To stimulate the regeneration process and prevent the wound to fail the healing, traditional therapies and natural products have been used with promising results. Using honey and essential oils in a homemade wound-healing salve. Authors observed that the other gel concentrations were less effective in the stimulation of the healing process, probably due to the low concentration (5% gel) and cytotoxic effects (10% gel). The number of maggots introduced into the wound depends on the maggot properties (e.g., age and size) and patient health (e.g., wound size, and content of necrotic tissue), but an average amount of 510 maggots/cm2 of wound surface area is usually used, remaining in the site during 4872h.120,124126, (A) Free maggots suspended in isotonic saline solution before application onto the wound. FOIA Before Traditional treatments for chronic skin wounds are based on daily wound management: debridement to remove necrotic and/or infected tissue, off-loading to release pressure in the wound, and application of skin dressings to absorb wound exudate or to provide a moist environment ( 13 ). Das S, Mishra B, Gill K, Ashraf MS, Singh AK, Sinha M, Sharma S, Xess I, Dalal K, Singh TP, and Dey S: Isolation and characterization of novel protein with anti-fungal and anti-inflammatory properties from Aloe vera leaf gel. McLennan SV, Bonner J, Milne S, Lo L, Charlton A, Kurup S, Jia J, Yue DK, and Twigg SM: The anti-inflammatory agent propolis improves wound healing in a rodent model of experimental diabetes. It has emerged as a viable treatment option for chronic, non-healing wounds when traditional . Download Download PDF. Olczyk P, Komosinska-Vassev K, Winsz-Szczotka K, Stojko J, Klimek K, and Kozma EM: Propolis induces chondroitin/dermatan sulphate and hyaluronic acid accumulation in the skin of burned wound. Indeed, the use of simple paper tape alone has shown promise. Kwakman PH, de Boer L, Ruyter-Spira CP, Creemers-Molenaar T, Helsper JP, Vandenbroucke-Grauls CM, Zaat SA, and te Velde AA: Medical-grade honey enriched with antimicrobial peptides has enhanced activity against antibiotic-resistant pathogens. The authors suggest that the anti-inflammatory effect can be mediated by the downregulation of transcription nuclear factor-B, p38 mitogen-activated protein kinase, and c-jun NH2-terminal kinase (JNK1/2). Oasis wound matrix is a natural skin substitute comprising small intestinal wall-based mucosal cells that are ideal for hard-to-heal non-burn wounds, donor skin graft sites, and superficial burn wounds. The development of good manufacturing practices and regulatory legislation also assume a pivotal role in order to improve the use of traditional therapies by the clinicians and to promote their integration into the national health system. Traditional dressings like gauzes, cotton wool, and natural or synthetic bandages are the most commonly used products in wound care applications.1,21 When applied to the wound, these products absorb high volumes of exudate, which may lead to the drying of the wound bed, and ultimately result in cell death and inhibition of the healing process. World Health Organization, 2012, Potential wound healing agents from medicinal plants: a review, Herbal medicines for wound healing among tribal people in Southern India: ethnobotanical and scientific evidences. A sterile and porous sheet of nylon mesh is also fixed onto the hydrocolloid dressing to cover the maggots, and a gauze pad is used for the drainage of exudate and liquefied necrotic tissue.120,122 In the constrained-access mode, maggots are introduced within small nylon bags (e.g., Biobag) or incorporated within dressings, avoiding the direct contact with the wound (Fig. Jurczak F, Dugr T, Johnstone A, Offori T, Vujovic Z, Hollander D, and on behalf of the AQUACEL Ag Surgical/Trauma Wound Study Group: Randomised clinical trial of hydrofiber dressing with silver versus povidoneiodine gauze in the management of open surgical and traumatic wounds, Soluble sugars, nonstarch polysaccharides, lignin, polysaccharides, glycoproteins, and antiseptic agents, Forms: solutions, creams, mucilage, gels, and dressings, Anti-inflammatory and antimicrobial activities; stimulate cell proliferation, collagen synthesis and angiogenesis; promote wound contraction, Antioxidant and anti-inflammatory activities; stimulate the healing process; improve wound contraction and epithelialization; increase the hydroxyproline and protein content in the wound, Essential oils and water-soluble ingredients; ferulic acid is the main active constituent, Forms: ethanol extracts, ferulic acid dissolved in DMSO, Stimulate the proliferation of human skin fibroblasts, the secretion of