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Recent Advances in Wound Healing: 2nd Edition
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Recent Advances in Wound Healing: 2nd Edition

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: 20 August 2025 | Viewed by 6431

Special Issue Editors

Dr. Alina Maria Holban

E-Mail Website
Guest Editor
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
Special Issues, Collections and Topics in MDPI journals
Dr. Carmen Curutiu

E-Mail Website
Guest Editor
Department of Microbiology, Faculty of Biology, University of Bucharest, 030018 București, Romania
Interests: microbiology; immunology; cellular biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are excited to announce the second edition of our Special Issue, “Recent Advances in Wound Healing”. The successful first edition of this thematic Special Issue showcased a range of interesting contributions and discussions (https://www.mdpi.com/journal/ijms/special_issues/F5X4ERFM6E).

Wound healing represents one of the most complex processes in the body and subjects the organism to the following sequential stages: haemostasias, inflammation, proliferation, and remodeling. Many cells in the body (platelets, macrophages, neutrophils, fibroblasts, and epidermal cells) are involved in this well-coordinated process. Any change in external or internal factors can disrupt the process, leading to the appearance of chronic wounds, which results in incomplete healing, the recurrence of the infection process, and a continuous need for treatment. This places an overwhelming burden on both the patient and the medical system. Due to the complexity of the process, a multidisciplinary approach to diagnosis and treatment is often required. Since many aspects of chronic wound healing are still a long way from being completely understand, our aim for this collection of papers is to highlight the progress that is currently being made by researchers in this field, as well as data from clinicians regarding the pathophysiology of wounds (acute or chronic) and the healing modalities currently available for these patients. Recent developments in the management of wound healing will also be addressed, such as new techniques for wound debridement, the development of topical antiseptics and antimicrobials for the fight 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 including stem cells and gene therapy.

Dr. Alina Maria Holban
Dr. Carmen Curutiu
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

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

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Published Papers (6 papers)

