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Background: Experimental studies of wound healing often use survival analysis and time to event outcomes or differences in wound area at a specific time point. However, these methods do not use a potentially large number of observations made over the course of a trial and may be inefficient. A model-based approach can leverage all trial data, but there is little guidance on appropriate models and functional forms to describe wound healing., Methods: We derive a general statistical model and review a wide range of plausible mathematical models to describe wound healing. We identify a range of possible derived estimands and their derivation from the models. Using data from a trial of an intervention to promote ulcer healing in patients affected by leprosy that included three measurement methods repeated across the course of the study, we compare the goodness-of-fit of the models using a range of methods and estimate treatment effects and healing rate functions with the best-fitting models., Results: Overall, we included 5,581 ulcer measurements of 1,578 unique images from 130 patients. We examined the performance of a range of models. The square root, log square root, and log quadratic models were the best fitting models across all outcome measurement methods. The estimated treatment effects magnitude and sign varied by time post-randomisation, model type, and outcome type, but across all models there was little evidence of effectiveness. The estimated effects were significantly more precise than non-parametric alternatives. For example, estimated differences from the three outcome measurements at 42-days post-randomisation were - 0.01 cm 2 (-0.77, 0.74), -0.44 cm 2 (-1.64, 0.76), and 0.11 cm 2 (-0.87, 1.08) using a non-parametric method versus - 0.03 cm 2 (-0.14, 0.06), 0.06 cm 2 (-0.05, 0.17), and 0.03 cm 2 (-0.07, 0.17) using a square-root model., Conclusions: Model-based analyses can dramatically improve the precision of estimates but care must be taken to carefully compare and select the best fitting models. The (log) square-root model is strongly recommended reflecting advice from a century ago., (© 2024. The Author(s).)

Ethnopharmacological Relevance: The species Jatropha gossypiifolia, popularly known as "pinhão-roxo", is distributed throughout Brazil, is commonly employed for topical or oral administration in treating wounds, inflammations, and snake bites. Given the significant impact of snakebites on public health and the limitations of antivenom, coupled with the diverse molecular composition of this plant species, investigating its healing and antidermonecrotic capacities is relevant., Aim of the Study: This study aimed to develop a topical nanoemulsion incorporating the hydroethanolic extract of J. gossypiifolia leaves, to evaluate its therapeutic potential, particularly in terms of its efficacy in wound healing and inhibition of dermonecrosis induced by B. erythromelas venom (BeV)., Material and Methods: The extract of J. gossypiifolia (JgE) leaves was obtained by maceration and remaceration. The phytochemical analysis was conducted and J. gossypiifolia nanoemulsion (JgNe) was obtained, characterized and assessed for stability. The cytotoxicity was determined in normal cells (erythrocytes and 3T3) using hemolytic assay and cell viability assay using crystal violet staining. The antioxidant activity was evaluated by the reduction of ABTS and DPPH radicals. The evaluation of wound healing was conducted in vivo following treatment with JgNe, wherein the percentage of wound closure and inflammatory mediators. The skin irritation test was assessed in vivo by applying JgNe directly to the animal's skin. In vitro, the antivenom capacity was evaluated through enzymatic inhibition assays (phospholipase A 2 and hyaluronidase) of BeV. Additionally, the in vivo antidermonecrotic activity of JgNe was evaluated by measuring the reduction of the dermonecrotic halo., Results: The HPLC-DAD analysis identified flavonoids, specifically vitexin, luteolin derivatives and apigenin derivatives. In addition, 95.08 ± 5.46 mg of gallic acid/g of extract and 137.92 ± 0.99 mg quercetin/g extract, was quantified. JgNe maintained stability over a 4-week period. Moreover, JgE and JgNe demonstrated no cytotoxicity in human erythrocytes and murine fibroblasts at tested concentrations (32.25-250 μg/mL). Additionally, exhibited significant antioxidant activity by reducing ABTS and DPPH radicals. The treatment with JgNe did not induce skin irritation and accelerated wound healing, with significant wound closure observed from 5th day and reduction in nitrite levels, myeloperoxidase activity, and cytokine. Both JgE and JgNe demonstrated in vitro inhibition of the phospholipase and hyaluronidase enzymes of BeV. Moreover, JgNe exhibited antidermonecrotic activity by reducing the dermonecrotic halo caused by BeV after 24 h., Conclusions: JgNe and JgE exhibited no cytotoxicity at the tested concentrations. Additionally, our findings demonstrate that JgNe has the ability to accelerate wound closure and reduce dermonecrosis caused by BeV, indicating to be promising formulation for complementary therapy to antivenom treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Negative pressure wound therapy is currently one of the most popular treatment approaches that provide a series of benefits to facilitate healing, including increased local blood perfusion with reduced localized oedema and control of wound exudate. The porous foam dressing is a critical element in the application of this therapy and its choice is based on its ability to manage exudate. Industry standards often employ aqueous solutions devoid of proteins to assess dressing performance. However, such standardized tests fail to capture the intricate dynamics of real wounds, oversimplifying the evaluation process. This study aims to evaluate the technical characteristics of two different commercial polyurethane foam dressings during negative pressure wound therapy. We introduce an innovative experimental model designed to evaluate the effects of this therapy on foam dressings in the presence of viscous exudates. Our findings reveal a proportional increase in dressing fibre occupancy as pressure intensifies, leading to a reduction in dressing pore size. The tests underscore the pressure system's diminished efficacy in fluid extraction with increasing fluid viscosity. Our discussion points to the need of establishing standardized guidelines for foam dressing selection based on pore size and the necessity of incorporating real biological exudates into industrial standards., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Cutaneous wounds, both acute and chronic, begin with loss of the integrity, and thus barrier function, of the skin. Surgery and trauma produce acute wounds. There are 22 million surgical procedures per year in the United States alone, based on data from the American College of Surgeons, resulting in a prevalence of 6.67%. Acute traumatic wounds requiring repair total 8 million per year, 2.42% or 24.2 per 1000. The cost of wound care is increasing; it approached USD 100 billion for just Medicare in 2018. This burden for wound care will continue to rise with population aging, the increase in metabolic syndrome, and more elective surgeries. To heal a wound, an orchestrated, evolutionarily conserved, and complex series of events involving cellular and molecular agents at the local and systemic levels are necessary. The principal factors of this important function include elements from the neurological, cardiovascular, immune, nutritional, and endocrine systems. The objectives of this review are to provide clinicians engaged in wound care and basic science researchers interested in wound healing with an updated synopsis from recent publications. We also present data from our primary investigations, testing the hypothesis that cannabidiol can alter cutaneous wound healing and documenting their effects in wild type (C57/BL6) and db/db mice (Type 2 Diabetes Mellitus, T2DM). The focus is on the potential roles of the endocannabinoid system, cannabidiol, and the important immune-regulatory wound cytokine IL-33, a member of the IL-1 family, and connective tissue growth factor, CTGF, due to their roles in both normal and abnormal wound healing. We found an initial delay in the rate of wound closure in B6 mice with CBD, but this difference disappeared with time. CBD decreased IL-33 + cells in B6 by 70% while nearly increasing CTGF + cells in db/db mice by two folds from 18.6% to 38.8% ( p < 0.05) using a dorsal wound model. We review the current literature on normal and abnormal wound healing, and document effects of CBD in B6 and db/db dorsal cutaneous wounds. CBD may have some beneficial effects in diabetic wounds. We applied 6-mm circular punch to create standard size full-thickness dorsal wounds in B6 and db/db mice. The experimental group received CBD while the control group got only vehicle. The outcome measures were rate of wound closure, wound cells expressing IL-33 and CTGF, and ILC profiles. In B6, the initial rate of wound closure was slower but there was no delay in the time to final closure, and cells expressing IL-33 was significantly reduced. CTGF + cells were higher in db/bd wounds treated with CBD. These data support the potential use of CBD to improve diabetic cutaneous wound healing.