collagen, and the expression of TGF- in, Contain two major classes of active compounds: alkaloids (, Forms: gels, aqueous extracts, hexane, and ethanolic extracts dissolved in DMSO, Anti-inflammatory and antibacterial activities; stimulate the proliferation and migration of fibroblasts, SM is the main antioxidant constituent, others include sesamolin and sesaminol, Forms: SM (purity>98%) and SM containing dexamethasone, Improve the wound tensile strength, wound contraction, and the hydroxyproline levels in both normal and delayed wound models in rats, Routes: intraperitoneal and intramuscular routes, Acids, alcohols, phenols, esters, anthraquinones, sterols, flavonoids, triterpenoids, saccharides, carotenoids, esters, ketones, lactones, lignans, and nucleosides, Forms: ethanol extract of plant leaves mixed with water, Improve the hydroxyproline content and reduce both the wound area and the epithelialization time in excision wounds in rats, Polyphenols, flavonoids, tannins, caffeine, and amino acids, Forms: pure vaseline and ethanolic plant extract (0.6%) ointment, Reduce the healing time and the wound length of incision wounds created in Wistar rats, Most bioactive constituents include terpenoids and polyphenols, such as carnosol, carnosic acid, and rosmarinic acid, Reduce the inflammation and improve the wound contraction, re-epithelialization, angiogenesis, and collagen deposition on full-thickness wounds in diabetic mice, Routes: topical and intraperitoneal injection. Wang SY, Wang JN, Lv DC, Diao YP, and Zhang Z: Clinical research on the bio-debridement effect of maggot therapy for treatment of chronically infected lesions, The use of maggot debridement therapy in the treatment of chronic wounds in hospitalised and ambulatory patients, Dumville JC, Worthy G, Bland JM, Cullum N, Dowson C, Iglesias C, Mitchell JL, Nelson EA, Soares MO, Torgerson DJ, and, VenUS II team: Larval therapy for leg ulcers (VenUS II): randomised controlled trial. Similar results were reported in another study conducted in surgical wounds created in rat models.107. de Almeida EB, Cordeiro Cardoso J, Karla de Lima A, de Oliveira NL, de Pontes-Filho NT, Oliveira Lima S, Leal Souza IC, and de Albuquerque-Jnior RL: The incorporation of Brazilian propolis into collagen-based dressing films improves dermal burn healing, Topical treatment of nonhealing venous leg ulcer with propolis ointment. To address this need, significant efforts have been performed in the research into traditional therapies as alternative clinical treatments for the treatment of these wounds. Materials (Basel). Bethesda, MD 20894, Web Policies The current gold-standard for healing serious wounds is a human skin graft. Current trends move to the development of innovative wound care treatments, combining the use of traditional healing agents and modern products/practices, such as nanofibers containing silver nanoparticles, Aloe veraloaded into alginate hydrogels, propolis into dressing films, and hydrogel sheets containing honey. However, the beneficial effects of the upregulation of cytokines and MMP-9 mRNA for the wound-healing process are not totally clarified by the authors. Among the first non-traditional interventions to enter the realm of U.S. hospitals in the late 1980s and early 1990s was Guided Imagery where a person was assisted in relaxation techniques to help reduce pain and anxiety. Skin wound healing is a multi-stage process that depends on the coordination of multiple cells and mediators. The ability to heal rapidly becomes impaired with aging and onset of disease processes, such as diabetes. Novel strategies for designing regenerative skin products for accelerated wound healing. World Health Organization, 2002, WHO: The Regional Strategy for Traditional Medicine in the Western Pacific (20112020). Oleogel-S10 (Episalvan ) is a drug containing triterpene-rich extract from birch bark which had been approved for treatment of partial thickness wounds in adults in the European Union ( Scheffler, 2019 ). Gupta A, Kumar R, Pal K, Singh V, Banerjee PK, and Sawhney RC: Influence of sea buckthorn (Hippophae rhamnoides L.) flavone on dermal wound healing in rats. Adv Wound Care (New Rochelle). Also, the same products have been observed to be effective in wounds which had persisted without healing for years, showing good response within 7 to . Hemostasis involves several events, such as vascular constriction, platelet aggregation, and fibrin clot formation, with subsequent development of a scab that provides strength, protection, and support to the damaged tissue.2123 During this process, platelets release several growth factors, including the transforming growth factor- (TGF-), epidermal growth