Experiences with a temporary synthetic skin substitute after decompressive craniectomy: a retrospective two-center analysis.

BACKGROUND: Decompressive craniectomy is a commonly performed procedure. It reduces intracranial pressure, improves survival, and thus might have a positive impact on several neurosurgical diseases and emergencies. Sometimes primary skin closure is not possible due to cerebral herniation or extensive skin defects. In order to prevent further restriction of the underlying tissue, a temporary skin expansion might be necessary. METHODS AND MATERIAL: We retrospectively reviewed patients in need for a temporary skin substitute because skin closure was not possible after craniectomy without violating brain tissue underneath in a time period of 6 years (2011-2016). With this study, we present initial experiences of Epigard (Biovision, Germany) as an artificial temporary skin replacement. We performed this analysis at two level-1 trauma centers (Trauma Center Murnau, Germany; University Hospital of St. Poelten, Austria). Demographic data, injury and surgical characteristics, and complication rates were analyzed via chart review. We identified nine patients within our study period. Six patients suffered from severe traumatic brain injury and developed pronounced cerebral herniation in the acute or subacute phase. Three patients presented with non-traumatic conditions (one atypical intracerebral hemorrhage and two patients with extensive destructive tumors invading the skull and scalp). RESULTS: A total of 20 Epigard exchanges (range 1-4) were necessary before skin closure was possible. A CSF fistula due to a leaky Epigard at the interface to the skin was observed in two patients (22%). Additional complications were four wound infections, three CNS infections, and three patients developed a shunt dependency. Three patients died within the first month after injury. CONCLUSIONS: Temporary skin closure with Epigard as a substitute is feasible for a variety of neurosurgical conditions. The high complication and mortality rate reflect the complexity of the encountered pathologies and need to be considered when counseling the patient and their families.

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.

A systematic review and meta-analysis of complications associated with acellular dermal matrix-assisted breast reconstruction.

BACKGROUND: Multiple outcome studies have been published on the use of acellular dermal matrix (ADM) in breast reconstruction with disparate results. The purpose of this study was to conduct a systematic review and meta-analysis to determine an aggregate estimate of risks associated with ADM-assisted breast reconstruction. METHODS: The MEDLINE, Web of Science, and Cochrane Library databases were queried, and relevant articles published up to September 2010 were analyzed based on specific inclusion criteria. Seven complications were studied including seroma, cellulitis, infection, hematoma, skin flap necrosis, capsular contracture, and reconstructive failure. A pooled random effects estimate for each complication and 95% confidence intervals (CI) were derived. For comparisons of ADM and non-ADM, the pooled random effects odds ratio (OR) and 95% CI were derived. Heterogeneity was measured using the I2 statistic. RESULTS: Sixteen studies met the inclusion criteria. The pooled complication rates were seroma (6.9%; 95% CI, 5.3%-8.8%), cellulitis (2.0%; 95% CI, 1.2%-3.1%), infection (5.7%; 95% CI, 4.3%-7.3%), skin flap necrosis (10.9%; 95% CI, 8.7%-13.5%), hematoma (1.3%; 95% CI, 0.6%-2.4%), capsular contracture (0.6%; 95% CI, 0.1%-1.7%), and reconstructive failure (5.1%; 95% CI, 3.8%-6.7%). Five studies reported findings for both the ADM and non-ADM patients and were used in the meta-analysis to calculate pooled OR. ADM-assisted breast reconstructions had a higher likelihood of seroma (pooled OR, 3.9; 95% CI, 2.4-6.2), infection (pooled OR, 2.7; 95% CI, 1.1-6.4), and reconstructive failure (pooled OR, 3.0; 95% CI, 1.3-6.8) than breast reconstructions without the use of ADM. The relation of ADM use to hematoma (pooled OR, 2.0; 95% CI, 0.8-5.2), cellulitis (pooled OR, 2.0; 95% CI, 0.9-4.3), and skin flap necrosis (pooled OR, 1.9; 95% CI, 0.6-5.4) was inconclusive. CONCLUSIONS: In the studies evaluated, ADM-assisted breast reconstructions exhibited a higher likelihood of seroma, infection, and reconstructive failure than prosthetic-based breast reconstructions using traditional musculofascial flaps. ADM is associated with a lower rate of capsular contracture. A careful risk/benefit analysis should be performed when choosing to use ADM in implant-based breast reconstruction.

