Topical Synthetic Platelets Loaded With Gentamicin Decrease Bacteria in Deep Partial-Thickness Burns.

INTRODUCTION: Prolonged inflammation and infection in burns may cause inadequate healing. Platelet granules contain anti-inflammatory mediators that impact wound healing. Synthetic platelets (SPs) avoid portability and storage difficulties of natural platelets and can be loaded with bioactive agents. We evaluated wound healing outcomes in deep partial-thickness (DPT) burns treated topically with SP loaded with antibiotics. MATERIALS AND METHODS: Thirty DPT burns were created on the dorsum of two Red Duroc hybrid pigs. Six wounds were randomized into five groups: SP alone, SP loaded with gentamicin vesicles, SP with gentamicin mixture, vehicle control (saline), or dry gauze. Wounds were assessed from postburn days 3-90. Primary outcome was re-epithelialization percentage at postburn day 28. Secondary outcomes included wound contraction percentage, superficial blood flow relative to normal skin controls, and bacterial load score. RESULTS: Results showed that re-epithelialization with the standard of care (SOC) was 98%, SP alone measured 100%, SP loaded with gentamicin vesicles was 100%, and SP with gentamicin mixture was 100%. Wound contraction was 5.7% in the SOC and was ∼10% in both the SP loaded with gentamicin vesicles and SP with gentamicin mixture groups. Superficial blood flow in the SOC was 102.5%, SP alone was 170%, the SP loaded was 155%, and gentamicin mixture 162.5%. Bacterial load score in the SOC was 2.2/5.0 and was significantly less at 0.8/5.0 in SP loaded with gentamicin vesicles (P > 0.05). SP and gentamicin mixture scored 2.7 and 2.3/5.0. CONCLUSIONS: Topical SP treatment did not significantly improve outcomes. However, SP loaded with gentamicin-infused vesicles decreased bacterial load.

Full-thickness skin columns: A method to reduce healing time and donor site morbidity in deep partial-thickness burns.

The current standard of care for the coverage of large wounds often involves split thickness skin grafts (STSGs) which have numerous limitations. One promising technique that has gained traction is fractional autologous skin grafting using full-thickness skin columns (FTSC). Harvesting occurs orthogonally by taking numerous individual skin columns containing the epidermis down through the dermis and transferring them to the wound bed. The purpose of this porcine study was to investigate the efficacy of implanting FTSCs directly into deep partial-thickness burn wounds, as well as examining donor site healing at the maximal harvest density. It was hypothesised that by utilising FTSCs, the rate of healing in deep partial thickness burns can be improved without incurring the donor morbidity seen in other methods of skin grafting. Deep partial-thickness burns were created on the dorsum of female red duroc swine, debrided 3 days later and FTSCs were implanted at varying expansion ratios directly into the burn wounds. At day 14, 1:50 expansion ratio showed significantly faster re-epithelialisation compared to the debrided burn control and 1:200. Donor sites (at 7%-10% harvest density) were 100% re-epithelialised by day 7. Additionally, the maximal harvest density was determined to be 28% in an ex vivo model, which then five donor sites were harvested at 28% density on a red duroc swine and compared to five STSG donor sites. At maximal harvest density, FTSC donor sites were significantly less hypopigmented compared to STSGs, but no significant differences were observed in re-epithelialisation, contraction, blood flow or dermal thickness. In conclusion, implantation directly into deep partial-thickness burns is a viable option for the application of FTSCs, favouring lower expansion ratios like 1:50 or lower. Little difference in donor site morbidity was observed between FTSC at a maximal harvest density of 28% and STSGs, exceeding the optimal harvest density.

Burn Scar Management and Reconstructive Surgery.

This chapter highlights the importance of a comprehensive burn scar treatment plan in approaching a burn survivor. General concepts of burn scar physiology and a practical system to describe burn scars based on cause, biology, and symptoms are presented. Common scar management modalities including nonsurgical, surgical, and adjuvant therapies are further discussed.

