Epidermal Allografts Research Articles

Outcome comparison of the most commonly employed wound coverage techniques in patients with massive burns ≥50% TBSA – A systematic review and meta-analysis

IntroductionEarly wound coverage is one of the most essential factors influencing the survival of extensively burned patients, especially those with a total body surface area (TBSA) burned greater than 50 %. In patients with limited donor sites available for autografting, techniques such as the Meek micrograft procedure or cultured epidermal allografts (CEA) have proven to be viable alternatives. In this systematic review and meta-analysis, we analyzed the outcomes of different wound coverage techniques in patients with massive burn injuries ≥ 50 % TBSA in the past 17 years. MethodsThe EMBASE, PUBMED, Google Scholar and MEDLINE databases were searched from inception to December 2022 for studies investigating major burn reconstruction (>50 % TBSA) with the use of one of: a) autografts, b) allografts, c) cell-based therapies, and d) Meek micrografting. The review was conducted in accordance with the PRISMA guidelines. The outcomes evaluated were mortality, length of hospital stay, graft take and number of operations performed. ResultsFollowing a two-stage review process, 30 studies with 1369 patients were identified for analysis. Methods of coverage comprised the original autografting, and the newer Meek micrografting, CEA autografting, and allografting. Pooled mean age of the entire cohort was 32.5 years ( ± SE 3.6) with mean burn size of 66.1 % ( ± 2.5). After pooling the data, advantages in terms of mortality rate, length of stay, graft take and number of required surgeries were seen for the Meek and CEA groups. Mortality was highest in patients treated with autografts (50 %) and lowest with cell-based therapy (11 %). Length of stay was longest with cell-based therapy (91 ± 16 days) and shortest with Meek micrografting (50 ± 24 days). Graft take was highest with autografts (96 ± 2 %) and lowest with cell-based therapy (72 ± 9 %). Average number of operations was highest with cell-based therapy (9 ± 4) and lowest with Meek micrografting (4 ± 2). ConclusionsComparison of the four techniques highlighted differences in terms of all outcomes assessed, and each technique was associated with different advantages. Interestingly autografting, the option with the highest graft take rate, was also associated with the highest mortality. This study not only serves to provide the first comparison of the most commonly used techniques in major burn reconstruction, but also highlights the need for prospective studies that directly compare the efficacy of the different techniques to ultimately establish whether a true superior option exists.

Management of the burn patient with human epidermal allograft cultured in vitro

In Mexico a biological dressing was developed based on the culture of human keratinocytes in vitro. As a result, these procedures allow the expansion of keratinocytes in approximately 10,000 times their initial number, used in the treatment to cover the areas affected by burns, being a more important factor in obtaining this adequate result in the healing with its respective advantages both in social and economic terms.

500 Wound Coverage for Massive Burn Injuries ≥50% TBSA – A Systematic Review and Meta-Analysis

Abstract Introduction Early wound coverage remains one of the most essential variables influencing survival of extensively burned patients, especially with a total burned surface area (TBSA) of more than 50%. In patients with limited donor sites, techniques such as e.g. the Meek micrograft procedure or cultured epidermal allografts have proven to be viable methods. In this systematic review (SR) and meta-analysis (MA) we studied the outcomes of different techniques for wound coverage in patients with massive burn injuries ≥50% TBSA within the last 17 years. Methods According to PRISMA guideline the medical databases PubMed, Cochrane, Embase, Web of Science Medical records were screened in 5 languages from 01/2005 until 01/2022 by three reviewers, independently. Inclusion criteria were prospective or retrospective studies on patients with massive burns of ≥50% TBSA. Results After a two-stage review process, 33 studies were identified for the SR and MA. Regions of publication were Asia (n=15), North America (n=8), Europe (n=7), Australia (n=3). In total, 1678 patients with a mean age of 31.4 ± 14.2 years were included. The male to female ratio was 2.25 : 1. Mean TBSA was 66,5 ± 12.2%. Methods of wound coverage consisted of Meek micrografts, cultured epithelial autografts and/or allografts. The mean length of stay was 76.5 ± 32.4 days. Initial graft-take was 78,0 ± 15.8%. Grafting techniques did neither substantially differ in the length of stay nor the healing rate. Conclusions In patients with massive burn injuries of ≥50% TBSA the length of stay and the healing rates were comparable between Meek micrograft procedure, cultured epithelial allografts and combined techniques. Applicability of Research to Practice Wound coverage by Meek micrograft procedure with expansion of up to 1:10 and a potential combination with cultured epithelial allografts should be considered early in patients with massive burn injury.

