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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.

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.

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.)

Background: Skin and its mucus are known to be the first barrier of defence against any external stressors. In fish, skin wounds frequently appear as a result of intensive culture and also some diseases have skin ulcers as external clinical signs. However, there is no information about the changes produced by the wounds in the mucosae. In the present paper, we have studied the alterations in the proteome map of skin mucus of gilthead seabream during healing of experimentally produced chronic wounds by 2-DE followed by LC-MS/MS. The corresponding gene expression changes of some identified skin proteins were also investigated through qPCR., Results: Our study has successfully identified 21 differentially expressed proteins involved in immunity and stress processes as well as other metabolic and structural proteins and revealed, for the first time, that all are downregulated in the skin mucus of wounded seabream specimens. At transcript level, we found that four of nine markers (ighm, gst3, actb and krt1) were downregulated after causing the wounds while the rest of them remained unaltered in the wounded fish. Finally, ELISA analysis revealed that IgM levels were significantly lower in wounded fish compared to the control fish., Conclusions: Our study revealed a decreased-expression at protein and for some transcripts at mRNA levels in wounded fish, which could affect the functionality of these molecules, and therefore, delay the wound healing process and increase the susceptibility to any infection after wounds in the skin of gilthead seabream.

The objective of this study was to analyse the changes of inflammatory cytokines level in traumatic rat serum after maggot secretions intervention. Acute traumatic rats were randomly divided into three groups that included maggot secretions group, negative group, and the control group. TNF-α, IL-6, SOD, LPO levels were measured by radioimmunoassay. The experimental results showed that TNF-α, IL-6, and SOD levels in the model group were significantly increased; LPO level was decreased and showed significant differences. Thus, the content of inflammatory cytokines in acute skin wounds could be reduced by maggot secretions, which play a role in enhancing wound healing.

Wound management presents a significant global challenge, necessitating a comprehensive understanding of wound care products and clinical expertise in selecting dressings. Bioactive dressings (BD) represent a diverse category of dressings, capable of influencing wound healing through various mechanisms. These dressings, including honey, hyaluronic acid, collagen, alginates, and polymers enriched with polyhexamethylene biguanide, chitin, and chitosan derivatives, create a conducive environment for healing, promoting moisture balance, pH regulation, oxygen permeability, and fluid management. Interactive dressings further enhance targeted action by serving as substrates for bioactive agents. The continuous evolution of BDs, with new products introduced annually, underscores the need for updated knowledge in wound care. To facilitate dressing selection, a practical algorithm considers wound exudate, infection probability, and bleeding, guiding clinicians through the process. This algorithm aims to optimize wound care by ensuring the appropriate selection of BDs tailored to individual patient needs, ultimately improving outcomes in wound management. [ABSTRACT FROM AUTHOR]

Wound management presents a significant global challenge, necessitating a comprehensive understanding of wound care products and clinical expertise in selecting dressings. Bioactive dressings (BD) represent a diverse category of dressings, capable of influencing wound healing through various mechanisms. These dressings, including honey, hyaluronic acid, collagen, alginates, and polymers enriched with polyhexamethylene biguanide, chitin, and chitosan derivatives, create a conducive environment for healing, promoting moisture balance, pH regulation, oxygen permeability, and fluid management. Interactive dressings further enhance targeted action by serving as substrates for bioactive agents. The continuous evolution of BDs, with new products introduced annually, underscores the need for updated knowledge in wound care. To facilitate dressing selection, a practical algorithm considers wound exudate, infection probability, and bleeding, guiding clinicians through the process. This algorithm aims to optimize wound care by ensuring the appropriate selection of BDs tailored to individual patient needs, ultimately improving outcomes in wound management.

Catecholamines play an important regulatory role in cutaneous wound healing. The exact role of dopamine in human epidermis has yet to be fully elucidated. Current published evidence describes its differential effects on two separate families of G protein coupled receptors: D1-like and D2-like dopamine receptors. Dopamine may enhance angiogenesis and wound healing through its action on dopamine D1 receptors, while impairing wound healing when activating D2 receptors. This review summarizes the evidence for the role of dopamine in wound healing and describes potential mechanisms behind its action on D1 versus D2-like receptors in the skin.

