Wound Healing: From Basic to Clinical Research

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 30 June 2025 | Viewed by 12358

Special Issue Editor


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Guest Editor
Department of Vascular and Endovascular Surgery, University Hospital of Dusseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany
Interests: wound healing; tissue regeneration; wound infection; antiseptics and antimicrobials

Special Issue Information

Dear Colleagues,

It is my distinct pleasure to introduce this Special Issue of Biomedicines, focusing on the comprehensive and diverse theme of "Wound Healing: From Basic to Clinical Research". Wound healing stands as a fundamental aspect of medical science, intricately weaving together basic biological processes with clinical interventions to promote tissue repair and regeneration.

In this collection of articles, we embark on a journey through the intricate landscape of wound healing, delving into the latest advancements in both basic science and clinical practice. From elucidating potential molecular mechanisms underlying cellular responses to tissue defects to exploring innovative therapeutic strategies aimed at enhancing wound closure and tissue regeneration, each contribution encapsulates the multifaceted nature of wound healing research.

As a Guest Editor, I have the privilege of witnessing the remarkable breadth and depth of expertise showcased by our contributors. Their invaluable insights and discoveries are poised to significantly impact our understanding of wound healing and pave the way for novel therapeutic interventions.

I extend my heartfelt invitation and gratitude to all the authors, reviewers, and editorial staff who will contribute to the realization of this Special Issue. It is my hope that this collection will serve as a catalyst for further exploration and collaboration in the ever-evolving field of wound healing research.

Dr. Julian-Dario Rembe
Guest Editor

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Keywords

  • wound healing
  • clinical research in wound healing
  • in vitro experiments in wound healing
  • in vivo experiments in wound healing
  • cytokines in wound healing
  • chronic wounds
  • pressure sores/ulcers
  • scar formation

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Published Papers (14 papers)