Delivery of topical gentamicin cream via platform wound device to reduce wound infection-A prospective, controlled, randomised, clinical study.

The platform wound device (PWD) is a wound coverage system that is designed to decrease wound infection rates by allowing for direct delivery of topical antibiotics and antimicrobials while creating a sealed, protective barrier around the area of injury. This study evaluated the safety and efficacy of the PWD as a protective dressing and a delivery system for topical antibiotics compared to the current standard of care (SoC). This was a multi-center, prospective, randomised, controlled clinical trial. The wounds were treated with the PWD with gentamicin cream or SoC dressings. The wounds were evaluated before the start of treatment and after 48-96 hours via clinical assessment, photographs, and qualitative bacterial swabs for bacterial analysis. The delivery of gentamicin via the PWD was safe and did not cause any adverse effects. The treatment decreased both inflammation and bacterial growth during the study period. No significant differences in the SoC were observed. The PWD is a transparent and impermeable polyurethane chamber that encloses and protects the injured area. The delivery of topical gentamicin via the PWD was safe and effective. Clinical assessment for infection found the PWD to be non-inferior to the current SoC treatment options.

Evaluation of Topical Off-The-Shelf Therapies to Improve Prolonged Field Care of Burn-Injured Service Members.

INTRODUCTION: Burns are common injuries on the battlefield. Given austere environments, surgical debridement of injured service members is often not feasible in these settings. Delays in surgical debridement create a risk of infection and deranged healing for burn patients. As such, this study attempts to identify the best commercially available off-the-shelf (OTS) therapies with field-deployable potential to improve prolonged field care (PFC) of burn-injured soldiers. METHODS: Deep partial-thickness (DPT) burns (25 cm2) were created on the dorsum of 5 anesthetized pigs utilizing a thermocouple burn device at 100°C for 15 seconds. Nonsurgical debridement was done 1-hour after burn creation using sterile saline water and gauze to remove excess eschar tissue. Animals were then randomized into 5 experimental groups, and OTS therapies were applied to 6 of the 12 created DPT burns. The remaining 6 burns were treated with 1% silver sulfadiazine cream (Ascend Laboratories, LLC, Parsippany, NJ) as the PFC standard of care (SOC) controls. The 5 randomized OTS therapies were: irradiated sterile human skin allograft (IHS), biodegradable temporizing matrix (BTM), polylactic acid skin substitute, hyaluronic acid ester matrix (HAM), and decellularized fish skin graft (FSG). Wounds were serially assessed on post-burn days 3, 7, 14, 21, and 28. Assessments were conducted using a combination of photographs, histology, and quantitative bacteriology. Endpoints included burn wound progression, re-epithelialization, wound contraction, scar elevation index, and colony-forming units (CFU). RESULTS: The analysis demonstrated that by day 3, the FSG prevented burn wound progression the most efficiently. In terms of wound healing, the results showed re-epithelialization percentages close to 100% by day 28 for all treatment groups. No statically significant differences were observed. Quality of healing analyses demonstrated that the BTM-treated wounds had contracted less and the difference to the IHS-treated wounds was statistically significant (P < .05). As regards to antimicrobial properties, the CFU results showed no statistically significant differences between the OTS therapies and the SOC on days 3, 7, and 14. CONCLUSIONS: The impact of Food and Drug Administration-approved OTS therapies was compared to the current PFC SOC for the treatment of DPT burns in a porcine model. Several topical options exist for the management of burns prior to definitive treatment in the operating room and warrant further evaluation. These therapies are actively used on civilian burn counterparts and have far-forward, field-deployable potential for use at the point of injury so that injured service members may not need evacuation to higher roles of care and combat power may be preserved. Our results demonstrated that all the studied OTS therapies performed well when compared to the SOC in terms of burn wound progression, wound healing, quality of healing, and quantitative bacteriology.