Objective: To describe the use of a novel wound dressing that delivers nitric oxide (NO) to naturally occurring traumatic wounds in dogs., Animals: 24 client-owned dogs with 30 wounds., Methods: Dogs were presented with acute traumatic wounds requiring open wound management. Wounds were bandaged with a novel NO wound dressing and reassessed as needed for continued open wound management until wounds healed by second intention or wound closure was recommended. Dogs could be removed from the study at any point at the clinician's discretion., Results: All wounds had the novel NO wound dressing used during open wound management until wound closure was recommended. Median time to wound closure was 6 days (range, 2 to 42). There were no complications directly attributed to the use of the novel wound dressing that clinically affected the dogs. Three wounds dehisced following wound closure. Wound healing was confirmed in 19 dogs with 25 wounds, with 3 dogs lost to follow-up prior to suture removal. Only 7.1% of wounds had clinical signs consistent with wound infection following wound closure., Clinical Relevance: The novel NO wound dressing was easy to use and well tolerated in dogs with naturally occurring traumatic wounds. It can be used throughout all phases of wound healing, simplifying open wound management.

Objective: While the use of negative pressure wound therapy (NPWT) with reticulated open cell foam (ROCF) is well established, the characteristics of ROCF do not allow for extended-wear use. There is the potential for dressing tissue ingrowth if left in place for greater than the recommended 2-3 days. An easy to use, novel peel and place dressing has been designed for extended wear with the wound management advantages of ROCF while alleviating the challenges of tissue ingrowth. Approach: Paraspinal, full-thickness or deep muscle excisional wounds were created in 11 and 2 swine, respectively, dressings applied with continuous negative pressure at -125 mmHg, and dressings changed weekly. Full-thickness excisional wounds were treated for 13 days and deep muscle wounds for 35 days. Wound dimensions were assessed. Granulation tissue thickness and re-epithelialization were measured via digital morphometry. Tissue quality, fibrinous material prevalence, and dressing removal peel force were analyzed. Results: The peel and place dressing substantially reduces dressing tissue ingrowth, is easy to remove with markedly low dressing peel force and promotes more granulation tissue at day 13 than ROCF with an interface layer. The extended-wear peel and place dressing, when applied to deep muscle wounds with weekly dressing changes, was applied for a total of 35 days. Successful wound closure was evident without any negative impact on wound healing. Innovation: This study assessed the wound management capabilities of an extended-wear peel and place NPWT dressing used until wound closure. Conclusion: The peel and place dressing is a suitable extended-wear NPWT dressing.

Diabetic wounds (DWs) pose a significant health burden worldwide, with their management presenting numerous challenges. Biopolymeric formulations have recently gained attention as promising therapeutic approaches for diabetic wound healing. These formulations, composed of biocompatible and biodegradable polymers, offer unique properties such as controlled drug release, enhanced wound closure, and reduced scarring. In this review, we aim to provide a comprehensive overview of the current state of research and future prospects regarding the application of biopolymeric formulations for diabetic wound healing. The review begins by highlighting the underlying pathophysiology of DWs, including impaired angiogenesis, chronic inflammation, and compromised extracellular matrix (ECM) formation. It further explores the key characteristics of biopolymeric materials, such as their biocompatibility, biodegradability, and tunable physicochemical properties, which make them suitable for diabetic wound healing applications. The discussion further delves into the types of biopolymeric formulations utilized in the treatment of DWs. These include hydrogels, nanoparticles (NP), scaffolds, films, and dressings. Furthermore, the review addresses the challenges associated with biopolymeric formulations for diabetic wound healing. In conclusion, biopolymeric formulations present a promising avenue for diabetic wound healing. Their unique properties and versatility allow for tailored approaches to address the specific challenges associated with DWs. However, further research and developments are required to optimize their therapeutic efficacy, stability, manufacturing processes, and regulatory considerations. With continued advancements in biopolymeric formulations, the future holds great promise for improving the management and outcomes of DWs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Aims: Bacteria in wounds can lead to stagnation of wound healing as well as to local or even systemic wound infections up to potentially lethal sepsis. Consequently, the bacterial load should be reduced as part of wound treatment. Therefore, the efficacy of simple mechanical wound debridement should be investigated in terms of reducing bacterial colonisation., Patients and Methods: Patients with acute or chronic wounds were assessed for bacterial colonisation with a fluorescence camera before and after mechanical wound debridement with sterile cotton pads. If bacterial colonisation persisted, a second, targeted wound debridement was performed., Results: A total of 151 patients, 68 (45.0%) men and 83 (55.0%) women were included in this study. The male mean age was 71.0 years and the female 65.1 years. By establishing a new analysis method for the image files, we could document that the bacterial colonised areas were distributed 21.9% on the wound surfaces, 60.5% on the wound edges (up to 0.5 cm) and 17.6% on the wound surroundings (up to 1.5 cm). One mechanical debridement achieved a significant reduction of bacterial colonised areas by an average of 29.6% in the wounds, 18.9% in the wound edges and 11.8% in the wound surroundings and was increased by performing it a second time., Conclusions: It has been shown that even a simple mechanical debridement with cotton pads can significantly reduce bacterial colonisation without relevant side effects. In particular, the wound edges were the areas that were often most contaminated with bacteria and should be included in the debridement with special attention. Since bacteria remain in wounds after mechanical debridement, it cannot replace antimicrobial therapy strategies, but offer a complementary strategy to improve wound care. Thus, it could be shown that simple mechanical debridement is effective in reducing bacterial load and should be integrated into a therapeutic approach to wounds whenever appropriate., (© 2024 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

The emerging evidence has indicated the role of microRNAs (miRNA) in various physiological or pathological processes. Also, documents have suggested that exercise, by affecting miRNA regulation, may enhance burn wound healing. The current study aims to systematically review the role of exercise in regulating miRNAs related to burn wound healing to provide potential therapeutic targets. A comprehensive, systematic search was performed in different international electronic databases, such as Embase, PubMed and Google Scholar search engine, Science Direct, ProQuest and Ovid using keywords extracted from Medical Subject Headings from 2010 to September 2023. The keywords, including 'exercise' AND 'burn wound' AND 'microRNA' and finally, six cases were achieved. Evidence has indicated that exercise may promote the healing of burn wounds by regulating certain miRNAs. Studies have found that exercise regulates the expression of miRNAs such as mir-155, miR-21, let-7a, miR-146a, miR-122 and mir-210 in burn wound tissue, which regulate inflammation and angiogenesis. These findings suggest that miRNAs may play a role in the positive effect of exercise on burn wound healing. However, further research is needed to understand the mechanisms involved fully., (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Hard-to-heal wounds can be detrimental to patients' quality of life. Currently, there is scarcity of therapeutic alternatives to mainstay surgical treatment, which uses the principles of tissue debridement, temporary wound coverage, and subsequent tissue reconstruction. Here, a new approach is proposed that harnesses the regenerative power of autologous peripheral blood, through a process termed hypoxia-adjusted in vitro preconditioning. The effectiveness of this method is demonstrated with six cases of surgical wounds, including two cases of large full-thickness dermal wounds that developed as a result of skin necrosis following abdominoplasty and buttock-lift procedures in heavy smokers, as well as a case of extensive inflammatory tissue damage that occurred following breast surgery. While these wounds differed in size (4-160 cm 2 ), geometry and location, all of them could be managed conservatively with topical application of growth factor-enriched hypoxia preconditioned serum derived from the patient's own peripheral blood. This treatment led to complete wound closure by latest 135 days. The finding of complete skin regeneration even in large (>10 cm 2 ), full-thickness wounds, where initially no dermal tissue was available in the wound bed, strongly suggests that the treatment targeted key cellular regenerative mechanisms, including differentiation, angiogenesis, granulation tissue induction, contraction and epithelialization. The method is readily clinically applicable, cost effective, and overcomes limitations of the classic reconstructive approach.

