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Interactions of cytokines, growth factors, and proteases in acute and chronic wounds
Abstract
A healing wound represents a complex series of interactions between cells, soluble mediators, and extracellular matrix. Within this multifaceted environment, there are multiple regulatory points which control the ordered series of events that lead to normal tissue repair. An alteration in this physiologic network can lead to the development of a chronic wound. This article presents an update on the numerous mediators that exist within the wound environment in both acute normal healing and chronic nonhealing wounds. We also present a hypothesis which may provide a conceptual pathophysiologic mechanism with which to understand all chronic wounds.
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“Elevated levels of IL-1β have been found in wounds of diabetic humans and mice (12,15,19,20)”
From Sustained Inflammasome Activity in Macrophages Impairs Wound Healing in Type 2 Diabetic Humans and Mice (2014) · cites this paper as [19]
In the citing paper
“Chronic wounds are typically associated with a persistent inflammatory response that involves accumulation of Mp (19,26–28)”
From Sustained Inflammasome Activity in Macrophages Impairs Wound Healing in Type 2 Diabetic Humans and Mice (2014) · cites this paper as [19]
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“Due to poor leukocyte chemotaxis and phagocytosis, diminished macrophage activity in the wound matrix, decreased collagen synthesis and deposition, and reduced growth factor release, wound recovery in diabetes patients is often slower than in healthy persons [5, 6].”
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“Furthermore, adherent MSC secrete antiinflammatory cytokines such as IL-10, IL-13, and IL-1-RA that would reduce chronic inflammation observed in nonhealing wounds.(44) Interestingly, we observed that adherent BM-dMSC and ASC secrete GM-CSF which is likely to have significant patient benefit for chronic wounds when ap…”
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“Off-Label Use of rhPDGF and Its Limitations Off-label uses of rhPDGF have been reported in specialty journals showing the promise of rhPDGF to actively promoting the healing of chronic irradiated wounds.(4,12) In the otolaryngology literature, rhPDGF has been used to improve the healing of previously irradiated dermal…”
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“Matrix metalloproteinases (MMPs) take part in many physiological and pathological processes, such as morphogenesis, wound healing, tissue repair, and remodelling [6] and increasing cell”
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Use of a gelling fibre dressing in complex surgical or chronic wounds: a case series
Ivins, N. M., Braumann, C., Kirchhoff, J.-B., Waldemar, U., & Jones, N. J. (2018) · Journal of Wound Care · doi:10.12968/jowc.2018.27.7.444 · Cited by 7
(2015) · Journal of Transplantation & Stem Cell Biology · doi:10.13188/2374-9326.1000007 · Cited by 7
“Extracellular matrix formation is disturbed, cell proliferation and migration is impaired [12,13].”
BackgroundNew developments in functional medical textiles and their mechanism of action
Edwards, J. V., & Goheen, S. C. (2011) · Elsevier eBooks · doi:10.1533/9780857092878.291 · Cited by 7
Limb Salvage: A review of stem cell and growth factor therapies for diabetic foot ulcers
Metwaly, A., Ismail, S., Nagy, Y. M., et al. (2025) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2025.113036 · Cited by 6
Drabik, M., & Granicka, L. H. (2026) · Journal of Applied Biomedicine · doi:10.1016/j.bbe.2025.12.001 · Cited by 7
Sandora, N., Fitria, N. A., Kusuma, T. R., Winarno, G. A., Tanjunga, S. F., & Wardhana, A. (2022) · PLoS ONE · doi:10.1371/journal.pone.0262007 · Cited by 6
“MMPs also impairs the growth factors and their target cell receptors [58].”
Background
Metadata
- Authors
- Mast, B. A., & Schultz, G. S.
- Affiliations
- University of Florida Health (US)
- University of Florida (US)
- Corresponding author
- Mast, Bruce A.
- Venue
- Wound Repair and Regeneration
- Publisher
- Wiley
- Published
- 1996-10
- Volume
- 4
- Issue
- 4
- Pages
- 411-420
- ISSN
- 1067-1927 (ISSN-L)
- 1524-475X
- OpenAlex
- W1970955409
- Cited by
- 598
- References
- 0
- Citations by year
- 2026: 14 · 2025: 25 · 2024: 26 · 2023: 23 · 2022: 23 · 2021: 37 · 2020: 32 · 2019: 31 · 2018: 39 · 2017: 24 · 2016: 25 · 2015: 24 · 2014: 24 · 2013: 33 · 2012: 30
- FWCI
- 4.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Wound Repair and Regeneration (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Wound Healing and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- chronic wounds, acute wound healing, cytokines, growth factors, proteolytic enzymes, extracellular matrix, tissue repair
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