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.
“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]
Chronic wounds are typically associated with a persistent inflammatory response that involves accumulation of macrophages.
“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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“c wounds (modified from Mast and Schultz (1996)).”
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“Also, it has been found that degradation can be blocked by the addition of MMP inhibitors (101).”
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“It has often been assumed that excess proteolytic activity, characterized as inflammation, is secondary to an increased microbial burden in the wound, but the evidence from studies such as those described above and others suggests that elevated MMP levels can also occur in the absence of infection.(17,34) In 2002, Wri…”
ResultSelf-citationGlucose Toxic Effects on Granulation Tissue Productive Cells: The Diabetics’ Impaired Healing
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“Interestingly, TNFA levels are elevated in chronic wounds (Mast & Schultz, 1996), suggesting that it may have a detrimental effect on healing and may perpetuate inflammation and inhibit tissue growth.”
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“When combined with impaired cellular and systemic host responses to stress, it establishes a deleterious pathophysiological cycle that perpetuates chronic non-healing [9,10].”
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“6,7 In spite of a multidisciplinary approach (including glycemic control, daily local care, foot off-loading, antibiotic therapy, and surgical revascularization), chronic diabetic foot ulcers require a long time to achieve complete healing.”
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Approaches to cutaneous wound healing: basics and future directions
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Therapeutic role of growth factors in treating diabetic wound
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Nerve growth factor and tissue repair remodeling: trkANGFR and p75NTR, two receptors one fate
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“Neutrophils exert their main role by early phagocytosis of wound debris and release an array of cytokines and growth factors, representing the first signals to activate migration mainly of fibroblasts (FBs) and epithelial cells [6,7].”
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A Patient-Specific in silico Model of Inflammation and Healing Tested in Acute Vocal Fold Injury
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“At the heart of the response to phonotrauma is the intertwined process of inflammation and wound healing [36–42].”
BackgroundDiabetic foot ulcers — a comprehensive review
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Angiogenic response to extracorporeal shock wave treatment in murine skin isografts
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“The inability to progress through the inflammatory phase of wound healing to complete epithelialization is characteristic of chronic wounds, where prolonged and aberrant accumulation of matrix metalloproteinases (MMPs) impedes cell migration and downregulation of tissue inhibitors of MMPs, hinders neovascularization e…”
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“This suggests that prolonged inXammation may also impair healing of chronic ulcers by the adverse action of cytokines that induce migration of inXammatory cells, stimulate secretion of proteinases [ 20 ], aVect the growth and viability of diVerent cell types, and diminish the integrity of the extracellular matrix [25].”
BackgroundInfluentialThe Role of Doxycycline as a Matrix Metalloproteinase Inhibitor for the Treatment of Chronic Wounds
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“Mast and Schultz (1996) summarized acute and chronic wound environments at the molecular level.”
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“They demonstrate that NO very efficiently supressed IL-1 and TNF- -induced RANTES expression n keratinocytes.”
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Wound dressings as growth factor delivery platforms for chronic wound healing
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“The treatment of wounds with exogenous GFs is often ineffective since GFs rapidly diffuse from the administration site and are readily digested or deactivated by enzymes such as proteases in the wound area [47].”
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Alginate-based composite sponge containing silver nanoparticles synthesized in situ
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- 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 › Rehabilitation › 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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