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Research

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16 pages, 2439 KiB  
Article
SIRT1 Mediates the Effects of Sera from Athletes Who Engage in Aerobic Exercise Training in Activating Cells for Wound Healing
by Raffaella Belvedere, Nunzia Novizio, Berenice Stefanelli, Carmine Sellitto, Mariangela Palazzo, Marta Trucillo, Antonio De Luca, Emanuela De Bellis, Graziamaria Corbi, Amelia Filippelli, Valeria Conti and Antonello Petrella
Biomedicines 2025, 13(5), 1041; https://doi.org/10.3390/biomedicines13051041 - 25 Apr 2025
Viewed by 85
Abstract
Background/Objectives: Exercise training (ET) can improve wound healing and prevent the recurrence of skin lesions. Aerobic ET stimulates the NAD+-dependent deacetylase sirtuin 1 (SIRT1). The beneficial effects of ET and SIRT1 activation in wound healing have been characterized when considered separately. This study [...] Read more.
Background/Objectives: Exercise training (ET) can improve wound healing and prevent the recurrence of skin lesions. Aerobic ET stimulates the NAD+-dependent deacetylase sirtuin 1 (SIRT1). The beneficial effects of ET and SIRT1 activation in wound healing have been characterized when considered separately. This study aimed to investigate the potential role of SIRT1 as a mediator of the effects of sera isolated from athletes who regularly participate in aerobic ET (middle-distance running, MDR) on cells primarily involved in wound healing. Methods: Human keratinocytes, fibroblasts and endothelial cells were conditioned with sera from middle-distance runners and age-matched sedentary subjects (sed). Cell motility, angiogenesis and the expression of key biomarkers of cell activation were evaluated in the presence or absence of the selective SIRT1 inhibitor EX-527. Results: Higher SIRT1 activity was detected in all of the cell lines conditioned with the MDR group sera compared with that in the cells in the sed group sera. The involvement of SIRT1 was demonstrated by EX-527’s selective inhibition. Alongside the increase in SIRT1 activity, a marked increase in migration, invasion and angiogenesis was observed. The levels of E-cadherin decreased while those of integrin β1 and vinculin increased in the keratinocytes and fibroblasts conditioned with the MDR group sera compared to these values with the sed group sera, respectively. Increased levels of differentiation markers, such as involucrin in the keratinocytes, FAP1α in the fibroblasts and CD31 in the endothelial cells, were observed with the MDR group sera compared to these values using the sed group sera. Conclusions: The ex vivo/in vitro approach used here links aerobic ET-induced SIRT1 activity to proper tissue regeneration. Full article
(This article belongs to the Special Issue Wound Healing: From Basic to Clinical Research)
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18 pages, 6450 KiB  
Article
Inhibition of Th2 Differentiation Accelerates Chronic Wound Healing by Facilitating Lymphangiogenesis
by Bracha L. Pollack, Jeremy S. Torrisi, Geoffrey E. Hespe, Gopika Ashokan, Jinyeon Shin, Babak J. Mehrara and Raghu P. Kataru
Biomedicines 2025, 13(5), 1026; https://doi.org/10.3390/biomedicines13051026 - 24 Apr 2025
Viewed by 189
Abstract
Background/Objectives: Chronic wounds pose a significant healthcare burden, and there remains no effective animal model for study. We aimed to develop a mouse model of chronic wounds that remain open for at least 4 weeks and to investigate the role of the [...] Read more.
Background/Objectives: Chronic wounds pose a significant healthcare burden, and there remains no effective animal model for study. We aimed to develop a mouse model of chronic wounds that remain open for at least 4 weeks and to investigate the role of the lymphatic system in wound healing. Methods: Full-thickness excisional wounds were created on the dorsal surface of mouse tails to simulate chronic wounds. Lymphatic drainage was assessed using FITC–dextran lymphangiography. Histology and immunofluorescence were used to analyze immune cell infiltration. The effect of inhibiting Th2 differentiation via IL-4 and IL-13 neutralization on wound closure was also evaluated. Results: Our chronic wound model was successful, and wounds remained open for 4 weeks. Impaired lymphatic drainage was observed extending beyond the wound area. Increased CD4+ T-helper cell infiltration and Th2 cell accumulation were observed in the impaired lymphatic drainage zone. Inhibition of IL-4 and IL-13 accelerated wound healing. Conclusions: Impaired lymphatic drainage and Th2-mediated inflammation contribute to delayed healing, and gradients of lymphatic fluid flow are associated with spatial differences in lymphangiogenesis. Targeting Th2 cytokines may offer a novel therapeutic approach for chronic wounds. Full article
