Direct comparison of reproducibility and reliability in quantitative assessments of burn scar properties.

INTRODUCTION: Determining the efficacy of anti-scar technologies can be difficult as qualitative, subjective assessments are often utilized instead of systematic, objective measures. Perceptions regarding the reliability of instruments for quantitative measurements along with their high cost and increased data collection time may discourage their use, leading to use of scar scales which are relatively quick and low-cost. To directly evaluate the reliability of instruments for quantitative measurements of scar properties, instruments and two qualitative scales were compared by assessing a variety of cutaneous scars. METHODS: Scar height and surface texture were evaluated using a 3D scanner and a mold/cast technique. Scar color was evaluated by using a spectroscopy-based tool, the Mexameter®, and digital photography with image analysis. Scar biomechanics were evaluated using the BTC-2000™, Dermal Torque Meter (DTM®), and ballistometer®. The Vancouver Scar Scale (VSS) and Patient and Observer Scar Assessment Scale (POSAS) were used to qualitatively evaluate the same scar properties. Intraclass correlation coefficients (ICC) were used to determine inter- and intra-user reliability (poor, moderate, good, excellent) with all instruments and the kappa reliability statistic was used to asses inter-user reliability (poor, fair, moderate, good, very good) for VSS and POSAS. Time for measurement collection and after collection analysis was also recorded. RESULTS: The Mexameter® was the most reliable method for evaluating erythema and pigmentation compared to digital photography and image processing, POSAS and VSS. Digital photography and analysis was more reliable than POSAS and VSS. Assessment of scar height was significantly more reliable when using a 3D scanner versus VSS and POSAS. The 3D scanner and mold-cast techniques also offered an additional benefit of providing an absolute value of scar height relative to the surrounding tissue. Intra-user reliability for all mechanical tests was moderate to good. Inter-user reliability was greater when using the BTC-2000™ and ballistometer® versus the DTM®. All quantitative measurements took less than 90 s for collection, with the exception of the mold/cast technique. CONCLUSION: Non-invasive instruments allow scar properties to be quantitatively assessed with high sensitivity and as a function of time and/or treatment without the need for biopsy collection. Overall, the reliability of scar assessments was significantly improved when quantitative instruments were utilized versus scar scales. Quantitative assessment of color and biomechanics were swift, requiring less than 90 s per measurement while assessments of texture and height required additional analysis time after collection. With proper training of clinical staff and well-defined protocols for measurement collection, reliable, quantitative assessments of scar properties can be collected with little disruption to the clinical workflow.

Safety, feasibility, and acceptability of patient-controlled anxiolysis with dexmedetomidine for burn-care dressing changes: an open-label, single-arm, pilot study.

Anxiety is common among patients with burn injury, occurring frequently surrounding wound care. Few pharmacologic interventions targeting anxiety in burn injury have been evaluated. This study aimed to evaluate patient-controlled anxiolysis using dexmedetomidine (PCA-DEX) in patients undergoing burn dressing changes. This was a prospective, open-label, single-arm pilot study to determine the feasibility, safety, and acceptability of PCA-DEX. PCA-DEX included a loading dose, continuous infusion, and patient-administered boluses during dressing changes for up to 5 days. Vital signs were monitored throughout PCA-DEX. Procedural pain and anxiety were evaluated before and after each dressing change. Nursing and patient satisfaction were evaluated after each dressing change. Twenty patients were included; 9 (45%) males and 11 females (55%) with a mean age of 45.1 ± 16.9 years and median total body surface area burn injury of 7 [IQR 4-9.5]%. Median heart rate and systolic blood pressure prior to PCA-DEX on day 1 were 82 [75-97] bpm and 147 [128-170] mmHg. Overall PCA-DEX was tolerated well with a median heart rate of 72 [66-82] bpm and systolic blood pressure 115 [99-141] mmHg after PCA-DEX. One patient was withdrawn due to severe bradycardia (heart rate < 45 bpm) not attributed to PCA-DEX; 4 patients experienced mild hypotension (systolic blood pressure 85-89/diastolic blood pressure 45-49 mmHg), all of which resolved without intervention. The majority of both nurses and patients were either satisfied or highly satisfied with PCA-DEX overall (78.1% for nursing, 86.5% for patients). PCA-DEX is a novel, safe and feasible method of anxiolysis during burn dressing changes with high patient and nurse satisfaction rates. A randomized, controlled trial is warranted to confirm the efficacy of PCA-DEX.

