Deep Dermal Wounds Research Articles

Suprathel® causes less bleeding and scarring than Mepilex® Transfer in the treatment of donor sites of split-thickness skin grafts

Split-thickness skin grafts are routine in the treatment of deep dermal burns and various other wounds. Healing of the donor site of the graft has an impact on the total recovery of the patient. We conducted a prospective clinical study at Tampere University Hospital to compare the effect of two adhesive wound dressings, Suprathel® and Mepilex® Transfer. The donor sites of 22 split-thickness skin grafts were studied, each of which was covered with Suprathel® and Mepilex® Transfer dressings side by side. Significantly less pain and bleeding was associated with Suprathel® treatment compared with Mepilex® Transfer (p < 0.05). Suprathel® produced a better scar at the three months' follow-up as measured using the Vancouver Scar Scale (VSS). The results show that Suprathel® is a better dressing for the donor sites than Mepilex® Transfer.

New biological temporary skin cover Xe-Derma ® in the treatment of superficial scald burns in children

Background Xe-Derma ® is a new dry sterile biological cover derived from acellular pig dermis. Hydrated Xe-Derma ® displays bio-mechanical features similar to the normal skin. The aim of the present study was to compare the efficacy of Xe-Derma ® with hydrocolloid dressing Askina THINSite ® for treatment of superficial burns in children in a prospective study. Materials and methods In a prospective study, 86 patients (5 months to 7 years of age) with superficial scald burns on a surface area of 1–35% BSA were enrolled. In the course of the study, 43 patients were treated with Xe-Derma ® and 43 patients with Askina THINSite ®. We collected data including the percentage of BSA covered with biological or synthetic material, epithelization time, the number of complete conversions (deepening of 100% of covered area into deep dermal wound) under each cover, the number and extent of partial conversions (deepening of less then 100% of covered area into deep dermal wound), infectious complications, the number of reapplications of the temporary cover and the extent in square centimetres of dressing material needed for successful healing of 1% BSA. Results No significant difference in the epithelization time, percentage of conversion from superficial to deep dermal burns and percentage of infectious complication was detected between the two groups. However, patients in the Xe-Derma ® group were burned on a more extensive burn surface area ( p ≤ 0.028). Xe-Derma ® showed adherence to the wound and therefore there has been no need to be changed The number of reapplications and therefore also the number of square centimetres needed for successful healing of 1% BSA were statistically higher in the Askina THINSite ® group ( p < 0.01) due to increased secretion and accumulation of fluid underneath this hydrocoloid cover. The minimal frequency of changes of this biological cover material brings a significant benefit to pediatric patients. Conclusion Acellular pig dermis Xe-Derma ® represents a reliable biological cover material. It is an advantageous alternative to synthetic temporary skin covers in the treatment of superficial scald burns in children.

Biologic and synthetic skin substitutes: An overview

ABSTRACTThe current trend of burn wound care has shifted to more holistic approach of improvement in the long-term form and function of the healed burn wounds and quality of life. This has demanded the emergence of various skin substitutes in the management of acute burn injury as well as post burn reconstructions. Skin substitutes have important roles in the treatment of deep dermal and full thickness wounds of various aetiologies. At present, there is no ideal substitute in the market. Skin substitutes can be divided into two main classes, namely, biological and synthetic substitutes. The biological skin substitutes have a more intact extracellular matrix structure, while the synthetic skin substitutes can be synthesised on demand and can be modulated for specific purposes. Each class has its advantages and disadvantages. The biological skin substitutes may allow the construction of a more natural new dermis and allow excellent re-epithelialisation characteristics due to the presence of a basement membrane. Synthetic skin substitutes demonstrate the advantages of increase control over scaffold composition. The ultimate goal is to achieve an ideal skin substitute that provides an effective and scar-free wound healing.

Biologic and synthetic skin substitutes: An overview

The current trend of burn wound care has shifted to more holistic approach of improvement in the long-term form and function of the healed burn wounds and quality of life. This has demanded the emergence of various skin substitutes in the management of acute burn injury as well as post burn reconstructions. Skin substitutes have important roles in the treatment of deep dermal and full thickness wounds of various aetiologies. At present, there is no ideal substitute in the market. Skin substitutes can be divided into two main classes, namely, biological and synthetic substitutes. The biological skin substitutes have a more intact extracellular matrix structure, while the synthetic skin substitutes can be synthesised on demand and can be modulated for specific purposes. Each class has its advantages and disadvantages. The biological skin substitutes may allow the construction of a more natural new dermis and allow excellent re-epithelialisation characteristics due to the presence of a basement membrane. Synthetic skin substitutes demonstrate the advantages of increase control over scaffold composition. The ultimate goal is to achieve an ideal skin substitute that provides an effective and scar-free wound healing.

