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The four stages of wound repair.

The four stages of wound repair.

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The treatment of skin wounds is a key research domain owing to the important functional and aesthetic role of this tissue. When the skin is impaired, bacteria can soon infiltrate into underlying tissues which can lead to life-threatening infections. Consequently, effective treatments are necessary to deal with such pathological conditions. Recently...

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... wound healing, in any tissue, is a normal biological process and it involves four complex steps: homeostasis/coagulation; inflammation, migration and proliferation; re-epithelialization and restoration [30] (Figure 1). Each phase of the wound healing process is influenced by a series of essential mediators, like platelets and cytokines, inflammatory cells, cellular and extracellular matrix, proteinases, growth factors and inhibitors [31]. ...

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... In current clinical practice, doctors still rely on qualitative markers such as swelling or erythema (that is, superficial reddening of the skin) to identify wound infections, which are often difficult to judge in the early stages of biofilm development. With quantitative biophysical signals recorded by our smart bandage, we can provide treatment when clinically used markers are still ambiguous, enabling timely treatment of chronic wounds, reduction in hospital readmissions and medical cost and improvement in patient wound-healing outcomes 44 . We further validated our system in a streptozotocin (STZ)-induced diabetic excisional wound model 45 , also observing an accelerated time to wound closure, improved dermal collagen fiber heterogeneity and increased vascularization (Supplementary Figs. ...
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‘Smart’ bandages based on multimodal wearable devices could enable real-time physiological monitoring and active intervention to promote healing of chronic wounds. However, there has been limited development in incorporation of both sensors and stimulators for the current smart bandage technologies. Additionally, while adhesive electrodes are essential for robust signal transduction, detachment of existing adhesive dressings can lead to secondary damage to delicate wound tissues without switchable adhesion. Here we overcome these issues by developing a flexible bioelectronic system consisting of wirelessly powered, closed-loop sensing and stimulation circuits with skin-interfacing hydrogel electrodes capable of on-demand adhesion and detachment. In mice, we demonstrate that our wound care system can continuously monitor skin impedance and temperature and deliver electrical stimulation in response to the wound environment. Across preclinical wound models, the treatment group healed ~25% more rapidly and with ~50% enhancement in dermal remodeling compared with control. Further, we observed activation of proregenerative genes in monocyte and macrophage cell populations, which may enhance tissue regeneration, neovascularization and dermal recovery.
... In most cases a bacterial load of more than 10 5 viable bacteria per g of wound tissue is considered as an indication of infection [67,68]. Infection occurs when the microorganisms continue to replicate to the extent of invading and damaging soft tissues thus triggering an immune response [69]. ...
... Therefore, as the wound matures into a chronic wound, anaerobes are frequently present at the wound site. Most chronic wounds contain mixed populations of microorganisms, the most common bacterial strains found at the wound site include S. aureus, MRSA, beta-haemolytic Streptococci, E. coli, P. aeruginosa [69,71,72]. ...
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... The aminoglycoside gentamicin (Gm) and the fluoroquinolone ciprofloxacin (Cip) are broad-spectrum antibiotics commonly used to treat wounds containing P. aeruginosa and S. aureus infections (Serra et al., 2015;Negut et al., 2018). These antibiotics display high activity against nonresistant strains of both species. ...