Catecholamines play an important regulatory role in cutaneous wound healing. The exact role of dopamine in human epidermis has yet to be fully elucidated. Current published evidence describes its differential effects on two separate families of G protein coupled receptors: D1-like and D2-like dopamine receptors. Dopamine may enhance angiogenesis and wound healing through its action on dopamine D1 receptors, while impairing wound healing when activating D2 receptors. This review summarizes the evidence for the role of dopamine in wound healing and describes potential mechanisms behind its action on D1 versus D2-like receptors in the skin.

Since its conceptualization in the 1980s, the provisional matrix has often been characterized as a simple fibrin-containing scaffold for wound healing that supports the nascent blood clot and is functionally distinct from the basement membrane. However subsequent advances have shown that this matrix is far from passive, with distinct compositional differences as the wound matures, and providing an active role for wound remodeling. Here we review the stages of this matrix, provide an update on the state of our understanding of provisional matrix, and present some of the outstanding issues related to the provisional matrix, its components, and their assembly and use in vivo.

Wound healing is essential for survival. This is a multistep process involving a number of different cell types. In the skin wounding triggers an acute inflammatory response, with the innate immune system contributing both to protection against invasive organisms and to triggering the invasion of inflammatory cells into the wounded area. These cells release a variety of cytokines and growth factors that stimulate the proliferation and migration of dermal and epidermal cells to close the wound. In particular, wounding activates stem cells in the interfollicular epidermis (IFE) and hair follicles (HF) to proliferate and send their progeny to re-epithelialize the wound. β-catenin and calcium signaling are important for this activation process. Mice lacking the VDR when placed on a low calcium diet have delayed wound healing. This is associated with reduced β-catenin transcriptional activity and proliferation in the cells at the leading edge of wound closure. These data suggest that vitamin D and calcium signaling are necessary components of the epidermal response to wounding, likely by regulating stem cell activation through increased β-catenin transcriptional activity.

Radiotherapy for cancer treatment is often associated with skin damage that can lead to incapacitating hard-to-heal wounds. No permanent curative treatment has been identified for radiodermatitis. This study provides a detailed characterization of the dose-dependent impact of ionizing radiation on skin cells (45, 60, or 80 grays). We evaluated both early and late effects on murine dorsal skin with a focus on the healing process after two types of surgical challenge. The irradiated skin showed moderate to severe damage increasing with the dose. Four weeks after irradiation, the epidermis featured increased proliferation status while the dermis was hypovascular with abundant α-SMA intracellular expression. Excisional wounds created on these tissues exhibited delayed global wound closure. To assess potential long-lasting side effects of irradiation, radiodermatitis features were followed until macroscopic healing was notable (over 8 to 22 weeks depending on the dose), at which time incisional wounds were made. Severity scores and biomechanical analyses of the scar tissues revealed that seemingly healed irradiated skin still displayed altered functionality. Our detailed investigation of both the acute and chronic repercussions of radiotherapy on skin healing provides a relevant new in vivo model that will instruct future studies evaluating the efficacy of new treatments for radiodermatitis.

BACKGROUND: Tissue-engineered skin has a good application prospect in promoting skin tissue wound repair and scarless healing. OBJECTIVE: To review the current research progress, application and value of tissue-engineered skin in vivo and in vitro. METHODS: A computer was used to search the relevant articles in the CNKI database and PubMed database. The Chinese and English search terms were “mesenchymal stem cells; growth factors; skin; wounds; skin repair; wound healing; regenerative medicine; tissue engineering; scaffolds”. The domestic and foreign related application articles on tissue-engineered skin construction in the treatment of skin tissue injury in recent years were checked, and the research progress of mesenchymal stem cells, growth factors, scaffold materials and dressings for new treatment methods for tissue repair was also summarized. The articles irrelevant to the subject of this article were excluded, and 78 articles were finally included for the result analysis. RESULTS AND CONCLUSION: The construction of tissue-engineered skin involves the selection of seed cells, the application of growth factors, and the combination of multiple elements of scaffold materials. Mesenchymal stem cells are one of the important sources of tissue-engineered skin seed cells. Growth factors optimize the tissue culture environment, and scaffold materials provide appropriate mechanical support. Therefore, how to select appropriate seed cells, growth factors and scaffold materials to construct tissue-engineered skin to treat wounds and speed up repair is the focus and research direction that should be explored in the future. In addition, the development of wound materials is also a new field. [ABSTRACT FROM AUTHOR]

