670 Delayed Enzymatic Debridement of Burn Wounds using the Proteolytic Gel SN514

2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S191-S192
Author(s):  
Angela R Jockheck-Clark ◽  
Randolph Stone ◽  
Michelle Holik ◽  
Lucy Schaffer ◽  
Shanmugasundaram Natesan ◽  
...  

Abstract Introduction Thermal burns account for 5–10% of casualties sustained in present-day conflicts and are expected to be one of the most common wounds to occur in future conflicts. In prolonged field care (PFC) situations, medical evacuation could be delayed for days. During this time, burn wounds can become infected, detrimentally impact neighboring tissue, and cause systemic immune responses. Therefore, it is essential to test and evaluate non-surgical debridement agents that could be implemented prior to reaching a Role 3 military treatment facility. This work details how the proprietary proteolytic gel SN514 impacts burn debridement when applied within a PFC-like timeline. SN514 contains an enzyme formulation that is thermostable, easy to apply, and selectively degrades non-viable tissue in vitro and in vivo. Methods Deep-partial thickness contact burns were created using an established porcine model and covered with gauze or an antimicrobial incise drape. Four days later, the burns were treated with one of five treatments: 0.2% SN514, 0.8% SN514, a vehicle control, gauze, or an antimicrobial silver dressing. Treatments were re-applied every 24 hours for 72 to 96 hours. The effects of the treatment regiments were compared histologically. Biopsies were also taken to monitor bacterial contamination levels. Results Burns treated with SN514 were partially debrided and visually distinct from those treated with gauze, the silver dressing, or the vehicle control. Preliminary analyses suggest that SN514-treated burns that had been covered with “dry” gauze had a much lower debridement efficiency than those treated with the incise drape. This suggests that SN514 debridement efficiency may depend on the presence of a moist eschar. Preliminary analyses also suggest that there was little difference in burn wound bacterial counts among the five treatment groups. Conclusions SN514 is able to debride burns that experienced delayed treatment, without any evidence of harm to the surrounding tissue or evidence of exacerbating the original burn injury. SN514-treated wounds displayed little to no blood loss and did not increase burn wound infection levels compared to wounds treated with gauze or an antimicrobial silver dressing.

Polymers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 3116
Author(s):  
Thien Do ◽  
Tien Nguyen ◽  
Minh Ho ◽  
Nghi Nguyen ◽  
Thai Do ◽  
...  

(1) Background: Wounds with damages to the subcutaneous are difficult to regenerate because of the tissue damages and complications such as bacterial infection. (2) Methods: In this study, we created burn wounds on pigs and investigated the efficacy of three biomaterials: polycaprolactone-gelatin-silver membrane (PCLGelAg) and two commercial burn dressings, Aquacel® Ag and UrgoTulTM silver sulfadiazine. In vitro long-term antibacterial property and in vivo wound healing performance were investigated. Agar diffusion assays were employed to evaluate bacterial inhibition at different time intervals. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time-kill assays were used to compare antibacterial strength among samples. Second-degree burn wounds in the pig model were designed to evaluate the efficiency of all dressings in supporting the wound healing process. (3) Results: The results showed that PCLGelAg membrane was the most effective in killing both Gram-positive and Gram-negative bacteria bacteria with the lowest MBC value. All three dressings (PCLGelAg, Aquacel, and UrgoTul) exhibited bactericidal effect during the first 24 h, supported wound healing as well as prevented infection and inflammation. (4) Conclusions: The results suggest that the PCLGelAg membrane is a practical solution for the treatment of severe burn injury and other infection-related skin complications.


Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1153
Author(s):  
Verena Schneider ◽  
Daniel Kruse ◽  
Ives Bernardelli de Mattos ◽  
Saskia Zöphel ◽  
Kendra-Kathrin Tiltmann ◽  
...  

