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Search Results (1,361)

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Keywords = chronic wounds

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18 pages, 1545 KiB  
Review
Harnessing Mesenchymal Stromal Cells for Advanced Wound Healing: A Comprehensive Review of Mechanisms and Applications
by Khrystyna Nasadiuk, Tomasz Kolanowski, Cezary Kowalewski, Katarzyna Wozniak, Tomasz Oldak and Natalia Rozwadowska
Int. J. Mol. Sci. 2025, 26(1), 199; https://doi.org/10.3390/ijms26010199 (registering DOI) - 29 Dec 2024
Abstract
Chronic wounds and injuries remain a substantial healthcare challenge, with significant burdens on patient quality of life and healthcare resources. Mesenchymal stromal cells (MSCs) present an innovative approach to enhance tissue repair and regeneration in the context of wound healing. The intrinsic presence [...] Read more.
Chronic wounds and injuries remain a substantial healthcare challenge, with significant burdens on patient quality of life and healthcare resources. Mesenchymal stromal cells (MSCs) present an innovative approach to enhance tissue repair and regeneration in the context of wound healing. The intrinsic presence of MSCs in skin tissue, combined with their roles in wound repair, ease of isolation, broad secretory profile, and low immunogenicity, makes them especially promising for treating chronic wounds. This review explores the current landscape of MSC application, focusing on preclinical and clinical data across chronic wounds, diabetic ulcers, burns, non-union bone fractures, lower extremity venous ulcers, pressure ulcers, and genetic skin conditions like epidermolysis bullosa. Special emphasis is given to the mechanisms through which MSCs exert their regenerative effects, underscoring their potential in advancing wound healing therapies and supporting the broader field of regenerative medicine. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms on Wound Healing)
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<p>The mechanism of therapeutic effect of MSCs in wound healing.</p>
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<p>Paracrine effects of MSCs in wound healing.</p>
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24 pages, 3898 KiB  
Systematic Review
A Systematic Review of Spironolactone Nano-Formulations for Topical Treatment of Skin Hyperandrogenic Disorders and Chronic Wounds
by Saedah Dereiah, Muhammad Usman Ghori and Barbara R. Conway
Pharmaceutics 2025, 17(1), 27; https://doi.org/10.3390/pharmaceutics17010027 - 27 Dec 2024
Viewed by 326
Abstract
Background/Objectives: Spironolactone (SP), an aldosterone inhibitor widely used to treat androgen-dependent disorders such as acne, hirsutism, and alopecia, has demonstrated therapeutic potential in both oral and topical formulations. However, SP’s low solubility and poor bioavailability in conventional formulations have driven the development of [...] Read more.
Background/Objectives: Spironolactone (SP), an aldosterone inhibitor widely used to treat androgen-dependent disorders such as acne, hirsutism, and alopecia, has demonstrated therapeutic potential in both oral and topical formulations. However, SP’s low solubility and poor bioavailability in conventional formulations have driven the development of novel nanocarriers to enhance its efficacy. This review systematically examines recent advancements in SP-loaded nanocarriers, including lipid nanoparticles (LNPs), vesicular nanoparticles (VNPs), polymeric nanoparticles (PNPs), and nanofibers (NFs). Methods: A search strategy was developed, and the relevant literature was systematically searched using databases such as Scopus, PubMed, and Google Scholar. The review process, including screening, inclusion, and exclusion criteria, adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: A comprehensive analysis of 13 eligible research articles, corresponding to 15 studies, highlights key aspects such as encapsulation efficiency, stability, particle size, and in vitro and in vivo efficacy. Six studies focused on lipid nanoparticles (LNPs), including solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), which were found to improve SP’s bioavailability and skin permeation. Another six studies investigated vesicular nanoparticles (VNPs), such as ethosomes and niosomes, demonstrating superior skin targeting and penetration capabilities. Two studies on polymeric nanoparticles (PNPs) showed effectiveness in delivering SP to hair follicles for the treatment of alopecia and acne. Additionally, one study on SP-loaded nanofibers indicated significant potential for topical rosacea therapy. Conclusions: SP-loaded nanocarrier systems represent promising advancements in targeted topical therapy. However, further clinical studies are required to optimize their safety, efficacy, and delivery mechanisms. Full article
(This article belongs to the Section Physical Pharmacy and Formulation)
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<p>Search strategy for literature screening according to PRISMA guidelines [<a href="#B23-pharmaceutics-17-00027" class="html-bibr">23</a>].</p>
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<p>(<b>a</b>) Cumulative studies published on SP nanocarriers over the years, (<b>b</b>) studies published each year categorized by the type of nanocarrier, (<b>c</b>) classification of the various SP nanocarriers based on the current literature review, and (<b>d</b>) different nanoparticulate formulations and their clinical applications for various skin conditions.</p>
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<p>Overall assessment of risk of bias across six domains covered in the eligible studies.</p>
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<p>Schematic illustration showing the structural features and arrangement of SP-loaded solid lipid nanoparticles (SLNs).</p>
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<p>Schematic illustration showing the structural features and arrangement of SP-loaded nanostructured lipid carriers (NLCs).</p>
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<p>Schematic illustration showing the structural features and arrangement of SP-loaded LeciPlexes.</p>
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<p>Schematic illustration showing the structural features and arrangement of SP-loaded ceresomes.</p>
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<p>Schematic representation of SP-loaded HA-enriched ceresomes showing the structural features and arrangement.</p>
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<p>Schematic representation of SP-loaded niosomes showing the structural features and arrangement.</p>
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<p>Schematic representation of SP-loaded ethosomes showing the structural features and arrangement.</p>
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<p>Schematic representation of SP-loaded phytosome showing the structural features and arrangement.</p>
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18 pages, 3980 KiB  
Article
Nutritional Status in a Group of Patients with Wounds Due to Diabetic Foot Disease and Chronic Venous Insufficiency
by Skórka Mateusz, Bazaliński Dariusz, Więch Paweł, Kłęk Stanisław, Kozieł Dorota and Sierżantowicz Regina
J. Clin. Med. 2025, 14(1), 43; https://doi.org/10.3390/jcm14010043 - 25 Dec 2024
Viewed by 261
Abstract
Background: Wound healing is a complex physiological process that begins immediately upon injury. Nutritional status significantly affects the course of regenerative processes. Malnutrition can prolong the inflammatory phase, limit collagen synthesis, and increase the risk of new wound formation. The issue of malnutrition [...] Read more.