Analytical solution of the Pennes equation for burn-depth determination from infrared thermographs

A serious problem in emergency medicine is the correct evaluation of skin burn depth to make the appropriate choice of treatment. In clinical practice, there is no difficulty in classifying first- and third-degree burns correctly. However, differentiation between the IIa (superficial dermal) and IIb (deep dermal) wounds is problematic even for experienced practitioners. In this work, the use of surface skin temperature for the determination of the depth of second-degree burns is explored. An analytical solution of the 3D Pennes steady-state equation is obtained assuming that the ratio between burn depth and the burn size is small. The inverse problem is posed in a search space consisting of geometrical parameters associated with the burned region. This space is searched to minimize the error between the analytical and experimental skin surface temperatures. The technique is greatly improved by using local one-dimensionality to provide the shape of the burned region. The feasibility of using this technique and thermography to determine skin burn depth is discussed.

A randomised controlled trial of amniotic membrane in the treatment of a standardised burn injury in the merino lamb

Burn injury is associated with disabling scar formation which impacts on many aspects of the patient's life. Previously we have shown that the fetus heals a deep dermal burn in a scarless fashion. Amniotic membrane (AM) is the outermost fetal tisue and has beeen used as a dressing in thermal injuries, though there is little data to support this use. To assess the efficacy of AM in scar minimisation after deep dermal burn wound, we conducted a randomised controlled study in the 1-month lamb. Lambs were delivered by caesarian section and the amniotic membranes stored after which lambs were returned to their mothers post-operatively. At 1 month, a standardised deep dermal burn was created under general anaesthesia on both flanks of the lamb. One flank was covered with unmatched AM, the other with paraffin gauze. Animals were sequentially euthanased from Day 3–60 after injury and tissue analysed for histopathology and immunohistochemically for α-smooth muscle actin (αSMA) content. AM resulted in reduced scar tissue as assessed histopathologically and reduced αSMA content. This study provides the first laboratory evidence that AM may reduce scar formation after burn injury.

Accuracy of early burn depth assessment by laser Doppler imaging on different days post burn

Background Accurate diagnosis of burn depth is essential in selecting the most appropriate treatment. Early assessment of burn depth by clinical means only has been shown to be inaccurate, resulting in unnecessary operations or delay of grafting procedures. Laser Doppler imaging (LDI) was reported as an objective technique to determine the depth of a burn wound, but the accuracy on very early days post burn has never been investigated yet. Methods In 40 patients with intermediate depth burns, we prospectively evaluated and compared the accuracy of the LDI measurements with the clinical assessments on days 0, 1, 3, 5, 8. Clinical evaluation of the depth of the burn was performed by two observers blinded to the LDI images. Accuracies were assessed by comparison with outcome: healing times longer than 21 days were considered to be equivalent to a biopsy finding of a deep dermal wound. Obviously superficial and full thickness wounds were excluded. LDI flux level was used for LDI prediction of outcome: less than 220 PU to predict non-healing at day 21. Results The accuracies of burn depth assessments on the day of burn and post burn days 0, 1, 3, 5 and 8 using LDI were 54%, 79.5%, 95%, 97% and 100% compared with clinical assessment accuracies of 40.6%, 61.5%, 52.5%, 71.4% and 100%, respectively. LDI accuracy was significantly higher than clinical accuracy on day 3 ( p < 0.001) and day 5 ( p = 0.005). Burn depth conversion was also considered. This is the first study to quantify the advantage of LDI scanning over clinical assessments during these important early after burn days.

