Topical treatment of burn wounds remains challenging because eschar formation, inflammation and impaired vascularization can limit drug penetration and tissue repair. Here, we introduce a flexible large-area microneedle patch for sustained local delivery of extracellular matrix-derived peptides to deep partial-thickness burn wounds. The microneedles were composed of cellulose acetate phthalate and hydroxypropyl methylcellulose and included a transparent water-soluble backing layer to aid placement and allow dissolution after application. The patch delivered two peptides with previously reported biological activity: TSN6, associated with angiogenic responses and TSN18, associated with cell proliferation and epithelial repair. The microneedles retained sharp conical geometry after peptide loading, showed sufficient compressive strength for skin insertion and produced consistent microchannels in ex vivo porcine skin. In vitro studies showed peptide-dependent release over 48 h: TSN18 reached approximately 50% release within 12 h and exceeded 80% release by 48 h, whereas TSN6 was released more slowly, reaching 45% when loaded alone and 58% when co-loaded with TSN18. In a porcine deep partial-thickness burn model, TSN18-treated wounds showed lower burn depth than SSD-treated wounds at day 4 (1174 ± 35 vs. 1628 ± 178 μm, p < 0.05). Co-delivery of TSN6 and TSN18 preserved more dermis than the scrambled peptide control (1667 ± 134 vs. 938 ± 194 μm, p < 0.05) and increased neoepidermal thickness at day 20 compared with scrambled peptide and SSD controls (417 ± 45 vs. 237 ± 25 and 265 ± 16 μm, respectively). Although consistent improvements in macroscopic wound closure and re-epithelialization were not observed across peptide-treated groups, these results show that microneedle-mediated peptide delivery can improve selected tissue-level measures of burn injury and epidermal repair.

The gold standards for coverage of wounds that cannot be primarily closed are full thickness skin grafts (FTSGs) and split thickness skins graft (STSGs). FTSGs harvest sites generally require primary closure, which limits availability, especially when treating larger wounds. STSGs have many shortcomings, including donor site morbidity. Fractional autologous skin replacement can be utilized in conjunction with or in lieu of STSGs to both improve graft outcomes of large wounds and to decrease donor site morbidity. Skin can be mechanically or chemically fractionated. Fractionated skin can be advantageous, as adnexal structures provide additional functionality without donor site morbidity. In this review, we will discuss current and emerging techniques in fractional skin replacement.

There is a critical unmet need to improve the treatment of battlefield burns. Rapid and efficient wound protection and closure are essential to prevent infections, reduce pain, and minimize scarring. This study introduces a portable, field-applicable spray system designed to instantly apply a protective hydrogel coating with therapeutic agents to wounds of varying sizes and shapes for emergency treatments. By mimicking natural silk-spinning processes, the current spray-on hydrogel coating is optimized to create a self-standing, spider-web-like interwoven structure that supports tissue adhesion, cell viability, and vascular regeneration. In vivo testing in a porcine burn model demonstrates that these silk-based spray-on coatings, especially when combined with antibiotics, significantly accelerated healing in deep partial-thickness burns compared to standard treatments. This spray system supports rapid and effective performance for emergency medical use, offering an advancement in functional biomaterials.

IntroductionThermal injuries are caused by exposure to a wide variety of agents including heat, electricity, radiation, chemicals, and friction. Early intervention can decrease injury severity by preventing excess inflammation and mitigating burn wound progression for improved healing outcomes. Previous studies have demonstrated that cannabinoids can trigger anti-inflammatory responses and promote wound closure. Therefore, the purpose of this study was to investigate whether a topical application of Noneuphoric Phytocannabinoid Elixir 14 (NEPE14) containing a full complement of phytocannabinoids (< 0.3% delta-9-tetrahydrocannabinol or cannabidiol) and other phytochemicals would mitigate burn wound progression in the treatment of deep partial-thickness burn wounds.MethodsDeep partial-thickness burns were created on the dorsum of four anesthetized pigs and treated with NEPE14, Vehicle control, Silverlon, or gauze. The burns were assessed on postburn days 4, 7, and 14. Assessments consisted of digital photographs, Laser-Speckle imagery (blood perfusion), MolecuLight imagery (qualitative bacterial load), and biopsies for histology and immunohistochemistry (interleukin six and tumor necrosis factor-α).ResultsTopical treatment with NEPE14 significantly (P < 0.001) decreased inflammation (interleukin six and tumor necrosis factor-α) in comparison to control groups. It was also demonstrated that the reduction in inflammation led to mitigation of burn wound progression. In terms of wound healing and presence of bacteria, no statistically significant differences were observed.ConclusionsTopical treatment of deep partial-thickness burns with NEPE14 decreased wound inflammation and mitigated burn wound progression in comparison to control treatments.

