Keratinocyte Wound Healing Research Articles

Probiotic-Derived P8 Protein: Promoting Proliferation and Migration in Stem Cells and Keratinocytes.

Probiotics exert various effects on the body and provide different health benefits. Previous reports have demonstrated that the P8 protein (P8), isolated from Lactobacillus rhamnosus, has anticancer properties. However, its efficacy in stem cells and normal cells has not been reported. In this study, the effect of P8 on cell proliferation and wound healing was evaluated, investigating its underlying mechanism. Based on scratch assay results, we demonstrated that P8 treatment significantly increases wound healing by activating the cell cycle and promoting stem cell stemness. Cellular mechanisms were further investigated by culturing stem cells in a medium containing Lactobacillus-derived P8 protein, revealing its promotion of cell proliferation and migration. Also, it is found that P8 enhances the expression of stemness markers, such as OCT4 and SOX2, along with activation of the mitogen-activated protein kinase (MAPK) signaling and Hippo pathways. These results indicate that P8 can promote cell growth by increasing stem cell proliferation, migration, and stemness in a manner associated with MAPK and Hippo signaling, which could contribute to the increased wound healing after P8 treatment. Furthermore, P8 could promote wound healing in keratinocytes by activating the MAPK signaling pathways. These results suggest that P8 might be a promising candidate to enhance stem cell culture efficiency by activating cell proliferation, and enhance therapeutic effects in skin diseases.

Pectin oligosaccharides from Citri Reticulatae Pericarpium ‘Chachi’ promote wound healing in HaCaT keratinocytes by enhancing cell proliferation and migration

Pectin oligosaccharides from Citri Reticulatae Pericarpium ‘Chachi’ promote wound healing in HaCaT keratinocytes by enhancing cell proliferation and migration

M proteins of group A Streptococcus bind hyaluronic acid via arginine-arginine/serine-arginine motifs.

Tissue injury, including extracellular matrix (ECM) degradation, is a hallmark of group A Streptococcus (GAS) skin infection and is partially mediated by M proteins which possess lectin-like properties. Hyaluronic acid is a glycosaminoglycan enriched in the cutaneous ECM, yet an interaction with M proteins has yet to be explored. This study revealed that hyaluronic acid binding was conserved across phylogenetically diverse M proteins, mediated by RR/SR motifs predominantly localized in the C repeat region. Keratinocyte wound healing was decreased through the recruitment of hyaluronic acid by M proteins in an M type-specific manner. GAS strains 5448 (M1 serotype) and ALAB49 (M53 serotype) also bound hyaluronic acid via M proteins, but hyaluronic acid could increase bacterial adherence independently of M proteins. The identification of host-pathogen mechanisms that affect ECM composition and cell repair responses may facilitate the development of nonantibiotic therapeutics that arrest GAS disease progression in the skin.

Non-electrophilic NRF2 activators promote wound healing in human keratinocytes and diabetic mice and demonstrate selective downstream gene targeting

The transcription factor NRF2 plays an important role in many biological processes and is a promising therapeutic target for many disease states. NRF2 is highly expressed in the skin and is known to play a critical role in diabetic wound healing, a serious disease process for which treatment options are limited. However, many existing NRF2 activators display off-target effects due to their electrophilic mechanism, underscoring the need for alternative approaches. In this work, we investigated two recently described non-electrophilic NRF2 activators, ADJ-310 and PRL-295, and demonstrated their efficacy in vitro and in vivo in human keratinocytes and Leprdb/db diabetic mice. We also compared the downstream targets of PRL-295 to those of the widely used electrophilic NRF2 activator CDDO-Me by RNA sequencing. Both ADJ-310 and PRL-295 maintained human keratinocyte cell viability at increasing concentrations and maintained or improved cell proliferation over time. Both compounds also increased cell migration, improving in vitro wound closure. ADJ-310 and PRL-295 enhanced the oxidative stress response in vitro, and RNA-sequencing data showed that PRL-295 activated NRF2 with a narrower transcriptomic effect than CDDO-Me. In vivo, both ADJ-310 and PRL-295 improved wound healing in Leprdb/db diabetic mice and upregulated known downstream NRF2 target genes in treated tissue. These results highlight the non-electrophilic compounds ADJ-310 and PRL-295 as effective, innovative tools for investigating the function of NRF2. These compounds directly address the need for alternative NRF2 activators and offer a new approach to studying the role of NRF2 in human disease and its potential as a therapeutic across multiple disease states.

