Skin trauma, surgery, or burns can result in non-functional scar tissue, causing significant physiological and psychological harm to patients. Therefore, there is an urgent need for a treatment strategy that promotes rapid wound healing and suppresses scar formation. In this study, we developed a facile and injectable composite hydrogel system (PF-127@ERD) loaded with eriodictyol, which exhibits efficient sustained release of the scar-inhibiting compound at different stages of wound healing to facilitate rapid and scarless closure. Our findings revealed that PF-127@ERD not only stops bleeding and reduces local oxidative stress damage in skin wounds but also regulates the inflammatory microenvironment by inhibiting the expression of relevant inflammatory factors while promoting fibroblast migration. Furthermore, PF-127@ERD inhibits excessive collagen deposition and regulates the expression of genes associated with scar formation, thereby promoting scar-free wound healing. In a rat model of full-layer skin defects, skin wound tissue treated with PF-127@ERD healed faster, exhibited more orderly collagen alignment, and showed reduced scar tissue formation compared to other groups. This process may be due to its inhibition of ferroptosis-related pathways. Therefore, this straightforward hydrogel system based on the skin repair stage (PF-127@ERD) holds great potential for scarless wound healing.

Deer antlers are the only mammalian organs that periodically regenerate from permanent bony protuberances (pedicles). Antler regeneration relies on the presence of pedicle periosteum (PP) and starts from regenerative healing of wounds created following the hard antler casting. Interestingly, PP deletion (removal of local factors) abolishes antler regeneration and the transition to velvet skin (shiny and hair sparsely populated) but cannot inhibit regenerative wound healing although the healed tissue is of pedicle type (scalp-like); this indicates that systemic factors from circulating blood contribute to the generic regenerative wound healing. Subsequently, we created full-thickness excisional (FTE) skin wounds on the forehead region in sika deer. Different healing outcomes ensued, namely regeneration or formation of a scar, depending on whether the intervention took place during the period of antler regeneration (ARP; spring-summer) or in the period where antler regeneration does not occur (non-ARP; winter). Forehead wounds during ARP exhibited regenerative healing, whereas during the non-ARP, healing took place but with a scar. Therefore, systemic factors from the circulating blood during the ARP must be responsible for this outcome. Topical application of deer blood plasma (a source of systemic factors) from ARP to FTE wounds in rats promoted regenerative healing, whereas, that from non-ARP failed to do so. Further evaluation showed that regenerative healing was achieved through increased cell proliferation, impaired inflammatory response, reduced myofibroblast transformation, and orchestrated collagen remodeling accompanied by an increase in the ratio of TGF-β3 to TGF-β1. Comparative proteomics analysis of deer plasma identified some highly up-regulated factors from the plasma in ARP (ARPP) with regeneration-stimulating-potential, such as IGF1 and PRG4. Topical application of IGF1 or IGF1 + PRG4 to rat FTE wounds greatly promoted regenerative healing; particularly in the combination of IGF1 and PRG4 group. In summary, our findings convincingly demonstrate that the systemic factors from deer blood taken during ARP contain factors capable of inducing regenerative wound healing and that this effect is not species-specific. Because there are almost no restrictions on the supply of deer blood in ARP, our findings have laid the foundation for devising effective therapies for scar-less wound healing in the clinical setting.

Hydrogels are promising dressings for wound healing as they resemble the native extracellular matrix that provides a microenvironment for skin wound healing. Herein, we have developed composite hydrogels by incorporating ZiF-8@GO into the polymeric mixture of chitosan (CS), polyvinyl alcohol (PVA), and carrageenan (CG). These were analyzed using FTIR, XRD, SEM-EDX, and DSC to study their structural, surface morphology, elemental analysis, and thermal stability. The physicochemical properties were studied in different media under various pH at 37 °C. The degradation was performed in phosphate buffer saline solution at 37 °C under 7.4 pH, and the wettability was conducted to study the hydrophilicity and hydrophobicity. All the composite hydrogels are hemocompatible and exhibit excellent anti-bacterial activities against Gram-positive and Gram-negative bacteria. We have performed in-vitro biological assays using fibroblast (3t3) cell lines, and increasing ZiF-8@GO increased cell viability and proliferation. The wound contraction was also performed using an in-vivo wound healing model using SD-rat, and hydrogel (CPC-Z@GO-3) was found to heal the wound quickly without any scar formation. These hydrogels have exhibited excellent physicochemical characteristics and biological properties, which would be promising composite polymeric materials for wound repair and regeneration.

Due to poor angiogenesis under the wound bed, wound treatment remains a clinical challenge. Therefore, there is an urgent need for new dressings to combat bacterial infections, accelerate angiogenesis, and accelerate wound healing. In this study, we prepared carbon dots nanomaterial (PF-CDs) derived from traditional Chinese medicine paeoniflorin using a simple green one pot hydrothermal method. The average particle size of the CSs we prepared was 4 nm, and a concentration of 200 μg ml-1was ultimately selected for experiments. Subsequently, PF-CDs were loaded into the chitosan hydrogel to form a new type of wound dressing CSMA@PF-CDs hydrogel. CSMA@PF-CDs demonstrated positive biocompatibility by promoting a 20% increase in cell proliferation and strong antibacterial activity. In comparison to the control group, CSMA@PF-CDs enhanced the expression level of anti-inflammatory factors by at least 2.5 times and reduces the expression level of pro-inflammatory factors by at least 3 times. Furthermore, CSMA@PF-CDs promoted the migration of Human umbilical vein endothelial cells and increased vascular endothelial growth factor expression by 5 times. The results ofin vivoexperiments indicate that CSMA@PF-CDs significantly promoted the healing of back wounds in rats. These characteristics make it a promising material for repairing infected wounds and a potential candidate for clinical skin regeneration applications.

Background: Diabetic foot ulcers (DFUs) remain a major complication of diabetes, characterized by impaired wound healing, high infection risk, and an increased likelihood of limb amputation. Platelet-rich plasma (PRP) has emerged as a promising adjunctive therapy due to its regenerative properties, promoting angiogenesis, modulating inflammation, and accelerating tissue repair. Methods: This literature review explores the current evidence regarding the use of PRP in the management of DFUs. It was conducted using the PubMed database to evaluate the efficacy of PRP in DFUs. The search was restricted to studies published in the last 10 years, including randomized controlled trials, meta-analyses, and systematic reviews. The inclusion criteria focused on studies assessing PRP as a standalone treatment or in combination with other wound care strategies, evaluating key clinical outcomes such as wound healing rates, infection control, tissue regeneration, and amputation prevention. Results: A total of 35 studies met the inclusion criteria, including 11 meta-analyses, 15 review articles, and 9 clinical trials. PRP demonstrated potential benefits in accelerating wound healing, reducing inflammation, and promoting granulation tissue formation. Additionally, PRP combined with negative-pressure wound therapy (NPWT) showed superior outcomes in reducing amputation rates. However, findings varied based on patient characteristics, PRP preparation techniques, and treatment protocols. Conclusions: PRP represents a valuable adjunct in DFU management, contributing to improved healing outcomes and reduced complications. However, the lack of standardized protocols and variability in clinical results highlight the need for further large-scale, multicenter studies to establish its definitive role in diabetic wound care.

