Cultured Epidermal Autografts Research Articles

Treating epidermolytic ichthyosis and ichthyosis with confetti with epidermal autografts cultured from revertant skin.

No efficient treatment has been established yet for epidermolytic ichthyosis (EI) caused by pathogenic variants in KRT1 or KRT10. Patients with ichthyosis with confetti (IWC) show multiple normal-appearing spots, caused by the revertant somatic recombination of pathogenic variants that occurs at each spot independently. Additionally, some patients with EI have large areas of normal skin due to revertant postzygotic mosaicism. To assess the feasibility transplanting cultured epidermal autografts (CEAs) produced from revertant epidermal keratinocytes in patients with EI and IWC. We performed a clinical trial of treatment with CEAs produced from each patient's own revertant epidermal keratinocytes as a proof-of-concept study. This is a single-arm, open (masking not used), uncontrolled, single-assignment, treatment purpose study. The primary outcome was the rate of areas without the recurrence of ichthyosis lesions 4 weeks after the final transplant (%). The secondary outcome was the rate of areas without the recurrence of ichthyosis lesions 24 weeks after initial transplantation (%). We successfully produced CEAs from the genetically confirmed revertant skin of the two mosaic EI patients and one IWC patient and genetically confirmed that CEAs mainly consist of revertant wild-type cells by amplicon sequencing and droplet digital PCR analysis. Single-cell RNA sequencing analysis confirmed the normal proliferation and safety profiling of CEAs. CEAs were transplanted to desquamated lesional sites of the patients. Four weeks after this transplantation, the rate of areas without the recurrence of ichthyosis lesions in the three cases was 39.52%, 100.0%, and 100.0% respectively, although the recurrence of ichthyosis lesions was seen at the site of CEA transplantation in all three patients at 24 weeks after transplantation. CEAs from normal skin have the potential to be a safe and local treatment option for EI and IWC. jRCTb041190097.

Retrospective Review of Outcomes Related to Early Therapy Intervention Following Application of Cultured Epidermal Autografts in Severely Burned Patients.

Cultured epidermal autografts (CEA) have since become more prevalent in the treatment of burn-injured patients with limited available donor sites for adequate wound closure, resulting in decreased mortality rates and an increased number of these patients requiring burn therapy services to achieve optimal functional outcomes at discharge. However, the use and postoperative management of CEA continues to be controversial due in large to the physiological fragility and expense of CEA, leading to variable postoperative treatment practices across burn centers. As such, minimal research is available regarding patient outcomes following CEA application, specifically related to burn therapy intervention. Thus, a retrospective chart review was conducted on a series of 10 patients, 18 years of age or older, admitted to a single, American Burn Association (ABA) verified burn center, between April 2015 and April 2023, who required CEA, and received pre- and postoperative treatment by burn therapists in accordance with center-specific burn rehabilitation guidelines. The resulting patient outcomes, in response to early implementation of therapy interventions post-CEA surgery, demonstrated optimal functional status for patients upon discharge, and positive long-term implications.

CEA graft take after combining with a modified MEEK procedure

Resourceful surgical planning for coverage of large burns has led to refinement of early innovative procedures including meshed split thickness skin grafts (STSG), MEEK procedure, and use of cultured epidermal autografts (CEAs). The use of STSG remains standard of care for burn wound coverage; however, manual expansion of STSG is limited due to shortcomings with expansion rates greater than 4:1. The MEEK micrografting method is a method of preparing skin grafts with a device instead of manually with an autograft mesher, allowing reliable expansion rates of autografts up to 9:1. Although the CEA indication for use includes both with and without STSG, use of meshed STSG placed under CEA has been reported to minimize shear forces and hasten graft take. The purpose of this study was to evaluate success of graft take in patients receiving MEEK and CEA for wound coverage in extensive burns at a single burn center experienced in the use of both MEEK and CEA. Data in 15 patients who received both MEEK and CEA for the treatment of large burns (mean total body surface area [TBSA] of 66%) demonstrated a high rate of successful engraftment (87%), and an overall 73% survival rate.

