved and the patient’s thirst was relieved following fluid infusion and debridement of the injured areas. Silver sulphadiazine was applied to the wounds and covered with dry dressings. Fluid input in the first 24 h totalled 3350 ml, achieving a diuresis of 40-50 ml per h. The patient was treated with 2100 ml fluid and his urine output was 1540 ml in the second 24 h.
On day 5 post-burn, the wounds in both lower extremities were excised to the extent of the fascia under general anaesthesia (Fig. 3).

Fig. 2 - Deep partial-thickness wound in both lower extremities.

Fig. 3 - Wounds in both lower extremities excised to the extent of the fascia.

Meshed J1 Jayya Acellular Dermis® (Beijing Jayya Life Tissue Engineering Co., Ltd, Beijing, China), a kind of acellular ADM like Alloderm®, was then placed in the haemostatic tissue bed of the left knee joint and secured by suture (Fig. 4). The right knee joint served as control (Fig. 5).

Fig. 4 - Meshed acellular ADM (J1 Jayya Acellular Dermis®).

Fig. 5 - Left knee joint covered with meshed acellular ADM, right joint serving as control.

The wounds in both lower extremities were then overlaid with microskin autografting, which was performed as described by Zhang with slight modifications.5 In brief, thin split-thickness autogenous skin (3% TBSA) was harvested using a compressed-air-powered dermatome (Zimmer Corp., Denver, OH) from the scalp of the patient as needed at a depth of 0.2 mm, cut into tiny pieces smaller than 1 mm3 using a pair of fine scissors, and then immersed in normal saline. The minced skin gradually floated with the epithelial side upwards. The floating particles of skin were removed from the saline and evenly spread on a piece of silk cloth with a spoon, keeping the epithelial side upwards. A large sheet of homograft was taken out of a supra-low temperature refrigerator and thawed in normal saline at 37 °C, after which some holes were made in it using a scalpel for exudation drainage. The large sheet of homograft was placed over the microskin grafts on the silk cloth, the dermal side of the homograft making contact with the epithelial side of the micrografts. The homograft and the silk cloth were turned over together and the cloth was carefully removed, leaving the micrografts in contact with the homograft (Fig. 6).

Fig. 6 - Large sheet of homograft with autogenous microskin with dermal side upwards.

This time the microskin grafts were also turned over with the dermal side up (the same as the homograft). The prepared homograft-autograft was transplanted onto the excised burn wound in both lower extremities and secured in sheets to the wound margin using a combination of staples and unabsorbable sutures (Figs. 7, 8).

Fig. 7 - Left lower extremity further overlaid with autogenous microskin and large sheet of homograft.

Fig. 8 - Right lower extremity, serving as control, covered only with autogenous microskin and large sheet of homograft.

Gentamycin- impregnated Vaseline gauze, followed by an additional layer of outer bulk gauze wrap, completed the dressings, which remained intact for seven days. On day 6 post-operation, the intravenous catheter was removed and its bacterial culture was found to be negative. The outer dressing was first changed on day 7 after grafting. The success of the initial graft take was determined at day 10, when all dressings were removed (Fig. 9).

Fig. 9 - Microskin autograft and homograft taking well 10 days after operation.

At 19 days post-application, the wounds in both lower extremities had almost completely resurfaced (Fig. 10).

Fig. 10 - Wounds in both lower extremities almost completely resurfaced 19 days after operation

The remaining wounds were dressed with silver sulphadiazine 1% and changed every two days. On day 68 post-burn, the residual 3% TBSA defects were covered with split-thickness autografts. After this procedure, all the wounds were closed and the patient was discharged on day 79 after the injury.
Follow-up at six months revealed well-healed and stable skin of acellular ADM and microskin autografts on the left knee. However, the skin of right knee was unstable and there was a chronic and residual ulcer with a diameter of 1 cm (Fig. 11).

Fig. 11 - At 6-month follow-up, skin of right knee unstable and chronic residual ulcer 1 cm in diameter.

Both legs showed some significant hypertrophic scars. The left knee joint (acellular ADM-grafted site) showed mild contractures, while the right knee joint, not covered with acellular ADM but directly with traditional microskin autografts, developed significant contracture (Fig. 12).