factor (EGF), insulin-like growth factor-1, and platelet-derived growth factor (PDGF), which are responsible for the activation of fibroblasts, endothelial cells, and macrophages in the surrounding environment.20,24 The inflammatory phase, occurring simultaneously with the hemostasis, is characterized by the release of several proinflammatory cytokines, cationic peptides, proteases, reactive oxygen species, and growth factors, allowing the wound cleaning.2,20 Growth factors like TGF-, PDGF, fibroblast growth factor, and EGF play an important role in the communication between cells and their ECM, stimulating cell recruitment, proliferation, morphogenesis, and differentiation.23,24 After bleeding, the healing process involves the migration and infiltration of inflammatory cells into the wound. Pereira R, Tojeira A, Vaz D, Mendes A, and Brtolo P: Preparation and characterization of films based on alginate and Aloe vera, Degradation behavior of biopolymer-based membranes for skin tissue regeneration. van der Plas MJ, van der Does AM, Baldry M, Dogterom-Ballering HC, van Gulpen C, van Dissel JT, Nibbering PH, and Jukema GN: Maggot excretions/secretions inhibit multiple neutrophil pro-inflammatory responses, The biobag - a new device for the application of medicinal maggots, Maggots n chips: a novel approach to the treatment of diabetic ulcers. Its chemical composition includes carbohydrates like fructose (40%), glucose (30%), and sucrose (5%); water (20%); amino acids (5%); antioxidants; vitamins; minerals; and enzymes.17,76 Honey can be collected from different sources, which may result in different chemical compositions and, consequently, various levels of therapeutic activity.8,77,78 The use of honey as a natural healing agent has been increasing in healthcare, primarily, due to its ability to provide topical nutrition to the wound, reduce inflammation, and absorb the excess of exudate, this way avoiding maceration.17,75 Several therapeutic activities have been assigned to the honey, including antibacterial, anti-inflammatory, antifungal, and the ability to stimulate angiogenesis, granulation, wound contraction, and epithelialization.77,7981 Honey also provides a debriding effect, reduces edema, and deodorizes the wound.79. Athikomkulchai S, Awale S, Ruangrungsi N, Ruchirawat S, and Kadota S: Tylkowski B, Trusheva B, Bankova V, Giamberini M, Peev G, and Nikolova A: Extraction of biologically active compounds from propolis and concentration of extract by nanofiltration. Traditional therapies include aloe vera, calendula officinalis, honey, propolis, traditional dressings, silver, phenytoin, etc; Modern therapies include modern dressings, bioengineered. The https:// ensures that you are connecting to the The first phase of the healing process, the hemostasis, starts immediately after injury and aims to control the bleeding and to limit the spread of microorganisms within the body. For many people undergoing treatment for cancer or acute and chronic disease management, traditional therapies can assist in the restoration of skin functionality, barrier repair, stress relief and wound healing, pain relief, mental fatigue and anxiety and the aesthetics of the skin by improving hydration and reducing inflammation (Amiel et al . Table 1 presents an overview of some plants under investigation for wound-healing applications.46,3044, Examples of some plants currently investigated for wound-healing applications. National Library of Medicine Frog skin and its secretions have also been explored in traditional medicine as ointment or temporary dressing that cover the wound, preventing the penetration of pathogens and the dehydration.18,75, Honey is a highly viscous and superconcentrated acidic sugar solution (pH=4.0) derived from nectar gathered and modified by the honeybee Apis melfera. This Paper. Zahedi P, Rezaeian I, Ranaei-Siadat S-O, Jafari S-H, and Supaphol P: A review on wound dressings with an emphasis on electrospun nanofibrous polymeric bandages. Porshinsky BS, Saha S, Grossman MD, Beery PR, Ii, and Stawicki SP: Clinical uses of the medicinal leech: a practical review. Although several clinical practices have been tested in order to prevent delayed healing and improve the healing process, the treatment options for chronic wounds are still very limited. Felder JM, 3rd, Hechenbleikner E, Jordan M, and Jeng J: Increasing the options for management of large and complex chronic wounds with a scalable, closed-system dressing for maggot therapy. Scaffold-seeded macrophage transplantation to a skin wound site accelerates healing. Even though no significant differences in the mean healing time between the wounds treated with honey and hydrogel were