Cultured Epithelial Autograft Combined with Micropatterned Dermal Template Forms Rete Ridges In Vivo.

For patients with large, full-thickness burn wounds, sufficient donor sites for autografting are not available, and thus, alternate strategies must be used to close these wounds. Cultured epithelial autografts (CEAs) can aid in closing these wounds but are often associated with slow deposition of basement membrane proteins, leading to blistering and graft loss. Rete ridges and dermal papillae present at the dermal-epidermal junction (DEJ) play a key role in epidermal adhesion and skin homeostasis. Promoting the development of an interdigitated DEJ may enhance basement membrane protein deposition and provide enhanced physical interlock of the epidermis and dermis. To develop a dermal template with stable dermal papillae, an electrospun collagen scaffold was seeded with human dermal fibroblasts. Ridged topographies were patterned into the cell-seeded dermal template using laser ablation, creating wide and shallow (ActiveFX) or narrow and deep (DeepFX) wells. Micropatterned or flat (control) dermal templates were combined with CEAs immediately before grafting to full-thickness excisional wounds on immunodeficient mice. CEAs grafted in conjunction with ridged templates showed rete ridge formation at 2 weeks after grafting and led to increased epidermal thickness, proliferation, and stemness compared to templates with a flat DEJ. As this technology is further developed, the dermal papilla-containing dermal templates may be utilized in combination with CEAs to improve adhesion and clinical function. Impact statement Cultured epithelial autografts (CEAs) serve as an adjunct to conventional split-thickness autograft in patients with very large burns, but they are susceptible to blistering that can reduce engraftment. Blistering results, in part, from relatively slow basement membrane deposition after grafting. This study demonstrates that basement membrane deposition and rete ridge formation are enhanced by combination of CEAs with a micropatterned, cell-seeded dermal template. These findings may lead to improved treatment and increased survival in patients with very large burns.

Guidelines for Thrombolytic Therapy for Frostbite.

The data are insufficient to support standardized treatment of all patients with frostbite with thrombolytic therapy. The following guidelines, however, should be applied to all patients with cyanosis persisting proximal to the distal phalanx (Grade 3 or 4 frostbite injury) and demonstrated loss of perfusion at or proximal to the middle phalanx immediately after rewarming.

The impact of serum zinc normalization on clinical outcomes in severe burn patients.

INTRODUCTION: Patients with thermal burns become zinc deficient due to exudative losses, increased urinary excretion, and reduction of carrier proteins which results in impaired immunity, wound healing and glucose control. Previous trials have demonstrated improved wound healing utilizing fixed zinc supplementation, but none have assessed the potential benefits associated with normalizing serum zinc concentrations. The objective of this study was to compare the impact of zinc normalization on clinical outcomes in patients with severe thermal burns. METHODS: This retrospective, single-center study of patients with at least 10% total body surface area (TBSA) burn and three serum zinc concentrations compared the ratio of hospital length of stay (LOS) over TBSA burned (LOS/TBSA index) between those with normal (≥60 mcg/mL) and non-normal (<60 mcg/mL) serum zinc concentrations; delineated by the third measurement. Secondary outcomes were time to 90% epithelialization, infection incidence, and percentage of blood glucose values greater than 180 mg/dL. Data are reported as median [25-75% interquartile range] for continuous variables and frequency (percent) for categorical variables. RESULTS: A total of 56 patients were included for evaluation (11 normal and 45 non-normal). Burn size was 20.5% TBSA [11-29] for those with normal zinc and 27.3% [22-36] for non-normal; number of grafts for each group was 1 [0-1] vs 2 [1-3] respectively. LOS/TBSA index did not differ significantly between groups (1.10 normal vs. 1.21 non-normal, unadjusted p = 0.69; p = 0.75 adjusting for number of grafts). Time to 90% epithelialization was reduced in the normal group (27.5 vs. 57 days, p = 0.02), but this did not remain statistically significant after adjustment for %TBSA and number of grafts (p = 0.18). The groups did not differ significantly in incidence of infection or hyperglycemia in either unadjusted or adjusted analyses. CONCLUSIONS: This was the first study, to our knowledge, to assess the clinical impact of normalizing serum zinc levels in patients with severe burns. Our results suggest the normalization of serum zinc levels through individualized zinc supplementation is not associated with improvement in clinical outcomes during hospitalization and therefore fixed-dose zinc supplementation without acquisition of serum zinc measurements should be considered.