A novel approach for wound treatment using dried cultured epidermal allograft: A phase I/II, single-center, open-label clinical trial

BackgroundAutologous cultured epidermis (CE) is successfully used in burn care, but it requires a manufacturing time of three weeks and is very expensive owing to its custom-made nature of treatment. To compensate this disadvantage, dried allogeneic CE promises a novel therapeutic approach; and previous reports have demonstrated its efficacy in promoting wound healing using a murine skin defect model. Herein, a prospective clinical study was conducted to confirm the safety and efficacy of dried allogeneic CE for wound treatment. MethodsDried CE was manufactured using donor keratinocytes obtained from excess surgical skin and applied to skin defects that were at least 3 cm in length and less than 10 % of the body surface area of the patients. The patients were observed for 14 days after CE application. The primary endpoint was the incidence of adverse events and the secondary endpoint was the percentage of wound healed since baseline, on days 7 and 14. Furthermore, as a stratified analysis, the percentage of wound healed, specified as deep dermal burns, was calculated. ResultsSix patients (five burns and one skin ulcer after necrotizing fasciitis) enrolled in the study. As a serious adverse event, a local infection was observed in one patient, which resolved by debridement and conventional skin grafting. Other adverse events that were potentially related to this treatment included two cases of skin erosion, and one case of systemic fever. No unresolved adverse events remained at the end of the study period. The percentage of wound healed was 73.4 ± 19.2 % on Day 7, and 92.2 ± 11.8 % on Day 14. When the targeted disease was restricted to deep dermal burns, the percentage of wound healed was 69.9 ± 28.9 % on Day 7 and 90.5 ± 13.2 % on Day 14. ConclusionTreatment with dried CE was safely performed without any unresolved severe adverse effects. Dried CE is a new and promising modality for skin defect treatment, such as burns and ulcers, and is expected to compensate for the disadvantages of autologous CE. However, large-scale clinical trials are required to confirm their efficacy.

Interrogation of RDEB Epidermal Allografts after BMT Reveals Coexpression of Collagen VII and Keratin 15 with Proinflammatory Immune Cells and Fibroblasts

Recessive dystrophic epidermolysis bullosa (RDEB) is a devastating genodermatosis characterized by dysfunctional collagen VII protein resulting in epithelial blistering of the skin, mucosa, and gastrointestinal tract. There is no cure for RDEB, but improvement of clinical phenotype has been achieved with bone marrow transplantation and subsequent epidermal allografting from the bone marrow transplant donor. Epidermal allografting of these patients has decreased wound surface area for up to 3 years after treatment. This study aimed to determine the phenotype of the epidermal allograft cells responsible for durable persistence of wound healing and skin integrity. We found that epidermal allografts provide basal keratinocytes coexpressing collagen VII and basal stem cell marker keratin 15. Characterization of RDEB full-thickness skin biopsies with single-cell RNA sequencing uncovered proinflammatory immune and fibroblast phenotypes potentially driven by the local environment of RDEB skin. This is further highlighted by the presence of a myofibroblast population, which has not been described in healthy control human skin. Finally, we found inflammatory fibroblasts expressing profibrotic gene POSTN, which may have implications in the development of squamous cell carcinoma, a common, lethal complication of RDEB that lacks curative treatment. In conclusion, this study provides insights into and targets for future RDEB studies and treatments.

Use of Cultivated Epidermal Allograft in Chronic Wounds: A Novel Therapeutic Alternative.