found, honey proved to be a safe and cost-effective healing agent. This article gives a general overview about the recent advances in traditional therapies for skin wound healing, focusing on the therapeutic activity, action mechanisms, and clinical trials of the most commonly used natural compounds. Burd A, Kwok CH, Hung SC, Chan HS, Gu H, Lam WK, and Huang L: A comparative study of the cytotoxicity of silver-based dressings in monolayer cell, tissue explant, and animal models, In vivo wound healing of diabetic ulcers using electrospun nanofibers immobilized with human epidermal growth factor (EGF). Traditional therapies based on natural origin compounds for skin wound: Honey, pollen and unsaponifiable matter of vegetable derived mixture This is a two . Barajas-Farias LM, Prez-Carren JI, Arce-Popoca E, Fattel-Fazenda S, Alemn-Lazarini L, Hernndez-Garca S, Salcido-Neyoy M, Cruz-Jimnez FG, Camacho J, and Villa-Trevio S: A dual and opposite effect of Calendula officinalis flower extract: chemoprotector and promoter in a rat hepatocarcinogenesis model. The authors have no other affiliations or financial involvement in commercial associations that might create conflict of interest with the article. 2021 Dec 28;7(2):e10279. 2016 May 1;5(5):230-241. doi: 10.1089/wound.2013.0505. Although many studies have focused on the local . Traditional approaches to wound healing. The most common adverse reactions include pain and discomfort associated to the escaping maggots, which are easily solved through the administration of analgesics and the immobilization of maggots within dressings.120,122124,126 Contra-indications for maggot therapy include open wounds in the abdominal cavity, septic arthritis, and pyoderma gangrenosum in patients with immunosuppressive therapy.123. HHS Vulnerability Disclosure, Help Traditional and novel chronic wound treatments and their major tissue effects. Although these products are in general less expensive than the modern treatments, they can be sensitive to the geographic location and season, and exhibit batch-to-batch variation, which can lead to unexpected allergic reactions, side effects, and contradictory clinical results. On the other hand, the release of maggot secretions from the hydrogel dressing into 3T3 fibroblasts and HaCaT (keratinocytes) model wound promotes a significant increase in the wound closure rate after 12h of incubation, suggesting beneficial effects of maggot secretions in the wound-healing process. To avoid this variability, it is necessary to improve the standardization and the quality control assessment of AV products. Any disruption leads to abnormal wound healing [3]. Cazander G, Pawiroredjo JS, Vandenbroucke-Grauls CM, Schreurs MW, and Jukema GN: Synergism between maggot excretions and antibiotics, Promotion of human dermal fibroblast migration, matrix remodelling and modification of fibroblast morphology within a novel 3D model by Lucilia sericata larval secretions. Avoiding unhelpful foods and beverages, including high-sugar items, processed foods and alcohol. official website and that any information you provide is encrypted Oksuz H, Duran N, Tamer C, Cetin M, and Silici S: Effect of propolis in the treatment of experimental Staphylococcus aureus keratitis in rabbits. Aim of this study is to compare NPWT to traditional treatment after STSG for any indication in patients aged 18 to 99. Rossiter K, Cooper AJ, Voegeli D, and Lwaleed BA: Honey promotes angiogeneic activity in the rat aortic ring assay. This plant has exhibited effectiveness on wounds and abscesses with fast healing power as compared to some synthetic antibiotic drugs (Bakari et al., 2012-2018). Basic Definitions and Introduction.- Natural Course of Wound Repair Versus Impaired Healing in Chronic Skin Ulcers.- Milestones in the History of Wound Healing.- Etiology and Mechanisms of Cutaneous Ulcer Formation.- Determining Etiology: History and Physical Examination.- Determining Etiology: Biopsy and Laboratory Investigation.- Tan MK, Adli DSH, Tumiran MA, Abdulla MA, and Yusoff KM: The efficacy of gelam honey dressing towards excisional wound healing. government site. Ukiya M, Akihisa T, Yasukawa K, Tokuda H, Suzuki T, and Kimura Y: Anti-Inflammatory, anti-tumor-promoting, and cytotoxic activities of constituents of marigold (Calendula officinalis) flowers. Introduction. Traditional therapies and compounds are, Influence of fibroin/aloe gel film dressings on the wound healing of normal rat, Processing steps in the fabrication of PMMA nanofibers that contain silver nanoparticles through, MeSH Laboratorial research works in animal models showed that honey significantly improves the healing rate, reduce the scar formation, and inhibit the bacterial growth in burns and acute wounds.8,89,90 Recently, Wang et al.8 developed an hydrogel dressing composed of gelatin (20 wt.