Fractional CO2 laser ablation of porcine burn scars after grafting: Is deeper better?

INTRODUCTION: Fractional CO2 lasers have been used in clinical settings to improve scarring following burn injury. Though used with increasing frequency, the appropriate laser settings are not well defined and overall efficacy of this therapy has not been definitively established. As it has been proposed that for thick hypertrophic scars proportionally greater fluence and thus deeper ablation into the scar tissue would be most effective, the goal of this study was to examine the role of ablation depth on scar outcomes in a highly-controlled porcine model for burn scars-after grafting. METHODS: Properties of laser ablated wells were quantified on ex vivo pig skin as a function of laser energy (20, 70 or 150mJ). Full-thickness burn wounds were created on the dorsum of red Duroc pigs with the eschar excised and grafted with a split-thickness autograft meshed and expanded 1.5:1. After four weeks of healing, sites were treated with either 20, 70, or 150mJ pulse energy from a fractional CO2 laser at 5% density or left untreated as a control. Sites were treated every four weeks with three total sessions. Scar area, pigmentation, erythema, roughness, histology, and biomechanics were evaluated prior to each laser treatment at day 28, 56, and 83, as well as four weeks after the final laser treatment, day 112. Additional biopsies were collected at day 112 for gene expression analysis. RESULTS: The depth of the laser ablated wells increased with increasing pulse energy while the width of the wells was smaller in the 20mJ group and not significantly different in the 70 and 150mJ groups. Scar properties (area, color, biomechanics) were not significantly altered by laser therapy at any of the laser energies tested versus controls. Average scar roughness was improved by laser therapy in a dose dependent manner with scars treated with 150mJ of energy having the smoothest surface; however, these changes were not statistically significant. Assessment of matrix metalloproteinase 9 gene expression showed a slight upregulation in scars treated with 70 or 150mJ versus control scars and scars treated with 20mJ pulse energy. CONCLUSION: The current study demonstrated that the properties of the ablative well (depth and width) are not linearly correlated with laser pulse energy, with only a small increase in well depth at energies between 70 and 150mJ. Overall, the study suggests that there is little difference in outcomes as a function of laser energy. Fractional CO2 laser therapy did not result in any statistically significant benefit to scar properties assessed by quantitative, objective measures, thus highlighting the need for additional clinical investigation of laser therapy efficacy with non-treated controls and objective measures of outcome.

One center's experience developing a burn outpatient registry.

INTRODUCTION: Recent advances in burn care have resulted in the transition of care from inpatient to outpatient. There is a growing appreciation that with improved survival, meaningful markers of quality need to include recovery of form, function, and reconstruction. Capture of the data describing care delivered in the outpatient setting is being missed. METHODS: Development of our outpatient database included providers, registrar, program manager, and outpatient nursing staff. Data points were included if they described the population, and epidemiology of our patients, were useful for programmatic changes and improvements as well as anticipated research focus areas. RESULTS: The database platform chosen was Midas+™ because it was in use by hospital quality and integrated with the electronic medical record. Fields were customized based on changing program needs and are updated for new programs or outcomes measures. Reports can be easily built and both outpatients and inpatients are included. This allows for longitudinal tracking of burn patients. Ongoing additions to original data points include variables to track outcomes related to laser therapy for scar management, time to custom garment donning, and to track functional outcomes. Epidemiologic data collected is used to target high-risk populations for prevention and outreach efforts. Outcome data is used for evaluation of programs and care. CONCLUSIONS: High quality databases serve to measure effectiveness of care and offer insight for areas of improvement. There is a clear need for inclusion of outpatient activity in the National Burn Registry (NBR).

Role of Early Application of Pressure Garments following Burn Injury and Autografting.

