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Cellular and Molecular Mechanisms on Wound Healing
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Cellular and Molecular Mechanisms 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: closed (20 March 2025) | Viewed by 8528

Special Issue Editors

Prof. Dr. Manuela Martins-Green

E-Mail Website
Guest Editor
Department of Cell Biology & Neuroscience, University of California, Riverside, CA 92521, USA
Interests: wound repair and regeneration; prostate cancer growth and metastasis
Dr. Athena Soulika

E-Mail Website
Guest Editor
Shriners Hospitals for Children-Northern California, Sacramento, CA, USA
Interests: wound healing; inflammation; immune responses; myeloid cells; burn wound injury; chemokines; cytokines
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Understanding the complex processes involved in wound healing is profoundly important because proper responses to injuries and the triggering of healing are critical for survival.  Wound healing in general follows four distinct phases: re-establishing hemostasis, inflammation, the development of healing tissue to repair the damage, and the remodeling of newly formed tissue to restore the original tissue. Responses to injury and healing occur in all parts of the body. Internal-tissue wound healing is generally not faced with microorganism infection, whereas the healing of skin wounds involves infection more often than not. Despite the numerous studies designed to understand acute/normal wound healing processes, the findings have not significantly informed the changes that occur when wounds do not heal normally or do not heal at all. In this Special Issue, we endeavor to present reviews of the findings that we have accumulated on the specific processes of acute/normal healing, exploring the molecular mechanisms of wound healing and what goes array when wounds do not heal or heal abnormally.

Prof. Dr. Manuela Martins-Green
Dr. Athena Soulika
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.

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Keywords

  • inflammation
  • re-epithelialization
  • scar formation
  • regeneration
  • hypertrophic scar
  • chronic wounds

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Published Papers (4 papers)

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Research

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17 pages, 5638 KiB  
Article
MicroRNA Signature in an In Vitro Keratinocyte Model of Diabetic Wound Healing
by Hsin-Chung Tsai, Gary Ro-Lin Chang, Min-Che Tung, Min-Yu Tu, I-Chien Chen, Yu-Hsien Liu, Abdulkadir Cidem and Chuan-Mu Chen
Int. J. Mol. Sci. 2024, 25(18), 10125; https://doi.org/10.3390/ijms251810125 - 20 Sep 2024
Viewed by 1247
Abstract
Treating diabetic wounds effectively remains a significant clinical challenge. Emerging studies suggest that microRNAs (miRNAs) play crucial roles in various physiological and pathological processes and hold promise as therapeutic tools. This study investigates the miRNA expression profile in keratinocytes using a cell model [...] Read more.
Treating diabetic wounds effectively remains a significant clinical challenge. Emerging studies suggest that microRNAs (miRNAs) play crucial roles in various physiological and pathological processes and hold promise as therapeutic tools. This study investigates the miRNA expression profile in keratinocytes using a cell model of diabetic wounds. Microarray analysis revealed that 43 miRNAs from wounded keratinocytes incubated under diabetic conditions (high glucose/hypoxia) exhibited a two-fold change in expression compared to those incubated under normal conditions (low glucose/normoxia). Quantitative RT-PCR confirmed significant differences in the expression of eight miRNAs, with miR-3138 and miR-3679-5p being further analyzed for their roles in keratinocyte migration. Transfection with a miR-3138 mimic and a miR-3679-5p inhibitor indicated that upregulation of miR-3138 and downregulation of miR-3679-5p enhance keratinocyte migration in both normal and diabetic wounds. Pathway and gene ontology (GO) analyses identified potential pathways and functional annotations associated with miR-3138 and miR-3679-5p in diabetic wound healing. Potential human gene targets of miR-3138 and miR-3679-5p were predicted using a three-way comparison of the TargetScan, miRDB, and DIANA databases. This study elucidates the miRNA expression signature of human keratinocytes in a diabetes-like environment, providing deeper insights into the pathogenesis of diabetic wounds. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms on Wound Healing)
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Review

