ArticlePloS one2014
A novel model of chronic wounds: importance of redox imbalance and biofilm-forming bacteria for establishment of chronicity.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
- Regenerative Microbiology: Harnessing Bacterial Antagonism and Spatiotemporal Signaling for Diabetic Wound Repair.Smart medicine · 2026Review
- Antibiofilm, Antimicrobial, and Anti-inflammatory Potential of Rubus chamaemorus Rhizome, Leaf, and Fruit Extracts.Chemistry & biodiversity · 2026Article
- MC1R determines healing outcomes in acute and chronic cutaneous wounds.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- African Medicinal Plants in Cutaneous Wound Repair: A Comprehensive Analysis of the Role of Phytochemicals.International wound journal · 2025Review
- The Impact of the Skin Microbiome and Oxidative Stress on the Initiation and Development of Cutaneous Chronic Wounds.Antioxidants (Basel, Switzerland) · 2025Review
- Creating an Extremely Long-lasting Neuroischemic Wound Model.JID innovations : skin science from molecules to population health · 2025Article
- Redox-Responsive Hydrogels Loaded with an Antibacterial Peptide as Controlled Drug Delivery for Healing Infectious Wounds.Advanced healthcare materials · 2024Article
- Defining the activity of pro-reparative extracellular vesicles in wound healing based on miRNA payloads and cell type-specific lineage mapping.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Melatonin/Sericin Wound Healing Patches: Implications for Melanoma Therapy.International journal of molecular sciences · 2024Review
- Development of Antioxidant and Antimicrobial Membranes Based on Functionalized and Crosslinked Chitosan for Tissue Regeneration.International journal of molecular sciences · 2024Article
- Functionalization of Bacterial Cellulose with the Antimicrobial Peptide KR-12 via Chimerical Cellulose-Binding Peptides.International journal of molecular sciences · 2024Article
- Skewing cPLAScience signaling · 2023Article
- Signaling Pathways Associated with Chronic Wound Progression: A Systems Biology Approach.Antioxidants (Basel, Switzerland) · 2022Article
- Current research on fungi in chronic wounds.Frontiers in molecular biosciences · 2022Review
- Biofilm model on mice skin wounds.Acta cirurgica brasileira · 2022Article
- Bone Marrow Mesenchymal Stem Cells Support Acute Myeloid Leukemia Bioenergetics and Enhance Antioxidant Defense and Escape from Chemotherapy.Cell metabolism · 2020Article
- Skin Microbiota and its Interplay with Wound Healing.American journal of clinical dermatology · 2020Review
- Ultrasound-mediated therapies for the treatment of biofilms in chronic wounds: a review of present knowledge.Microbial biotechnology · 2020Review
- Lignin/poly(butylene succinate) composites with antioxidant and antibacterial properties for potential biomedical applications.International journal of biological macromolecules · 2020Article
- Keratinocyte Function in Normal and Diabetic Wounds and Modulation by FOXO1.Journal of diabetes research · 2020Review
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Chronic wounds have a large impact on health, affecting ∼6.5 M people and costing ∼$25B/year in the US alone. We previously discovered that a genetically modified mouse model displays impaired healing similar to problematic wounds in humans and that sometimes the wounds become chronic. Here we show how and why these impaired wounds become chronic, describe a way whereby we can drive impaired wounds to chronicity at will and propose that the same processes are involved in chronic wound development in humans. We hypothesize that exacerbated levels of oxidative stress are critical for initiation of chronicity. We show that, very early after injury, wounds with impaired healing contain elevated levels of reactive oxygen and nitrogen species and, much like in humans, these levels increase with age. Moreover, the activity of anti-oxidant enzymes is not elevated, leading to buildup of oxidative stress in the wound environment. To induce chronicity, we exacerbated the redox imbalance by further inhibiting the antioxidant enzymes and by infecting the wounds with biofilm-forming bacteria isolated from the chronic wounds that developed naturally in these mice. These wounds do not re-epithelialize, the granulation tissue lacks vascularization and interstitial collagen fibers, they contain an antibiotic-resistant mixed bioflora with biofilm-forming capacity, and they stay open for several weeks. These findings are highly significant because they show for the first time that chronic wounds can be generated in an animal model effectively and consistently. The availability of such a model will significantly propel the field forward because it can be used to develop strategies to regain redox balance that may result in inhibition of biofilm formation and result in restoration of healthy wound tissue. Furthermore, the model can lead to the understanding of other fundamental mechanisms of chronic wound development that can potentially lead to novel therapies.
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