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Focus on Wound Healing 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 7201

Special Issue Editor


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Guest Editor
Department of Experimental and Clinical Medicine, University of Florence, 50121 Firenze, FI, Italy
Interests: trauma surgery; space surgery; emergency surgery; damage associated molecular patterns in trauma; COVID-19 in pandemic time and surgery; the frail patient
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Special Issue Information

Dear Colleagues,

The skin is the largest organ of our body and protects it from mechanical damage, microbial infections, thermal injuries, and more, which is why its integrity and wound healing are so important for survival. Regulation of wound healing is a complex process that follows a sophisticated temporal sequence. In this issue, readers will find an overview of research on wound healing from different points of view, spanning from the molecular and biological aspects, wound care and treatment, to the role of immune innate response and tissue regeneration, also including burns, skin grafting, and infections. Additionally, other aspects must be considered, such as nutritional status, concomitant pathological, acute and/or chronic diseases, as well as recent achievements in local medications and closure techniques such as negative pressure therapy.

As volume 1 of Special Issue “Focus on Wound Healing” is successful. we reopen this issue again in the /International Journal of Molecular Sciences/ (https://www.mdpi.com/journal/ijms, ISSN 1422-0067, IF 6.208, JCR Category Q1). The aim of this second issue is to offer a general “landscape” of the delicate and complex process of wound healing. 

Dr. Desire' Pantalone
Guest Editor

Manuscript Submission Information

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Keywords

  • tissue repair mechanisms in wound healing
  • nutritional status in wound repair
  • photobiomodulation in wound healing
  • molecular mechanisms in wound healing
  • tissue regeneration
  • role of fibroblasts in wound healing
  • burns and wound healing
  • tissue repair by grafting
  • damage-associated molecular patterns and pathogen-associated molecular patterns in wound healing
  • hydrogel in wound repair and other local medications
  • mast cell activity in acute and chronic wound healing

Published Papers (4 papers)

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Research

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15 pages, 4303 KiB  
Article
Graft–Host Interaction and Its Effect on Wound Repair Using Mouse Models
by Nicole Garcia, Md Mostafizur Rahman, Carlos Luis Arellano, Ilia Banakh, Chen Yung-Chih, Karlheinz Peter, Heather Cleland, Cheng Hean Lo and Shiva Akbarzadeh
Int. J. Mol. Sci. 2023, 24(22), 16277; https://doi.org/10.3390/ijms242216277 - 13 Nov 2023
Viewed by 1141
Abstract
Autologous skin grafting has been commonly used in clinics for decades to close large wounds, yet the cellular and molecular interactions between the wound bed and the graft that mediates the wound repair are not fully understood. The aim of this study was [...] Read more.
Autologous skin grafting has been commonly used in clinics for decades to close large wounds, yet the cellular and molecular interactions between the wound bed and the graft that mediates the wound repair are not fully understood. The aim of this study was to better understand the molecular changes in the wound triggered by autologous and synthetic grafting. Defining the wound changes at the molecular level during grafting sets the basis to test other engineered skin grafts by design. In this study, a full-thickness skin graft (SKH-1 hairless) mouse model was established. An autologous full-thickness skin graft (FTSG) or an acellular fully synthetic Biodegradable Temporising Matrix (BTM) was grafted. The wound bed/grafts were analysed at histological, RNA, and protein levels during the inflammation (day 1), proliferation (day 5), and remodelling (day 21) phases of wound repair. The results showed that in this mouse model, similar to others, inflammatory marker levels, including Il-6, Cxcl-1, and Cxcl-5/6, were raised within a day post-wounding. Autologous grafting reduced the expression of these inflammatory markers. This was different from the wounds grafted with synthetic dermal grafts, in which Cxcl-1 and Cxcl-5/6 remained significantly high up to 21 days post-grafting. Autologous skin grafting reduced wound contraction compared to wounds that were left to spontaneously repair. Synthetic grafts contracted significantly more than FTSG by day 21. The observed wound contraction in synthetic grafts was most likely mediated at least partly by myofibroblasts. It is possible that high TGF-β1 levels in days 1–21 were the driving force behind myofibroblast abundance in synthetic grafts, although no evidence of TGF-β1-mediated Connective Tissue Growth Factor (CTGF) upregulation was observed. Full article
(This article belongs to the Special Issue Focus on Wound Healing 2.0)
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12 pages, 2995 KiB  
Article
Dual CXCR4/IL-10 Gene-Edited Human Amniotic Mesenchymal Stem Cells Exhibit Robust Therapeutic Properties in Chronic Wound Healing
by Seong-Ho Han, Dong-Sik Chae and Sung-Whan Kim
Int. J. Mol. Sci. 2022, 23(23), 15338; https://doi.org/10.3390/ijms232315338 - 5 Dec 2022
Cited by 6 | Viewed by 1545
Abstract
Although stem cells have attracted attention as a novel therapeutic solution for tissue regeneration, their minimal efficacy remains controversial. In the present study, we aimed to investigate the enhanced therapeutic property of CXCR4/IL-10 dual angiogenic/anti-inflammatory gene knock-in amniotic mesenchymal stem cells (AMM) in [...] Read more.
Although stem cells have attracted attention as a novel therapeutic solution for tissue regeneration, their minimal efficacy remains controversial. In the present study, we aimed to investigate the enhanced therapeutic property of CXCR4/IL-10 dual angiogenic/anti-inflammatory gene knock-in amniotic mesenchymal stem cells (AMM) in a wound-healing model. Dual CXCR4 and IL-10 genes were inserted into the AMM genome using transcription-activator-like effector nuclease (TALEN). Matrigel tube formation and anti-inflammatory effects were assessed in vitro, and efficacy was tested in vivo in a diabetic wound-healing model. CXCR4/IL-10-expressing amniotic MSCs (AMM/CI) strongly expressed CXCR4 and IL-10 genes and robustly promoted tube formation and anti-inflammatory potential. AMM/CI transplantation resulted in accelerated wound healing, as well as high engraftment and re-epithelialization potential. Transplanted AMM/CI also exhibited high angiogenic and decreased pro-inflammatory gene expression in the wound tissue, indicating direct therapeutic effects on wound healing. Taken together, these data indicate that dual angiogenic/anti-inflammatory gene knock-in may be a novel approach to enhance the therapeutic effects of stem cells, and transplantation of AMM/CI can be an alternative therapeutic option in chronic wound healing. Full article
(This article belongs to the Special Issue Focus on Wound Healing 2.0)
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Review