Fig. 12 - At 6-month follow-up, left knee joint (acellular ADM grafted site) showing mild contractures; right knee joint, not covered with acellular ADM but directly with traditional microskin autografts, developing significant contracture. Left knee joint movement range much larger that of right knee joint.

The “skin” of the co-graft-covered site appeared thicker and more elastic. The movement range of the left knee joint was much larger than that of the right knee joint.

Discussion

It is always a challenging problem for a burn surgeon to be confronted with a patient with extensive full-thickness burns and insufficient viable skin available for autografting. The Integra Dermal Regeneration Template®, an artificial skin system, has been demonstrated to provide early wound coverage and has been used effectively to treat deep excised wounds of the skin.# However, the use of Integra® is limited in the developed countries owing to its high expense, while in the developing countries such as China very few patients can afford it.
In 1986, Zhang and his colleagues first described a new technique of skin graft called the microskin autograft.5,7 In this method the expansion ratio of the recipient site to the donor area can be greater than 10:1.7 Owing to the high utilization rate of the donor site and the simple procedure, microskin grafting has come to be one of the most important methods in China for the treatment of extensive burns with limited areas of normal skin.8 It has significantly reduced mortality and infectious morbidity in patients with major burns.8,9 Despite these favourable reports with microskin grafting, concerns about the poor cosmetic and functional results, especially in the joint area, remain problematic owing to the lack of dermis. To circumvent these problems associated with conventional microskin autografts, the allograft dermis, consisting of composite skin, has been utilized in order to improve cosmetic and functional results in adults.
In this paper, we report a co-graft of acellular ADM and autogenous microskin in a 6-yr-old child with major burns. The patient sustained a 72% TBSA burn, more than half being deep partial-thickness. Since 1996 our burns centre has gained considerable experience with the microskin autograft: since January 2006, 68 patients with major burns have had such microskin autografts. The general outcome of this experience is that the microskin autograft should be applied at the level of the fascia, which has a good blood supply. A fascial excision is therefore indicated for deep wounds in patients with 70% TBSA or more, unless very healthy deep dermis can be left.

Conclusion

J1 Jayya Acellular Dermis® is an acellular dermal matrix with a normal collagen-bundling organization and an intact basement membrane complex, which is derived from cadaver tissue. Thorough debridement, haemostasis, and securing are indispensable for application. In the patient we have described, J1 Jayya Acellular Dermis® and the overlying microskin autograft exhibited an excellent take. At the 6-month follow-up, the co-graft skins had a good elastic texture in comparison to the traditional microskin autograft and no ulceration appeared. The left knee joint had a larger range of movement than the right knee joint, i.e. the control site overlaid with traditional microskin autograft. Scar quality and joint function were both significantly improved in the co-graft site. These results suggest that the co-graft of acellular dermal matrix and autogenous microskin may be an effective way to repair this functional site in children with extensive burns and to improve the functional and cosmetic results. However, further research is required to confirm the findings and provide more information on long-term effects.

Acellular Dressings and Skin Substitutes......

Single-Element Biologic Systems

Wound coverage with amniotic membrane
Human amniotic membranes obtained from the placenta after delivery have been used for decades to cover burn wounds. These membranes are readily available in large supply in major hospitals and can be prepared relatively inexpensively. They possess most of the characteristics of an ideal skin substitute: excellent adherence to the wound, very low immunogenicity, decrease of pain, bacterial control, and stimulation of healing. Moreover, a great advantage of the amniotic membrane is its translucency, allowing inspection of the wound.
Amniotic membranes can be applied on superficial second-degree burns, donor sites, and deep second-degree burns after early debridement. They are also useful to cover 1:3 meshed autografts, and they have been reported to be extremely effective in sterilizing contaminated wounds and cleaning burns of bacteria within 3-5 days. Nevertheless, amniotic membranes have to be changed daily and need to be covered with gauze to prevent desiccation because they display less efficacy in preventing water loss compared with homograft or xenograft. In addition, they do not allow long-term coverage and could be dissolved early by the wound. Amniotic membranes can be kept refrigerated for 6 weeks, or they can be frozen for longer storage and banking purposes.
Acellular human dermis
Acellular human dermis substitute (eg, AlloDerm; LifeCell Corporation, Branchburg, NJ) is essentially healthy human dermis with all the cellular material removed. It is then virus-screened and preserved by freeze-drying. Different, mostly nonrandomized control studies or case presentations using AlloDerm showed a variation in results relating to dressing technique. Thinner grafts overlying the AlloDerm exhibited better take, which was deemed advantageous in terms of the donor site. Its use has now been described in various applications with some degree of success.
Acellular human dermis is prepared from cadaver skin by extensive washing and purification followed by high-dose x-ray radiation and either deep freezing or glycerol preservation. Because of the limited donor population and the extensive and both time-consuming and money-consuming security tests, allogenic human skin cannot cover all needs and is very expensive.
Wound coverage with xenogenic grafts
The ideal xenogenic material used for dermal substitution should have the following clinical properties:

