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New Molecular Insights into Scar and Wounds

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 (20 January 2025) | Viewed by 7985

Special Issue Editor


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Guest Editor
Department of Methodology, Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland
Interests: plastic surgery; wound healing; gene therapy; microsurgery; experimental surgery; flap physiology; neuroregeneration; eye-tracking

Special Issue Information

Dear Colleagues,

The complexity of wound healing and subsequent scarring triggers the need for both basic and translational studies in the field. The prevalence of wound healing impairments boosts the drive to an applicatory approach in the field.

Yet, since numerous physiological and molecular processes are involved in wound healing (e.g. inflammation, fibrosis, cell migration, angiogenesis, matrix remodeling, etc.), there are endless targets for novel therapies. Without deepening the knowledge of the mechanism of wound healing or scarring search for novel, or implementation of preexisting therapies may be hampered. Recent advancements in wound healing research showed increasing importance in deciphering the role of the HIF-1α pathway, along with further studies on certain cytokines like TGF-β IFN-γ. Controversies on macrophage M1/M2 shift and their targeting in wound healing are also addressed with intense research. The role of M2 macrophages and certain cytokines (especially TGF-β and IFN-γ) seems to be pivotal in scar maturation, which if disrupted, may produce hypertrophic scar or keloids. Exploration of these and many other mechanisms is particularly crucial in chronic wounds. Of those, most of the studies focus on diabetic wound healing, due to its challenging nature in management. Also, impaired immunological response, excessive matrix metalloproteinase (MMP) activity, explicit oxidative stress increase, and impaired remodeling lead to prolonged healing and poor scar quality. All of the above are profoundly studied and may pose a target for novel therapies. But for the improvement of the wound healing mechanisms, successful therapies are studied relying on woundbed augmentation with stem cells of different origins. Understanding the mechanism underlying their efficiency may lead to further exciting discoveries.  

Those topics are especially invited for submission in this Special Issue.

Thus, in this Special Issue authors are encouraged to submit papers that fill the gap in the knowledge of wound healing and scarring. Due to the aforementioned nature of the topic, a dual approach is needed for advancement in the fields—experimental use of novel pharmaceuticals or devices (wound dressings) followed by studies concerning exploration of the underlying mechanism of (un)successful therapies.

Articles that aim to contribute to this Special Issue should address the topic via well-designed studies. Papers should concern molecular aspects of wound healing—either in basic research or in. applicatory approach. Relevant and innovative systematic reviews and meta-analyses are also allowed for submission to this Special Issue.

Dr. Wiktor Pascal
Guest Editor

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Keywords

  • wound healing
  • chronic wound
  • diabetes 
  • scar
  • therapy
  • keyword
  • hypoxia
  • oxidative stress
  • fibrosis
  • molecular pathway
  • translational/applicatory studies
  • animal model
  • human model
  • in vitro
  • HIF1-alpha
  • TGF-beta
  • stem cells

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Published Papers (3 papers)

