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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (25 March 2024) | Viewed by 29212

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Dr. Alina Maria Holban

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Department of Microbiology, Faculty of Biology, University of Bucharest, 030018 București, Romania
Interests: microbiology; immunology; new antimicrobial agents; host–pathogen signaling; infection control; antimicrobial nanomaterials
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Dr. Carmen Curutiu

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Department of Microbiology, Faculty of Biology, University of Bucharest, 030018 București, Romania
Interests: microbiology; immunology; cellular biology
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Dear Colleagues,

Wound healing represents one of the most complex processes in the body, subjecting organisms to many sequential stages: haemostasis, inflammation, proliferation, and remodelling. Many cells of the body (platelets, macrophages, neutrophils, fibroblasts, and epidermal cells) are involved in a very well-coordinated process. Any change in external or internal factors can disrupt the process, leading to the appearance of chronic wounds, resulting in incomplete healing, the recurrence of the infectious process, and a continuous need for treatment, meaning an overwhelming burden for both patients and medical systems. Due to the complexity of the process, a multidisciplinary approach to diagnoses and treatments is often required. Since many aspects of chronic wound healing are far from completely understood, this collection of papers aims to display the progress of researchers in the field as well as the data from clinicians regarding the pathophysiology of wounds (acute or chronic) to date, in addition to currently available modalities to achieve healing in such patients. Recent developments in the management of wound healing are also addressed, such as the following: new techniques of wound debridement, the development of topical antiseptics and antimicrobials for fighting against multidrug-resistant bacteria from chronic wound biofilms, the investigation of growth factors and other new biologic wound products, skin substitutes, interactive dressings, or tissue engineering techniques—stem cells and gene therapy.

Dr. Alina Maria Holban
Dr. Carmen Curutiu
Guest Editors

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Keywords

management of wounds
nanobiomaterials
infection control
chronic wound
biofilm infections
wound dressings
tissue engineering
wound healing

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Published Papers (9 papers)

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Research

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15 pages, 3981 KiB

Open AccessArticle

A Standardized Porcine Model for Partial-Thickness Wound Healing Studies: Design, Characterization, Model Validation, and Histological Insights

by Alexandru-Cristian Tuca, Ives Bernardelli de Mattos, Martin Funk, Danijel Markovic, Raimund Winter, Thomas Lemarchand, Daniela Kniepeiss, Stephan Spendel, Bernd Hartmann, Christian Ottoman and Lars-Peter Kamolz

Int. J. Mol. Sci. 2024, 25(14), 7658; https://doi.org/10.3390/ijms25147658 - 12 Jul 2024

Cited by 1 | Viewed by 1971

Abstract

Wound healing is a complex process that is still not fully understood despite extensive research. To address this, we aimed to design and characterize a standardized porcine model for the evaluation of wound healing, dressings, cell therapies, and pharmaceutical agents. Using a standardized approach, we examined the wound healing process in 1.2 mm-deep dermatome wounds at defined positions in 11 female pigs. Unlike previous studies that have only described/analyzed selected punch biopsies, we performed and described histological analyses along the complete wound length using quantitative morphometric methods. All animals remained fully healthy following surgery and showed no signs of infection. Our histopathological evaluation using a predetermined grading score and quantitative manual morphometry demonstrated the impact of different tissue sampling methods, sampling sites, and residual dermis thickness on wound healing. Our study presents a reproducible model for wound healing evaluation and demonstrates the usefulness of porcine models for assessing dermal and epidermal wound healing. The use of histological analyses over the complete wound length provides advantages over previous studies, leading to the possibility of a deeper understanding of the wound healing process. This model could potentially facilitate future research on novel wound dressings and local wound healing therapies. Full article

(This article belongs to the Special Issue Recent Advances in Wound Healing)

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31 pages, 7162 KiB

Open AccessArticle

Surface Topography, Microbial Adhesion, and Immune Responses in Silicone Mammary Implant-Associated Capsular Fibrosis

by Ines Schoberleitner, Leoni Baier, Michaela Lackner, Lisa-Maria Zenz, Débora C. Coraça-Huber, Wendy Ullmer, Annabelle Damerum, Klaus Faserl, Stephan Sigl, Theresia Steinkellner, Selina Winkelmann, Bettina Sarg, Daniel Egle, Christine Brunner and Dolores Wolfram

Int. J. Mol. Sci. 2024, 25(6), 3163; https://doi.org/10.3390/ijms25063163 - 9 Mar 2024

