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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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“In this study, we take the following relationship: g(F, c, ρ) = Fρ 1 + aI I Ic c , (17) where 1/(1 + aI I Ic c) is the inhibition of the synthesis of the generic MMP due to the presence of the signaling molecule.”
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“Whereas there are several possible reasons for this discrepancy, it now seems likely that the proinflammatory environment of the chronic wound adversely affects the stability and activity of the applied growth factors (29, 50).”
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“Wound healing progresses through three overlapping phases: inflammation, proliferation, and tissue remodeling (1, 2).”
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“The chronic wound environment has been shown to have an excess of factors that are normally key in normal wound healing, such as TNF-α and the MMPs, and these are considered to contribute to an inability of the wound to heal.(10,11,23) While GM-CSF has been shown to be crucial in normal wound healing, the excess seen…”
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“MMP-9) unter gleichzeitiger Verminderung von MMPInhibitoren (TIMP-1) und einzelner Wachstumsfaktoren, wie PDGF [36].”
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BackgroundPre-clinical evaluation of liposomal gene transfer to improve dermal and epidermal regeneration
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Effects of a Phenol-Enriched Purified Extract from Olive Mill Wastewater on Skin Cells
Schlupp, P., Schmidts, T., Pössl, A., Wildenhain, S., Franco, G. L., Franco, A. L., & Franco, B. L. (2019) · Cosmetics · doi:10.3390/cosmetics6020030 · Cited by 19
Ishii, T., Takashimizu, I., Casco‐Robles, M. M., Taya, Y., Yuzuriha, S., Toyama, F., Maruo, F., Kishi, K., & Chiba, C. (2021) · Biomedicines · doi:10.3390/biomedicines9121892 · Cited by 19
Goldberg, S. R., & Diegelmann, R. F. (2012) · Critical Care Nursing Clinics of North America · doi:10.1016/j.ccell.2012.03.002 · Cited by 19
Prior injury accelerates subsequent wound closure in a mouse model of regeneration
Davis, T. A., Longcor, J. D., Hicok, K. C., & Lennon, G. G. (2005) · Cell and Tissue Research · doi:10.1007/s00441-005-1107-7 · Cited by 19
“Moreover, matrix metalloproteinases (MMPs) have been recognized as normal constituents in the woundhealing process and remodeling of extracellular matrix components (Baker and Leaper 2000; Madden and Peacock 1971; Parks 1999; Mast and Schultz 1996; Madlener et al. 1998).”
BackgroundNanoemulsion mediated approaches for wound healing
Tohamy, H. S. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-22027-2.00025-7 · Cited by 18
Nanotechnology approaches for skin wound regeneration using drug-delivery systems
García-Orue, I., Gainza, G., Villullas, S., Pedraz, J. L., Hernández, R. M., & Igartúa, M. (2016) · Elsevier eBooks · doi:10.1016/b978-0-323-42865-1.00002-7 · Cited by 19
Eggers, B., Stope, M. B., Marciniak, J., Mustea, A., Deschner, J., Nokhbehsaim, M., & Kramer, F. (2022) · Cells · doi:10.3390/cells11172740 · Cited by 18
“This is important for tissue remodelling, as effective wound healing requires a fine-tuned balance of collagen production, deposition and degradation [16].”
BackgroundDefinition of infection in chronic wounds by Dutch nursing home physicians
Rondas, A., Schols, J. M. G. A., Stobberingh, E. E., & Price, P. (2009) · International Wound Journal · doi:10.1111/j.1742-481x.2009.00604.x · Cited by 18
Malignant Transformation in Diabetic Foot Ulcers—Case Reports and Review of the Literature
Dörr, S. L., Lucke-Paulig, L., Vollmer, C., & Lobmann, R. (2019) · Geriatrics · doi:10.3390/geriatrics4040062 · Cited by 19
“In partic lar, TNFα and interleukin 1β (IL 1β) lead to sust ined chronic infla matio [5,7].”
BackgroundInfluentialFuture Structure and Properties of Mechanism-Based Wound Dressings
Edwards, J. V. (2006) · Springer eBooks · doi:10.1007/1-4020-3794-5_2 · Cited by 17
Bovine colostrum promotes growth and migration of the human keratinocyte HaCaT cell line
Kovacs, D., Cardinali, G., Aspite, N., & Picardo, M. (2009) · Growth Factors · doi:10.3109/08977190903211077 · Cited by 17
Mayer, D., Armstrong, D. G., Schultz, G., Percival, S. L., Malone, M., Romanelli, M., Keast, D. H., & Jeffery, S. (2018) · Journal of Wound Care · doi:10.12968/jowc.2018.27.9.594 · Cited by 17
Self-citationSantana, H., Sotolongo, J., González, Y. A., et al. (2014) · Biologicals · doi:10.1016/j.biologicals.2014.07.005 · Cited by 17
“This can be a limitation for topical formulations because the active agent bioavailability is affected by necrotic tissue, sepsis, inflammation and wound proteases [10].”
BackgroundPirayesh, A., Dessy, L. A., Rogge, F. J., Hoeksema, H., Sinove, Y., Antonia, A. D., Jawad, M. A., Gilbert, P. M., Rubino, C., Scuderi, N., et al. (2007) · Acta chirurgica Belgica · doi:10.1080/00015458.2007.11680145 · Cited by 17
“The characterization of wound microenvironment and the processes that cause progression of acute wounds into chronic wounds have been the focus of considerable research (15-18).”
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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