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18 pages, 1545 KiB  
Review
Harnessing Mesenchymal Stromal Cells for Advanced Wound Healing: A Comprehensive Review of Mechanisms and Applications
by Khrystyna Nasadiuk, Tomasz Kolanowski, Cezary Kowalewski, Katarzyna Wozniak, Tomasz Oldak and Natalia Rozwadowska
Int. J. Mol. Sci. 2025, 26(1), 199; https://doi.org/10.3390/ijms26010199 - 29 Dec 2024
Cited by 1 | Viewed by 1822
Abstract
Chronic wounds and injuries remain a substantial healthcare challenge, with significant burdens on patient quality of life and healthcare resources. Mesenchymal stromal cells (MSCs) present an innovative approach to enhance tissue repair and regeneration in the context of wound healing. The intrinsic presence [...] Read more.
Chronic wounds and injuries remain a substantial healthcare challenge, with significant burdens on patient quality of life and healthcare resources. Mesenchymal stromal cells (MSCs) present an innovative approach to enhance tissue repair and regeneration in the context of wound healing. The intrinsic presence of MSCs in skin tissue, combined with their roles in wound repair, ease of isolation, broad secretory profile, and low immunogenicity, makes them especially promising for treating chronic wounds. This review explores the current landscape of MSC application, focusing on preclinical and clinical data across chronic wounds, diabetic ulcers, burns, non-union bone fractures, lower extremity venous ulcers, pressure ulcers, and genetic skin conditions like epidermolysis bullosa. Special emphasis is given to the mechanisms through which MSCs exert their regenerative effects, underscoring their potential in advancing wound healing therapies and supporting the broader field of regenerative medicine. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms on Wound Healing)
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19 pages, 1844 KiB  
Review
The Potential of Mesenchymal Stem/Stromal Cells in Diabetic Wounds and Future Directions for Research and Therapy—Is It Time for Use in Everyday Practice?
by Damian Sieńko, Ilona Szabłowska-Gadomska, Anna Nowak-Szwed, Stefan Rudziński, Maksymilian Gofron, Przemysław Zygmunciak, Małgorzata Lewandowska-Szumieł, Wojciech Stanisław Zgliczyński, Leszek Czupryniak and Beata Mrozikiewicz-Rakowska
Int. J. Mol. Sci. 2024, 25(22), 12171; https://doi.org/10.3390/ijms252212171 - 13 Nov 2024
Cited by 1 | Viewed by 1703
Abstract
The treatment of diabetic wounds is impaired by the intricate nature of diabetes and its associated complications, necessitating novel strategies. The utilization of mesenchymal stem/stromal cells (MSCs) as a therapeutic modality for chronic and recalcitrant wounds in diabetic patients is an active area [...] Read more.
The treatment of diabetic wounds is impaired by the intricate nature of diabetes and its associated complications, necessitating novel strategies. The utilization of mesenchymal stem/stromal cells (MSCs) as a therapeutic modality for chronic and recalcitrant wounds in diabetic patients is an active area of investigation aimed at enhancing its therapeutic potential covering tissue regeneration. The threat posed to the patient and their environment by the presence of a diabetic foot ulcer (DFU) is so significant that any additional therapeutic approach that opens new pathways to halt the progression of local changes, which subsequently lead to a generalized inflammatory process, offers a chance to reduce the risk of amputation or even death. This article explores the potential of MSCs in diabetic foot ulcer treatment, examining their mechanisms of action, clinical application challenges, and future directions for research and therapy. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms on Wound Healing)
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13 pages, 1687 KiB  
Review
Assessing Animal Models to Study Impaired and Chronic Wounds
by Shayan Saeed and Manuela Martins-Green
Int. J. Mol. Sci. 2024, 25(7), 3837; https://doi.org/10.3390/ijms25073837 - 29 Mar 2024
Cited by 6 | Viewed by 3099
Abstract
Impaired healing wounds do not proceed through the normal healing processes in a timely and orderly manner, and while they do eventually heal, their healing is not optimal. Chronic wounds, on the other hand, remain unhealed for weeks or months. In the US [...] Read more.
Impaired healing wounds do not proceed through the normal healing processes in a timely and orderly manner, and while they do eventually heal, their healing is not optimal. Chronic wounds, on the other hand, remain unhealed for weeks or months. In the US alone, chronic wounds impact ~8.5 million people and cost ~USD 28–90 billion per year, not accounting for the psychological and physical pain and emotional suffering that patients endure. These numbers are only expected to rise in the future as the elderly populations and the incidence of comorbidities such as diabetes, hypertension, and obesity increase. Over the last few decades, scientists have used a variety of approaches to treat chronic wounds, but unfortunately, to date, there is no effective treatment. Indeed, while there are thousands of drugs to combat cancer, there is only one single drug approved for the treatment of chronic wounds. This is in part because wound healing is a very complex process involving many phases that must occur sequentially and in a timely manner. Furthermore, models that fully mimic human chronic wounds have not been developed. In this review, we assess various models currently being used to study the biology of impaired healing and chronic non-healing wounds. Among them, this paper also highlights one model which shows significant promise; this model uses aged and obese db/db−/− mice and the chronic wounds that develop show characteristics of human chronic wounds that include increased oxidative stress, chronic inflammation, damaged microvasculature, abnormal collagen matrix deposition, a lack of re-epithelialization, and the spontaneous development of multi-bacterial biofilm. We also discuss how important it is that we continue to develop chronic wound models that more closely mimic those of humans and that can be used to test potential treatments to heal chronic wounds. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms on Wound Healing)
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