Background: Wound healing is a complex physiological process that begins immediately upon injury. Nutritional status significantly affects the course of regenerative processes. Malnutrition can prolong the inflammatory phase, limit collagen synthesis, and increase the risk of new wound formation. The issue of malnutrition is becoming increasingly prevalent and remains a significant concern, particularly among older adults dealing with chronic conditions. Methods: The study was conducted at the Wound Treatment Clinic of the Specialist Hospital at the Podkarpackie Oncology Center in Brzozów, Poland, over 12 months (31 December 2022 to 31 December 2023). A prospective assessment was carried out on 106 patients with chronic wounds. The sample selection was purposeful, based on the following criteria: individuals with hard-to-heal vascular wounds related to diabetic foot disease or venous insufficiency, who provided informed consent to participate after reviewing the study concept. The assessment included a questionnaire and biochemical blood analysis. Further evaluations covered wound characteristics and classification based on clinical scales. The morphotic and biochemical blood parameter assessment included albumin concentration, hemoglobin, C-reactive protein (CRP), and the nutritional risk index (NRI). Results: A larger wound area was associated with lower morphotic values in both groups. Exudate levels and severity in chronic venous insufficiency (CVI) patients and diabetic foot disease (DFD) were associated with lower hemoglobin, albumin, and NRI values. At the same time, the depth of tissue structure damage correlated with the measured biochemical parameters. Conclusions: NRI values and morphotic blood parameters, along with albumin, hemoglobin, and CRP levels, are closely associated with wound characteristics, including surface area, exudate level, and the severity of tissue destruction. The greater the destruction of tissue structures, the higher the risk of malnutrition and wound infection, as indicated by biochemical assessment. Full article
(This article belongs to the Special Issue Clinical Management and Outcomes in Wound Healing)
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<p>Graphical description of the selection of the study group.</p>
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<p>Assessment of participants according to the Barthel scale.</p>
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<p>Comparison of biochemical parameters between the patients with CVI and those with DFD (median values).</p>
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<p>Median albumin values in CVI and DFD patient groups with different wound areas.</p>
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<p>Median HGB values in CVI and DFD patient groups with different wound areas.</p>
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<p>Median CRP values in CVI and DFD patient groups with different wound areas.</p>
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<p>Median NRI values in CVI and DFD patient groups with different wound areas.</p>
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<p>Median albumin values in CVI and DFD patient groups with different NPIAP/EPUAP values.</p>
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<p>Median HGB values in CVI and DFD patient groups with different NPIAP/EPUAP values.</p>
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<p>Median CRP values in CVI and DFD patient groups with different NPIAP/EPUAP values.</p>
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<p>Median NRI values in CVI and DFD patient groups with different NPIAP/EPUAP values.</p>
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18 pages, 9926 KiB  
Article
Cannabidiol-Loaded Lipid Nanoparticles Incorporated in Polyvinyl Alcohol and Sodium Alginate Hydrogel Scaffold for Enhancing Cell Migration and Accelerating Wound Healing
by Sarawut Lapmanee, Sakkarin Bhubhanil, Natthawut Charoenphon, Anjaree Inchan, Phichaporn Bunwatcharaphansakun, Mattaka Khongkow and Katawut Namdee
Gels 2024, 10(12), 843; https://doi.org/10.3390/gels10120843 - 20 Dec 2024
Viewed by 495
Abstract
Chronic wounds represent a persistent clinical challenge due to prolonged inflammation and impaired tissue repair mechanisms. Cannabidiol (CBD), recognized for its anti-inflammatory and pro-healing properties, shows therapeutic promise in wound care. However, its delivery via lipid nanoparticles (LNPs) remains challenging due to CBD’s [...] Read more.
Chronic wounds represent a persistent clinical challenge due to prolonged inflammation and impaired tissue repair mechanisms. Cannabidiol (CBD), recognized for its anti-inflammatory and pro-healing properties, shows therapeutic promise in wound care. However, its delivery via lipid nanoparticles (LNPs) remains challenging due to CBD’s inherent instability and low bioavailability. This study developed and characterized a novel hydrogel scaffold composed of CBD-loaded LNPs (CBD/LNPs) integrated into a polyvinyl alcohol (PVA) and sodium alginate (SA) matrix, designed to enhance wound repair and mitigate inflammation. The characteristics of the hydrogel scaffold were observed including the degree of swelling and LNPs’ release profiles. Furthermore, in the results, CBD/LNPs displayed enhanced stability and reduced cytotoxicity compared to unencapsulated CBD. In vitro assays demonstrated that CBD/LNPs significantly promoted fibroblast migration in gap-closure wound models and reduced intracellular reactive oxygen species, supporting their potential as a biocompatible and efficacious agent for cellular repair and oxidative stress attenuation. In vivo experiments using adult male Wistar rats with aseptic cutaneous wounds revealed that treatment with CBD/LNP-PVA/SA hydrogel scaffold significantly accelerated wound closure relative to blank hydrogel controls, demonstrating a substantial reduction in the wound area over time. Histological analysis confirms notable improvements in skin morphology in wounds treated with CBD/LNP-PVA/SA hydrogel scaffold with evidence of accelerated epithelialization, enhanced collagen deposition, and increased dermal thickness and vascularization. Additionally, skin histology showed a more organized epidermal layer and reduced inflammatory cell infiltration in CBD/LNP-PVA/SA hydrogel scaffold-treated wounds, corresponding to a 35% increase in the wound closure rate by day 28 post-treatment. These findings suggest that CBD/LNP-PVA/SA hydrogel scaffolds facilitate inflammation resolution and structural wound healing through localized, sustained CBD delivery. The dual anti-inflammatory and wound-healing effects position CBD/LNP-PVA/SA hydrogel scaffold as a promising approach for chronic wound management. Future investigations are warranted to elucidate the mechanistic pathways by which CBD modulates the skin architecture and to explore its translational applications in clinical wound care. Full article
(This article belongs to the Special Issue Synthesis and Applications of Hydrogels (2nd Edition))
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<p>Swelling behavior of polyvinyl alcohol and sodium alginate (PVA/SA) hydrogel scaffold. Degree of swelling observed in hydrogel compositions containing varying percentages of sodium alginate (SA 25%, 50%, 75%, and 100%) and swelling ratio percentage measured at different time points (0, 15, 30, and 45 min). Significant differences were observed, with ** <span class="html-italic">p</span>  &lt;  0.01 and *** <span class="html-italic">p</span>  &lt;  0.001 compared to SA 0% at the starting point (0 min), as presented in the graph.</p>
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<p>Release behavior of polyvinyl alcohol and sodium alginate (PVA/SA) hydrogel scaffold. (<b>A</b>) The degree of release was evaluated in hydrogel compositions containing varying percentages of sodium alginate (SA) incorporated with CBD/LNPs, including formulations with 25%, 50%, 75%, and 100% SA. (<b>B</b>) Release percentages measured at different time points (0 min, 15 min, 30 min, 1 h, 2 h, 4 h, 8 h, and 24 h). Significant differences were observed, with * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span>  &lt;  0.01, and *** <span class="html-italic">p</span>  &lt;  0.001 compared to SA 25%, as presented in the graph.</p>
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<p>Characteristics, cytotoxicity, and antioxidant activity of cannabidiol-loaded lipid nanoparticles (CBD/LNPs). (<b>A</b>) Morphology of CBD/LNPs as demonstrated by Transmission Electron Microscopy (TEM); (<b>B</b>) Cell viability relative to the control in fibroblast-cultured cells exposed to CBD/LNPs; (<b>C</b>) Radical oxidative stress levels induced by hydrogen peroxide exposure were measured by the fluorescent intensity of dichlorofluorescein (DCF) relative to the control group, referring to untreated cells exposed only to the medium without any treatment. The analysis was conducted in fibroblast cultures treated with CBD/LNPs. Data are expressed as mean  ±  SEM (<span class="html-italic">n</span> = 4). * <span class="html-italic">p</span>  &lt;  0.05, ** <span class="html-italic">p</span>  &lt;  0.01, and *** <span class="html-italic">p</span>  &lt;  0.001 compared to the blank group.</p>
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<p>Effects of cannabidiol-loaded lipid nanoparticles (CBD/LNPs) on wound healing in fibroblast-cultured cells. (<b>A</b>) Human dermal fibroblast cells were treated with 50 ppm CBD/LNPs or 100 ng/mL FGF (positive control). A scratch wound assay was monitored at 0, 24, and 48 h post-scratch and compared to untreated control cells. (<b>B</b>) Percentage of wound gap closure at 24 and 48 h, calculated relative to the initial scratch width (T<sub>0</sub>). Data are expressed as mean  ±  SEM (<span class="html-italic">n</span>  =  3). *** <span class="html-italic">p</span>  &lt;  0.001 compared to the control group.</p>
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<p>Effects of cannabidiol-loaded lipid nanoparticles incorporated in polyvinyl alcohol and sodium alginate (CBD/LNP-PVA/SA) hydrogel scaffold on wound healing in rat skin. (<b>A</b>) Time-dependent progression of wound closure in rats treated with PVA/SA hydrogel (Blank) and CBD/LNP-PVA/SA hydrogel. (<b>B</b>) Percentage of wound area contraction calculated on days 3, 7, 14, 21, and 28 post-treatment. Data are expressed as mean  ±  SEM (<span class="html-italic">n</span> = 3 per time point). * <span class="html-italic">p</span>  &lt;  0.05 and ** <span class="html-italic">p</span>  &lt;  0.01 compared to the blank group on the respective day.</p>
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<p>Effects of cannabidiol-loaded lipid nanoparticles incorporated into polyvinyl alcohol and sodium alginate (CBD/LNP-PVA/SA) hydrogel scaffold on histopathological changes in rat skin on days 3, 7, 14, 21, and 28 post-wounding, as assessed by H&amp;E and Masson’s trichrome staining. Photographs show wound sections from rats treated with PVA/SA (Blank) and CBD/LNP-PVA/SA hydrogel scaffold. Hematoxylin-stained nucleic acids and nuclei, eosin-stained proteins, and collagen are visualized in blue–green. Scale bar = 200 μm.</p>
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21 pages, 1533 KiB  
Article
Treatment of High-Grade Chronic Osteomyelitis and Nonunions with PerOssal®: A Retrospective Analysis of Clinical Efficacy and Patient Perspectives
by Jonas Armbruster, Florian Bussmann, Holger Freischmidt, Gregor Reiter, Paul Alfred Gruetzner and Jan Siad El Barbari
J. Clin. Med. 2024, 13(24), 7764; https://doi.org/10.3390/jcm13247764 - 19 Dec 2024
Viewed by 308
Abstract
Background/Objectives: Traditional autologous bone grafts as a treatment for bone defects have drawbacks like donor-site morbidity and limited supply. PerOssal®, a ceramic bone substitute, may overcome those drawbacks and could offer additional benefits like prolonged, local antibiotic release. This study [...] Read more.