Chronic wounds represent a frequent cause of consultation for plastic and reconstructive surgeons. The use of epidermal culture stands out because they provide complete epithelialization, adequate aesthetic-functional results, and no morbidity for the patient. Epifast® is a pre-manufactured cultured epidermal allograft derived from the amplification in vitro of human keratinocytes. A prospective longitudinal multicenter study was carried out in four chronic wound reference centers, which were in charge of plastic and reconstructive surgery services. For a standardized wound bed preparation, the protocol synthesized by the acronym "TIME" was used. At the end of the "TIME" protocol, the pre-fabricated allograft was applied and removed 7 days after its application. A total of 133 patients with diagnosis of chronic wound were included in the study. The median age was 69.3 ± 13.6 years. The most common comorbidity found was diabetes mellitus type 2 in 71.4% of the patients (n = 95) and systemic arterial hypertension in 60.2% of the patients (n = 80). The most frequent location of chronic wounds was seen in the lower extremity with 45.1% (n = 60). The mean duration for it to close was 46 ± 14 days, in which they closed within the first 3 months in 93% (n = 125) of the cases. About 91.7% (n = 122) of the wounds achieved total closure. Cultured epidermal allograft, combined with a meticulous technique and an adequate selection of patients, represents a safe and effective tool for chronic wounds.

Immune tolerance of allogeneic haematopoietic cell transplantation supports donor epidermal grafting of recessive dystrophic epidermolysis bullosa chronic wounds.

Chronic wounds, a common morbidity in recessive dystrophic epidermolysis bullosa (RDEB), lack definitive therapies. To assess allogeneic epidermal skin grafts in terms of wound healing and durability over time. In a prospective, open-label clinical trial for postallogeneic haematopoietic cell transplantation (post-alloHCT) patients with RDEB, up to nine chronic wounds per patient were grafted over 1year. Epidermal grafts measuring 5 cm2 were obtained from related alloHCT donors in the outpatient setting using the CELLUTOMETM Epidermal Harvesting System. Wounds were photographed and symptom inventories completed at baseline and 6, 12 and 52weeks after grafting. The trial was registered at ClinicalTrials.gov (NCT02670837). Between August 2016 and January 2019, eight patients with RDEB received a total of 35 epidermal allografts at a median of 1157days (range 548-2884) post-alloHCT. The median (interquartile range) percentage reductions in wound surface area were 75% (52-94), 95% (72-100) and 100% (97-100) at 6, 12 and 52weeks postgraft, respectively, each significantly reduced from baseline (P<0·001). Donor harvest sites healed quickly without scarring. Biopsy evaluation at 1year of an epidermal allograft site revealed wildtype type VII collagen (immunofluorescence), anchoring fibrils (electron microscopy), and full-thickness skin whole-DNA donor chimerism of 42% (compared with 16% in concurrently biopsied native skin). This strategy subsequently supported release of RDEB pseudosyndactyly. The immune tolerance established by alloHCT supports successful adoptive transfer of donor epidermal grafts. Persistence of donor grafts in a single patient beyond 1year and observed migration of donor-grafted cells into adjacent wound suggest that epidermal allografts include nonterminally differentiated cells and/or trigger recruitment of donor bone-marrow-derived cells to mediate wound healing.

355 Regeneration of the Entire Human Epidermis by Transgenic Epidermal Stem Cell Transplants and its Implications for the Treatment of Burns

We recently performed the regeneration of almost an entire human epidermis by transplantation of genetically modified epidermal stem cells in a 7-year-old patient suffering from terminal Junctional Epidermolysis Bullosa (JEB). JEB is caused by mutations of genes encoding for basement membrane components, LAMB3 in this case, leading to severe skin lesions with often lethal outcome. These defects present in a similar fashion to deep partial-thickness burns with loss of epidermis but remaining dermal wound bed. Epidermal stem cells were procured via skin biopsy and transduced using a retroviral vector expressing the full-length LAMB3 cDNA. The transduced stem cells were then cultured using a modified culture protocol providing an optimal environment for the preservation of most potent epidermal stem cells, termed holoclones. We then transplanted 0,85m2 of autologous transgenic keratinocyte cultures after our patient had lost over 80% total body surface area of its epidermis. We performed a 2-year follow-up with clonal tracing and in-depth skin structure assessment using skin biopsies and optical coherence tomography. We also tested skin physiology parameters and mechanical stress resistance. We regenerated 80% of the child’s epidermis with autologous transgenic keratinocytes. Clonal tracing demonstrated, formally for the first time in humans, that the new epidermis was sustained by a finite number of holoclones. Two years after transplant, the patient demonstrated a high quality skin enabling a full range of motion, sebum production, and partial hair growth. Transepidermal water loss and skin elasticity were comparable to healthy skin. Sebum production was intact without the need for any more ointment application one year after transplant. In this study, we show that autologous transgenic keratinocyte cultures can regenerated an entire functional epidermis on a 7-year-old child after life-threatening loss of its original epidermis. We provide evidence for a high quality functional epidermis 2 years after transplantation that is sustained by a finite number of highly regenerative stem cells. Besides providing the first potential cure for JEB, this technology may enable a novel treatment of deep partial-thickness burns that is superior to split-thickness skin grafting or transplantation of regular cultured epidermal allografts.