Acellular dermal matrix masking detection of recurrent breast carcinoma: a novel complication.

Acellular dermal matrix (ADM) use in prosthetic breast reconstruction has become increasingly popular. Several benefits have been reported with this technique including diminished donor-site morbidity and improved aesthetic outcomes. Recently, in an effort to ascertain the overall safety and efficacy of this approach, an emphasis has been placed on identifying potential postoperative complications. This report describes a unique complication experienced with ADM use in which ADM conceals the detection of recurrent breast carcinoma.

Negative-pressure wound therapy combined with artificial dermis (Terudermis) followed by split-thickness skin graft might be an effective treatment option for wounds exposing tendon and bone: A retrospective observation study.

ABSTRACT: Skin grafts are not suitable for closing tendon- or bone-exposing wounds, which require flap surgery. Dermal regeneration templates have value for closing such wounds, but the disadvantages of the technique include implantation failures because of infection, hematoma formation, or inappropriate immobilization. Negative-pressure wound therapy was reported to increase graft acceptance in difficult wounds.This retrospective case series of 65 patients evaluated negative-pressure therapy combined with artificial dermis for the treatment of acute or chronic tendon- or bone-exposing wounds. The artificial dermis was placed after adequate wound-bed preparation, with simultaneous application of a vacuum-assisted closure system. Split-thickness skin grafting was performed after the implanted artificial dermis had become established.The overall success rate was 88.1% (59/67): 88.6% (39/44) in the chronic wounds group and 87% (20/23) in the acute-trauma group separately. The overall mean survival time of artificial dermis in success cases was 13.24 ±â€Š7.14 days. In separately, the survival time of artificial dermis had no statistically difference in chronic wound group (13.64 ±â€Š7.53 vs 12.60 ±â€Š5.86. P = .943), but had significant statistical difference in acute trauma group (12.45 ±â€Š6.44 days vs 23.33 ±â€Š4.04 days, P = .018). Also, comorbidity of PAOD was found a strong risk factor of failure in chronic wound group (100% vs 23.1%, P < 0.001).We concluded that artificial dermis combined with negative-pressure therapy followed by split-thickness skin grafting might be a reliable and effective option for surgical reconstruction of tendon- or bone-exposing wounds, and could decreasing waiting periods of autologous skin graft.

Wound care: the role of advanced wound healing technologies.

Wound repair and regeneration is a highly complex combination of matrix destruction and reorganization. While major hurdles remain, advances over the past generation have improved the clinician's armamentarium in the medical and surgical management of this problem. The purpose of this manuscript is to review the current literature regarding the pragmatic use of three of the most commonly employed advanced therapies; namely, bioengineered tissue, negative pressure wound therapy, and hyperbaric oxygen therapy with a focus on the near-term future of wound healing, including stem cell therapy.

Advances in Dermoepidermal Skin Substitutes for Diabetic Foot Ulcers.