Analysis of the Utility of CO2 and Pulse-Dye Lasers Together and Separately in the Treatment of Hypertrophic Burn Scars.

INTRODUCTION: Hypertrophic burn scars (HTBSs) remain a significant source of morbidity. Contemporary treatment has evolved to use CO2 lasers and/or pulse-dye lasers (PDLs) to reduce scar thickness (ST) and erythema. This study seeks to compare treatment efficacy with CO2 or PDL individually and in combination. METHODS: Patients undergoing laser treatments for HTBSs were enrolled. Three 3 × 3 cm squares of HTBSs were randomized to receive treatment with CO2 laser, PDL or CO2 + PDL. Patients underwent 3 treatments, 4 to 6 weeks apart and were followed up over 3 to 6 months. Scar assessments occurred at each visit before treatment and consisted of photographs, ultrasound, colorimetry, and the Patient and Observer Scar Assessment Score. RESULTS: Twenty-five patients were enrolled. Twenty completed 2 treatments (80%) and 11 completed all 3 treatments (44%). Median initial ST was 0.3 cm. Median time since injury was 8 months. Hypertrophic burn scars treated with CO2 or PDL showed a significant decrease in Patient and Observer Scar Assessment Scale score from visit 1 to 3 (P = 0.01 and 0.01, respectively). When separated by ST, thick scars (≥0.3 cm) showed a significant decrease in thickness between visit 1 and 2 using all laser modalities (CO2 + PDL, P = 0.01; CO2, P = 0.02; PDL, P = 0.03). Thin scars (<0.3 cm) showed a reduction in thickness by visit 3 after CO2 + PDL or PDL alone (P = 0.01 and 0.04, respectively). Separating scars by age, younger scars (<9 months) showed a significant reduction in thickness between visit 1 and 2 for CO2 treatment (P = 0.04), and between visit 2 and 3 for CO2 + PDL treatment (P = 0.04). Hypertrophic burn scars treated with PDL did not demonstrate a significant reduction in thickness until visit 3 (P = 0.002). Older scars (≥9 months) showed a significant reduction in thickness between visit 1 and 2 only after CO2 + PDL (P = 0.01). CONCLUSIONS: Hypertrophic burn scars of varying ages, etiologies, and thicknesses were examined in this study with greater degree of early reduction seen in thicker scars using all laser modalities of CO2, PDL or in combination. However, there was no clinically meaningful benefit found with combination as compared with individual treatment. These data support the use of laser to improve HTBS but does not support one modality or combination of modalities over another.

Impact of dermal matrix thickness on split-thickness skin graft survival and wound contraction in a single-stage procedure.

Optimal treatment of full-thickness skin injuries requires dermal and epidermal replacement. To spare donor dermis, dermal substitutes can be used ahead of split-thickness skin graft (STSG) application. However, this two-stage procedure requires an additional general anaesthetic, often prolongs hospitalisation, and increases outpatient services. Although a few case series have described successful single-stage reconstructions, with application of both STSG and dermal substitute at the index operation, we have little understanding of how the physical characteristics of dermal substitutes affects the success of a single-stage procedure. Here, we evaluated several dermal substitutes to optimise single-stage skin replacement in a preclinical porcine model. A porcine full-thickness excisional wound model was used to evaluate the following dermal substitutes: autologous dermal graft (ADG; thicknesses 0.15-0.60 mm), Integra (0.4-0.8 mm), Alloderm (0.9-1.6 mm), and chitosan-based hydrogel (0.1-0.2 mm). After excision, each wound was treated with either a dermal substitute followed by STSG or STSG alone (control). Endpoints included graft take at postoperative days (PODs) 7 and 14, wound closure at POD 28, and wound contracture from POD 28-120. Graft take was highest in the STSG alone and hydrogel groups at POD 14 (86.9% ± 19.5% and 81.3% ± 12.3%, respectively; P < .001). There were no differences in graft take at POD 7 or in wound closure at POD 28, though highest rates of wound closure were seen in the STSG alone and hydrogel groups (93.6% ± 9.1% and 99.8% ± 0.5%, respectively). ADG-treated wounds demonstrated the least amount of wound contracture at each time point. Increase dermal substitute thickness was associated with worse percent graft take at PODs 14 and 28 (Spearman ρ of -0.50 and -0.45, respectively; P < .001). In this preclinical single-stage skin reconstruction model, thinner ADG and hydrogel dermal substitutes outperformed thicker dermal substitutes. Both substitute thickness and composition affect treatment success. Further preclinical and clinical studies to optimise this treatment modality are warranted.

