The use of dermal substitutes in burn surgery: Acute phase

Major burns represent a challenge in autologous skin coverage and may lead to severe functional and cosmetic sequelae. Dermal substitutes are increasingly becoming an essential part of burn care during the acute phase of treatment. In the long term dermal substitutes improve functional and cosmetic results and thus enhance quality of life. In the chronic wound setting, dermal substitutes are used to reconstruct and improve burn scars and defects. Despite the potential of dermal substitutes, further research is required to strengthen scientific evidence regarding their effects and also to develop new technologies and products. Furthermore, dermal substitutes have a pivotal role in future research strategies as they have the potential to provide adequate scaffold for stem cells, tissue engineering, and regenerative medicine with conceivable application of obtaining long‐lasting and scarless artificial skin. This review discusses the status quo of dermal substitutes and novel strategies in the use of dermal substitutes with a focus on burn care.     

Wundunterdrucktherapie bei Schwerbrandverletzten

Negative pressure wound therapy has been used for many years for surgical, traumatic and chronic lesions. During the last 3 years negative pressure wound therapy was consistently pursued as a concept in adults with severe burn injuries in the burn center at the trauma center in Murnau. A total of 48 patients with severe burn injuries to a total body surface area (TBSA) of up to 90% were treated with negative pressure wound therapy. This therapy was used during all stages of treatment from the initial phases of debridement to split thickness skin grafting after debridement. Intensive care parameters and surgical parameters of tissue repair were recorded during the whole intensive care phase. These parameters were compared to data of burn patients who received conservative therapy. All patients with severe burn injuries treated with negative pressure wound therapy showed a significant reduction in redressing. Furthermore, outstanding wound conditioning and excellent take rates after split thickness skin grafting were observed. Intensive care parameters and surgical parameters of wound healing showed patients treated with negative pressure wound therapy were more stable in comparison to patients treated conservatively. Negative pressure wound therapy was shown to be an excellent option especially in the treatment of severe burn patients from initial debridement to final split skin grafting.     

Denatured acellular dermal matrix seeded with bone marrow mesenchymal stem cells for wound healing in mice

It is the basic task of burn therapy to cover the wound with self-healthy skin timely and effectively. However, for patients with extensive burns, autologous skin is usually insufficient, and allogenic or heterogeneous skin leads to strong immune response. It is vital to choose an appropriate treatment for deep extensive burns. Nowadays, the dermal substitute combined with bone marrow mesenchymal stem cells (BM-MSCs) is a prospective strategy for burn wound healing. Denatured acellular dermal matrix (DADM), as one of dermal substitutes, which prepared by burn skin discarded in escharotomy, not only maintains a certain degree of 3D structure of collagen, but also has good biocompatibility. In this study, the preparation method of DADM was improved and DADM was seeded with BM-MSCs. Then BM-MSCs-seeded DADM (DADM/MSCs) was implanted into mice cutaneous wound, and the effect of DADM/MSCs dermal substitute was assessed on skin regeneration. As a result, BM-MSCs survived well and DADM/MSCs scaffolds significantly promoted wound healing in terms of angiogenesis, re-epithelialization and skin appendage regeneration. DADM/MSCs scaffold may represent an alternative promising therapy for wound healing in deep extensive burns.     

The mouse dorsal skin fold chamber as a means for the analysis of tissue engineered skin

The therapy of extensive and deep burn wounds is still a challenging task for reconstructive plastic surgery. The outcome is generally not satisfactory, neither from the functional nor from the aesthetic aspect. Several available skin substitutes are used but there is need for optimization of new skin substitutes which have to be tested in vitro as well as in vivo. Here, we show that the dorsal skin fold chamber preparation of mice is well suited for the testing of skin substitutes in vivo. Dermal skin constructs consisting of matriderm^® covered with a collagen type I gel were inserted into full thickness skin wounds in the skin fold chambers. The skin substitutes integrated well into the adjacent skin and got epithelialized from the wound edges within 11 days. The epithelialization by keratinocytes is the prerequisite that also cell-free dermal substitutes might be used in the case of the lack of sufficient areas to gain split thickness skin grafts. Further advantage of the chambers is the lack of wound contraction, which is common but undesired in rodent wound healing. Furthermore, this model allows a sophisticated histological as well as immunohistochemical analysis. As such, we conclude that this model is well suited for the analysis of tissue engineered skin constructs. Besides epithelialization the mode and extend of neovascularization and contraction of artificial grafts may be studied under standardized conditions.     

