Search Results (2,356)

Cutaneous leishmaniasis is a zoonotic disease caused by Leishmania parasites and leads to chronic, non-healing skin lesions. Although current drugs can control the disease, their use is limited by systemic side effects, low efficacy, and inadequate lesion penetration. Therefore, innovative local delivery systems are required to enhance drug penetration and reduce systemic toxicity. To address these challenges, silver nanoparticles (AgNPs) were synthesized using propolis extract through a green synthesis approach, and a tri-layer wound dressing composed of polyvinyl alcohol and gelatin containing synthesized AgNPs and Glucantime was fabricated by electrospinning. Characterization (SEM-EDX, FTIR, TGA) confirmed uniform morphology, chemical structure, and thermal stability; the wound dressing exhibited hydrophilicity, antioxidant activity, and biphasic release. Biological evaluations against Leishmania tropica demonstrated significant antiparasitic activity. Promastigote viability decreased from 76.3% in neat fibers to 31.6% in nanofibers containing AgNPs and 7.9% in tri-layer nanofibers containing both AgNPs and Glucantime. Similarly, the amastigote infection index dropped from 410 in controls to 250 in neat nanofibers, 204 in AgNPs-containing nanofibers, and 22 in tri-layer nanofibers containing AgNPs and Glucantime. The tri-layer nanofibers demonstrated enhanced antileishmanial activity over AgNPs-containing fibers, confirming synergistic efficacy. All nanofibers were biocompatible, supporting their use as a safe platform for cutaneous leishmaniasis treatment. Full article

Background: Wound healing contributes to restoring skin integrity. However, scars affect soft tissue in all its layers, including the superficial and deep fascia; moreover, it has been demonstrated that the fibroblasts leading the scarring process develop from progenitors located in the superficial fascia. In the past, research into scar etiology has focused primarily on the dermal and epidermal layers, leaving the role of the fasciae largely overlooked. Many patients presenting with surgical or traumatic scars complain of the increased stiffness and thickness of the scar, reduced extensibility of the area surrounding it, and chronic pain persisting even after the healing process has been completed. The purpose of this systematic review is to investigate the non-invasive tools and methods employed for the objective evaluation of scars that involve fascial layers. Methods: A systematic literature search was conducted on PubMed and WOS. Registration DOI: 10.17605/OSF.IO/SDR3Q. Results: A total of 11 articles were selected; the etiologies of scars were surgical, traumatic, and other (keloids). The investigations were conducted using ultrasound, magnetic resonance imaging, strain elastography, and shear wave elastography on the visceral fasciae, superficial fascia, hypodermis, and musculoskeletal fasciae. Sliding of fasciae was assessed by ultrasound; thickness of fasciae was assessed by ultrasound and magnetic resonance imaging; stiffness was assessed by shear wave elastography and strain elastography; and the qualitative assessment was performed via ultrasound. Conclusions: Our literature review showed that ultrasound, magnetic resonance imaging, strain elastography, and shear wave elastography are currently adopted for investigating the sliding, thickness, stiffness, and qualitative features of scars involving fascial layers. Moreover, our research showed the existence of a gap in the scientific literature on this topic. Full article

Hard-to-heal wounds remain a significant challenge for healthcare professionals, particularly in aging populations. Although most chronic wounds are associated with diabetes or chronic venous insufficiency, rare etiologies should also be considered. One such cause is envenomation by Phoneutria spp. (native to South America, rare in Europe). Their venom contains potent neurotoxins. While systemic manifestations are more commonly reported, localized necrotic skin lesions may also occur. This case report presents a rare chronic wound following a suspected Phoneutria spider bite and highlights the importance of an individualized, multimodal treatment approach. A 61-year-old male patient with a progressive thigh wound following a spider bite sustained during work. Despite initial self-treatment and pharmacotherapy the wound deteriorated. The patient was admitted to the authors’ facility, where surgical treatment included necrosectomy and a sandwich graft using an acellular dermal matrix combined with a split-thickness skin graft. Adjunctive therapies included negative pressure wound therapy and hyperbaric oxygen therapy. After discharge, outpatient wound care was continued. Treatment was monitored with photographic documentation and serial microperfusion measurements. Complete wound closure was achieved after 4 months of specialized therapy. Management of chronic wounds requires a multidisciplinary and individualized approach with surgical intervention, advanced wound care and specialized outpatient follow-up. Full article