559 Nursing Management of Multiple Concurrent Pediatric Patients with Cultured Epidermal Autografts

IntroductionFor patients with large areas of full-thickness burns and limited autologous donor sites, cultured epidermal autografts (CEAs) can provide life-saving coverage. Nursing care of a patient with CEAs can be challenging due to the fragility of these grafts and compounded by the critical status of the patient. Care of a single patient with CEAs can prove challenging, but in cases in which multiple patients receive CEAs concurrently, these challenges are amplified.MethodsThree pediatric patients with large burn injuries were admitted on a single day to a large academic hospital with a Burn Center (Table 1). Nursing care of these children with concurrent CEA placement required an all-hands-on-deck approach and collaboration between the Burn Center (BC) and the Pediatric Intensive Care Unit (PICU) with regards to staffing, care, and positioning. Consistent primary RNs from both the BC and PICU staffed patients and volunteered to work additional shifts during a period of high census. To meet patient needs, the multi-disciplinary care team developed a schedule for CEA exposure, wound care, and therapy interventions.ResultsTo meet the needs of these patients under the current staffing pattern, a team schedule was developed (Table 2).Table 2. Care Schedule0300-0400 Night shift staff removed anterior and extremity dressings with patients in supine.0800-0900 Therapy staff arrived early during the day shift to perform therapy interventions with anterior CEAs exposed. Multi-disciplinary teams applied anterior and extremity dressings, positioned patients prone, and removed dressings from posterior CEA sites.1700-1800 After approximately six to eight hours of CEA exposure, teams reapplied dressings and positioned patients supine.ConclusionsStaff followed this schedule for these patients until their CEAs were determined to be integrated. Planning and collaboration among all members of the treatment team are integral to the successful care of pediatric patients with CEAs. A schedule for wound care, turning, and CEA exposure can improve staff communication, ease hand-offs, and ensure optimal quality of care for multiple patients with these large burn injuries.

Cultured epidermal autografts for treatment of stable vitiligo: Quantitative analysis of color matching with surrounding normally pigmented skin.

Cultured epidermal autografts (CEA) are surgical therapeutic alternatives for patients with stable vitiligo resistant to conventional medical treatments. In the present study, we assessed color matching before and at 12 months after CEA treatment. Eleven patients with 16 vitiligo lesions were included in this prospective study. The recipient sites were prepared by CO2 laser superficial ablation and subjected to CEA application. We clinically evaluated and categorized the color matching of the repigmented skin as well as the percentage of repigmentation. We also obtained three color values (L*a*b*) for the vitiligo lesions and surrounding normally pigmented skin. We then calculated the color differences between the two regions and compared them before and at 12 months after treatment. The mean percentage of repigmentation was 63.3% at 12 months. Six of the 16 lesions were categorized as “same as” and had color difference values of ≤5 at 12 months after treatment. Clinical evaluation of the color matching coincided well with the calculated color difference values. CEA application after CO2 laser superficial ablation was useful for treating vitiligo assessed by the percentage of repigmentation and color matching. Quantification of color differences may be a useful parameter for evaluating color matching in vitiligo.

Safety and efficacy of basic fibroblast growth factors for deep second–degree burn patients