%), honey (20 wt.%), and chitosan (0.5 wt.%) for the treatment of burn injuries. New insights in the combination of traditional products with modern treatments and future challenges in the field are also highlighted. Chronic wounds, such as venous ulcers and ischemic wounds, are characterized by the disruption of the normal regeneration process, usually as a result of bacterial colonization, vascular insufficiency, and diabetes, leading to a complicated and delayed healing process.24,25 Such wounds represent one of the most debilitating, painful, and costly skin conditions, being a critical medical and social problem for both patients and countries. Michalsen A, Klotz S, Ldtke R, Moebus S, Spahn G, and Dobos GJ: Effectiveness of leech therapy in osteoarthritis of the knee: a randomized, controlled trial. 1-3 The skin has three different layers: including epidermis, dermis, and hypodermis, which intrinsically are self-renewable and have various functions. (B) The experimental scheme used to test the effect of the delivery of maggot extract from a hydrogel wound dressing onto model wounds in monolayer cell culture.11 To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/wound. An overview of electrospun membranes loaded with bioactive molecules for improving the wound healing process. These enzymes liquefy and dissolve the necrotic tissue, solubilize fibrin clots, and degrade ECM molecules (e.g., fibronectin, laminin, and acid-solubilized collagens I and III), facilitating the digestion by the larvae and stimulating the healing.130,131 Maggots also play an important role in the elimination of bacteria and other pathogens from the wound, including antibiotic-resistant bacteria, such as methicillin-resistant S. aureus and vancomycin-resistant Enterococcus.129,132 An in vivo study showed that maggot therapy is efficient in the treatment of patients with bacteria-infected wounds, but this effect is most pronounced in wounds that contain Gram-positive bacteria.133 The actuating mechanisms behind the antimicrobial activity of larvae are not yet completely understood, though laboratorial and clinical evidence point out that bacterial ingestion and digestion, the high levels of wound exudate, the secretion of natural bactericidal agents (e.g., lucifensin), and the alkalinity of the wounds play a crucial role in the inhibition/elimination of biofilm formation and bacterial growth.120,121,128,134,135 Recent works investigated the synergetic effects between maggot ES and commercial antibiotics on the viability of bacteria and biofilm breakdown.136,137 These works reveal that maggot ES act synergistically with some antibiotics without affecting their therapeutic activity, allowing the effective biofilm breakdown with consequent elimination of derived bacteria. Wound Healing Activities of Gundelia tournefortii L Extract and Milk-Cream Ointment on Second-Degree Burns of Rat Skin - Setareh Javanmardi, Iman Safari, Faranak Aghaz, Mozafar Khazaei, 2021 It has been reported that the in vivo use of C. officinalis extracts at high concentrations produces genotoxic effects in a rat hepatocarcinogenesis model, while clinical trials show either no side effects,7 or the occurrence of allergic dermatitis in 2.03% of the treated patients.74, Animal-origin products, like honey and propolis, have been used in wound care since ancient times due to their therapeutic properties. To stimulate the regeneration process and prevent the wound to fail the healing, traditional therapies and natural products have been used with promising results. The next time you get a paper cut or burn your hand while cooking, pay attention to how quickly it heals. Cazander G, Pritchard DI, Nigam Y, Jung W, and Nibbering PH: Multiple actions of Lucilia sericata larvae in hard-to-heal wounds, Medicinal leech therapy (hirudotherapy): a brief overview. Opasanon S, Muangman P, and Namviriyachote N: Clinical effectiveness of alginate silver dressing in outpatient management of partial-thickness burns. Federal government websites often end in .gov or .mil. Hirudin also acts as a bacteriostatic and bactericidal agent.149,152 Other compounds with relevant biologically active properties (e.g., antibacterial, anti-inflammatory, vasodilation, and analgesic) include calin, destabilase, hirustatin, bdellins, hyaluronidase, tryptase inhibitor, eglins, factor Xa inhibitor, acetylcholine, and histamine like.149 Leech therapy has been extensively employed in wound healing to remove stagnant blood from wounds after reconstruction or plastic surgery, due to the ability of leeches to absorb blood through either puncture the skin or bite, and to release therapeutic compounds (e.g., hirudin) directly into the lesion.152 During the application, leeches absorb the stagnant blood and restore the normal blood flow, oxygenation, and nutrient supply to the affected area, reducing the venous pressure and promoting the healing process.149 In a recent systematic review, Whitaker et al.153 evaluated the current scientific evidence regarding the use of medicinal leeches in plastic and reconstructive surgery for the treatment of diverse skin conditions. Hyperbaric oxygen therapy is being used in wound care facilities to improve tissue oxygenation and wound healing. 