Effectiveness and Safety of a Thermosensitive Hydrogel Cultured Epidermal Allograft for Burns.

To retest the safety and effectiveness of a thermosensitive hydrogel-type cultured epithelial allograft (KeraHeal-Allo; MCTT, Seoul, South Korea) and identify the subjective experience of patients and doctors with this product. Prospective interventional phase 3 study in 3 burn centers near Seoul, South Korea. Thirty-three patients with deep second-degree burns larger than 200 cm (for intervention and control sites of 100 cm each) were enrolled. A cultured epithelial allograft containing 2 × 10/1.5 mL keratinocytes was applied to each patient's intervention site. Three principal investigators (1 in each institution) evaluated the effectiveness of the allograft at their institution and the others'. Researchers administered a subjective satisfaction survey during each patient's last visit. The primary end point of the study was the re-epithelialization period. The re-epithelialization period for the intervention was 2.8 ± 2.2 days faster than that of control sites at other institutions (P < .001) and 2.5 ± 3.4 days faster than that of control sites in the same institution (P < .001). There were no reported adverse events. Satisfaction scores provided by patients and doctors showed significantly high scores on all items. This type of cultured epithelial allograft is safe and well received by patients and providers and promotes re-epithelialization.

A clinical trial designed to evaluate the safety and effectiveness of a thermosensitive hydrogel-type cultured epidermal allograft for deep second-degree burns

This study is a phase 1 and 2 clinical trial for investigating the safety profile, effective treatment dose and effectiveness of the newly developed thermosensitive hydrogel-type cultured epidermal allograft.For phase 1, the keratinocytes were divided into 3 groups as follows, with 5 patients in each group: (1) low-dose group (6.7×106/1.5mL), (2) medium-dose group (2×107/1.5mL), and (3) high-dose group (6.0×107/1.5mL). The second phase of the trial proceeded with 10 cases after choosing the most effective dose based on the analysis of the first phase.When comparing re-epithelialization time, medium- and high-dose group showed significantly shorter re-epithelialization time than low-dose group (p=0.003 and p=0.002). A total of 15 cases, 5 cases selected from phase 1 and 10 cases test in phase 2 with the medium dose, were compared with the re-epithelialization period. The re-epithelialization period was 9.6±4.0 days in the test site and 12.4±4.8 days in the control site. In the test site, re-epithelialization was 2.8±1.8 days faster than in the control site (p<0.0001). There was no significant adverse reaction in our clinical trial.In conclusion, this new type of CEAllo accelerates wound healing time and shows the safety.

An outcome analysis and long-term viability of cryopreserved cultured epidermal allografts: assessment of the conservation of transplantable human skin allografts