IntroductionBurn injuries are common afflictions; however, conservative wound care frequently leads to poor treatment compliance and physical disability in deep burn patients. Therefore, regenerative biologic materials, which are more effective for tissue repair, are required, particularly for deep second-degree burns. A novel spray formulation of basic fibroblast growth factors (bFGF) was produced by synthesizing fibroblast growth factor proteins. In this post-marketing surveillance (PMS) study, we assessed the safety and efficacy of bFGF and indirectly compared this formulation with cultured epidermal autografts (CEAs) for treating deep second-degree burns. Materials and methodsA total of 3173 patients treated at 15 hospitals were used for PMS of bFGF in South Korea for six years. In total, 1630 patients with deep second–degree burns were selected for assessing adverse events (AEs) of bFGF treatments. Efficacy was evaluated according to time periods until re-epithelialization, and clinical usefulness of bFGF was indirectly compared with that of CEAs. ResultsAEs occurred in 37 patients (2.3%) and included application site pain (1.7%) and contact dermatitis (0.6%). All AEs were mild and were evaluated as probably unrelated with bFGF. The average time for re-epithelialization was 8 days; this time span was significantly longer after major burns (9.7 days) than after minor (7.8 days) or moderate burns (7.9 days). Most treated burn wounds (99.8%) were assessed as improved. The indirect comparison included 534 patients using the same inclusion criteria for CEA patients (n = 35). The bFGF treatment demonstrated superior efficacy compared to CEAs by significantly reducing the average day to application (5.4 vs. 8.8 days) and re-epithelialization time (7.1 vs. 13.7 days). ConclusionOur study demonstrated that bFGF is a compelling regenerative therapy with competitive clinical efficacy and safety for deep second–degree burns and reduced treatment time, which is expected to reduce medical costs, particularly for deep second–degree burn patients.

Interest of interleukin-1β priming on various sources of MSC for wound healing: role of interleukin-6, a MSC secreted factor

Background & Aim Deep and extensive skin wounds and burns are treated with autologous Split-Thickness Skin Grafts, with a possible combination of adjuvant therapy, or grafted with Cultured Epidermal Autografts (CEAs) when donor sites are limited. Despite many years of use and the allowing of patient survival, CEA still fail to provide satisfactory clinical outcomes due to poor engraftment rates and reduced skin functionality. In the past few decades, Mesenchymal Stromal Cells (MSCs) therapy have been proposed as a novel therapeutic tool to promote wound healing through anti-inflammatory, pro-trophic and pro-remodeling effects. MSCs are also able to interact with their environment and modify their secretory profile depending on cellular, molecular or physical environment. Our team recently shown that, IL-1β-primed gingival MSCs promoted wound healing in vitro, and in vivo through the secretion of a mix of secreted products and extracellular vesicles. Paracrine mechanism involving MMPs and TGF-βs signaling has been shown to be implicated in MSC primed effect on wound healing. Preliminary results also indicated that IL-6 could also been involved. Therefore, in the present work, we investigated whether other source of MSC could respond similarly to Interleukin 1β to favor wound healing through the secretion of extracellular vesicles and secreted products. Methods, Results & Conclusion Naive and IL-1β-primed MSCs from gingival or bone marrow sources were evaluated in in vitro models of migration, inflammation and Dermal-Epidermal Junction (DEJ) formation. Extracellular vesicles and IL-6 expression were analyzed by NTA and ELISA respectively in the Conditioned Media (CM) of MSC culture. To investigate the mechanism of action of IL-6 in particular, we used human recombinant IL-6 at the concentration found in IL-CM by ELISA and specific blocking antibody in our different in vitro models. Preliminary results indicated that both MSC sources responds similarly to Interleukin-1β priming and have been shown to promote skin cell migration, favor extracellular matrix deposition and reduce inflammation. In vivo studies will be performed to confirm the results observed in vitro. Overall, these results underline the benefit of the IL-1β priming strategy in the treatment of severe skin defects using MSC and epidermal substitute. We hope that this approach could soon improve the current medical treatment of full-thickness burn wounds.

