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Biomedicines
Special Issues
Wound Healing: From Mechanisms to Therapeutic Approaches
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Wound Healing: From Mechanisms to Therapeutic Approaches

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 31 July 2025 | Viewed by 2374

Special Issue Editor

Dr. Stefano Bacci

E-Mail Website
Guest Editor
Research Unit of Histology and Embryology, Department of Biology, University of Florence, Florence, Italy
Interests: photobiology; photoimmunology; phototherapy; targeted therapies; photobiomodulation; wound healing; basic sciences
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

A wound determines a cascade of chemical and morphological events, aimed at hemostasis, the prevention or arrest of infection, the removal of damaged tissue, and finally tissue repair. A disturbance or alteration of these events creates the conditions for the formation of a chronic wound, keloids, or hypertrophic scars that are not easily resolved by therapy. Obviously, a thorough knowledge of the cells and molecules involved in the tissue response to trauma is important to actively control the response to surgical operations and therapies used that are currently assuming ever greater importance in the control of wounds. Therefore, the aim of this Special Issue is to stimulate research and clinical interest in this exciting field and to serve as a point of reference for those involved in addressing the problems posed by wounds and their healing.

Dr. Stefano Bacci
Guest Editor

Manuscript Submission Information

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Keywords

  • wound healing
  • acute wounds
  • chronic wounds
  • keloids
  • hypertrophic scar
  • therapies
  • photobiomodulation
  • neuroimmunomodulation

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Published Papers (3 papers)

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Research

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13 pages, 2537 KiB  
Article
Molecular Insights into the Interaction of Cathepsin D and Iron in Chronic Wound Healing: Exploring Therapeutic Potential and Mechanisms
by María Rodríguez-Moreno and Isabel Legaz
Biomedicines 2025, 13(3), 544; https://doi.org/10.3390/biomedicines13030544 - 21 Feb 2025
Viewed by 512
Abstract
Background: Chronic wounds, such as diabetic ulcers, often fail to progress through healing due to persistent inflammation, infections, and extracellular matrix (ECM) imbalances. Cathepsin D, an aspartate protease active in acidic environments, plays a pivotal role in wound healing by mediating inflammatory responses, [...] Read more.
Background: Chronic wounds, such as diabetic ulcers, often fail to progress through healing due to persistent inflammation, infections, and extracellular matrix (ECM) imbalances. Cathepsin D, an aspartate protease active in acidic environments, plays a pivotal role in wound healing by mediating inflammatory responses, ECM remodeling, and macrophage phenotype transitions. Its dysregulation, however, can impair healing, highlighting the need for targeted modulation of its activity. The aim of this study was to investigate the molecular interaction between Fe2+ and cathepsin D’s catalytic core and ionic zipper under physiological and acidic conditions to identify strategies to enhance tissue repair and accelerate the healing of chronic wounds. Methods: The molecular structure of active cathepsin D was obtained from the Protein Data Bank (PDB) and analyzed using UCSF Chimera. Molecular interactions between cathepsin D and ferrous ions (Fe2+) were studied, focusing on key residues (D33 and D231) and ionic zipper residues (E5, E180, and D187). Results: Our results showed that the active form of cathepsin D, a 96 kDa dimer, consisted of heterodimers with distinct amino acid chains, where residues D33 and D231 formed the active site, and E5, E180, and D187 constituted the ionic zipper. A functional pocket containing the conserved residues D33 and D231, essential for proteolytic activity, was identified. At physiological pH (~7.5), D33 exhibited the most potent interactions with Fe2+, with interaction energies of −7 × 1017 J at oxygen atoms of the carboxylate group (OD1) and α-carbon (CA) atoms, whereas D231 showed slightly lower energies of −6 × 1017 J at γ-carbon atom (CG) and CA atoms. At acidic pH (~4), E5 was the primary interacting residue, with the shortest distance to Fe2+ (2.69 Å), and showed stable interactions across several atoms, emphasizing its role in metal binding. Conclusions: pH conditions strongly influence the interaction of cathepsin D with Fe2. At physiological pH, residues D33 and D231 demonstrate robust and energetically efficient binding with Fe2+. At the same time, under acidic conditions, E5 emerges as the primary residue involved, potentially affecting the ionic zipper of cathepsin D. These insights provide a molecular foundation for targeting specific residues to modulate cathepsin D activity, presenting promising opportunities for therapeutic strategies aimed at improving chronic wound healing. Full article
(This article belongs to the Special Issue Wound Healing: From Mechanisms to Therapeutic Approaches)
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21 pages, 4317 KiB  
Article
Topical Application of VitB6 Ameliorates PM2.5-Induced Dry Eye via NFκB Pathway in a Murine Model
by Jinyu Hu, Yanmei Zeng, Liying Tang, Lei Ye, Cheng Chen, Qian Ling, Xiaoyu Wang, Liangqi He, Xu Chen, Yixin Wang, Qianmin Ge and Yi Shao
Biomedicines 2025, 13(3), 541; https://doi.org/10.3390/biomedicines13030541 - 21 Feb 2025
Viewed by 553
Abstract
Background/Objectives: Dry eye (DE) is mainly characterized by dryness, foreign body sensation, eye pain and visual impairment. Their possible causes are mainly inflammation, tissue damage and neurosensory abnormalities, and vitamin B6 (VitB6) attenuates the inflammatory response by modulating the NF-κB pathway to quench [...] Read more.
Background/Objectives: Dry eye (DE) is mainly characterized by dryness, foreign body sensation, eye pain and visual impairment. Their possible causes are mainly inflammation, tissue damage and neurosensory abnormalities, and vitamin B6 (VitB6) attenuates the inflammatory response by modulating the NF-κB pathway to quench reactive oxygen species (ROS). The aim of this experiment was to investigate the therapeutic effect of VitB6 eye drops on particulate matter 2.5 (PM2.5)-induced dry eye in mice. Methods: Mice induced with the dry eye group were first induced using PM2.5 eye drops in a standard environment for 14 days, and then treated with different concentrations of VitB6 eye drops for 14 consecutive days. The phenol red cotton test was used to measure tear production. Ocular inflammation index and tear film function were evaluated by slim microscopy. Hematoxylin–eosin (HE) staining was used to observe conjunctival and corneal structure. Periodate–Schiff (PAS) staining was used to quantify conjunctival goblet cells. Corneal cell apoptosis was determined by TUNEL assay. The expression of keratin 10 (K10) and p-NF-κB p65 was detected by immunofluorescent staining and Western blot analysis. Results: Mice using only the PM2.5 model all exhibited varying degrees of dry eye symptoms. VitB6 treatment increased tear secretion and reduced inflammatory indices in mice with increased nerve density and number of branches in the basement membrane of the corneal epithelium. Conclusions: We found that administering VitB6 eye drops has a therapeutic effect in PM2.5-induced DE. This observation suggests that VitB6 may be useful in the clinical therapy of DE. Full article
(This article belongs to the Special Issue Wound Healing: From Mechanisms to Therapeutic Approaches)
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Review