Stromal vascular fraction improves deep partial thickness burn wound healing

ObjectiveThe practice of early burn wound excision and wound closure by immediate autologous skin or skin substitutes is the preferred treatment in extensive deep partial and full-thickness burns. To date there is no proven definite medical treatment to decrease burn wound size and accelerate burn wound healing in modern clinical practice. Stromal vascular fraction is an autologous mixture that has multiple proven beneficial effects on different kinds of wounds. In our study, we investigated the effects of stromal vascular fraction on deep partial-thickness burn wound healing.MethodsIn this study, 20 Wistar albino rats were used. Inguinal adipose tissue of the rats was surgically removed and stromal vascular fraction was isolated. Thereafter, deep second-degree burns were performed on the back of the rats by hot water. The rats were divided into two groups in a randomized fashion. The therapy group received stromal vascular fraction, whereas the control group received only physiologic serum by intradermal injection. Assessment of the burn wound healing between the groups was carried out by histopathologic and immuno-histochemical data.ResultsStromal vascular fraction increased vascular endothelial growth factor, proliferating cell nuclear antigen index, and reduced inflammation of the burn wound. Furthermore, vascularization and fibroblastic activity were achieved earlier and observed to be at higher levels in the stromal vascular fraction group.ConclusionsStromal vascular fraction improves burn wound healing by increasing cell proliferation and vascularization, reducing inflammation, and increasing fibroblastic activity.     

Skin resurfacing for the burned patient

It has been estimated that 2 million people per year have burns requiring medical attention in the United States. The available and expert clinicians in dedicated burn centers around the country have cared successfully for these patients and given them a second chance at a functional life. It still behooves current-day plastic surgeons to be knowledgeable and adept in their care, not only because they may be called upon at times to manage some of the smaller acute burns, but also because many of the general principles of burn reconstruction and wound management are relevant to other areas of general plastic surgery. Acute burns should be dealt with like any other major trauma with the ABCs of aggressive resuscitation and airway management. Like any other wound, debridement and nutrition are important (i.e., early escharectomy of the burn wound and enteral nutrition during the hypermetabolic state). Early coverage of the open wound is essential to limit bacterial colonization and prevent infection and to reduce fluid and electrolyte and heat loss. If autografts are not available immediately, temporary coverage with one of the above-mentioned barrier materials should be used. Still, autografts, when available, should be the burn surgeon's first choice. Donor sites may be reharvested to provide more autograft than was anticipated with large-percentage TBSA burns. Physicians should keep in mind the advantages (and disadvantages) of using the scalp and back. As far as research and technological advances in the area of plastic surgery, burn surgery may be the most progressive, with the evolution of biologic tissue-engineered skin substitutes and the research of growth factors in healing. Further improvements in tissue engineering and technology should result in even more effective skin substitutes and hence better functional and aesthetic outcomes with economic efficiency in large burns.     

Artificial skin reduces nutritional requirements in a severely burned child

An 11 year old boy had 60% BSA burns excised and artificial skin (Integra(R)) applied. None of the burn wound was grafted. At 3 weeks post burn his serum biochemistry was normal, except for a low serum albumin. Mean energy intake for the first 3 weeks was half his non-burned requirement and mean protein intake was close to his non-burned requirement. This is the first report to show that a reduction in nutritional requirements may be observed using skin substitutes.     

