Topical Wound Research Articles

A review of the Turned-down Onto Pericapsular-tissue Hemisectioned Amputated Toe (TOPHAT) flap for wound coverage during ray amputations of the toes

IntroductionExposure of the adjacent Metatarsal-Phalangeal Joint (MTPJ) commonly occurs after application of Topical Negative Pressure Wound Therapy (TNPWT) for a ray amputation wound. This is due to mechanical soft tissue erosion or trauma to the adjacent digital artery from direct pressure effect. This results in toe gangrene requiring a ray amputation and ultimately a larger wound bed. We describe the use of the Turned-down Onto Pericapsular-tissue Hemisectioned Amputated Toe (TOPHAT) flap – a filleted toe flap to protect the adjacent MTPJ capsule combined with a novel Negative Pressure Wound Therapy with instillation and dwell-time (NPWTi-d) dressing technique. The flap protects the adjacent joint capsule and reduces the wound burden whilst allowing the wound to benefit from TNPWT, thereby accelerating wound healing. Material and methodsA retrospective review was conducted of patients with toe gangrene requiring ray amputation that underwent the TOPHAT flap on in our institution from 2019 and 2020. Complications such as wound dehiscence, hematoma, flap necrosis and secondary infection were recorded. Other outcomes recorded were time taken to final skin grafting and time taken for complete wound epithelialization. Results9 patients underwent treatment with the TOPHAT flap. 2 patients had flap necrosis. 7 patients progressed to definitive skin coverage with skin grafting. One patient subsequently had progressive arterial disease despite successful skin grafting and required above knee amputation. The mean time to final skin grafting and complete wound epithelialization was 49.5 days and 107.5 days respectively. All patients were satisfied with the outcomes and were able to return to their pre-morbid function. ConclusionsThe TOPHAT flap has a consistent vascular supply that provides durable soft tissue coverage. It is a robust and easily reproducible technique to accelerate wound healing after ray amputations even in patients with peripheral vascular disease.

613 Bacteria induce skin regeneration via IL-1β signaling

Environmental factors that enhance regeneration are largely unknown. We hypothesized that skin bacteria modulate regeneration. Here, we assessed low, medium, and high levels of bacterial burden in wound healing and Wound Induced Hair follicle Neogenesis (WIHN), a rare adult organogenesis model. WIHN levels and stem cell markers indeed correlated with bacterial counts, being lowest in germ free (GF) (fold= -17.9, n=13, p=1.9X10-6), intermediate in conventional specific pathogen free (SPF), and highest even in mice infected with pathogenic Staphylococcus aureus (fold= 3.3, n=12, p=7.5X10-5). We identified IL-1β and keratinocyte-dependent IL-1R-MyD88 signaling as necessary and sufficient for bacteria to promote regeneration. Finally, in a small clinical trial, we found that a topical broad-spectrum antibiotic slowed skin wound healing. These results demonstrate a novel role for IL-1β to control morphogenesis and counter conventional notions that infection inhibits regeneration with a need for full sterility of small wounds.

671 Burn Wound Healing Effect of Bromelain-loaded Chitosan Nanofibers

Abstract Introduction Bromelain is a mixture of proteolytic enzymes present in all tissues of pineapple (Ananas comosus). It is known as an efficient debriding agent in burn treatment and has been shown to effectively and selectively debride burn eschar. In this study, the efficiency of bromelain-loaded chitosan nanofibers for burn wounds repair was investigated in animal model. Methods Chitosan nanofibers containing bromelain were prepared by electrospinning method. The physicochemical characteristics of the synthetized nanofibers, release profile and activity of bromelain loaded in nanofibers were evaluated. The burn healing effect of bromelain-loaded nanofibers were studied in the induced burn wounds in rats for 21 days. The efficacy of treatment was assessed by evaluating changes in wound closer and histological analysis at different time point. Results Successful electrospinning of bromelain-loaded chitosan nanofibers resulted in uniform and bead-less nanofibers which released bromelain up to 48h. The formulation kept bromelain enzyme activity after 6-month storage at 4 °C and did not show any cytotoxicity on human dermal fibroblasts. Moreover, in vivo study in a rat burn model confirmed the safety and efficacy of applying bromelain loaded nanofibers in burn wound healing when a significant improve in wound closer was observed in bromelain loaded group and histopathological studies showed more effects on re-epithelialization, debridement and more reduction of necrosis compared to chitosan alone. Conclusions Together, these results suggest that bromelain chitosan nanofiber possesses great wound healing activity and could be considered as an effective natural topical burn wound healing treatment.