Cultured Epidermal Autografts from Clinically Revertant Skin as a Potential Wound Treatment for Recessive Dystrophic Epidermolysis Bullosa

Inherited skin disorders have been reported recently to have sporadic normal-looking areas, where a portion of the keratinocytes have recovered from causative gene mutations (revertant mosaicism). We observed a case of recessive dystrophic epidermolysis bullosa treated with cultured epidermal autografts (CEAs), whose CEA-grafted site remained epithelized for 16 years. We proved that the CEA product and the grafted area included cells with revertant mosaicism. Based on these findings, we conducted an investigator-initiated clinical trial of CEAs from clinically revertant skin for recessive dystrophic epidermolysis bullosa. The donor sites were analyzed by genetic analysis, immunofluorescence, electron microscopy, and quantification of the reverted mRNA with deep sequencing. The primary endpoint was the ulcer epithelization rate per patient at 4 weeks after the last CEA application. Three patients with recessive dystrophic epidermolysis bullosa with 8 ulcers were enrolled, and the epithelization rate for each patient at the primary endpoint was 87.7%, 100%, and 57.0%, respectively. The clinical effects were found to persist for at least 76 weeks after CEA transplantation. One of the three patients had apparent revertant mosaicism in the donor skin and in the post-transplanted area. CEAs from clinically normal skin are a potentially well-tolerated treatment for recessive dystrophic epidermolysis bullosa.

HGF, MMPs and TGF-β1 contribute to INTERLEUKIN-1β primed mesenchymal stromal cells effect on wound healing and epidermal substitute engraftment

Background & Aim In spite of several research advances in the field of skin tissue engineering and regenerative medicine, little progress has been made in the management of major burns. Since the 1980s, deep and extensive skin wounds and burns are treated with autologous Split-Thickness Skin Grafts, or Cultured Epidermal Autografts (CEAs) when donor sites are limited. While CEAs allow patient survival in most critical cases, poor engraftment rates and reduced skin functionality limit the clinical use of CEAs. In the past few decades, Mesenchymal Stromal Cells (MSCs) therapy has emerged as a new strategy to promote wound healing through anti-inflammatory, anti-microbial, pro-trophic and pro-remodeling effects. MSCs are also able to interact with their environment and modify their secretory profile depending on cellular, molecular or physical priming cues. Thus, the present work aims to assess the benefit and mechanism of action of Interleukin-1β (IL-1β) primed MSCs or their secretory products on wound healing and epidermal substitute engraftment. Methods, Results & Conclusion Naive and IL-1β-primed MSCs or their Conditioned Media (CM) were evaluated in in vitro models of migration, inflammation and Dermal-Epidermal Junction (DEJ) formation, and in an in vivo skin excisional and epidermal substitute grafting mouse model. We showed that the IL-1β priming potentiates the MSC efficacy through the reduction of inflammation and the promotion of cell migration, DEJ remodeling and epidermal substitute engraftment. These positive effects were partly mediated by MSC paracrine secretions which targeted downstream p38MAPK, SMAD and MMP signalings. Among priming-induced secreted factors, MMP-1, MMP-9, HGF and TGF-β1 were found to play key roles in the resolution of wound healing. These results underline the benefit of the IL-1β priming strategy in the treatment of severe skin defects using MSC and epidermal substitute. We hope that this approach could soon improve the current medical treatment of full-thickness burn wounds.

Twenty-Five Years' Experience and Beyond with Cultured Epidermal Autografts for Coverage of Large Burn Wounds in Adult and Pediatric Patients, 1989-2015.

This report summarizes the characteristics of 954 burned patients treated with cultured epidermal autografts (CEA), the largest number of patients to date. Data collected include patient demographics, survival, and final graft take. Source data were provided by the treating physician or attending burn team. Safety data were provided by the treating physician, attending burn team, and the pharmacovigilance database. In this dataset collected between 1989 and 2015, 954 patients were treated with cultured epidermal autographs for burns. Three hundred twenty-five (34%) were pediatric patients and 628 (66%) were adult (≥22 years of age); age unknown for one patient. The mean percentage total BSA (TBSA) burned was 67% (±17), median graft take at discharge was 75%, and overall survival at discharge was 84% (804/954). Survival rates were similar for pediatric and adult patients (89% vs 82%, respectively) and higher than the similar patient population reported in the National Burn Repository. Median graft take at discharge was also similar for pediatric and adult patients (80% vs 73%, respectively). The most frequently reported adverse reactions were infections in both pediatric and adult patients. There were no signals of increased risk of adverse reactions in pediatric compared with adult patients. When used as an adjunct to conventional split-thickness skin grafting for treatment of large burns in pediatric and adult patients, the analysis in this report shows an increased survival rate for patients treated with CEA compared with that reported for patients in the National Burn Repository with comparable burns.