"Flypaper technique" a modified expansion method for preparation of postage stamp autografts

The gold standard for management of extensive burn has been early excision, temporary allografting and final autografting. However, "lack of donor skin" is a challenge condition when autografting in the treatment of extensive burns. Designing an efficient and easy to apply expansion method may improve burn care quality and shorten the hospital stay period. From December 1998 to May 2004, we have performed fly paper technique postage stamp skin autografting for eight major burn patients in the Kaohsiung Medical University Hospital. By using a quick cutting plate, chessboard tray and petrolatum gauze, the skin islands can be uniformly located and correctly oriented on gauze. Then, the gauze with skin islands was grafted on to the wound. The wound healing time depends on the size of skin islands and expansion ratio. This method allows true expansion ratio up to nine times. The average wound healing times are 27.2 days for six times expansion and 34 days for nine times expansion. However, the burn scar needs further compression therapy to improve the cosmetic result. In comparison with the mesh technique, the skin islands are independent of each other, any dislodgement of a skin island will not interfere with the surrounding skin squares. When compared with the modified Meek technique, this method also offers rapid wound reepithilization but with lower cost. This flypaper technique is worthy of consideration in dealing with the extensive burns.     

Vertical (two-layer) skin grafting: new reserves for autologic skin

The main, permanent source of burn coverage continues to be autologic skin. In patients with major burns, the amount of available autologic skin may be insufficient. Consequently, severe wounds are covered after debridement with other biological or synthetic skin substitutes. Another source of skin reserves for wound coverage is the use of cultured keratinocyte sheet graft alone or with any dermal substitute. Some of these materials provide only temporal coverage and are often costly and time-consuming in preparation. These factors can be critical in burned patients. To expand the effective means of wound coverage, the authors sought a new source of autologic skin. The dermal grafts that were the marginal product of skin harvesting were meshed and grafted on the debrided third-degree burn, granulated wound, or muscle. The authors observed good dermal grafts "take" with rapid or slow epithelialization. They saw no the delay in donor site healing where the skin grafts overlapped. The histological difference in usual skin grafts and dermal grafts was studied after their harvesting and "taking."     

Best-practice algorithms for the use of a bilayered living cell therapy (Apligraf®) in the treatment of lower-extremity ulcers

Tissue-engineered skin substitutes such as Apligraf have emerged over the past 20 years as among the most carefully studied and efficacious of the advanced wound modalities. These products have been proven as effective enhancements to general wound care, promoting wound closure particularly in instances where conventional wound care fails. Marketed for hard-to-heal wounds since 1998, Apligraf has become part of standard wound care in many wound centers across the United States. Despite this situation, few general wound care guidelines incorporate advanced and active wound-healing technologies, such as tissue-engineered skin products. Because of this deficiency, appropriate patient selection and proper use of these product remain largely unaddressed within the general wound care community. Here, we describe the development of guidelines surrounding optimal use of the bilayered living cell therapy, Apligraf, in the treatment of the two types of lower extremity ulcers for which the product is FDA approved: venous leg ulcer and diabetic foot ulcer. The guidelines detailed in this article focus on the identification and selection of patients who are at risk for failure of standard wound care therapy and thus appropriate for Apligraf treatment. The intended audience for these guidelines is the general wound care practitioner, for whom the developed treatment algorithms and accompanying figure legends should provide practical, user-friendly direction simplifying both patient selection and appropriate use of Apligraf within the context of good wound-healing practice.     

Keratinocytes in the treatment of severe burn injury: an update

Burns are among the most life‐threatening physical injuries, in which fast wound closure is crucial. The surgical burn care has evolved considerably throughout the past decennia resulting in a shift of therapeutic goals. Therapies aiming to provide coverage of the burn have been replaced by treatments that have both functional as aesthetic outcomes. The standard in treating severe burns is still early excision followed by skin grafting. The use of cultured keratinocytes to cover extensive burn wounds appeared very promising at first, but the technique still has several limitations of which the long time to culture, the major costs, the risk of infection and the need for an adequate dermal layer limit clinical application. The introduction of dermal substitutes, composite grafts, tissue engineering based on stem cell application have been advocated. The aim of this review is to assess the use of cultured keratinocytes in terms of technical aspects, clinical application, limitations and future perspectives. Cultured keratinocytes are expected to keep playing a role in wound healing, especially in the field of chronic wounds. In severe burns, despite its limitations, keratinocytes can be beneficial if implemented as one of the elements in a broader wound management.     