Significance: Negative pressure wound therapy (NPWT) has been in practice for decades, proving its utility in many applications, ranging from acutely infected wounds to complex combat wounds and skin grafting. It has been routinely demonstrated that NPWT has superior wound healing outcomes compared with previous standard-of-care therapies. However, the technique involves some challenges related to each of the components that comprise the therapy. The purpose of this article is to highlight the challenges, introduce the recent advancements, and discuss about the future directions in NPWT systems.Recent Advances: New techniques and materials have been developed to improve the currently used NPWT systems with promising results when utilized with appropriate indications. Many advancements have been introduced in modes of negative pressure delivery, pumps, interface dressings, adhesive dressings, and tubing technology.Critical Issues: An optimal NPWT system would avoid the common problems such as failure to deliver negative pressure due to loss of an airtight seal or tissue ingrowth into the interface dressing causing painful dressing changes and bleeding. Other challenges include infection control and patient pain and discomfort that may contribute to noncompliance.Future Directions: Many studies have been performed to evaluate the optimal combination of settings and components in various wounds; however, there is still no clear "best" answer for many specific patient-wound scenarios. Novel and emerging tissue engineering and regenerative medicine approaches could potentially be utilized in the future NPWT systems and thus, this review will discuss some novel ideas for future considerations.

INTRODUCTION:Immediate evacuation of burn casualties can be challenging in austere environments, and it is predicted to be even more difficult in future multi-domain battlespaces against near-peer foes. Therefore, a need exists to treat burn wounds at the point of injury to protect the exposed injury for an extended period. In this study, we compare two commercially available FDA-approved therapies to the current gold standard of care (GSOC), excisional debridement followed by the application of split-thickness skin graft, and the standard for prolonged field care, silver sulfadiazine (SSD) cream. The shelf-stable therapies evaluated were irradiated human skin (IHS) allograft and polylactic acid (PLA). Our objective was to study whether they have the potential capability to reduce the need for evacuation to a burn center for surgical intervention so that the combat power can be preserved in the field. MATERIALS AND METHODS:Sixteen burns (50 cm2) were created on the dorsum of four anesthetized swine. All materials were sterile, but a sterile field was not utilized in order to simulate the prolonged field care setting. The wounds were then treated with PLA, IHS, and SSD cream, and the remaining wounds (designated GSOC) were also treated with SSD cream. On post-operative day (POD) 3, sterile surgical debridement and skin grafting (1:4) were performed on the GSOC wounds. Burn healing was followed for either PODs 10, 14, 21, or 28, wherein one animal was humanely euthanized at each time point; each represented a time point of the healing process. A full-thickness excisional biopsy was taken from each wound immediately after euthanasia to give a cross-section view of the wound edge to edge. Wound healing was determined by the histological analysis of wound re-epithelialization, epidermal thickness, rete ridges, and scar elevation index and macroscopically using noninvasive imaging systems. RESULTS:The PLA and IHS treatments did not need to be reapplied to the wounds during the course of the experiment, unlike SSD, which was reapplied at each assessment time point. In terms of re-epithelialization, on POD 10, IHS and SSD were similar to the GSOC; on POD 14, all treatments were similar; on POD 21, PLA and IHS were similar to SSD; finally, on POD 28, re-epithelialization was similar in all groups. On POD 28, scar elevation index and rete ridges/mm were similar to all groups, and epidermal and dermal thickness for PLA and IHS were similar to GSOC. CONCLUSIONS:This preclinical study demonstrated that the use of the PLA and the IHS dressings resulted in similar outcomes to the GSOC-treated burns in several key metrics of wound healing. These therapies represent a potentially useful tool in current and future battlespaces, where surgical intervention is not possible. The products are lightweight and, more importantly, stable at room temperature for their entire shelf lives. This would allow for easy storage and transport by medical practitioners in the field.