Burns affect millions every year and a model to mimic the pathophysiology of such injuries in detail is required to better understand regeneration. The current gold standard for studying burn wounds are animal models, which are under criticism due to ethical considerations and a limited predictiveness. Here, we present a three-dimensional burn model, based on an open-source model, to monitor wound healing on the epidermal level. Skin equivalents were burned, using a preheated metal cylinder. The healing process was monitored regarding histomorphology, metabolic changes, inflammatory response and reepithelialization for 14 days. During this time, the wound size decreased from 25% to 5% of the model area and the inflammatory response (IL-1β, IL-6 and IL-8) showed a comparable course to wounding and healing in vivo. Additionally, the topical application of 5% dexpanthenol enhanced tissue morphology and the number of proliferative keratinocytes in the newly formed epidermis, but did not influence the overall reepithelialization rate. In summary, the model showed a comparable healing process to in vivo, and thus, offers the opportunity to better understand the physiology of thermal burn wound healing on the keratinocyte level.


2017 ◽  
Vol 99 (6) ◽  
pp. 432-438 ◽  
Author(s):  
JE Greenwood

The skin graft was born in 1869 and since then, surgeons have been using split skin grafts for wound repair. Nevertheless, this asset fails the big burn patient, who deserves an elastic, mobile and robust outcome but who receives the poorest possible outcome based on donor site paucity. Negating the need for the skin graft requires an autologous composite cultured skin and a material capable of temporising the burn wound for four weeks until the composite is produced. A novel, biodegradable polyurethane chemistry has been used to create two such products. This paper describes the design, production, optimisation and evaluation of several iterations of these products. The evaluation has occurred in a variety of models, both in vitro and in vivo, employing Hunterian scientific principles, and embracing Hunter’s love and appreciation of comparative anatomy. The process has culminated in significant human experience in complex wounds and extensive burn injury. Used serially, the products offer robust and elastic healing in deep burns of any size within 6 weeks of injury.


2017 ◽  
Vol 61 (5) ◽  
Author(s):  
Judith Steenbergen ◽  
S. Ken Tanaka ◽  
Lynda L. Miller ◽  
Stephanie A. Halasohoris ◽  
Jeremy R. Hershfield

ABSTRACT The in vitro activity and in vivo efficacy of omadacycline (OMC) were evaluated against the causative pathogens of anthrax and plague, Bacillus anthracis and Yersinia pestis, respectively. MICs of OMC were determined by broth microdilution according to CLSI guidelines for 30 isolates each of Y. pestis and B. anthracis. The in vivo efficacy of omadacycline was studied at a range of dosages in both a postexposure prophylaxis (PEP) murine model of anthrax and plague as well as in a delayed treatment model of inhalational anthrax. Omadacycline was active in vitro against Y. pestis (MIC90 of 1 μg/ml) and B. anthracis (MIC90 of 0.06 μg/ml). Omadacycline was less active in vitro than ciprofloxacin (CIP) against Y. pestis (CIP MIC90 of 0.03 μg/ml) but was more potent in vitro against B. anthracis (CIP MIC90 of 0.12 μg/ml). In the mouse model of infection, the survival curves for all treatment cohorts differed significantly from the vehicle control (P = 0.004). The median survival for the vehicle-treated controls was 6 days postchallenge, while all antibiotic-treated mice survived the entire study. Omadacycline treatment with 5, 10, or 20 mg/kg of body weight twice daily for 14 days had significant efficacy over the vehicle control in the treatment of aerosolized B. anthracis. Additionally, for postexposure prophylaxis treatment of mice infected with Y. pestis, the survival curves for omadacycline (40 mg/kg twice daily), ciprofloxacin, and doxycycline cohorts differed significantly from the vehicle control (P < 0.0001). Omadacycline is potent and demonstrates efficacy against both B. anthracis and Y. pestis. The well-characterized oral and intravenous pharmacokinetics, safety, and tolerability warrant further assessment of the potential utility of omadacycline in combating these serious biothreat organisms.


Pharmaceutics ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 883
Author(s):  
Mateusz Stojko ◽  
Jakub Włodarczyk ◽  
Michał Sobota ◽  
Paulina Karpeta-Jarząbek ◽  
Małgorzata Pastusiak ◽  
...  