In palliative care, alternative routes for drug application besides the oral and intravenous administration are frequently necessary. Up-to-date, very little is known about the familiarity, use and perceived relevance of inhalative medications for symptom control among palliative care practitioners.

We conducted an anonymous online survey among palliative care physicians throughout Germany between 09/2021 and 04/2022. The questionnaire covered participants' sociodemographics, as well as familiarity, perceived relevance and prescription practices regarding 21 nebulised drugs. Analysis was performed using methods of descriptive statistics.

108 fully completed questionnaires were analysed. Most of the participants were employed in palliative care for 5 + years. The administration of normal saline, mucoactive drugs, bronchodilators and steroids via nebulisation was a widely known and frequently used technique among the participants, as evidenced by its regular use in clinical routine. About 50% of the participants reported to know epinephrine and tranexamic acid for anti-oedematous or haemostyptic effects, respectively. Both drugs were considered "relevant" by more than 60% of the prescribers. Only a minority of participants reported to know and use nebulised opioids, iloprost, several antibiotics, heparin, ketamine and lidocaine.

Our survey shows that nebulised drugs are prescribed and considered relevant in palliative care. However, for several of the mentioned medications only limited data is available regarding use and effectivity. There is also uncertainty to what extent the existing data may be transferable into routine palliative care setting. Therefore, more evidence should be generated.

Not applicable.

Wound healing is one of the fundamental problems faced by the medical profession. Thus, there is a need for the development of biomaterials that are safe, economically viable, possess anti-inflammatory and antibacterial characteristics, and enhance wound healing. In this study, we designed a nanomicelle of Bletilla striata polysaccharide (BSP) self-loaded with Azithromycin (AZI). The properties are improved by physically blending Carbomer 940 (CBM) with Gelatin (GEL) to serve as the hydrogel matrix. The preparation was made by combining the nanomicelle, used as the precursor solution, with the gel matrix. It was designed to treat wound infections and promote healing. Relevant experiments indicate its excellent biocompatibility. The hydrogel not only promotes cell migration, proliferation, angiogenesis, and collagen deposition associated with skin healing, but also regulates the polarization of macrophages from the M1 to M2 phenotype, as well as the expression of related factors. Additionally, in vitro experiments demonstrate its good antibacterial activity. In addition, we demonstrated the gel's anti-inflammatory, antibacterial, and pro-healing effects in acute wounds and methicillin-resistant Staphylococcus aureus (MRSA) wounds. Therefore, the nanomicellar gel enhances antibacterial activity and related immune regulation, offering a new direction in the treatment of acute and chronic wounds.

Fibroblast Growth Factor 21 (FGF21), a pivotal member of the fibroblast growth factor family, exhibits multifaceted biological functions, including the modulation of pro-inflammatory cytokines and metabolic regulation. Recent research has revealed that in impaired skin tissues, FGF21 and its receptors are upregulated and play a significant role in accelerating the wound healing process. However, the clinical application of FGF21 is severely limited by its short in vivo half-life: this factor is often degraded by enzymes before it can exert its therapeutic effects. To address this limitation, the transdermal drug delivery system (TDDS) has emerged as an innovative approach that enables sustained drug release, significantly prolonging the therapeutic duration. Leveraging genetic recombination technology, research teams have ingeniously fused FGF21 with cell-penetrating peptides (CPPs) to construct recombinant FGF21 complexes. These novel conjugates can efficiently penetrate the epidermal barrier and achieve sustained and stable pharmacological activity through TDDS. This review systematically analyzes the potential signaling pathways by which FGF21 accelerates skin wound repair, summarizes the latest advancements in TDDS technology, explores the therapeutic potential of FGF21, and evaluates the efficacy of CPP fusion tags. The manuscript not only proposes an innovative paradigm for the application of FGF21 in skin injury treatment but also provides new insights into its use in transdermal delivery, marking a significant step toward overcoming existing clinical therapeutic challenges. From a clinical medical perspective, this innovative delivery system holds promise for addressing the bioavailability issues of traditional FGF21 therapies, offering new strategies for the clinical treatment of metabolism-related diseases and wound healing. With further research, this technology holds vast potential for clinical applications in hard-to-heal wounds such as diabetic foot ulcers and burns.

Every skin injury leaves a scar with inferior mechanical properties, which can lead to limitations in function and quality of life. Consistent therapeutic support during wound healing can ensure optimal formation of new tissue. The greatest challenge in scar treatment is the dosage of therapeutic interventions: stimuli must meet the requirements of the tissue in its current state. However, excessive strain on the structure must be avoided to enable proper and undisturbed wound healing. Optimal treatment is based on the patient's fundamental conditions and is adjusted to the specific requirements of the healing tissue throughout the phases of wound healing. Continuous monitoring of the healing process, constant adjustment and selection of techniques, and consistent implementation of manual interventions are essential, particularly in the later stages of scar formation. It is crucial to involve patients in the independent treatment and care of scar tissue to increase the time under adequate tension and maintain the tissue in the best possible condition.

This study intends to investigate the green synthesis of silver (Ag) and gold (Au) nanoparticles (NPs) using Echinophora platyloba extract and to evaluate the antioxidant and anti-inflammatory effects of the synthesized NPs and the extract. In this study, aqueous and hydroalcoholic extracts of E. platyloba were prepared, which were used for the biosynthesis of Ag and Au NPs. Dynamic light scattering (DLS), zeta potential analysis, transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) spectroscopy, UV-Vis spectroscopy, and X-ray diffraction (XRD) methods were used to characterize the green NPs. The antioxidant effect of the NPs was estimated using in vitro methods, including reducing power (RP), ferric reducing/antioxidant power (FRAP), and 2,2-diphenyl-1-picrylhydrazyl (DPPH). To evaluate the anti-inflammatory and antioxidant activity of E. platyloba extract and Ag and Au NPs, we used the carrageenan method. In our experiment, the extract and the synthesized NPs were administered orally to the mice 2 h before the carrageenan injection. The subsequent inhibition of inflammation and reduction of paw thickness were quantified. To evaluate their antioxidant effect, malondialdehyde (MDA), and total antioxidant capacity (TAC) levels were measured. Levels of pro-inflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), were also quantified. In this study, the results indicate that the synthesized Ag and Au NPs have antioxidant and anti-inflammatory effects. The most promising results were observed in the groups that received the Ag NPs.