BACKGROUND: Pressure garment therapy, used for reduction of postburn scarring, is commonly initiated after complete healing of the wound or autograft. Although some clinicians have suggested that earlier treatment may improve outcomes, the effect of early initiation of therapy has not been studied in a controlled environment. METHODS: Full-thickness burns were created on red Duroc pigs, burn eschar was excised, and the wound bed was grafted with split-thickness autografts. Grafts were treated with pressure garments immediately, 1 week (early), or 5 weeks (delayed) after grafting with nontreated grafts as controls. Scar morphology, biomechanics, and gene expression were measured at multiple time points up to 17 weeks after grafting. RESULTS: Grafts that received pressure within 1 week after grafting exhibited no reduction in engraftment rates. Immediate and early application of pressure resulted in scars with decreased contraction, reduced scar thickness, and improved biomechanics compared with controls. Pressure garment therapy did not alter expression of collagen I, collagen III, or transforming growth factor ß1 at the time points investigated; however, expression of matrix metalloproteinase 1 was significantly elevated in the immediate pressure garment therapy group at week 3, whereas the delayed pressure garment therapy and control groups approached baseline levels at this time point. CONCLUSIONS: Early application of pressure garments is safe and effective for reducing scar thickness and contraction and improving biomechanics. This preclinical study suggests that garments should be applied as soon as possible after grafting to achieve greatest benefit, although clinical studies are needed to validate the findings in humans.

Survey of national and local practice of compression therapy timing for burn patients in the United States.

OBJECTIVE: Compression therapy (CT) has been an important, but debated, treatment for burn scars. To better understand one source of variation in observed outcomes after CT, an evaluation of CT timing of application is needed. MATERIALS AND METHODS: Following IRB approval, 126 burn centers were contacted to complete a 17-question survey regarding the center's practice pattern for compression garment therapy. Locally, study subjects were identified between March 1, 2014 and December 31, 2015 and medical records examined for timing of garment ordering, delivery and fitting. RESULTS: The majority believed that compression therapy is beneficial. Most centers reported using custom-fit and pre-fabricated garments, and a goal time of application between 2-4 weeks (42%) and 4-6 weeks (36%). After the garments are ordered, 61% of centers estimate that it takes 2-4 weeks for them to arrive. No significant differences in practices were found among centers treating pediatric patients only, adults only or both. Locally, the mean number of weeks between the date of original injury and garment order placement was 9.1 weeks with an additional 8.7 weeks between the date of order and date of delivery. CONCLUSIONS: The current study identified that although the national reporting of time to garment application is estimated to be between 2-6 weeks at the majority of burn centers including our own, we found our center to be well in excess of 17 weeks. The findings offer an opportunity for local improvement, and raise the possibility of similar incongruity between goals and practice at other centers.

Incidence of oxandrolone induced hepatic transaminitis in patients with burn injury.

The benefits of oxandrolone in burn patients has led to its accepted use in the burn care community, however details regarding the most common adverse effect, transaminitis, remains unclear. The purpose of this study was to determine the incidence of transaminitis in patients with burn injury and identify risk factors associated with the development of transaminitis. This single-center, retrospective risk factor analysis compared burn patients on oxandrolone with and without the development of transaminitis, defined as any aspartate aminotransferase or alanine aminotransferase value >100mg/dL. Patient demographics, past medical history, lab values, and burn characteristics were recorded. Overall 28 out of 66 (42%) patients developed transaminitis. The transaminitis group had a significantly higher proportion of other concomitant medications with a transaminitis risk (p=0.045). No significant difference in liver dysfunction or length of stay was observed between the two groups. Oxandrolone induced transaminitis is occurring in patients significantly more frequently than previously reported warranting further research to guide monitoring requirements, use of concomitant medications, and to determine if rechallenging after resolution should be considered.

MRI compatibility of silver based wound dressings.

As silver dressings gain more widespread use, it is more likely that patients with silver-based dressings will also undergo magnetic resonance imaging (MRI). In current practice, these dressings are removed prior to imaging due to concerns over heating and image distortion. As dressing changes can be painful, the need to remove dressings simply for MRI may increase pain and contribute to opioid dependency. To examine the need for dressing removal, American Society for Testing and Materials International standards for assessing device deflection and torque were performed on 5 silver containing and 3 non-silver control dressings. Magnetically induced heating and image distortion were examined in a porcine hind limb wound dressed with control and test dressings. The limb was scanned in a clinical high field 3T MRI scanner using a series of standard MRI sequences (Survey, T1-weighted SE, T1-weighted IR TSE, T2-weighted TSE, DUAL TSE, and FLAIR). Deflection and torsion were not detected in control or silver-based dressings. For all combinations of dressings and MRI scans, average heating was between 0-0.2°C. Additionally, dressings, in dry and hydrated forms, caused no image distortion in any MRI scan performed. Evaluation of MRI safety and compatibility revealed no concerns for safety or image distortion in any of the silver-containing wound dressings tested thus it would be acceptable to leave these dressings intact during MRI. The ability to leave dressings in place during imaging will provide a significant benefit to patient care by reducing pain associated with dressing removal.

