Topical Noneuphoric Phytocannabinoid Elixir 14 Reduces Inflammation and Mitigates Burn Progression.

INTRODUCTION: Thermal 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. METHODS: Deep 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). RESULTS: Topical 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. CONCLUSIONS: Topical treatment of deep partial-thickness burns with NEPE14 decreased wound inflammation and mitigated burn wound progression in comparison to control treatments.

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.

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.

Characterization of a Human Platelet Lysate-Loaded Keratin Hydrogel for Wound Healing Applications In Vitro.

One of the promising approaches to facilitate healing and regenerative capacity includes the application of growth-factor-loaded biomaterials. Human platelet lysate (hPL) derived from platelet-rich plasma through a freeze-thaw process has been used as a growth factor rich therapeutic in many regenerative applications. To provide sustained local delivery of the hPL-derived growth factors such as epidermal growth factor (EGF), the hPL can be loaded into biomaterials that do not degrade rapidly in vivo. Keratin (KSO), a strong filamentous protein found in human hair, when formulated as a hydrogel, is shown to sustain the release of drugs and promote wound healing. In the current study, we created a KSO biomaterial that spontaneously forms a hydrogel when rehydrated with hPL that is capable of controlled and sustained release of pro-regenerative molecules. Our study demonstrates that the release of hPL is controlled by changing the KSO hydrogel and hPL-loading concentrations, with hPL loading concentrations having a greater effect in changing release profiles. In addition, the 15% KSO concentration proved to form a stable hydrogel, and supported cell proliferation over 3 days without cytotoxic effects in vitro. The hPL-loaded keratin hydrogels show promise in potential applications for wound healing with the sustained release of pro-regenerative growth factors with easy tailoring of hydrogel properties.