Our study aims to investigate the effect of negative pressure wound therapy (NPWT) on microRNA-155 (miR-155) in the granulation tissue of patients suffering from diabetic foot ulcers (DFUs) and its correlation with wound healing. A total of sixty patients diagnosed with DFUs were randomly assigned to either the NPWT group (n = 40) or the Non-NPWT group (n = 20) in a 2:1 ratio. After debridement, the NPWT group received NPWT treatment for one week, while the Non-NPWT group underwent routine dressing therapy. The expression of miR-155 in DFU granulation tissues was evaluated by qRT-PCR before and after treatment for one week. Following termination, wound healing rates were assessed in the NPWT group, and the correlation between variations in miR-155 expression (ΔmiR-155) and wound healing was analyzed pre and post NPWT treatment. In vitro experiments were conducted to investigate the effects of negative pressure on variations of miR-155 expression, as well as proliferation, migration, and apoptosis in normal human dermal fibroblasts (NHDFs). The NPWT group showed a decrease in miR-155 expression in wound granulation tissue compared with pre-treatment [4.12 (1.22, 14.85) vs. 6.83 (2.15, 15.72), P < 0.05]. Conversely, there was no statistically significant difference in miR-155 expression in wound granulation tissue between pre-treatment and post-treatment in the Non-NPWT group (P > 0.05). However, analysis revealed a positive correlation between ΔmiR-155 and wound healing rate after 4 weeks in the NPWT group (χ2 = 4.829, P = 0.028). The in vitro experiments showed a significant decrease in miR-155 expression in NHDFs under negative pressure measured at -125 mmHg (P < 0.05). This reduction in miR-155 expression, in turn, enhanced the proliferation and migration ability while decreasing the apoptosis rate of NHDFs by targeting the upregulation of fibroblast growth factor 7 (FGF7) gene expression (P < 0.05). It is concluded that NPWT promotes DFU healing by reducing the expression of miR-155 in granulation tissue and the efficacy of NPWT correlated with altered miR-155 expression in wound tissue.

The self-renewal ability and multipotency of stem cells give them great potential for use in wound healing. Stem cell-derived exosomes, owing to their close biological resemblance to their parent cells, offer a more efficient, safer, and economical approach for facilitating cellular communication and interactions within different environments. This potential makes them particularly valuable in the treatment of both acute and chronic wounds, such as lacerations, burns, and diabetic ulcers. Long non-coding RNAs (lncRNAs) enclosed in exosomes, as one of the leading actors of these extracellular microvesicles, through interaction with miRNAs and regulation of various signaling pathways involved in inflammation, angiogenesis, cell proliferation, and migration, could heal the wounds. Exosome-derived lncRNAs from stem cells facilitate extracellular matrix remodeling through interaction between macrophages and fibroblasts. Moreover, alongside regulating the expression of inflammatory cytokines, controlling reactive oxygen species levels, and enhancing autophagic activity, they also modulate immune responses to support wound healing. Regulating the expression of genes and signaling pathways related to angiogenesis, by increasing blood supply and accelerating the delivery of essential substances to the wound environment, is another effect exosomal lncRNAs derived from stem cells for wound healing. These lncRNAs can also enhance skin wound healing by regulating homeostasis, increasing the proliferation and differentiation of cells involved in the wound-healing process, and enhancing fibroblast viability and migration to the injury site. Ultimately, exosome-derived lncRNAs from stem cells offer valuable and novel insights into the molecular mechanisms underlying improved wound healing. They can pave the way for potential therapeutic strategies, fostering further research for a better future. Meanwhile, exosomes derived from mesenchymal stem cells, due to their exceptional regenerative properties, as well as the lncRNAs derived from these exosomes, have emerged as one of the innovative tools in wound healing. This review article aims to narrate the cellular and molecular roles of exosome-derived lncRNAs from stem cells in enhancing wound healing with a focus on mesenchymal stem cells.

Previously we suggested a new pharmaceutical derived from coordination complex of Co3+ with polyacrylic acid (PAA) exhibiting hemostatic and microbicidal activity, namely Hestatin. Differences in the physiological activity of Hestatin synthesized from PAA 10 kDa (Hestatin 10) and 200 kDa (Hestatin 200) were shown. We tested the acute toxicity of Hestatin and its effect on the healing rate of sterile wounds in rats. Free 10 kDa PAA, emulsion wax, emulsion wax carrying resveratrol, and dexpanthenol were tested for comparison. Hestatin 10 exhibited no acute toxicity when administered intragastrically at dosages of 5 g per kg. Hestatin 10 surpassed all tested drugs in its wound healing ability. Histological analysis of skin sections of rats in the area of healing defects showed an increased rate of synthesis of reticular fibers compared to the placebo. In the early stages of wound healing (inflammatory phase), Hestatin 10 stimulated taxis of mast cells (MCs) to the wound bottom but not to the wound perimeter. At the final stage of wound healing (remodeling phase), Hestatin 10 promoted MC evacuation from the skin defect area. This effect is the opposite of the well-known wound-healing agents (dexpanthenol and resveratrol), which enhance MC infiltration into the defect area in the remodeling phase.

Deer antlers are the only mammalian appendages that can fully regenerate from periosteum of pedicles (PP). This regeneration process starts from regenerative healing of wounds. Removal of PP abolishes antler regeneration, however, the regenerative cutaneous wound healing proceeds, indicating that some factors in the circulation contribute to this healing. In this study, we produced a wound in the scalp of deer either in antler regeneration period (ARP) (n = 3) or in non-ARP (n = 3). Results showed full regeneration took place only when the wound was created during ARP. Interestingly, topical application of systemic factors from ARP (n = 9) promoted regenerative wound healing in rats. Comparative proteomics analysis (n = 3) revealed that PRG4 and IGF-1 were high during ARP, and topical application of PRG4 + IGF-1 promoted restoration in rat FTE wounds. We believe that, ultimately, incorporating systemic factors into advanced wound care modalities could offer new opportunities for regenerative healing in the clinical setting.

To study the age-adjusted regenerative potential of platelet-rich plasma (PRP) in a culture of dermal fibroblast cells with analysis of proliferative, migratory and metabolic activity of cells after their stimulation with PRP from donors of different ages.

To prepare PRP, we used one of the classic protocols for one-stage centrifugation of whole blood from healthy donors divided into age groups: the first group (n=10) - donors aged 30-40 years, the second group (n=10) - donors aged 60-70 years. We used hTERT-HDFa (d220) cell line and added donor PRP to the experimental wells at concentrations of 10%. Samples without PRP comprised group 0 (K). The same medium without PRP supplemented with 10% FBS was used as a positive control (group 0 (K 10% FBS)). We analyzed metabolic activity of cells (MTT test) and migration activity of fibroblasts in "scratch assay". We estimated intensity of reactive oxygen species (ROS) release, morphological characteristics of cells and mechanisms of cell death (fluorescence microscopy).