Itching following burns: epidemiology and predictors

Itching (pruritus) following burns is a well-known clinical problem. However, there are no long-term prospective studies that document the course and the extent of the problem. Studies on risk factors are anecdotal. To study self-reported itching in a multicentre cohort among adults with burns at 3, 12 and 24 months postburn. Further, to examine psychological and injury characteristics in relation to itching at these three points in time. Itching was assessed as part of a self-report scar complaint list in a prospective longitudinal cohort study. Injury characteristics, demographics and self-reported post-traumatic stress symptoms were examined as possible risk factors in three linear regression models. A total of 510 persons participated. The reported prevalence rates of mild to severe itching were as high as 87%, 70% and 67% at the three respective points in time. Significant predictors of itching at all three points in time were deep dermal injury and early post-traumatic stress symptoms. Along with these, total burned surface area and female gender were predictors at 3 months postburn. Itching remains a significant problem over a 2-year period. Individuals having undergone surgical procedures and experiencing early post-traumatic distress are more likely to suffer from long-term and persistent itching. Implications regarding practice and research are discussed.

Expression profile of proteins involved in scar formation in the healing process of full‐thickness excisional wounds in the porcine model

Scar formation in deep dermal wounds is associated with excessive collagen deposition and contraction. Increased collagen synthesis and decreased collagen degradation are the mechanisms through which this form of fibrosis can occur. Another factor might be a different kind of collagen cross-linking seen in fibrotic skin diseases. This type of cross-linking is dependent on the enzyme lysyl hydroxylase-2b. In this study, we examined the expression profile of the potential key players in scar formation in time in healing of acute wounds. Collagen types I and III, lysyl hydroxylase-2b, alpha-smooth muscle actin, transforming growth factor betas, and the matrix metalloproteinases and their inhibitor mRNA levels were determined. All genes examined show distinct expression patterns over time. The expression of lysyl hydroxylase-2b peaks at day 7, and precedes collagen types I and III expression. Eight weeks after wounding, the scars showed an increased level of lysyl hydroxylase-2b-mediated collagen cross-linking. This study shows that the fibrosis-specific type of cross-linking of collagen seen in human hypertrophic scarring also plays a role in this animal model of wound healing. Moreover, the expression of the putative gene responsible for this type of cross-linking, the lysyl hydroxylase-2b, is elevated during wound healing.

Cooling of the burn wound: The ideal temperature of the coolant

Background The beneficial effects of cooling a fresh burn wound were well demonstrated. However, there are still conflicting reports as to the optimum temperature of coolant, duration of application and effects in limiting tissue damage. A study was undertaken to investigate this, the importance of the temperature of, and the time period of application of the coolant. Materials and methods Four identical deep dermal wounds were created on the back of 10 anaesthetised pigs. Each animal served as an independent experimental model. The effectiveness of cooling was monitored by measuring intradermal temperatures. The animals were divided into two groups; using ice water and tap water as the coolants. In each pig one wound was not cooled (wound 1). Three were cooled; one immediately for 30 min in group 1 and for 4 h in group 2 (wound 2). The other two wounds were cooled after 30 min for 30 min and 3 h (wounds 3 and 4, respectively). Results It was found that the temperature of the coolant was crucial. When ice water of 1–8 °C (group 1) was used more necrosis than in the wounds that were not cooled was seen. When tap water was used at 12–18 °C (group 2) it was demonstrated clinically and histologically that the cooled wounds had less necrosis than the uncooled wounds and thus healed faster. In group 2 the beneficial effects of cooling were still present when delayed for half an hour. Conclusion First aid cooling of a burn wound with tap water is an effective method of minimising the damage sustained during a burn, and is universally and immediately available. Ice water cooling is associated with an increase in tissue damage.

Bone marrow‐derived myofibroblasts recruited to the upper dermis appear beneath regenerating epidermis after deep dermal burn injury

Fibroblasts and myofibroblasts migrating to sites of tissue repair after injury may not only be locally recruited but could also be recruited from the bone marrow. However, the characteristics and functional roles, if any, of these cells in wound healing are poorly understood. Here, we show unequivocally that bone marrow-derived fibroblasts do contribute to deep dermal burn wound healing. Bone-marrow stromal cells were collected from femurs of male Lewis rats, cultured for a week, and then the adherent cells were labeled with the fluorescent marker PKH-26. These cells stained positive for alpha-smooth muscle actin and prolyl 4-hydroxylase, but did not express RM-4 (a macrophage marker), CD34, or cytokeratin, characteristic of myofibroblastic differentiation. When injected intravenously into Lewis rats, they homed to the bone marrow. Five days after transplantation, a deep dermal burn was made on the back of the rat, and biopsies were taken 7, 10, and 14 days later. PKH-positive cells were not found at day 7, but by day 10, they were easily detected mainly in the upper dermis close beneath the regenerating epidermis. These PKH-positive cells still stained for alpha-SMA and prolyl 4-hydroxylase, but not RM4. Thus, it is suggested that myofibroblasts originating in the bone marrow contribute not only to promotion of granulation but also enhancement of dermal-epidermal interaction after thermal injury.