• Be hemostatic and possess good adherence to any wound bed (including cartilage and bone surfaces); fully cover the wound surface without any dead spaces
• Adhere immediately to the wound borders
• Cover the whole wound area and protect it against infectious agents and the loss of water and tissue fluids
• Cover the wound area, reducing or eliminating pain
• Lack any specific inflammation-stimulatory agents and not produce any foreign body reaction, granuloma formation, or acute or chronic immunologic rejection
• Serve as a natural matrix for host granulation tissue formation and coordinate fibroblast proliferation and angiogenesis with early tubular formation and capillary development
• Serve as a natural surface, promoting host epithelial cell proliferation, reepithelization, and basal membrane structure development, and create a stable connection between the new, developed connective tissue and the new, proliferated epidermis
• Promote a normal epidermal differentiation and enhance the maturation of epidermis, which covers the healing wound (natural collagen matrix)
• Because of 1-7, protect against both the contracture of wound borders and typical scar formation
• Be fully transparent and allow excellent clinical observation of the wound area and the healing process

Tissues of animal origin have been used for thousands of years to cover extensive wounds. Although it has become evident in this century that xenograft achieves only temporary wound coverage, its unlimited availability under well-controlled conditions still makes animal skin a favorable wound covering.
Porcine skin is the most common source of xenograft because of its high similarity to human skin. Sterility is an essential concern with xenogeneic tissues transplanted on wounds. Ionizing radiation appears to be the most suitable method for a guarantee of this sterility and for application in mass production. In addition, irradiation coupled with freeze-drying seems to decrease the antigenic properties of the pigskin graft and to increase its potential to inhibit bacterial growth. Thus, pigskin is a well-suited temporary dressing for the coverage of second-degree burns, especially after early excision. It usually promotes scar-free healing, with an average healing period of about 10 days.
In addition, pigskin provides a suitable overlay to cover widely meshed (1:8 to 1:12) autografts. Because freeze-drying and irradiation are expensive, a low-cost alternative preservation technique was successfully developed by using 98% glycerin as the antiseptic followed by storage at room temperature for 20-300 days.
To cover wounds with a dermal matrix to favor graft take of cultured epidermal sheets and to prevent rejection of xenogeneic tissues, efforts have been made to develop nonimmunogenic artificial dermal matrices. Such dermal components must promote the prompt coverage of the largest excised full-thickness wounds, control fluid loss, and prevent infections. Recent advances in the technology of in vitro tissue reconstruction have made it possible to approach these requirements.
Acellular Matrices and Combination Products
The engineering of skin tissue and the development of a skin substitute have been studied from a variety of approaches. The acellular collagen-chondroitin sulfate material proposed by Yannas et al^[6] represented one of the first attempts at engineering a dermal component to substitute the volume of missing tissue. Bello and coworkers^[7] proposed a bilayered model of skin by using contracted collagen lattices containing living dermal fibroblasts covered in a 2-step procedure with in vitro–reconstructed epidermal sheets.
Native collagen and native collagen–containing products have been proposed for covering superficial wounds, for tissue augmentation, or for hemostatics in visceral surgery. The practical use of soluble collagen for wound healing is limited because of problems with storage stability and the time required to prepare enriched collagen solutions. Traditional collagen pads or Vlieses manufactured out of solubilized collagen material are not suitable for these purposes because of their high compression after application onto the wound surface and their lack of transparency. This last phenomenon is of great importance because of the possibility of permanent visual control of the wound during each healing phase.