To assess the viability of cultured epithelium and preserved by freezing for periods varying from one month to one year. Samples of cultured epithelium were incubated in cryoprotectant medium (Group A), packed in aluminum envelopes and packed in polystyrene boxes. The boxes were subjected to a temperature of-70 ºC. After freezing for a period of time ranging from one to 12 months, cultured epithelial samples were assessed for their viability by vital staining (Trypan blue) and metabolic analysis based on glucose consumption and lactate production. Samples of not frozen cultured epithelium (Group B) were also tested for viability and the results obtained were used as comparison parameter for the variation of viability. Statistical analysis between the group A and B indicate that the mean age of the donors (p=0.51) and the culture time (p=1.18) showed no statistical difference. In 30 days we obtained 37% of the original viability of cultured epithelium, 25% at six months and one year, less than 15%. This trend was confirmed statistically with a reduction of approximately 1.8% of the original viability epithelium cultured every 30 days of storage. In the analysis by lactate production, similar results were observed. In the analysis by the glucose consumption results were not significant. The viability indices show statistically significant difference between the group A and B (p<0.0001). Although cryopreserved cultured epithelium showed significant reduction of viability, all samples remained viable. It was also found that the viability of cryopreserved cultured epithelial decreased as a function of storage time.

Cryopreserved, cultured, allogenic, human epidermal grafts for the treatment of chronic ischemic ulcers: A report on two cases

Cultured, allogenic, human epidermal grafts have been successfully used to treat extensive burns, donor sites, leg ulcers, and eroded areas in recessive dystrophic epidermolysis bullosa. The following report describes the use of cryopreserved cultured human epidermal allografts in the treatment of long-standing ischemic ulcers unresponsive to conventional medical therapy in two patients who had previously undergone unsuccessful vascular reconstructive surgery. A marked reduction in ulcer size as well as rapid pain relief was achieved in both patients. In selected cases the use of epidermal grafts as a biologic topical therapy could represent an alternative to other medical treatments. However, thus far, only a few cases have been reported and the uncertain short- and long-term results as well as the excessive costs may limit the widespread application of this treatment modality.

Cutaneous Wound Healing

Overall, burns are smaller than 20 years ago, but even small burns can leave patients with debilitating scars. The management of the burn wound and resultant scarring requires the integration of multiple disciplines. Despite our best efforts, the evaluation and treatment of burn wounds and burn scars has not been completely elucidated. The purpose of this work is to describe the state of knowledge regarding wound healing, both what is known and what is not known, and to recap the priorities set by the breakout sessions of the Burn State of the Science: Research meeting. Wound challenges in 2007 include wound coverage for patients with extensive full-thickness burns, management of donor sites and partial-thickness burns, and reduction of long-term morbidity from burn scars. Early excision and grafting of the burn wound have indisputably impacted burn survival more than any other intervention during the past 30 years.1 Removing the burn wound has been reported to decrease infection, shorten hospital length of stay, reduce the need for reconstructive surgery, and return patients to their premorbid level of function sooner.2 These clinical advances have created a standard of care that emphasizes use of sheet skin grafts whenever possible with meshed grafts recommended for coverage of burns in patients with larger full-thickness wounds.3,4 Larger wounds may benefit from coverage with skin substitutes. Existing skin substitutes include both dermal replacement templates and epidermal cultures.5 Dermal substitutes, such as Integra (Integra Life Sciences Corp., Plainsboro, NJ), replace the cutaneous connective tissue and provide a template for ingrowth of indigenous cells from the wound bed.6,7 Dermal substitutes have been reported to reduce scar formation and improve wound pliability. Keratinocyte grafts restore the epidermal layer and restore the cutaneous barrier to infection and fluid loss. Cultured epidermal allografts, which have gained popularity for treatment of nonhealing chronic wounds, have limited applicability in definitive burn treatment because of rejection. Reports of successful treatment of large burns with cultured dermal–epidermal autografts8,–12 have not yet progressed to multicenter trials because of their expense and complexity of fabrication.13 Whereas development of these products has advanced the field, time of preparation and expense limit their availability for treatment of patients with extensive burn injuries.