Background/Objectives: Traditional autologous bone grafts as a treatment for bone defects have drawbacks like donor-site morbidity and limited supply. PerOssal®, a ceramic bone substitute, may overcome those drawbacks and could offer additional benefits like prolonged, local antibiotic release. This study investigates the clinical and radiological outcomes, including patient-reported outcomes, of using PerOssal® in nonunions (NU) and high-grade chronic osteomyelitis (COM). Methods: A single-center, retrospective study, investigating patients treated with PerOssal® between January 2020 and December 2023. Collected data include patient characteristics as well as various surgical and outcome parameters including the Lower Extremity Functional Scale (LEFS). Results: A total of 82 patients were analyzed. Reinfection occurred in 19.5% of cases. Osseous integration of PerOssal® was achieved in 89% of cases, higher in cavitary defects (91.5%) than segmental defects (72.7%). The revision rate was 32.9%, mainly due to wound healing disorders and reinfections. Mean LEFS score was 53.4 which was heavily influenced by sex (male: 50.7 vs. female: 63.4), revision surgery (no: 55.7 vs. yes: 49.1), reinfection (no: 56.6 vs. yes: 39.4), and osseous integration of PerOssal® (yes: 55.8 vs. no: 38.4). Conclusions: PerOssal® demonstrates promising outcomes in treating NUs and high-grade COM, especially in cavitary defects, with high osseous integration rates and acceptable functional results. However, reinfection remains a concern, particularly with difficult-to-treat pathogens and extensive surgical histories. Early, comprehensive surgical intervention and tailored antibiotic strategies are essential. Patient selection, defect characteristics, and comorbidities significantly influence success. Further research is needed to optimize treatment protocols. Full article
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<p>LEFS Outcome measurement: (<b>a</b>) mean LEFS score for all localizations (53.4 ± 2.5) and specific localizations of the lower extremity or pelvis. No statistically significant difference was observed; (<b>b</b>) analysis for main drivers for worse LEFS via linear regression showed highest differences in dependence on sex, infection, revision, and failed integration. Accordingly, direct comparison of LEFS showed significantly worse LEFS scores for male patients, patients who had reinfection, or in whom integration of the bone substitute failed. Revision in general lowered the LEFS score but statistical analysis remained non-significant. Medians are the black horizontal lines; interquartile range is the height of the rectangle; minimum and maximum value are the whiskers. LEFS: Lower Extremity Functional Scale; ns = not significant, * = <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>Analysis of reinfection: (<b>a</b>) percentage of reinfection in general and split up in between different initial diagnoses; (<b>b</b>) influence of chronic kidney disease on reinfection rate; (<b>c</b>) infection rate in different localizations; (<b>d</b>) mean previous surgeries in patients without and with reinfection. CKD is chronic kidney disease, COM is chronic osteomyelitis, SNU is septic nonunion, ANU is aseptic nonunion; ns = not significant, * = <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>Analysis of revision: (<b>a</b>) percentage breakdown of reasons for revision surgeries in general and categorized by the presence or absence of reinfection; (<b>b</b>) impact of bacterial testing on revision rate; (<b>c</b>) Kaplan–Meier survival analysis of PerOssal<sup>®</sup>; (<b>d</b>) average time between index surgery and first revision for different complications; (<b>e</b>) correlation between the number of revision surgeries and the time between the index surgery and the first revision. Black lines indicate linear regression with 95% confidence intervals. WHD is wound healing disorder; ns = not significant; * = <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>Analysis of integration of PerOssal<sup>®</sup> in cavitary defects or consolidation of nonunions after usage of PerOssal<sup>®</sup> in segmental defects: (<b>a</b>) overall percentage across all analyzed patients; (<b>b</b>) percentage in cavitary compared to segmental defects; (<b>c</b>) percentage in patients with and without reinfection. *** = <span class="html-italic">p</span> &lt; 0.001.</p>
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12 pages, 266 KiB  
Article
Physiotherapy Intervention in the Treatment of Venous Ulcers: Results from a Delphi Panel
by Sabrina Medeiros, Alexandre Rodrigues and Rui Costa
J. Vasc. Dis. 2024, 3(4), 508-519; https://doi.org/10.3390/jvd3040038 - 18 Dec 2024
Viewed by 375
Abstract
Background/Objectives: Venous ulcers are the most common type of ulcerated wounds in the lower limbs and result from chronic venous insufficiency. The treatment of venous ulcers is multidisciplinary, with physiotherapy intervention serving as an adjuvant therapy in managing these wounds. This study investigated [...] Read more.
Background/Objectives: Venous ulcers are the most common type of ulcerated wounds in the lower limbs and result from chronic venous insufficiency. The treatment of venous ulcers is multidisciplinary, with physiotherapy intervention serving as an adjuvant therapy in managing these wounds. This study investigated physiotherapeutic interventions for the management of venous ulcers. Methods: This was an exploratory and descriptive study using the Delphi method. The panel comprised 12 experts in wound care, including 25.0% physicians, 41.7% nurses, and 33.3% physiotherapists. Two rounds of analysis were conducted. A quantitative analysis was performed to assess the level of agreement in responses, while qualitative analysis was applied to the experts’ comments. Results: In the first round, consensus varied between 80% and 100%, and in the second round, it ranged from 83.3% to 100%. In the second round, all interventions obtained at least 80% consensus. The interventions included the use of compression therapy and therapeutic exercise: resistance training (2–3 sets of 10–25 repetitions, 3 times/day, for at least 12 weeks), aerobic exercise (at least 30 min, 3 times/week, for 12 weeks), stretching, balance training, and the use of a vibrating platform. Conclusions: Physiotherapy may be beneficial as an adjuvant therapy alongside specific local treatments for venous ulcers. Therapeutic exercise and compression therapy are commonly utilized interventions that could support overall treatment outcomes. Full article
(This article belongs to the Section Peripheral Vascular Diseases)
17 pages, 10232 KiB  
Article
Angiogenesis Dynamics: A Computational Model of Intravascular Flow Within a Structural Adaptive Vascular Network
by Sahar Jafari Nivlouei, Ana Guerra, Jorge Belinha, Naside Mangir, Sheila MacNeil, Christiane Salgado, Fernando Jorge Monteiro and Renato Natal Jorge
Biomedicines 2024, 12(12), 2845; https://doi.org/10.3390/biomedicines12122845 - 13 Dec 2024
Viewed by 385
Abstract
Background: Understanding vascular development and the key factors involved in regulating angiogenesis—the growth of new blood vessels from pre-existing vasculature—is crucial for developing therapeutic approaches to promote wound healing. Computational techniques offer valuable insights into improving angiogenic strategies, leading to enhanced tissue regeneration [...] Read more.