Pogostemon cablin Extract Promotes Wound Healing through OR2AT4 Activation and Exhibits Anti-Inflammatory Activity.

Skin healing occurs through an intricate process called wound healing which comprises four phases: coagulation and hemostasis, inflammation, cellular proliferation, and remodeling. Chronic wounds often arise because of prolonged or excessive inflammation, which hinders the healing process and wound closure. Despite the recognized efficacy of Pogostemon cablin (patchouli) in wound healing, the precise mechanism of action of Pogostemon cablin extract (PCE) on inflammation and wound healing remains poorly understood. In this study, we investigated the effects of PCE on cell proliferation and wound healing, as well as its anti-inflammatory activity, using in vitro experiments. We found that PCE increased cell proliferation and expression of the cell proliferation marker Ki67 and accelerated wound healing in human keratinocytes through the activation of OR2AT4. Furthermore, PCE exhibited anti-inflammatory effects by decreasing the levels of pro-inflammatory cytokines interleukin-6 and -8 in lipopolysaccharide-treated and TNF-α-exposed THP-1 and HaCaT cells, respectively. Overall, these findings suggest that PCE holds therapeutic potential by promoting cell proliferation, facilitating wound healing, and exerting anti-inflammatory effects.

Wound healing effect of polydeoxyribonucleotide derived from Hibiscus sabdariffa callus via Nrf2 signaling in human keratinocytes

There has been a growing interest in skin recovery in both the medical and cosmetics fields, leading to an increasing number of studies reporting diverse materials being utilized for this purpose. Among them, polydeoxyribonucleotide (PDRN) is known for its efficacy in skin repair processes, while Hibiscus sabdariffa (HS) is recognized for its antioxidant, hypolipidemic, and wound healing properties, including its positive impact on mammalian skin and cells. We hypothesized that these characteristics may have a germane relationship during the healing process. Consequently, we induced calli from HS and then extracted PDRN for use in treating human keratinocytes. PDRN (5 μg/mL) had considerable wound healing effects and wrinkle improvement effects. To confirm its function at the molecular level, we performed real-time polymerase chain reaction, western blotting, and immunocytochemistry. Furthermore, genes related to wound healing (MMP9, Nrf2, KGF, VEGF, SOD2, and AQP3) were significantly upregulated. Additionally, the protein expression of MMP9, AQP3, and CAT, which are closely related to wound healing and antioxidant cascades, was considerably enhanced. Based on cellular morphology and molecular-level evidence, we propose that PDRN from calli of HS can improve wound healing in human keratinocytes. Furthermore, its potential to serve as a novel material in cosmetic products is demonstrated.

Enhanced prokaryotic expression, purification, and biological activities of human keratinocyte growth factor

Keratinocyte growth factor (KGF), also known as fibroblast growth factor 7 (FGF7), plays a critical role in embryonic development, cell proliferation, and differentiation. However, efficient production of recombinant KGF remains a challenge due to its low expression levels and high tendency for aggregation in Escherichia coli. This study aimed to enhance the expression and solubility of KGF by employing different protein tags—PDIb'a', MBP, and His—fused to the N-terminus of KGF. Among these, H-PDIb'a'-KGF demonstrated superior stability and was selected for large-scale production and purification. The purified KGF was confirmed through liquid chromatography with tandem mass spectrometry analysis, which showed an 81% fragment mass identification coverage. Biological activity assessments using human breast cancer MCF-7 cells indicated that purified KGF significantly increased cell proliferation, with an EC50 of 6.4 ± 0.5 pM. Interestingly, PDIb'a' alone also exhibited a stimulatory effect on MCF-7 cells. Furthermore, the purified KGF enhanced the wound healing of HaCaT keratinocytes in a dose-dependent manner. These findings provide valuable insights into the efficient production and functional characterization of recombinant KGF for potential applications in therapeutic interventions.