Cited by 4 | Viewed by 2516

Abstract

Breast cancer is the most common cancer in women globally, often necessitating mastectomy and subsequent breast reconstruction. Silicone mammary implants (SMIs) play a pivotal role in breast reconstruction, yet their interaction with the host immune system and microbiome remains poorly understood. This study investigates the impact of SMI surface topography on host antimicrobial responses, wound proteome dynamics, and microbial colonization. Biological samples were collected from ten human patients undergoing breast reconstruction with SMIs. Mass spectrometry profiles were analyzed for acute and chronic wound proteomes, revealing a nuanced interplay between topography and antimicrobial response proteins. 16S rRNA sequencing assessed microbiome dynamics, unveiling topography-specific variations in microbial composition. Surface topography alterations influenced wound proteome composition. Microbiome analysis revealed heightened diversity around rougher SMIs, emphasizing topography-dependent microbial invasion. In vitro experiments confirmed staphylococcal adhesion, growth, and biofilm formation on SMI surfaces, with increased texture correlating positively with bacterial colonization. This comprehensive investigation highlights the intricate interplay between SMI topography, wound proteome dynamics, and microbial transmission. The findings contribute to understanding host–microbe interactions on SMI surfaces, essential for optimizing clinical applications and minimizing complications in breast reconstruction. Full article

(This article belongs to the Special Issue Recent Advances in Wound Healing)

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22 pages, 8074 KiB

Open AccessArticle

Healing of Skin Wounds in Rats Using Creams Based on Symphytum Officinale Extract

by Sorin Marian Mârza, Adela Maria Dăescu, Robert Cristian Purdoiu, Mădălina Dragomir, Mariana Tătaru, Iulia Melega, Andras-Laszlo Nagy, Adrian Gal, Flaviu Tăbăran, Sidonia Bogdan, Mirela Moldovan, Emoke Pall, Camelia Munteanu, Klara Magyari and Ionel Papuc

Int. J. Mol. Sci. 2024, 25(6), 3099; https://doi.org/10.3390/ijms25063099 - 7 Mar 2024

Cited by 4 | Viewed by 2662

Abstract

Rosmarinic acid is a well-known natural antioxidant and anti-inflammatory compound, and it is one of the polyphenolic compounds found in comfrey plants. Comfrey root also contains allantoin, which helps with new skin regeneration. This study aimed to investigate the healing and skin regeneration process of skin wounds in Wistar rats using creams based on comfrey extract and to correlate the results with active compounds in the extract. The obtained results showed that comfrey root is rich in bioactive compounds, including allantoin, salvianolic acid, and rosmarinic acid, which are known for their great free radical scavenging activity, and the high antioxidant activity of the extract may be mainly due to these compounds. The obtained extract has an antimicrobial effect on Staphylococcus aureus (1530.76/382.69), Escherichia coli (6123.01/6123.01), and Pseudomonas aeruginosa (6123.01/6123.01). The macroscopic evaluation and the histological analysis of the skin defects 14 days after the intervention showed faster healing and complete healing in the skin excisions treated with oil-in-water cream with 20% extract of comfrey as the active ingredient. Full article

(This article belongs to the Special Issue Recent Advances in Wound Healing)

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14 pages, 6754 KiB

Open AccessArticle

Nanofat Accelerates and Improves the Vascularization, Lymphatic Drainage and Healing of Full-Thickness Murine Skin Wounds

by Ettore Limido, Andrea Weinzierl, Emmanuel Ampofo, Yves Harder, Michael D. Menger and Matthias W. Laschke

Int. J. Mol. Sci. 2024, 25(2), 851; https://doi.org/10.3390/ijms25020851 - 10 Jan 2024

Cited by 9 | Viewed by 1989

Abstract

The treatment of wounds using the body’s own resources is a promising approach to support the physiological regenerative process. To advance this concept, we evaluated the effect of nanofat (NF) on wound healing. For this purpose, full-thickness skin defects were created in dorsal skinfold chambers of wild-type mice. These defects were filled with NF generated from the inguinal subcutaneous adipose tissue of green fluorescent protein (GFP)⁺ donor mice, which was stabilized using platelet-rich plasma (PRP). Empty wounds and wounds solely filled with PRP served as controls. Wound closure, vascularization and formation of granulation tissue were repeatedly analyzed using stereomicroscopy, intravital fluorescence microscopy, histology and immunohistochemistry over an observation period of 14 days. PRP + NF-treated wounds exhibited accelerated vascularization and wound closure when compared to controls. This was primarily due to the fact that the grafted NF contained a substantial fraction of viable GFP⁺ vascular and lymph vessel fragments, which interconnected with the GFP⁻ vessels of the host tissue. Moreover, the switch from inflammatory M1- to regenerative M2-polarized macrophages was promoted in PRP + NF-treated wounds. These findings indicate that NF markedly accelerates and improves the wound healing process and, thus, represents a promising autologous product for future wound management. Full article