Background: Understanding vascular development and the key factors involved in regulating angiogenesis—the growth of new blood vessels from pre-existing vasculature—is crucial for developing therapeutic approaches to promote wound healing. Computational techniques offer valuable insights into improving angiogenic strategies, leading to enhanced tissue regeneration and improved outcomes for chronic wound healing. While chorioallantoic membrane (CAM) models are widely used for examining fundamental mechanisms in vascular development, they lack quantification of essential parameters such as blood flow rate, intravascular pressure, and changes in vessel diameter. Methods: To address this limitation, the current study develops a novel two-dimensional mathematical model of angiogenesis, integrating discrete and continuous modelling approaches to capture intricate cellular interactions and provide detailed information about the capillary network’s structure. The proposed hybrid meshless-based model simulates sprouting angiogenesis using the in vivo CAM system. Results: The model successfully predicts the branching process with a total capillary volume fraction deviation of less than 15% compared to experimental data. Additionally, it implements blood flow through the capillary network and calculates the distribution of intravascular pressure and vessel wall shear stress. An adaptive network is introduced to consider capillary responses to hemodynamic and metabolic stimuli, reporting structural diameter changes across the generated vasculature network. The model demonstrates its robustness by verifying numerical outcomes, revealing statistically significant differences with deviations in key parameters, including diameter, wall shear stress (p < 0.05), circumferential wall stress, and metabolic stimuli (p < 0.01). Conclusion: With its strong predictive capability in simulating intravascular flow and its ability to provide both quantitative and qualitative assessments, this research enhances our understanding of angiogenesis by introducing a biologically relevant network that addresses the functional demands of the tissue. Full article
(This article belongs to the Special Issue Angiogenesis and Related Disorders)
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<p>Evolution angiogenesis toward the released VEGF in the CAM assay on EDD 14.</p>
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<p>In vivo capillary network from CAM vs. In silico results, along with the corresponding total capillary volume fractions (third column).</p>
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<p>Validation of the intravascular flow modelling. (<b>A</b>) Capillary diameter changes in different values of IP in compare with experimentally determined diameters from Pries et al., 2001 [<a href="#B19-biomedicines-12-02845" class="html-bibr">19</a>]. (<b>B</b>) The metabolic stimuli changes as a function of flow rate inside the capillaries vs. the experimental data from Pries et al., 2001 [<a href="#B19-biomedicines-12-02845" class="html-bibr">19</a>]. (<b>C</b>) Distribution of hydrodynamic stimuli obtained from wall shear stress and (<b>D</b>) intravascular blood pressure, in comparison with the corresponding measured data from Pries et al., 2001 [<a href="#B19-biomedicines-12-02845" class="html-bibr">19</a>].</p>
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<p>In vivo capillary network from CAM images (first column) compared with in silico results for various network configurations, illustrating intravascular pressure distribution and corresponding diameter changes. (<b>A</b>) Comparison with experimental blood flow observations reported in [<a href="#B51-biomedicines-12-02845" class="html-bibr">51</a>] (A—artery and V—vein). (<b>B</b>,<b>C</b>) Comparison with CAM images from the current experimental study.</p>
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<p>Sprouting angiogenesis: (<b>A</b>) VEGF concentration (g mm<sup>−3</sup>); (<b>B</b>) vascular network development resulting from tip cell migration and stalk cell proliferation in different time steps.</p>
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<p>Intravascular flow: pressure distribution (<b>left</b>); diameter of each capillary segment (<b>right</b>).</p>
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<p>Shear stress analysis, total effective shear stress distribution (<math display="inline"><semantics> <mrow> <msub> <mrow> <mi>τ</mi> </mrow> <mrow> <mi>T</mi> </mrow> </msub> </mrow> </semantics></math>) (<b>left</b>), shear stress changes in neo-vessels across different diameters (<b>right</b>).</p>
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16 pages, 10610 KiB  
Article
Enhanced Wound Healing and Autogenesis Through Lentiviral Transfection of Adipose-Derived Stem Cells Combined with Dermal Substitute
by Shiqi Wang, Dinghui Gao, Mingyu Li, Qian Wang, Xuanyu Du and Siming Yuan
Biomedicines 2024, 12(12), 2844; https://doi.org/10.3390/biomedicines12122844 - 13 Dec 2024
Viewed by 618
Abstract
Background: Burns and chronic ulcers may cause severe skin loss, leading to critical health issues like shock, infection, sepsis, and multiple organ failure. Effective healing of full-thickness wounds may be challenging, with traditional methods facing limitations due to tissue shortage, infection, and lack [...] Read more.