Advancements in the treatment of burns have considerably improved overall survival rates, but they have also highlighted several long-term sequelae related to the injury. Hypertrophic scars can impair function, reduce quality of life, and require multiple procedures as well as physical therapy. The purpose of this study was to investigate the effects of topical application of anti-inflammatory drugs in the treatment of burns. Up to 15 deep-partial thickness burns were created on the dorsum of four anesthetized swine. Subsequently, the burn wounds were randomized to receive amiloride, celecoxib, dexamethasone or minocycline mixed in a hydrogel. Silver sulfadiazine cream and blank hydrogel acted as controls. The animals were followed for 90 days and the wounds were assessed on days 3, 7, 14, 28 and 90 post-burn. Assessments were performed using photographs (macroscopic healing, contraction), laser-speckle imaging (blood perfusion), 3D camera (scarring, pigmentation), and histology (inflammation, burn depth, epidermal maturation). Inflammation was present in all burn wound histology specimens and peaked on day 7 in all groups. Regardless of the treatment the burns progressed and were deeper on day 7 in comparison to day 3. The burns were 50 - 80 % healed by day 14, but no significant differences were observed. No differences in epidermal thickness, rete ridges, contraction, hypopigmentation, or scar elevation were seen on day 90. Topical anti-inflammatories did not significantly decrease inflammation or mitigate burn wound progression in deep partial thickness burns in pigs. Also, no significant differences in wound healing or quality of healing were observed.

Introduction: Prolonged inflammation and infection in burns may cause inadequate healing. Platelet granules contain anti-inflammatory mediators that impact wound healing. Syn-thetic 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 bac-terial 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 w10% in both the SP loaded with gentamicin vesicles and SP with gentamicin mixture groups. Su-perficial 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 signifi-cantly 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. 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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.

Objective: Despite advances in the use of topical and parenteral antimicrobial therapy and the practice of early tangential burn wound excision to manage bacterial load, 60% of the mortality from burns is attributed to bacterial biofilm infection. A low electric field (∼1 V) generated by the novel FDA-cleared wireless electroceutical dressing (WED) was previously shown to significantly prevent and disrupt burn biofilm infection in preclinical studies. Based on this observation, the purpose of this clinical trial was to evaluate the efficacy of the WED dressing powered by a silver-zinc electrocouple in the prevention and disruption of biofilm infection. Approach: A prospective, randomized, controlled, single-center clinical trial was performed to evaluate the efficacy of the WED compared with standard-of-care (SoC) dressing to treat biofilms. Burn wounds were randomized to receive either SoC or WED. Biopsies were collected on days 0 and 7 for histology, scanning electron microscopy (SEM) examination of biofilm, and for quantitative bacteriological analyses. Results: In total, 38 subjects were enrolled in the study. In 52% of the WED-treated wounds, little to no biofilm could be detected by SEM. WED significantly lowered or prevented increase of biofilm in all wounds compared with the pair-matched SoC-treated wounds. Innovation: WED is a simple, easy, and rapid method to protect the wound while also inhibiting infection. It is activated by a moist environment and the electrical field induces transient and micromolar amounts of superoxide anion radicals that will prevent bacterial growth. Conclusion: WED decreased biofilm infection better compared with SoC. The study was registered in clinicaltrials.gov as NCT04079998.

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.

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.

Inaccurate tangential excision of burn eschar can remove viable tissue, potentially delaying healing. An ArF excimer laser operating at 193nm can effectively ablate eschar, without collateral damage to surrounding and underlying healthy tissue.