Utilization of a Novel Negative Pressure Platform Wound Dressing on Surgical Incisions: A Case Series.

Closed incision negative pressure therapy (ciNPT) has been shown to improve wound healing for patients at high risk for wound complications. Current devices consist of opaque interface dressings that do not allow ongoing visual evaluation of the surgical incision and utilize a negative pressure of -80 mm Hg to -125 mm Hg. The Negative Pressure Platform Wound Dressing (NP-PWD) was developed to address these aspects. This case series is the first evaluation of the NP-PWD in a clinical setting. METHODS: Patients aged 18-85 undergoing an operation with an anticipated incision and primary closure were screened. Demographics, comorbidities, and operation performed were recorded. Following closure, the incision was measured and photographed before NP-PWD placement. The NP-PWD was removed at the first postoperative check (POC) between postoperative days (PODs) 3-5. Subjects were followed until PODs 9-14. POCs consisted of incision assessment, measurement, photography, and adverse event monitoring. RESULTS: A total of 8 patients with 10 incisions were included in the study. Five patients were men. Median age was 56 years (IQR 53-74 years). All incisions were intact and without inflammation or infection at all POCs. Three adverse events, including small blisters and interruption of therapy, were noted. CONCLUSIONS: This case series reports that patients tolerated the NP-PWD on closed surgical incisions well and that all incisions were intact without evidence of inflammation or infection after 2 weeks of follow-up. Future controlled, clinical studies should further examine the safety and efficacy of the use of the NP-PWD.

Fractionated Ablative Carbon Dioxide Laser Therapy Decreases Ultrasound Thickness of Hypertrophic Burn Scar: A Prospective Process Improvement Initiative.

INTRODUCTION: Carbon dioxide (CO2) laser treatment is routinely used to treat hypertrophic burn scars (HBS). Although prior research has documented subjective improvement in HBS after treatment, there is little data evaluating objective changes in scar characteristics after therapy. The aim of our process improvement project was to evaluate changes to scar thickness (ST) using high-frequency ultrasound in patients with HBS undergoing CO2 laser therapy. METHODS: Ultrasound measurements of ST were obtained from patients with HBS before initial and at each subsequent treatment. ST, reduction in ST per treatment, and percentage reduction in ST from baseline were tabulated. Post hoc analyses examining the effect of initial ST and scar maturity on outcome were performed. First, patients were grouped by baseline ST into thicker (group 1, initial ST ≥ median value) and thinner (group 2, initial ST < median value) scar groups. Second, patients were divided into quartiles based on time from injury to treatment. Outcomes at each time point were compared with either Mann-Whitney U or Kruskal-Wallis tests, with Bonferonni corrections performed for post hoc subgroup analyses. Significance was set at P < 0.05. RESULTS: Twenty-one consecutive patients with HBS treated with CO2 laser were included. All patients completed 1 or more treatment, 48% completed 2 or more treatments, and 28% completed 3 treatments. Median initial ST was 0.71 cm (0.44-0.98 cm), and median scar maturity was 7.5 months (4.9-9.8 months). Overall, ST decreased over the treatment course (P < 0.001), with post hoc analysis demonstrating that 2 treatments were required to achieve a significant ST reduction (P < 0.01). On subgroup analysis comparing initial ST, ST decreased significantly in group 1 (thicker scars) overall (P < 0.001) but not in group 2 (P = 0.109). ST reduction was greatest after 1 treatment in group 1 (P = 0.022) and group 2 (P = 0.061). Percent reduction was greater in group 1 relative to group 2 after 1 treatment (P = 0.016). On subgroup analysis of scar maturity, there were no significant differences in either baseline ST or ST at any subsequent visit. CONCLUSIONS: Fractionated ablative CO2 laser treatment improved ST after 1 to 2 treatments. Patients with thicker scars demonstrated greater ST reduction than those with thinner scars. Ultrasound adequately assessed treatment response.