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Chronic wounds infected by Pseudomonas aeruginosa and Staphylococcus aureus are a relevant health problem worldwide because these pathogens grow embedded in a network of polysaccharides, proteins, lipids, and extracellular DNA, named biofilm, that hinders the transport of antibiotics and increases their antimicrobial tolerance. It is necessary to investigate therapies that improve the penetrability and efficacy of antibiotics. In this context, our main objectives were to study the relationship between P. aeruginosa and S. aureus and how their relationship can affect the antimicrobial treatment and investigate whether functionalized silver nanoparticles can improve the antibiotic therapy. We used an optimized in vitro wound model that mimics an in vivo wound to co-culture P. aeruginosa and S. aureus biofilm. The in vitro wound biofilm was treated with antimicrobial combinatory therapies composed of antibiotics (gentamycin and ciprofloxacin) and biofilm-dispersing free or silver nanoparticles functionalized with enzymes (α-amylase, cellulase, DNase I, or proteinase K) to study their antibiofilm efficacy. The interaction and colocalization of P. aeruginosa and S. aureus in a wound-like biofilm were examined and detailed characterized by confocal and electronic microscopy. We demonstrated that antibiotic monotherapy is inefficient as it differentially affects the two bacterial species in the mixed biofilm, driving P. aeruginosa to overcome S. aureus when using ciprofloxacin and the contrary when using gentamicin. In contrast, dual-antibiotic therapy efficiently reduces both species while maintaining a balanced population. In addition, DNase I nanoparticle treatment had a potent antibiofilm effect, decreasing P. aeruginosa and S. aureus viability to 0.017 and 7.7%, respectively, in combined antibiotics. The results showed that using nanoparticles functionalized with DNase I enhanced the antimicrobial treatment, decreasing the bacterial viability more than using the antibiotics alone. The enzymes α-amylase and cellulase showed some antibiofilm effect but were less effective compared to the DNase I treatment. Proteinase K showed insignificant antibiofilm effect. Finally, we proposed a three-dimensional colocalization model consisting of S. aureus aggregates within the biofilm structure, which could be associated with the low efficacy of antibiofilm treatments on bacteria. Thus, designing a clinical treatment that combines antibiofilm enzymes and antibiotics may be essential to eliminating chronic wound infections.
... To inhibit the growth of pathogenic bacteria such as E. coli in wounds, must be a property that hydrogels should have for wound healing (Negut et al. 2018). The growth of this bacteria in wounds makes healing difficult (Edwards and Harding 2004). ...
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... 19 Among the available essential oils for wound care there are Melaleuca oils. 20 Melaleuca is a botanical genus, referring to species that come from the Myrtaceae family, from Australia, Malaysia, or Polynesia. 21 Melaleuca alternifolia oil, commonly known as "tea tree" oil, consists Artigo mostly of cyclic monoterpenes, 16 , 21 being medicinally used due to its antifungal, antioxidant, antimicrobial activities. ...
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NaCMC is a biocompatible polymer that can be crosslinked with citric acid to form a gel matrix. Melaleuca oils have antimicrobial and anti-inflammatory properties with potential for wound healing. The goal of this work was to investigate the characteristics of NaCMC-Melaleuca oils gels. The gels were characterized by FTIR, TGA, mechanical analysis, and in vitro swelling and S. aureus inhibition tests. The oils were characterized using chromatography, presenting high values of (1,8 cineol/terpinen-4-ol), and evaluated for confirmation of their effect against S. aureus. The samples showed physical interactions between NaCMC, citric acid and the Melaleuca oils. Erosion in saline solution was higher in the gels with oils, attributable to interference with crosslinking. The membranes presented high contribution of relaxation mechanism and low contribution of Fickian diffusion regarding the swelling ability. The presence of the oils increased thermal stability and diminished gel fraction and mechanical properties, indicating that the oils interact with the matrix anchoring the chains. Although melaleuca oils themselves were active against S. aureus and CA was responsible for the NaCMC hydrogels activity, the incorporation of melaleuca oils in NaCMC gels was not reported previously. This report indicates that NaCMC hydrogel may be a proper matrix for essential oils incorporation.
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... Such use of nanoparticles in wound healing is thought to enhance healing through promoting the antimicrobial and anti-inflammatory activities of herbal extracts (Pannerselvam et al. 2017;Rajendran et al. 2018;Permana et al. 2021). Nanotechnology promotes sustainable use of medicines, improves health outcomes and helps minimise side effects (Negut et al. 2018;Patra et al. 2018). As such, in vivo wound antimicrobial activities of B. boehmii crude extracts and their synthesised silver nanoparticles were evaluated. ...