Wound healing is a complex process influenced by age, systemic conditions, and local factors. The wound microbiota's crucial role in this process is gaining recognition. This concise review outlines wound microbiota impacts on healing, emphasizing distinct phases like hemostasis, inflammation, and cell proliferation. Inflammatory responses, orchestrated by growth factors and cytokines, recruit neutrophils and monocytes to eliminate pathogens and debris. Notably, microbiota alterations relate to changes in wound healing dynamics. Commensal bacteria influence immune responses, keratinocyte growth, and blood vessel development. For instance, Staphylococcus epidermidis aids keratinocyte progression, while Staphylococcus aureus colonization impedes healing. Other bacteria like Group A Streptococcus spp. And Pseudomonas affect wound healing as well. Clinical applications of microbiota-based wound care are promising, with probiotics and specific bacteria like Acinetobacter baumannii aiding tissue repair through molecule secretion. Understanding microbiota influence on wound healing offers therapeutic avenues. Tailored approaches, including probiotics, prebiotics, and antibiotics, can manipulate the microbiota to enhance immune modulation, tissue repair, and inflammation control. Despite progress, critical questions linger. Determining the ideal microbiota composition for optimal wound healing, elucidating precise influence mechanisms, devising effective manipulation strategies, and comprehending the intricate interplay between the microbiota, host, and other factors require further exploration.

A new recombinant proteolytic enzyme, isolated from maggot saliva, with fibrinolytic action has been investigated through a series of non-clinical toxicology and in-vitro/in-vivo pharmacology studies to explore its potential safety and efficacy as an enzymatic debridement agent for use in chronic wounds. Studies indicate that the enzyme has a good safety profile. When locally administered, it is not detrimental to wound healing, is non-sensitising and is rapidly inactivated in the systemic circulation. Adverse effects are limited, at very high concentrations, to transient erythema at the site of application. In-vitro testing indicates that the enzyme, whilst selective for fibrin, has additional proteolytic action against collagen and elastin, with enzymatic action for all three substrates being dose dependent. In-vivo, we used an established MRSA biofilm model, in which microbiological counts were used as a surrogate for debridement efficacy. Here, we showed that higher concentrations of the enzyme in a formulated proprietary gel, significantly reduced MRSA counts over a period of 2 to 14 days, and significantly improved the vascularity of the wound at 14 days. Together, these data support the potential for this maggot-derived proteolytic enzyme as a clinically effective debriding agent., (© 2022 SolasCure Ltd. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)

Chronic wounds occur for several reasons, such as trauma, accidents, and diseases. Diabetes has been one of the primary causes of non-healing wounds, and the number of people with diabetes is increasing in most countries. Wounds in diabetic people have a complex and prolonged treatment process, with high treatment costs to both healthcare providers and patients. They often have severe consequences, such as pain, wound infection, tissue necrosis, and even limb amputation. Various methods have been used to treat chronic wounds, but clinical success has been limited due to inefficient delivery to the wound bed. Microneedles (MNs), as new platforms, can offer an effective treatment, easy to use and non-invasive with less tissue damage, capable of delivering a wide range of drugs to accelerate the wound healing process. Different methods and materials can be used for this technique, and there are different geometric parameters such as needle length, tip angle, shape and radius, together with needle array density to optimize for the most effective treatment. This review paper will investigate the role of MNs in healing chronic wounds and discuss the most recent development in MN-based devices in the field and their effectiveness. The manuscript will also discuss the various types of MNs and their potential applications for delivering therapeutic agents. Finally, the challenges associated with using MNs to heal chronic wounds and future directions in this field are discussed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Delayed healing of traumatic wounds often stems from a dysregulated immune response initiated or exacerbated by existing comorbidities, multiple tissue injury or wound contamination. Over decades, approaches towards alleviating wound inflammation have been centered on interventions capable of a collective dampening of various inflammatory factors and/or cells. However, a progressive understanding of immune physiology has rendered deeper knowledge on the dynamic interplay of secreted factors and effector cells following an acute injury. There is a wide body of literature, both in vitro and in vivo, abstracted on the immunomodulatory approaches to control inflammation. Recently, targeted modulation of the immune response via biotechnological approaches and biomaterials has gained attention as a means to restore the pro-healing phenotype and promote tissue regeneration. In order to fully realize the potential of these approaches in traumatic wounds, a critical and nuanced understanding of the relationships between immune dysregulation and healing outcomes is needed. This review provides an insight on paradigm shift towards interventional approaches to control exacerbated immune response following a traumatic injury from an agonistic to a targeted path. We address such a need by (1) providing a targeted discussion of the wound healing processes to assist in the identification of novel therapeutic targets and (2) highlighting emerging technologies and interventions that utilize an immunoengineering-based approach. In addition, we have underscored the importance of immune engineering as an emerging tool to provide precision medicine as an option to modulate acute immune response following a traumatic injury. Finally, an overview is provided on how an intervention can follow through a successful clinical application and regulatory pathway following laboratory and animal model evaluation.

The Wound Healing Foundation (WHF) recognised a need for an unbiased consensus on the best treatment of chronic wounds. A panel of 13 experts were invited to a virtual meeting which took place on 27 March 2021. The proceedings were organised in the sub-sections diagnosis, debridement, infection control, dressings, grafting, pain management, oxygen treatment, outcomes and future needs. Eighty percent or better concurrence among the panellists was considered a consensus. A large number of critical questions were discussed and agreed upon. Important takeaways included that wound care needs to be simplified to a point that it can be delivered by the patient or the patient's family. Another one was that telemonitoring, which has proved very useful during the COVID-19 pandemic, can help reduce the frequency of interventions by a visiting nurse or a wound care center. Defining patient expectations is critical to designing a successful treatment. Patient outcomes might include wound specific outcomes such as time to heal, wound size reduction, as well as improvement in quality of life. For those patients with expectations of healing, an aggressive approach to achieve that goal is recommended. When healing is not an expectation, such as in patients receiving palliative wound care, outcomes might include pain reduction, exudate management, odour management and/or other quality of life benefits to wound care., (© 2022 The Authors. Wound Repair and Regeneration published by Wiley Periodicals LLC on behalf of The Wound Healing Society.)

Chronic wounds in limbs without infection are common. This study was to identify an economical, simple, and useful wet healing therapy for patients with chronic noninfectious wounds in the limbs, especially for low-income patients. In total, 56 patients with chronic limb wounds without infection from April 2018 to March 2019 were included. They underwent wound cleaning by iodine and wound covering by recombinant human epidermal growth factor gel, zinc oxide ointment, and erythromycin eye ointment at a 1:1:1 ratio and thickness of 0.8 cm. After applying the drug, a slight-pressure dressing was applied to the wound with a cotton pad and bandage, and the dressing was changed every 3 days. All the wounds completely healed within 12 to 45 days (26.2 ± 11.9 days). The healing time showed a positive correlation with the area of the wound ( r = 0.328, P < .05) and the course of disease ( r = 0.485, P < .01). The healing time of deep second-degree wounds was 17.2 ± 3.3 days, which was shorter than that of deep third-degree wounds (34.8 ± 8.4 days; P < .05). There was no significant difference in the healing time according to sex. Upper limb wounds healed faster than lower limb wounds (16 ± 2.7 days versus 31.7 ± 9.7 days, P < .05). The simple therapy required a low cost of 0.07 dollars per square centimeter for each dressing change. This wet healing therapy is easy, effective, relatively safe, and affordable, with no obvious side effects.