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Research

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20 pages, 6196 KiB  
Article
Phenotypic and Genotypic Bacterial Virulence and Resistance Profiles in Hidradenitis Suppurativa
by Corina Ioana Cucu, Călin Giurcăneanu, Elena Poenaru, Liliana Gabriela Popa, Mircea Ioan Popa, Mariana Carmen Chifiriuc, Veronica Lazăr, Alina Maria Holban, Irina Gheorghe-Barbu, Andrei-Alexandru Muntean, Costin Ștefan Caracoti and Mara Mădălina Mihai
Int. J. Mol. Sci. 2025, 26(8), 3502; https://doi.org/10.3390/ijms26083502 - 9 Apr 2025
Viewed by 384
Abstract
Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition, primarily affecting young individuals, with a significant impact on their quality of life due to recurrent, painful nodules, abscesses, and oozing sinus tracts, primarily affecting intertriginous areas. The pathogenesis of HS is multifactorial, involving [...] Read more.
Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition, primarily affecting young individuals, with a significant impact on their quality of life due to recurrent, painful nodules, abscesses, and oozing sinus tracts, primarily affecting intertriginous areas. The pathogenesis of HS is multifactorial, involving a complex interplay between genetic predisposition, immune dysregulation, microbial, and environmental factors. While it is known that cutaneous and gut microbiome contribute to innate immune dysregulation in HS, their precise involvement in disease pathogenesis remains unclear. Despite several studies investigating the microbiome of HS lesions, either by culture-dependent or independent methods, there is no data available on the interplay between bacterial virulence profiles, clinical manifestations, and the host immune response. This study aimed to explore the phenotypic and genotypic resistance and virulence profiles of microorganisms isolated from HS lesions (including the expression of soluble virulence factors and the ability to develop biofilms), with a special focus on Staphylococcus aureus (S. aureus), one of the most frequent infectious agents of HS. A total of 92 bacterial strains, belonging to 20 different bacterial species, were isolated from the HS lesions of 23 patients. The strains of Staphylococcus, Corynebacterium, and Enterococcus expressed the highest levels of soluble virulence factors, such as hemolysins, lecithinase, and lipase, which are involved in bacterial persistence, local invasivity, and tissue damage. Moreover, a significant variation among bacterial species was noted regarding the capacity to develop biofilms, with a potential impact on disease chronicization, bacterial tolerance to antibiotics, and immune defense mechanisms. The genetic characterization of methicillin-resistant staphylococci revealed the presence of adhesins, hemolysin and enterotoxin genes as well as methicillin and macrolides resistance genes. Our findings highlight the critical role of virulence determinants, including bacterial biofilms, in HS pathogenesis, emphasizing the need for targeted therapeutic strategies to disrupt biofilms and mitigate infection severity. Full article
(This article belongs to the Special Issue Recent Advances in Wound Healing: 2nd Edition)
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29 pages, 4698 KiB  
Article
In Vitro Studies of the Effect of Oil Emulsions from Transgenic Flax Varieties on the Treatment of Wound Healing and Care of Human Skin with the Tendency to Inflammation
by Izabela Jęśkowiak-Kossakowska, Tomasz Gębarowski, Katarzyna Skórkowska-Telichowska and Benita Wiatrak
Int. J. Mol. Sci. 2025, 26(6), 2544; https://doi.org/10.3390/ijms26062544 - 12 Mar 2025
Viewed by 708
Abstract
Excessive amounts of free-oxygen radicals produced during inflammation induce oxidative stress and lead to cell damage, thus delaying the transition of inflammation into the proliferation in the wound healing process. Oxidative stress on skin cells also plays an important role in the pathogenesis [...] Read more.
Excessive amounts of free-oxygen radicals produced during inflammation induce oxidative stress and lead to cell damage, thus delaying the transition of inflammation into the proliferation in the wound healing process. Oxidative stress on skin cells also plays an important role in the pathogenesis of inflammatory skin diseases. The aim of the planned in vitro studies was to assess the mechanisms of regenerative action and protection of cells against oxidative stress of three oil emulsions from transgenic (GMO) flax varieties M, B, and MB and a linseed emulsion from traditional NIKE linseed oil. Antioxidant and gene-protective properties were identified for the tested oil emulsions in a healthy cell model and in an in vitro model of cells under oxidative stress. The wound-healing regenerative potential of these linseed emulsions was also assessed in the proliferation, cell cycle, migration, and apoptosis and necrosis assays. The conducted research presented that the tested transgenic oil emulsions are safe for human skin because they do not induce the proliferation of skin cancer cells and, at the same time, induce the migration processes of normal human skin cells. Additionally, their use increases the ability to eliminate damaged cells. Transgenic linseed oils provide a gene-protective effect and an increased antioxidant effect, resulting in increased protection of skin cells against oxidative stress, which plays an important role in the pathogenesis of atopic dermatitis and psoriasis. Linen emulsion B has the best regenerative and protective properties against human epidermis cancer, which is probably due to the presence of an increased amount of stigmasterol in its composition along with the appropriate content of polyphenol compounds, as well as an increased amount of oleic and linoleic acids. Full article
(This article belongs to the Special Issue Recent Advances in Wound Healing: 2nd Edition)
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17 pages, 4710 KiB  
Article
Endothelial Dysfunction and Impaired Wound Healing Following Radiation Combined Skin Wound Injury
by Li Wang, Bin Lin, Min Zhai, Lisa Hull, Wanchang Cui and Mang Xiao
Int. J. Mol. Sci. 2024, 25(23), 12498; https://doi.org/10.3390/ijms252312498 - 21 Nov 2024
Viewed by 974
Abstract
Currently, there are no U.S. Food and Drug Administration (FDA)-approved medical countermeasures (MCMs) for radiation combined injury (RCI), partially due to limited understanding of its mechanisms. Our previous research suggests that endothelial dysfunction may contribute to a poor prognosis of RCI. In this [...] Read more.