(This article belongs to the Special Issue Wound Healing: From Basic to Clinical Research)
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17 pages, 11658 KiB  
Article
Promising Antimicrobial Activities of Essential Oils and Probiotic Strains on Chronic Wound Bacteria
by Mara-Mădălina Mihai, Beatrice Bălăceanu-Gurău, Alina Maria Holban, Cornelia-Ioana Ilie, Romina Maria Sima, Cristian-Dorin Gurău and Lia-Mara Dițu
Biomedicines 2025, 13(4), 962; https://doi.org/10.3390/biomedicines13040962 - 14 Apr 2025
Viewed by 305
Abstract
Background: Disruption of the natural balance of the skin microbiota can impair wound healing and contribute to chronic infections. Identifying the bacterial species involved and understanding their antimicrobial susceptibility profiles are essential for guiding treatment, especially given the growing threat of antibiotic resistance. [...] Read more.
Background: Disruption of the natural balance of the skin microbiota can impair wound healing and contribute to chronic infections. Identifying the bacterial species involved and understanding their antimicrobial susceptibility profiles are essential for guiding treatment, especially given the growing threat of antibiotic resistance. Methods: This study characterized the virulence and antibiotic resistance phenotypes of 43 bacterial strains isolated from chronic wounds. The antimicrobial activity of selected essential oils (sandalwood, ylang-ylang, sage, cajeput, and juniper), pharmaceutical products (propolis tinctures, usnic acid), and probiotic lactic acid bacteria strains (Lactobacillus spp., Lactococcus lactis) was assessed using qualitative and quantitative assays, including MIC, MICBA, and co-culture evaluations. Results: Gram-positive strains were more sensitive to essential oils than Gram-negative strains, with sandalwood, ylang-ylang, and propolis tincture showing the strongest antibacterial effects. These agents also showed significant biofilm inhibition. Probiotic strains exhibited antimicrobial activity against Staphylococcus aureus and Morganella morganii, with Lactobacillus paracasei and Lactobacillus rhamnosus being particularly effective in reducing bacterial growth and adhesion in vitro. Conclusions: Essential oils and probiotic strains demonstrate promising antimicrobial effects against chronic wound pathogens and may serve as alternative or adjunctive treatments to antibiotics. Further clinical research and standardization are necessary to establish their safety, efficacy, and optimal application protocols. Full article
(This article belongs to the Special Issue Wound Healing: From Basic to Clinical Research)
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17 pages, 3556 KiB  
Article
Lyophilized Extract from the Larvae of the Blowfly Lucilia sericata as a New Strategy for the Management of Chronic Wounds
by Norman-Philipp Hoff, Falk Peer Gestmann, Theresa Maria Jansen, Sarah Janßen, Sabine Petersdorf, Bernhard Homey, Peter Arne Gerber and Heinz Mehlhorn
Biomedicines 2025, 13(3), 582; https://doi.org/10.3390/biomedicines13030582 - 26 Feb 2025
Viewed by 526
Abstract
Background/Objectives: Chronic wounds represent a growing challenge for the aging population, significantly impairing their quality of life, increasing the frequency of medical consultations, and imposing substantial healthcare costs. Chronic wounds are prone to complications, including local and systemic infections, and in severe [...] Read more.
Background/Objectives: Chronic wounds represent a growing challenge for the aging population, significantly impairing their quality of life, increasing the frequency of medical consultations, and imposing substantial healthcare costs. Chronic wounds are prone to complications, including local and systemic infections, and in severe cases, amputations. The therapeutic use of live larvae from the blowfly Lucilia sericata (biological debridement) has regained attention for its ability to debride necrotic tissue and stimulate granulation. Despite its benefits, this therapy is constrained by the logistical challenges of producing and delivering live larvae and by patient adherence issues. Objectives: This study aimed to develop a lyophilized extract of Lucilia sericata larvae and evaluate its efficacy in treating chronic wounds. Methods: A lyophilized maggot extract (Larveel®, Alpha-Biocare GmbH, Neuss, Germany) of the larvae of Lucilia sericata was produced under GMP conditions. In a total of ten patients with chronic refractory wounds, the extract was used in individual therapeutic trials and its effect on bacterial colonization and wound healing was investigated. Wound healing was documented photographically and measured visually in terms of a reduction in the wound slough, an increase in the granulation tissue, and a reduction in the wound area. Results: Of the ten patients, three discontinued their treatment due to P. aeruginosa colonization. In seven patients, significant fibrin reduction, granulation, and wound healing occurred, with two achieving complete closure and four showing advanced epithelialization. Conclusions: In 7 of the 10 patients, the application of the extract led to a marked reduction in wound slough, and improved granulation and the progression of wound healing. These effects are likely attributable to the extract’s ability to disrupt bacterial biofilm formation. The findings suggest that this novel therapeutic approach may provide a practical and effective alternative to live larval therapy for managing chronic wounds. Full article
(This article belongs to the Special Issue Wound Healing: From Basic to Clinical Research)
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20 pages, 5013 KiB  
Article
In Vitro Effects of Low-Level Laser Therapy on the Viability and Secretory Activity of Resting Macrophages
by Aleksandra Matuła, Amelia Lizak, Ewa Stodolak-Zych, Aneta Bac, Joanna Homa, Beata Stenka and Anna Ścisłowska-Czarnecka
Biomedicines 2025, 13(2), 403; https://doi.org/10.3390/biomedicines13020403 - 7 Feb 2025
Viewed by 782
Abstract
Background/Objectives: Low-level laser therapy (LLLT) covers a wide range of parameters in terms of laser properties and dosage, which is important for its effects. It is important to select safe, optimal irradiation conditions to obtain the desired therapeutic effect of LLLT on [...] Read more.
Background/Objectives: Low-level laser therapy (LLLT) covers a wide range of parameters in terms of laser properties and dosage, which is important for its effects. It is important to select safe, optimal irradiation conditions to obtain the desired therapeutic effect of LLLT on cells. This article is focused on the selection of favourable (biostimulating) exposure conditions for LLLT, which are the beam application method (continuous [C] or pulsed [P] laser beam), radiation power and LLLT dose, on the viability and secretory activity regarding resting macrophages of the RAW 264.7 cell line. Methods: RAW 264.7 macrophages were seeded on 24-well tissue culture. ASTAR PhysioGo 400C apparatus with a spot applicator generating electromagnetic radiation in the infrared light range of 808 nm and power of 100 mW and 200 mW was used for laser irradiation of macrophages. Cells were treated with different doses of constant radiation 5 J/cm2/well or 10 J/cm2/well. Results: It was shown that the most beneficial radiation parameters for cells were obtained with a pulsed laser beam of 200 mW power and a dose of 5 J/cm2, which caused an increase in macrophage adhesion and viability, as well as an increase in NO secretion by macrophages and their TOS, with a simultaneous decrease in the secretion of TNF-α, MCP-1 and MMP-9 by cells. Conclusions: The research results presented above indicate that the effect of LLLT on resting macrophages modulates their biological activity, and the intensity of photobiostimulation depends on the irradiation parameters, including wavelength, power, dose and method of laser beam application. Full article
(This article belongs to the Special Issue Wound Healing: From Basic to Clinical Research)
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14 pages, 2111 KiB  
Article
Lower Levels of TAZ Expression Associated with Post-Surgical Wound Healing Complications in Soft Tissue Sarcoma Patients Treated with Preoperative Radiation
by Jacob D. Gylten, Jane E. Persons, Benjamin J. Miller, Qiang An, Munir R. Tanas and Stephanie J. T. Chen
Biomedicines 2025, 13(2), 344; https://doi.org/10.3390/biomedicines13020344 - 3 Feb 2025
Viewed by 737
Abstract
Background/Objectives: Pre-operative radiation (Pre-RT) decreases local recurrence following soft tissue sarcoma (STS) resection but carries the risk of wound healing complications (WHCs). This study evaluated skin specimens and clinical characteristics of STS patients to (1) compare patients with and without Pre-RT, (2) compare [...] Read more.