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Research

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20 pages, 2836 KiB  
Article
The Influence of N-Acetylcysteine-Enriched Hydrogels on Wound Healing in a Murine Model of Type II Diabetes Mellitus
by Albert Stachura, Marcin Sobczak, Karolina Kędra, Michał Kopka, Karolina Kopka and Paweł K. Włodarski
Int. J. Mol. Sci. 2024, 25(18), 9986; https://doi.org/10.3390/ijms25189986 - 16 Sep 2024
Viewed by 1519
Abstract
Diabetes mellitus (DM) severely impairs skin wound healing capacity, yet few treatment options exist to enhance this process. N-acetylcysteine (NAC) is an antioxidant that improves cellular proliferation and enhances wound healing in healthy animals, yet its use in the context of type II [...] Read more.
Diabetes mellitus (DM) severely impairs skin wound healing capacity, yet few treatment options exist to enhance this process. N-acetylcysteine (NAC) is an antioxidant that improves cellular proliferation and enhances wound healing in healthy animals, yet its use in the context of type II DM has not been studied. The aim of our research was to investigate the effect of topically applied NAC-enriched hydrogels on wound healing in a leptin-deficient murine wound model. Four excisional wounds were created on the backs of 20 db/db mice and were subsequently treated with hydrogels containing NAC at concentrations of 5%, 10% and 20% or placebo (control). Healing was monitored for 28 days; photographs of the wounds were taken on every third day. Wound tissues were harvested on days 3, 7, 14 and 28 to undergo histological examinations. Wounds treated with 5% NAC showed improved wound closure speed accompanied by an increased dermal proliferation area on microscopic assessment compared with other groups. Higher concentrations of NAC failed to show a beneficial effect on wound healing. 5% NAC improved early stages of wound healing in a murine model of type II DM by increasing wound closure speed, likely mediated by improved dermal proliferation. Full article
(This article belongs to the Special Issue New Molecular Insights into Scar and Wounds)
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14 pages, 5837 KiB  
Article
Pre-Incisional and Multiple Intradermal Injection of N-Acetylcysteine Slightly Improves Incisional Wound Healing in an Animal Model
by Wiktor Pascal, Antoni Smoliński, Mateusz Gotowiec, Marta Wojtkiewicz, Albert Stachura, Kacper Pełka, Michał Kopka, Kyle P. Quinn, Alan E. Woessner, Dariusz Grzelecki and Paweł Włodarski
Int. J. Mol. Sci. 2024, 25(10), 5200; https://doi.org/10.3390/ijms25105200 - 10 May 2024
Cited by 1 | Viewed by 2236
Abstract
The objective of this study was to investigate if delivering multiple doses of N-acetylcysteine (NAC) post-surgery in addition to pre-incisional administration significantly impacts the wound healing process in a rat model. Full-thickness skin incisions were carried out on the dorsum of 24 Sprague-Dawley [...] Read more.
The objective of this study was to investigate if delivering multiple doses of N-acetylcysteine (NAC) post-surgery in addition to pre-incisional administration significantly impacts the wound healing process in a rat model. Full-thickness skin incisions were carried out on the dorsum of 24 Sprague-Dawley rats in six locations. Fifteen minutes prior to the incision, half of the sites were treated with a control solution, with the wounds on the contralateral side treated with solutions containing 0.015%, 0.03% and 0.045% of NAC. In the case of the NAC treated group, further injections were given every 8 h for three days. On days 3, 7, 14 and 60 post-op, rats were sacrificed to gather material for the histological analysis, which included histomorphometry, collagen fiber organization analysis, immunohistochemistry and Abramov scale scoring. It was determined that scars treated with 0.015% NAC had significantly lower reepithelization than the control at day 60 post-op (p = 0.0018). Scars treated with 0.045% NAC had a significantly lower collagen fiber variance compared to 0.015% NAC at day 14 post-op (p = 0.02 and p = 0.04) and a lower mean scar width than the control at day 60 post-op (p = 0.0354 and p = 0.0224). No significant differences in the recruitment of immune cells and histological parameters were found. The results point to a limited efficacy of multiple NAC injections post-surgery in wound healing. Full article
(This article belongs to the Special Issue New Molecular Insights into Scar and Wounds)
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Review

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17 pages, 4497 KiB  
Review
Epidermal Growth Factor Intralesional Delivery in Chronic Wounds: The Pioneer and Standalone Technique for Reversing Wound Chronicity and Promoting Sustainable Healing
by Jorge Berlanga-Acosta, Ariana Garcia-Ojalvo, Jose Fernández-Montequin, Viviana Falcon-Cama, Nelson Acosta-Rivero, Gerardo Guillen-Nieto, Merardo Pujol-Ferrer, Miladys Limonta-Fernandez, Marta Ayala-Avila and Elof Eriksson
Int. J. Mol. Sci. 2024, 25(20), 10883; https://doi.org/10.3390/ijms252010883 - 10 Oct 2024
Cited by 2 | Viewed by 3449
Abstract
The early expectations about growth factors’ (GFs’) discovery as an undisputed therapeutic solution for chronic wounds progressively eclipsed when they failed to accelerate acute wound closure and restore the healing trajectory of stagnant ulcers. Critical knowledge about chronic wound biology and GF pharmacology [...] Read more.
The early expectations about growth factors’ (GFs’) discovery as an undisputed therapeutic solution for chronic wounds progressively eclipsed when they failed to accelerate acute wound closure and restore the healing trajectory of stagnant ulcers. Critical knowledge about chronic wound biology and GF pharmacology was a conundrum at that time. Diabetes undermines keratinocytes’ and fibroblasts’ physiology, impairing skin healing abilities. Diabetic ulcers, as other chronic wounds, are characterized by hyperinflammation, unbalanced proteolytic activity, catabolism, and free radical cytotoxicity. This hostile scenario for the chemical stability, integrity, and functionality of GFs led to the conclusion that topical administration may jeopardize GFs’ clinical effectiveness. Epidermal growth factor (EGF) has a proximal position in tissues homeostasis by activating survival and mitogenic pathways from embryonic life to adulthood. Seminal experiments disclosed unprecedented pharmacological bounties of parenterally administered EGF. Accordingly, the experience accumulated for more than 20 years of EGF intralesional infiltration of diabetic wound bottoms and edges has translated into sustained healing responses, such as low recurrences and amputation rates. This delivery route, in addition to being safe and tolerated, has shown to restore a variety of circulating biochemical markers ordinarily disturbed in diabetic conditions. EGF infiltration triggers a cascade of local fibroblast reactions, supporting its molecular integrity, prolonged mean residence time, and ultimately eliciting its receptor trafficking and nuclear translocation. The intralesional delivery route seems to warrant that EGF reaches wound fibroblasts’ epigenetic core, mitigating the consequences of metabolic memory imprinting. Full article
(This article belongs to the Special Issue New Molecular Insights into Scar and Wounds)
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