Currently, there are no U.S. Food and Drug Administration (FDA)-approved medical countermeasures (MCMs) for radiation combined injury (RCI), partially due to limited understanding of its mechanisms. Our previous research suggests that endothelial dysfunction may contribute to a poor prognosis of RCI. In this study, we demonstrated an increased risk of mortality, body weight loss, and delayed skin wound healing in RCI mice compared to mice with skin wounds alone or radiation injury (RI) 30 days post-insult. Furthermore, we evaluated biomarkers of endothelial dysfunction, inflammation, and impaired wound healing in mice at early time points after RCI. Mice were exposed to 9.0 Gy total-body irradiation (TBI) followed by skin wound. Samples were collected on days 3, 7, and 14 post-TBI. Endothelial dysfunction markers were measured by ELISA, and skin wound healing was assessed histologically. Our results show that endothelial damage and inflammation are more severe and persistent in the RCI compared to the wound-alone group. Additionally, RCI impairs granulation tissue formation, reduces myofibroblast presence, and delays collagen deposition, correlating with more severe endothelial damage. TGF signaling may play a key role in this impaired healing. These findings suggest that targeting the endothelial dysfunction and TGF-β pathways may provide potential therapeutic strategies for improving delayed wound healing in RCI, which could subsequently influence outcomes such as survival after RCI. Full article
(This article belongs to the Special Issue Recent Advances in Wound Healing: 2nd Edition)
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19 pages, 4917 KiB  
Article
Amino Acid-Based Protein-Mimic Hydrogel Incorporating Pro-Regenerative Lipid Mediator and Microvascular Fragments Promotes the Healing of Deep Burn Wounds
by Yan Lu, Shanchun Su, Chih-Chang Chu, Yuichi Kobayashi, Abdul-Razak Masoud, Hongying Peng, Nathan Lien, Mingyu He, Christopher Vuong, Ryan Tran and Song Hong
Int. J. Mol. Sci. 2024, 25(19), 10378; https://doi.org/10.3390/ijms251910378 - 26 Sep 2024
Viewed by 1356
Abstract
Pro-regenerative lipid mediator 1 (PreM1) is a specialized pro-resolving lipid mediator that promotes wound healing and regenerative functions of mesenchymal stem cells (MSCs), endothelial cells, and macrophages. The healing of third-degree (3°) burns and regenerative functions of MSCs are enhanced by ACgel1, an [...] Read more.
Pro-regenerative lipid mediator 1 (PreM1) is a specialized pro-resolving lipid mediator that promotes wound healing and regenerative functions of mesenchymal stem cells (MSCs), endothelial cells, and macrophages. The healing of third-degree (3°) burns and regenerative functions of MSCs are enhanced by ACgel1, an arginine-and-chitosan-based protein-mimic hybrid hydrogel. Adipose-tissue derived microvascular fragments (MVFs) are native vascularization units and a rich source of MSCs, endothelial cells, and perivascular cells for tissue regeneration. Here we describe an innovative PreM1-MVFs-ACgel1 construct that incorporated PreM1 and MVFs into ACgel1 via optimal design and fabrication. This construct delivered PreM1 to 3°-burn wounds at least up to 7 days-post-burn (dpb), and scaffolded and delivered MVFs. PreM1-MVFs-ACgel1 promoted the healing of 3°-burns in mice, including vascularization and collagen formation. The re-epithelization and closure of 3° burn wounds were promoted by ACgel1, MVFs, PreM1, MVFs-ACgel1, PreM1-ACgel1, or PreM1-MVFs-ACgel1 at certain time-point(s), while PreM1-MVFs-ACgel1 was most effective with 97% closure and 4.69% relative epithelial gap at 13 dpb compared to saline control. The PreM1-ACgel1 and MVFs-ACgel1 also promoted blood vessel regeneration of 3°-burns although PreM1-MVFs-ACgel1 is significantly more effective. These PreM1- and/or MVF-functionalized ACgel1 have nonexistent or minimal graft-donor requirements and are promising adjuvant therapeutic candidates for treating deep burns. Full article
(This article belongs to the Special Issue Recent Advances in Wound Healing: 2nd Edition)
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14 pages, 6064 KiB  
Article
Hypothermically Stored Amnion Is Robust and Provides a Scaffold for Supporting Wound Healing by Retaining the Characteristics of Native Tissue
by Katrina A. Harmon, Kelly A. Kimmerling, Justin T. Avery and Katie C. Mowry
Int. J. Mol. Sci. 2024, 25(19), 10347; https://doi.org/10.3390/ijms251910347 - 26 Sep 2024
Cited by 1 | Viewed by 1060
Abstract
Placental-derived products have been used since the early 1900s for wound applications and have shown clinical utility in supporting wound healing. A hypothermically stored amniotic membrane (HSAM) was developed using a proprietary process to allow for the retention of the extracellular matrix (ECM), [...] Read more.
Placental-derived products have been used since the early 1900s for wound applications and have shown clinical utility in supporting wound healing. A hypothermically stored amniotic membrane (HSAM) was developed using a proprietary process to allow for the retention of the extracellular matrix (ECM), viable cells, and key proteins. To evaluate its utility, we characterized the HSAM and compared it to a native unprocessed amniotic membrane (uAM) and a dehydrated amniotic membrane (dAM), as well as assessing the functionality of the HSAM as a scaffold to promote cell growth. The HSAM, uAM, and dAM were compared using scanning electron microscopy (SEM), histology, and thickness. Scaffold durability was assessed in vitro using mechanical testing and a simulated wound fluid (SWF) model. The ability of the HSAM to act as a scaffold was evaluated using an in vitro attachment model. The HSAM showed similar structural characteristics compared to the uAM; however, the dAM was significantly more compact. There were no significant differences between the HSAM and the uAM following degradation in an SWF model. ECM- and placental-related proteins were shared between the HSAM and uAM, and the HSAM enhanced the attachment and proliferation of fibroblasts in vitro. The HSAM is substantially similar to the uAM by retaining key regulatory proteins, resisting degradation in SWF, and acting as a scaffold for cellular growth and invasion. Full article
(This article belongs to the Special Issue Recent Advances in Wound Healing: 2nd Edition)
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Review