Objective: Cardiac pacemakers must be regularly replaced due to depleted batteries. A possible alternative is proposed by subcutaneous photovoltaic energy harvesting. The body's reaction to an implant can cause device encapsulation. Potential changes in spectral light transmission of skin can influence the performance of subcutaneous photovoltaic cells and has not yet been studied in large animal studies. Methods: Subcutaneous implants measuring changes in the light reaching the implant were developed. Three pigs received those implants and were analyzed for seven weeks. Spectral measurements with known irradiation were performed to identify possible changes in the transparency of the tissues above the implant during the wound healing process. A histological analysis at the end of the trial investigated the skin tissue above the subcutaneous photovoltaic implants. Results: The implants measured decreasing light intensity and shifts in the light's spectrum during the initial wound healing phase. In a later stage of tissue recovery, the implants measured a generally reduced light intensity compared to the healthy tissue after implantation. The spectral distribution of the measured light at the end of the trial was similar to the first measurements. The histological analysis showed subcutaneous granulation tissue formation for all devices. Conclusion: The varying reduction of light intensity reaching the implants means that safety margins must be sufficiently high to ensure the power. At the end of the wound healing process, the spectral distribution of the light reaching the implant is similar to healthy tissue. Significance: Optimizations of spectral sensitivity of photovoltaic cells are possible. [ABSTRACT FROM AUTHOR]

Objective: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and severe skin and mucosal reactions that are associated with high mortality. Despite the severity, an evidence-based treatment protocol for SJS/TEN is still lacking. Method: In this systematic review and meta-analysis, the PubMed database was searched using the following terms: [Stevens–Johnson syndrome] OR [toxic epidermal necrolysis] AND [therapy] OR [treatment] over a 20-year period (1999–2019) in the German and English language. All clinical studies reporting on the treatment of SJS/TEN were included, and epidemiological and diagnostic aspects of treatment were analysed. A meta-analysis was conducted on all comparative clinical studies that met the inclusion criteria. Results: A total of 88 studies met the inclusion criteria, reporting outcomes in 2647 patients. Treatment was either supportive or used systemic corticosteroid, intravenous immunoglobulin, plasmapheresis, cyclosporine, thalidomide or cyclophosphamide therapy. The meta-analysis included 16 (18%) studies, reporting outcomes in 976 (37%) patients. Systemic glucocorticoids showed a survival benefit for SJS/TEN patients in all analyses compared with other forms of treatment. Cyclosporine treatment also showed promising results, despite being used in a small cohort of patients. No beneficial effects on mortality could be demonstrated for intravenous immunoglobulins. Conclusion: Glucocorticoids and cyclosporine may be tentatively recommended as the most promising immunomodulatory therapies for SJS/TEN, but these results should be investigated in future prospective controlled trials. [ABSTRACT FROM AUTHOR]

Aims: Postoperative tendon adhesions contribute to functional disability and reconstructive failure. In this study, we present the long-term outcomes of a prospective study in which acellular dermal matrix (ADM) was used to prevent postoperative adhesion after tendon injury. Methods: The study was conducted between March 2014 and February 2017. Patients, aged 19–65 years, with an acute single flexor tendon injury in zones 1 or 2, distal to the palmar digital crease were candidates for the study. Patients were allocated to either an ADM treatment group or a control group without ADM treatment. Results: A total of 37 patients were enrolled in the study: 21 patients in the ADM group and 16 patients in the control group. At six months after surgery, the range of motion in the proximal interphalangeal joint was 81.0±5.1 degrees in the ADM group and 75.8±6.9 degrees in the control group. The range of motion in the distal interphalangeal joint was 79.9±7.1 in the ADM group and 71.2±5.7 degrees in the control group, with significant difference (p=0.03 and p<0.05, respectively). In addition, the total active motion was higher in the ADM group than in the control group. The patients' scores on the Patient Satisfaction Questionnaire were also significantly different, with higher satisfaction scores in the ADM group (p=0.02). The minimal follow-up period was six months. Conclusion: The use of ADM after tendon repair has the potential to significantly improve the outcome of tendon surgery in terms of range of motion. Declaration of interest: None of the authors has any financial interest in the products, devices, or drugs mentioned in this article. [ABSTRACT FROM AUTHOR]