PRP from donors aged 60-70 years reduced metabolic activity of hTERT-HDFa culture on the first day of experiment by 85.5% (p<0.001) compared to the first group. ROS release by fibroblasts after addition of plasma from donors aged 30-40 years was maximum in the first hours and decreased throughout the follow-up period. After addition of plasma from donors aged 60-70 years, ROS release did not show significant changes in the first hours, but significantly increased throughout the follow-up period. Microscopy revealed the highest percentage of viable cells in groups 0 (K 10% FBS) and 1 (donors aged 30-40 years). The highest percentage of necrosis and apoptosis was recorded in group 2 (donors 60-70 years).

In the first 24 hours, we revealed pro-oxidant stimulating effect of PRP from young donors with increase in metabolic activity and no cell necrosis. Addition of PRP from elderly donors on the first day was accompanied by lower metabolic activity of culture and higher percentage of cell necrosis and apoptosis. There was no difference in migration activity of cells depending on donor age.

Regeneration after tissue injury is a dynamic and complex process, and angiogenesis is necessary for normal physiological activities and tissue repair. Induced pluripotent stem cells are a new approach in regenerative medicine, which provides good model for the study of difficult-to-obtain human tissues, patient-specific therapy, and tissue repair. As an innovative cell-free therapeutic strategy, the main advantages of the treatment of induced pluripotent stem cells (iPSCs)-derived exosomes are low in tumorigenicity and immunogenicity, which become an important pathway for tissue injury. This review focuses on the mechanism of the angiogenic effect of iPSCs-derived exosomes on wound repair in tissue injury and their potential therapeutic targets, with a view to providing a theoretical basis for the use of iPSCs-derived exosomes in clinical therapy.

Improving mental health is crucial for patients who require wound treatment.

To analyze the effects of solution-focused brief therapy (SFBT) combined with vacuum sealing drainage on the psychological health of patients undergoing wound treatment, providing a basis for selecting wound treatment protocols.

A total of 102 patients undergoing wound treatment were included, with the study period from March 2020 to March 2024. Sex was not a factor, and patients were randomly assigned to two groups of 51 cases each. The control group received negative pressure wound therapy (NPWT), while the experimental group received NPWT plus SFBT. The recovery of wounds, granulation tissue scores, and psychological health levels were compared between the two groups. Statistical analysis was conducted using SPSS Windows software version 26.0 and GraphPad Prism 8.0.

Post-treatment, the levels of high-sensitivity C-reactive protein, white blood cell count, and lactate dehydrogenase in the experimental group were significantly lower than those in the control group (P < 0.05). The two groups had no significant difference in granulation tissue scores (P < 0.05). The psychological health level in the experimental group was significantly higher than in the control group (P < 0.05).

The combination of SFBT and NPWT accelerates wound healing, promotes granulation tissue growth, and improves psychological well-being, making it a valuable approach for clinical application.

Deer antlers, unique among mammalian organs for their ability to regenerate annually without scar formation, provide an innovative model for regenerative medicine. This study explored the potential of exosomes derived from antler mesenchymal stem cells (AMSC-Exo) to enhance skin wound healing.

We explored the proliferation, migration and angiogenesis effects of AMSC-Exo on HaCaT cells and HUVEC cells. To investigate the skin repairing effect of AMSC-Exo, we established a full-thickness skin injury mouse model. Then the skin thickness, the epidermis, collagen fibers, CD31 and collagen expressions were tested by H&E staining, Masson's trichrome staining and immunofluorescence experiments. MiRNA omics analysis was conducted to explore the mechanism of AMSC-Exo in skin repairing.

AMSC-Exo stimulated the proliferation and migration of HaCaT cells, accelerated the migration and angiogenesis of HUVEC cells. In the mouse skin injury model, AMSC-Exo stimulated angiogenesis and regulated the extracellular matrix by facilitating the conversion of collagen type III to collagen type I, restoring epidermal thickness to normal state without aberrant hyperplasia. Notably, AMSC-Exo enhanced the quality of wound healing with increased vascularization and reduced scar formation. MiRNAs in AMSC-Exo, especially through the miR-21-5p/STAT3 signaling pathway, played a crucial role in these processes.

This study underscores the efficacy of AMSC-Exo in treating skin wounds, suggesting a new approach for enhancing skin repair and regeneration.

Macrophages play a crucial role in the process of wound healing. In order to effectively inhibit excessive inflammation and facilitate skin wound healing, it is necessary to transform overactive M1 macrophages in injured tissues into the M2 type. In this study, we have successfully generated bioinspired nanovesicles (referred to as M2BNVs) from M2 type macrophages. These nanovesicles not only possess physical and biological properties that closely resemble exosomes, but also offer a simpler preparation process and more abundant yield. Owing to their distinctive endogenous cargo, M2BNVs have the ability to re-educate M1 macrophages, shifting their phenotype towards the M2 type which is known to promote healing and possess anti-inflammatory properties. Consequently, M2BNVs effectively improve the prevailing pro-inflammatory microenvironment within the wound. Furthermore, M2BNVs also facilitate wound tissue regeneration and angiogenesis. Collectively, our findings demonstrate the potential of M2BNVs in promoting wound healing in mice.

Given progressive population ageing and the increase in the number of patients with comorbidities, the management of chronic and/or hard-to-heal wounds (HHWs) nowadays represents a common problem in many clinical settings. In these cases, standard strategies may not be sufficient. Autologous grafting represent the gold standard for permanent wound closure, but is almost never realized when the skin loss is extensive/the patient is young. The grafting of homologous skin/dermal tissue procured from cadaver donors (i.e., allografting) represents the best alternative, especially when the dermal component is lost. This request supports the activities of skin bank establishments (including donor screening, skin procurement, processing, storage, and distribution) that are regulated by specific guidelines and need to continuously meet quality standard requirements. The aim of this work is to both give specific insights of all the procedures implied in allograft preparation as well as an overview of their practical application in the treatment of different HHWs. The particular characteristics of each skin/dermal allograft released by Siena Skin Bank (cryopreserved/glycerol-preserved skin/de-epidermized dermis, acellular lyophilized de-epidermized dermis/reticular dermis) are also discussed. The exemplificative series of HHWs managed in the Dermatology Department of Siena were classified according their etiology into post-traumatic, vascular (arterial/venous/mixed/lymphatic), inflammatory, surgical, and heat/chemical burns. Globally, the clinical advantages obtained include: acceleration of healing process, pain sparing, resistance to bacterial contamination, dermal regeneration (instead of scarring), and better aesthetic-functional outcome.