139 Topical Exogenous Nutrient and Saline Supplementation to Improve Skin Graft Survival: From Lab to Operating Room

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.

Developmental exposure to silver nanoparticles leads to long term gut dysbiosis and neurobehavioral alterations

Due to their antimicrobial properties, silver nanoparticles (AgNPs) are used in a wide range of consumer products that includes topical wound dressings, coatings for biomedical devices, and food-packaging to extend the shelf-life. Despite their beneficial antimicrobial effects, developmental exposure to such AgNPs may lead to gut dysbiosis and long-term health consequences in exposed offspring. AgNPs can cross the placenta and blood–brain-barrier to translocate in the brain of offspring. The underlying hypothesis tested in the current study was that developmental exposure of male and female mice to AgNPs disrupts the microbiome–gut–brain axis. To examine for such effects, C57BL6 female mice were exposed orally to AgNPs at a dose of 3 mg/kg BW or vehicle control 2 weeks prior to breeding and throughout gestation. Male and female offspring were tested in various mazes that measure different behavioral domains, and the gut microbial profiles were surveyed from 30 through 120 days of age. Our study results suggest that developmental exposure results in increased likelihood of engaging in repetitive behaviors and reductions in resident microglial cells. Echo-MRI results indicate increased body fat in offspring exposed to AgNPs exhibit. Coprobacillus spp., Mucispirillum spp., and Bifidobacterium spp. were reduced, while Prevotella spp., Bacillus spp., Planococcaceae, Staphylococcus spp., Enterococcus spp., and Ruminococcus spp. were increased in those developmentally exposed to NPs. These bacterial changes were linked to behavioral and metabolic alterations. In conclusion, developmental exposure of AgNPs results in long term gut dysbiosis, body fat increase and neurobehavioral alterations in offspring.

A Technique for Absolute Haemostasis

Background . Acute bleeding of parenchymal organs in blunt soft tissue traumas, sharp force injuries, bullet and shrapnel wounds is often life­threatening due to hypoxia combined with haemorrhagic shock. Hypoxia and haemorrhagic shock develop due to a continuous blood outflow from multiple gaping non­contractile blood vessels. A safe and effective organ­preserving surgery in parenchymal haemorrhage has not been developed to date. Materials and methods . A survey of scientific and patent literature has been conducted on techniques for parenchymal bleeding haemostasis based on topical cooling and heating­aided surgical interventions. Sources were mined in the Espacenet, Google Patent, eLibrary, Google Scholar, Web of Science, Scopus and PubMed databases. Results and discussion . An original method for parenchymal bleeding arrest was proposed in Russia at the end of the 20th century. The method is based on a safe transverse organ compression at vascular trunk to provide safe ischemia of the injured organ portion and using topical wound heating to trigger blood clotting. The compression is done with a surgical tool usually used for a gentle gastric or gut constriction. Mechanical compression is applied at a force that ensures a complete constriction of the organ’s blood vessels arresting blood outflow from gaping vessels of the wound. Local hyperthermia of the wound surface is provided by a solid sterile object application with a smooth and slippery surface at +42–45 °C. Ischaemia and heating of the bleeding part of parenchymal organ are halted in 5–15 min. An adequacy criterion for the method is absolute haemostasis. Conclusion . An immediate arrest of blood supply to the wound surface complemented by heating at +42–45°С untill absolute haemostasis has been shown a sole rapid haemostatic technique effective in all forms of parenchymal haemorrhage. The entire peritoneal surface irrigation with 50% glycerol of pH 7.4 at +37–42 °С is advised to prevent postoperative abdominal adhesions at completion of surgery.

Fuzzy rule-based model for outlier detection in a Topical Negative Pressure Wound Therapy Device

This paper proposes a novel method for offline outlier detection in nonlinear dynamical systems using an input–output dataset of a Topical Negative Pressure Wound Therapy Device, NPWT. The fundamental characteristics of an NPWT describe a chaotic system whose states vary over time and may result in unpredictable and possibly anomalous divergent behavior in the presence of perturbations and other unmodeled system dynamics, despite a quasi-stable controller. Bacterial Memetic Algorithm, BMA, is used to generate fuzzy rule-based models of the input–output dataset. The error definition in the fuzzy rule extraction features a novel application of the Canberra Distance. The optimal number of rules for identifying the outliers, validated against both artificial and real system datasets, is calculated from the sample of inferred fuzzy models. The optimal number of rules is two in both cases based on the maximum average-error-drop. Using three or more rules results in better error performance; however, the algorithm learns the nuances of the outlier patterns instead. Novel methods for creating the outlier list and determining the optimal number of rules for the outlier detection problem are proposed.