Background/Objectives: This 7-day rat tracheocutaneous fistula study considered the not-studied issues of tracheocutaneous fistula course, wound healing, and fistula in the NO-system relations. Therefore, we focused on fistulas’ severe course, tracheocutaneous fistula → air leak → compensatory diaphragmatic/abdominal “heaving”, NO-system failed relations, and therapy resolution. Stable gastric pentadecapeptide BPC 157 was proposed. Methods: Tracheocutaneous fistula rats received daily medication (/kg), alone or combined, BPC 157 therapy (10 µg, 10 ng, in drinking water or intraperitoneally) along with a triple NO-agent approach (L-NAME 5 mg, L-arginine 100 mg, and L-NAME+L-arginine, intraperitoneally). Results: Tracheocutaneous fistulas occurred as specific and NO-system-related as follows: NO system: blockade (L-NAME-aggravation) over-activity (L-arginine-amelioration) or immobilization (L-NAME+L-arginine oppose each other’s effects). Controls presented severe clinical signs of respiratory distress, failed healing, skin and tracheal defects, a not-healed and open, macro/microscopically, and fistulous tract that was well-formed and wide, tracheal shrinking below the fistula, and clinically, open-mouth breathing, “heaving abdomen”, cyanosis (bluish snout, ears, extremities), abundant secretion through the fistula, and weight loss. Fistula tissue NO level decreased, and the malondialdehyde (MDA) level increased. The BPC 157 therapy (both application routes) resulted in rapid recovery. Healing of defects (skin and trachea) and fistula closure, macro/microscopically, corresponded with clinical findings, avoiding observable clinical signs of dyspnea, reducing weight loss, and avoiding any sign of “heaving abdomen”. BPC 157-treated rats displayed regular breathing movements without observable signs of respiratory distress. Finally, when combined, BPC 157 therapy upgrades L-arginine amelioration, abolishes L-NAME-induced worsening, and restores full healing after NO immobilization (L-NAME+L-arginine). BPC 157 counteracted increase in NO level and counteracted increase in MDA level. Conclusions: Thus, first, acting systemically, BPC 157 reverses tracheocutaneous fistula course in rats. It acts through the NO system. Full article

Chronic diabetic wounds are characterized by persistent inflammation, impaired angiogenesis, oxidative stress, and defective tissue remodeling, leading to delayed healing. Cordyceps militaris, a medicinal fungus with known anti-inflammatory and antioxidant properties, has shown therapeutic potential in metabolic disorders; however, its role in diabetic wound repair remains unclear. In this study, we evaluated the wound-healing effects of an aqueous extract of C. militaris using in vitro keratinocyte models and a streptozotocin-induced diabetic mouse model. C. militaris treatment significantly accelerated wound closure, improved epidermal regeneration, and enhanced skin barrier integrity. Mechanistically, C. militaris restored HIF-1α and TGF-β1 expression, promoted cell proliferation and fibroblast activation, and increased the expression of matrix metalloproteinases MMP-1 and MMP-2, indicating enhanced extracellular matrix remodeling. In parallel, excessive inflammatory responses were attenuated, as evidenced by reduced IL-6 and TNF-α levels, along with activation of SIRT1/Nrf2/HO-1 antioxidant signaling pathways. Collectively, these findings demonstrate that C. militaris promotes a balanced wound-healing microenvironment and represents a promising natural therapeutic candidate for the treatment of diabetic wounds. Full article