Melatonin (5-methoxy-N-acetyltryptamine) is an indoleamine compound that plays a critical role in the regulation of circadian rhythms. While melatonin is primarily synthesized from the amino acid tryptophan in the pineal gland of the brain, it can also be produced locally in various tissues, such as the skin and intestines. Melatonin's effects in target tissues can be mediated through receptor-dependent mechanisms. Additionally, melatonin exerts various actions via receptor-independent pathways. In biological systems, melatonin and its endogenous metabolites often produce similar effects. While injuries are common in daily life, promoting optimal wound healing is essential for patient well-being and healthcare outcomes. Beyond regulating circadian rhythms as a neuroendocrine hormone, melatonin may enhance wound healing through (1) potent antioxidant properties, (2) anti-inflammatory actions, (3) infection control, (4) regulation of vascular reactivity and angiogenesis, (5) analgesic (pain-relieving) effects, and (6) anti-pruritic (anti-itch) effects. This review aims to provide a comprehensive overview of scientific studies that demonstrate melatonin's potential roles in supporting effective wound healing.

Soft tissue management is critical in bone augmentation surgery to prevent wound dehiscence. Several strategies for passive tissue primary closure have been explored. This article introduces a flap design known as the modified "Poncho" technique (MPT), integrated with customized titanium mesh-mediated bone regeneration, and investigates the healing quality during the initial stages of an incision.

The cohort consisted of 5 patients undergoing customized bone regeneration procedures, concerned primarily with the successful integration and healing of the augmented bone site without complications such as wound dehiscence or infection.

All patients were diagnosed with insufficient bone volume requiring augmentation to support future dental implants, necessitating the use of customized titanium mesh for guided bone regeneration.

The MPT was detailed and applied during the customized bone regeneration procedures. Postoperative evaluations included recording complications and using Landry's healing index at intervals of 3, 7, 14, and 30 days post-surgery to assess the technique's performance in early wound closure.

The study found that 95.7% of surgery sites experienced uneventful soft tissue healing within the observation period. Only 1 of 23 sites exhibited partial wound dehiscence at postsurgical days 14 and 30, accompanied by mild inflammation. The Landry's healing index increased from 3 ± 0.47 to a final value of 4.69 ± 1.06, indicating substantial improvement in healing over time.

The MPT shows promise as an innovative approach for promoting passive and predictable primary wound closure beneath a digitally customized titanium mesh for bone regeneration, demonstrating a high rate of successful healing and minimal complications during the early postoperative phase.

The complex composition of honey plays a crucial role in wound healing, exhibiting varying effects at different stages of the healing process. This study investigated seven honey varieties sourced from different regions of Romania using in vitro experimental models developed in macrophage-like, fibroblast, and keratinocyte cell lines to explore the mechanisms by which honey promoted the healing process. This study assessed the impact of honey on inflammatory cytokine production in macrophage-like cells, cell proliferation and collagen synthesis in fibroblasts, and cell proliferation and migration in keratinocytes. Additionally, correlation analysis was conducted to examine the relationship between honey composition and its biological properties. Honey varieties presented both anti- and pro-inflammatory effects. Moreover, they displayed dose-dependent pro-proliferative effects, stimulating collagen synthesis and cell migration, thereby enhancing the re-epithelialization process. The Pearson coefficient analysis indicated a strong positive correlation between biological activities and phenolic content. Additionally, there was a medium positive correlation with the ascorbic acid content and a medium negative correlation with the glucose content in the different honey varieties. Romanian honey varieties rich in phenolics showed potential in modulating inflammation, proliferation, collagen synthesis, and cell migration, suggesting their suitability for further evaluation and development of innovative dressings for skin tissue regeneration.

In this study, we green synthesized silver nanoparticles (Ag Nps) from Hybanthus enneaspermus leaves (HE-Ag NPs) and evaluated their antimicrobial and wound-healing properties. The synthesized HE-Ag NPs were characterized using various techniques, revealing face-centered polygonal structures, a well-dispersed appearance, and an average particle size of 42-51 nm. The antimicrobial effects of HE-Ag NPs and their embedded cotton fabrics were tested against several pathogens, showing effective inhibition of growth. The cytotoxicity and anti-inflammatory properties of HE-Ag NPs were assessed using MTT assays on L929 and RAW 264.7 cells and by measuring inflammatory cytokine levels in LPS-treated RAW 264.7 cells. HE-Ag NPs did not affect the viability of L929 and RAW 264.7 cells and significantly reduced inflammatory cytokine levels. In vivo studies using an excision wound model demonstrated that HE-Ag NPs-loaded ointment significantly increased hydroxyproline, total protein, and antioxidant levels and enhanced the wound contraction rate. These findings suggest that HE-Ag NPs have potent antimicrobial properties and promote wound healing, indicating their potential for use in topical ointments for wound care.

The present study aimed to conduct a comparative investigation of the biological properties of phenolic and polysaccharide extracts obtained using an ultrasound-assisted technique from Aloe vera gel and their effects on each stage of the wound healing process in in vitro experimental models. HPLC analysis showed that the phenolic extract contained aloin, ferulic, and caffeic acid, as well as quercetin dihydrate, as major compounds. Capillary zone electrophoresis indicated the prevalence of mannose and glucose in the polysaccharide extract. Cell culture testing revealed the anti-inflammatory properties of the phenolic extract at a concentration of 0.25 mg/mL through significant inhibition of pro-inflammatory cytokines-up to 28% TNF-α and 11% IL-8 secretion-in inflamed THP-1-derived macrophages, while a pro-inflammatory effect was observed at 0.5 mg/mL. The phenolic extract induced 18% stimulation of L929 fibroblast proliferation at a concentration of 0.5 mg/mL, enhanced the cell migration rate by 20%, and increased collagen type I synthesis by 18%. Moreover, the phenolic extract exhibited superior antioxidant properties by scavenging free DPPH (IC50 of 2.50 mg/mL) and ABTS (16.47 mM TE/g) radicals, and 46% inhibition of intracellular reactive oxygen species (ROS) production was achieved. The polysaccharide extract demonstrated a greater increase in collagen synthesis up to 25%, as well as antibacterial activity against Staphylococcus aureus with a bacteriostatic effect at 25 mg/mL and a bactericidal one at 50 mg/mL. All these findings indicate that the phenolic extract might be more beneficial in formulations intended for the initial phases of wound healing, such as inflammation and proliferation, while the polysaccharide extract could be more suitable for use during the remodeling stage. Moreover, they might be combined with other biomaterials, acting as efficient dressings with anti-inflammatory, antioxidant, and antibacterial properties for rapid recovery of chronic wounds.

The potential of biodegradable magnesium (Mg) skin staple has recently garnered widespread attention due to their biodegradability and biocompatibility rather than traditional stainless steel staples, the most commonly used in current clinical practice. The aim of this study is to evaluate the safety and mechanical properties of a novel biodegradable Mg skin staple.

A prototype of Mg skin staple was designed using a novel ZK60 Mg alloy. The mechanical properties of the staple were evaluated using a universal testing machine. The cytotoxicity of the staple was examined in vitro and the efficacy of the staple in wound closure was assessed in New Zealand rabbits for one and three weeks, respectively.