Couroupita guianensis bark decoction: From Amazonian medicine to the UHPLC-HRMS chemical profile and its role in inflammation processes and re-epithelialization

Ethnopharmacological relevanceIn the Amazon rainforest, the shamans of the Mayantuyacu site use the healing virtues of decoctions and teas from different parts of the Couroupita guianensis Aubl. (Lecythidaceae) trees as remedies in Ashaninka medicine. However, composition of the remedy and the underlying mechanism remain unclear. Aim of the studyThis study was designed to compare the metabolite profile of Couroupita guianensis bark decoction produced by Amazonian shamans with that obtained under standardised laboratory conditions and to investigate biological properties of both decoction and isolated constituents in skin wound healing process and inflammation. Materials and methodsThe chemical analyses were carried out by Ultra-High-Performance Liquid Chromatography coupled with UV and High-Resolution Mass Spectrometry detectors (UHPLC-UV-HRMS). 1D and 2D-NMR experiments were performed to identify the main decoction constituents. The decoction and pure compound effect on keratinocyte migration was determined by the in vitro wound healing model; the mechanism of action was elucidated by western blot analysis. ResultsUHPLC-UV-HRMS analysis revealed the occurrence of polyphenolic compounds as catechins, ellagitannins and, notably, of unusual sulphated derivatives of ellagic acid isolated for the first time from Couroupita guianensis bark. A new natural sulphated molecule [4-(2″-O-sulphate- β-D-glucuronopyranosyl) ellagic acid] was identified as the potential active compound responsible for the efficacy of bark decoction stimulating wound healing in human HaCaT keratinocytes. The molecular mechanism involved the induction of pro-migratory pathways mediated by ERK and AKT phosphorylation and the increase of MMP2 expression in HaCaT cells. At the same time, the treatment inhibited inflammation interfering with NFkB activation. ConclusionBeyond identifying a new bioactive compound, the overall results scientifically validate the traditional use of Couroupita guianensis bark decoction as an anti-inflammatory remedy. Moreover, the beneficial effects on keratinocytes suggest promising therapeutic applications in skin diseases.

Effect of Dermal Fibroblast Conditioned Medium on Keratinocytes Irrespective of Age Group

Skin aging causes delayed re-epithelialisation and impaired wound healing. Thus, supplementation of wound healing mediators and extracellular matrix (ECM) components may be a potential treatment strategy for age-related impaired wound healing. Fibroblasts secrete wound-healing factors and can be collected from used medium, i.e., dermal fibroblast conditioned medium (DFCM). In this study, we elucidated the effect of DFCM on the in vitro wound healing of keratinocytes isolated from different age groups (≥18–35, 36–54, ≥55 years) via cell attachment, growth rate, and wound healing rate assays. The DFCM was prepared by culturing confluent fibroblasts with serum-free keratinocyte-specific (DFCM-KM) and fibroblast-specific (DFCM-FM) medium. The cell attachment efficiency decreased with the increase of age. However, keratinocyte attachment was enhanced in the DFCM-KM group, where it was 1.24, 1.27, and 1.32 times higher of cells concentration for the ≥18–35-, 36–54-, and ≥55-year age groups, respectively, as compared to the control group. The keratinocytes from each age group demonstrated a similar growth profile for all culture conditions, where the DFCM-KM group exhibited a comparable growth rate with the control group whilst the DFCM-FM group exhibited a significantly lower growth rate compared to the other groups. In contrast, the DFCM-FM group demonstrated a significantly higher healing rate in all age groups as compared to the DFCM-KM and control groups. However, there was no significant difference between the healing rates of the DFCM-KM and control groups. In conclusion, DFCM-KM enhanced keratinocyte attachment while DFCM-FM enhanced the keratinocyte healing rate irrespective of donor age, which indicated the potential application of DFCM in wound healing in aged skin.