Cosmeceutical peptides (CPs), which modulate various biological activities, including skin regeneration and wound healing, have emerged as promising agents in skincare. In this study, we investigated the regenerative and wound healing potential of a short peptide, CP-02 (sequence CDARSDAR), using human dermal fibroblast cells (HDFs) in vitro and a zebrafish model in vivo. In HDFs, CP-02 treatment at concentrations of 50, 100, and 200 µg/mL significantly accelerated wound closure in a dose-dependent manner (p < 0.05) and upregulated the mRNA expression of CCND1, MYC, FGF2, EFG, and IL-8 at 12 h post-treatment. In amputated zebrafish larvae, exposure to CP-02 (5 µg/mL) for 72 h significantly increased fin regeneration, with a fin area of 3.5 mm² and fin-fold length of 0.2 mm, compared with those in controls (2 mm² and 0.07 mm, respectively). Intramuscular administration of CP-02 significantly improved the healing rates in wounded adult zebrafish to 58% and 76% on 12 and 16 days post wounding (dpw), respectively, compared with the vehicle (35% and 44%, respectively). Histological analysis (H&E staining) revealed reduced inflammatory cell infiltration, complete granulation, and re-epithelialization in the CP-02-treated tissues at 12 dpw. Furthermore, mRNA expression levels of tnf-α, il-1β, tgfb1, mmp9, mmp13, and timp2b were elevated in the CP-02 group at 4 dpw, whereas those of pro-fibrotic mediators, including acta2, ctgfb, cdh1, and col9a3 reduced in muscle tissue on 12 dpw. Collectively these findings demonstrate that CP-02 promotes effective, scar-reducing regeneration and wound healing, highlighting its strong potential as a therapeutic peptide for future skincare and cosmeceutical applications. Full article

The growing global threat of antimicrobial resistance (AMR), particularly in cutaneous wound infections, represents a significant clinical and economic challenge. Biofilm formation by multidrug-resistant pathogens, such as Acinetobacter baumannii, often complicates healing and leads to therapeutic failure. Antimicrobial peptides (AMPs) are a promising alternative to conventional antibiotics due to their potent membrane-disrupting mechanism of action and lower propensity to induce resistance. Background/Objectives: This study aimed to evaluate the antibacterial, antibiofilm, and in vivo efficacy of four snake venom-derived cathelicidin-like peptides—Btn (15-34) and BotrAMP14 from Bothrops atrox, and Ctn (15-34) and CrotAMP14 from Crotalus durissus—against multidrug-resistant A. baumannii, Escherichia coli, and Pseudomonas aeruginosa clinical isolates from skin infections, with emphasis on A. baumannii, a WHO priority pathogen. Methods: Minimal Inhibitory Concentration (MIC), Minimal Bactericidal Concentration (MBC), and Minimal Biofilm Inhibitory Concentration (MBIC) were determined against A. baumannii, Escherichia coli, and Pseudomonas aeruginosa. Time-kill kinetics, hemolytic activity, and cytotoxicity assays were performed. A murine skin wound infection model was established to evaluate in vivo antibacterial efficacy and safety. Results: MIC/MBC values ranged from 0.78 to 25 µM against planktonic cells. In comparison, MBIC ranged from 1.56 to 12.5 µM against biofilms. BotrAMP14 eradicated A. baumannii within 4 min, while CrotAMP14 achieved bactericidal action in 20 min at 1.56 µM. Both peptides exhibited no hemolytic activity up to 128 µM and low cytotoxicity (IC₅₀ > 128 µM). In vivo, BotrAMP14 and CrotAMP14 demonstrated significant antibacterial activity at 24 h and 48 h post-infection, respectively, surpassing that of meropenem. Conclusions: These findings suggest that BotrAMP14 and CrotAMP14 are promising topical antimicrobial agents for managing multidrug-resistant skin infections and may help address the urgent need for alternative therapies against antibiotic-resistant pathogens. Full article