Ruszczak et al^[8] proposed a treatment strategy for superficial and deep wounds and for tissue substitution in the form of a composite graft, a 2-step procedure based on xenogenous collagen implantation for dermis substitution and reconstructed keratinocyte allografts for surface covering. Transplanted basal keratinocytes supplied keratinocyte-derived signaling molecules and growth factors, which actively helped to restore a dermoepidermal exchange pathway and to stimulate healing. The collagen material (CollatampFascia; INNOCOLL Inc, US) was a ready-to-use, mechanically stable, in vivo noncontractible, primarily free of any nonbiologic and synthetic components, nonpyrogenic, biologically and immunologically neutral, and long-term preservable membrane. This material could be used both as a wound dressing and as an implant for healing chronic, acute, and surgical superficial or partial- or full-thickness wounds.
A novel collagen spongy matrix containing oxidized regenerated cellulose (ORC) named Promogran (Johnson & Johnson Wound management, NJ) has been introduced to both US and EU markets. Promogran has been designed to treat exuding wounds, including diabetic, venous and pressure ulcers. The matrix is composed of 45% ORC and 55% collagen. The ORC/collagen matrix binds to metalloproteases in chronic wound exudate without altering the activity of essential tissue growth factors, and it creates a milieu for moist wound healing.
Because metalloprotease levels may be elevated in chronic wounds and contribute to degradation of important extracellular matrix proteins and inactivate growth factors, their binding into the ORC/collagen matrix may have a positive effect on the physiological wound healing process. Promogran has been found to significantly increase the healing ratio of diabetic foot ulcers compared with a traditional moistened gauze procedure, especially in ulcers of less than 6 months' duration.
Both products described above are a single layer construct and may require additional moisture control barrier to complete the dressing.
An original method of Burke and Yannas' artificial skin is now called the Integra Dermal Regeneration Template and is commercialized. Burke and Yannas' artificial skin is a bilayer membrane composed of a dermal portion that consists of a porous lattice of fibers of a cross-linked bovine collagen and glycosaminoglycan (GAG) composite and an epidermal layer of synthetic polysiloxane polymer (silicone). The GAG that is used is chondroitin-6-sulfate; the degradation rate of the collagen-GAG sponge is controlled by glutaraldehyde-induced cross-links. The collagen-GAG dermal layer functions as a biodegradable template that induces organized regeneration of dermal tissue (neodermis) by the body and the infiltration of fibroblasts, macrophages, lymphocytes, and endothelial cells that form a neovascular network. As healing progresses, native collagen is deposited by the fibroblasts, and the collagen portion of artificial skin is biodegraded over approximately 30 days.
Serial biopsy samples, ranging from 7 days to 2 years after the application of the artificial skin, demonstrated that an intact dermis was achieved with regrowth of apparently normal papillary and reticular dermis. No scar formation appeared in the biopsy samples of patients examined. The superficial silicone layer of the Integra Dermal Regeneration Template is imbedded with monofilament nylon sutures to easily distinguish it from the collagen dermal layer. This pseudo epidermal layer must eventually be removed by the surgeon and is usually replaced by thin epidermal autografts during the 2-step transplantation. At present, the Integra Dermal Regeneration Template is approved in the United States only for the postexcisional treatment of life-threatening, full-thickness or deep partial-thickness thermal injury where sufficient autograft is not available at the time of excision or not desirable because of the physiological condition of the patient.
Another bilayer skin substitute used mostly for severe burns is Biobrane (Bertek Pharmaceuticals Inc, Morgantown, WVa). Biobrane is a biosynthetic wound dressing constructed of a silicon film with a nylon fabric partially imbedded into the film. The fabric presents to the wound bed a complex 3-dimensional (3-D) structure of trifilament thread to which collagen has been chemically bound and cross-linked. Blood/sera clot in the nylon matrix, thereby firmly adhering the dressing to the wound until epithelialization occurs.
Biobrane was introduced in 1979 for commercial use in the treatment of burn wounds and donor sites and has several advantages, including adherence, safety, control of evaporative water loss, flexibility, durability, bacterial barrier, ease of application and removal, availability, hemostatic properties, and cost-effectiveness. In comparison with pigskin and skin allografts, Biobrane showed superior wound adherence. The product has been found to significantly reduce local wound pain, to speed up the healing process, and to significantly prevent bacterial colonization of the wound surface.