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32 pages, 4411 KiB  
Review
SMI-Capsular Fibrosis and Biofilm Dynamics: Molecular Mechanisms, Clinical Implications, and Antimicrobial Approaches
by Ines Schoberleitner, Michaela Lackner, Débora C. Coraça-Huber, Angela Augustin, Anja Imsirovic, Stephan Sigl and Dolores Wolfram
Int. J. Mol. Sci. 2024, 25(21), 11675; https://doi.org/10.3390/ijms252111675 - 30 Oct 2024
Viewed by 1361
Abstract
Silicone mammary implants (SMIs) frequently result in capsular fibrosis, which is marked by the overproduction of fibrous tissue surrounding the implant. This review provides a detailed examination of the molecular and immunological mechanisms driving capsular fibrosis, focusing on the role of foreign body [...] Read more.
Silicone mammary implants (SMIs) frequently result in capsular fibrosis, which is marked by the overproduction of fibrous tissue surrounding the implant. This review provides a detailed examination of the molecular and immunological mechanisms driving capsular fibrosis, focusing on the role of foreign body responses (FBRs) and microbial biofilm formation. We investigate how microbial adhesion to implant surfaces and biofilm development contribute to persistent inflammation and fibrotic responses. The review critically evaluates antimicrobial strategies, including preoperative antiseptic protocols and antimicrobial-impregnated materials, designed to mitigate infection and biofilm-related complications. Additionally, advancements in material science, such as surface modifications and antibiotic-impregnated meshes, are discussed for their potential to reduce capsular fibrosis and prevent contracture of the capsule. By integrating molecular insights with clinical applications, this review aims to elucidate the current understanding of SMI-related fibrotic responses and highlight knowledge gaps. The synthesis of these findings aims to guide future research directions of improved antimicrobial interventions and implant materials, ultimately advancing the management of capsular fibrosis and enhancing patient outcomes. Full article
(This article belongs to the Special Issue Recent Advances in Wound Healing: 2nd Edition)
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