Boosted re-epithelialization with basic fibroblast growth factor in deep dermal burn wound

Boosted re-epithelialization with basic fibroblast growth factor in deep dermal burn wound

Skin wound healing in the first generation (F1) offspring of Yorkshire and red Duroc pigs: Evidence for genetic inheritance of wound phenotype

Fibroproliferative scars in humans often demonstrate familial inheritance patterns, and genetics may contribute to healing and scarring. Genetic factors may also influence the scarring phenotype in a porcine model. Healing of full thickness excisional skin wounds in Yorkshire pigs closely resembles normal healing in humans, while identical wounds in red Duroc pigs form hypercontracted, hyperpigmented scars. The present study has evaluated the healing process in the first generation cross (F1) of red Duroc and Yorkshire pigs. Gross and histologic analysis revealed that the F1 animals exhibit an intermediate healing phenotype, with some features of each parent breed. F1 full thickness wounds were significantly hypercontracted and fibrotic, but apigmented. Analysis of mRNA expression patterns for a panel of relevant molecules ( N = 32) in the F1 animals revealed some similarities to each parent breed, as well as unique patterns for other molecules. Furthermore, a depth dependency to the healing response was observed at the gross, histologic, and molecular levels, with deep dermal wounds healing similar to Yorkshire wounds. These findings suggest that the genetic contribution to scar phenotype in this animal model is complex. However, the results indicate that further understanding in this model may provide insights into risk factors for hypertrophic scarring in human burn patients.

Changes in VEGF and Nitric Oxide After Deep Dermal Injury in the Female, Red Duroc Pig—Further Similarities Between Female, Duroc Scar and Human Hypertrophic Scar

Changes in VEGF and Nitric Oxide After Deep Dermal Injury in the Female, Red Duroc Pig—Further Similarities Between Female, Duroc Scar and Human Hypertrophic Scar

A hypothesis of the healing of deep dermal burns and the significance for treatment.

Deep dermal burns heal by a combination of new connective tissue formation (granulation) and epithelialization. In deep dermal wounds, which are unhealed after 14 days of conservative treatment, epithelialization can be enhanced by abrasion either alone or combined with provision of a skin graft. Some 42 burn wounds in 25 patients treated by this method have healed quickly and with good results. This method represents a move away from the current trend of early tangential excision and grafting of burn wounds and raises the possibility of developing a regime with the advantages but not the disadvantages of early tangential excision and grafting.

Cytokine and Growth Factor mRNA Expression Patterns Associated with the Hypercontracted, Hyperpigmented Healing Phenotype of Red Duroc Pigs: A Model of Abnormal Human Scar Development?

Skin wounds in red Duroc pigs heal with the formation of hypercontractile, hyperpigmented scars, similar in some respects to human hypertrophic scars. The goal of this study was to characterize the mRNA expression patterns for a subset of relevant cytokines, growth factors, receptors, and transcription factors involved in the red Duroc scarring phenotype. Full-thickness and deep dermal wounds were created on the backs of juvenile female red Duroc pigs. Samples were taken every two weeks postwounding and total RNA and DNA were extracted and quantified. RT-PCR was performed using porcine gene-specific primers for 15 relevant molecules. The majority of molecules examined exhibited a biphasic pattern of expression, with peaks of expression at days 14 and 56 postinjury. The molecular expression pattern observed correlates well with the gross healing phenotype and matrix molecule expression patterns previously reported in red Duroc pigs. These findings enhance our understanding of the processes associated with fibroproliferative scar-formation.

Cytokine and Growth Factor mRNA Expression Patterns Associated with the Hypercontracted, Hyperpigmented Healing Phenotype of Red Duroc Pigs: A Model of Abnormal Human Scar Development?