Prescribed exercise regimen versus usual care and hypochlorous acid wound solution versus placebo for treating venous leg ulcers: study protocol for a randomised controlled trial (Factorial4VLU)

IntroductionCompression is the mainstay of treatment for venous leg ulcers (VLUs) and there are few effective adjuvant treatments. There is only observational evidence supporting the use of hypochlorous acid (HOCl)...

К‐carrageenan/Na‐alginate wound dressing with sustainable drug delivery properties

Despite К‐carrageenan (КC) merits as a biopolymer convenient for versatile medical applications, it exhibits limitations in processability and reactivity. To overcome such limitations, КC, in this study, was blended with Na‐alginate (SA) in different weight ratios and cross‐linked with potassium ions. The swelling and gel fraction properties demonstrate that the cross‐linked КC/SA matrix of a ratio of 66.7% is suitable to be applied as a topical wound dressing. Characterization of the prepared КC/SA/K+ gel film was performed using scanning electron microscope as well as FTIR. The in vitro release of chloramphenicol as a drug model from the nominated loaded film at pH 4.1 reached a constant value after about 3 hours. To enhance the antibacterial properties of the КC/SA/K+ film, silver nanoparticles as bioactive additive were loaded in combination with chloramphenicol, and the antibacterial properties of the loaded film were evaluated, and showed high antibacterial properties against both Gram‐positive and Gram‐negative bacteria.

Asiaticoside and polylysine-releasing collagen complex for effectively reducing initial inflammatory response using inflamed induced in vitro model

Inflammation is a significant clinical problem that can arise from full-thickness wounds or burn injuries or microbial disease. Although topical wound healing substances could promote rapid wound healing by preventing or reducing the consequences of inflammation, there still remains a need for the development of novel substances that can effectively reduce infection and inflammation in initial wound healing phase. In this study, collagen was combined with asiaticoside (AS) and ε-poly-l-lysine (εPLL). This complex was then applied to in vitro models of infection and inflammation. Collagen-AS coatings inhibited the initial inflammatory response to LPS through a sustained release of AS, and a bilayer coating-εPLL showed a notable antimicrobial effect using microbial infection test. In this study, we determined whether asiaticoside and εPLL have anti-inflammatory and antibacterial effects through different mechanisms. Collectively, the collagen-AS/εPLL complex indicated great therapeutic potentials for accelerate wound healing and the complex may be considered as a artificial scaffold substitute product to full-thickness wound healing.

Phytochemical profile, acute dermal toxicity and wound healing activity of Guettarda calyptrata A. Rich

Introduction: The leaves and barks of Guettarda calyptrata have been attributed to the property of healing wounds on the skin and mucous membranes. However, the scientific information about the phytochemical composition and biological properties is scarce. This research evaluates the chemical composition, dermal safety, and wound healing properties of a hydroalcoholic extract of G. calyptrata. Methods: Hydroalcoholic extract of G. calyptrata was obtained from leaves. The phytochemical profile was analyzed by phytochemical screening, thin layer chromatography, high performance liquid chromatography (HPLC), and quantification of phenols and flavonoids by Folin-Ciocalteu and aluminum chloride methods, respectively. An acute dermal toxicity test was performed in rats, and the healing activity was evaluated using the excision wound model at 100 mg/kg of the extracts. Statistical significance (P < 0.05) was determined by an analysis of variance followed by the Student-Newman-Keuls test. Results: The presence of alkaloids, saponins, terpenoids, phenolic compounds, rutin, and quercetin flavonoids, among others, was suggested. The extract did not cause toxicity at the dose of 2000 mg/kg and was able to reduce the size of the wounds during the seven days of the test, with a healing effect comparable to the silver sulfadiazine cream used as a positive control, favoring collagen deposition and re-epithelialization. Conclusion: This work makes an important contribution to the chemical composition and provides the first findings on the efficacy in the healing of topical wounds, which justify the use of G. calyptrata in traditional Cuban medicine.