A wound has been defined as a disruption of tissue integrity. Pain, bleeding, and the risk of infection are inherent features of wounds, while chronic wounds are often accompanied by serous exudate. Pain associated with chronic wounds is usually underestimated and inadequately addressed in routine clinical care, despite being considered by patients as one of the most burdensome factors affecting their quality of life. Traditionally, management of wound-related pain has relied primarily on systemic analgesics, commonly administered orally. However, recently, there has been accumulated interest in the potential of topical analgesics. Unfortunately, both systemic and local administrations of conventional analgesics (e.g., NSAIDs, opioids) might carry risks of adverse effects, including delayed wound healing and systemic absorption. In this review, we summarize current research on the use of local analgesia for painful wounds and explore the potential of topically applied peptides with analgesic activity as a promising alternative to conventional pain management strategies. We also discuss recent innovations in the development of therapeutic peptides, including those with anti-inflammatory and regenerative activities, which might further enhance outcomes in the wound healing process. Finally, we address challenges associated with topical peptide delivery across compromised skin barriers and examine strategies to overcome these limitations, while outlining future directions for formulation and clinical application of peptide-based wound therapies. Full article

Sunflower seeds have been reported to be a healthy natural source of polyphenols. This study aimed to explore the mechanisms of potential compounds in sunflower seed extract involved in wound healing; major compounds were investigated through network pharmacology and molecular docking. In an in vitro wound-healing assay applied using an immortalised human keratinocyte (HaCaT) cell model, 10 µg/mL of the sunflower seed extract promoted cell migration in HaCaT cells and led to complete wound closure after 24 h; at a 1 µg/mL concentration, it led to complete wound closure after 72 h. The sunflower seed extract presented moderate-to-strong antioxidant activity. Liquid chromatography–mass spectrometry and high-performance liquid chromatography were used to identify the major compounds present in the sunflower seed extract. Forty-seven compounds were identified, among which chlorogenic acid was the most abundant phenolic compound. Network pharmacology was used to identify wound-healing-related targets. In total, 252 proteins were linked to the 47 compounds. Cyto-Hubba analysis identified 10 hub proteins with a strong correlation with wound healing. Molecular docking was used to assess the ability of the major compounds in the sunflower seed extract to combat NF-κB1, EGFR, and MMP9. Chlorogenic acid showed higher binding affinity to all targets. Moreover, its pharmacokinetic properties were well distributed in the plasma (VDss = 0.377 log L/kg), and they were not a carcinogen and did not cause skin sensitisation. In conclusion, the findings suggest that the sunflower seed extract is a potential source of bioactive compounds that can enhance wound healing and can be developed to create a transdermal application. Full article

Oxidative stress caused by excessive reactive oxygen species (ROS) disrupts skin and oral epithelial homeostasis and contributes to skin aging, inflammation, periodontitis, and mucosal injury. As the principal defenders in both skin and oral mucosal tissues, keratinocytes are important responders to oxidative stress. However, most existing studies have examined skin or oral keratinocytes in isolation, with few comparative investigations of their tolerance, repair capacity, and antioxidant mechanisms under oxidative stress. In this study, we systematically compared immortalized oral keratinocytes (TIGK) and skin keratinocytes (HaCaT) under hydrogen peroxide (H₂O₂)-induced oxidative stress. Functional analyses, including cell survival, ROS accumulation, stress granule formation, in vitro wound healing, and proliferation recovery assays, were combined with transcriptomic profiling to evaluate differences in antioxidant and pro-oxidant systems. TIGK exhibited significantly higher survival rates, lower ROS accumulation, and superior migratory and proliferative recovery compared with HaCaT after oxidative insult. Transcriptomic analysis further revealed that TIGK consistently expressed higher levels of antioxidant genes and enzymes. In contrast, HaCaT showed greater ROS accumulation and relatively limited antioxidant defenses. The results show that oral and skin keratinocytes adopt distinct adaptive mechanisms under oxidative stress. The intrinsic redox advantage of oral keratinocytes provides new insights into their rapid wound-healing capacity and may inform strategies to enhance epithelial resilience. Full article