Background/Objectives: Pre-operative radiation (Pre-RT) decreases local recurrence following soft tissue sarcoma (STS) resection but carries the risk of wound healing complications (WHCs). This study evaluated skin specimens and clinical characteristics of STS patients to (1) compare patients with and without Pre-RT, (2) compare Pre-RT patients with and without WHCs, and (3) explore associations between clinical characteristics and WHCs. Methods: This retrospective study included 54 adults who underwent STS resection with primary closure (Pre-RT n = 30). A pathologist who was blinded to the clinical outcomes evaluated the skin specimens microscopically. Results: Irradiated skin had lower vessel density and was more likely to lack hair follicles and sebaceous glands, consistent with the effects of radiation. Irradiated skin was also more likely to include plasma cells. Irradiated skin demonstrated higher mean TAZ H-scores; however, within the Pre-RT subset, those patients who developed WHCs demonstrated comparatively lower TAZ. Conclusions: This novel finding may suggest that higher TAZ in irradiated skin reflects a response to injury but that comparatively lower TAZ in irradiated skin might contribute to WHCs. Future studies should consider more focused evaluation of TAZ in STS resections with Pre-RT as they may help to predict WHCs when used in combination with other histologic factors and could suggest a therapeutic target. Full article
(This article belongs to the Special Issue Wound Healing: From Basic to Clinical Research)
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18 pages, 3694 KiB  
Article
Development of a ZRS Reporter System for the Newt (Cynops pyrrhogaster) During Terrestrial Limb Regeneration
by Martin Miguel Casco-Robles, Ryosuke Ikeda, Fumiaki Maruo and Chikafumi Chiba
Biomedicines 2024, 12(11), 2505; https://doi.org/10.3390/biomedicines12112505 - 1 Nov 2024
Viewed by 1322
Abstract
Background: Newts, a type of urodele amphibian, offer remarkable insights into regenerative medicine due to their extraordinary tissue regeneration capabilities—a challenging feat in humans. During limb regeneration of adult newts, fascinating cellular and molecular processes are revealed, including scarless healing, de-differentiation of mature [...] Read more.
Background: Newts, a type of urodele amphibian, offer remarkable insights into regenerative medicine due to their extraordinary tissue regeneration capabilities—a challenging feat in humans. During limb regeneration of adult newts, fascinating cellular and molecular processes are revealed, including scarless healing, de-differentiation of mature cells, and regeneration of limbs and digits. Sonic hedgehog (Shh), crucial for vertebrate limb development, is regulated by the zone of polarizing activity regulatory sequence (ZRS) in the limb bud zone of polarizing activity (ZPA). The metamorphosed (terrestrial) newt can reactivate Shh during regeneration, facilitating proper limb patterning. Cell types capable of regulating the ZRS in metamorphosed newts remain unknown. The identification of such cell types provides invaluable insight into novel regenerative mechanisms. Objective: In this study, we developed the first newt ZRS reporter. Methods: We isolated and characterized the newt ZRS enhancer (nZRS), identifying conserved DNA binding sites. Several binding sites with medical relevance were conserved in the newt ZRS. In functional analysis, we developed a system composed of a transgenic nZRS reporter newt and a new newt anti-Shh antibody, which allowed Shh monitoring during limb regeneration. Results: We identified a group of Schwann cells capable of ZRS reporter and Shh protein expression during terrestrial limb regeneration. Conclusions: This system provides a valuable in vivo approach for future genetic studies of patterning during limb regeneration. Full article
(This article belongs to the Special Issue Wound Healing: From Basic to Clinical Research)
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22 pages, 3714 KiB  
Article
Assessment and Monitoring of the Wound Micro-Environment in Chronic Wounds Using Standardized Wound Swabbing for Individualized Diagnostics and Targeted Interventions
by Julian-Dario Rembe, Waseem Garabet, Jan-Wilm Lackmann, Sadaf Alizadehrahrouei, Matthias Augustin, Joachim Dissemond, Wiebke Ibing, Karl Köhrer, Klaus Pfeffer, Anna Rommerskirchen, Sebastian Alexander Scharf, Tobias Wienemann, Thorsten Wachtmeister, Hubert Schelzig and Ewa Klara Stuermer
Biomedicines 2024, 12(10), 2187; https://doi.org/10.3390/biomedicines12102187 - 26 Sep 2024
Cited by 1 | Viewed by 1398