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18 pages, 1280 KiB  
Review
Neutrophil Heterogeneity in Wound Healing
by Filippo Renò, Corinna Anais Pagano, Monica Bignotto and Maurizio Sabbatini
Biomedicines 2025, 13(3), 694; https://doi.org/10.3390/biomedicines13030694 - 12 Mar 2025
Viewed by 844
Abstract
Neutrophils are the most abundant type of immune cells and also the most underestimated cell defenders in the human body. In fact, their lifespan has also been extensively revised in recent years, going from a half-life of 8–10 h to a longer lifespan [...] Read more.
Neutrophils are the most abundant type of immune cells and also the most underestimated cell defenders in the human body. In fact, their lifespan has also been extensively revised in recent years, going from a half-life of 8–10 h to a longer lifespan of up to 5.4 days in humans; it has been discovered that their mechanisms of defense are multiple and finely modulated, and it has been suggested that the heterogeneity of neutrophils occurs as well as in other immune cells. Neutrophils also play a critical role in the wound healing process, and their involvement is not limited to the initial stages of defense against pathogens, but extends to the inflammatory phase of tissue reconstruction. Neutrophil heterogeneity has recently been reported at the presence of distinct subtypes expressing different functional states, which contribute uniquely to the different phases of innate immunity and wound healing. This heterogeneity can be induced by the local microenvironment, by the presence of specific cytokines and by the type of injury. The different functional states of neutrophils enable a finely tuned response to injury and stress, which is essential for effective healing. Understanding the functional heterogeneity of neutrophils in wound healing can unveil potential pathological profiles and therapeutic targets. Moreover, the understanding of neutrophil heterogeneity dynamics could help in designing strategies to manage excessive inflammation or impaired healing processes. This review highlights the complexity of neutrophil heterogeneity and its critical roles throughout the phases of wound healing. Full article
(This article belongs to the Special Issue Wound Healing: From Mechanisms to Therapeutic Approaches)
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