Topical antibiotics have long been used for the prevention and treatment of superficial skin and soft tissue infections; however, increasing evidence indicates that their clinical value is undermined by rising antimicrobial resistance, high rates of allergic sensitization, inadequate activity against biofilms, and a lack of wound-healing properties. Agents such as bacitracin, neomycin, polymyxin B, mupirocin, and fusidic acid act through narrow, target-specific mechanisms that facilitate resistance selection and provide limited benefit in chronic or polymicrobial wound environments. Contemporary antimicrobial stewardship frameworks therefore discourage routine use of topical antibiotics and increasingly favor non-antibiotic antiseptics with broad-spectrum activity and low resistance risk, including silver, iodine, polyhexamethylene biguanide, octenidine, and medical-grade honey. These modalities, however, primarily serve to reduce microbial burden and do not directly address the underlying biological impairments that prevent healing. Nitric oxide-releasing gels (NORGs) represent a novel class of topical antimicrobials that combine multi-target bactericidal activity with physiologic pro-healing effects. Nitric oxide exerts potent antimicrobial and antibiofilm effects via oxidative and nitrosative stress, disruption of metabolic pathways, inhibition of DNA replication, and interference with quorum sensing. Simultaneously, nitric oxide enhances angiogenesis, modulates inflammation, improves microvascular perfusion, and promotes fibroblast and keratinocyte function. Preclinical models and early-phase clinical studies demonstrate broad-spectrum efficacy—including activity against multidrug-resistant organisms—with favorable tolerability and minimal risk of resistance development. Although the current evidence base remains preliminary, NORGs offer a promising antimicrobial platform with the potential to reduce reliance on topical antibiotics while simultaneously addressing key barriers to wound healing. Larger randomized controlled trials, direct comparisons with established advanced dressings, and robust pharmacoeconomic evaluations are needed to define their optimal role within stewardship-aligned wound-care practice. Full article

Chronic diabetic wounds are often characterized by persistent hypoxia and poor healing outcomes, highlighting the need for regenerative grafts that not only promote tissue repair but also provide insights into the wound microenvironment. In this study, we introduce a novel strategy for diabetic ulcer treatment through the development of a structurally personalized skin graft. The graft is fabricated via 3D bioprinting of natural porcine skin extracellular matrix (psECM) and integrated with microsensors for oxygen monitoring. We established a porcine skin decellularization protocol that efficiently removed cellular components, while preserving the integrity of the ECM, as verified by DNA quantification and scanning electron microscopy. The resulting psECM bioink demonstrated rheological properties suitable for 3D printing, which depended on psECM concentration and exhibited temperature-responsive gelation behavior. Incorporation of LiNC-BuO oxygen microsensors into the bioink enabled real-time, non-invasive oxygen level monitoring within the printed constructs. Both in vitro and in vivo studies confirmed the cytocompatibility and low immunogenicity of the psECM-based grafts with embedded microsensors. Moreover, the 3D bioprinting technology enabled the manufacturing of grafts tailored to match individual wound geometries. The technological proof of concept presented herein for this multifunctional platform, which integrates the regenerative benefits of ECM scaffolds with advanced biosensing capabilities, represents a promising approach for enhancing future therapeutic outcomes in the management of diabetic ulcers. Full article