Abstract
Background/Objectives: Patient-specific diagnostic and therapeutic approaches are important in the care of people with chronic wounds. The heterogeneity of underlying disease profiles and the diversity of the wound micro-environment make generalized approaches difficult. While high-throughput molecular diagnostic methods are increasingly widespread and available, [...] Read more.
Background/Objectives: Patient-specific diagnostic and therapeutic approaches are important in the care of people with chronic wounds. The heterogeneity of underlying disease profiles and the diversity of the wound micro-environment make generalized approaches difficult. While high-throughput molecular diagnostic methods are increasingly widespread and available, the analysis of objective biomolecular disease patterns has not found its way into everyday wound management. The aim of this study is to evaluate the use of wound swab samples for the analysis of biomarkers and disease patterns in people with chronic wounds. Methods: A sample cohort from the multicenter “Wound-BIOME” project was analyzed. The project aims to comprehensively investigate the local micro-environment of chronic wounds of various entities, healing tendencies and regeneration stages at the biomolecular level. A sample collection and handling protocol suitable for everyday use was tested and evaluated regarding feasibility for multiplex immunoassay, proteomics, small RNA sequencing (miRNA) and metagenome analyses (microbiomics). Results: It could be shown that standard wound swabs are well-suited for the analysis of the complex wound micro-environment using various high-throughput methods. Despite the sample heterogeneity, the quality was adequate to analyze biomolecular patterns. Conclusions: Initial analyses of protein signatures, microbial wound communities and miRNA patterns show promising results for future individualized diagnostics and targeted interventions. Full article
(This article belongs to the Special Issue Wound Healing: From Basic to Clinical Research)
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13 pages, 5726 KiB  
Article
Increased Susceptibility to Mechanical Stretch Drives the Persistence of Keloid Fibroblasts: An Investigation Using a Stretchable PDMS Platform
by Jihee Kim, Chihyeong Won, Seoyoon Ham, Heetak Han, Sungsik Shin, Jieun Jang, Sanghyeon Lee, Chaebeen Kwon, Sungjoon Cho, Hyeonjoo Park, Dongwon Lee, Won Jai Lee, Taeyoon Lee and Ju Hee Lee
Biomedicines 2024, 12(10), 2169; https://doi.org/10.3390/biomedicines12102169 - 24 Sep 2024
Viewed by 1547
Abstract
Background: Keloids are a common fibrotic disease of the skin, with the pathological hallmark of excessive extracellular matrix synthesis due to abnormal fibroblast activity. Since keloids clinically arise in areas of high mechanical tension, the mechanotransductory pathway may be attributed to its pathogenesis. [...] Read more.
Background: Keloids are a common fibrotic disease of the skin, with the pathological hallmark of excessive extracellular matrix synthesis due to abnormal fibroblast activity. Since keloids clinically arise in areas of high mechanical tension, the mechanotransductory pathway may be attributed to its pathogenesis. We aimed to establish a preclinical platform to elucidate the underlying mechanism of keloid development and its clinical persistence. Methods: We fabricated a mechanically stretchable polydimethylsiloxane cell culture platform; with its mimicry of the in vivo cyclic stretch of skeletal muscles, cells showed higher proliferation compared with conventional modalities. Results: In response to mechanical strain, TGF-β and type 1 collagen showed significant increases, suggesting possible TGF-β/Smad pathway activation via mechanical stimulation. Protein candidates selected by proteomic analysis were evaluated, indicating that key molecules involved in cell signaling and oxidative stress were significantly altered. Additionally, the cytoskeletal network of keloid fibroblasts showed increased expression of its components after periodic mechanical stimulation. Conclusions: Herein, we demonstrated and validated the existing body of knowledge regarding profibrotic mechanotransduction signaling pathways in keloid fibroblasts. Cyclic stretch, as a driving force, could help to decipher the tension-mediated biomechanical processes, leading to the development of optimized therapeutic targets. Full article
(This article belongs to the Special Issue Wound Healing: From Basic to Clinical Research)
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Review