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18 pages, 1962 KiB  
Review
The Potential of MSC-Based Cell-Free Therapy in Wound Healing—A Thorough Literature Review
by Hui Ma, Wing-Sum Siu and Ping-Chung Leung
Int. J. Mol. Sci. 2023, 24(11), 9356; https://doi.org/10.3390/ijms24119356 - 27 May 2023
Cited by 13 | Viewed by 2568
Abstract
A wound is an interruption of the normal anatomic structure and function of the skin, which is critical in protecting against foreign pathogens, regulating body temperature and water balance. Wound healing is a complex process involving various phases, including coagulation, inflammation, angiogenesis, re-epithelialization, [...] Read more.
A wound is an interruption of the normal anatomic structure and function of the skin, which is critical in protecting against foreign pathogens, regulating body temperature and water balance. Wound healing is a complex process involving various phases, including coagulation, inflammation, angiogenesis, re-epithelialization, and re-modeling. Factors such as infection, ischemia, and chronic diseases such as diabetes can compromise wound healing, leading to chronic and refractory ulcers. Mesenchymal stem cells (MSCs) have been used to treat various wound models due to their paracrine activity (secretome) and extracellular vehicles (exosomes) that contain several molecules, including long non-coding RNAs (lncRNAs), micro-RNAs (miRNAs), proteins, and lipids. Studies have shown that MSCs-based cell-free therapy using secretome and exosomes has great potential in regenerative medicine compared to MSCs, as there are fewer safety concerns. This review provides an overview of the pathophysiology of cutaneous wounds and the potential of MSCs-based cell-free therapy in each phase of wound healing. It also discusses clinical studies of MSCs-based cell-free therapies. Full article
(This article belongs to the Special Issue Focus on Wound Healing 2.0)
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Other

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9 pages, 2867 KiB  
Technical Note
Rose Bengal Induced Photothrombosis in CAM Integrated Human Split Skin Grafts—A Feasibility Study
by Georg Kornhäusel, Christian Smolle, Kathrin Kreuzer, Lars-Peter Kamolz and Nassim Ghaffari-Tabrizi-Wizsy
Int. J. Mol. Sci. 2023, 24(4), 3689; https://doi.org/10.3390/ijms24043689 - 12 Feb 2023
Cited by 1 | Viewed by 1310
Abstract
Wound healing is a complex process requiring an adequate supply of the wound area with oxygen and nutrients by neo-vascularization, to renew tissue. Local ischemia can result in the formation of chronic wounds. Since there is a lack of wound healing models for [...] Read more.
Wound healing is a complex process requiring an adequate supply of the wound area with oxygen and nutrients by neo-vascularization, to renew tissue. Local ischemia can result in the formation of chronic wounds. Since there is a lack of wound healing models for ischemic wounds, we aimed to develop a new one, based on chick chorioallantoic membrane (CAM) integrated split skin grafts and induction of ischemia with photo-activating Rose Bengal (RB) in a two-part study: (1) investigation of the thrombotic effect of photo-activated RB in CAM vessels and (2) investigation of the influence of photo-activated RB on CAM integrated human split skin xenografts. In both study phases, we observed a typical pattern of vessel changes after RB activation with a 120 W 525/50 nm green cold light lamp in the region of interest: intravascular haemostasis and a decrease in vessel diameter within 10 min of treatment. In total, the diameter of 24 blood vessels was measured before and after 10 min of illumination. Mean relative reduction of vessel diameter after treatment was 34.8% (12.3%–71.4%; p < 0.001). The results indicate that the present CAM wound healing model can reproduce chronic wounds without inflammation due to the statistically significant reduction of blood flow in the selected area using RB. Combined with xenografted human split skin grafts, we established the set up for a new chronic wound healing model for the research of regenerative processes following ischemic damage of the tissue. Full article
(This article belongs to the Special Issue Focus on Wound Healing 2.0)
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