The tensile strength of this Mg alloy is 258.4 MPa with 6.9% elongation. The treatment of HaCaT and L929 cells with the staple extract resulted in over 95% cell viability, indicating no cytotoxicity. In vivo, no tissue irritation was observed. No difference was found in wound healing between the Mg skin staple and the stainless steel staple after one and three weeks in the cutting wound on the back of rabbits. Some Mg skin staples spontaneously dislodged from the skin within three weeks, while others were easily removed.

Our results confirm the safety, biocompatibility, and functionality of the novel Mg skin staple in wound closure. The efficacy of the staple in wound closure was demonstrated to be as effectively as conventional staples, with the added benefit of decreased long-term retention of skin staples in the wounds.

Incorporation of luvangetin in nanoemulsions for antimicrobial and therapeutic use in infected wound healing.

Luvangetin nanoemulsions were prepared by high-speed shear method and characterized based on their appearance structure, average droplet size, polydispersity index (PDI), electric potential, storage stability. Optimized formulation of luvangetin nanoemulsion by Box-Behnken design (BBD). The antimicrobial activity and antimicrobial mechanism of luvangetin nanoemulsions against common hospital pathogens, ie, Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), were investigated using luvangetin nanoemulsions. The biosafety of luvangetin nanoemulsion was evaluated through cytotoxicity, apoptosis, and reactive oxygen species (ROS) assay experiments using human normal epidermal cells and endothelial cells. Finally, the effect of luvangetin nanoemulsion on healing of infected wounds was investigated in B6 mice.

Luvangetin nanoemulsion formulation consists of 2.5% sunflower seed oil, 10% emulsifier Span-20 and 7 minutes of shear time, and with good stability. Luvangetin nanoemulsion produces antibacterial activity against S. aureus and E. coli by disrupting the structure of bacterial cell membranes. Luvangetin nanoemulsion are biologically safe for HaCat and HUVEC. Luvangetin nanoemulsion showed good therapeutic effect on MRSA infected wounds in mice.

For the first time, developed a new formulation called luvangetin nanoemulsion, which exhibited superior antibacterial effects against Gram-positive bacteria. Luvangetin nanoemulsion has a favorable effect in promoting infected wound healing. We have combined luvangetin, which has multiple activities, with nanoemulsions to provide a new topical fungicidal formulation, and have comprehensively evaluated its effectiveness and safety, opening up new possibilities for further applications of luvangetin.

The protection for different skin types with impaired skin barrier in the market is insufficient.

To evaluate the efficacy and safety of a panthenol-enriched mask (La Roche-Posay Mask Pro) in addressing various skin barrier impairment subgroups, including dry sensitive, oily sensitive, and oily acne skin.

A total of 177 participants were enrolled in the study and divided into three subgroups based on their skin type. Participants used the mask following the specified protocol, with measurements taken for skin hydration, transepidermal water loss (TEWL), sebum content, and skin redness-factors that are directly influenced by skin barrier function. Assessments were conducted at baseline and after 1 day (tested 15 min post-application), 7 days, and 14 days of application using Sebumeter, Tewameter, Corneometer, Mexameter, and VISIA.

Results showed significant improvements in skin parameters across all subgroups. In the dry sensitive skin subgroup, the mask increased skin hydration, sebum content, and reduced redness. For the oily sensitive skin subgroup, the mask regulated sebum production and improved skin hydration. In the oily acne skin subgroup, the mask reduced sebum content, redness, TEWL, and post-inflammatory erythema and hyperpigmentation. Tolerance was excellent for all skin types, with no adverse reactions observed.

This study highlights the efficacy and safety of the panthenol-enriched LRP Mask Pro for individuals with distinct skin barrier impairment subgroups. The mask's versatile formulation and proven efficacy make it a valuable skincare product for addressing various skin concerns and achieving healthier, more balanced skin.

Injury to skin tissue is devastating for human health, making it imperative to devise strategies for hastening wound healing. Normal wound healing is a complex process comprising overlapping steps, including hemostasis, inflammatory response, proliferation, and matrix remodeling. This study investigated the effects of adipose stem cell-derived exosomes (ADSC-exos) on wound healing and the underlying mechanisms.

In vitro hydrogen peroxide (H2O2)-treated human keratinocyte (HaCaT) cell lines and in vivo animal wound models were established for this purpose. The cell migration was assessed using transwell and wound healing assays, while exosome biomarker expressions were studied using western blot. Moreover, adipose stem cells were identified using flow cytometry, alizarin red S and oil red O staining, and transmission electron microscopy.

Results indicated that H2O2 treatment inhibited the cell viability and migration of HaCaT cells while being promoted by ADSC-exos. Mechanistic investigations revealed that microRNA-let-7i-5p (let-7i-5p) in ADSC-exos was carried into the HaCaT cells, inhibiting the expression of growth arrest-specific-7 (GAS7). Rescue experiments further verified these results, which indicated that GAS7 overexpression reversed the effect of let-7i-5p on the viability and migration of HaCaT cells, suggesting ADSC-exos promoted wound healing via the let-7i-5p/GAS7 axis.

Adipose stem cell-derived-exos enhanced the viability and migration of HaCaT via carrying let-7i-5p and targeting GAS7, ultimately promoting wound healing in rats.

Diabetic wounds are a common complication of diabetes. The prolonged exposure to high glucose and oxidative stress in the wound environment increases the risk of bacterial infection and abnormal angiogenesis, leading to amputation. Microneedle patches have shown promise in promoting the healing of diabetic wounds through transdermal drug delivery. These patches target the four main aspects of diabetic wound treatment: hypoglycemia, antibacterial action, inflammatory regulation, and tissue regeneration. By overcoming the limitations of traditional administration methods, microneedle patches enable targeted therapy for deteriorated tissues. The design of these patches extends beyond the selection of needle tip material and biomacromolecule encapsulated drugs; it can also incorporate near-infrared rays to facilitate cascade reactions and treat diabetic wounds. In this review, we comprehensively summarize the advantages of microneedle patches compared to traditional treatment methods. We focus on the design and mechanism of these patches based on existing experimental articles in the field and discuss the potential for future research on microneedle patches.

Human amniotic membranes (hAMs) are widely used as wound management biomaterials, especially as grafts for corneal reconstruction due to the structure of the extracellular matrix and excellent biological properties. However, their fragile nature and rapid degradation rate hinder widespread clinical use. In this work, we engineered a novel self-powered electronic dress (E-dress), combining the beneficial properties of an amniotic membrane and a flexible electrical electrode to enhance wound healing. The E-dress displayed a sustained discharge capacity, leading to increased epidermal growth factor (EGF) release from amniotic mesenchymal interstitial stem cells. Live/dead staining, CCK-8, and scratch-wound-closure assays were performed in vitro. Compared with amniotic membrane treatment alone, the E-dress promoted cell proliferation and migration of mouse fibroblast cells and lower cytotoxicity. In a mouse full-skin defect model, the E-dress achieved significantly accelerated wound closure. Histological analysis revealed that E-dress treatment promoted epithelialization and neovascularization in mouse skin. The E-dress exhibited a desirable flexibility that aligned with tissue organization and displayed maximum bioactivity within a short period to overcome rapid degradation, implying great potential for clinical applications.