A burn wound is a complex systemic disease at multiple levels. Current knowledge of scar formation after burn injury has come from traditional biological and clinical studies. These are normally focused on just a small part of the entire process, which has limited our ability to sufficiently understand the underlying mechanisms and to predict systems behaviour. Scar formation after burn injury is a result of a complex biological system-wound healing. It is a part of a larger whole. In this self-organising system, many components form networks of interactions with each other. These networks of interactions are typically non-linear and change their states dynamically, responding to the environment and showing emergent long-term behaviour. How molecular and cellular data relate to clinical phenomena, especially regarding effective therapies of burn wounds to achieve minimal scarring, is difficult to unravel and comprehend. Complexity science can help bridge this gap by integrating small parts into a larger whole, such that relevant biological mechanisms and data are combined in a computational model to better understand the complexity of the entire biological system. A better understanding of the complex biological system of post-burn scar formation could bring research and treatment regimens to the next level. The aim of this review/position paper is to create more awareness of complexity in scar formation after burn injury by describing the basic principles of complexity science and its potential for burn care professionals.

Aims: Deep surgical site infection (SSI) is common after lower limb fracture. We compared the diagnosis of deep SSI using alternative methods of data collection and examined the agreement of clinical photography and in-person clinical assessment by the Centers for Disease Control and Prevention (CDC) criteria after lower limb fracture surgery., Methods: Data from two large, UK-based multicentre randomized controlled major trauma trials investigating SSI and wound healing after surgical repair of open lower limb fractures that could not be primarily closed (UK WOLLF), and surgical incisions for fractures that were primarily closed (UK WHiST), were examined. Trial interventions were standard wound care management and negative pressure wound therapy after initial surgical debridement. Wound outcomes were collected from 30 days to six weeks. We compared the level of agreement between wound photography and clinical assessment of CDC-defined SSI. We are also assessed the level of agreement between blinded independent assessors of the photographs., Results: Rates of CDC-defined deep SSI were 7.6% (35/460) after open fracture and 6.3% (95/1519) after closed incisional repair. Photographs were obtained for 77% and 73% of WOLLF and WHiST cohorts respectively (all participants n = 1,478). Agreement between photographic-SSI and CDC-SSI was fair for open fracture wounds (83%; k = 0.27 (95% confidence interval (CI) 0.14 to 0.42)) and for closed incisional wounds (88%; k = 0.29 (95% CI 0.20 to 0.37)) although the rate of photographically detected deep SSIs was twice as high as CDC-SSI (12% vs 6%). Agreement between different assessors for photographic-SSI (WOLLF 88%, k = 0.63 (95% CI 0.52 to 0.72); WHiST 89%; k = 0.61 (95% CI 0.54 to 0.69)); and wound healing was good (WOLLF 90%; k = 0.80 (95% CI 0.73 to 0.86); WHiST 87%; k = 0.57 (95% CI 0.50 to 0.64))., Conclusion: Although wound photography was feasible within the research context and inter-rater assessor agreement substantial, digital photographs used in isolation overestimated deep SSI rates, when compared to CDC criteria. Wound photography should not replace clinical assessment in pragmatic trials but may be useful for screening purposes where surgical infection outcomes are paramount. Cite this article: Bone Joint J  2021;103-B(12):1802-1808.

Background: Impaired potential of hypoxia-mediated angiogenesis lead poor healing of diabetic wounds. Previous studies have shown that extracellular vesicles from adipose derived stem cells (ADSC-EVs) accelerate wound healing with unelucidated mechanism. However, it is not yet clear about the underlying mechanism of ADSC-EVs in regulating the hypoxia-related PI3K/AKT/mTOR signaling pathway of vascular endothelial cells in diabetic wounds. Therefore, in this study, human derived ADSC-EVs (hADSC-EVs) isolated from adipose tissue were co-cultured with advanced glycosylation end product (AGE) treated human umbilical vein endothelial cells (HUVECs) in vitro and local injected into the wounds of diabetic rats., Methods: In vitro, the therapeutic potential of hADSC-EVs on AGE-treated HUVECs was evaluated by cell counting kit-8, scratching, and tube formation assay. Subsequently, the effects of hADSC-EVs on the PI3K/AKT/mTOR/HIF-1α signaling pathway were also assayed by qRT-PCR and western blot. In vivo, the effect of hADSC-EVs on diabetic wound healing in rats were also assayed by closure kinetics, Masson staining and HIF-1α-CD31 immunofluorescence., Results: hADSC-EVs were spherical in shape with an average particle size of 198.1 ± 91.5 nm, and were positive for CD63, CD9 and TSG101. hADSC-EVs promoted the expression of PI3K-AKT-mTOR-HIF-1α signaling pathway of AGEs treated HUVECs with improved the potential of proliferation, migration and tube formation, and improve the healing and angiogenesis of diabetic wound in rats. However, the effect of hADSC-EVs described above can be blocked by PI3K-AKT inhibitor both in vitro and vivo., Conclusion: Our findings indicated that hADSC-EVs accolated the healing of diabetic wounds by promoting HIF-1α-mediated angiogenesis in the PI3K-AKT-mTOR depend manner., (© 2021. The Korean Tissue Engineering and Regenerative Medicine Society.)

Competing Interests: AB is the founder and Scientific Director of Science of Skin. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

There is a vast number of wound dressings to choose from, which can make selecting the most suitable dressing for a wound a daunting prospect. This article highlights how the wound can guide the doctor's decision. Although all wound dressings are intended to achieve optimal wound healing and protection from contamination, they do so to varying degrees depending on the qualities of the dressing and the wound itself. This article looks at a range of dressings, from traditional to newer dressings, and evaluates their benefits and contraindications to help determine where they are best suited for use in wound management.

Chronic wounds are a common and debilitating condition associated with aging populations that impact more than 6.5 million patients in the United States. We have previously demonstrated the efficacy of daily topical 1% valsartan in treating wounds in diabetic mouse and pig models. Despite these promising results, there remains a need to develop an extended-release formulation that would reduce patient burden by decreasing the frequency of daily applications. Here, we used nanotechnology to self-assemble valsartan amphiphiles into a filamentous structure (val-filaments) that would serve as a scaffold in wound beds and allow for steady, localised and tunable release of valsartan amphiphiles over 24 days. Two topical treatments of this peptide-based hydrogel on full-thickness wounds in Zucker Diabetic Fatty rats resulted in faster rates of wound closure. By day 23, all val-filament treated wounds were completely closed, as compared to one wound closed in the placebo group. Mechanistically, we observed enrichment of proteins involved in cell adhesion and energetics pathways, downregulation of Tgf-β signalling pathway mediators (pSmad2, pSmad3 and Smad4) and increased mitochondrial metabolic pathway intermediates. This study demonstrates the successful synthesis of a sustained-release valsartan filament hydrogel, its impact on mitochondrial energetics and efficacy in treating diabetic wounds., (© 2021 The Wound Healing Society.)

Aims: Tamanu is a plant oil derived from the fruit and seeds of the Calophyllum inophyllum tree. Although scientific data on tamanu oil are limited, it is recommended worldwide for the treatment of abrasions, burns, diabetic wounds and scars. This study aimed to compare the wound healing efficacy of the topical use of tamanu oil with a reference drug in rats., Methods: Uniform wounds were induced on the dorsum of 21 rats, randomly divided into three groups. The control group received normal saline; the tamanu group received tamanu oil; and the centella group was treated with Centella asiatica . Wound healing was clinically evaluated using wound healing scoring and wound contraction. A biopsy was taken from the wound sites of each rat on days 7, 14 and 21 for histopathological evaluation., Results: Wound contraction was significantly lower in the tamanu group compared with the other groups. On day 7, the intensity of macrophage infiltration and mature granulation tissues were significantly higher in the centella and tamanu groups than in the control group. Fibrosis and collagen density were higher in the tamanu group than the other groups on day 7., Conclusion: In wound healing in rats, tamanu oil accelerated the formation of macrophage-granulation tissues-fibrosis and resulted in less wound contraction.