Anti-human Leukocyte Antigen Immune Sensitization Effects of Cryopreserved Allograft and Blood Transfusion.

Vascularized composite allotransplantation (VCA) is the most advanced reconstructive technique available to patients who suffer devastating burns to the limbs or face. However, VCA requires donor-recipient matching. Burn patients have been reported to experience sensitization, or the development of anti-human leukocyte antigen antibodies, during resuscitation and wound coverage, potentially precluding them from future VCA. This study sought to investigate the contributions of both blood and allograft to sensitization in burn patients. Four groups were compared: burn patients who received blood products and allograft (group 1), burn patients who received blood products only (group 2), trauma patients who received blood products only (group 3), and healthy volunteer controls (group 4). The average calculated panel-reactive antibody (indicating sensitization) was higher in group 1 compared to group 4 (P = .035). Additionally, the incidence of severe sensitization was higher in group 1 relative to the other groups (P = .049). When comparing groups of patients who had no sensitization, mild sensitization, moderate sensitization, and severe sensitization, there were no significant differences in age, sex, blood products received, total body surface area burned, or allograft used between groups, though severely sensitized patients tended to have greater total body surface area involvement and received more units of packed red blood cells and allograft (P = .079, P = .196, and P = .072, respectively). We therefore conclude that while burn patients who received allograft and blood demonstrated a higher incidence of anti-human leukocyte antigen sensitization relative to healthy controls, this difference cannot solely be attributed to either allograft use or transfusion.

Single-stage Composite Skin Reconstruction Using a Dermal Regeneration Template.

BACKGROUND: Composite reconstruction with a dermal substitute followed by skin graft is sometimes used for reconstructing high-quality skin while preserving donor sites. This often necessitates 2 separate procedures, additional general anesthetic, and longer hospitalization. Concurrent use of dermal substitutes and skin graft in a single stage has been previously reported in small series. Here, we report our experience with single-stage skin reconstruction with Integra and split-thickness skin graft for coverage of wounds post burn eschar excision and post burn scar contracture release. METHODS: This is a retrospective review of consecutive operations from 2013 to 2017 in which single-stage bilayer reconstruction (SSBR) was performed. Data were obtained from electronic medical records and perioperative photographs. RESULTS: In this 5-year period, 13 surgical sites were identified in which SSBR was used in 8 subjects. Average and median graft take was 86.2% and 95%, respectively. Graft take was over 90% in 10 out of 13 cases. One case required regrafting after initial graft failure. CONCLUSIONS: In the appropriate setting, SSBR is a practical technique in covering wounds post burn eschar excision and post burn scar contracture release resulting in reasonable graft take. Use of noncontaminated wound beds is crucial. Although there is risk of regrafting, it is not clear whether this risk is any higher than in split-thickness skin grafting alone. This study was unable to evaluate contribution of dermal substitute to contraction, function, and mobility, nor how hypothesized improvement of skin quality compares to the original thick dermal substitute. We recommend further investigation.

Advancements in Regenerative Strategies Through the Continuum of Burn Care.