Background:Skin wounds in red Duroc pigs heal with the formation of hypercontractile, hyperpigmented scars, similar in some respects to human hypertrophic scars. ObjectiveThe goal of this study was to characterize the mRNA expression patterns for a subset of relevant cytokines, growth factors, receptors, and transcription factors involved in the red Duroc scarring phenotype.Methods:Full-thickness and deep dermal wounds were created on the backs of juvenile female red Duroc pigs. Samples were taken every two weeks postwounding and total RNA and DNA were extracted and quantified. RT-PCR was performed using porcine gene-specific primers for 15 relevant molecules.Results:The majority of molecules examined exhibited a biphasic pattern of expression, with peaks of expression at days 14 and 56 postinjury.Conclusions:The molecular expression pattern observed correlates well with the gross healing phenotype and matrix molecule expression patterns previously reported in red Duroc pigs. These findings enhance our understanding of the processes associated with fibroproliferative scar-formation.

Produit de thérapie cellulaire Dermagen ® pour le traitement de plaies difficiles

Epidermal sheets were developed for the treatment of hard-to-heal skin wounds. Products currently marketed in France, e.g. Epibase, are very efficient but not totally satisfactory in cases of very deep dermal injury which often occurs in burn victims. A function dermis or "dermis equivalent" association a three-dimensional matrix (dermal substrate) and allogenic dermal fibroblasts able to secrete numerous cytokines, growth factors, and protease inhibitors, was developed in our biotechnology laboratory using good manufacturing standards (ISO9000). This cell therapy product which is histologically and physiologically close to normal dermis is obtained after culturing fibroblasts obtained from a microbiologically and virologically validated cell bank for 21 days in a patented collagenous sponge. Our laboratories successfully developed a freezing process allowing preservation of the product at -80 C. This allows us to perform high-performance quality control of the batches. The product is easy to use and instructions can be described in a few lines. When clinicians order one or more Dermagen sheets, depending on the wound area to treat, Dermagen is thawed and culturel at 37 C for 48 to 72 hours. Metabolic activity is recovered and the product is then packaged in a specific blister with a semi-solid medium to ensure good viability during transportation. In some indications, Dermagen acts like a true transplant and in others like a biological dressing secreting numerous mediators such as growth factors or matrix proteins.

Deep dermal burn injury results in scarless wound healing in the ovine fetus

Early to mid-term fetuses heal cutaneous incisional wounds without scars; however, fetal response to burn injury has not been ascertained. We present a fetal model of thermal injury and subsequent analysis of fetal and lamb response to burn injury. A reproducible deep dermal burn injury was created in the fetus by application of water at 66 degrees C for 7 seconds, and at 82 degrees C for 10 seconds to the lamb. Macroscopically, the area of fetal scald was undetectable from day 7 post injury, while all lamb scalds were readily identified and eventually healed with scarring. Using a five-point histopathology scoring system for alteration in tissue morphology, differences were detected between control and scalded skin at all stages in lamb postburn, but no difference was detected in the fetal model after day 7. There were also large differences in content of alpha-smooth muscle actin and transforming growth factor-beta1 between control and scalded lamb and these differences were statistically significant at day 14 (P < 0.01). This novel model of fetal and lamb response to deep dermal injury indicates that the fetus heals a deep burn injury in a scarless fashion. Further elucidation of this specific fetal process of burn injury repair may lead to improved outcome for patients with burn injury.

Changes in VEGF and nitric oxide after deep dermal injury in the female, red Duroc pig—further similarities between female, Duroc scar and human hypertrophic scar

Despite decades of research, our understanding of human hypertrophic scar is limited. A reliable animal model could significantly increase our understanding. We previously confirmed similarities between scarring in the female, red, Duroc pig and human hypertrophic scarring. The purpose of this study was to: (1) measure vascular endothelial growth factor (VEGF) and nitric oxide (NO) levels in wounds on the female Duroc; and (2) to compare the NO levels to those reported for human hypertrophic scar. Shallow and deep wounds were created on four female Durocs. VEGF levels were measured using ELISA and NO levels with the Griess reagent. VEGF and NO levels were increased in deep wounds at 10 days when compared to shallow wounds ( p < 0.05). At 15 weeks, VEGF and NO levels had returned to the level of shallow wounds. At 21 weeks, VEGF and NO levels had declined below baseline levels in deep wounds and the NO levels were significantly lower ( p < 0.01). We found that VEGF and NO exhibit two distinctly different temporal patterns in shallow and deep wounds on the female Durocs. Furthermore, NO is decreased in female, Duroc scar as it is in human, hypertrophic scar further validating the usefulness of the model.