Introduction Hypertrophic burn scars (HTBSs) remain a significant source of morbidity. Contemporary treatment has evolved to use CO 2 lasers and/or pulse-dye lasers (PDLs) to reduce scar thickness (ST) and erythema. This study seeks to compare treatment efficacy with CO 2 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 CO 2 laser, PDL or CO 2 + 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 CO 2 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 (CO 2 + PDL, P = 0.01; CO 2 , P = 0.02; PDL, P = 0.03). Thin scars (<0.3 cm) showed a reduction in thickness by visit 3 after CO 2 + 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 CO 2 treatment ( P = 0.04), and between visit 2 and 3 for CO 2 + 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 CO 2 + 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 CO 2 , 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.

Abstract Introduction Burn injuries are common to all military conflicts. In combat, eradication and prevention of burn wound infection is complicated by high rates of soft tissue contamination and prolonged delays to definitive stateside care. Furthermore, in the battlefield setting the salvage rate for infected burned extremities is low. Therefore, a simple, easy, non-invasive and rapid method to protect the wound, while also inhibiting infection, would represent a significant advance in the treatment of combat burn wounds. The purpose of this clinical trial was to investigate the efficacy of an FDA approved disposable and easily portable, wireless electroceutical dressing (WED) in the treatment of burn wounds. The hypothesis was that a low electric field generated by the moisture-activated WED will reduce infection load, improve graft survival and take, enhance wound healing and restore skin barrier function of biofilm infected wounds. Methods A phase I, prospective, randomized, controlled clinical trial was performed to evaluate the efficacy of the WED dressing as compared to the standard of care (SoC) dressing to prevent and disrupt biofilms. Subjects were screened from inpatient admissions for traumatic burns >300cm2 in size. In total 38 subjects were enrolled to the study. Subject burn wounds were divided into two parts and randomized to receive either the SoC dressing or the WED dressing. Dressings were changed on day 4, removed on day 7 and the burns were followed for 30 days. Small biopsies were collected on days 4 and 7 for histology, SEM examination of biofilm and for quantitative bacteriological analysis. In addition, non-invasive wound imaging techniques were utilized to study wound healing. Furthermore, Vancouver scar scale and patient observer scar assessment were used to evaluate quality of healing. Results The results showed that at the time of dressing removal, non-grafted burns that were treated with the WED dressing presented statistically significantly less biofilm in comparison to the SoC treated burns (p < 0.05). The results also demonstrated that the WED dressing was more efficient at eradicating biofilm than the SoC dressing. At the time of the dressing removal, biofilm score [0-3] had decreased in 48% of the WED dressing treated burns in comparison to 28% in the SoC treated burns. In terms of wound healing and quality of healing no significant differences were observed between the WED and the SoC dressings. Conclusions This trial demonstrated that the WED dressing was more efficient against biofilm infection than the SoC dressing. In addition, the study concluded that the WED dressing performed equally well as the SoC in terms of burn wound healing.

Abstract Introduction Infection and prolonged inflammation in deep partial-thickness burns can lead to inadequate healing. In addition to their role in hemostasis, activated platelets also contain granules with anti-inflammatory properties which may impact wound healing. However, portability and storage of platelets remain a challenge. Synthetic platelet-mimetics (SPM) avoid these difficulties, but like natural platelets, SPM have vesicles that can transport bioactive agents, such as antibiotics. We sought to evaluate wound healing outcomes in deep partial-thickness burns treated topically with SPM. Methods A total of 30 circular, deep partial-thickness burns were created on the dorsum of 2 porcine models. Each wound measured 5cm in diameter and was standardized using a thermocoupled burn device. Sets of six wounds were randomized into five groups: SPM, gentamicin alone, SPM with gentamicin, a vehicle control (saline), or dry gauze (the standard of care, SOC). Additionally, two separate 5cm diameter circular areas were demarcated to serve as normal skin controls. Wounds were assessed at post-burn days 3, 7, 14, 21, 28, 60 and 90 with a variety of non-invasive imaging and punch biopsies. Treatments were re-applied at each assessment. The primary outcome was the amount of wound re-epithelialization, measured histologically, at post-burn day 28. Secondary outcomes consisted of the percentage of wound contraction, amount of superficial blood flow, and mean bacterial load. Results The amount of wound re-epithelialization in wounds treated with SPM was 96% whereas those treated with the SOC measured only slightly less at 92% (p = 0.56). The percentage of wound contraction was 39% in the SPM with gentamicin group, while in the SOC group contraction was higher at 45% (p = 0.20). Moreover, superficial blood flow in the SPM group was measured to be 168% of normal skin controls, while wounds in the SPM with gentamicin group were slightly lower at 160%, and in wounds treated with the SOC blood flow was 110% of normal skin controls (p = 0.27). The mean bacterial load in each group was measured at post-burn day 3 and notably consisted of bacterial load being the lowest in wounds treated with gentamicin alone at 17/100, meanwhile in wounds treated with the SOC or those in the SPM with gentamicin group, mean bacterial loads were significantly higher at 43/100 and 47/100, respectively (p = 0.02). Conclusions SPM applied to deep partial-thickness burns did not significantly improve measured outcomes over the SOC. Although numerical improvements were shown in all measured outcomes, no significant differences were noted. The theoretical and observed potential for SPM to improve wound healing deserves additional evaluation in larger preclinical studies.