Background: Burns and chronic ulcers may cause severe skin loss, leading to critical health issues like shock, infection, sepsis, and multiple organ failure. Effective healing of full-thickness wounds may be challenging, with traditional methods facing limitations due to tissue shortage, infection, and lack of structural support. Methods: This study explored the combined use of gene transfection and dermal substitutes to improve wound healing. We used the DGTM (genes: DNP63A, GRHL2, TFAP2A, and MYC) factors to transfect adipose-derived stem cells (ADSCs), inducing their differentiation into keratinocytes. These transfected ADSCs were then incorporated into Pelnac® dermal substitutes to enhance vascularization and cellular proliferation for better healing outcomes. Results: Gene transfer using DGTM factors successfully induced keratinocyte differentiation in ADSCs. The application of these differentiated cells with Pelnac® dermal substitute to dermal wounds in mice resulted in the formation of skin tissue with a normal epidermal layer and proper collagen organization. This method alleviates the tediousness of the multiple transfection steps in previous protocols and the safety issues caused by using viral transfection reagents directly on the wound. Additionally, the inclusion of dermal substitutes addressed the lack of collagen and elastic fibers, promoting the formation of tissue resembling healthy skin rather than scar tissue. Conclusion: Integrating DGTM factor-transfected ADSCs with dermal substitutes represents a novel strategy for enhancing the healing of full-thickness wounds. Further research and clinical trials are warranted to optimize and validate this innovative approach for broader clinical applications. Full article
(This article belongs to the Section Biomedical Engineering and Materials)
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<p>Diagrammatic summary of this study.</p>
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<p>Identification of ADSCs. (<b>A</b>) A Morphology of human ADSCs at 12 h and 72 h; scale bar: 100 μm. (<b>B</b>) Flow cytometry detection of ADSCs. ADSCs were positive for the markers CD73, CD90, and CD105 (blue peaks) and negative for the markers CD34 and CD45 (red peaks). The table summarizes the percentage of cells expressing each marker (mean ± SEM). (<b>C</b>) ADSC lipogenicity assay; scale bar: 100 μm. (<b>D</b>) ADSC osteogenicity assay; scale bar: 100 μm.</p>
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<p>Identification of ADSCs<sup>DGTM+</sup>. (<b>A</b>) Statistical graph of RT-PCR detection of the expression of transfected genes <span class="html-italic">GRHL</span>, <span class="html-italic">TFAP2</span>, <span class="html-italic">MYC</span>, and <span class="html-italic">TP63</span> in ADSCs<sup>DGTM+</sup>, ***, <span class="html-italic">p</span> &lt; 0.001. (<b>B</b>) Representative graph of immunohistochemistry detection of the expression of the keratinocyte-specific marker KRT14 in ADSCs<sup>DGTM+</sup> and ADSCs<sup>DGTM−</sup>. (<b>C</b>) WB detection of keratinocyte-specific markers KRT14 and CDH1 expression in ADSC, ADSCs<sup>DGTM+</sup> and ADSCs<sup>DGTM-</sup>. (<b>D</b>) Representative fluorescent staining of expression of keratinocyte-specific markers KRT14, CY3 (Pelnac<sup>®</sup> staining), and DAPI in the ADSCs + Pelnac<sup>®</sup> group, ADSCs<sup>DGTM+</sup> + Pelnac<sup>®</sup> group and ADSCs<sup>DGTM-</sup> + Pelnac<sup>®</sup> group.</p>
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<p>Construction of dermal substitute–ADSCs<sup>DGTM+</sup> complexes. (<b>A</b>) Observation of dermal substitute–ADSCs<sup>DGTM+</sup> complexes under inverted fluorescence microscope; scale bar: 200 μm. (<b>B</b>) Observation of dermal substitute–ADSCs<sup>DGTM+</sup> complexes under scanning electron microscope at different magnifications. The red arrow in the middle image points to the pore. (<b>C</b>,<b>D</b>) Observation of the proliferation of ADSCs<sup>DGTM+</sup> grown in Pelnac<sup>®</sup> by culturing ADSCs<sup>DGTM+</sup> alone within 9 days under an inverted fluorescence microscope and statistical graphs; scale bar: 200 μm.</p>
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<p>Dermal substitute–ADSCs<sup>DGTM+</sup> complexes fill full-thickness defective wounds. (<b>A</b>) Flowchart of animal experiments. (<b>B</b>) Representative images of skin regeneration. Mice wounds were divided into the following groups: blank, Pelnac<sup>®</sup> ADSCs + Pelnac<sup>®</sup>, and ADSCs<sup>DGTM+</sup> + Pelnac<sup>®</sup>. (<b>C</b>) Temporal variation of skin regeneration. (<b>D</b>) HE staining of mice in each group of the wound. (<b>E</b>) MASSON staining of mice in each group of the wound. (<b>F</b>) Statistical graph of the percentage of wound healing over time for each group. (<b>G</b>) Statistical graph of the thickness of re-epithelialization of the wound in each group. (<b>H</b>) Statistical graph of the proportion of wound collagen in each group. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, n = 4.</p>
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<p>Dermal substitute–ADSCs<sup>DGTM+</sup> complexes promote wound cell proliferation and revascularization. (<b>A</b>) Representative immunofluorescence staining of CD31, Ki67, and DAPI in the whole layer defect wounds of neoplastic skin of each wound group. (<b>B</b>) Immunofluorescence staining of CD31 in neoplastic whole skin defect wounds in each group. (<b>C</b>) Immunofluorescence staining of Ki67 in neoplastic whole skin defect wounds in each group; ** <span class="html-italic">p</span> &lt; 0.01, n = 4.</p>
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<p>Dermal substitute–ADSCs<sup>DGTM+</sup> complexes involved in the filling of full-thickness defective skin. (<b>A</b>) Representative fluorescent staining of KRT14, HLA-ABC, and DAPI in the wounds of mice in the ADSCs + Pelnac<sup>®</sup> and ADSCs<sup>DGTM+</sup> + Pelnac<sup>®</sup> groups. (<b>B</b>,<b>C</b>) Representative plots of average fluorescence intensity of different channels in the ADSCs<sup>DGTM+</sup> + Pelnac<sup>®</sup> group and ADSCs + Pelnac<sup>®</sup> group.</p>
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15 pages, 4268 KiB  
Article
Carbonized Plant Powder Gel for Rapid Hemostasis and Sterilization in Regard to Irregular Wounds
by Zhong Liu, Shaolei Ding, Guodong Zhang, Bingyu Yan, Chao Zhang, Pihang Yu, Yunze Long and Jun Zhang
Nanomaterials 2024, 14(24), 1992; https://doi.org/10.3390/nano14241992 - 12 Dec 2024
Viewed by 511
Abstract
Irregularly shaped wounds cause severe chronic infections, which have attracted worldwide attention due to their high prevalence and poor treatment outcomes. In this study, we designed a new composite functional dressing consisting of traditional Chinese herb carbonized plant powder (CPP) and a polyacrylic [...] Read more.
Irregularly shaped wounds cause severe chronic infections, which have attracted worldwide attention due to their high prevalence and poor treatment outcomes. In this study, we designed a new composite functional dressing consisting of traditional Chinese herb carbonized plant powder (CPP) and a polyacrylic acid (PAA)/polyethylenimine (PEI) gel. The rapid gelation of the dressing within 6–8 s allowed the gel to be firmly attached to an irregularly shaped wound surface and avoided powder detachment. In addition, through an infrared thermography analysis, a coagulation assay, and a morphological examination of regenerative tissue in animal wound models, it was found that the dressing substrates had synergistic effects on photothermal sterilization, rapid hemostasis, and anti-inflammatory activity, thereby achieving an 88% wound closure rate on the 9th day after the formation of the wound. This multifunctional hemostatic material is expected to be adaptable to irregular wounds and promote rapid wound healing. Full article
(This article belongs to the Section Biology and Medicines)
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<p>(<b>a</b>) Schematic diagram of the preparation process of PAA/PEI/CPP powder. (<b>b</b>) SEM image of the powder and analysis image of Al, O, K, S, and C elements. (<b>c</b>) FTIR spectra of CPP, PAA/PEI powder, and PAA/PEI/CPP powder. (<b>d</b>) SEM image of the gel powder and local enlargement. (<b>e</b>) Adhesion test of PAA/PEI/CPP powder on pig skin and between different materials. (<b>f</b>) CPP particles before being ground. (<b>g</b>) Freeze-dried PAA/PEI hydrogel powder before being ground. (<b>h</b>) Freeze-dried PAA/PEI/CPP gel powder before being ground.</p>
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<p>(<b>a</b>) The white PAA/PEI powder and black PAA/PEI/CPP powder after adding deionized water. (<b>b</b>) Water absorption rate (*** <span class="html-italic">p</span> &lt; 0.001). (<b>c</b>) Mechanical performance. (<b>d</b>) Storage modulus (G′) and loss modulus (G″) of PAA/PEI hydrogel and PAA/PEI/CPP gel (*** <span class="html-italic">p</span> &lt; 0.001). (<b>e</b>) Storage modulus (G′) and loss modulus (G″) as a function of frequency in PAA/PEI hydrogel and PAA/PEI/CPP gel. (<b>f</b>) PAA/PEI/CPP powder gelling time after water absorption (time-dependent curves of storage modulus G′ and loss modulus G″ measured using a rheometer at 37 °C).</p>
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<p>(<b>a</b>) Temperature variations in different groups after laser irradiation for 3 min. (<b>b</b>) Images of bacteriostatic effects against <span class="html-italic">E. coli</span> and <span class="html-italic">S. aureus</span> in different groups. (<b>c</b>) Live cell staining of mouse embryonic fibroblasts after 24 h culture in different groups. (<b>d</b>) Bacterial growth in different periods. (<b>e</b>) Colony forming unit in different periods.</p>
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<p>(<b>a</b>) Coagulation effect of various materials on a 96-well plate. (<b>b</b>) Image of blood clot formation in an in vitro coagulation experiment.</p>
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<p>(<b>a</b>) Wound recovery status in various periods. (<b>b</b>) Wound area percentage in various periods (** <span class="html-italic">p</span> &lt; 0.01). (<b>c</b>) H&amp;E and Masson staining of each group in different periods (the blue arrow indicates inflammatory cells, the green arrow indicates hair follicles, the red arrow indicates blood vessels, and the yellow arrow indicates collagen fibers).</p>
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17 pages, 860 KiB  
Review
Artificial Intelligence in Wound Care: A Narrative Review of the Currently Available Mobile Apps for Automatic Ulcer Segmentation
by Davide Griffa, Alessio Natale, Yuri Merli, Michela Starace, Nico Curti, Martina Mussi, Gastone Castellani, Davide Melandri, Bianca Maria Piraccini and Corrado Zengarini
BioMedInformatics 2024, 4(4), 2321-2337; https://doi.org/10.3390/biomedinformatics4040126 - 11 Dec 2024
Viewed by 554
Abstract
Introduction: Chronic ulcers significantly burden healthcare systems, requiring precise measurement and assessment for effective treatment. Traditional methods, such as manual segmentation, are time-consuming and error-prone. This review evaluates the potential of artificial intelligence AI-powered mobile apps for automated ulcer segmentation and their application [...] Read more.