This manuscript describes the development of a nano-sized synthetic smectic clay hydrogel (LAP) that enables controlled oxygen delivery, making it a promising candidate for treating skin wound infections and promoting healing. LAP is an ingredient in various dermatological products, including powders, creams and emulsions. We investigated the antibacterial effect of the LAP hydrogel by incorporating calcium peroxide (CPO), an oxygen-releasing agent, and measuring the size of the inhibitory halo. We found that CPO hydrogels in LAP showed a significant increase in oxygen release during the first five hours, especially at low CPO concentrations. For example, the hydrogel with 5% CPO showed a controlled release profile with a final percentage oxygen release of 2.47 ± 0.01% after 5 h. In contrast, the hydrogels with 10% and 20% CPO achieved lower final oxygen release values, 0.67 ± 0.01% and 0.75 ± 0.01%, respectively, suggesting that the encapsulation efficiency of LAP is higher at higher concentrations. LAP also proved to be an effective oxygen barrier and showed inherent antimicrobial activity. The research confirmed the antibacterial properties of the hydrogel, with inhibition sites observed against both E. coli and S. aureus. These results emphasize the potential of this hydrogel to serve as an effective tool for wound treatment by providing sustained oxygenation and fighting microbial infections. Full article

Background/Objectives: Bioresorbable polylactic acid (PLA) matrices have shown promise in supporting wound healing through their biocompatibility, tissue integration, and potential involvement in immune regulatory mechanisms. This study aimed to analyze the clinical performance of a PLA-based matrix in the treatment of chronic wounds under real-world conditions in a single-center setting. Methods: This retrospective study included patients with chronic wounds treated with the polylactic acid matrix at Evangelisches Waldkrankenhaus Spandau between February 2023 and February 2025. Wounds were surgically debrided in the operating room prior to matrix application. The matrix remained in place until resorption or detachment, with reapplications occurring at a mean interval of approximately 14 days. Data was anonymized and analyzed descriptively. Results: A total of 14 patients with 16 chronic wounds were treated in this study. The mean patient age was 76.1 years. The most common underlying causes were ischemia and trauma, with an average wound size of 23.6 cm². Complete wound closure was achieved in 15 out of 16 cases (93.8%), with a mean time to complete wound closure of 72.9 days. The average duration of hospitalization was 24.8 days. Conclusions: The polylactic acid matrix demonstrated a high rate of short-term wound closure in a heterogeneous cohort of chronic wounds, with a mean time to closure of 73 days and no requirement for skin grafting. Further prospective studies with standardized long-term follow-up are warranted. Full article

Background/Objectives: Phytochemicals are known to be active contributors to a healthy life, providing valuable wound healing benefits. Methods: This research took an innovative approach that successfully overcame the bioavailability limits of herbal extracts, by entrapping CentellaA with HypericumP in nanostructured lipid carriers (NLCs) and hybrid hyaluronic acid (HA-NLCs) as valuable formulations with enhanced bioactivity. Results: NLCs and HA-NLCs showed excellent entrapping efficiency values for CentellaA and HypericumP ranging from 89.5 to 95.3%. Co-entrapping of CentellaA:HypericumP in a weight ratio of 4:1 and 2:1 led to diameters of 221.4 ± 2.08 nm for NLC-CentellaA-HypericumP and 220.3 ± 1.74 nm for hybrid HA-NLC-CentellaA-HypericumP. The bimodal calorimetric profile of NLCs contributed to a lower degree of lipid core structural organization. HA-NLC-CentellaA showed the safest biocompatibility behavior with BJ skin cells. Conclusions: The cells treated with NLC-CentellaA exhibited a favorable scratch wound closure and promoted the fastest BJ cell migration. NLC- and HA-NLC herbal extracts remodeled the cytoskeleton of BJ fibroblast cells. The morphological fluorescence changes revealed that the fibroblast cells retained intact their cytoskeleton, characteristic of a viable cell with no obvious stress. An active motility of cells treated with NLCs in the wound area was detected, indicating strong pro-migratory properties; e.g., for NLC-CentellaA, the wound was almost closed after 30 h. Designing NLCs with HA adaptability to reinforce the skin wound healing action represents a desired step for the development of herbal products that meets the challenge of combining the benefits of phytochemicals and nanotechnology to create value-added herbal products. Full article