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23 pages, 1947 KiB  
Review
Microbiome and Postbiotics in Skin Health
by Santosh Kumar Prajapati, Lalitha Lekkala, Dhananjay Yadav, Shalini Jain and Hariom Yadav
Biomedicines 2025, 13(4), 791; https://doi.org/10.3390/biomedicines13040791 - 25 Mar 2025
Viewed by 1283
Abstract
The skin microbiome, a diverse and dynamic ecosystem of microorganisms, plays a pivotal role in maintaining skin health by interacting with skin cells, immune components, and structural barriers. It is essential for skin homeostasis, immune defense, and protection against pathogenic colonization. Dysbiosis in [...] Read more.
The skin microbiome, a diverse and dynamic ecosystem of microorganisms, plays a pivotal role in maintaining skin health by interacting with skin cells, immune components, and structural barriers. It is essential for skin homeostasis, immune defense, and protection against pathogenic colonization. Dysbiosis in the microbiome has been implicated in numerous dermatological conditions, including acne, eczema, psoriasis, and rosacea. Acne, the most prevalent skin condition, affects up to 85% of individuals at some point in their lives, while eczema and psoriasis impose significant public health and economic burdens. The composition of the skin microbiome varies across skin types and anatomical sites, with sebaceous, moist, and dry areas fostering distinct microbial communities. Emerging therapeutic strategies such as microbiome-targeted treatments offer novel avenues for addressing skin diseases. Among these approaches, postbiotics have gained significant attention for their safety and efficacy. Unlike probiotics, postbiotics are non-viable microbial cells or their metabolites, which reduce safety concerns while providing functional benefits such as UV protection and wound healing. This review consolidates current insights into the role of the skin microbiome in health and disease, emphasizing postbiotics as a promising therapeutic strategy by exploring the clinical and commercial potential of microbiome-based treatments, particularly postbiotics, and their ability to redefine dermatological care and improve patient outcomes. Full article
(This article belongs to the Special Issue Wound Healing: From Basic to Clinical Research)
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19 pages, 9168 KiB  
Review
The Journey of Copper-Impregnated Dressings in Wound Healing: From a Medical Hypothesis to Clinical Practice
by Gadi Borkow and Eyal Melamed
Biomedicines 2025, 13(3), 562; https://doi.org/10.3390/biomedicines13030562 - 24 Feb 2025
Viewed by 1032
Abstract
Background/Objectives. Chronic wounds pose a substantial global healthcare burden exacerbated by aging populations and the increasing prevalence of conditions such as diabetes, peripheral vascular disease, and venous insufficiency. Impaired physiological repair mechanisms, including angiogenesis, collagen synthesis, and re-epithelialization, hinder the healing process in [...] Read more.
Background/Objectives. Chronic wounds pose a substantial global healthcare burden exacerbated by aging populations and the increasing prevalence of conditions such as diabetes, peripheral vascular disease, and venous insufficiency. Impaired physiological repair mechanisms, including angiogenesis, collagen synthesis, and re-epithelialization, hinder the healing process in chronic wounds. Many of these physiological processes are dependent on their interaction with copper. We hypothesized that the targeted delivery of copper ions to the wound bed would enhance healing. Methods. Wound dressings impregnated with copper oxide microparticles were designed to ensure the controlled release of copper ions. The efficacy of these dressings was evaluated using non-infected wound models, including diabetic mouse models compared against control and silver dressings. Outcome measures included wound closure rates, epidermal skin quality assessed by histopathological examination, and gene expression profiling. Clinical applications were assessed through diverse case studies and controlled trials involving chronic wound management. Results. Copper dressings significantly accelerated wound closure and enhanced angiogenesis compared to control and silver dressings. Histopathological analyses revealed faster granulation tissue formation, epidermal regeneration, and neovascularization. Gene expression studies showed upregulation of critical angiogenic factors such as VEGF and HIF-1α. Investigations and clinical observations corroborated improved healing across various chronic wound types, including non-infected wounds. Conclusions. Copper is essential for wound healing, and copper-impregnated dressings provide a promising solution for chronic wound management. By enhancing angiogenesis and tissue regeneration, these dressings go beyond antimicrobial action, offering a cost-effective and innovative alternative to conventional therapies. Copper dressings represent a transformative advancement in addressing the challenges of chronic wound care. Full article
(This article belongs to the Special Issue Wound Healing: From Basic to Clinical Research)
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14 pages, 1373 KiB  
Review
Effects of Carbon Dioxide Therapy on Skin Wound Healing
by José Prazeres, Ana Lima and Gesiane Ribeiro
Biomedicines 2025, 13(1), 228; https://doi.org/10.3390/biomedicines13010228 - 18 Jan 2025
Cited by 1 | Viewed by 1071
Abstract
Promoting rapid healing is a concern in skin wound treatment, as the increased pain and the loss of functional ability when wounds become chronic create a complex problem to manage. This scoping review aimed to explore the literature and synthesize existing knowledge on [...] Read more.
Promoting rapid healing is a concern in skin wound treatment, as the increased pain and the loss of functional ability when wounds become chronic create a complex problem to manage. This scoping review aimed to explore the literature and synthesize existing knowledge on the therapeutic use of CO2 in treating cutaneous wounds. The literature was selected using previously defined inclusion and exclusion criteria, and 22 articles were selected for data extraction. The most researched type of injury was chronic wounds located on the extremities of the limbs. Carboxytherapy was performed in five different ways: subcutaneous, intradermal, or intralesional injections; in hot water baths with temperatures ranging from 30 to 42 °C; transcutaneous application; intra-abdominal insufflation; and a paste for transcutaneous local application. The main effects of CO2 therapy described were as follows: improved blood flow and local oxygenation, reduction of the inflammatory process, increased collagen production, and improved clinical aspects of wounds, with faster healing. Carboxytherapy can be considered a good alternative for treating skin wounds, although further studies should be pursued to elucidate its molecular mechanisms and enhance its efficacy. Full article
(This article belongs to the Special Issue Wound Healing: From Basic to Clinical Research)
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Other