(This article belongs to the Special Issue Recent Advances in Wound Healing)

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17 pages, 4651 KiB

Open AccessArticle

Differential Effects of Overexpression of Wild Type and Kinase-Dead MELK in Fibroblasts and Keratinocytes, Potential Implications for Skin Wound Healing and Cancer

by Łukasz Szymański, Krystyna Lieto, Robert Zdanowski, Sławomir Lewicki, Jean-Pierre Tassan and Jacek Z. Kubiak

Int. J. Mol. Sci. 2023, 24(9), 8089; https://doi.org/10.3390/ijms24098089 - 30 Apr 2023

Cited by 2 | Viewed by 2195

Abstract

Maternal embryonic leucine-zipper kinase (MELK) plays a significant role in cell cycle progression, mitosis, cell migration, cell renewal, gene expression, embryogenesis, proliferation, apoptosis, and spliceosome assembly. In addition, MELK is known to be overexpressed in multiple types of cancer and is associated with cancer proliferation. Tumorigenesis shares many similarities with wound healing, in which the rate of cell proliferation is a critical factor. Therefore, this study aimed to determine the involvement of MELK in the regulation of cell division in two cell types involved in this process, namely fibroblasts and keratinocytes. We examined how temporal overexpression of wild-type and kinase-dead MELK kinase variants affect the rate of proliferation, viability, cell cycle, and phosphorylation state of other kinases involved in these processes, such as ERK1/2, AKT1, MAPK9, p38, and p53. We explored if MELK could be used as a therapeutic stimulator of accelerated wound healing via increased proliferation. We observed that aberrant expression of MELK results in abnormal proliferation, altered cell cycle distribution, and decreased viability of the cells, which challenge the utility of MELK in accelerated wound healing. Our results indicate that, at least in healthy cells, any deviation from precisely controlled MELK expression is harmful to fibroblasts and keratinocytes. Full article

(This article belongs to the Special Issue Recent Advances in Wound Healing)

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18 pages, 2621 KiB

Open AccessArticle

miRNome and Proteome Profiling of Human Keratinocytes and Adipose Derived Stem Cells Proposed miRNA-Mediated Regulations of Epidermal Growth Factor and Interleukin 1-Alpha

by Hady Shahin, Sallam Abdallah, Jyotirmoy Das, Weihai He, Ibrahim El-Serafi, Ingrid Steinvall, Folke Sjöberg, Moustafa Elmasry and Ahmed T. El-Serafi

Int. J. Mol. Sci. 2023, 24(5), 4956; https://doi.org/10.3390/ijms24054956 - 4 Mar 2023

Cited by 4 | Viewed by 2902

Abstract

Wound healing is regulated by complex crosstalk between keratinocytes and other cell types, including stem cells. In this study, a 7-day direct co-culture model of human keratinocytes and adipose-derived stem cells (ADSCs) was proposed to study the interaction between the two cell types, in order to identify regulators of ADSCs differentiation toward the epidermal lineage. As major mediators of cell communication, miRNome and proteome profiles in cell lysates of cultured human keratinocytes and ADSCs were explored through experimental and computational analyses. GeneChip^® miRNA microarray, identified 378 differentially expressed miRNAs; of these, 114 miRNAs were upregulated and 264 miRNAs were downregulated in keratinocytes. According to miRNA target prediction databases and the Expression Atlas database, 109 skin-related genes were obtained. Pathway enrichment analysis revealed 14 pathways including vesicle-mediated transport, signaling by interleukin, and others. Proteome profiling showed a significant upregulation of the epidermal growth factor (EGF) and Interleukin 1-alpha (IL-1α) compared to ADSCs. Integrated analysis through cross-matching the differentially expressed miRNA and proteins suggested two potential pathways for regulations of epidermal differentiation; the first is EGF-based through the downregulation of miR-485-5p and miR-6765-5p and/or the upregulation of miR-4459. The second is mediated by IL-1α overexpression through four isomers of miR-30-5p and miR-181a-5p. Full article