Generalized Pustular Psoriasis of Von Zumbusch in a Balinese Elderly: A Rare Case Report

Generalized pustular psoriasis (GPP) of von Zumbusch is a unique and rare type of psoriasis. The severe inflammatory skin disease has been postulated of having its relation to immunogenetics and exacerbated by various factors. Most GPP cases are sporadic, characterized by cutaneous manifestations of severe erythroderma, scaling skin, the lake of pustules, and may be accompanied by extracutaneous manifestations, including acute respiratory distress syndrome, heart failure, and sepsis. This investigation reported GPP in an elderly man with prior untreated psoriasis vulgaris and pneumonia, which, to our knowledge, was the first case in our secondary regential hospital, Bangli Medika Canti Hospital. The patient underwent systemic and topical corticosteroid therapy, intravenous ceftriaxone, wound dressing, and moisturizer, which yielded a satisfactory result. We present a case and literature review of this distinct phenomenon.

Preparation and characterization of Terminalia bellerica loaded PCL nanofibrous mats for biomedical applications

Wounds are big challenges to the wound care professionals. Topical wound care products and wound dressings are evolved every day. Advanced dressings are produced by incorporating antimicrobial agents, growth factors and herbal extracts to enhance the wound healing process. Nanofibres are the recent focus as drug delivery vehicle for the delivery of drugs to the target site. The aim of the study is to prepare Terminalia bellerica loaded PCL nanofibrous mats by electrospinning and to characterize the nanofibres for biomedical applications. Terminalia bellerica is one of the ingredients of Triphala which play important role as rejuvenating agent. The increasing concentration of Terminalia loaded PCL nanofibrous mats shows increased fiber diameter, wettability and Water uptake property. The wettability of the PCL was decreased from 113.3 ± 3.62 to 59.98 ± 4.99, 44.96 ± 7.04 and 34.34 ± 3.45 respectively for the Terminalia loaded PCL nanofibres. The 5% herbal loaded PCL nanofibrous mats shows antimicrobial activity against gram negative bacteria. Further, Terminalia loaded PCL mats were found to be nontoxic and is responsible for the cell adhesion and proliferation and is useful as the potential candidate for wound dressing applications.

Reduced Hospitalizations and Amputations in Patients with Diabetic Foot Ulcers Treated with Cyclical Pressurized Topical Wound Oxygen Therapy: Real World Outcomes

Background: This study sought to examine the real-world impact of multimodality cyclical-pressure topical wound oxygen therapy (TWO2) on hospitalizations and amputations in patients with diabetic foot ulcer (DFU) compared to patients without TWO2. Methods: We conducted a retrospective review of deidentified patient medical records at 2 US Veterans Affairs hospitals between January 2012 and January 2020. DFU patients were assigned to TWO2 or NO TWO2 cohorts based on their treatment records. Patients received appropriate standard of care and may have received other advanced wound treatments, including skin substitutes, negative pressure wound therapy, and growth factors. Primary study outcomes were patients requiring hospitalization and/or amputation within 360 days of initial wound documentation. Findings: Among unmatched cohorts of 202 DFU patients (91 TWO2, 111 NO TWO2), 6·6% and 12·1% of TWO2 patients had hospitalizations and amputations, respectively, compared to 54·1% and 41·4% of NO TWO2 patients within 360 days (P < 0·0001, P < 0·0001), representing 88% and 71% reductions. Among propensity score matched cohorts of 140 DFU patients (70 TWO2, 70 NO TWO2), compared to NO TWO2, 82% fewer TWO2 patients were hospitalized (7·1% vs 40·0%, P < 0·0001) and 73% fewer TWO2 patients had amputations (8·6% vs. 31·4%, P = 0·0007). Logistic regression among matched cohorts demonstrated nearly 9-fold and 5-fold higher risk of hospitalization and amputation, respectively, for NO TWO2 vs. TWO2. Interpretation: This retrospective cohort study demonstrates that treating DFU patients with TWO2 leads to significant reductions in hospitalizations and amputations in the real-world setting. Funding: AOTI Ltd. Declaration of Interest: This study was sponsored by AOTI Ltd. (Galway, Ireland). Health Advances received consultative reimbursement from AOTI, and T.N. received consultative reimbursement from Health Advances for his independent performance of the statistical analysis. R.G.F. has received research funding from and is a consultant for AOTI. M.G.G. has received research funding and is a consultant for AOTI. A.M.L. has received research funding from AOTI. No other potential conflicts of interest relevant to this article were reported. Ethical Approval: The protocol 18 was approved by the Institutional Review Board at each facility.