Diabetic foot ulcers (DFUs) are one of the major complications of diabetes, representing a leading cause of hospitalisation and non-traumatic lower limb amputations. Multidisciplinary management, patient education, glucose control, debridement, off-loading, infection control, and adequate perfusion are the mainstays of standard care. Despite all these, at least 30% of DFUs fail to heal within 20 weeks. Therefore, dermoepidermal skin substitutes (DSS) have been used as a new therapeutic adjunct for DFUs. This brief review outlines the recent advances in DSS for the treatment of DFUs. PubMed and Cochrane databases were systematically searched in May to July 2018 for systematic reviews published after 2013 and for randomised controlled trials (RCTs). A retrospective evaluation of 28 RCTs was performed. Rates of complete wound closure and time to healing were examined for 17 commonly available DSS. Healing rates after 12 weeks and time to complete closure in DFUs are heterogeneous among the 28 RCT. The best healing rates at 12 weeks were accomplished with dermal cellular substitutes (Epifix®, 100% and Amnioband®, 85%) and with dermal acellular substitutes (Allopatch®, 80% and Hyalograft®, 78.8%). Based on these studies, DSS used in conjunction with standard care appear to improve the healing rates of DFUs, as compared with standard care alone. Nonetheless, new studies with more homogeneous samples are needed to ascertain the role of ulcer size, duration, depth and/or type in the efficacy of DSS. Moreover, future RCTs should include patients with severe comorbidities, in order to be more representative of clinical reality.

Microbiology of infected acellular dermal matrix (AlloDerm) in patients requiring complex abdominal closure after emergency surgery.

BACKGROUND: Acellular dermal matrix (AlloDerm) has recently been introduced as an option for complex abdominal closure for patients with loss of abdominal wall domain secondary to intra-abdominal sepsis or necrotizing fasciitis. AlloDerm has been touted as a promoter of neovascularization and collagen deposition. Currently, the rate of AlloDerm infection in contaminated cases is unknown. Our objective was to determine if the organisms cultured during source control would infect AlloDerm. METHODS: The medical records of patients who required complex abdominal closure with AlloDerm in a tertiary-care hospital were reviewed from January to December, 2005. For each patient demographic, the reason for urgent surgery, American Society of Anesthesiologists (ASA) class, Acute Physiology and Chronic Health Evaluation (APACHE) II score, serum albumin concentration, culture results of purulent fluid obtained during surgery, and culture results of biopsies of infected-appearing AlloDerm (change of color, delayed granulation, odor) were collected. Data are presented as mean +/- standard error of the mean. RESULTS: Seventeen patients required the use of AlloDerm for tension-free closure of the abdominal wall after surgery for source control in necrotizing fasciitis (13%) or intra-abdominal sepsis (87%). The mean age was 61 +/- 2 years; 73% of the patients were Caucasian, the remainder being African American. The mean APACHE II score was 23.7 +/- 2.0, and the median ASA class was 3. The mean preoperative albumin concentration was 2.27 +/- 0.26 g/dL. Most (76%) of the patients had a wound vacuum-assisted closure system placed over the AlloDerm. Four patients (24%) were noted to have an infection of the AlloDerm graft at 24 +/- 10 days postoperatively. The cultures obtained at operation and from infected AlloDerm show similar organisms (Pseudomonas in two, Escherichia coli and methicillin-resistant Staphylococcus aureus in one each). Infected AlloDerm was coated with silver sulfadiazene and moistened dressings, and all four patients had complete resolution of the AlloDerm infection with an adequate bed of granulation tissue, allowing skin grafting. CONCLUSION: Patients with contaminated abdomens who require complex closure with AlloDerm are at risk of developing infection of their graft material with organisms similar to those present at the time of surgery. Once culture results are obtained, topical antimicrobials with activity against the cultured organisms may be employed as part of the AlloDerm dressings to prevent infection and promote healing.

Clinical experiences of using a cellulose dressing on burns and donor site wounds.

These preliminary results suggest this temporary skin substitute reduces pain and achieves comparable healing rates to other dressings. Furthermore, its transparency enables regular inspection of the wound bed for signs of infection.

Spray on skin for diabetic foot ulcers: an open label randomised controlled trial.