Burn appearance and spontaneous healing: A prospective study

In a prospective study to correlate initial burn wound appearance with burn wound appearance after 21 days of conservative wound care, it was found that all burn appearances (except the presence of thrombosed capillaries and charred, ‘leathery’ skin) were associated with a high probability of spontaneous healing. These findings emphasize the difficulty of selecting those burn wounds likely to benefit from early excision and grafting unless, of course, the burn is obviously fullthickness.     

028 Clinical Trials of Allogenic Cultured Dermal Substitute for the Treatment of Burn Wounds

Aim: Recently, various types of cultured skin substitutes have been developed and some of them are used clinically. This study was designed to evaluate the efficacy of allogenic cultured dermal substitute which was applied to burn injuries in clinical trials such as deep dermal burns and dermal burns. Methods: Allogenic cultured dermal substitute (CDS) was simply applied to the burn wound, over which covering materials were applied to protect CDS. Results: The application of CDS to deep dermal burns was proved to facilitate healthy granulation tissue formation at early stage and epithelialization from the outer margins. When CDS applied to the debrided wound surface of dermal burns, an excellent wound bed was generated which was suitable for the graft take of an autologous patch. Conclusion: CDS provides an excellent epithelialization and granulation for burn wounds.     

Burn wound healing and skin substitutes.

Burn wound healing is a complex process in the biological objectives and mechanisms defined by the initial injury. In this paper the use of keratinocytes as a skin substitute is used to illustrate some of the problems associated with the development and use of skin substitutes. Skin substitute development must always be viewed against the biological and clinical background in order to provide maximum assistance to the challenging task of treating burn wounds.     

Necrotizing fasciitis after a honey bee sting

Necrotizing soft-tissue infections such as necrotizing fasciitis continue to have a high morbidity and mortality. More and more, these difficult cases are being referred to burn centers for specialized wound and critical care treatment. The case of a necrotizing soft-tissue infection after a honeybee sting is reported. To the best of our knowledge, it is the first documented case of necrotizing fasciitis caused by invasive group A Streptococcus from a bee sting. A 56-year-old man was stung by a bee in the left upper gluteal region. The sting was removed by the patient. Within hours, erythema, swelling, itching, and pain developed. On day 7, after the bee sting, the patient was admitted to a general surgery department with progressive skin and soft-tissue necrosis around the hip and the upper left leg. Because of the rapidly deteriorating condition, the patient was referred to our burn ICU with the picture of a progressive necrotizing fasciitis. The skin necrosis required immediate epifascial necrectomy. Additionally local therapy with topical antiseptics was performed. The surface was temporarily covered with xenograft, definitive coverage was achieved with autologuous skin graft transplantation. Advancements in wound care and critical care, which have become standard in the treatment protocols of patients with necrotizing soft-tissue infections, have markedly improved the prognosis. However, these infections continue to be a source of high morbidity and mortality and significant healthcare resource consumption. These challenging patients are best served with prompt diagnosis, immediate radical surgical debridement, and aggressive critical care management. Referral to a burn center may help to provide best possible surgical intervention, wound care, and critical care management.     

深度烧伤修复重建与康复治疗相关问题探讨

With the advances in resuscitation,infection control,and metabolic management,the treatment strategies for burn patients have improved remarkably in the last half century.As a result,more patients with deep burn wound survived,and how to optimize the burn wound care aiming at recovery of the normal appearance and physiologic function of patients has been investigated and discussed widely through both the whole treat-ment strategy making and the new techniques performing.In the present discussion,early tissue reconstruction as well as early wound covering and repair are emphasized by summarizing the improved aesthetic and functional effects obtained by applying the principles of plastic surgery in early burn wound repair,the use of composite skin grafting,the grafting with split-thickness autografts on the preserved denatured dermis or on the preserved healthy fat tissue.etc.Besides these,more attention should be given to the repair and reconstruction in specialized functional parts of the body,such as head and face,neck,hand,female breast.perineum,and joint areas,after a deep burn.The role of rehabilitation during and after the burn wound treatment process is elucidated by demonstrating its potential biophysical mechanism and preventing scar deformity.Adequate treatment of deep burn wound demands a number of important measures in-eluding the timing of surgery,adoption of essential techniques,suitable types of wound covering materials,motivated rehabilita-tion,and necessary psychological therapy.The optimal recovery of damaged part of body after burn should depend on the similar-ity of rebuild tissue structure to simulate the nature of the origi-nal tissue in the cellular,histological,anatomic characteristics,which is the aim of all burn wound care and the basis of the ap-pearance and function repair or reconstruction.     