517 Successful Posterior Cultured Epidermal Autograft Placement to a Major Burn Victim: A University Burn Center Experience and Review of the Literature

Large total body-surface area (TBSA) full thickness burns carry significant mortality and morbidity. Patients affected with >50% TBSA involvement battle potential complications for months. Those patients that survive and recover from the aggressive fluid resuscitation in the first 48 hours are then challenged by donor site limitation and graft availability to cover their massive full-thickness wounds. When autologous donor sites are limited, cultured epidermal autografts (CEA) can be advantageous and even life-saving. A 28 year old male presented 10 hours post-burn with approximately 45 percent full thickness burns to his back, buttock, perineum, pelvis, and circumferential bilateral lower extremities, in hypovolemic shock and with loss of sensation in his perineum and lower extremities. Forty-eight hours after admission, an infraclavicular full thickness specimen of skin was taken and sent for CEA processing. During his ICU stay he suffered numerous complications, ultimately recovering enough to receive multiple cadaveric grafts before finally receiving 6:1 meshed split-thickness skin graft to a wound area of approximately 4500 square centimeters to his back and bilateral posterior thighs. CEA was applied over this widely meshed autograft. Eight days after grafting, the CEA had 90% take. He was discharged to an inpatient rehabilitation facility two months after admission and is now home functioning with the assistance of family. CEA technology and understanding has made great strides in early and complete coverage of extensive burns that have limited available autograft. This is the first documented case of an epidermal autograft having a greater than 90% take on large area posterior full-thickness burns. Proper wound preparation and CEA grafting technique as well as aggressive off-loading and intense ICU nursing can be attributed to this success. CEA provides a means to expeditious wound closure in large burns with limited donor site availability and can successfully be used to cover both anterior and posterior surface areas.

Skin-Derived Stem Cells for Wound Treatment Using Cultured Epidermal Autografts: Clinical Applications and Challenges.

The human skin fulfills important barrier, sensory, and immune functions—all of which contribute significantly to health and organism integrity. Widespread skin damage requires immediate treatment and coverage because massive skin loss fosters the invasion of pathogens, causes critical fluid loss, and may ultimately lead to death. Since the skin is a highly immunocompetent organ, autologous transplants are the only viable approach to permanently close a widespread skin wound. Despite the development of tissue-saving autologous transplantation techniques such as mesh and Meek grafts, treatment options for extensive skin damage remain severely limited. Yet, the skin is also a rich source of stem and progenitor cells. These cells promote wound healing under physiological conditions and are potential sources for tissue engineering approaches aiming to augment transplantable tissue by generating cultured epidermal autografts (CEAs). Here, we review autologous tissue engineering strategies as well as transplantation products based on skin-derived stem cells. We further provide an overview of clinical trial activities in the field and discuss relevant translational and clinical challenges associated with the use of these products.

First experience using cultured epidermal autografts in Taiwan for burn victims of the Formosa Fun Coast Water Park explosion, as part of Japanese medical assistance

On June 27, 2015, a flammable starch-based powder exploded at Formosa Fun Coast in Taipei, Taiwan, injuring 499 people, and more than 200 people were in critical condition with severe burns. Although a cultured epidermal autograft (CEA) was not approved or used in clinical practice, the Taiwan Food and Drug Administration requested a Japanese CEA manufacturer to donate CEA for the burn victims as part of international medical assistance. The authors cooperated in this project and participated in the patient selection, wound bed management for CEA, and technical assistance for CEA use. Here, we provide an overview of the project. Nine patients were enrolled, and two patients were excluded from the skin biopsy; seven skin biopsies were collected approximately 1 month after the disaster. The average TBSA% burned was 81.0%, and the mean age was 20.1 years. CEA was grafted in five patients; wound closure had been obtained in one patient, and one patient was severely ill at the time of grafting. The CEA was combined with a wide split auto mesh graft or patch graft. The mean re-epithelization rate at 4 weeks after the grafting was 84.2% by patient, and all of the patients survived. Although this project had many obstacles to overcome, CEA grafting was successful and contributed to wound closure and survival.