Aims: We describe the development of a novel porcine eschar model and compare the debridement efficacy of various concentrations of a novel bromelain-based enzymatic agent with collagenase., Methods: Full thickness excisional wounds were created on pigs and injected intradermally with various doses of doxorubicin. Wounds were monitored for a period of 46 days for the development of eschar and wound closure. After determining the optimal concentration and dose of doxorubicin resulting in non-healing eschars, these conditions were used to create additional wounds on another set of animals. The resulting eschars were treated with various concentrations of a novel bromelain-based enzymatic agent (EscharEx-02) or collagenase. The primary endpoint was greater than 95% removal of the central eschar., Results: Consistent eschars composed of two distinct areas (a central area of exudate and slough representing the hard-to-heal wound bed, and a peripheral area of full-thickness mummified necrosis) were seen after injection of doxorubicin (0.5 ml/cm 2 of stock solution 0.75mg/ml) at one and six days after wound creation. Complete removal of the central eschar was achieved in all wounds after five and eight treatments with 5% and 2% EscharEx-02 respectively. Complete removal of the central eschar with collagenase was achieved in 0% and 82% of the wounds after 10 and 16 treatments respectively., Conclusions: We describe a porcine model for creating eschars similar to hard-to-heal wounds in humans. A novel bromelain-based enzymatic debridement agent was more effective than a commercially available collagenase in removing eschars in this wound model.

In consultation with academia and the Pharmaceuticals and Medical Devices Agency (PMDA), we have developed guidance for drafting protocols for clinical trials concerning medical devices for the healing of hard-to-heal wounds without ischaemia. The guidance summarises the validity of single-arm trials for hard-to-heal wounds, the definition of hard-to-heal wounds without ischaemia, methods of patient enrolment and clinical endpoints. This review focuses on the logical thinking process that was used when establishing the guidance for improving the efficiency of clinical trials concerning medical devices for hard-to-heal wounds. We particularly focused on the feasibility of conducting single-arm trials and also tried to clarify the definition of hard-to-heal wounds. If the feasibility of randomised control trials is low, conducting single-arm trials should be considered for the benefit of patients. In addition, hard-to-heal wounds were defined as meeting the following two conditions: wounds with a wound area reduction <50% at four weeks despite appropriate standards of care; and wounds which cannot be closed by a relatively simple procedure (for example, suture, skin graft and small flaps). Medical devices for hard-to-heal wound healing are classified into two types: (1) devices for promoting re-epithelialisation; and (2) devices for improving the wound bed. For medical devices for promoting re-epithelialisation, we suggest setting complete wound closure, percent wound area reduction or distance moved by the wound edge as the primary endpoint in single-arm trials for hard-to-heal wounds. For medical devices for improving the wound bed, we suggest setting the period in which wounds can be closed by secondary intention or a simple procedure, such as the primary endpoint.

Older adults are at high risk of developing chronic wounds due to numerous changes that occur with aging. It is reasonable to consider chronic wounds as a geriatric syndrome-highly prevalent, multifactorial, and associated with substantial morbidity and mortality. Due to the morbidity and cost associated with chronic wounds, prevention, early diagnosis, and treatment are important. The most common chronic wounds presenting in older adults are pressure and vascular wounds, including those associated with diabetes. Atypical wounds are also common and should raise the suspicion for skin malignancy. Diagnosis is primarily clinical and assessment should include documentation of wound characteristics, such as location, size and depth, presence of slough, drainage, odor, and infection. The mainstay of treatment is based on the TIME principle: Tissue debridement, Infection control, Moisture balance, and optimal wound Edges. The use of protein supplements has been shown to improve wound healing in subsets of older adults. In addition to wound care and optimizing nutrition, disease-specific wound therapy forms an integral part of wound management. Pressure reduction for pressure injury, compression therapy for venous wounds, evaluation of arterial circulation with ABI or arterial Doppler and iCC for diabetic ulcers form the mainstays of therapy. Atypical wounds may present as chronic ulcers and should be biopsied. The goals of treatment should be realistic and for some older adults, palliative wound management may be more appropriate., (© 2021 The American Geriatrics Society.)

When the integrity of the skin got damaged, an endogenous electric field will be generated in the wound and a series of physiological reactions will be initiated to close the wound. The existence of the endogenous electric field of the wound has a promoting effect on all stages of wound healing. For wounds that cannot heal on their own, the exogenous electric field can assist the treatment. In this review, the effects of exogenous electrical stimulation on wound healing, such as the inflammation phase, blood flow, cell proliferation and migration, and the wound scarring is overviewed. This article also reviews the new electrical stimulation methods that have emerged in recent years, such as small power supplies, nanogenerators (NGs), and other physical, chemical or biological strategies. These new electrical stimulation methods and devices are safe, low-cost, stable, and small in size. The challenge and perspective are discussed for the future trends of the electrical stimulation treatment in accelerating skin wound healing., (© 2021 Wiley-VCH GmbH.)

Significance: Prolonged inflammation and impaired angiogenesis are the two principal factors that prevent successful wound healing, which is exacerbated in people with diabetes. There is a significant need for new wound healing treatments that target both these factors simultaneously. This review discusses the emerging evidence that high-density lipoproteins (HDL) have pleiotropic wound healing benefits. Recent Advances: Numerous in vitro and in vivo studies have demonstrated the anti-inflammatory and proangiogenic effects of HDL. In endothelial cells, HDL mediate these effects through interaction with the scavenger receptor SR-BI, which activates the PI3K/Akt pathway, causing a decrease in inflammatory protein production and an increase in proangiogenic growth factors. In macrophages, HDL inhibit inflammation through suppression of the nuclear factor kappa B activation pathway. This review details the molecular disturbances that cause impaired wound healing in diabetes with a particular focus on inflammation and angiogenesis and the pathways in which HDL provide benefit. Critical Issues: Diabetic foot ulcers (DFUs) impose a major public health challenge worldwide. It is estimated that 20% patients with DFUs require amputation, which is accompanied by a significant social and economic burden. To date, there are no therapeutic agents with pleiotropic effects that actively improve wound healing, highlighting a therapeutic void for this complex disease.

A monofilament fibre debridement pad has been found to be a rapid and effective mechanical method of removing dry skin, biofilm and debris from acute and chronic wounds with minimal patient discomfort. Evidence of its impact on prescribing and wound healing, however, has been more limited. The aim of this audit was to show evidence of the monofilament fibre debridement pad's impact on wound treatment costs through an analysis of NHS wound-care prescribing data in England. A dataset for 486 uniquely identified patients who had been newly prescribed the monofilament fibre debridement pad was obtained from the NHS Business Services Authority. All data were anonymised. Costs were identified for the six months before and six months after the month of first prescription of the monofilament fibre debridement pad. The total cost of wound-care prescribing fell by 14% or £101,723 in the six months after the intervention compared with the six months before. The average monthly expenditure per patient fell from £244 before the intervention to £209 (n=486) after. These results indicate that use of the monofilament fibre debridement pad could reduce prescribing costs and the use of antimicrobial and negative pressure therapies. Further research is warranted to investigate the clinical role of the monofilament fibre debridement pad in wound healing.