Staphylococcus aureus is one of the most common bacterial isolates found in wounds. Thus, innovative dressings, such as hydrogels, are interesting vehicles for incorporating bioactive compounds like those from Melaleuca alternifolia essential oil (MaEO). In this study, we evaluated the antimicrobial and anti-inflammatory potential of MaEO incorporated into an alginate and chitosan hydrogel for treating wounds infected by S. aureus. The hydrogel incorporated with MaEO 1% (HMa 1%) was homogeneous with a bright pale-yellow color and the characteristic smell of Melaleuca. The incorporation of MaEO 1% does not affect the stability of the hydrogel, which was stable up to 90 days of storage. The Scanning electron microscopy analysis revealed that hydrogels showed irregular surfaces and interconnected porous structures with accumulations of oil crystals distributed throughout the formulation. HMa 1% has a high moisture content (95.1%) and can absorb simulated wound fluid. Regarding the antimicrobial effects, HMa 1% reduced the growth of S. aureus ATCC 6538 in both in vitro conditions and in an ex vivo model of wounds using porcine skin. In addition, the dairy topical treatment of murine skin lesions with HMa 1% induced a significant reduction of the wound area, inflammation score, and bacterial load, as well as tissue re-epithelialization and modulation of inflammatory mediators. Therefore, hydrogel incorporated with MaEO 1% has excellent potential to be used in the pharmacotherapy of infected wounds.

Cutaneous wound healing is a complex biological process involving a series of well-coordinated events aimed at restoring skin integrity and function. Various experimental models have been developed to study the mechanisms underlying skin wound repair and to evaluate potential therapeutic interventions. This review explores the diverse array of skin wound healing models utilized in research, ranging from rodent excisional wounds to advanced tissue engineering constructs and microfluidic platforms. More importantly, the influence of lipids on the wound healing process is examined, emphasizing their role in enhancing barrier function restoration, modulating inflammation, promoting cell proliferation, and promoting remodeling. Lipids, such as phospholipids, sphingolipids, and ceramides, play crucial roles in membrane structure, cell signaling, and tissue repair. Understanding the interplay between lipids and the wound microenvironment provides valuable insights into the development of novel therapeutic strategies for promoting efficient wound healing and tissue regeneration. This review highlights the significance of investigating skin wound healing models and elucidating the intricate involvement of lipids in the healing process, offering potential avenues for improving clinical outcomes in wound management.

The severe quality of life and economic burden imposed by non-healing skin wounds, infection risks, and treatment costs are affecting millions of patients worldwide. To mitigate these challenges, scientists are relentlessly seeking effective treatment measures. In recent years, extracellular vesicles (EVs) have emerged as a promising cell-free therapy strategy, attracting extensive attention from researchers. EVs mediate intercellular communication, possessing excellent biocompatibility and stability. These features make EVs a potential tool for treating a plethora of diseases, including those related to wound repair. However, there is a growing focus on the engineering of EVs to overcome inherent limitations such as low production, relatively fixed content, and targeting capabilities of natural EVs. This engineering could improve both the effectiveness and specificity of EVs in wound repair treatments. In light of this, the present review will introduce the latest progress in the design methods and experimental paradigms of engineered EVs applied in wound repair. Furthermore, it will comprehensively analyze the current clinical research status and prospects of engineered EVs within this field.

The demand for innovative therapeutic interventions to expedite wound healing, particularly in vulnerable populations such as aging and diabetic patients, has prompted the exploration of novel strategies. Mesenchymal stem cell (MSC)-based therapy emerges as a promising avenue for treating acute and chronic wounds. However, its clinical application faces persistent challenges, notably the low survivability and limited retention time of engraftment in wound environments. Addressing this, a strategy to sustain the viability and functionality of human MSCs (hMSCs) in a graft-able format has been identified as crucial for advanced wound care. Hydrogel microparticles (HMPs) emerge as promising entities in the field of wound healing, showcasing versatile capabilities in delivering both cells and bioactive molecules/drugs. In this study, gelatin HMPs (GelMPs) were synthesized via an optimized mild processing method. GelMPs with distinct diameter sizes were sorted and characterized. The growth of hMSCs on GelMPs with various sizes was evaluated. The release of wound healing promoting factors from hMSCs cultured on different GelMPs were assessed using scratch wound assays and gene expression analysis. GelMPs with a size smaller than 100 microns supported better cell growth and cell migration compared to larger sizes (100 microns or 200 microns). While encapsulation of hMSCs in hydrogels has been a common route for delivering viable hMSCs, we hypothesized that hMSCs cultured on GelMPs are more robust than those encapsulated in hydrogels. To test this hypothesis, hMSCs were cultured on GelMPs or in the cross-linked methacrylated gelatin hydrogel (GelMA). Comparative analysis of growth and wound healing effects revealed that hMSCs cultured on GelMPs exhibited higher viability and released more wound healing activities in vitro. This observation highlights the potential of GelMPs, especially those with a size smaller than 100 microns, as a promising carrier for delivering hMSCs in wound healing applications, providing valuable insights for the optimization of advanced therapeutic strategies.

Sensitive skin is a common condition affecting a significant proportion of the population, and there is a growing demand for effective and safe management.

To evaluate the efficacy and safety of a cream containing panthenol, prebiotics, and probiotic lysate as an optimal care for facial sensitive skin.

A total of 110 participants (64 in group A and 46 in group B) with facial sensitive skin applied the cream twice daily for 28 days. Group A evaluated their sensitive skin, product efficacy, and product use experience at D0 (15 min), D1, D14, and D28. In group B, skin barrier function-related indicators were measured at baseline and on D1, D7, D14, and D28. Dermatologists evaluated tolerance for all participants.

After 28 days of use, in group A, 100% of participants reported mildness and comfort with product use. Participants demonstrated significant improvements in skin barrier function-related indicators, including increased stratum corneum moisture content, reduced erythema index, elevated sebum content, decreased trans-epidermal water loss, and diminished skin redness parameter a* value (all p < 0.05). Dermatologist evaluations revealed excellent tolerance among all participants.

The panthenol-enriched cream with prebiotics and probiotic lysate exhibited substantial clinical efficacy in ameliorating facial sensitive skin conditions, coupled with a high safety profile.

In postoperative wound healing after surgical operations or ablative laser treatments, recent studies suggest the timely use of non-ablative fractional laser treatments with the aim to improve wound healing and prevent pathological scar formation. However, the underlying molecular mechanisms are poorly understood. The aim of this study was to investigate the effects of laser-assisted scar healing (LASH) at the molecular level and to combine it with already established wound healing-promoting local treatments.