The selection of dressing is crucial for the wound healing process. Traditional dressings protect against contamination and mechanical damage of an injured tissue. Alternatives for standard dressings are regenerating systems containing a polymer with an incorporated active compound. The aim of this research was to obtain a biodegradable wound dressing releasing propolis in a controlled manner throughout the healing process. Dressings were obtained by electrospinning a poly(lactide-co-glycolide) copolymer (PLGA) and propolis solution. The experiment consisted of in vitro drug release studies and in vivo macroscopic treatment evaluation. In in vitro studies released active compounds, the morphology of nonwovens, chemical composition changes of polymeric material during degradation process, weight loss and water absorption were determined. For in vivo research, four domestic pigs, were used. The 21-day experiment consisted of observation of healing third-degree burn wounds supplied with PLGA 85/15 nonwovens without active compound, with 5 wt % and 10 wt % of propolis, and wounds rinsed with NaCl. The in vitro experiment showed that controlling the molar ratio of lactidyl to glycolidyl units in the PLGA copolymer gives the opportunity to change the release profile of propolis from the nonwoven. The in vivo research showed that PLGA nonwovens with propolis may be a promising dressing material in the treatment of severe burn wounds.


2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Nitin K. Upadhyay ◽  
Ratan Kumar ◽  
M. S. Siddiqui ◽  
Asheesh Gupta

The present investigation was undertaken to evaluate the healing efficacy of lyophilized aqueous leaf extract of Sea buckthorn (Hippophae rhamnoidesL., family Elaeagnaceae) (SBT) and to explore its possible mechanism of action on experimental burn wounds in rats. The SBT extract, at various concentrations, was applied topically, twice daily for 7 days. Treatment with silver sulfadiazine (SSD) ointment was used as reference control. The most effective concentration of the extract was found to be 5.0% (w/w) for burn wound healing and this was further used for detailed study. The SBT-treated group showed faster reduction in wound area in comparison with control and SSD-treated groups. The topical application of SBT increased collagen synthesis and stabilization at the wound site, as evidenced by increase in hydroxyproline, hexosamine levels and up-regulated expression of collagen type-III. The histological examinations and matrix metalloproteinases (MMP-2 and -9) expression also confirmed the healing efficacy of SBT leaf extract. Furthermore, there was significant increase in levels of endogenous enzymatic and non-enzymatic antioxidants and decrease in lipid peroxide levels in SBT-treated burn wound granulation tissue. The SBT also promoted angiogenesis as evidenced by anin vitrochick chorioallantoic membrane model andin vivoup-regulated vascular endothelial growth factor (VEGF) expression. The SBT leaf extract had no cytotoxic effect on BHK-21 cell line. In conclusion, SBT aqueous leaf extract possesses significant healing potential in burn wounds and has a positive influence on the different phases of wound repair.


2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Jia-Ru Wu ◽  
Yu-Chu Lu ◽  
Sung-Jen Hung ◽  
Jung-Hsing Lin ◽  
Kai-Chih Chang ◽  
...  

“San Huang Powder,” a nonsterile milled herb powder, is frequently used to treat burn wounds in traditional Chinese herbal medicine. However, treating a wound with a nonsterile dressing or reagent is not compatible with the current guidelines in modern medicine. Therefore, we investigated the bactericidal and anti-inflammatory activities of four herb extracts used in “San Huang Powder” in vitro. Meanwhile, an in vivo porcine model with superficial second-degree burns was used for the experiments since the size and skin composition of pigs are the closest to that of the human body. The minimal bactericidal concentration (MBC) of the herb extracts was determined. The in vitro assay indicated that Rhubarb and Phellodendron bark extracts decreased the levels of inflammatory cytokines, IL-8, and GM-CSF on LPS-induced HMEC-1 cells. In accordance with this result, the histopathological evaluation results showed that the efficacy of “San Huang Powder” containing both herb materials was much better than the group without Rhubarb. Our results not only provide a basis to understand why “San Huang Powder” has been used to clinically treat wounds without sterilization directly since ancient times but also show the advantages of using multiple herb materials simultaneously on wound sites to prevent infection during treatment. Rhubarb is the recommended ingredient involved in the preparation of “San Huang Powder” to ensure the healing efficacy of burn wounds.


2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Fang Wu ◽  
Difei Bian ◽  
Yufeng Xia ◽  
Zhunan Gong ◽  
Qian Tan ◽  
...  