Burns are caused by several mechanisms including flame, scald, chemical, electrical, and ionizing and non-ionizing radiation. Approximately half a million burn cases are registered annually, of which 40 thousand patients are hospitalized and receive definitive treatment. Burn care is very resource intensive as the treatment regimens and length of hospitalization are substantial. Burn wounds are classified based on depth as superficial (first degree), partial-thickness (second degree), or full-thickness (third degree), which determines the treatment necessary for successful healing. The goal of burn wound care is to fully restore the barrier function of the tissue as quickly as possible while minimizing infection, scarring, and contracture. The aim of this review is to highlight how tissue engineering and regenerative medicine strategies are being used to address the unique challenges of burn wound healing and define the current gaps in care for both partial- and full-thickness burn injuries. This review will present the current standard of care (SOC) and provide information on various treatment options that have been tested pre-clinically or are currently in clinical trials. Due to the complexity of burn wound healing compared to other skin injuries, burn specific treatment regimens must be developed. Recently, tissue engineering and regenerative medicine strategies have been developed to improve skin regeneration that can restore normal skin physiology and limit adverse outcomes, such as infection, delayed re-epithelialization, and scarring. Our emphasis will be centered on how current clinical and pre-clinical research of pharmacological agents, biomaterials, and cellular-based therapies can be applied throughout the continuum of burn care by targeting the stages of wound healing: hemostasis, inflammation, cell proliferation, and matrix remodeling.

A Survey of Temperature Management Practices Among Burn Centers in North America.

Maintaining body temperature is a unique challenge with burn care. We sought to describe core temperature goals in the operating room (OR) and the methods used to achieve and maintain these goals, along with current methods of warming in the intensive care unit (ICU), the perception of effect of increased ambient temperature on work performance, and concerns with contamination of sterile fields due to increased ambient temperature. A 24 question survey was disseminated to burn centers in the United States and Canada. The questions included demographics, target core and ambient temperatures, warming methods, and beliefs on ambient temperature's effects. Of 121 burn centers, 52 questionnaires were completed (43% response rate). The majority of centers targeted a core temperature between 36 and 38°C in the OR and an ambient temperature between 75 and 95°F in the ICU. The most common methods for maintaining core temperature included warmed ambient temperature, forced air devices, and intravenous fluids. Although the majority of centers reported the belief that increased ambient temperature benefits patients, many also reported that there is a negative impact on staff performance and risk of staff perspiration contaminating sterile fields. Burn centers reported a range of target core temperatures and methods to reach target temperatures. More than a third of respondents perceived a negative impact work performance while more than half acknowledged the potential for contamination of sterile fields. A prospective observational study is needed to determine actual temperature regulation practice patterns and its impact on outcomes.

Scaffold-Free, Size-Controlled Three-Dimensional Culture of Rabbit Adipose-Derived Stem Cells.

Adipose-derived stem cells are capable of self-renewal and differentiation along multiple cell lineages, and have potential applications in a wide range of therapies. ASCs are commonly cultured as monolayers on tissue culture plastic, but there are indications that they may lose their cell-specific properties with time in vitro. There has been a growing interest in culturing adherent cells using three-dimensional techniques based on the understanding that growing cells on plastic surfaces cannot truly recapitulate 3D in vivo conditions. Here we describe a novel method for generating and culturing rabbit ASCs as scaffold-free 3D cell aggregates using micropatterned wells via a forced aggregation technique.

Accelerated epithelialization and improved wound healing metrics in porcine full-thickness wounds transplanted with full-thickness skin micrografts.