Cryopreserved and lyophilized cultured epidermal allografts in the treatment of leg ulcers: a pilot study

In the conservative therapy of venous leg ulcers modern types of dressings are used most frequently. In the past 20 years 'active wound dressings' - cultured epidermal keratinocytes as autografts and allografts - were also introduced in the management of leg ulcers. The aim of our study was to compare the effect of cryopreserved and lyophilized cultured epidermal allografts in the treatment of venous leg ulcers. Evaluation of the therapy was documented as photodocumentation, planimetry, healing time and evaluation of pain relief over a 3-month period after application. Fifty patients with venous leg ulcers were selected. Twenty-five patients (group I) were treated with cryopreserved keratinocytes and 25 (group II) with lyophilized keratinocytes. The final evaluation 3 months after the application of allografts showed 84% of healed ulcers in group I and 80% in group II. The number of healed ulcers and the healing rate both showed no statistically significant differences. The size of the ulcer was reduced by half during the first week in both groups. The size differences during the first week are statistically significant in both groups and they are comparable (P < 0.001). The intensity of the pain was statistically significantly reduced during the first week after application in both groups (P < 0.001). The cryopreserved and lyophilized cultured allografts are comparable in healing rate, course of healing and relief of pain, and also in planimetric changes during the healing of venous leg ulcers. Lyophilized allografts are more convenient for routine use than cryopreserved allografts as they can be stored at room temperature. These results could give rise to the more frequent use of lyophilized allografts in slow-healing venous leg ulcers.

Cultured epidermal allografts: Quantitative evaluation of their healing effect in deep dermal burns.

This study summarizes the Brno Burn Centre experience with the application of cultured epidermal allografts (CEAl) in the treatment of deep dermal burns. In a prospective randomised trial on 30 patients with deep dermal burns CEAl obtained from young healthy and examined donors and fixed on tulle grass carrier (Grasolind) were compared with empty Grasolind as the lowest layer of dressing. All the other layers were identical.Both kinds of dressing were applied simultaneously on the same deep dermal burn wound between 6th and 10th day after burn. Six days later the non-healed wound areas were recorded through painting on cellophane membrane and scanned in the computer. The percentage of wound reduction was calculated and statistically evaluated.The reduction of the non-epithelialized wound area was 86.5% when covered through CEAl and only 71.2% when covered with tulle grass (Grasolind) only. This difference is statistically significant.In conclusion it can be stated that cultured epidermal allografts strongly stimulate reepithelialisation in deep dermal burns.

Cryopreserved cultured epidermal allografts achieved early closure of wounds and reduced scar formation in deep partial-thickness burn wounds (DDB) and split-thickness skin donor sites of pediatric patients

Burn treatment in children is associated with several difficulties, e.g. available skin replacement is small, donor area could expand, and subsequent hypertrophic scar and contracture could become larger along with their physical growth. In order to have better clinical results, the authors prepared cryopreserved cultured epidermal allografts from excess epidermal cells of other patients, and applied the epidermal allografts to 55 children, i.e. 43 cases of deep partial-thickness burn wounds (DDB) due to scald burn and 12 cases with split-thickness skin donor sites. In the 43 DDB patients, epithelialization was confirmed 9.1±3.6 days (mean±S.D.) after treatment. In 10 of the 43 patients, epithelialization was comparable between the area which received the epidermal allografts (grafted area) and the area which did not receive the epidermal allografts but was covered with usual wound dressing (non-grafted area). As a result, epithelialization day was 7.9±1.7 in grafted areas and 20.5±2.3 in non-grafted areas. In the 12 patients with split-thickness skin donor sites, epithelialization was confirmed 6.3±0.9 days after treatment. Epithelialization of the grafted and non-grafted areas was comparable in 8 of the 12 patients, and it was 6.5±1.1 days and 14.1±1.6 days, respectively. In these 10 DDB patients and 8 split-thickness skin donor site patients, redness and scar formation were also milder in the grafted area. The 55 patients have been followed up for 1–8 years (mean, 4.75 years), and scar formation was suppressed in both DDB and split-thickness skin donor sites. These findings showed that cryopreserved cultured epidermal allografts achieve early closure of the wounds and good functional outcomes.

Tissue-engineered skin. Current status in wound healing.