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Brachystegia boehmii leaf extracts are ethnopharmacological known to treat microbial infections in burn wounds. Coupling the action of the traditional plant medicine and nanotechnology gives rise to innovative strategies for healing burn wounds. This study aimed to determine the effect of B. boehmii extracts and their green synthesised nanoparticles on bacteria which infect burn wounds. The effects of water, chloroform and methanolic leaf extracts were compared with the effects of the phytosynthesised silver nanoparticles on burn wound infectious bacteria. Dried leaves were extracted using the maceration technique, followed by filtration and concentration of the filtrate using a rotavapor. Drying was achieved by using a centrivap and appropriate masses were dissolved in dimethyl sulfoxide to achieve 100 mg/ml concentrations. Silver nanoparticles were synthesised using the methanol extract of the plant leaves and characterised using a UV–VIS spectrophotometer. The disc diffusion method was used to assess the bacterial susceptibility levels with Ciprofloxacin as the positive control and DMSO and 1 mM silver nitrate as the negative controls. The green synthesised silver nanoparticles produced a yellowish colour with a peak at 420 nm wavelength. They exhibited antibacterial activity against all five bacteria; Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus and Staphylococcus epidermidis comparable to those of the B. boehmii leaf solvent extracts. A zone of inhibition of 20 ± 1.00 mm was obtained on the action of B. boehmii leaf extract against P. aeruginosa. Plant synthesised nanoparticles exhibited broad spectrum antibacterial activity and hence are potential future burn wound antibacterial therapeutics.
... When a skin injury occurs, microorganisms around the surrounding tissue would invade the wound and initiate an infection [3]. The presence of pathogens interferes with the inflammation stage and, as a result, delays the proliferation and remodeling stage which leads to tissue damage [4][5]. An infected wound takes longer to heal than the normal healing process [6]. ...
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... Phenolic compounds can be extensively used in the treatment of different bacterial infections without causing a simultaneous toxic effect on tissues, and on the other hand, are cost-effective treatment options [10,11]. The antibacterial mechanisms of phenols are considered to be related to the inhibition of the nuclear factor-kappa B (NF-κB) pathway, but also other signaling pathways, including transforming growth factor-beta (TGF-β) and mitogen-activated protein kinase pathway are considered [2,12,13]. The effectiveness of different phytochemicals varies, as they play a particular role in the different phases of wound healing. ...
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This study aimed to highlight the importance of phytochemical-based formulations in the treatment of wounds with different etiologies, avoiding the possible side effects generated by conventional treatments. We present the preparation method of novel topical formulations (cream, ointment, and hydrogel) based on mixed extracts of Ocimum basilicum and Tifolium pratense along with evidence of their antimicrobial and antioxidant effect in vitro. The anti-inflammatory and wound healing properties of the new formulations were evaluated against different chronic inflammatory processes by presenting three clinical cases of chronic skin diseases. The clinical cases presented in our study revealed good outcomes of the cream formulation in the case of dyshidrotic eczema, ointment formulation in the case of hypertrophic scar, and hydrogel formulation in the case of psoriasis lesions. The best effect was noticed after 6 days of topical application of hydrogel on psoriatic plaques, resulting in a significant reduction of erythematous plaques.
... According to a market research study, due to advancing technology, expensive wound care procedures, and increasing geriatric population, wound closure and dressing market will expand to $15 billion and $22 billion by 2022 and 2024, respectively. In progressing biomedical research era, several methods such as conventional and advanced dressing, biomaterial-based matrices, growth factors (GFs), cell-based therapies, and nanotechnology procedures are used to overcome wound healing complications (Gimble et al. 2007;Engel et al. 2008;Mason and Dunnill 2008;Negut et al. 2018). However, due to the economic burden of wound healing procedures, there is a great demand for effective, economical, and sideeffect-free healing strategies. ...
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Rise in the incidences of chronic degenerative diseases with aging makes wound care a socio-economic burden and unceasingly necessitates a novel, economical, and efficient wound healing treatment. Platelets have a crucial role in hemostasis and thrombosis by modulating distinct mechanistic phases of wound healing, such as promoting and stabilizing the clot. Platelet-rich plasma (PRP) contains a high concentration of platelets than naïve plasma and has an autologous origin with no immunogenic adverse reactions. As a consequence, PRP has gained significant attention as a therapeutic to augment the healing process. Since the past few decades, a robust volume of research and clinical trials have been performed to exploit extensive role of PRP in wound healing/tissue regeneration. Despite these rigorous studies and their application in diversified medical fields, efficacy of PRP-based therapies is continuously questioned owing to the paucity of large samplesizes, controlled clinical trials, and standard protocols. This review systematically delineates the process of wound healing and involvement of platelets in tissue repair mechanisms. Additionally, emphasis is laid on PRP, its preparation methods, handling, classification,application in wound healing, and PRP as regenerative therapeutics combined with biomaterials and mesenchymal stem cells (MSCs).