Wound Healing Potential of Selected Drug molecules Obtained From Terpenoids

Skin is the vital organ of the human system; however, due to its high exposure to the external environment, it was susceptible to various traumatic conditions. During the time of trauma human body played a significant role in the activation of various biological processes for enhancing the wound healing activity in case of damaged tissues. However, in case of skin tissue defects, to enhance the angiogenesis minimal scar formation, several pharmaceutical products were paving their way into the market. Now a days there was a rising worldwide utilization of several bioactive compounds obtained from terpenoids. Terpenoids are 5-carbon compound isoprene with oxygen-containing functional groups were isolated from several plants demonstrates a wide range of activities such as antioxidant, anti-inflammatory and anti-microbial activity. Furthermore, due to their excellent cytoprotective activity, terpenoids based products had played a significant role in wound healing activity. Moreover, in our study, because of their excellent wound healing capability, we reviewed about the few drug molecules such as Tocopherol, Farnesol, Betulin, Retenoic acid, Coenzyme Q10. However, now a day's terpenoids were utilized in several wound-healing formulations because of their excellent anti-inflammatory, re-vascularization and re-epithelization characteristics. Finally, this review focuses on the role of a few drug products obtained from terpenoids as an ideal topical wound healing agent in modern medicine.

Challenges and Management in Wound Care.

Wounds have been one of the most prominent pathologies since the beginning of humanity. For the last 5 decades, a drastic improvement of healing has been observed, thanks to new medical devices based on fluid aspiration capacities and the development of negative pressure wound therapy. Negative-pressure wound therapy was initially designed for a double action, fluid aspiration and mechanical stimulation of wound edges by a foam. Successive technical evolutions of negative pressure wound therapy were declined since 1997 when Argenta and Morykwas first presented their solution. The adjunct of instillation in 2009 was considered as the first interactive dressing, allowing topical wound solutions to sequentially reach the wound, in alternance with negative pressure. Other devices based on the same principle were designed to prevent postoperative infections when placed over a suture after surgery. This long evolution could enhance the armamentarium of possible solutions, considerably reducing the wound healing time.

Management of Acute and Traumatic Wounds With Negative-Pressure Wound Therapy With Instillation and Dwell Time.

A promising and useful development of negative-pressure wound therapy (NPWT) is the addition of instillation and dwell time of topical wound solutions (NPWTi-d). Uses of NPWTi-d include acute and traumatic wounds, whereby wound closure may be facilitated via wound cleansing and promotion of granulation tissue formation. This systematic review summarizes publications on NPWTi-d in the treatment of acute and traumatic wounds. A systematic review was performed analyzing articles from major clinical databases. Only clinical studies ≥10 patients reporting on the application of NPWTi-d in acute and traumatic wounds were included. One hundred ninety-two articles were retrieved, of which 10 articles met inclusion criteria. Of those, 2 were lesser-quality randomized controlled trials, comparative studies or prospective cohorts, 2 were retrospective studies, and 6 retrospective cohort studies. In total, included publications reported 109 patients with acute and traumatic wounds treated with NPWTi-d. Data from these studies indicated the potential for reduction in bacterial bioburden through wound cleansing and promotion of granulation tissue formation, thereby facilitating wound closure, reduced length of therapy and hospital time. However, for most publications, different wound causes and subsequently no isolated results for acute and traumatic wounds were reported. NPWTi-d has promise to be effective in facilitating wound closure and reducing the time for wound closure. The present systematic review demonstrates a relatively low level of evidence available to objectively support this effect. To underline these positive results, large prospective, randomized controlled trials are necessary to manifest the role of NPWTi-d in the daily clinical routine for this wound category.