Tissue-engineered skin is a significant advance in the field of wound healing and was developed due to limitations associated with the use of autografts. These limitations include the creation of a donor site which is at risk of developing pain, scarring, infection and/or slow healing. A number of products are commercially available and many others are in development. Cultured epidermal autografts can provide permanent coverage of large area from a skin biopsy. However, 3 weeks are needed for graft cultivation. Cultured epidermal allografts are available immediately and no biopsy is necessary. They can be cryopreserved and banked, but are not currently commercially available. A nonliving allogeneic acellular dermal matrix with intact basement membrane complex (Alloderm) is immunologically inert. It prepares the wound bed for grafting allowing improved cultured allograft 'take' and provides an intact basement membrane. A nonliving extracellular matrix of collagen and chondroitin-6-sulfate with silicone backing (Integra) serves to generate neodermis. A collagen and glycosaminoglycan dermal matrix inoculated with autologous fibroblasts and keratinocytes has been investigated but is not commercially available. It requires 3 to 4 weeks for cultivation. Dermagraft consists of living allogeneic dermal fibroblasts grown on degradable scaffold. It has good resistance to tearing. An extracellular matrix generated by allogeneic human dermal fibroblasts (TransCyte) serves as a matrix for neodermis generation. Apligraf is a living allogeneic bilayered construct containing keratinocytes, fibroblasts and bovine type I collagen. It can be used on an outpatient basis and avoids the need for a donor site wound. Another living skin equivalent, composite cultured skin (OrCel), consists of allogeneic fibroblasts and keratinocytes seeded on opposite sides of bilayered matrix of bovine collagen. There are limited clinical data available for this product, but large clinical trials are ongoing. Limited data are also available for 2 types of dressing material derived from pigs: porcine small intestinal submucosa acellular collagen matrix (Oasis) and an acellular xenogeneic collagen matrix (E-Z-Derm). Both products have a long shelf life. Other novel skin substitutes are being investigated. The potential risks and benefits of using tissue-engineered skin need to be further evaluated in clinical trials but it is obvious that they offer a new option for the treatment of wounds.

Cryopreserved, cultured, allogenic, human epidermal grafts for the treatment of chronic ischemic ulcers: A report on two cases

Cultured, allogenic, human epidermal grafts have been successfully used to treat extensive burns, donor sites, leg ulcers, and eroded areas in recessive dystrophic epidermolysis bullosa. The following report describes the use of cryopreserved cultured human epidermal allografts in the treatment of long-standing ischemic ulcers unresponsive to conventional medical therapy in two patients who had previously undergone unsuccessful vascular reconstructive surgery. A marked reduction in ulcer size as well as rapid pain relief was achieved in both patients. In selected cases the use of epidermal grafts as a biologic topical therapy could represent an alternative to other medical treatments. However, thus far, only a few cases have been reported and the uncertain short- and long-term results as well as the excessive costs may limit the widespread application of this treatment modality.

Treatment of Epidermolysis bullosa with Human Cultured Epidermal Allografts

Junctional epidermolysis bullosa letalis type Herlitz Pearson is a genetically determined, life-threatening disease. Effective therapy has been lacking to date. Therefore any therapy that improves wound healing would be beneficial for these patients. Cultured epidermal grafts are known to enhance wound epithelialization and have been used with success in some epidermolysis bullosa disorders. Encouraged by these reports, we grafted cultured allogeneic keratinocytes to an infant with a junctional epidermolysis bullosa letalis type.

Randomized trial comparing cryopreserved cultured epidermal allografts with hydrocolloid dressings in healing chronic venous ulcers

Cultured epidermal allografts have been successfully used to treat a variety of wounds. Their postulated mechanism of action is through release of cytokines that stimulate epithelialization. On the basis of previous experience we expected ulcers treated with cryopreserved cultured allografts (CCAs) to be healed by 6 weeks. Hydrocolloid dressings (HCDs) have also been reported to be effective in the treatment of venous ulcers. Our purpose was to compare the effectiveness of CCAs with HCDs in healing chronic venous ulcers. Forty-three patients with 47 ulcers were enrolled in a randomized controlled trial. Ulcers not healed by 6 weeks were changed to the other treatment. No difference in the number of healed ulcers between the two groups was observed at 6 weeks. Healing rate, percent reduction of initial ulcer size, and radial progression toward wound closure were significantly greater for CCAs than for HCDs. Pain relief was not significantly different. CCAs achieve more rapid healing and greater reduction in ulcer size than HCDs.