8600 Rockville Pike Federal government websites often end in .gov or .mil. However, the use of some therapies is largely supported by wisdom and experience acquired over years, rather than by strong scientific evidence. The wound-healing activity of honey-based products (e.g., solutions, gels, and dressings) has been investigated in both laboratorial studies and clinical trials. Chronic or non-healing wounds resulting from the dysregulation of this process represent a challenge for the healthcare system. Significance: The regeneration of healthy and functional skin remains a huge challenge due to its multilayer structure and the presence of different cell types within the extracellular matrix in an organized way. about navigating our updated article layout. Macroscopic image of Ag+/PVA aqueous solution (A) and transmission electron microscopy images of Ag/PVA linear assembly (B) and Ag/PMMA nanofiber (C).161 AIBN, 2,2-Azobis(isobutyronitrile); MMA, methyl methacrylate; PMMA, poly(methyl methacrylate); PVA, poly(vinyl alcohol). These findings suggest that the development of innovative formulations that contain honey and antimicrobial peptides represent a promising alternative to overcome the just-mentioned limitation. However, there are some important limitations pointed out by the authors that can influence the overall success rate, including the lack of information about the flap size and the administration of antibiotics, as well as the variable number of leeches and time interval between leech applications. Therapeutic Exosomes for Skin Wound Healing. Current trends move to the development of innovative wound care treatments, combining the use of traditional healing agents and modern products/practices, such as nanofibers containing silver nanoparticles, Aloe vera loaded into alginate hydrogels, propolis into dressing films, and hydrogel sheets containing honey. stages of wound healing. National and international authorities (e.g., WHO) have been establishing general guidelines and priorities concerning to the improvement in the safety and quality of traditional medicines/therapies as a way to promote their use, rationalize the medical costs, and extend the access to the healthcare. The use of biopolymers may be a solution to tackle the difficulties such as combining with growth factors and cells that can trigger wound healing. The antibacterial activity of propolis has been studied against a broad spectrum of bacteria, including Gram-positive, Gram-negative, yeasts, and antibiotic-resistant bacteria. Traditional medicine is a common practice in different regions of the world, such as Africa, Asia, and Latin America, contributing to increase the access of population to the healthcare. Among the great variety of silver-based products, SSD is one of the most used, being considered the gold standard for the topical treatment of burns.157,158 Several laboratorial studies have shown the excellent antimicrobial properties of silver-based products against a wide range of microorganisms, including Gram-negative, Gram-positive, and antibiotic-resistant bacteria.159161 These studies suggest that the mechanisms by which silver in ionic form (Ag+) interferes with the normal metabolism of bacteria involve the accumulation of silver ions inside the cells and their binding with negatively charged components in proteins and nucleic acids, which leads to the protein denaturation and structural modifications in the cell walls/membranes.13,157,161,162 Besides the relatively safety and potent bactericidal effect of silver, its use is strongly limited by the cytotoxic effects in mammalian cells.13,163,164 Poon and Burd163 showed that silver from either a silver nitrate solution or a commercial dressing is highly toxic for keratinocytes and fibroblasts in monolayer culture in a dose-dependent manner. Nevertheless, in the last few years, several laboratories focused their research activities on the mechanisms behind the therapeutic efficacy of traditional healing