Objectives: This study is aimed at assessing the safety and effectiveness of an advanced flowable wound matrix (FWM) in the treatment of hard-to-heal vascular leg ulcers that often involve deep structures, are irregular and/or tunnelled or excavated. Methods: Records of patients seen at our Vascular Surgery Unit, at the University of Campania 'Luigi Vanvitelli', for hard-to-heal vascular leg ulcers between January 2018 and January 2020 were retrospectively reviewed. For each wound aetiology, area and complications were recorded and evaluated. Every patient received one or more applications of FWM and was followed up. Results: A total of 22 patients (18 female/four male), mean age 63±8.5 years, were treated. The initial wound area ranged from 4–58cm2. After wound bed preparation, FWM was applied. Treatment was well tolerated and effective—rate of complications was low, graft take was very satisfactory, and no graft loss, rejection or superimposed infections were observed. Healing time was short: 85% of ulcers healed after 12 weeks. Most importantly, there was a decrease in the rate and level of amputations as compared with standard wound care. Conclusions: The data presented indicate that FWM is an option for the treatment of hard-to-heal vascular leg ulcers, particularly for those with an irregular cavity. Declaration of interest: The authors have no conflicts of interest. [ABSTRACT FROM AUTHOR]

Objective: Due to the similarities of glabrous skin, the plantar region is an excellent donor area for covering complex palmar–plantar wounds. However, taking grafts from the plantar area often results in significant morbidity at the donor site or non-integration of the graft due to the greater thickness of the plantar corneal layer. Method: This is a prospective case series including patients with burns or wounds who have been treated with a dermal graft using the bilaminar 'trapdoor' technique. This procedure is used to remove a thin graft from the deep plantar dermis after the partial elevation of the first layer including the entire epidermis and superficial part of the dermis. Results: At the donor area in the four patients in this case series, we observed healing at around 10 days, and absence of hypertrophic scar in all patients. There was complete re-epithelialisation between two and three weeks from the periphery to the centre of the deep dermal graft, and from the glandular epithelium transferred with the graft. During the follow-up, patients presented aesthetic and functional features of glabrous and amelanotic skin, with similar resistance to those of the adjacent areas of the wound in the palmar–plantar region. Conclusion: This technique has some advantages, such as less surgical time, minimal morbidity in the plantar donor area, easy integration of the grafts, and maintenance of the functional and aesthetic properties of glabrous skin both in the plantar donor area and in the palmar–plantar recipient region. Declaration of interest: The authors have no conflicts of interest to declare. [ABSTRACT FROM AUTHOR]

Surgical incision infection of multidrug-resistant microorganisms (e.g., methicillin-resistant Staphylococcus aureus, MRSA) is a severe cause of poor wound healing, which is prevalent in healthcare facilities and constitutes a huge infectious disease burden in the world. The purpose of this study is to investigate the medical application and possible mechanisms of the cold atmospheric plasma jet on infected wounds. In this article, the New Zealand rabbit in vivo wound infected with MRSA is used as the wound healing animal model. The helium atmospheric-pressure dielectric-barrier-discharge (AP-DBD) plasma jet is employed to treat the wounds infected with MRSA. The wound healing, histological, and cytokine analyses are conducted to evaluate the efficacy of the helium AP-DBD plasma jet on the MRSA-infected wound healing process. The experimental results show that the helium AP-DBD plasma jet treatment on the wounds infected with MRSA can regulate the secretion of the cytokines, limit the inflammatory response and cell excessive proliferation, accelerate the process of re-epithelialization, and consequently, promote the wound healing process and the inactivation of the bacteria. [ABSTRACT FROM AUTHOR]