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 rho 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.

Abstract Introduction Combat-related burn wounds can be caused by exposure to a wide variety of agents including heat, electricity, radiation, chemicals, and friction. Early intervention can decrease injury severity by preventing excess inflammation and improve long term healing outcomes. In recent years, numerous studies have demonstrated that cannabinoids can trigger anti-inflammatory responses and promote wound closure. This study investigates whether a proprietary, non-euphoric, topical cannabinoid formulation (NEPE-14) facilitates burn wound healing when compared with Silverlon®, the military standard of care for burns incurred while in the field. Methods Forty-eight deep-partial thickness burns were created on the dorsum of four anesthetized swine (Sus scrofa domestica) using a thermocoupled burn device at 100°C. One hour following burn, biopsies from each site were collected and either NEPE-14, NEPE-14 Vehicle Control, Silverlon®, or dry gauze was placed on the wound. Wounds were assessed on post-burn days (PBD) 3, 7 and 14. Assessments consisted of digital photographs, Laser-Speckle imagery (blood perfusion), FLIR imagery, MolecuLight® imagery and biopsies for histology and immunohistochemistry. Results By PBD 14, no significant differences in re-epithelialization or contraction were observed between any of the tested treatment groups. Silverlon® had the highest percent re-epithelialization with 42%, and the Vehicle control has the lowest percent re-epithelialization with 28 %. Both NEPE-14 and dry gauze performed intermediately with 29% and 34% re-epithelialization, respectively. On PBD 14, the wounds of the NEPE-14 treated wounds contracted 8%, the vehicle control 7%, Silverlon® treated wounds 10%, and gauze treated wounds showed 9% contraction compared with the original wound area. Blood perfusion at PBD 14 indicated that NEPE-14 treated wounds had the lowest amount of observed blood flow and the gauze treated wounds contained the highest amount of observed blood flow. However, no statistically significant differences were observed. Conclusions No statistically significant results were seen between treatment groups for contraction, re-epithelialization, or blood perfusion. Although not significant, blood perfusion results indicate that NEPE-14 treatment had the lowest amount of blood flow, which can be seen as an indicator of healthy underlying tissue and a wound re-epithelializing. At PBD 14, all treatment groups had slightly contracted after increasing in wound area on PBD 3 and 7, which is a pattern seen in similar burn injury studies. We are currently awaiting histological analysis to strengthen our re-epithelialization results and evaluate burn wound progression.

