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Molecular and Cellular Perspectives on Wound Healing
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Molecular and Cellular Perspectives on Wound Healing

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: 20 June 2025 | Viewed by 8953

Special Issue Editors

Dr. Ermelindo C. Leal

E-Mail Website
Guest Editor
Center for Neuroscience and Cell Biology, Faculty of Medicine, University of Coimbra, Rua Larga, Polo I, 1st Floor, 3004-504 Coimbra, Portugal
Interests: diabetes; diabetic complications; wound healing; immunomodulation; inflammation; angiogenesis; stem cells; infection; aging; quality control; metabolism; signaling pathways
Special Issues, Collections and Topics in MDPI journals
Dr. Eugenia Carvalho

E-Mail Website
Guest Editor
Center for Neuroscience and Cell Biology, Faculty of Medicine, University of Coimbra, Rua Larga, Polo I, 1st Floor, 3004-504 Coimbra, Portugal
Interests: diabetes and complications; wound healing; obesity; insulin resistance; inflammation; immunosuppressive agents; metabolism; signaling pathways

Special Issue Information

Dear Colleagues,

Wound healing is a complex biological process that entails several well-coordinated sequential stages regulated by numerous cellular and molecular factors to efficiently repair damaged tissue. Alterations to these cellular and molecular events can lead to impaired wound healing, resulting in chronic wounds or less functional regenerated tissue. Therefore, understanding the mechanisms of wound healing will allow for the development of innovative approaches aimed to improve tissue regeneration.

In this Special Issue, we welcome both basic and translational research on the cellular and molecular mechanisms of wound healing, as well as biomarkers and novel molecules with the potential to become specific targets for future therapeutic interventions, and the mechanisms behind wound healing failure. We encourage the submission of original research articles or critical reviews and aim to discuss the future directions of emerging research.

Dr. Ermelindo C. Leal
Dr. Eugenia Carvalho
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

 

Keywords

  • chronic wound healing
  • scarring
  • biomarkers
  • inflammation
  • angiogenesis
  • infection
  • extracellular matrix
  • biomaterials
  • tissue regeneration
  • therapeutic targets
  • innovative therapies

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Published Papers (4 papers)