Objectives: In this review and meta-analysis, we analyse the evidence to compare the efficacy of honey and povidone iodine-based dressings on the outcome of wound healing., Method: A systematic literature search was performed using PRISMA guidelines in academic databases including MEDLINE, Scopus, Embase and CENTRAL. A meta-analysis was carried out to assess the effect of honey and povidone iodine-based dressings on mean healing duration, mean hospital stay duration and visual analogue scale (VAS) score of pain., Results: From the search, 12 manuscripts with a total of 1236 participants (mean age: 40.7±11.7 years) were included. The honey-based dressings demonstrated a medium-to-large effect in reduction of mean healing duration (Hedge's g: -0.81), length of hospital stay (-3.1) and VAS score (-1.2) as compared with the povidone iodine-based dressings. We present evidence (level 1b) in favour of using honey for improvement of wound recovery as compared with povidone iodine., Conclusion: This review and meta-analysis demonstrate beneficial effects of honey-based dressings over povidone iodine-based dressings for wound recovery.

Objective: To demonstrate the efficacy of the SafeZone UVC (Ushio Inc., Japan) 222 nm ultraviolet C (UVC) light to reduce bacterial burden in pressure ulcers (PUs) in human patients. This research is the first human clinical trial using 222 nm UVC in eradicating bacteria in human wounds., Method: Patients with Stage 2 or 3 (as defined by the revised National Pressure Ulcer Advisory Panel Pressure Injury Staging System) sacral or gluteal pressure ulcers (PUs) were subjected to four sessions of 222 nm UVC light therapy over two weeks. Pre- and post-UVC therapy, wound cultures were taken and quantitative analysis of bacterial colony forming units (CFU) were performed., Results: A total of 68 UV light sessions across 16 different patients were conducted. Of these sessions, 59 (87.0%) sessions showed a reduction in CFU counts, with 20 (29.4%) showing complete eradication of bacteria. Bacteria identified included meticillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa and Klebsiella Pneumoniae . The overall median reduction in CFU of the 68 sessions was 78.9%. No adverse events were reported in any of the UV sessions., Conclusion: In this study, 222 nm UVC light was safe and effective in reducing bacterial CFU counts in sacral and gluteal PUs across numerous different species of bacteria.

Objective: Management of any wound, either acute or hard-to-heal, might involve the use of multiple and different wound dressings in its treatment. This approach is necessary to overcome the myriad of clinical challenges the wound presents, as well as any underlying comorbidities that might affect the clinical outcomes. This article describes the clinical effectiveness of a coordinated wound dressing treatment regimen., Method: This was an open-labelled non-comparative study involving patients with a variety of hard-to-heal and acute wounds of differing levels of severity, but all of which required removal of devitalised tissue to enable wound healing to progress. The first phase used the hydroresponsive wound dressing HydroClean (PAUL HARTMANN AG, Germany). The PUSH score was used as the primary measurement parameter., Results: A total of 86 patients (38 male/48 female), with a mean age of 67.7±21.7 years, took part in the study. The results showed that the hydroresponsive dressing was effective in managing wound exudate production and promoting wound cleansing and debridement, supporting good wound bed preparation. Wound closure was observed in 16/86 (18.6%) wounds at the end of the study (20 weeks). This enabled clinicians to switch to alternative wound dressings to promote subsequent clinical healing outcomes., Conclusion: In this study, the hydroresponsive wound dressing was highly effective in preparing a clean wound bed such that the next stage of wound healing could be supported.

Objective: Approximately three million people in the US have hard-to-heal pressure ulcers (PUs), including 10% of hospitalised patients. Healing depends on ulcer stage and patient comorbidities. Despite advances in nutrition and wound care, PUs can take months or years to reach complete closure. To date, clinical studies have focused on single modality therapy. However, there is no one therapy that can address all of the deficits in these complex, hard-to-heal wounds. A commonly used treatment for PUs, negative pressure wound therapy (NPWT), has demonstrated improved healing in Stage 3 and 4 PUs. NPWT entails applying suction to a porous sponge fitted into the wound cavity and sealed with an occlusive dressing. Negative pressure facilitates wound healing by removing wound fluid containing harmful proteases, stimulating the formation of granulation tissue and promoting wound contracture. However, it does not affect biofilm formation. We hypothesised that adding an antibiofilm agent might increase the effectiveness of NPWT in recalcitrant PUs., Method: A prospective case series was conducted in outpatient wound care centres and a skilled nursing facility to examine the combination of a biofilm-disrupting antimicrobial agent (Blast-X, Next Science, US) in combination with NPWT (VAC, 3M, US) in healing and reducing bacterial burden in treatment-resistant pressure ulcers. Patients consented to application of the antibiofilm agent and NPWT three times per week for four weeks. The wounds were measured, imaged for bacteria and tested for host and bacterial protease activity weekly., Results: Of the 10 patients, four dropped out of the study before the end of the four weeks. Of the remaining six, four patients experienced a reduction in wound surface area and volume, reduced protease activity and lower bacterial levels., Conclusion: The results of this study showed that multimodal therapy, including NPWT and biofilm disruption, may restart the healing of stagnant treatment-resistant PUs.

Objective: Polysaccharide-based biomaterials are extensively used in wound care healing due to their unique liquid absorption, gelling properties and biocompatibility properties. They play an important role in controlling infections of highly exuding hard-to-heal wounds. The main objective of this study was to develop silver-containing polysaccharide-based tricomponent antibacterial fibres for use in these complex wounds., Method: The fibres were developed by coating silver-containing alginate and psyllium fibres with hydrolysed chitosan. Dope solution containing alginate, psyllium and silver carbonate was extruded into a coagulation bath containing calcium chloride and hydrolysed chitosan. The developed fibres were tested for liquid absorption, swelling and antibacterial properties against a control fibre (of alginate and psyllium)., Results: The developed fibres showed comparatively better liquid absorption, gelling and antibacterial properties than the control fibres., Conclusion: The study concluded that developed fibres could be a preferred choice for application on hard-to-heal wounds with high levels of exudate, to support infection control and faster healing.

Background: Aloe vera has been reported as a topical antibiotic and healing agent for wounds, but advantages of oral administration and mechanisms of wound healing have not been reported. Present study focuses on the evaluation of effects of oral administration of Aloe vera for excisional cutaneous wounds in Sprague Dawley rats., Methods: Sprague Dawley (SD) rats were inflicted with excisional wounds and were either treated with Aloe vera orally (Aloe vera) or kept untreated (wound). In contrast, healthy rats were kept as control group. Wound area was measured from day 7th to day 21st. Collagen content was estimated by hydroxyproline assay. Histology was analysed by hematoxylin and eosin staining. Angiogenesis was observed by indirect ELISA for Insulin like Growth Factor (IGF-1) and Vascular Endothelial Growth Factor (VEGF) protein from skin, serum and bone marrow. Chemotaxis was evaluated by RT-PCR analysis for Stromal cell-Derived Factor-1 (SDF-1) and C-X-C chemokine receptor type 4 (CXCR-4) from skin and bone marrow., Results: Aloe vera healed wounds earlier than untreated rats with gradual improvement in wound areas and collagen content. Aloe vera also improved the expression of IGF-1 and VEGF in skin and bone marrow indicating an improvement in angiogenesis. RT- PCR analysis showed increased expression of genes for chemotaxis (SDF-1 and CXCR-4) in skin and bone marrow., Conclusion: Aloe vera improves healing by increasing collagen content, improving angiogenesis and chemotaxis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The use of biological dressings has recently emerged in the management of burns and wounds. The aim of the present study was to evaluate the Nile tilapia skin as a biological dressing for full-thickness cutaneous metacarpal wounds in donkeys. The study was conducted on nine clinically healthy donkeys (n = 9). Here, fish skin dressings were obtained from fresh Nile tilapia (Oreochromis niloticus and sterilized by immersion in silver nanoparticles (AgNPs) solution for 5 min, with no change in collagen content. Bilateral, circular full-thickness excisional skin wounds (2 cm in diameter) were created on the dorsal aspect of the mid-metacarpals of each donkey. Wounds on the right metacarpals (treated wounds, n = 9) were dressed with sterile fish skins, while wounds on the left metacarpals (control wounds, n = 9) were dressed with sterile non-adherent dressing pads without any topical applications. Wound dressings were changed weekly. Wounds were evaluated microbiologically, grossly, and histologically on days 7, 14, and 21 post-wound inductions., Results: Fish skin-dressed wounds showed a significant (P < 0.0001) reduction in microbial counts (Total viable bacterial count, Staphylococcal count, and Coliform count), a significant (P < 0.0001) decrease in the wound size, and a significant reduction (P < 0.0001) in the epithelial gap compared to the untreated wounds. No frequent dressing changes were needed., Conclusions: Fish skin dressing accelerated the wound healing process and efficiently inhibited the local microbial activity and exuberant granulation tissue formation suggesting its reliable and promising application for metacarpal wounds of donkeys.