Active wound coverings: bioengineered skin and dermal substitutes

Extensive skin loss and chronic wounds present a significant challenge to the clinician. With increased understanding of wound healing, cell biology, and cell culture techniques, various synthetic dressings and bioengineered skin substitutes have been developed. These materials can protect the wound, increase healing, provide overall wound coverage, and improve patient care. The ideal skin substitute may soon become a reality.     

Modeling early thermal injury using an ex vivo human skin model of contact burns

BackgroundEarly mechanisms underlying the progressive tissue death and the regenerative capability of burn wounds are understudied in human skin. A clinically relevant, reproducible model for human burn wound healing is needed to elucidate the early changes in the human burn wound environment. This study reports a reproducible contact burn model on human skin that explores the extent of tissue injury and healing over time, and defines the inter-individual variability in human skin to enable use in mechanistic studies on burn wound progression and healing.MethodsUsing a customized burn device, contact burns of various depths were created on human skin by two operators and were evaluated for histologic depth by three raters to determine reproducibility. Early burn wound progression and wound healing were also evaluated histologically after the thermally injured human skin was cultured ex vivo for up to 14 days.ResultsBurn depths were reproducibly generated on human skin in a temperature- or time-dependent manner. No significant difference in operator-created or rater-determined depth was observed within each patient sample. However, significant inter-individual variation was identified in burn depth in ten patient samples. Burn-injured ex vivo human skin placed into culture demonstrated differential progression of cell death and collagen denaturation for high and low temperature contact burns, while re-epithelialization was observed in superficial burn wounds over a period of 14 days.ConclusionThis model represents an invaluable tool to evaluate the inter-individual variability in early burn wound progression and wound healing to complement current animal models and enhance the translation of preclinical research to improvements in patient care.     

Genetic modification of cultured skin substitutes by transduction of human keratinocytes and fibroblasts with platelet-derived growth factor-A

Gene therapy promises the potential for improved treatment of cutaneous wounds. This study evaluated whether genetically modified cultured skin substitutes can act as vehicles for gene therapy in an athymic mouse model of wound healing. Human keratinocytes and fibroblasts were genetically engineered by retroviral transduction to overexpress human platelet-derived growth factor-A chain. Three types of skin substitutes were prepared from collagen-glycosaminoglycan substrates populated with fibroblasts and keratinocytes: HF-/HK-, containing both unmodified fibroblasts and keratinocytes; HF-/HK+, containing unmodified fibroblasts and modified keratinocytes; and HF+/HK-, containing modified fibroblasts and unmodified keratinocytes. Skin substitutes were cultured for two weeks before grafting to full-thickness wounds on athymic mice. The modified skin substitutes secreted significantly elevated levels of platelet-derived growth factor throughout the culture period. Expression of retroviral platelet-derived growth factor-A mRNA was maintained after grafting to mice, and was detected in all HF-/HK+ grafts and one HF+/HK- graft at two weeks after surgery. Although no differences were seen between control and modified grafts, the results suggest that genetically modified cultured skin substitutes can be a feasible mechanism for cutaneous gene therapy. The cultured skin model used for these studies has advantages over other skin analogs containing only epidermal cells; because it contains both fibroblasts and keratinocytes, it therefore offers greater opportunities for genetic modification and potential modulation of wound healing.     

The enhanced Total Body Wrap—The new frontier in dressing care for burns

The management of extensive burns with their associated high fluid exudate following burn excision and skin grafting has always posed a challenge in burn wound care. The ideal dressing should protect the wound from physical damage and micro-organisms; be comfortable and durable; allow high humidity at the wound; and be able to allow maximal activity for wound healing without retarding or inhibiting any stage of the process.