Isolation and Cultivation of Adult Human Keratinocyte Stem Cells for Regeneration of Epidermal Sheets

Background: Keratinocyte stem cell is one of the adult stem cells that inhabits the skin and contributes to skin function and renewal. Adult stem cells are best defined by their capacity to self-renew, and to maintain tissue function for a long period of time. These findings indicate the importance of these cells for clinical applications including regenerative medicine, tissue engineering and gene therapy. In full-thickness damage or injury including burns, the cultured epidermal autografts (CEAs) may be placed directly onto muscle or fascia. Methods: A small split thickness skin biopsy (1 12أ—'> 2 cm) was obtained aseptically to isolate stem cells. The biopsy was cut into thin pieces and treated with trypsin at 4° C overnight (cold trypsin method) to obtain a single-cell suspension. The cells were seeded at a density of 3×104 cells/cm2 onto a preformed mitomycine-C treated 3T3 cell as feeder layer in DMEM medium supplemented with 10% fetal bovine serum (FBS) and other special supplements. Clonogenic keratinocytes divided and colonies quickly expanded and pushed away the 3T3 feeder layer cells, which then detached from the culture vessel and eliminated with medium changes. Primary cultures were usually subcultured when the cells were in exponential growth phase .Colonies of keratinocytes were expanded and after 7-10 days fused and formed a coherent stratified epithelium. Confluent cultured epithelia were detached enzymatically as coherent sheets from the surface of the culture flasks and transferred onto petrolatum- impregnated gauze.Histological studies of cultured epithelium were also carried out. Results: In our experience from 1 cm2 of skin sample, 2,5- 4×106 cells were obtained. It resulted in keratinocytes suspensions which consisted at least 90% single cells. Cultured keratinocytes proliferated and after 8-10 days became confluent. The area of cultured epithelium detached from T-25 and T-75 culture flasks was approximately 12-15 cm2 and 35-40 cm2 respectively. Histological studies showed that 10-day old cultured epithelium had 3-4 cell layers consisting of small basal cells and big scquamous cells with large nucleus. Also in the basal layer few melanocytes with melanin pigments in the cells cytoplasm were found.The 20-day old cultured epithelium had 8-10 layers consisting of small and round basal cells, scquamous cells and 2-3 layers of keratinized cells. Conclusion: Culture of keratinocyte stem cells could result in multilayer epithelium that creates a good cosmetic appearance upon transplantation. This could re-generate an epidermis that is resistant to trauma and infections. It can be considered as an appropriate substitution in skin loss conditions. Keywords: Epidermal Sheets, Skin Adult Stem cells, Keratinocyte.

A retrospective study of the use of cultured epidermal autografts (CEA) in severe burn patients

A retrospective study of the use of cultured epidermal autografts (CEA) in severe burn patients

The Combination of Cultured Epidermal Autograft (CEA) and Split Thickness Skin Graft Technique (Meek) in Therapy for Severe Burns

In our treatment of severely burned patients cultured epidermal autografts (CEA) are indicated when the burned surface is more than 65% TBSA (total burn surface area). Therefore laboratory cultured sheets of keratinocytes are used. Since the cultured skin is extremely sensitive to pressure and friction, the available autologous skin is transplanted on the bearing surfaces of the patient. Due to the limited amount of available autologous skin a high expansion ratio is necessary. This can be reached with the help of the Meek technique. Therefore the early wound closure of the severely burned patient is favoured by a combination of CEA transplantation and Meek autografting.