Synthetic or semisynthetic dressings

Silicones
Silicone dressings consist of chemically and biologically inert, usually transparent, silicon sheets or gels. Some of the silicone membranes are porous to allow gas and moisture exchange between the wound surface and the environment. Other silicone membranes are nonpermeable to ensure a fully occlusive wound environment.
Silicone dressings not only work as antiadhesives but also may reduce hypertrophic and keloid scarring. Silicone has been found to be useful in flattening of scarring tissue; increasing elasticity; and reducing discoloration, making the scars more cosmetically acceptable. Additionally, silicone or siliconized membranes have been found useful in covering split-skin donor sites or fresh meshgrafts. Moreover, silicone membranes work as an epidermislike portion in combination engineered skin substitutes (as previously mentioned).
Barrier films
Barrier films are protective polymers dissolved in a fast-drying carrier solvent, which, ideally, should be noncytotoxic, be pain reducing on application to broken skin, protect skin from loosing moisture or from exogenic fluids, protect from skin stripping, and be compatible with clothing. Such dressings may be applied as fluids, which quickly polymerize on the wound surface or as industrially prepared membranes made mostly from polyurethane or polylactate.
Foams
Foams mostly consist of polyurethane porous sponges or polyurethane foam films with or without adhesive borders. Most of them are suitable for use on light-to-medium exuding wounds. Many types of foams may be left on the wound surface for up to 7 days, depending on exudate volume. Foams are not recommended for any kind of dry wounds. Besides the usual range of sizes, anatomically shaped dressings are available for specific wound locations (eg, sacral region, heel).
Tissue adhesives
Tissue adhesives have been developed to exchange suturing in some, mostly small and not-too-deep wounds that can heal by primary intention. Moreover, such products may be used in the form of surface covering liquid bandages. Currently used tissue adhesives contain cyanoacrylate components, including bucrylate, enbucrilate, and mecrylate, which polymerize in an exothermic reaction on contact with either a fluid or a basic substance. Such a process leads to the forming of a strong, flexible, waterproof band.
Tissue adhesives are used for simple lacerations, which otherwise might require the use of fine sutures, staples, or skin strips, producing cosmetic results similar or better than traditional suturing. This is a needless and mostly painless method of wound repair that does not require follow-up visits for suture removal.
Tissue adhesives provide the strength of healed tissue seen at 7 days. Special attention is necessary to ensure that wound edges are appropriately adapted and that no adhesive passes between wound borders.
Hyaluronic acid
Vapor-permeable films (also known as semipermeable films), made of materials that can be found in some tissues, are now becoming popular wound dressings. Most of them are made of industrially manufactured and purified hyaluronic acid. Hyalograft 3D and Laserskin (HYAFF-11) are indicated for use on diabetic foot ulcers and venous leg ulcers. Entirely composed of a benzyl ester derivative of hyaluronic acid, they may be used as membranes for direct wound dressing or as scaffolds for the cultivation of fibroblasts and keratinocytes for further transplantation.
Hydrogels
Hydrogel dressings contain a large portion of water, often more than 70-90%. They have some important characteristics of an ideal dressing. Hydrogels can cool the surface of the wound, resulting in marked pain reduction. Moreover, hydrogels maintain the moist wound environment and are mostly suitable for use on dry or necrotic wounds or on lightly exuding wounds. They are suitable for use at all stages of wound healing except for infected or heavily exuding wounds. Hydrogels are a good alternative for classic wet dressings. In some cases, however, hydrogels may macerate the healthy skin (mostly wound border areas), decreasing the keratinocyte reepithelialization ratio or leading to overwetting of split-skin donor sites. Hydrogels are available as sheet dressings or gels.
Hydrocolloids
Hydrocolloid dressings are much more complicated than hydrogels because they contain a variety of constituents, such as methylcellulose, pectin, gelatin, and polyisobutylene. Some of them also contain alginate. After contact with the wound surface, hydrocolloids slowly absorb fluids, leading to a change in the physical state of the dressing and to the formation of gel covering the wound. Thus, they are called interactive dressings.