Introduction: Chronic ulcers significantly burden healthcare systems, requiring precise measurement and assessment for effective treatment. Traditional methods, such as manual segmentation, are time-consuming and error-prone. This review evaluates the potential of artificial intelligence AI-powered mobile apps for automated ulcer segmentation and their application in clinical settings. Methods: A comprehensive literature search was conducted across PubMed, CINAHL, Cochrane, and Google Scholar databases. The review focused on mobile apps that use fully automatic AI algorithms for wound segmentation. Apps requiring additional hardware or needing more technical documentation were excluded. Vital technological features, clinical validation, and usability were analysed. Results: Ten mobile apps were identified, showing varying levels of segmentation accuracy and clinical validation. However, many apps did not publish sufficient information on the segmentation methods or algorithms used, and most lacked details on the databases employed for training their AI models. Additionally, several apps were unavailable in public repositories, limiting their accessibility and independent evaluation. These factors challenge their integration into clinical practice despite promising preliminary results. Discussion: AI-powered mobile apps offer significant potential for improving wound care by enhancing diagnostic accuracy and reducing the burden on healthcare professionals. Nonetheless, the lack of transparency regarding segmentation techniques, unpublished databases, and the limited availability of many apps in public repositories remain substantial barriers to widespread clinical adoption. Conclusions: AI-driven mobile apps for ulcer segmentation could revolutionise chronic wound management. However, overcoming limitations related to transparency, data availability, and accessibility is essential for their successful integration into healthcare systems. Full article
(This article belongs to the Section Imaging Informatics)
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<p>Example of automated wound assessment process using AI-powered mobile app.</p>
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<p>The radar charts provide a visual comparison of various wound monitoring apps based on six key criteria, namely platform availability, regulatory approval, inter-reliability, peer-reviewed studies, the disclosure of methods/algorithms, and the use of public datasets. Each chart represents a single app, highlighting strengths and weaknesses across these categories.</p>
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16 pages, 2175 KiB  
Article
Antibiofilm, Anti-Inflammatory, and Regenerative Properties of a New Stable Ozone-Gel Formulation
by Carla Russo, Giuseppe Curcio, Alessandro Graziani, Antonella Mencacci and Donatella Pietrella
Pharmaceutics 2024, 16(12), 1580; https://doi.org/10.3390/pharmaceutics16121580 - 11 Dec 2024
Viewed by 553
Abstract
Background/Objectives: Chronic skin wounds are characterized by inflammation, persistent infections, and tissue necrosis. The presence of bacterial biofilms prolongs the inflammatory response and delays healing. Ozone is a potent antimicrobial molecule, and many formulations have been used in the advanced therapeutic treatment [...] Read more.
Background/Objectives: Chronic skin wounds are characterized by inflammation, persistent infections, and tissue necrosis. The presence of bacterial biofilms prolongs the inflammatory response and delays healing. Ozone is a potent antimicrobial molecule, and many formulations have been used in the advanced therapeutic treatment of chronic wounds. The aim of this work was to determine the antimicrobial, anti-inflammatory, and regenerative activity of a stable ozone-gel formulation over time. Methods: The antimicrobial property was assessed by measuring the minimal inhibitory concentration and the antibiofilm activity. The anti-inflammatory effect was evaluated by TNF-α determination, and the regenerative effect was measured by scratch assay. Results: The ozone gel demonstrated antimicrobial and antibiofilm activity in all ATCC microorganisms examined and on most clinical isolates. Higher concentrations of the ozone gel were also useful in the dispersion of preformed biofilm. The ozone gel also showed anti-inflammatory activity by reducing the production of TNF-α and regenerative activity in human fibroblasts and keratinocytes. Conclusions: Given all these antimicrobial, anti-inflammatory, and regenerative characteristics, the ozone gel could be, in this formulation, used in the treatment of wounds. The ozone-gel formulation described here retains stability for over 30 months, which facilitates its use compared to formulations that lose efficacy quickly. Full article
(This article belongs to the Special Issue Recent Advances in Biomaterials for Wound Healing)
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<p>Cytotoxicity of ozone gel on human PBMC. Results are expressed as the percentage of live cells with respect to untreated cells, assumed to be 100. The results are expressed as mean ± standard deviation (SD) of two independent experiments conducted in triplicate. The statistical analysis was performed with a two-tailed Student’s <span class="html-italic">t</span>-test. ** <span class="html-italic">p</span> &lt; 0.01, ozone-gel-treated cells vs. untreated cells.</p>
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<p>Effect of ozone gel on TNF-α production by human PBMC. Cells were pre-stimulated with LPS and then treated with ozone gel or were co-stimulated. Data represent the mean ± SD of three independent experiments. The statistical analysis was performed with a two-tailed Student’s <span class="html-italic">t</span>-test. * <span class="html-italic">p</span> &lt; 0.05, LPS+ozone-gel-treated cells vs. LPS-treated cells.</p>
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<p>Regenerative effect of ozone gel on human dermal fibroblasts (<b>A</b>) and keratinocytes (<b>B</b>). The regenerative activity was performed by a scratch assay. The distance between the edges of the scratch was monitored under the microscope (20× magnification) for 2 or 3 days as indicated, and photos were taken. The distances were recorded, and the results are expressed as mean ± SD of the measurements by microscope (n = 6) carried out in two independent experiments.</p>
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<p>Regenerative effect of ozone gel on human dermal fibroblasts (<b>A</b>) and keratinocytes (<b>B</b>). The regenerative activity was performed by a scratch assay. The distance between the edges of the scratch was monitored under the microscope (20× magnification) for 2 or 3 days as indicated, and photos were taken. The distances were recorded, and the results are expressed as mean ± SD of the measurements by microscope (n = 6) carried out in two independent experiments.</p>
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25 pages, 2431 KiB  
Review
Green Tea Catechins and Skin Health
by Xin-Qiang Zheng, Xue-Han Zhang, Han-Qing Gao, Lan-Ying Huang, Jing-Jing Ye, Jian-Hui Ye, Jian-Liang Lu, Shi-Cheng Ma and Yue-Rong Liang
Antioxidants 2024, 13(12), 1506; https://doi.org/10.3390/antiox13121506 - 10 Dec 2024
Viewed by 816
Abstract
Green tea catechins (GTCs) are a group of bioactive polyphenolic compounds found in fresh tea leaves (Camellia sinensis (L.) O. Kuntze). They have garnered significant attention due to their diverse health benefits and potential therapeutic applications, including as antioxidant and sunscreen agents. [...] Read more.