BACKGROUND: One Australian loses a limb every 3 h as a result of infected diabetic foot ulcers (DFU). This common condition accounts for substantial morbidity and mortality for affected individuals and heavy economic costs for the health sector and the community. There is an urgent need to test interventions that improve wound healing time, prevent amputations and recurrent ulceration in patients presenting with DFU whilst improving quality of life and reducing health care costs. METHODS: One hundred and fifty eligible participants will be randomised to receive an autologous skin cell suspension, also termed 'spray-on' skin (ReCell®) or standard care interventions for their DFU. The primary outcome is complete wound healing at 6 months, but participants will be followed up for a total of 12 months to enable secondary outcomes including total overall costs, ulcer free days at 12 months and quality of life to be assessed. DISCUSSION: Outpatient costs for dressings, home nursing visits and outpatient appointments are key cost drivers for DFU. If spray-on skin is effective, large cost savings to WA Health will be realised immediately through a shortened time to healing, and through a higher proportion of patients achieving complete healing. Shortened healing times may enable participants to return to work earlier. Any economic benefits are likely to be amplified across Australia and other similar demographic settings where aging populations with increased diabetes rates are considered major future challenges. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12618000511235. Registered on 9 April 2018.

The use of acellular, fetal bovine dermal matrix for acute, full-thickness wounds.

BACKGROUND: Skin substitutes may be used as part of the management of acute surgical wounds. The ideal skin substitute should be biocompatible, inexpensive, free of potential pathogens, easy to store, prepare, and utilize. OBJECTIVE: To discuss the authors' direct clinical experience with an acellular, fetal bovine dermal matrix for the treatment of Mohs micrographic surgery (MMS) wound management. METHODS: After the cutaneous malignancies were cleared by MMS, a sheet of the product was prepared according to the manufacturer's instructions, trimmed to fit the defect, and then secured to the wound to enhance contact with the wound bed. RESULTS: Between June 2006 and July 2007, the product was used on a total of 10 wounds in 7 patients. Comorbidities included organ transplantation, Sezary syndrome with hepatitis C, and graft-versus-host disease. Seventy percent of the lesions were located on the lower extremities. The average defect area was 13.4 cm2 (range: 4.0-32.0 cm2). The dermal substitute was fully incorporated in 80% of defects and those that did not fully incorporate had exposed bone and tendon without the periosteum and peritendon, respectively. CONCLUSION: Skin substitutes may provide temporary coverage of acute, full-thickness surgical wounds allowed to heal by second intent. They may facilitate wound management with acceptable aesthetic outcomes. Alternate reconstructive options, however, such as cutaneous flaps, should be considered when there is exposed bone and/or tendon without their periosteum and/or peritendon.

Bioengineered skin substitutes for the management of burns: a systematic review.

OBJECTIVE: To assess the safety and efficacy of bioengineered skin substitutes in comparison with biological skin replacements and/or standard dressing methods in the management of burns, through a systematic review of the literature. METHODS: Literature databases were searched up to April 2006, identifying randomised controlled trials. RESULTS: Twenty randomised controlled trials were included in this review. The numerous sub-group analyses and the diversity of skin substitutes limited the ability to draw any conclusions from it. However, the evidence suggested that bioengineered skin substitutes, namely Biobrane, TransCyte, Dermagraft, Apligraf, autologous cultured skin, and allogeneic cultured skin, were at least as safe as biological skin replacements or topical agents/wound dressings. The safety of Integra could not be determined. For the management of partial thickness burns, the evidence suggested that bioengineered skin substitutes, namely Biobrane, TransCyte, Dermagraft, and allogeneic cultured skin, were at least as efficacious as topical agents/wound dressings or allograft. Apligraf combined with autograft was at least as efficacious as autograft alone. For the management of full thickness burns, the efficacy of autologous cultured skin could not be determined based on the available evidence. The efficacy of Integra could not be determined based on the available evidence. CONCLUSIONS: Additional methodologically rigorous randomised controlled trials with long-term follow-up would strengthen the evidence base for the use of bioengineered skin substitutes.

[Biological evaluation of artificial skin substitute].