Split-thickness skin grafting (STSG) is the current gold standard for treatment of extensive burn and traumatic skin injuries. However, STSG is limited by donor-site morbidity and availability, and often leads to scarring and wound contracture. Furthermore, these thin grafts lack dermal elements such as nerves and adnexa which are important in recapitulating normal skin function. Methods of fractional skin replacement either as minced STSGs or microscopic skin tissue columns have been proposed, though these techniques have not been fully characterized and lack evidence of regenerated adnexal structures. Here, we describe an alternative method of fractional skin replacement using full-thickness skin micrografts containing deep dermal components and intact adnexa. Full-thickness wounds measuring 3 cm in diameter and 2 cm apart were created on adult female Yorkshire swine. Full-thickness skin tissue columns (FTSTCs) 1.5 mm in diameter with intact adnexa and subcutaneous tissue were obtained using a suction-assisted device. Explant culture was initiated to demonstrate the capacity of FTSTCs to act as reservoirs of viable and proliferative epidermal and dermal cells. FTSTCs were applied directly to excisional wounds at three different expansion ratios (1:16, 1:40, 1:100) in fibrin sealant. Biopsies were collected at defined time points postwounding and processed for histology and immunohistochemistry. Wounds grafted with FTSTCs showed enhanced reepithelialization and epidermal differentiation over untreated control wounds in a dosage dependent manner. Adnexal structures such as hair follicles and sweat glands were only evident in FTSTC-treated wounds. Furthermore, whereas ungrafted wounds were marked by extensive infiltration of α-Smooth Muscle Actin+ (α-SMA+ ) myofibroblasts at POD 60, α-SMA expression was sparse and largely limited to perivascular cells in FTSTC-treated wounds. The number of Ki67+ cells was also greatly reduced in FTSTC-treated wounds. Transplantation of FTSTCs containing intact adnexa improved wound healing parameters in porcine full-thickness wounds and may have implications for the treatment of large, traumatic wounds.

Ultrahigh dose gentamicin alters inflammation and angiogenesis in vivo and in vitro.

Skin quality outcome after skin grafting is adversely affected by wound bed inflammation. Neomycin, gentamicin, and other aminoglycoside antibiotics are known to modulate inflammation, and topical application affords the use of higher doses than are possible to use systemically. Previous data suggest that clinically relevant doses of neomycin, but not gentamicin, may impair angiogenesis, which is critical to the durable survival of skin grafts. The role of gentamicin at ultrahigh doses compared with clinically relevant neomycin doses in regulating inflammatory expression and angiogenesis has been examined. In a porcine skin replacement excisional wound model, continuous exposure to gentamicin increased anti-angiogenic and inflammatory expression at 7 days postgrafting. In in vitro studies, gentamicin also impaired angiogenesis in a human umbilical vein endothelial cell (HUVEC) tube formation model, increased the expression of the anti-angiogenic gene C-X-C motif chemokine 10 (CXCL10) in HUVECs and macrophages, and increased pro-inflammatory cytokine expression of macrophages in a dose-dependent manner. Neomycin exerted similar effects in vitro at clinically relevant doses on HUVEC tube formation and macrophage pro-inflammatory expression. CXCL10 was upregulated in macrophages, but did not exhibit a change in HUVECs with neomycin treatment. Ultrahigh doses of gentamicin and clinically relevant doses of neomycin affect inflammation and angiogenesis in in vivo and in vitro models. These findings suggest that topical administration of aminoglycosides have the potential to adversely influence early skin graft survival.

Perioperative Temperature Management During Burn Care.

Major physiologic alterations following a severe thermal injury disrupt thermal homeostasis and predispose burn patients to hypothermia. An important recommendation in many clinical practice guidelines is to increase the ambient temperature during the care of severely burned patients in the operating room and intensive care unit to mitigate the loss of thermoregulation, prevent hypothermia, and minimize the impact of hypermetabolism. However, the scientific support for this recommendation remains unclear. This review summarizes the current knowledge regarding the pathophysiology and treatment of thermal injury-induced hypermetabolism and hypothermia, with special emphasis on alterations in ambient temperature. Current evidence on the value of increasing ambient temperature during the care of severely burned patients in the operating room or intensive care unit is limited, with minimal human studies investigating physiologic benefit or potential adverse effects.

Antecedent thermal injury worsens split-thickness skin graft quality: A clinically relevant porcine model of full-thickness burn, excision and grafting.