Effect of cold atmospheric microwave plasma (CAMP) on wound healing in canine keratinocytes.

Cutaneous wound healing is a biological process that occurs upon skin injury and involves different mechanisms to repair tissue damage. Improper healing or prolonged curation period of wound lesions may induce unpleasant complications. Cold atmospheric microwave plasma (CAMP) is an upcoming medical therapeutic option for skin infection and wound treatment. However, the molecular mechanisms of CAMP-mediated canine wound healing are not well characterized. Wound-healing activity was examined to elucidate the biological effects and molecular mechanisms of CAMP. Canine keratinocytes (CPEKs) were treated using CAMP, and their wound-healing activities were evaluated. The molecular mechanisms of that effect were examined, based on RNA-Seq analysis data, and verified using immunoblotting and polymerase chain reaction. It was found that the CAMP-treated cells exhibited a significant increase in cell migration evaluated by scratch assay in human keratinocytes (HaCaT) and canine keratinocytes (CPEK). Additionally, CAMP-treated CPEK cells showed a significant positive effect on cell invasion. The RNA-Seq data revealed that CAMP alters different genes and pathways in CPEK cells. Gene expression involved in the cell cycle, cell proliferation, angiogenesis, cell adhesion, and wound healing was upregulated in CAMP-treated cells compared with gas-activated media used as a control. The Hippo pathway was also analyzed, and the protein and mRNA levels of YAP were significantly increased in CAMP-treated cells. CAMP-treated CPEK cells indicated the downregulation of E-cadherin and upregulation of vimentin, Snail, and Slug at transcription and translation levels, contributing to a favorable effect on cell migration. Our findings suggested that CAMP treatment provided beneficial effects on the curative wound process through the induction of genes involved in wound healing, promotion of EMT, and increase in the molecular targets in the Hippo signaling pathway.

TRPV3-ANO1 interaction positively regulates wound healing in keratinocytes

Transient receptor potential vanilloid 3 (TRPV3) belongs to the TRP ion channel super family and functions as a nonselective cation channel that is highly permeable to calcium. This channel is strongly expressed in skin keratinocytes and is involved in warmth sensation, itch, wound healing and secretion of several cytokines. Previous studies showed that anoctamin1 (ANO1), a calcium-activated chloride channel, was activated by calcium influx through TRPV1, TRPV4 or TRPA1 and that these channel interactions were important for TRP channel-mediated physiological functions. We found that ANO1 was expressed by normal human epidermal keratinocytes (NHEKs). We observed that ANO1 mediated currents upon TRPV3 activation of NHEKs and mouse skin keratinocytes. Using an in vitro wound-healing assay, we observed that either a TRPV3 blocker, an ANO1 blocker or low chloride medium inhibited cell migration and proliferation through p38 phosphorylation, leading to cell cycle arrest. These results indicated that chloride influx through ANO1 activity enhanced wound healing by keratinocytes.

Immune-enhancing effect of water-soluble beta-glucan derived from enzymatic hydrolysis of yeast glucan

Immunostimulants play an important role in the treatment of immunodeficiency. Macrophages are the first line in our immune defense system and play a critical role in the immune response. Therefore, finding new and better substances to induce an immune response by activating macrophages is an attractive research topic, especially in the fields of immunopharmacology and cancer prevention. Keratinocytes actively crosstalk with immune cells during wound repair, so enhancing the function of keratinocytes is also an important part of improving immunity. Beta-glucans are naturally occurring polysaccharides, consisting of d-glucose monomers linked by beta-glycosidic bonds. Several studies have investigated the immunomodulatory effects of beta-glucan, such as its anti-inflammatory and antibacterial properties. However, the use of yeast cell wall glucan has been limited because it is not soluble in water. In this study, we produced low-molecular-weight water-soluble yeast glucan (WSY glucan) and confirmed various aspects of its immune-enhancing effect. The structure of the beta-(1→3) and (1→6) bonds of WSY glucan were confirmed by nuclear magnetic resonance spectroscopy (1H-NMR) analysis. Our results showed that treatment with WSY glucan significantly and dose-dependently induced the production of inflammatory mediators (prostaglandin E2 (PGE2) and nitric oxide (NO)) and pro-inflammatory cytokines (tumor necrosis factor (TNF)-α and interleukin (IL)-6) in macrophages. In addition, WSY glucan treatment showed changes in the morphological structure of the macrophages and promoted phagocytic activity of the macrophages and wound healing in keratinocytes. Based on these results, WSY glucan is considered as a potential candidate for the treatment of diseases related to the weakening of the immune system without the limitation of insolubility.