Multiple kinds of Artificial Skin Substitute are now available. However, except for the Homo Skin Graft there is no Artificial Skin Substitute that can be used as permanent Artificial Skin Substitute. During the past 20 years, more and more scholars around the world have expressed increased interests in the research and development of Artificial Skin Graft that can be utilized as satisfying permanent Artificial Skin Substitute. We conducted our research on the biological evaluation of medical devices of Collagen-Chitosan(C-C) Artificial Skin Substitute according to the National Standard (GB/T16886. 1-1997). The following experiments were conducted: (1)Cytotoxicity, (2)Systemic toxicity(acute toxicity), (3)Haemocompatibility, (4)Sensitization, (5)Intracutaneous reactivity, (6)Pyrogen test, (7)Genotoxicity. The experiment results demonstrate that all biological functional indexes of the Artificial Skin Graft meet the National Standards. Therefore, we conclude that C-C Artificial Skin Graft is characteristic of good biological compatibility. It is non-irritant and has no systemic and cellular toxicity, no genotoxicity, no pyrogen, and no allergen.

An Outbreak of Severe Group A Streptococcus Infections Associated with Podiatric Application of a Biologic Dermal Substitute.

OBJECTIVE: To describe an outbreak of severe Group A Streptococcus (GAS) infections that appeared to be associated with use of a biologic dermal substitute on foot wounds DESIGN: Retrospective cohort study of cases and similar uninfected patients SETTING/PATIENTS: Patients attending the podiatry clinic at a Veterans Affairs Medical Center between July 2011 and November 2011 INTERVENTIONS: Microbiology laboratory data were reviewed for the calendar year, a case definition was established and use of the biologic dermal substitute was discontinued. Staff were cultured to identify potentially colonized employees. A case-cohort study was designed to investigate risk factors for disease. Emm typing and pulsed field gel electrophoresis (PFGE) were performed to identify strain similarity. RESULTS: In 10 months, 14 cases were identified, and 4 of these patients died. All strains were emm type 28 and were identical according to PFGE. Discontinuation of biologic dermal substitute use halted the outbreak. A prior stroke was more common in the case cohort vs uninfected patient cohorts. The number of patients attending the clinic on 13 probable transmission days was significantly higher than on nontransmission days. We identified 2 patients who were present in the clinic on all but 1 probable transmission day. Surveillance cultures of podiatry clinic staff and cultures of the same lot of retained graft material were negative. CONCLUSIONS: A carrier was not identified, and we believe the outbreak was associated with inter-patient transmission likely due to lapses in infection control techniques. No additional cases have been identified in >3 years following the resumption of dermal substitute use in May 2012.

The efficacy and safety of Dermagraft in improving the healing of chronic diabetic foot ulcers: results of a prospective randomized trial.

OBJECTIVE: To determine if a human fibroblast-derived dermal substitute could promote the healing of diabetic foot ulcers. RESEARCH DESIGN AND METHODS: A randomized, controlled, multicenter study was undertaken at 35 centers throughout the U.S. and enrolled 314 patients to evaluate complete wound closure by 12 weeks. Patients were randomized to either the Dermagraft treatment group or control (conventional therapy). Except for the application of Dermagraft, treatment of study ulcers was identical for patients in both groups. All patients received pressure-reducing footwear and were allowed to be ambulatory during the study. RESULTS: The results demonstrated that patients with chronic diabetic foot ulcers of >6 weeks duration experienced a significant clinical benefit when treated with Dermagraft versus patients treated with conventional therapy alone. With regard to complete wound closure by week 12, 30.0% (39 of 130) of Dermagraft patients healed compared with 18.3% (21 of 115) of control patients (P = 0.023). The overall incidence of adverse events was similar for both the Dermagraft and control groups, but the Dermagraft group experienced significantly fewer ulcer-related adverse events. CONCLUSIONS: The data from this study show that Dermagraft is a safe and effective treatment for chronic diabetic foot ulcers.

Graftskin, a human skin equivalent, is effective in the management of noninfected neuropathic diabetic foot ulcers: a prospective randomized multicenter clinical trial.