Green tea catechins (GTCs) are a group of bioactive polyphenolic compounds found in fresh tea leaves (Camellia sinensis (L.) O. Kuntze). They have garnered significant attention due to their diverse health benefits and potential therapeutic applications, including as antioxidant and sunscreen agents. Human skin serves as the primary barrier against various external aggressors, including pathogens, pollutants, and harmful ultraviolet radiation (UVR). Skin aging is a complex biological process influenced by intrinsic factors such as genetics and hormonal changes, as well as extrinsic factors like environmental stressors, among which UVR plays a pivotal role in accelerating skin aging and contributing to various dermatological conditions. Research has demonstrated that GTCs possess potent antioxidant properties that help neutralize free radicals generated by oxidative stress. This action not only mitigates cellular damage but also supports the repair mechanisms inherent in human skin. Furthermore, GTCs exhibit anti-carcinogenic effects by inhibiting pathways involved in tumor promotion and progression. GTCs have been shown to exert anti-inflammatory effects through modulation of inflammatory signaling pathways. Chronic inflammation is known to contribute significantly to both premature aging and various dermatological diseases such as psoriasis or eczema. By regulating these pathways effectively, GTCs may alleviate symptoms associated with inflammatory conditions. GTCs can enhance wound healing processes by stimulating angiogenesis. They also facilitate DNA repair mechanisms within dermal fibroblasts exposed to damaging agents. The photoprotective properties attributed to GTCs further underscore their relevance in skincare formulations aimed at preventing sun-induced damage. Their ability to screen UV light helps shield underlying tissues from harmful rays. This review paper aims to comprehensively examine the beneficial effects of GTCs on skin health through an analysis encompassing in vivo and in vitro studies alongside insights into molecular mechanisms underpinning these effects. Such knowledge could pave the way for the development of innovative strategies focused on harnessing natural compounds like GTCs for improved skincare solutions tailored to combat environmental stresses faced by the human epidermis. Full article
(This article belongs to the Special Issue Antioxidants for Skin Health)
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<p>Molecular structure of partial catechins.</p>
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<p>Antiproliferative effects on skin cancer cells. Red arrows indicate increases, and green arrows indicated decreases.</p>
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<p>Effects of GTCs on closure of skin wounds.</p>
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<p>DNA protection effects of GTCs.</p>
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<p>Effects of GTCs in promoting angiogenesis.</p>
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<p>Effects of GTCs in regulating immune responses.</p>
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<p>Beneficial effects of GTCs on skin health.</p>
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10 pages, 631 KiB  
Perspective
Nano-Delivery Revolution: Harnessing Mesenchymal Stem Cell-Derived Exosomes’ Potential for Wound Healing
by Pawan Kumar Raghav and Zoya Mann
Biomedicines 2024, 12(12), 2791; https://doi.org/10.3390/biomedicines12122791 - 9 Dec 2024
Viewed by 506
Abstract
Stem cell transplantation has proven effective in treating acute and chronic wounds, but its limitations, such as low cellular viability and the need for specialized transportation, highlight the necessity for alternative approaches. This review explores the potential of engineered exosomes, containing identified miRNAs/peptides, [...] Read more.
Stem cell transplantation has proven effective in treating acute and chronic wounds, but its limitations, such as low cellular viability and the need for specialized transportation, highlight the necessity for alternative approaches. This review explores the potential of engineered exosomes, containing identified miRNAs/peptides, as a more stable and efficient cell-free therapy for regenerative medicine, particularly in wound healing. The discussion emphasizes the benefits of exosomes, including their stability, reduced damage, and consistent biological activity, paving the way for innovative applications like lyophilized exosomes, mist spray delivery, and exosome-based scaffolds. The exploration of cell-free therapy in this review holds promising implications for advancing wound-healing strategies. Full article
(This article belongs to the Section Drug Discovery, Development and Delivery)
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<p>Schematic diagram depicting the workflow for identifying target biomarkers and designing suitable exosomes-based products. Wound-healing biomarkers can be retrieved by literature mining, which regulates inflammation, apoptosis, proliferation, and angiogenesis. The biomolecules can be used either as cargo-loading or with MSC-derived exosomes. Finally, these exosomes can be used further as lyophilized, mist spray, and two or three-dimensional scaffolds.</p>
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13 pages, 1953 KiB  
Article
Skin Function Improvement and Anti-Inflammatory Effects of Goat Meat Extract
by In-Seon Bae, Van-Ba Hoa, Jeong-Ah Lee, Won-Seo Park, Dong-Gyun Kim, Hyoun-Wook Kim, Pil-Nam Seong and Jun-Sang Ham
Foods 2024, 13(23), 3934; https://doi.org/10.3390/foods13233934 - 5 Dec 2024
Viewed by 677
Abstract
Chronic skin conditions, such as atopic dermatitis, are characterized by a weakened skin barrier and persistent inflammation. Traditional treatments can frequently cause substantial side effects, emphasizing the need for safer alternatives. This study investigated the anti-inflammatory properties of goat meat extract and its [...] Read more.