Quantitative assessment of cell viability and apoptosis in cultured epidermal autografts: application to burn therapy.

Cultured epidermal autografts (CEA) have been used in the treatment of burns for almost two decades but the clinical results are still inconsistent. In a group of 37 patients with extensive burn wounds admitted to the University Hospital of Lausanne, CEA take ranged between 10 and 100% with a mean of 65%. To investigate CEA efficacy in burns, twelve CEA preparations were tested for their biological properties with particular emphasis on the balance between cell viability and apoptosis. Apoptosis was evaluated by in situ end-labeling (TUNEL), detection of DNA fragments in CEA extracts and analysis of caspase-3 activity. All CEA samples displayed a high cell viability (> 90%) and a low apoptosis rate (< 6%). However, several biological parameters including the activity of transglutaminase showed wide interindividual variability suggesting that CEA therapeutic efficacy could be partly determined by intrinsic biological factors.

Clinical evaluation of skin substitutes

Having established the design principles for cultured skin substitutes and a directory defining many of those currently available, the next stage is to review some of the animal and clinical studies utilising these materials. The aim is not to provide a comprehensive list of all in vivo studies published, but rather, at this early stage, to tease out certain characteristics of each category of graft materials, on a range of cutaneous defects. Aside from the clinical data that has accumulated through the years on the use of cultured epidermal autografts (CEA), there are few large-scale multi-centre prospective trials for the newer tissue engineered skin substitutes. Nevertheless, even at this early stage there are preliminary indications of where the materials may show promise clinically, and where further research and development can be guided by both positive and negative in vivo performance.

Cost-efficacy of cultured epidermal autografts in massive pediatric burns.

To assess the efficacy of cultured epidermal autografts (CEA) for closure of burn wounds in pediatric burn patients with full-thickness burns of more than 90% total body surface area. Paucity of donor sites in massive burns makes the use of expanded skin of paramount importance. CEA techniques have been used in burned patients with differing and controversial results. The true impact and the efficacy of such techniques in massive burns remain uncertain. Patients with full-thickness burns of more than 90% body surface area treated between May 1988 and May 1998 were studied. Patients grafted with CEA were compared with patients grafted with conventional meshed autografts. Rates of death and complications, length of hospital stay (LOS), hospital cost, acute readmissions for reconstruction, and quality of scars were studied as outcome measures. Patients treated with CEA had a better quality of burn scars but incurred a longer LOS and higher hospital costs. Both groups had comparable readmissions for open wounds, but patients treated with CEA required more reconstructive procedures during the first 2 years after the injury. The incidence of sepsis and pneumonia in both groups was comparable. Conventional meshed autografts are superior to CEA for containing hospital cost, diminishing LOS, and decreasing the number of readmissions for reconstruction of contractures. However, the use of CEA provides better scar quality such that perhaps future research should focus on bioengineered dermal templates to promote take and diminish long-term fragility.

Naturally occurring growth factors in porcine wounds treated with autologous keratinocytes in a liquid environment

A step toward an improved understanding of the complex mechanisms of growth factor interactions may lie in the detection of endogenous growth factors during normal wound healing. The findings of this study on standardized full thickness wounds in swine, provide direct evidence that growth factors were present in the wound fluid in the picogram range (highest concentrations ranging from 1273 pg/ml for transforming growth factor-beta (TGFβ) to 85.6 pg/ml for platelet-derived growth factor-AB (PDGF-AB ) during healing. The presence of transplanted autologous keratinocyte suspensions and cultured epithelial sheet graft had no significant effect upon the observed growth factor levels, although transplanted keratinocyte cell suspensions (KCS) and cultured epidermal autografts (CEA) did accelerate healing in comparison to control wounds in our model (KCS treated wounds healed in 13.2±0.9 days, CEA in 13.7 days±0.8 and control wounds in 14.7 days±0.3). The variable occurrence of growth factors during normal wound healing may suggest possible mechanisms of growth factor interaction which could have an impact on the future design of their therapeutic use.