Hydrocolloids ensure the moist wound environment, promote the formation of granulation tissue, and provide pain relief by covering nerve endings with both gel and exudate. These dressings are marketed with or without adhesive borders. Depending on the choice of product, hydrocolloids are suitable for the dressing of both acute wounds and chronic wounds, for desloughing, and for different stages of light-to-heavily exuding wounds.
Initially, hydrocolloid wound dressings need to be changed daily (depending of the exudate level), but, once the exudate has diminished, dressings may be left on the wound surface for up to 7 days. With a few exceptions, hydrocolloids require a secondary dressing to be fixed in place. Hydrocolloids should not be used on infected wounds.
Calcium alginates
Alginates are highly absorbable biodegradable dressings derived from seaweed (eg, Kaltostat, Tegagen, SorbSan, SeaSorb, Algisite M, Algosteril). They contain the building blocks of mannuronic acid (M) and glucuronic acid (G). The high M alginates are soft and gel-like, whereas the high G alginates are more stable and ribbon- or rope-like.
Large quantities of alginates are used each year to treat exudating wounds, such as leg ulcers, pressure sores, and infected surgical wounds. In addition to controlling exudate by ion exchange, alginates are believed to exert a bioactive effect by activating macrophages within the chronic wound bed to generate proinflammatory signals (eg, tumor necrosis factor-alpha [TNF-alpha], interleukin 1, interleukin 6 [IL-6], interleukin 12). This may then initiate a resolving inflammatory response characteristic of healing wounds. Chronic wounds are now well known to be characterized by macrophage-rich inflammation, and any putative macrophage defects probably relate to the functional status of the macrophages present at the wound site.
In vitro studies have demonstrated that some dressings containing alginates can activate macrophages, as evidenced by their increased production of TNF-alpha. Research is currently underway to modulate alginate dressings to enhance these effects and to incorporate antimicrobial silver into alginate preparations (eg, Acticoat Absorbent). In addition, new preparations (eg, AGA-100) that have a reduced cytotoxicity to cells, such as fibroblasts, compared with both Kaltostat and Sorbsan, are being developed.
Alginates are not the dressing of choice for infected wounds and should not be applied to dry or drying wounds. Most alginates require a secondary dressing.
Dressings containing an antimicrobial agent
An important consideration in the design of new dressings is their ability to combat microbial infection. Many dressings now exploit bioactive properties to promote healing and to control infection. These dressings include the now well-known sustained-release iodine and silver dressings (eg, Iodosorb, Actisorb Silver 220). Silver metal and its salts have been used for several generations under many different formulations (eg, ointments, pulvers, foams, films). Possible reasons for the antimicrobial effect of silver include (1) interference with bacterial electron and ion transport; (2) binding to bacterial DNA, which may impair cell replication; (3) interaction with cell membrane, which may damage its structural and receptor function; and (4) formation of insoluble and metabolically ineffective compounds.
The ideal silver dressing will contain a concentration of silver to exert an effective antibacterial effect without or with only limited systemic absorption. However, locally applied silver compounds may react with wound fluid and form black silver sulphide, giving the skin a gray discoloration. The use of silver nitrate solution is more likely to cause this phenomenon than modern silver dressings.
One of the widely used silver dressings is Actisorb Plus, an activated charcoal cloth impregnated with silver. It is reported to absorb bacteria, which are then inactivated by the silver. Now marketed as Actisorb Silver 220, it is intended for use over partial- or full-thickness wounds, such as pressure ulcers, venous ulcers, diabetic ulcers, and acute and chronic wounds, and it is claimed to be the only dressing currently available in the United States that "combines broad-spectrum antimicrobial action, bacterial toxin management and odor control."^[9]