Effect of a DACC-coated dressing on keratinocytes and fibroblasts in wound healing using an in vitro scratch model

Wound dressings that exert an antimicrobial effect in order to prevent and treat wound infections can be harmful to the wound healing process. Dressings with hydrophobic coatings, however, have been suggested to both reduce the microbial load and promote the healing process. Therefore, the potential effects of a dialkylcarbamoyl chloride (DACC)-coated dressing on fibroblasts and keratinocytes in wound healing were studied using mechanical scratch wounding of confluent cell layers as an in vitro model. Additionally, gene expression analysis by qRT-PCR was used to elucidate the longitudinal effects of the DACC-coated dressing on cell responses, specifically inflammation, growth factor induction and collagen synthesis. DACC promoted cell viability, did not stick to the cell layers, and supported normal wound healing progression in vitro. In contrast, cells became attached to the uncoated reference material, which inhibited scratch closure. Moreover, DACC slightly induced KGF, VEGF, and GM-CSF expression in HaCaT cells and NHDF. Physiological COL1A1 and COL3A1 gene expression by NHDF was observed under DACC treatment with no observable effect on S100A7 and RNASE7 levels in HaCaT cells. Overall, the DACC coating was found to be safe and may positively influence the wound healing outcome.Graphical abstract

Probing Piezo1 diffusion heterogeneity via single particle tracking and machine learning

The mechanically-activated ion channel Piezo1 plays diverse roles in various physiological processes, including neural stem/progenitor cell differentiation, vascular development, and keratinocyte wound healing. Piezo1 is activated by diverse mechanical cues and is thought to be gated by membrane tension. Interestingly, the channel was recently found to be mobile in the plasma membrane. However, Piezo1 subcellular diffusion regulation and how this behavior may contribute to channel function are poorly understood.

The role of keratinocyte function on the defected diabetic wound healing

Non-healing wounds are a major complication of diabetes that can lead to limb amputation and disability in the patients. The normal process of wound repair progresses through well-defined stages including hemostasis, inflammation, proliferative, and remodeling, which may be impaired in diabetic wounds. In recent years, it has been reported that keratinocytes, the major cell type in human skin, play a key role in the healing process of wounds. In this overview, firstly is provided a summary of the wound healing process and briefly reviewed the role of keratinocytes in wound healing. Then, summarized a set of evidence about the impaired keratinocytes activities in diabetic wounds, and clinical trials focused mainly on improving keratinocytes in the context of diabetic wound therapeutics. Keratinocytes can produce signaling molecules that act in a paracrine and autocrine way, causing pleiotropic effects on various cell types. The affected cells respond to keratinocytes by creating several signaling molecules, which also adjust keratinocyte activation through wound healing. In diabetic wounds, disruption of various biological mechanisms leads to dysfunction of keratinocytes including impaired migration, adhesion, and proliferation. The function of abnormal keratinocytes can lead to poor diabetic wound healing. Taken together, clarification of molecular and functional disturbances of keratinocyte cells and applying them in diabetic wounds can contribute to the enhanced treatment of diabetic wounds. Based on the location of keratinocytes in the epidermis and the central role of keratinocytes in the diabetic wound healing process, applying keratinocytes has great potential for the treatment of diabetic burn wounds.

Tremella fuciformis Inhibits Melanogenesis in B16F10 Cells and Promotes Migration of Human Fibroblasts and Keratinocytes.