OBJECTIVE: We assessed in a randomized prospective trial the effectiveness of Graftskin, a living skin equivalent, in treating noninfected nonischemic chronic plantar diabetic foot ulcers. RESEARCH DESIGN AND METHODS: In 24 centers in the U.S., 208 patients were randomly assigned to ulcer treatment either with Graftskin (112 patients) or saline-moistened gauze (96 patients, control group). Standard state-of-the-art adjunctive therapy, which included extensive surgical debridement and adequate foot off-loading, was provided in both groups. Graftskin was applied at the beginning of the study and weekly thereafter for a maximum of 4 weeks (maximum of five applications) or earlier if complete healing occurred. The major outcome of complete wound healing was assessed by intention to treat at the 12-week follow-up visit. RESULTS: At the 12-week follow-up visit, 63 (56%) Graftskin-treated patients achieved complete wound healing compared with 36 (38%) in the control group (P = 0.0042). The Kaplan-Meier median time to complete closure was 65 days for Graftskin, significantly lower than the 90 days observed in the control group (P = 0.0026). The odds ratio for complete healing for a Graftskin-treated ulcer compared with a control-treated ulcer was 2.14 (95% CI 1.23-3.74). The rate of adverse reactions was similar between the two groups with the exception of osteomyelitis and lower-limb amputations, both of which were less frequent in the Graftskin group. CONCLUSIONS: Application of Graftskin for a maximum of 4 weeks results in a higher healing rate when compared with state-of-the-art currently available treatment and is not associated with any significant side effects. Graftskin may be a very useful adjunct for the management of diabetic foot ulcers that are resistant to the currently available standard of care.

Tissue-engineered skin substitutes.

The last two years have seen new tissue-engineered skin substitutes come onto the market and begin to resolve the various roles to which each is best suited. It is becoming evident that some of the very expensive cell-based products have cost-benefit advantage despite their high price and are valuable within the restricted applications for which they are intended. The use of skin substitutes for testing purposes has extended from epidermal keratinocytes to other integumentary epithelia and into preparations containing multiple cell types in which reactions resulting from paracrine interactions can be examined. Challenges remain in the application of gene therapy techniques to skin substitutes, both the control of transgene expression and in the selection of suitable genes to transfect. A coming challenge is the production of tissue-engineered products without the use of animal products other than human cells. A challenge that may be diminishing is the importance of acute rejection of allogeneic tissue-engineered skin substitutes.

Measurement of DNA biomarkers for the safety of tissue-engineered medical products, using artificial skin as a model.

To test the hypothesis that the process of tissue engineering introduces genetic damage to tissue-engineered medical products, we employed the use of five state-of-the-art measurement technologies to measure a series of DNA biomarkers in commercially available tissue-engineered skin as a model. DNA was extracted from the skin and compared with DNA from cultured human neonatal control cells (dermal fibroblasts and epidermal keratinocytes) and adult human fibroblasts from a 55-year-old donor and a 96-year-old donor. To determine whether tissue engineering caused oxidative DNA damage, gas chromatography/isotope-dilution mass spectrometry and liquid chromatography/isotope-dilution mass spectrometry were used to measure six oxidatively modified DNA bases as biomarkers. Normal endogenous levels of the modified DNA biomarkers were not elevated in tissue-engineered skin when compared with control cells. Next, denaturing high-performance liquid chromatography and capillary electrophoresis-single strand conformation polymorphism were used to measure genetic mutations. Specifically, the TP53 tumor suppressor gene was screened for mutations, because it is the most commonly mutated gene in skin cancer. The tissue-engineered skin was found to be free of TP53 mutations at the level of sensitivity of these measurement technologies. Lastly, fluorescence in situ hybridization was employed to measure the loss of Y chromosome, which is associated with excessive cell passage and aging. Loss of Y chromosome was not detected in the tissue-engineered skin and cultured neonatal cells used as controls. In this study, we have demonstrated that tissue engineering (for TestSkin II) does not introduce genetic damage above the limits of detection of the state-of-the-art technologies used. This work explores the standard for measuring genetic damage that could be introduced during production of novel tissue-engineered products. More importantly, this exploratory work addresses technological considerations that need to be addressed in order to expedite accurate and useful international reference standards for the emerging tissue-engineering industry.