Current standard of care for full-thickness burn is excision followed by autologous split-thickness skin graft placement. Skin grafts are also frequently used to cover surgical wounds not amenable to linear closure. While all grafts have potential to contract, clinical observation suggests that antecedent thermal injury worsens contraction and impairs functional and aesthetic outcomes. This study evaluates the impact of antecedent full-thickness burn on split-thickness skin graft scar outcomes and the potential mediating factors. Full-thickness contact burns (100°C, 30s) were created on the backs of anesthetized female Yorkshire Pigs. After seven days, burn eschar was tangentially excised and covered with 12/1000th inch (300µm) split-thickness skin graft. For comparison, unburned wounds were created by sharp excision to fat before graft application. From 7 to 120days post-grafting, planimetric measurements, digital imaging and biopsies for histology, immunohistochemistry and gene expression were obtained. At 120days post-grafting, the Observer Scar Assessment Scale, colorimetry, contour analysis and optical graft height assessments were performed. Twenty-nine porcine wounds were analyzed. All measured metrics of clinical skin quality were significantly worse (p<0.05) in burn injured wounds. Histological analysis supported objective clinical findings with marked scar-like collagen proliferation within the dermis, increased vascular density, and prolonged and increased cellular infiltration. Observed differences in contracture also correlated with earlier and more prominent myofibroblast differentiation as demonstrated by α-SMA staining. Antecedent thermal injury worsens split-thickness skin graft quality, likely by multiple mechanisms including burn-related inflammation, microscopically inadequate excision, and dysregulation of tissue remodeling. A valid, reliable, clinically relevant model of full-thickness burn, excision and skin replacement therapy has been demonstrated. Future research to enhance quality of skin replacement therapies should be directed toward modulation of inflammation and assessments for complete excision.

The Burn Wound Microenvironment.

Significance: While the survival rate of the severely burned patient has improved significantly, relatively little progress has been made in treatment or prevention of burn-induced long-term sequelae, such as contraction and fibrosis. Recent Advances: Our knowledge of the molecular pathways involved in burn wounds has increased dramatically, and technological advances now allow large-scale genomic studies, providing a global view of wound healing processes. Critical Issues: Translating findings from a large number of in vitro and preclinical animal studies into clinical practice represents a gap in our understanding, and the failures of a number of clinical trials suggest that targeting single pathways or cytokines may not be the best approach. Significant opportunities for improvement exist. Future Directions: Study of the underlying molecular influences of burn wound healing progression will undoubtedly continue as an active research focus. Increasing our knowledge of these processes will identify additional therapeutic targets, supporting informed clinical studies that translate into clinical relevance and practice.

Functional and subjective assessment of burn contracture release in a mission setting.

OBJECTIVE: Burns and subsequent contractures are common in developing nations. Contracture release is performed to treat such patients with functional limitations. The aim of this study is to evaluate post-operative functional and psychosocial outcomes following contracture release in a mission setting. METHODS: During a surgical mission in Mumbai, India, 39 patients burn contractures underwent surgical release. A total of 31 patients (64% female, mean age 27 years) chose to participate in the study. Patients were scored preoperatively and postoperatively using a SF-36 validated survey and AMA impairment guideline assessment. RESULTS: Thirty-one patients completed questionnaires pre-operative and 6-weeks post operatively. Twenty-four patients completed a survey 3-months post operatively (77.4%). Among those enrolled, 67% were women with the majority sustaining <20% total body surface area burns (70.7%) but had multiple contractures (80.6%). SF-36 physical component score increased from a mean score of 49.8 preoperatively to 55.6 by 3 months following contracture release (P<0.001). The SF-36 mental component score similarly increased from 38.8 to 51.1 by 3 months (P<0.001). AMA Whole Person Impairment (WPI) scores improved from 40.3% impairment pre-operative to 26.6% at 6-weeks post-operative (P<0.001). CONCLUSIONS: Patients SF-36 and WPI scores improved following burn contracture release, confirming both functional and psychologic improvement following surgery. During the acute post-operative period, this study suggests that contracture release in a mission setting is of benefit to patients.