Clinical challenges of chronic wounds: searching for an optimal animal model to recapitulate their complexity
Open accessAbstract
The efficient healing of a skin wound is something that most of us take for granted but is essential for surviving day-to-day knocks and cuts, and is absolutely relied on clinically whenever a patient receives surgical intervention. However, the management of a chronic wound – defined as a barrier defect that has not healed in 3 months – has become a major therapeutic challenge throughout the Western world, and it is a problem that will only escalate with the increasing incidence of conditions that impede wound healing, such as diabetes, obesity and vascular disorders. Despite being clinically and molecularly heterogeneous, all chronic wounds are generally assigned to one of three major clinical categories: leg ulcers, diabetic foot ulcers or pressure ulcers. Although we have gleaned much knowledge about the fundamental cellular and molecular mechanisms that underpin healthy, acute wound healing from various animal models, we have learned much less about chronic wound repair pathology from these models. This might largely be because the animal models being used in this field of research have failed to recapitulate the clinical features of chronic wounds. In this Clinical Puzzle article, we discuss the clinical complexity of chronic wounds and describe the best currently available models for investigating chronic wound pathology. We also assess how such models could be optimised to become more useful tools for uncovering pathological mechanisms and potential therapeutic treatments.
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It is unlikely that animal models that perfectly recapitulate the complex network of pathological factors in chronic human wounds will be developed in the near future.
“Furthermore, based on current knowledge, it is unlikely that animal models that perfectly recapitulate the complex network of pathological factors in chronic human wounds will be developed in the near future (Fig. 3) (20).”
From Wound repair and regeneration: Mechanisms, signaling, and translation (2014) · cites this paper as [20]
Many mouse models of pathological wound healing accurately mirror some systemic causes of impaired healing, such as diabetes in db/db mice, but seldom account for other important associations such as age and wound microbial load.
“Also important to note is that many models of pathological wound healing in mice, although accurately mirroring some of the systemic causes of impaired healing—for example, the diabetic (db/db) mouse—seldom make allowance for other important associations, such as age and wound microbial load.”
From Wound repair and regeneration: Mechanisms, signaling, and translation (2014) · cites this paper as [20]
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- Authors
- Nunan, R., Harding, K. G., & Martin, P.
- Affiliations
- University of Bristol (GB)
- Cardiff University (GB)
- Corresponding author
- Nunan, Robert
- Venue
- Disease Models & Mechanisms
- Publisher
- The Company of Biologists
- Published
- 2014-11-01
- Volume
- 7
- Issue
- 11
- Pages
- 1205-1213
- ISSN
- 1754-8403 (ISSN-L)
- 1754-8411
- PMC
- PMC4213725
- OpenAlex
- W2129322966
- Cited by
- 542
- References
- 71
- Citations by year
- 2026: 31 · 2025: 63 · 2024: 58 · 2023: 41 · 2022: 85 · 2021: 58 · 2020: 52 · 2019: 34 · 2018: 53 · 2017: 31 · 2016: 27 · 2015: 7 · 2014: 1
- FWCI
- 21.36
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Disease Models & Mechanisms (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Bristol Research (University of Bristol) (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Wellcome Trust (097791)
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetic Foot Ulcer Assessment and Management
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- chronic wounds, animal models, wound healing, diabetic foot ulcer, leg ulcers, pressure ulcers, model validation, diabetic wound healing, skin barrier dysfunction
- MeSH terms
- Animals, Chronic Disease, Wound Healing, Wounds and Injuries, Models, Animal
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