We irradiated full-thickness 3D skin models with a fractional ablative Er:YAG laser to set standardized lesions to the epidermal and upper dermal layer. Subsequently, LASH was induced by irradiating the models with either a fractional non-ablative 1540 nm Er:Glass or 1550 nm diode laser. In addition, we tested the combination of non-ablative fractional laser treatment and topical aftercare with a dexpanthenol-containing ointment (DCO).

Histological analysis revealed that models irradiated with the 1540 nm Er:Glass or 1550 nm diode laser exhibited accelerated but not complete wound closure after 16 h. In contrast, additional topical posttreatment with DCO resulted in complete wound closure. At gene expression level, both non-ablative laser systems showed similar effects on epidermal differentiation and mild anti-inflammatory properties. The additional posttreatment with DCO enhanced the wound-healing effects of LASH, especially the upregulation of epidermal differentiation markers and anti-inflammatory cytokines at the gene expression level.

This in vitro study deciphers the biological effects of LASH with a fractional non-ablative 1540 nm Er:Glass or a 1550 nm diode laser in 3D skin models. These data help to better understand the biological properties of the LASH technique and is important to optimize its application.

The complete healing of skin wounds has been a challenge in clinical treatment. Self-healing hydrogels are special hydrogels formed by distinctive physicochemically reversible bonds, and they are considered promising biomaterials in the biomedical field owing to their inherently good drug-carrying capacity as well as self-healing and repair abilities. Moreover, natural polymeric materials have received considerable attention in skin tissue engineering owing to their low cytotoxicity, low immunogenicity, and excellent biodegradation rates. In this paper, we review recent advances in the design of self-healing hydrogels based on natural polymers for skin-wound healing applications. First, we outline a variety of natural polymers that can be used to construct self-healing hydrogel systems and highlight the advantages and disadvantages of different natural polymers. We then describe the principle of self-healing hydrogels in terms of two different crosslinking mechanisms-physical and chemical-and dissect their performance characteristics based on the practical needs of skin-trauma applications. Next, we outline the biological mechanisms involved in the healing of skin wounds and describe the current application strategies for self-healing hydrogels based on these mechanisms. Finally, we analyze and summarize the challenges and prospects of natural-material-based self-healing hydrogels for skin applications.

Pantothenic acid, also referred to as vitamin B5, is a water-soluble vitamin that has essential functions in the body as a component of coenzyme A (CoA) and acyl carrier protein (ACP). It is widely distributed in animal and plant-source foods. Nutritional deficiency of pantothenic acid is rare and toxicity negligible. Information on pantothenic acid intakes in the Nordic countries is limited and biomarker data from Nordic and Baltic populations is missing. Due to a lack of data, no dietary reference values (DRVs) were given for pantothenic acid in the Nordic Nutrition Recommendations (NNR) since 2012. The aim of this scoping review was to examine recent evidence relevant for updating the DRVs for NNR2023. Scientific literature since 2012 on associations of pantothenic acid with health-related issues in Nordic and Baltic countries was searched. No health concerns related to pantothenic acid were identified.

Chronic wounds, especially those that are hard-to-heal, constitute a serious public-health problem. Although progress has been made in the development of wound dressings for healing, there is little high-quality evidence of their efficacy, with no evidence of superiority in the use of one hydrogel over another. To evaluate the superiority of a hydrogel (EHO-85), containing Olea europaea leaf extract (OELE), over a standard hydrogel (SH), the promotion and/or improvement of healing of difficult-to-heal wounds was compared in a prospective, parallel-group multicenter, randomized, observer-blinded, controlled trial ("MACAON"). Non-hospitalized patients with pressure, venous or diabetic foot-ulcers difficult-to-heal were recruited and treated with standard care, and EHO-85 (n = 35) or VariHesive (n = 34) as SH. Wound-area reduction (WAR; percentage) and healing rate (HR; mm2/day) were measured. EHO-85 showed a statistically significant superior effect over VariHesive. At the end of the follow-up period, the relative WAR decreased by 51.6% vs. 18.9% (p < 0.001), with a HR mean of 10.5 ± 5.7 vs. 1.0 ± 7.5 mm2/day (p = 0.036). EHO-85 superiority is probably based on its optimal ability to balance the ulcer bed, by modulating pH and oxidative stress. That complements the wetting and barrier functions, characteristics of conventional hydrogels. These results support the use of EHO-85 dressing, for treatment of hard-to-heal ulcers. Trial Registration AEMPS:PS/CR623/17/CE.

The quest for an ideal wound dressing has been a longstanding challenge due to the complex nature of wound healing, including stages of haemostasis, inflammation, maturation and remodelling, with overlapping timelines. This makes it difficult to find a single dressing that optimally supports all phases of wound healing. In addition, the ideal wound dressing should possess antibacterial properties and be capable of effectively debriding and lysing necrotic tissue. Copper is an essential trace element that participates in many of the key physiological wound healing processes.

Copper stimulates secretion of various cytokines and growth factors, thus promoting angiogenesis, granulation tissue formation, extracellular matrix proteins secretion and re-epithelialisation. Harnessing this knowledge, we have used copper oxide-impregnated wound dressings in numerous cases and observed their benefits throughout the entire wound healing process.

This led us to postulate the 'continuum of care' hypothesis of copper dressings. In this study we describe four cases of hard-to-heal wounds of various aetiologies, in which we applied copper dressings consistently across all stages of wound healing, with rapid uneventful healing.

We believe we have successfully implemented the continuum of care principle.

Agents that will accelerate wound healing maintain their clinical importance in all aspects. The aim of this study is to determine the antimicrobial activity of zinc oxide nanoparticles (ZnO NPs) ZnO nanoparticles obtained by green synthesis from Capparis spinosa L. extract and their effect on in vitro wound healing. ZnO NPs were synthesized and characterized using Capparis spinosa L. extract. ZnO NPs were tested against nine ATCC-coded pathogen strains to determine antimicrobial activity. The effects of different doses (0.0390625-20 µg/mL) of NPs on cell viability were determined by MTT assay. The effect of ZnO NPs doses (0.0390625 µg/mL, 0.078125 µg/mL, 0.15625 µg/mL, 0.3125 µg/mL, 0.625 µg/mL, 1.25 µg/mL) that increase proliferation and migration on wound healing was investigated in an in vitro wound experiment. Cell culture medium obtained from the in vitro wound assay was used for biochemical analysis, and plate alcohol-fixed cells were used for immunohistochemical staining. It was determined that NPs formed an inhibition zone against the tested Gram-positive bacteria. The ZnO NPs doses determined in the MTT test provided faster wound closure in in-vitro conditions compared to the DMSO group. Biochemical analyses showed that inflammation and oxidative status decreased, while antioxidant levels increased in ZnO NPs groups. Immunohistochemical analyses showed increased expression levels of Bek/FGFR2, IGF, and TGF-β associated with wound healing. The findings reveal the antimicrobial effect of ZnO nanoparticles obtained using Capparis spinosa L. extract in vitro and their potential applications in wound healing.