Early cessation of pressure garment therapy results in scar contraction and thickening.

Pressure garment therapy is often prescribed to improve scar properties following full-thickness burn injuries. Pressure garment therapy is generally recommended for long periods of time following injury (1-2 years), though it is plagued by extremely low patient compliance. The goal of this study was to examine the effects of early cessation of pressure garment therapy on scar properties. Full-thickness burn injuries were created along the dorsum of red Duroc pigs. The burn eschar was excised and wound sites autografted with split-thickness skin. Scars were treated with pressure garments within 1 week of injury and pressure was maintained for either 29 weeks (continuous pressure) or for 17 weeks followed by cessation of pressure for an additional 12 weeks (pressure released); scars receiving no treatment served as controls. Scars that underwent pressure garment therapy were significantly smoother and less contracted with decreased scar height compared to control scars at 17 weeks. These benefits were maintained in the continuous pressure group until week 29. In the pressure released group, grafts significantly contracted and became more raised, harder and rougher after the therapy was discontinued. Pressure cessation also resulted in large changes in collagen fiber orientation and increases in collagen fiber thickness. The results suggest that pressure garment therapy effectively improves scar properties following severe burn injury; however, early cessation of the therapy results in substantial loss of these improvements.

Structural, Chemical, and Mechanical Properties of Pressure Garments as a Function of Simulated Use and Repeated Laundering.

Pressure garments are widely employed for management of postburn scarring. Although pressure magnitude has been linked to efficacy, maintenance of uniform pressure delivery is challenging. An understanding of garment fabric properties is needed to optimize pressure delivery for the duration of garment use. To address this issue, compression vests were manufactured using two commonly used fabrics, Powernet or Dri-Tek Tricot, to achieve 10% reduction in circumference for a child-sized mannequin. Applied pressure was tracked on five anatomical sites over 23 hours, before laundering or after one and five laundering cycles. Load relaxation and fatigue of fabrics were tested before laundering or after one and five laundering cycles, and structural analysis via scanning electron microscopy was performed. Prior to laundering, pressure vests fabricated using Powernet or Dri-Tek Tricot generated a maximum pressure on the mannequin of 20 and 23 mm Hg, respectively. With both fabrics, pressure decreased during daily wear. Following five laundering cycles, Dri-Tek Tricot vests delivered a maximum of 7 vs 15 mm Hg pressure for Powernet at the same site. In cyclic tensile and load relaxation tests, exerted force correlated with fabric weave orientation with greatest force measured parallel to a fabric's long axis. The results demonstrate that Powernet exhibited the greatest applied force with the least garment fatigue. Fabric orientation with respect to the primary direction of tension was a critical factor in pressure generation and maintenance. This study suggests that fabrication of garments using Powernet with its long axis parallel to patient's body part circumference may enhance the magnitude and maintenance of pressure delivery.

Effect of skin graft thickness on scar development in a porcine burn model.

Animal models provide a way to investigate scar therapies in a controlled environment. It is necessary to produce uniform, reproducible scars with high anatomic and biologic similarity to human scars to better evaluate the efficacy of treatment strategies and to develop new treatments. In this study, scar development and maturation were assessed in a porcine full-thickness burn model with immediate excision and split-thickness autograft coverage. Red Duroc pigs were treated with split-thickness autografts of varying thickness: 0.026in. ("thin") or 0.058in. ("thick"). Additionally, the thin skin grafts were meshed and expanded at 1:1.5 or 1:4 to evaluate the role of skin expansion in scar formation. Overall, the burn-excise-autograft model resulted in thick, raised scars. Treatment with thick split-thickness skin grafts resulted in less contraction and reduced scarring as well as improved biomechanics. Thin skin autograft expansion at a 1:4 ratio tended to result in scars that contracted more with increased scar height compared to the 1:1.5 expansion ratio. All treatment groups showed Matrix Metalloproteinase 2 (MMP2) and Transforming Growth Factor ß1 (TGF-ß1) expression that increased over time and peaked 4 weeks after grafting. Burns treated with thick split-thickness grafts showed decreased expression of pro-inflammatory genes 1 week after grafting, including insulin-like growth factor 1 (IGF-1) and TGF-ß1, compared to wounds treated with thin split-thickness grafts. Overall, the burn-excise-autograft model using split-thickness autograft meshed and expanded to 1:1.5 or 1:4, resulted in thick, raised scars similar in appearance and structure to human hypertrophic scars. This model can be used in future studies to study burn treatment outcomes and new therapies.