Objective: To determine the number of specialised wound care units/clinics (SWCUs) in Spain, at present, and to describe their most important characteristics., Method: This was an observational study with a descriptive-analytical, cross-sectional, multicentre approach, where the studied population consisted of SWCUs in Spain. A specific data-collection questionnaire was designed using a modified Delphi method, consisting of four rounds, with the collaboration of 10 wound experts. The final questionnaire included 49 items distributed across four dimensions/areas with a content validity index (CVI-Total for pertinence=0.96 and CVI-Total for relevance=0.94., Results: A total of 42 SWCUs were included in the study. Most SWCUs were based in hospitals (n=15, 35.7%) or healthcare centres, covering a specific healthcare area (n=17, 40.5%). SWCU coordinators were primarily nurses (n=33, 78.6%). Staff members' professions in SWCUs included registered nurses (n=38 units, 92.7%), nursing assistants (n=8 units, 19.5%), podiatrists (n=8 units, 19.5%), vascular surgeons (n=7 units, 17%), osteopaths (n=2 units, 4.8%) and medical doctors from different specialties (n=3 units, 7.2%). For wound aetiology, the most prevalent wounds managed were diabetic foot ulcers (n=38 units, 90.5%), followed by venous leg ulcers (n=36 units, 85.7%) and arterial ischaemic ulcers (n=36 units, 85.7%). A statistically significant association was found between the number of staff members in a SWCU and the existence of resistance/opposition barriers when developing a SWCU (Chi-square test, p=0.049; Cramér's V=0.34; 34%), as well as between resistance/opposition barriers when developing a SWCU and a nurse as coordinator of a SWCU (MacNemar test, p=0.007, Cramér's V=0.35; 35%)., Conclusion: The typical SWCU implemented in Spain is located in a hospital or integrated in a healthcare structure that offers coverage to a whole health area and providing services for people with hard-to-heal wounds (wound management and prevention) and health professionals (advice, consultancy and training/education). Despite the growing number of SWCUs in Spain, the future of this new organisational model is uncertain, as there can be barriers to creating them and some deficiencies, such as low staff numbers, which need to be addressed.

Wound-related problems following breast surgery are common. Delayed wound healing can lead to poor cosmesis and, among breast cancer patients, can result in delays in receiving adjuvant treatment. The aim of our review was to look at the literature in relation to the role of negative pressure wound therapy in oncoplastic breast surgery, as at the time of writing, there is no consensus on the use of prophylactic negative pressure dressings in closed wounds following breast surgery.

Objective: In critical limb ischaemia (CLI), first-line therapy is revascularisation, but alternative treatment options are needed in certain cases. Maggot debridement therapy (MDT) is historically considered to be contraindicated in ischaemic ulcers. Wound care in patients with CLI is becoming increasingly diverse with the development of novel revascularisation strategies; therefore, CLI now needs to be reconsidered as an indication for MDT., Method: We retrospectively reviewed five legs with CLI (five male, one female) treated with MDT between January 2013 and December 2017. Changes in skin perfusion pressure (SPP) around the ulcer before and after MDT were evaluated. One or two cycles of MDT were performed (eight in total). We also evaluated the proportion of necrotic tissue in the ulcer and the presence of exposed necrotic bone. The proportion of necrotic tissue in the ulcer was classified as NT 1+ (<25%), NT 2+ (25-50%), NT 3+ (50-75%) or NT 4+ (>75%)., Results: When the proportion of necrotic tissue was >50%, with no exposed necrotic bone in the wound, an increase in SPP was observed after five (62.5%) of eight cycles of MDT. And with a proportion of necrotic tissue of <25% and/or exposed necrotic bone in the wound, a decrease in SPP was observed after three (37.5%) of eight cycles. Wound healing was accelerated in the presence of increased SPP., Conclusion: Effective MDT with increased SPP requires an ulcerative state of necrotic tissue grade > NT 3+, with no exposed necrotic bone.

Objective: Tie-over dressing is the most frequently used technique of skin grafting. However, many deficiencies affecting the outcome have been reported. We hereby introduce a modified method, termed the 'extra-wound fixation technique', for skin dressing, and evaluate the complications and clinical outcomes., Method: In this retrospective cross-sectional study we analysed the medical records of patients treated between January 2012 and December 2017. All patients received full thickness skin grafts. Patients were divided equally into to groups: patients were treated using the extra-wound fixation technique, and the remaining, randomly selected patients treated using the traditional tie-over method. The extra-wound fixation technique uses the traditional tie-over dressing method followed by additional stitches made in healthy skin locating 0.5-1.0 cm laterally to the wound edge. The follow-up outcomes between the two groups were compared using the Chi-square test., Results: A total of 38 patients took part (19 patients in each group). The follow-up duration was 1-6 months. No raised edges were observed in any of the patients. Prolonged follow-up demonstrated that the grafted skin texture became soft with a thin layer of adipose tissue, and elasticity was gradually improved along with the regeneration of dermoelastic fibre. The colour was similar to the normal skin with a smooth surface. Compared with the traditional method, the extra-wound fixation technique significantly improved the survival of the grafted skin (p=0.008), reduced the risk of laceration of the skin (p=0.001), and eliminated crater rim-like appearances (p=0.020)., Conclusion: The extra-wound fixation technique could be used for different skin grafts and improve clinical outcomes compared with the traditional tie-over dressing method.

Objective: Accelerating the process of wound healing, reducing infection risks, and decreasing pain and discomfort in the burn area are important goals of burn treatment. To achieve these goals, the use of biosynthetic wound dressings has increased in recent years. Suprathel (PolyMedics Innovations, Germany) is a biosynthetic wound dressing used to treat both partial-thickness burns and split-thickness skin graft (STSG) donor sites, full-thickness wounds, large-scale abrasions, and scar revisions., Method: This study is a systematic review of empirical evidence reported on the application of the biosynthetic wound dressing in burns up to 2017. Keywords such as 'Suprathel', 'effectiveness', 'safety', and 'cost' were searched in PubMed, Cochrane, Scopus and Embase databases., Results: A total of 14 publications were identified, based on the inclusion and exclusion criteria. The findings reported in the literature reviewed were classified in terms of safety, effectiveness and cost-effectiveness of use of the biosynthetic wound dressing. Regarding safety and effectiveness, the dressing was found to yield desirable results, particularly for partial thickness burns and STSG donor sites. As of 2017 no health economics assessments have been carried out., Conclusion: Despite the desirable advantages of the biosynthetic wound dressing with respect to its effectiveness, safety and ease of use, its major limitation was found to be its cost. However, in the absence of comprehensive studies on the quantification of all factors, there is scant scientific evidence for making reliable conclusions from this systematic review.