Natural skin whiteners have been investigated for centuries. The development of preparations that safely achieve whitening of hyper-pigmented skin lesions is a challenge for the cosmetics industry. Furthermore, promoting rapid wound healing and minimizing inflammation in injured skin are key to prevent from abnormal pigmentation in scar tissue. Natural products, including the fungus Tremella fuciformis (TF), are attracting attention as potential sources of lead compounds for these applications. We investigated the in vitro effects of TF on melanogenesis in murine B16F10 cells. Melanin and tyrosinase levels were measured after treatment with TF. Wound healing in human keratinocytes (HaCaT) and fibroblasts (Detroit 551) was also determined via cell migration assay prior to TF exposure. TF significantly decreased melanin content and tyrosinase expression in a concentration-dependent manner in B16F10 cells. Furthermore, TF promoted wound healing in human HaCaT keratinocytes and Detroit 551 fibroblasts. TF proved effectively on inhibiting melanogenesis and promoting wound healing in vitro, demonstrating its potential as a novel skin-whitening agent. However, further clinical studies of safety and efficacy are required.

Antimicrobial oxygen-loaded nanobubbles as promising tools to promote wound healing in hypoxic human keratinocytes

Chronic wounds (CWs) are typically characterized by persistent hypoxia, exacerbated inflammation, and impaired skin tissue remodeling. Additionally, CWs are often worsened by microbial infections. Oxygen-loaded nanobubbles (OLNBs), displaying a peculiar structure based on oxygen-solving perfluorocarbons such as perfluoropentane in the inner core and polysaccharydes including chitosan in the outer shell, have proven effective in delivering oxygen to hypoxic tissues. Antimicrobial properties have been largely reported for chitosan. In the present work chitosan/perfluoropentane OLNBs were challenged for biocompatibility with human skin cells and ability to promote wound healing processes, as well as for their antimicrobial properties against methicillin-resistant Staphylococcus aureus (MRSA) and Candida albicans. After cellular internalization, OLNBs were not toxic to human keratinocytes (HaCaT), whereas oxygen-free NBs (OFNBs) slightly affected their viability. Hypoxia-dependent inhibition of keratinocyte migratory ability after scratch was fully reversed by OLNBs, but not OFNBs. Both OLNBs and OFNBs exerted chitosan-induced short-term bacteriostatic activity against MRSA (up to 6 h) and long-term fungistatic activity against C. albicans (up to 24 h). Short-term antibacterial activity associated with NB prolonged adhesion to MRSA cell wall (up to 24 h) while long-term antifungal activity followed NB early internalization by C. albicans (already after 3 h of incubation). Taken altogether, these data support chitosan-shelled and perfluoropentane-cored OLNB potential as innovative, promising, non-toxic, and cost-effective antimicrobial devices promoting repair processes to be used for treatment of MRSA- and C. albicans-infected CWs.

147 Cereus grandiflorus (Cactus) Flower Extract – A New Natural Skin Anti-Aging Ingredient with Multiple Properties

Skin aging signs are the result of the combination of several phenomena such as chronic exposure to exposome and the slowdown of repair processes and cell renewal. Identify an efficient natural ingredient, which can act both on the prevention of stress and on the stimulation of endogenous repair mechanisms, is a challenging target. Cereus grandiflorus belongs to the Cactaceae family (cactus). It is native from the desert regions of the Antilles, tropical America, and Mexico. Its flowers, sweet scented, bloom with white petals only at night during six hours. This medicinal flower is traditionally used to treat heart diseases. It is rich in sugars such as glucose, and fructose, amino acids, acids (citric, fumaric, malonic), alcaloids and flavonoids, which are known for their cosmetic properties. The present study aimed at evaluating the cosmetic benefits of this natural hydro- glycerin extract of Cereus grandiflorus flowers from Moroccan geographical origin. The measured cosmetic benefits of the ingredient were its antioxidant and anti-inflammatory properties as well the impact of the extract on keratinocyte metabolism and migration and corneocyte desquamation. In in vitro tests, this extract showed a broad-spectrum antioxidant action (Anti 1O2, OH°, anti O2°-, ORAC test). Moreover, it showed preventive effect on IL-6 release by keratinocytes in inflammatory state induced by phorbol 12-myristate 13-acetate (PMA). This reduction of IL-6 release suggests a potential anti-inflammatory effect. Using the Mito TrackerTM red and green FM, we showed that this extract increases keratinocyte and fibroblast mitochondrial activities. In an artificial keratinocyte wound healing test, the extract stimulated cells migration. Finally, we demonstrated that the extract decreases the stratum corneum cohesion in an ex vivo skin model, presenting a similar peeling effect as glycolic acid. Taken together, these results suggest that the Cereus grandiflorus extract appears as a valuable cosmetic ingredient towards skin protection, recovery and refinement of skin texture.