Incidence of Unplanned 30-Day Readmissions in Adult Burn Patients in the United States.

This study characterizes adult burn readmissions in the United States using a nationally representative hospital inpatient sample. Readmission rates, diagnoses, and risk factors are discussed. We analyzed the 2013 and 2014 Nationwide Readmission Database for adult burn patients. The data were weighted to estimate national 30-day readmission rates. Principal readmission diagnoses were sorted into burn-specific or other readmission categories. We used multivariable logistic regression to assess the effects of patient and hospital stay risk factors on readmissions. An estimated 42,957 U.S. adult burn patients were discharged between January and November of 2013 and 2014. Of these patients, an estimated 3203 had unscheduled readmissions within 30 days (all-cause readmission rate: 7.5%, 95% CI: 6.7-8.2). An estimated 55.4 per cent of unplanned readmissions were for burn-specific principal readmission diagnoses. Burn-specific readmission was associated with burn severity and increased with both patient age and the number of comorbidities. Patients whose length of stay was less than 1 day per % total body surface area (%TBSA) burned had higher readmission risk (Adjusted odds ratio = 2.10, 95% CI = 1.48-2.99). The results of logistic regression models were similar for burn-specific readmissions and all-cause readmissions. In a nationally representative sample of adult burn patients, 4.1 per cent had unplanned 30-day readmissions for burn-specific reasons; 7.5 per cent were readmitted for any reason. Patient comorbidities and discharge before 1 day per %TBSA from the hospital impact readmission risk. Healthcare providers can use this information to identify at-risk patients, modify their treatment plans, and prevent readmissions.

Effects of early combinatorial treatment of autologous split-thickness skin grafts in red duroc pig model using pulsed dye laser and fractional CO2 laser.

BACKGROUND AND OBJECTIVE: The use of pulsed dye laser (PDL) and fractional CO2 (FX CO2 ) laser therapy to treat and/or prevent scarring following burn injury is becoming more widespread with a number of studies reporting reduction in scar erythema and pruritus following treatment with lasers. While the majority of studies report positive outcomes following PDL or FX CO2 therapy, a number of studies have reported no benefit or worsening of the scar following treatment. The objective of this study was to directly compare the efficacy of PDL, FX CO2 , and PDL + FX CO2 laser therapy in reducing scarring post burn injury and autografting in a standardized animal model. MATERIALS AND METHODS: Eight female red Duroc pigs (FRDP) received 4 standardized, 1 in. x 1 in. third degree burns that were excised and autografted. Wound sites were treated with PDL, FX CO2 , or both at 4, 8, and 12 weeks post grafting. Grafts receiving no laser therapy served as controls. Scar appearance, morphology, size, and erythema were assessed and punch biopsies collected at weeks 4, 8, 12, and 16. At week 16, additional tissue was collected for biomechanical analyses and markers for inflammatory cytokines, extracellular matrix (ECM) proteins, re-epithelialization, pigmentation, and angiogenesis were quantified at all time points using qRT-PCR. RESULTS: Treatment with PDL, FX CO2 , or PDL + FX CO2 resulted in significantly less contraction versus skin graft only controls with no statistically significant difference among laser therapy groups. Scars treated with both PDL and FX CO2 were visually more erythematous than other groups with a significant increase in redness between two and three standard deviations above normal skin redness. Scars treated with FX CO2 were visually smoother and contained significantly fewer wrinkles. In addition, hyperpigmentation was significantly reduced in scars treated with FX CO2 . CONCLUSIONS: The use of fractional carbon dioxide or pulsed dye laser therapy within 1 month of autografting significantly reduced scar contraction versus control, though no statistically significant difference was detected between laser modalities or use of both modalities. Overall, FX CO2 therapy appears to be modestly more effective at reducing erythema, and improving scar texture and biomechanics. The current data adds to prior studies supporting the role of laser therapy in the treatment of burn scars and indicates more study is needed to optimize delivery protocols for maximum efficacy. Lasers Surg. Med. 50:78-87, 2018. © 2017 Wiley Periodicals, Inc.

Scar formation following excisional and burn injuries in a red Duroc pig model.