Efficacy and application of a novel topical anaesthetic wound formulation for treating cattle with Foot‐and‐Mouth disease: A field trial in Cameroon

Recently, a wound dressing formulation, (Tri‐Solfen®, Medical Ethics Pty Ltd, Australia; TS) registered for use in ruminant husbandry in Australia, was registered for Foot‐and‐Mouth Disease (FMD) therapy in large ruminants in Laos, following clinical observations of improved welfare and healing following treatment of FMD lesions. In November 2019, an FMD outbreak in Cameroon provided an opportunity for a field trial, comparing clinical responses and recoveries to treatments on a sample of cattle (n = 36) comprising three equal groups of animals (n = 12), comparing responses to three treatments: (i) the application to lesions of TS, (ii) the administration of parenteral oxytetraycline commonly used for FMD in Cameroon; and (iii) an untreated control group (C). Appetite scores, lesion healing scores, and changes in dimensions of lesions, were recorded over a 15‐day study period. Cattle treated with TS achieved both superior appetite and lesion healing scores with more rapid reduction in dimensions of lesions than other groups. Farmer observations indicated the TS treatment group had a more rapid return to eating with cessation of excessive salivation, and more rapid return of mobility (walking) with absence of overt lameness. The findings indicate that although mortality is usually low in FMD outbreaks, the disease is a debilitating and painful disorder with negative animal welfare impacts that should be addressed. All farmers expressed their desire that the product be made available for use in their region and modelling indicates that TS therapy imposes no additional financial burden on farmers, with the treatment likely to be provided at a similar or reduced cost to current treatment choices. As use of antibiotics for treatment of a viral disease potentially increases pressures for development of antimicrobial resistance and residues in the food chain, TS as an alternative non‐antimicrobial therapy should be promoted for wider use in FMD outbreaks.

With west on fire, UC Davis burn center team carries on.

The tight-knit burn center team at UC Davis Health is working nonstop to save victims of California’s horrific 2020 wildfire season. “We’re in a marathon, with lots of little sprints,” said Tina Palmieri, assistant chief of burn surgery at Shriners Hospital for Children of Northern California and director of the UC Davis Regional Burn Center. “Sometimes we’re seeing a lot of patients, very critically ill, all at the same time. Logistically, that’s pretty challenging.” Patients with extensive burns require skilled topical and surgical wound care for a prolonged period and are subject to a host of complications, including sepsis and organ failure. Palmieri said these patients require, on average, about 40 different medications, which underscores the importance of having pharmacists on the burn center’s team. “The complex nature of burns really requires the integration of people with different skill sets,” Palmieri said. “I think having a pharmacist on rounds for...

Multifunctional Synthetic Amphiphile for Niche Therapeutic Applications: Mitigation of MRSA Biofilms and Potential in Wound Healing.

The relentless menace of implant- and skin wound-associated infections caused by methicillin-resistant Staphylococcus aureus (MRSA) biofilms demands the design of therapeutics that have an edge over conventional antibiotics. The present study reports the potential of pluri-active amphiphiles having a 12-carbon alkyl chain and a salicaldehyde head group (C1) or a napthaldehyde head group (C2) in mitigating wound site- and implant-associated MRSA biofilms and as a topical wound healing agent. The amphiphiles impeded S. aureus MRSA 100 biofilm formation on collagen both on extraneous addition and on impregnation into collagen and inflicted damage to MRSA cells embedded in collagen matrix infused with simulated wound fluid, with C1 being more potent than C2. Adhesion of the MRSA biofilm was hampered on C1-coated orthopedic stainless-steel wire, while eluates from C1-coated wires were non-toxic to HEK 293 cells, highlighting the prospect of C1 as an implant-associated antibacterial coating. Upon treatment with C1, expression of the adhesin fnbA gene was low in the MRSA biofilm and downregulated in non-adherent MRSA cells, while δ-toxin (hld) gene expression in the MRSA biofilm increased, implying that C1 hindered cell-cell adhesion and planktonic-biofilm transition and also reduced biofilm adhesion. Oral administration of C1 (300 and 1000 mg/kg) was non-toxic to BALB/c mice as evidenced in stable hematological parameters and normal histopathological features of vital organs. Topical application of C1 (50 and 100 mg/kg) on a skin excision wound in female BALB/c mice resulted in effective wound closure, fibrous tissue proliferation, and tissue reorganization. Confocal microscopy revealed that topical application of C1 in an ex vivo murine skin explant could alleviate invasion of skin by MRSA, while solution-based studies indicated subdued MRSA adhesion onto the skin explants. The pluri-active synthetic amphiphile C1 provides a framework for developing antibacterials that hold translational potential as a therapeutic for implant- and skin wound-associated MRSA infections.