The main component of plasma medicine is the use of low-temperature plasma (LTP) as a powerful tool for biomedical applications. LTP generates high reactivity at low temperatures and can be activated with noble gases with molecular mixtures or compressed air. LTP reactive species are quickly produced, and are a remarkably good source of reactive oxygen and nitrogen species including singlet oxygen (O 2 ), ozone (O 3 ), hydroxyl radicals (OH), nitrous oxide (NO), and nitrogen dioxide (NO 2 ). Its low gas temperature and highly reactive non-equilibrium chemistry make it appropriate for the alteration of inorganic surfaces and delicate biological systems. Treatment of oral biofilm-related infections, treatment of wounds and skin diseases, assistance in cancer treatment, treatment of viruses' infections (e.g. herpes simplex), and optimization of implants surfaces are included among the extensive plasma medicine applications. Each of these applications will be discussed in this review article., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: It is estimated that 2% of the population in developing countries suffer from a chronic wound, making it a hidden phenomenon that is increasing as populations age. The ease of access to maggot therapy has made it increasingly attractive for implementation. This study aimed to explore the effectiveness of maggot therapy as compared to hydrogel dressings in the healing of chronic wounds., Methods: An electronic literature search until October 2019 was performed using Medline, Embase, and Cumulative Index of Nursing and Allied Health Literature. The eligibility criteria were chronic wound patients with an intervention that involved a comparison of any maggot species with hydrogel dressings., Results: The full text of five studies, involving 580 patients with chronic wounds, was retrieved. Four studies used the Lucilia sericata species. The maggot therapy facilitated faster and more effective debridement of non-viable tissue. It enabled faster development of granulation tissue and increased reduction in the wound surface area compared to hydrogel dressings. Maggot therapy had no effect on disinfection or complete healing rate for the wound., Conclusion: Maggot therapy should be considered for faster wound debridement, granulation tissue development, and wound surface area reduction as well as in surgical contraindications. This review can be used as a guide to assist clinicians in identifying patients who may benefit from maggot therapy., Competing Interests: The authors declare no conflict of interests.

Chronic wounds often are the result of bone deformities, compounded by musculotendinous and ligamentous imbalance. Sensory neuropathy places patients at greater risk for acute wounds to develop into chronic wounds. Etiologies of these deforming forces include Charcot neuroarthropathy, trauma, and congenital and acquired neuromuscular disorders. Management of these deformities ranges from simple relief of pressure with soft inserts to bracing for mechanical instability. Correction of more complex deformities requires resection of bone, osteotomies, fusions, and external fixation. Tendon and ligament imbalance must be addressed at all levels of deformity. Postoperatively, patients must be re-evaluated for continuation of orthoses and bracing., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to assess the clinical effectiveness of surgically implanted cryopreserved human umbilical cord allograft in treating hard-to-heal wounds with and without osteomyelitis., Method: In this single-centre, retrospective investigation, wounds (average size 6.9±10.1cm 2 ) were included for analysis that had failed prior standard wound care for an average of 14.4±8.0 weeks., Results: After surgical implantation of cryopreserved umbilical cord between the deep tissue planes, 20 (95%) of the 21 wounds included in the study achieved complete closure in a median time of 7.8 weeks (range: 1-68) despite presence of residual osteomyelitis in 15 cases. A total of 12 wounds (57.1%) healed by 12 weeks, and 16 (76.2%) wounds healed by 24 weeks. A patient who presented with a limb-threatening calcaneal ulcer that was complicated by osteomyelitis at the time of treatment required subsequent amputation. No adverse events or complications related to cryopreserved umbilical cord were observed., Conclusion: The results suggest that surgical implantation of cryopreserved umbilical cord allograft may be a safe and effective treatment in improving healing of hard-to-heal wounds. Further prospective, randomised controlled trials are warranted.

Objective: To assess the safety and efficacy of a surfactant-based technology for the management of burns., Method: In a retrospective review, paediatric patients with different types of burns were treated with the gel technology. In some patients, the treatment was combined with a topical antimicrobial agent. Primary objectives of the review were the assessment of healing, healing times and ease of use of the material., Results: The wounds of 15 paediatric patients with different types of burns, particularly with regard to depth and anatomical location, were evaluated using a retrospective chart review. It was found that the surfactant gel technology, with or without the topical antimicrobial agent, assisted in autolytic debridement, and that time to re-epithelialisation was short and within the range of those obtained with other established treatments., Conclusion: The number of patients and wounds in this evaluation is small but the study indicates that the gel technology provides a safe and effective way to treat smaller burns in paediatric patients.

Objective: The use of honey for wound treatment and care purposes is based on thousands of years of history. The development of science and in vitro/in vivo studies have demonstrated that honey contributes to wound healing by showing therapeutic effects by means of the bioactive compounds it contains. The aim of this systematic review was to evaluate the place of honey in wound treatment by investigating the randomized controlled studies., Method: 30 publications which were obtained as a result of the scans in the databases and which comply with the evaluation criteria were included in the review., Results: In the results of the study, it was reported that honey in acute and chronic wounds provided rapid epithelization and wound contraction in wound healing, had anti-inflammatory and debridement effect, decreased the pain, ensured infection control, shortened the time of wound healing and was cost-effective., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interests regarding the publication of this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: The elderly are at high risk for developing chronic skin wounds, but the effects of intrinsic aging on skin healing are difficult to isolate due to common comorbidities like diabetes. Our objective is to use multiphoton microscopy (MPM) to find endogenous, noninvasive biomarkers to differentiate changes in skin wound healing metabolism between young and aged mice in vivo . Approach: We utilized MPM to monitor skin metabolism at the edge of full-thickness, excisional wounds in 24- and 4-month-old mice of both sexes for 10 days. MPM can assess quantitative biomarkers of cellular metabolism in vivo by utilizing autofluorescence from the cofactors nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD). Results: An optical redox ratio of FAD/(NADH+FAD) autofluorescence and NADH fluorescence lifetime imaging revealed dynamic changes in keratinocyte function during healing. Aged female mice demonstrated an attenuation of keratinocyte proliferation during wound healing detectable optically through a higher redox ratio and longer NADH fluorescence lifetime. By measuring the correlation between NADH lifetime and the optical redox ratio at each day, we also demonstrate sensitivity to the proliferative phase of wound healing. Innovation: Label-free MPM was used to longitudinally monitor individual wounds in vivo , which revealed age-dependent differences in wound metabolism. Conclusion: These results indicate in vivo MPM can provide quantitative biomarkers of age-related delays in healing, which can be used in the future to provide patient-specific wound care., Competing Interests: J.D.J., A.E.W., H.E.R., A.V., and K.P.Q. declare no conflicting financial interests. The content of this article was expressly written by the authors listed. No ghostwriters were used to write this article., (Copyright 2020, Mary Ann Liebert, Inc., publishers.)

Most chronic wounds are related to comorbidities, for which no clinical trials are performed. This retrospective propensity matched-cohort study examined data from 2 074 000 lower extremity wounds across 644 institutions to determine the effectiveness of TheraSkin plus standard of care (SOC; n = 1997) versus SOC alone (n = 1997). Multivariate modelling comparing outcomes such as healing rates, percent area reductions (PARs), amputations, recidivism, treatment completion, and medical transfers were evaluated. A higher proportion of wounds in the treatment group compared with the controls were more likely to close (68.3% versus 60.3%), particularly wounds with exposed structures (64% versus 50.4%) and with lower recidivism at 6 months (24.9% versus 28.3%). The control group was 2.75x more likely to require amputation than the treatment group. The combination of propensity matching and logistic regression analysis on a particularly large database demonstrated that wounds treated with TheraSkin had higher healing rates, higher PARs (78.7% versus 68.9%), fewer amputations, lower recidivism, higher treatment completion (61.0% versus 50.6%), and lower medical transfers (16.1% versus 23.5%) than SOC alone. This study considered data from complex wounds typically excluded from controlled trials and supports the idea that real-world evidence studies can be valid and reliable., (© 2019 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)