compounds, increasing the knowledge about their action mechanisms and biological activities. The healing mechanism of propolis remains a controversial issue, though this characteristic is likely due to the synergetic effects between the chemical constituents and its antibacterial and anti-inflammatory activities. These issues are of outstanding relevance to improve the safety use of traditional therapies, as well as to fully or partially integrate them into the national health systems. Abstract Significance: The regeneration of healthy and functional skin remains a huge challenge due to its multilayer structure and the presence of different cell types within the extracellular matrix in an organized way. Muangman P, Pundee C, Opasanon S, and Muangman S: A prospective, randomized trial of silver containing hydrofiber dressing versus 1% silver sulfadiazine for the treatment of partial thickness burns. These bacteria are introduced into the wounds during the leech attachment, leading to an infection incidence rate in a range of 2.420%.154 Even though A. hydrophila is resistant to penicillin and first-generation cephalosporins due to the production of beta-lactamase, prophylactic antibiotic therapy can be used to prevent local infections during the leech therapy.154,156. Aloe vera extract contains tannic acid and a type of polysaccharide that helps the wound healing process. Silver is a broad-spectrum antimicrobial agent that is commonly used in the treatment of skin lesions, in particular, wounds and burns. Laboratorial studies have also identified several biologically active constituents in the ES products that play a crucial role in diverse phases of the wound-healing process. Sehn E, Hernandes L, Franco SL, Gonalves CC, and Baesso ML: Dynamics of reepithelialisation and penetration rate of a bee propolis formulation during cutaneous wounds healing. The AV gel also retains the ability to stimulate the fibroblast proliferation, collagen synthesis, and angiogenesis.30,49,50 Although these properties are mainly due to the synergy established between the plant constituents,45,47 several authors claim that the biological activity of polysaccharides (e.g., acemannan, mannose-6-phosphate, pectic acid, galactan, and glucomannan) and glycoproteins (e.g., lectins), present in the leaf pulp, play a major role in the wound-healing process, being responsible for specific properties like anti-inflammatory, antifungal, or cell stimulation.51,52 The cell-stimulating properties of AV are related to the composition of polysaccharides and the binding ability of mannose to some receptors present in the surface of fibroblasts.45,48 Glycerin-Based Hydrogel for Infection Control. One wound was treated with AV, while the other one was topically treated with SSD for comparison. Please enable it to take advantage of the complete set of features! Eshghi F, Hosseinimehr SJ, Rahmani N, Khademloo M, Norozi MS, and Hojati O: Effects of Aloe vera cream on posthemorrhoidectomy pain and wound healing: results of a randomized, blind, placebo-control study. Aloe vera Applied to wounds for over 5000 years by Egyptians, Romans, indigenous peoples of Africa Asia, and the Americas, Aloe veracontinues to be a first-line treatment for burns, ulcers, and surgical wounds [34]. Search type Research Explorer Website Staff directory. To overcome these important limitations, alternative formulations that contain silver ions have been developed and tested, like silver loaded within hydrogel dressings,165 nanoparticles,166 and nanofibers containing silver nanoparticles (Fig. This article gives a general overview about the recent advances in traditional therapies for skin wound healing, focusing on the therapeutic activity, action mechanisms, and clinical trials of the most commonly used natural compounds. Traditional therapies have a wide range of therapeutic properties and, consequently, found different clinical applications, but they cannot permanently substitute the use of high-effective drugs, advanced practices, and innovative cellular therapies. However, a significant number of the available research works are based on poor methodologies involving a small number of studies with few patients. Besides the important progress regarding the development of novel extraction methods, purification procedures, quality control assessment, and treatment protocols, the exact mechanisms of action, side effects, and safety of these compounds need further research. Current trends move to the development of innovative wound care treatments, combining the use of traditional healing agents and modern products/practices, such as nanofibers containing silver nanoparticles, Aloe vera loaded into alginate