Jump to: Research, Review

11 pages, 2102 KiB  
Perspective
Deciphering Pain and Pruritus in Keloids from the Perspective of Neurological Dysfunction: Where Are We Now?
by En Yang, Ruoqing Xu, Hanrui Zhang, Wenzheng Xia, Xin Huang and Tao Zan
Biomedicines 2025, 13(3), 663; https://doi.org/10.3390/biomedicines13030663 - 8 Mar 2025
Viewed by 560
Abstract
Keloids are a typical skin fibroproliferative disease that can cause severe aesthetic and functional concerns. Pain and pruritus are the most common clinical symptoms of keloids, but the mechanisms underlying these symptoms remain unclear. The peripheral nervous system plays a pivotal role in [...] Read more.
Keloids are a typical skin fibroproliferative disease that can cause severe aesthetic and functional concerns. Pain and pruritus are the most common clinical symptoms of keloids, but the mechanisms underlying these symptoms remain unclear. The peripheral nervous system plays a pivotal role in the transmission of superficial sensation signals. Mounting evidence has shown potential correlations between disturbance in the peripheral nervous system and pain and pruritus in keloids. Here, we summarize the role of neurological dysfunction in the development of pain and pruritus, with a specific focus on neuroanatomical alterations, the dysfunction of sensory nerves, and neurogenic inflammation. Full article
(This article belongs to the Special Issue Wound Healing: From Basic to Clinical Research)
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10 pages, 1808 KiB  
Case Report
Management of Foot Ulcers and Chronic Wounds with Amniotic Membrane in Comorbid Patients: A Successful Experience
by Mónica Rodríguez-Valiente, Ana M. García-Hernández, Cristina Fuente-Mora, Javier Sánchez-Gálvez, Eva María García-Vizcaino, Elena Tristante Barrenechea, Gregorio Castellanos Escrig, Sergio David Liarte Lastra and Francisco Jose Nicolás
Biomedicines 2024, 12(10), 2380; https://doi.org/10.3390/biomedicines12102380 - 18 Oct 2024
Viewed by 1374
Abstract
Chronic wounds are defined as those with disturbances in normal healing. They involve symptoms like exudate, odor, pain or impaired mobility, severely impacting life quality. In the case of patients with additional comorbidities, these are known to aggravate the healing impairment. Amniotic membrane [...] Read more.
Chronic wounds are defined as those with disturbances in normal healing. They involve symptoms like exudate, odor, pain or impaired mobility, severely impacting life quality. In the case of patients with additional comorbidities, these are known to aggravate the healing impairment. Amniotic membrane (AM) is gaining attention for its regenerative potential, as it has shown promise in treating hard-to-heal wounds, such as diabetic foot ulcers. This work examines a series of five patients who, while suffering an array of other chronic conditions, were treated with AM for the management of non-healing chronic ulcers. Inclusion criteria involved patients with lesions that have been active at least for six weeks and resistant to multiple treatments, accompanied by complex underlying pathologies affecting cardiovascular, immune or renal functions. Exclusion criteria included untreated active infections and patients undergoing other experimental treatments. The mean age of the patients was 68.4 ± 5.2 years. Wounds were treated once a week with AM, following standardized procedures. The variables measured included pain levels, microorganism presence, wound reduction and the number of AM applications to recovery. The median pain VAS score decreased significantly from seven at the start to two at the end of procedures. Four out of five patients achieved complete epithelialization, while the remaining patient showed significant reductions of 40% in wound size after 14 months. Our results confirm how the application of AM is a safe and effective resource for the management of chronic wounds in patients with serious comorbidities, enhancing patients’ quality of life, firstly by reducing pain, later by allowing recovery. Future research, including molecular analyses of wound exudates before and after AM treatment, can contribute to better understanding and fine tuning of this therapeutic resource. Full article
(This article belongs to the Special Issue Wound Healing: From Basic to Clinical Research)
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