Centella asiaticaherbs have been prescribed as a traditional medicine for wound healing in China and Southeast Asia for a long time. They contain many kinds of triterpenoid compounds, mainly including glycosides (asiaticoside and madecassoside) and corresponding aglycones (asiatic acid and madecassic acid). To identify which is the major active constituent, a comprehensive and comparative study of these compounds was performed.In vitro, primary human skin fibroblasts, originating from healthy human foreskin samples, were treated with various concentrations of asiaticoside, madecassoside, asiatic acid, and madecassic acid, respectively. Cell proliferation, collagen synthesis, MMP-1/TIMP-1 balance, and TGF-β/Smad signaling pathway were investigated.In vivo, mice were orally administered with the four compounds mentioned above for two weeks after burn injury. The speed and quality of wound healing, as well as TGF-β1levels in skin tissues, were examined. Interestingly, in contrast to prevalent postulations, asiaticoside and madecassoside themselves, rather than their corresponding metabolites asiatic acid and madecassic acid, are recognized as the main active constituents ofC. asiaticaherbs responsible for burn wound healing. Furthermore, madecassoside is more effective than asiaticoside (P=0.0446for procollagen type III synthesisin vitro,P=0.0057for wound healing speed, andP=0.0491for wound healing patternin vivo, correspondingly).


2020 ◽  
Vol 41 (Supplement_1) ◽  
pp. S79-S80
Author(s):  
Jahnabi Roy ◽  
Lori Estes ◽  
Robert J Christy ◽  
Hitesh Handa ◽  
Shanmugasundaram Natesan

Abstract Introduction The future of multi-domain battlefield operation requires wound dressings to prevent infection at the point of injury. Majority of antimicrobial agents only target wound infection while other healing events are left to their natural fates. Nitric oxide (NO) acts against both gram-positive and -negative bacteria and has the potential to positively affect wound healing. In this study we have developed a novel wound dressing integrated with a NO donor - S-nitroso- glutathione (GSNO) in a hybrid formulation of alginate and poly(vinyl alcohol) (PVA) to prevent/treat burn wound infection. Methods The NO releasing wound dressing was fabricated using PVA, alginate, and glycerol, crosslinked with CaCl2 incorporating GSNO. Thereafter, release kinetics were measured up to 4 days. The antibacterial efficacy was determined against both P. aeruginosa and S. aureus. Then the biocompatibility of the NO wound dressing was assessed using in vitro fibroblast proliferation and wound healing assay. Finally, the efficacy of the wound dressing was assessed in vivo using a 3-cm diameter porcine burn wound infection model. Results The Alginate-PVA-GSNO dressing showed a desired physiological level NO flux of 4.42 × 10-10 mol cm-2 min-1 for 72 hours. Alginate−PVA−GSNO dressings showed ~3 log reduction in S. aureus and ~2 log reduction in P. aeruginosa CFU/mg when compared to control. The NO-releasing dressing improved fibroblast proliferation and migration resulting in complete closure of the wound within 48 h in vitro. The safety and efficacy of NO-releasing dressing were successfully established in the both P. aeruginosa and S. aureus infected porcine burn wounds. Histological assessments are carried out to determine the effect of NO-releasing dressing on overall healing process. Conclusions This study shows Alginate−PVA-GSNO wound dressing provides antimicrobial and wound healing properties in vitro. Preliminary in vivo wound healing studies established the safety and efficacy profile of NO-releasing dressing to treat burn wounds. Applicability of Research to Practice An easy to apply, field deployable and effective antimicrobial wound dressing is still a major requisite for combat burn wounds. NO delivering alginate-PVA based wound dressing may be an ideal candidate to inhibit infection as well as promote the wound healing process.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Erfan Dashtimoghadam ◽  
Farahnaz Fahimipour ◽  
Andrew N. Keith ◽  
Foad Vashahi ◽  
Pavel Popryadukhin ◽  
...  

AbstractCurrent materials used in biomedical devices do not match tissue’s mechanical properties and leach various chemicals into the body. These deficiencies pose significant health risks that are further exacerbated by invasive implantation procedures. Herein, we leverage the brush-like polymer architecture to design and administer minimally invasive injectable elastomers that cure in vivo into leachable-free implants with mechanical properties matching the surrounding tissue. This strategy allows tuning curing time from minutes to hours, which empowers a broad range of biomedical applications from rapid wound sealing to time-intensive reconstructive surgery. These injectable elastomers support in vitro cell proliferation, while also demonstrating in vivo implant integrity with a mild inflammatory response and minimal fibrotic encapsulation.


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