Another new generation product, Acticoat, the silver antimicrobial barrier dressing, consists of a rayon/polyester nonwoven core laminated (by sonic welds) between an upper and lower layer of silver-coated, high-density polyethylene mesh (HDPE). The laminations are held in place with ultrasound welds. The silver-coated HDPE layers are designed to be barriers against microbial infection of a wound.
Acticoat is now available as both a nonabsorbable form and an absorbent antimicrobial barrier dressing effective to bacterial penetration. In its absorbable form, Acticoat is a calcium alginate dressing using novel silver-coating technologies in a dressing designed to prevent wound adhesion, to control bacterial growth, and to facilitate burn wound care. The barrier functions of the dressing may help reduce infection in moderately-to-heavily exuding partial- and full-thickness wounds, including decubitus ulcers, venous stasis ulcers, surgical wounds, first- and second-degree burns, grafts, and donor sites. The sustained-release of broad-spectrum ionic silver activity protects the dressing from bacterial contamination, whereas the alginate absorbs excess wound fluid to form a gel that maintains a moist environment for optimal wound healing.
In a new multilayer Acticoat (Acticoat-7), the silver antimicrobial barrier dressing consists of 2 rayon/polyester nonwoven inner cores laminated (by sonic welds) between 3 layers of silver-coated HDPE. The laminations are held in place with ultrasound welds. The silver-coated HDPE layers are designed to be barriers against microbial infection of a wound. Such products can provide an effective antimicrobial barrier for up to 5-7 days against 150 pathogens, including both methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). See Smith & Nephew; Acticoat 7.
A number of controlled clinical studies have been performed to evaluate the safety and the efficacy of Acticoat. In a matched-pair, randomized, prospective clinical study for the treatment of burns, Acticoat was assessed for its ease of use, patient comfort, and antimicrobial effectiveness compared with standard care in the same institution. In general, the results were promising, with patients reporting less pain on removal with Acticoat and nurses reporting no significant difference in ease of application. The frequency of burn wound sepsis and the occurrence of secondary bacteriemia were both reduced.
A comprehensive laboratory study of the antimicrobial activity of Acticoat has also been reported. In a number of tests, Acticoat demonstrated improved antimicrobial performance over existing silver-based products. In addition to killing bacteria more rapidly, it had the lowest minimum inhibitory concentration and minimum bactericidal concentration. In a controlled study on donor site wounds, Allevyn showed significantly better results than Acticoat with respect to time to healing and extent of reepithelialization. No significant differences were seen in the incidence of bacterial cultures, and, while scarring appeared initially worse with Acticoat, this resolved by 3 months. Overall, the findings did not support the use of Acticoat for this application, although they did support its continued use for burn sites.
A comparison was made of home-care costs of local wound care in surgical patients.^[10] Seventy-six patients were randomized between occlusive and gauze dressings. Patient groups were similar with regard to age, wound size, and etiology. Dressing-change frequency in the occlusive group (median: 0.6/d) was significantly (P = .008) lower than in the gauze group (1.1/d). Mean daily material costs of modern dressings were Euro 5.31 vs. Euro 0.71 in the gauze group (mean difference, Euro 4.60; 95% confidence interval, Euro 2.68-6.83). Daily total (material plus nursing) costs showed no difference between the groups (mean difference, Euro 2.86; 95% confidence interval, Euro 6.50-10.25). Wound healing in the gauze-treated group tended to be quicker than in the occlusive dressing group (medians: 30 vs 48 d, respectively; log-rank P = .060).
At least in this study, the use of occlusive dressings did not lead to a reduction in costs and wound healing time compared with gauze dressings for surgical patients receiving wound care at home.
Local collagen-based drug delivery systems
Collagen-based dermal matrices (sponges or transparent, semipermeable membranes) containing gentamicin have been successfully used for the treatment of infected burn wounds and for the prevention of wound infection in large-surface wounds, including severe burns. Such matrices (Sulmycin-Implant, Collatamp-G, INNOCOLL Inc, US) are commercially available and are distributed by Schering-Plough, United States, in many countries