Skin replacements. The biotechnological quest for optimal wound closure.

Extensive skin loss from a variety of conditions is associated with significant functional morbidity and loss of life. In many patients, a limited number of donor sites available for harvesting autologous split-thickness skin grafts prevents early, effective, and permanent wound closure. In the past 25 years, significant biotechnological advancements have been made in defining the criteria and manufacturing ingredients in materials that could serve as skin replacements for permanent wound closure. The optimal skin replacement should have the functional and cosmetic properties of the dermis and the epidermis. It should provide rapid, functional wound coverage and barrier protection to microorganisms, normalize fluid flux and hypermetabolism, and provide long-term stability without contraction or hypertrophic scarring. In addition, the optimal skin replacement should be nontoxic, easily stored and used, and relatively cost-effective. This report will discuss the two major skin replacement designs available today, cultured keratinocyte grafts and bioartificial bilaminate systems, outline the advantages and disadvantages of each material, report the results of clinical trials for each, and speculate on the potential for each material to serve as a practical skin replacement.

Bilayered bioengineered skin substitute (Apligraf): a review of its use in the treatment of venous leg ulcers and diabetic foot ulcers.

UNLABELLED: The bilayered bioengineered skin substitute (BBSS) [Apligraf] is used for the treatment of venous leg ulcers and diabetic foot ulcers. It has an epidermal layer formed from human keratinocytes and a dermal layer composed of human fibroblasts in a bovine type I collagen matrix. BBSS does not contain any antigen-presenting cells such as Langerhans cells, dermal dendritic cells, endothelial cells or leucocytes. In clinical trials, there was no evidence of clinical rejection and immunological tests indicated no humoral or cellular response to the keratinocytes or fibroblasts of BBSS. Further clinical trials are required to identify the exact mechanism of action of BBSS in chronic wounds. BBSS plus compression therapy was well tolerated and was superior in efficacy to compression therapy alone in a multicentre, randomised trial in patients with venous leg ulcers. At 6 months' follow-up, complete wound healing occurred in 63 versus 49% of patients and the median time to wound closure was 61 versus 181 days. In a subgroup of patients with hard-to-heal ulcers (>1 year's duration), wound healing was achieved in significantly more patients (47 vs 19%) and the median time to wound healing was significantly shorter (181 days vs not attained). In a multicentre, randomised trial, BBSS was well tolerated and effective in patients with full-thickness neuropathic diabetic foot ulcers. Ulcer healing occurred in significantly more patients (56 vs 38%) and the median time to wound healing was shorter (65 vs 90 days) with BBSS than with saline-moistened gauze at 12 weeks' follow-up. Patients in both groups also received standard diabetic foot care. The cost effectiveness of BBSS in patients with chronic ulcers has yet to be examined in well designed, prospective clinical trials. However, according to a modelled analysis incorporating data from a multicentre randomised trial, BBSS was cost effective in patients with hard-to-heal venous leg ulcers. The average annual medical cost of managing patients with ulcers of >1 year's duration was estimated to be 20,041 US dollars per patient treated with BBSS plus compression therapy and 27,493 US dollars per patient treated with compression therapy alone (1996 costs). CONCLUSIONS: Clinical trials have shown that BBSS in conjunction with standard compression therapy was effective and well tolerated in patients with venous leg ulcers, especially patients with ulcers of >6 months' duration or that extended to the subcutaneous tissue. In addition, BBSS in conjunction with standard diabetic foot care was effective and well tolerated in patients with full-thickness neuropathic diabetic foot ulcers. BBSS represents a useful adjuvant to standard ulcer therapy in patients with venous leg ulcers or full-thickness neuropathic diabetic foot ulcers that do not respond to conventional ulcer therapy.