The Ambivalent Role of Skin Microbiota and Adrenaline in Wound Healing and the Interplay between Them.

After skin injury, wound healing sets into motion a dynamic process to repair and replace devitalized tissues. The healing process can be divided into four overlapping phases: hemostasis, inflammation, proliferation, and maturation. Skin microbiota has been reported to participate in orchestrating the wound healing both in negative and positive ways. Many studies reported that skin microbiota can impose negative and positive effects on the wound. Recent findings have shown that many bacterial species on human skin are able to convert aromatic amino acids into so-called trace amines (TAs) and convert corresponding precursors into dopamine and serotonin, which are all released into the environment. As a stress reaction, wounded epithelial cells release the hormone adrenaline (epinephrine), which activates the β2-adrenergic receptor (β2-AR), impairing the migration ability of keratinocytes and thus re-epithelization. This is where TAs come into play, as they act as antagonists of β2-AR and thus attenuate the effects of adrenaline. The result is that not only TAs but also TA-producing skin bacteria accelerate wound healing. Adrenergic receptors (ARs) play a key role in many physiological and disease-related processes and are expressed in numerous cell types. In this review, we describe the role of ARs in relation to wound healing in keratinocytes, immune cells, fibroblasts, and blood vessels and the possible role of the skin microbiota in wound healing.

Fatty acid potassium improves human dermal fibroblast viability and cytotoxicity, accelerating human epidermal keratinocyte wound healing in vitro and in human chronic wounds.

Effective cleaning of a wound promotes wound healing and favours wound care as it can prevent and control biofilms. The presence of biofilm is associated with prolonged wound healing, increased wound propensity to infection, and delayed wound closure. Anionic potassium salts of fatty acids are tested with commonly used anionic surfactants, such as sodium laureth sulphate (SLES) and sodium lauryl sulphate/sodium dodecyl sulphate (SLS/SDS). The normal human dermal cells demonstrated significantly greater viability in fatty acid potassium, including caprylic acid (C8), capric acid (C10), lauric acid (C12), oleic acid (C18:1), and linoleic acid (C18:2), than in SLES or SLS after a 24‐hour incubation. Cytotoxicity by LDH assay in a 5‐minute culture in fatty acid potassium was significantly lower than in SLES or SLS. in vitro wound healing of human epidermal keratinocytes during the scratch assay in 24‐hour culture was more significantly improved by fatty acid treatment than by SLES or SLS/SDS. In a live/dead assay of human epidermal keratinocytes, C8K and C18:1K demonstrated only green fluorescence, indicating live cells, whereas synthetic surfactants, SLES and SLS, demonstrated red fluorescence on staining with propidium iodide, indicating dead cells after SLES and SLS/SDS treatment. Potassium salts of fatty acids are useful wound cleaning detergents that do not interfere with wound healing, as observed in the scratch assay using human epidermal keratinocytes. As potassium salts of fatty acids are major components of natural soap, which are produced by natural oil and caustic potash using a saponification method, this may be clinically important in wound and peri‐wound skin cleaning. In human chronic wounds, natural soap containing fatty acid potassium increased tissue blood flow based on laser speckle flowgraphs after 2 weeks (P < .05), in addition to removing the eschars and debris. Wound cleansing by natural soap of fatty acid potassium is beneficial for wound healing.