Chronic skin conditions, such as atopic dermatitis, are characterized by a weakened skin barrier and persistent inflammation. Traditional treatments can frequently cause substantial side effects, emphasizing the need for safer alternatives. This study investigated the anti-inflammatory properties of goat meat extract and its effects on improving skin function. We conducted wound healing assays using HaCaT cells and analyzed the expression of key skin barrier-related genes. Additionally, the anti-inflammatory effects of goat meat extract were assessed in HaCaT cells stimulated with TNFα and IFNγ, as well as in LPS-treated RAW264.7 cells. Mechanistic studies focused on the activation of mitogen-activated protein kinase (MAPK) pathways. The results showed that goat meat extract significantly promoted wound closure in HaCaT cells and upregulated the expression of filaggrin, loricrin, and involucrin. The extract also reduced the production of pro-inflammatory cytokines and chemokines in both HaCaT and RAW264.7 cells. Furthermore, it inhibited the activation of the JNK, p38, and ERK pathways in TNFα/IFNγ-stimulated HaCaT cells. These findings suggest that goat meat extract improves skin barrier function and exhibits anti-inflammatory effects, indicating its potential as a therapeutic agent for chronic skin. Further research is required to investigate the in vivo effects of goat meat extract and validate its therapeutic potential. Full article
(This article belongs to the Section Meat)
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<p>Effect of goat meat extract on HaCaT cell migration. (<b>a</b>) HaCaT cell migration was visualized and recorded using a 4× objective lens with a microscope camera at 0, 8, and 24 h post-scratching. (<b>b</b>) Cell migration was assessed using the wound healing assay. The data are presented as mean ± SD from three separate experiments. ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>Effect of goat meat extract on the expression of genes related to skin barrier improvement. mRNA expression levels of (<b>a</b>) skin differentiation markers (filaggrin, loricrin, and involucrin) and (<b>b</b>) barrier function-related genes (occludin, claudin1, claudin 4, tricellulin, and HBD3) were determined via qRT-PCR analysis. (<b>c</b>) The mRNA expression of HAS1, HAS2, and HAS3 in HaCaT cells treated with goat meat extract was analyzed by qRT-PCR analysis. (<b>d</b>) Protein levels of filaggrin, loricrin, involucrin, HAS1, HAS2, and HAS3 were evaluated, with β-actin serving as a control. The data are presented as mean ± SD from three separate experiments. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>Impact of goat meat extract on physical barrier function and skin hydration. HaCaT cells were exposed to goat meat extract at concentrations of 50, 100, and 200 µg/mL for 24 h. Levels of (<b>a</b>) filaggrin, (<b>b</b>) aquaporin, and (<b>c</b>) hyaluronic acid were assessed using ELISA. The results are presented as mean ± SD from three independent experiments. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01.</p>
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<p>Effect of goat meat extract on the production of chemokines and pro-inflammatory cytokines. (<b>a</b>) CTSS, (<b>b</b>) MDC/CCL22, (<b>c</b>) TARC/CCL17, (<b>d</b>) RANTES/CCL5, (<b>e</b>) TNFα, (<b>f</b>) IL-1, and (<b>g</b>) IL-6 levels were measured using ELISA. The data are presented as mean ± SD from three separate experiments. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>Impact of goat meat extract on pro-inflammatory cytokine production. (<b>a</b>) NO, (<b>b</b>) TNFα, (<b>c</b>) IL-1, and (<b>d</b>) IL-6 levels were quantified by ELISA. Data are expressed as mean ± SD from three independent experiments. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01.</p>
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<p>Effect of goat meat extract on TNFα and IFNγ induced MAPK signaling in HaCaT cells. Cells were pretreated with goat meat extract at concentrations of 50, 100, and 200 µg/mL for 1 h, followed by TNFα and IFNγ exposure for 1 h. (<b>a</b>) Western blot analysis was performed to assess the expression of p-JNK, JNK, p-p38, p38, p-ERK, and ERK. In cells treated with goat meat extract, the JNK inhibitor SP600125, p38 inhibitor SB203580, and ERK inhibitor PD98059 were applied. The levels of (<b>b</b>) IL-1, (<b>c</b>) CTSS, (<b>d</b>) MDC/CCL22, and (<b>e</b>) TARC/CCL17 were measured in HaCaT cells using ELISA. Data are expressed as mean ± SD from three independent experiments. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001.</p>
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13 pages, 5662 KiB  
Article
Bioengineered Extracellular Vesicle Hydrogel Modulating Inflammatory Microenvironment for Wound Management
by Yunfei Mu, Liwen Ma, Jia Yao, Dan Luo and Xianguang Ding
Int. J. Mol. Sci. 2024, 25(23), 13093; https://doi.org/10.3390/ijms252313093 - 5 Dec 2024
Viewed by 593
Abstract
Chronic wounds, frequently arising from conditions like diabetes, trauma, or chronic inflammation, represent a significant medical challenge due to persistent inflammation, heightened infection risk, and limited treatment solutions. This study presents a novel bioengineered approach to promote tissue repair and improve the healing [...] Read more.
Chronic wounds, frequently arising from conditions like diabetes, trauma, or chronic inflammation, represent a significant medical challenge due to persistent inflammation, heightened infection risk, and limited treatment solutions. This study presents a novel bioengineered approach to promote tissue repair and improve the healing environment. We developed a bioactive hydrogel patch, encapsulated zeolitic imidazolate framework-8 (ZIF-8) into extracellular vesicles (EVs) derived from anti-inflammatory M2 macrophages, and synthesized ZIF@EV, then embedded it in the sodium alginate matrix. This hydrogel structure enables the controlled release of therapeutic agents directly into the wound site, where it stimulates endothelial cell proliferation and promotes new blood vessel formation. These processes are key components of effective tissue regeneration. Crucially, the EV-infused patch influences the immune response by polarizing macrophages towards an M2 phenotype, shifting the wound environment from inflammation toward regenerative healing. When applied in a murine model of chronic wounds, the EV hydrogel patch demonstrated notable improvements in healing speed, quality, and tissue integration compared to traditional approaches such as growth factor therapies and foam dressings. These promising findings suggest that this bioactive hydrogel patch could serve as a versatile, practical solution for chronic wound management, providing an adaptable platform that addresses both the biological and logistical needs of wound care in clinical settings. Full article
(This article belongs to the Special Issue Recent Research of Nanomaterials in Molecular Science)
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<p>Synthesis of ZIF@EV–Gel ink. (<b>A</b>) Schematic illustration of the synthetic process of ZIF@EV nanoparticles and corresponding TEM images of the prepared ZIF@EV. Scale bar: 100 nm. (<b>B</b>) NTA of the prepared ZIF@EVs demonstrating the average size of around 180 nm. (<b>C</b>) Zeta potential of EV and ZIF@EV. (<b>D</b>) The gelation of ZIF@EV–Gel ink. (<b>E</b>) SEM image of the macrostructure of ZIF@EV–Gel ink. Scale bar: 3 μm. (<b>F</b>) The degradation curve of ZIF@EV forms the Gel. (<b>G</b>) The continuous release profile of ZIF@EV from Gel. ns denotes non-significant difference.</p>
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<p>Angiogenesis ability of ZIF@EV. (<b>A</b>) Representative images of the transwell migration assay of HUVECs under the treatment of ZIF@EV. Scale bar, 200 μm. (<b>B</b>) Quantification of the migratory capacity of HUVECs. (<b>C</b>) Images of HUVEC migration under ZIF@EV treatment at different time points. Scale bar, 200 μm. (<b>D</b>) Corresponding quantification of HUVEC migration at different time points. (<b>E</b>) Formation of tubes by HUVECs with various treatments. (<b>F</b>) percentage area of vessels as a representation of tube formation capability in various groups (n = 3). ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, and **** <span class="html-italic">p</span> &lt; 0.0001.</p>
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<p>ZIF@EV induced macrophage polarization into M2 phenotype. (<b>A</b>) Representative image of macrophages under different treatments. Scale bar, 50 μm. (<b>B</b>) Flow cytometry analysis of CD206+ macrophages. (<b>C</b>) Flow cytometry analysis of CD86+ macrophages. (<b>D</b>) Quantification of CD206+ macrophages (n = 3). (<b>E</b>) Histogram analysis of CD206+ macrophages. (<b>F</b>) Quantification of the ratio of M1 and M2 macrophages (n = 3). (<b>G</b>) Relative protein expression of M1 and M2 macrophage markers after macrophages incubated with various treatments (n = 3). The color contour from blue to red denotes the intensified signal. **** <span class="html-italic">p</span> &lt; 0.0001.</p>
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<p>In vivo wound healing efficacy of ZIF@EV-Gel. (<b>A</b>) Representative image of wound size on different days. (<b>B</b>) Fluorescence images of cutaneous wounds extracted at 6 and 12 h after different treatments. The color contour from blue to red denotes the intensified signal. (<b>C</b>) Hematoxylin and eosin (HE) and Masson stain of the wounded skin on day 12. Scale bar = 100 μm. (<b>D</b>) Quantification of wound size in different groups. (<b>E</b>) Quantitative analysis of epidermal thickness. (<b>F</b>) Quantitative analysis of collagen deposition (n = 3). * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, and **** <span class="html-italic">p</span> &lt; 0.0001.</p>
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<p>Therapeutic mechanism of ZIF@EV-Gel ink. ZIF@EV-Gel accelerated wound healing in vivo. (<b>A</b>) Image of immunofluorescence staining to assess the formation of new blood vessels and the inflammatory status of the wounds. The blue color indicate nucleus and red color indicate the presence of CD31 and CD206 separately. (<b>B</b>) bactericidal effects of ZIF@EV-Gel. (<b>C</b>) Quantification of blood vessels with various treatments. (<b>D</b>) Quantitative analysis of activated M2 macrophages in epidermal tissues. **** <span class="html-italic">p</span> &lt; 0.0001.</p>
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