Objective: The use of emollients to lubricate dry skin to prevent diabetic foot ulcers (DFUs), especially in neuroischaemic feet, has been recommended. This study analyses the effect of daily topical application of hyperoxygenated fatty acids emulsion on transcutaneous oxygen pressure (TcPO2) in the feet of neuropathic and neuroischaemic patients with diabetes. Method: Patients with diabetes and no active foot ulcer were included in this longitudinal, prospective, non-comparative clinical trial. The evolution of TcPO2 (mmHg) values after the application of the tested emulsion (Corpitol Emulsion, Laboratoires Urgo Medical, France) was evaluated for a three-month period. Modifications of skin features (skin dryness, skin shedding and skin colour) were also analysed. TcPO2 was performed using a TCM400 device (Radiometer, Denmark). Results: A total of 50 patients were included in the study. Patients with neuroischaemia showed a significant increase in TcPO2 values (35.69±13.88mmHg) after two months' application of the tested emulsion that remained at month three (day 60: 42.34±10.98mmHg; p=0.006; day 90: 41.62±10.88mmHg; p=0.011). Skin dryness and shedding showed an improvement from baseline to the end of the study in both groups, secondary to the use of the tested emulsion (p<0.001 and p<0.001, respectively). Skin colour also showed differences from baseline to the final visit in the neuroischaemic patients (p=0.029). Patients with neuropathy did not show any change in skin colour from baseline to the final visit. Conclusions: Analysis of the use of the tested emulsion showed an increase in TcPO2 and an improvement in skin trophism in patients with neuroischaemic foot. [ABSTRACT FROM AUTHOR]

Dextrin and dextrin-polyethylene oxide (DEX/PEO) fibers in the submicron range were produced by electrospinning of single and blend polymer solutions. The morphology, intermolecular interactions, and mechanical properties of dextrin microfibers with and without PEO were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, Raman spectroscopy, X-ray diffraction, nuclear magnetic resonance spectroscopy, and uniaxial tensile testing. Spectroscopic results confirmed hydrogen bond formation, evidencing dextrin as a molecular entanglement source for fiber mechanical reinforcement. The uniaxial tensile tests demonstrated a synergistic mechanical reinforcement effect that varied with blend composition. Equal weight ratio blends supported a maximum tensile strength with a high elastic modulus and demonstrated to be more elastic and resistant to breaking, even than pristine PEO fibers. Moreover, elastic moduli of blend fiber mats were found to lie within the value range for human skin, thus providing the DEX/PEO meshes with potential applicability as skin tissue scaffolds. This synthesis approach proved the feasible and inexpensive fabrication process of natural-synthetic polymer hybrid fibers that combine the biocompatibility, biodegradability, and encapsulating capability of dextrin with the mechanical strength and flexibility of PEO for the development of scaffolds for tissue engineering and topical drug delivery applications in skin wound healing., INTRODUCTION Electrospinning has garnered much interest in the production of scaffolds and excipients for tissue regeneration, since it is a versatile process for the electrostatic formation of nano- and microfibers [...]

Objective The microcirculatory response of intact human skin to exposure with di CAP for different durations with a focus on the effect of implied mechanical pressure during plasma treatment was investigated. Methods Local relative hemoglobin, blood flow velocity, tissue oxygen saturation, and blood flow were monitored noninvasively for up to 1 hour in 1-2 mm depth by optical techniques, as well as temperature, pH values, and moisture before and after skin stimulation. The experimental protocol (N = 10) was set up to differentiate between pressure- and plasma-induced effects. Results Significant increases in microcirculation were only observed after plasma stimulation but not after pressure stimulus alone. For a period of 1 h after stimulation, local relative hemoglobin was increased by 5.1% after 270 seconds diCAP treatment. Tissue oxygen saturation increased by up to 9.4%, whereas blood flow was doubled (+106%). Skin pH decreased by 0.3 after 180 seconds and 270 seconds diCAP treatment, whereas skin temperature and moisture were not affected. Conclusions diCAP treatment of intact skin notably enhances microcirculation for a therapeutically relevant period. This effect is specific to the plasma treatment and not an effect of the applied pressure. Prolonged treatment durations lead to more pronounced effects. [ABSTRACT FROM AUTHOR]

Skin tears are frequently encountered in emergency and unscheduled care, and are prevalent in older people. Patients may present soon after an acute skin tear, or at a later stage when the wound presentation is different and there are complications. This article describes evidence-based recommendations and strategies for the prevention, assessment and management of skin tears, discusses risk factors and explains when to refer patients for specialist management. [ABSTRACT FROM AUTHOR]