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Research

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19 pages, 3855 KiB  
Article
Bone Morphogenetic Protein 7 Improves Wound Healing in Diabetes by Decreasing Inflammation and Promoting M2 Macrophage Polarization
by Jessica Da Silva, Ana Figueiredo, Yu-Hua Tseng, Eugenia Carvalho and Ermelindo C. Leal
Int. J. Mol. Sci. 2025, 26(5), 2036; https://doi.org/10.3390/ijms26052036 - 26 Feb 2025
Viewed by 1059
Abstract
Diabetic foot ulcers (DFUs) are a devastating complication of diabetes, presenting limited treatment success rates due to their complex pathophysiology. Bone morphogenetic protein 7 (BMP7) confers tissue protective and regenerative functions, but its potential role in diabetic wound healing is unknown. The aim [...] Read more.
Diabetic foot ulcers (DFUs) are a devastating complication of diabetes, presenting limited treatment success rates due to their complex pathophysiology. Bone morphogenetic protein 7 (BMP7) confers tissue protective and regenerative functions, but its potential role in diabetic wound healing is unknown. The aim of this study was to investigate the effects of topical BMP7 treatment in wound healing using a streptozotocin-induced diabetic mouse model. The expression of markers of wound healing progression were detected using RT-PCR or immunohistochemistry. Overall, BMP7 improved wound closure, as well as maturation of granulation tissue and collagen deposition, as evidenced by hematoxylin and eosin and Masson’s trichrome histological analysis. The expression of inflammatory markers (IL-6, TNF-α) and matrix metalloproteinase-9 were decreased in BMP7-treated wounds, together with the number of pro-inflammatory M1 macrophages and T lymphocytes. The number of anti-inflammatory M2 macrophages was increased in BMP7-treated wounds. Moreover, BMP7 decreased oxidative stress and increased Ki67+ cells and CD31+ cells, indicating induced proliferation and angiogenesis in the wound bed compared to the control wounds. Finally, BMP7 activated the ERK pathway and suppressed the p38 pathway in diabetic wounds. Together, our data suggest that BMP7 enhanced skin wound healing in diabetes by decreasing local inflammation and oxidative stress, which promoted a regenerative environment for collagen deposition, wound maturation, cell proliferation, and angiogenesis. These findings underline BMP7 as a potential therapeutic agent for the treatment of skin wounds in diabetes. Full article
(This article belongs to the Special Issue Molecular and Cellular Perspectives on Wound Healing)
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17 pages, 2402 KiB  
Article
Dysregulated S100A9 Expression Impairs Matrix Deposition in Chronic Wounds
by Sandra Franz, Marta Torregrossa, Ulf Anderegg, Anastasia Ertel and Anja Saalbach
Int. J. Mol. Sci. 2024, 25(18), 9980; https://doi.org/10.3390/ijms25189980 - 16 Sep 2024
Viewed by 1341
Abstract
Chronic non-healing wounds are characterized by persistent inflammation, excessive matrix-degrading proteolytic activity and compromised extracellular matrix (ECM) synthesis. Previous studies showed that S100A8/A9 are strongly dysregulated in delayed wound healing and impair the proper function of immune cells. Here, we demonstrate an unrecognized [...] Read more.
Chronic non-healing wounds are characterized by persistent inflammation, excessive matrix-degrading proteolytic activity and compromised extracellular matrix (ECM) synthesis. Previous studies showed that S100A8/A9 are strongly dysregulated in delayed wound healing and impair the proper function of immune cells. Here, we demonstrate an unrecognized pathological function of S100A9 overexpression in wounds with impaired healing that directly affects ECM functions in fibroblasts. S100A9 was analyzed in two different mouse models mimicking the features of the two most prominent types of non-healing wounds in humans. Db/db mice were used as a model for diabetes-associated impaired wound healing. Iron-overloaded mice were used to mimic the conditions of impaired wound healing in chronic venous leg ulcers. The skin wounds of both mouse models are characterized by delayed wound closure, high and sustained expression of pro-inflammatory mediators and a substantially decreased ECM deposition, all together the hallmarks of non-healing wounds in humans. The wounds of both mouse models also present a solid and prolonged expression of S100A8 and S100A9 that coincides with a compromised ECM deposition and that was confirmed in chronic wounds in humans. Mechanistically, we reveal that S100A9 directly affects ECM deposition by shifting the balance of expression of ECM proteins and ECM degrading enzymes in fibroblasts via toll-like-receptor 4-dependent signaling. Consequently, blocking S100A9 during delayed wound healing in db/db mice restores fibroblast ECM functions eliciting increased matrix deposition. Our data indicate that the dysregulation of S100A9 directly contributes to a compromised ECM deposition in chronic wounds and further suggests S100A9 as a promising therapeutic target to improve tissue repair in chronic wounds. Full article
(This article belongs to the Special Issue Molecular and Cellular Perspectives on Wound Healing)
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10 pages, 2382 KiB  
Article
LincRNA-EPS Promotes Proliferation of Aged Dermal Fibroblast by Inducing CCND1
by Liping Zhang, Iris C. Wang, Songmei Meng and Junwang Xu
Int. J. Mol. Sci. 2024, 25(14), 7677; https://doi.org/10.3390/ijms25147677 - 12 Jul 2024
Cited by 1 | Viewed by 1435
Abstract
The aging process is linked to numerous cellular changes, among which are modifications in the functionality of dermal fibroblasts. These fibroblasts play a crucial role in sustaining the healing of skin wounds. Reduced cell proliferation is a hallmark feature of aged dermal fibroblasts. [...] Read more.
The aging process is linked to numerous cellular changes, among which are modifications in the functionality of dermal fibroblasts. These fibroblasts play a crucial role in sustaining the healing of skin wounds. Reduced cell proliferation is a hallmark feature of aged dermal fibroblasts. Long intergenic non-coding RNA (lincRNAs), such as LincRNA-EPS (Erythroid ProSurvival), has been implicated in various cellular processes. However, its role in aged dermal fibroblasts and its impact on the cell cycle and its regulator, Cyclin D1 (CCND1), remains unclear. Primary dermal fibroblasts were isolated from the skin of 17-week-old (young) and 88-week-old (aged) mice. Overexpression of LincRNA-EPS was achieved through plasmid transfection. Cell proliferation was detected using the MTT assay. Real-time PCR was used to quantify relative gene expressions. Our findings indicate a noteworthy decline in the expression of LincRNA-EPS in aged dermal fibroblasts, accompanied by reduced levels of CCND1 and diminished cell proliferation in these aging cells. Significantly, the overexpression of LincRNA-EPS in aged dermal fibroblasts resulted in an upregulation of CCND1 expression and a substantial increase in cell proliferation. Mechanistically, LincRNA-EPS induces CCND1 expression by sequestering miR-34a, which was dysregulated in aged dermal fibroblasts, and directly targeting CCND1. These outcomes underscore the crucial role of LincRNA-EPS in regulating CCND1 and promoting cell proliferation in aged dermal fibroblasts. Our study provides novel insights into the molecular mechanisms underlying age-related changes in dermal fibroblasts and their implications for skin wound healing. The significant reduction in LincRNA-EPS expression in aged dermal fibroblasts and its ability to induce CCND1 expression and enhance cell proliferation highlight its potential as a therapeutic target for addressing age-related skin wound healing. Full article
(This article belongs to the Special Issue Molecular and Cellular Perspectives on Wound Healing)
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Review

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24 pages, 4979 KiB  
Review
Hydrogel Wound Dressings Accelerating Healing Process of Wounds in Movable Parts
by Pengcheng Yu, Liqi Wei, Zhiqi Yang, Xin Liu, Hongxia Ma, Jian Zhao, Lulu Liu, Lili Wang, Rui Chen and Yan Cheng
Int. J. Mol. Sci. 2024, 25(12), 6610; https://doi.org/10.3390/ijms25126610 - 15 Jun 2024
Cited by 14 | Viewed by 4708
Abstract
Skin is the largest organ in the human body and requires proper dressing to facilitate healing after an injury. Wounds on movable parts, such as the elbow, knee, wrist, and neck, usually undergo delayed and inefficient healing due to frequent movements. To better [...] Read more.
Skin is the largest organ in the human body and requires proper dressing to facilitate healing after an injury. Wounds on movable parts, such as the elbow, knee, wrist, and neck, usually undergo delayed and inefficient healing due to frequent movements. To better accommodate movable wounds, a variety of functional hydrogels have been successfully developed and used as flexible wound dressings. On the one hand, the mechanical properties, such as adhesion, stretchability, and self-healing, make these hydrogels suitable for mobile wounds and promote the healing process; on the other hand, the bioactivities, such as antibacterial and antioxidant performance, could further accelerate the wound healing process. In this review, we focus on the recent advances in hydrogel-based movable wound dressings and propose the challenges and perspectives of such dressings. Full article
(This article belongs to the Special Issue Molecular and Cellular Perspectives on Wound Healing)
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