Abstract Introduction Burns are common injuries in the battlefield. Given austere environments, prolonged field care (PFC) is often necessary. 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) dressings with field-deployable potential. Methods Deep-partial thickness burns (1" diameter) were created on the dorsum of 3 anesthetized pigs utilizing a thermocoupled burn device at 100°C for 15s. Non-surgical debridement was done 1-h post-burn creation and either an OTS dressing or standard-of-care (SOC) treatment (Silver Sulfadiazine) was applied to the wound in order to simulate a PFC environment. OTS dressings were randomized and included irradiated sterile human skin allograft (ISHSA), alloplastic absorbable skin substitute (AASS), and synthetic polyurethane dermal matrix (SPDM). 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 (SEI), and colony forming units (CFU). Results No statistically significant differences in burn wound progression were seen on days 3 and 7 for the ISHSA or SPDM and the SOC. The differences between the AASS and the SOC were statistically significant on both days (p≤0.05). Day 21 re-epithelialization results for the ISHSA, AASS, SPDM and SOC treated wounds were 30%, 85%, 95%, and 78% re-epithelialized, respectively. The difference between the AASS and the SOC was statistically significant (p≤0.05). Results showed that by day 28, wound contraction for the ISHSA, AASS, SPDM and SOC treated wounds were 65%, 80%, 82%, and 78%, respectively. No statistically significant differences in wound contraction were seen for any of the OTS dressings and the SOC. SEI showed no statistically significant difference in scar hypertrophy between the OTS dressings and the SOC on day 28. CFU results showed no statistically significant differences between the OTS dressings and the SOC on days 3 and 7. Conclusions Three OTS dressings were compared to the SOC for use in the PFC setting. Generally, all the dressings performed well when compared to the SOC in terms of burn wound progression, re-epithelialization, wound contraction, SEI, and CFU. Although significant differences in burn progression and re-epithelialization for burns treated with AASS were seen. In the future, we hope to continue to discover and test various OTS dressings to determine their appropriateness for use in the PFC setting.

Abstract Introduction Skin grafting of poorly vascularized wound beds, (e.g. exposed fascia, tendon, or bone) is often a multi-stage procedure, resulting in persistent open wounds and long-term complications such as scarring and contracture. Single-stage skin replacement could mitigate these downsides. Here we present the addition of topical nutrients and negative-pressure wound therapy (NPWT) + saline instill to improve graft take, and a case report of treatment of a non-healing wound in a single-stage procedure. Methods Ex vivo, STSGs (12/1000ths in) were harvested from swine (Sus scrofa domestica) post-euthanasia and transferred into wells with distilled water, PBS, Tyrode’s Buffer, high (4.5g/L) and low (2g/L) glucose DMEM, EpiLife, or William’s E (WE) media for 7 days, followed by performance of biochemical analyses and immunohistochemistry. In vivo, 20 full-thickness 5cm-diameter excisional wounds on the dorsum of two anesthetized swine were treated with dermal substitutes (DS, 0.4mm, 0.8mm, 1.2mm, or 1.6mm thickness), STSG, and NPWT with or without intermittent saline instill (3x daily, 300mL, 15-minute soak). Re-epithelialization was assessed at day 7 and 14. Lastly, a chronic 800cm2 left knee wound was treated with NPWT + instill (every 3.5 hours, 80mL, 10-minute soak, 3-day duration) over a 12/1000ths inch STSG. Results DMEM with high glucose (DMEM-HG) and WE produced the most lactic acid and enzymatic carbonate. Lactate dehydrogenase activity was lowest with WE. DMEM-HG had the highest glucose consumption but the most unconsumed glucose, with WE resulting in the next highest amount. Immunohistochemistry showed DMEM-HG or WE had the most dividing and least dying cells. In the porcine model, DS of 0.8mm, 1.2mm, and 1.6mm thicknesses inhibited graft take significantly (p< 0.01, p=0.02, p< 0.01, respectively) for all NPWT alone wounds. Addition of saline instill showed significant improvement in graft take (p=0.03) for 0.8mm DS wounds. 1.2mm and 1.6mm DS wounds continued to show significantly decreased graft take (p=0.03 and p=0.02, respectively). All 0.4mm DS wounds performed similar to control. Clinically, following NPWT removal on post-op day 3, almost complete STSG take was observed without exudate, pus, or malodor within the wound bed. Conclusions While additional studies are ongoing to determine the optimal nutrient supplementation, WE performed the best overall thus far. In vivo, 0.8mm DS created a successful model of a poorly vascularized wound bed, as NPWT + instill overcame this thickness. The novel use of NPWT + instill treatment over STSG clinically shows promise to improve graft take in the future.