hydrogels, propolis into dressing films, and hydrogel sheets containing honey. Recent developments on novel extraction procedures, purification methods, processing methodologies, and clinical treatments allowed a significant increase in the quality, efficacy, and safety of traditional therapies. Percival SL, Thomas J, Linton S, Okel T, Corum L, and Slone W: The antimicrobial efficacy of silver on antibiotic-resistant bacteria isolated from burn wounds. Marine and Agro-Industrial By-Products Valorization Intended for Topical Formulations in Wound Healing Applications. Therefore, a biodegradable, bioactive hydrogel wound dressing could be an effective alternative option. However, other agents with high healing-stimulation properties should be subsequently applied in order to reduce the healing time and to improve the properties of the new skin. Boateng JS, Matthews KH, Stevens HNE, and Eccleston GM: Wound healing dressings and drug delivery systems: a review. He is also editor-in-chief of Virtual and Physical Prototyping Journal published by Taylor & Francis, and member of the Editorial Board of several journals like the Biofabrication Journal, the Rapid Prototyping Journal, the International Journal of Precision Engineering and Manufacturing, the Journal of Biomaterials and Tissue Engineering, the ISRN Tissue Engineering, and the International Journal on Mechatronics and Manufacturing Systems. Careers. Proposed underlying mechanisms suggest that maggot ES increase the permeability of the cell wall, which facilitates the action of antibiotics.137 The use of maggot therapy is also associated to the stimulation of the healing process by increasing tissue oxygenation, fibroblast proliferation,120,138 angiogenesis,139 and the formation of granulation tissue.12 These effects are mainly attributed to the maggot ES and its constituents (e.g., serine proteinases), rather than the isolated removal of dead/necrotic tissue. Development of a stem cell spheroid-laden patch with high retention at skin wound site. Jull A, Walker N, Parag V, Molan P, and Rodgers A: Randomized clinical trial of honey-impregnated dressings for venous leg ulcers. These works allowed the development of novel products and clinical practices that are currently used by the clinicians and surgeons in the treatment of different types of skin injuries. Liu X, Lee PY, Ho CM, Lui VC, Chen Y, Che CM, Tam PK, and Wong KK: Silver nanoparticles mediate differential responses in keratinocytes and fibroblasts during skin wound healing. Although the human skin has a natural ability to promote the self-regeneration after damage, this capacity can be compromised under specific conditions, like extensive skin loss, deep burns, chronic wounds, nonhealing ulcers, and diabetes.20,23 An inappropriate healing process can lead the wound to enter in a chronic state, which increases the risk of infection and affects the patient health and his/her quality of life. Lund-Nielsen B, Adamsen L, Kolmos HJ, Rrth M, Tolver A, and Gottrup F: The effect of honey-coated bandages compared with silver-coated bandages on treatment of malignant wounds-a randomized study, Wound healing with honey - a randomised controlled trial, Beneficial effects of honey dressings in wound management. Nowadays, birch bark is clinically proven to be effective for wound healing. Patients of radiation wound and other non-healing wounds need ongoing and personalized wound care in a comfortable, refreshing, and attractive environment. Nitric oxide (NO) is an important endogenous molecule that plays several roles in biological systems. AV is a cactus-like plant that belongs to the Liliaceae Family, growing in tropical climates.45 From the processing of fresh plant leafs, two main products are obtained: (1) a bitter yellow juice, usually known as Aloe vera latex or aloe juice, and (2) a clear mucilaginous gel obtained from the parenchymal tissue, commonly referred as Aloe vera gel or mucilage.4547 Aloe juice was approved by the U.S. Food and Drug Administration as a laxative and cathartic agent.48 AV gel is the most valuable product for the treatment of skin lesions, being composed of a water fraction (9999.5%) and a solid fraction (0.51.0%) containing several biologically active compounds, such as soluble sugars, nonstarch polysaccharides, lignin, lipids, vitamins (B1, B2, B6, and C), enzymes (acid phosphatase, alkaline phosphatase, amylase, and lipase), salicylic acids, proteins, and minerals (sodium, calcium, magnesium, and potassium).45,47 Several therapeutic activities have been attributed to the AV gel, including anti-inflammatory, antiseptic, and antimicrobial properties. 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