Source Page can be found here... 

http://emedicine.medscape.com/article/1127868-overview#aw2aab6b7

Skin replacement using autologous grafts....

Autologous and Allogenic Skin Replacement

The best way to cover large surface wounds is the transplantation of the patient's own skin (ie, split-thickness skin grafts) from an adjacent undamaged area that matches closely in terms of texture, color, and thickness. This surgical procedure inflicts an injury on the donor site analogous to a superficial second-degree burn, allowing spontaneous healing in 2-3 weeks, usually without scarring.
Autograft is the method of choice to achieve definitive coverage of burned skin with good quality of healed skin. This technique has been improved by expanding the surface of the skin graft with a mesh apparatus, depending on the needs of the patient. Recently, as much as 25-30 times expansion has been described. However, excessive meshing usually results in healed skin that is more susceptible to infections and has a basketlike pattern, a major drawback for aesthetic appearance. An alternative is the Meek island graft or sandwich graft. This method allows easier handling of widely expanded autografts than meshed skin. In addition, because the autograft islands are not mutually connected, failure of a few of them does not affect the overall graft take. The Meek technique has been reported to be superior to the mesh procedure for expansion ratios of more than 1:6.
In large surface burns, early closure of burn wounds with autologous skin grafts is limited by the lack of adequate donor sites. A delay of 2-3 weeks is necessary to wait for healing of donor sites before harvesting them again. The split-skin graft from the initial donor site can usually be reharvested 2-3 times and healed autografted wounds. This coverage process is time consuming and, thus, induces high risks of morbidity and mortality, mainly due to bacterial invasion.
Cuono and coworkers^[3] proposed a 2-step procedure using composite autologous-allogenic skin replacement (de-epidermized skin allografts for dermis substitution and autologous, in vitro–reconstructed epidermis for surface covering) in burns. Compton et al^[4] , as well as Hefton and coworkers^[5] , preferred the use of both autologous, in vitro–reconstructed and allogenic, in vitro–reconstructed epidermal grafts for large-surface wounds.
Although the use of epidermal autografts has markedly advanced the management of extensive burns and saved lives, this technique has major limitations, as follows: (1) at least 3 weeks is needed for growth of cultured epidermal sheets in the laboratory, thus delaying the coverage of wounds; (2) epidermal sheets need to be grafted on a clean wound bed because they are highly sensible to bacterial infection and toxicity of residual antiseptics; (3) the success of the treatment strongly depends on the dexterity of the laboratory and surgical teams, from the production of the sheets to their graft and care after grafting because this material is very fragile; (4) the regeneration of the dermal compartment underneath the epidermis is a lengthy process, and skin remains fragile for at least 3 years and usually blisters; and (5) the aesthetic aspect of the healed skin is less acceptable than the one obtained with a split-thickness graft.
It was recognized early that any successful artificial skin or skinlike material must replace all of the functions of skin and, therefore, consist of a dermal portion and an epidermal portion. It was clinically apparent that a deep burn or other deep and/or large-surface wounds could not be completely closed promptly after injury by using the patient's available autograft donor sites. Moreover, in certain clinical situations (eg, elderly and young individuals), the donor sites themselves (if taken at standard thickness) create new wounds that often take a long time to heal and create additional metabolic stress, infection risk, and scarring.

Wound coverage with allogenic skin

One of the main differences between the cultured epidermal sheet and a split-thickness autograft is the lack of the dermal structure from the cultured autograftable sheets. The absence of dermis is perceived as the major cause for a lower percentage of graft takes and higher fragility and blistering after epidermal sheet transplantation compared to split-thickness autograft. A dermal component protects the basal layer of the epidermis and has a significant impact on the postgrafting biologic responses of the epithelial cells to the differentiation and wound-healing processes.
After early debridement of deep and extensive burns, temporary closure of the wound is usually achieved with cadaver allograft before autografting with cultured epidermal sheets. Instead of completely removing cadaver skin before sheet transplantation, an excision of allogeneic epidermis can be performed with a dermatome to only maintain the allogeneic dermis on the wound. Because nonliving dermis alone may not be rejected, autologous cultured epidermal sheets can be grafted onto it, thus greatly enhancing healing. Indeed, cultured epidermal sheets grafted onto homograft dermis display early rete ridge development and anchoring fibril regeneration, in addition to a graft take of 95%.
Knowing that devitalization of allografts reduces their antigenicity, the use of allogeneic cadaver skin as a biologic dressing is now widely accepted and is usually preferred to synthetic dressings. The preservation of allografts can be performed by different techniques, such as freeze-drying, glutaraldehyde fixation, or glycerolization.
Cryopreservation of homografts with glycerol is the most popular method of cadaver skin processing because freeze-drying is too expensive and glutaraldehyde fixation has proven less efficient. Moreover, skin preservation can reduce the risk of virus transmission from skin grafting, providing time to rid the donor skin of pathogens. Indeed, incubation of cadaver skin for several hours at 37°C in glycerol displays a significant virucidal and bactericidal effect. To provide sufficient cadaver skin instantly accessible for the patient with a burn, skin banks, such as the Euro Skin Bank in Beverwijk, The Netherlands, have been well developed through the years. However, allogenic skin banking has a significantly higher cost compared with xenogeneic skin banking and biologic dressings.