Scar research is challenging because rodents do not naturally form excessive scars, and burn depth, size, and location cannot be controlled in human longitudinal studies. The female, red Duroc pig model has been shown to form robust scars with biological and anatomical similarities to human hypertrophic scars. To more closely mimic the mode of injury, recreate the complex chemical milieu of the burn wound environment and enhance scar development, an animal model of excessive burn-induced scarring was developed and compared with the more commonly used model, which involves excisional wounds created via dermatome. Standardized, full-thickness thermal wounds were created on the dorsum of female, red Duroc pigs. Wounds for the dermatome model were created using two different total dermatome settings: ∼1.5 mm and ≥ 1.9 mm. Results from analysis over 150 days showed that burn wounds healed at much slower rate and contracted more significantly than dermatome wounds of both settings. The burn scars were hairless, had mixed pigmentation, and displayed fourfold and twofold greater excess erythema values, respectively, compared with ∼1.5 mm and ≥ 1.9 mm deep dermatome injuries. Burn scars were less elastic, less pliable, and weaker than scars resulting from excisional injuries. Decorin and versican gene expression levels were elevated in the burn group at day 150 compared with both dermatome groups. In addition, transforming growth factor-beta 1 was significantly up-regulated in the burn group vs. the ∼1.5 mm deep dermatome group at all time points, and expression remained significantly elevated vs. both dermatome groups at day 150. Compared with scars from dermatome wounds, the burn scar model described here demonstrates greater similarity to human hypertrophic scar. Thus, this burn scar model may provide an improved platform for studying the pathophysiology of burn-related hypertrophic scarring, investigating current anti-scar therapies, and development of new strategies with greater clinical benefit.

Inflammatory responses, matrix remodeling, and re-epithelialization after fractional CO2 laser treatment of scars.

BACKGROUND AND OBJECTIVE: Fractional CO2 laser therapy has been used to improve scar pliability and appearance; however, a variety of treatment protocols have been utilized with varied outcomes. Understanding the relationship between laser power and extent of initial tissue ablation and time frame for remodeling could help determine an optimum power and frequency for laser treatment. The characteristics of initial injury caused by fractional CO2 laser treatment, the rates of dermal remodeling and re-epithelialization, and the extent of inflammation as a function of laser stacking were assessed in this study in a porcine scar model. MATERIALS AND METHODS: Full-thickness burn wounds were created on female Red Duroc pigs followed by immediate excision of the eschar and split-thickness autografting. Three months after injury, the resultant scars were treated with a fractional CO2 laser with 70 mJ of energy delivered as either a single pulse or stacked for three consecutive pulses. Immediately prior to laser treatment and at 1, 24, 96, and 168 hours post-laser treatment, transepidermal water loss (TEWL), erythema, and microscopic characteristics of laser injury were measured. In addition, markers for inflammatory cytokines, extracellular matrix proteins, and re-epithelialization were quantified at all time points using qRT-PCR. RESULTS: Both treatments produced erythema in the scar that peaked 24 hours after treatment then decreased to basal levels by 168 hours. TEWL increased after laser treatment and returned to normal levels between 24 and 96 hours later. Stacking of the pulses did not significantly increase the depth of ablated wells or extend the presence of erythema. Interleukin 6 and monocyte chemoattractant protein-1 were found to increase significantly 1 hour after treatment but returned to baseline by 24 hours post laser. In contrast, expression of transforming growth factor ß1 and transforming growth factor ß3 increased slowly after treatment with a more modest increase than interleukin 6 and monocyte chemoattractant protein-1. CONCLUSIONS: In the current study, the properties of the ablative zones were not directly proportional to the total amount of energy applied to the porcine scars with the use of triple stacking, resulting in only minor increases to microthermal zone (MTZ) depth and width versus a single pulse. Re-epithelialization and re-establishment of epidermal barrier function were observed in laser treated scars by 48 hours post therapy. Finally, many of the inflammatory genes up-regulated by the laser ablation returned to baseline within 1 week. As a whole, these results suggest that microthermal zones created by FXCO2 treatment re-epithelialize rapidly with the inflammatory response to the laser induced injury largely resolved within 1 week post treatment. Further study is needed to understand the relationship between laser stacking and MTZ properties in human scars in order to evaluate the clinical applicability of the stacking technique. Lasers Surg. Med. 49:675-685, 2017. © 2017 Wiley Periodicals, Inc.