(This article belongs to the Special Issue Recent Advances in Wound Healing)

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11 pages, 2341 KiB

Open AccessArticle

siRNA-Mediated MELK Knockdown Induces Accelerated Wound Healing with Increased Collagen Deposition

by Lukasz Szymanski, Sławomir Lewicki, Tomasz Markiewicz, Szczepan Cierniak, Jean-Pierre Tassan and Jacek Z. Kubiak

Int. J. Mol. Sci. 2023, 24(2), 1326; https://doi.org/10.3390/ijms24021326 - 10 Jan 2023

Cited by 3 | Viewed by 2747

Abstract

Skin wounds remain a significant problem for the healthcare system, affecting the clinical outcome, patients’ quality of life, and financial costs. Reduced wound healing times would improve clinical, economic, and social aspects for both patients and the healthcare system. Skin wound healing has been studied for years, but effective therapy that leads to accelerated wound healing remains to be discovered. This study aimed to evaluate the potential of MELK silencing to accelerate wound healing. A vectorless, transient knockdown of the MELK gene using siRNA was performed in a murine skin wound model. The wound size, total collagen, type 3 collagen, vessel size, vessel number, cell proliferation, cell apoptosis, number of mast cells, and immune infiltration by CD45, CD11b, CD45, and CD8a cells were evaluated. We observed that treatment with MELK siRNA leads to significantly faster wound closing associated with increased collagen deposition. Full article

(This article belongs to the Special Issue Recent Advances in Wound Healing)

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Review

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20 pages, 1061 KiB

Open AccessReview

Probiotics in Wound Healing

by Valentina Alexandra Bădăluță, Carmen Curuțiu, Lia Mara Dițu, Alina Maria Holban and Veronica Lazăr

Int. J. Mol. Sci. 2024, 25(11), 5723; https://doi.org/10.3390/ijms25115723 - 24 May 2024

Cited by 16 | Viewed by 6866

Abstract

Wound infections caused by opportunistic bacteria promote persistent infection and represent the main cause of delayed healing. Probiotics are acknowledged for their beneficial effects on the human body and could be utilized in the management of various diseases. They also possess the capacity to accelerate wound healing, due to their remarkable anti-pathogenic, antibiofilm, and immunomodulatory effects. Oral and topical probiotic formulations have shown promising openings in the field of dermatology, and there are various in vitro and in vivo models focusing on their healing mechanisms. Wound dressings embedded with prebiotics and probiotics are now prime candidates for designing wound healing therapeutic approaches to combat infections and to promote the healing process. The aim of this review is to conduct an extensive scientific literature review regarding the efficacy of oral and topical probiotics in wound management, as well as the potential of wound dressing embedding pre- and probiotics in stimulating the wound healing process. Full article

(This article belongs to the Special Issue Recent Advances in Wound Healing)

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18 pages, 1953 KiB

Open AccessReview

Current Knowledge and Perspectives of Phage Therapy for Combating Refractory Wound Infections

by Bo Wang, Lin Du, Baiping Dong, Erwen Kou, Liangzhe Wang and Yuanjie Zhu

Int. J. Mol. Sci. 2024, 25(10), 5465; https://doi.org/10.3390/ijms25105465 - 17 May 2024

Cited by 14 | Viewed by 3745

Abstract

Wound infection is one of the most important factors affecting wound healing, so its effective control is critical to promote the process of wound healing. However, with the increasing prevalence of multi-drug-resistant (MDR) bacterial strains, the prevention and treatment of wound infections are now more challenging, imposing heavy medical and financial burdens on patients. Furthermore, the diminishing effectiveness of conventional antimicrobials and the declining research on new antibiotics necessitate the urgent exploration of alternative treatments for wound infections. Recently, phage therapy has been revitalized as a promising strategy to address the challenges posed by bacterial infections in the era of antibiotic resistance. The use of phage therapy in treating infectious diseases has demonstrated positive results. This review provides an overview of the mechanisms, characteristics, and delivery methods of phage therapy for combating pathogenic bacteria. Then, we focus on the clinical application of various phage therapies in managing refractory wound infections, such as diabetic foot infections, as well as traumatic, surgical, and burn wound infections. Additionally, an analysis of the potential obstacles and challenges of phage therapy in clinical practice is presented, along with corresponding strategies for addressing these issues. This review serves to enhance our understanding of phage therapy and provides innovative avenues for addressing refractory infections in wound healing. Full article

(This article belongs to the Special Issue Recent Advances in Wound Healing)

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