PERSPECTIVE ARTICLE: Growth factors and cytokines in wound healing
Abstract
Wound healing is an evolutionarily conserved, complex, multicellular process that, in skin, aims at barrier restoration. This process involves the coordinated efforts of several cell types including keratinocytes, fibroblasts, endothelial cells, macrophages, and platelets. The migration, infiltration, proliferation, and differentiation of these cells will culminate in an inflammatory response, the formation of new tissue and ultimately wound closure. This complex process is executed and regulated by an equally complex signaling network involving numerous growth factors, cytokines and chemokines. Of particular importance is the epidermal growth factor (EGF) family, transforming growth factor beta (TGF-beta) family, fibroblast growth factor (FGF) family, vascular endothelial growth factor (VEGF), granulocyte macrophage colony stimulating factor (GM-CSF), platelet-derived growth factor (PDGF), connective tissue growth factor (CTGF), interleukin (IL) family, and tumor necrosis factor-alpha family. Currently, patients are treated by three growth factors: PDGF-BB, bFGF, and GM-CSF. Only PDGF-BB has successfully completed randomized clinical trials in the Unites States. With gene therapy now in clinical trial and the discovery of biodegradable polymers, fibrin mesh, and human collagen serving as potential delivery systems other growth factors may soon be available to patients. This review will focus on the specific roles of these growth factors and cytokines during the wound healing…
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The prevalence of drug induced gingival overgrowth varies significantly and depends upon the population being investigated.
“However, the prevalence varies significantly and depends upon the population being investigated [ 21].”
From An Update on the Mechanisms of Phenytoin Induced Gingival Overgrowth (2019) · cites this paper as [21]
Deregulation of key proinflammatory cytokines such as IL-1β and TNFα prolongs the inflammatory phase and delays healing.
“As a result, deregulation of several key proinflammatory cytokines, such as IL-1β and tumor necrosis factor–α (TNFα), prolong the inflammatory phase and delay healing (26, 29).”
From Wound repair and regeneration: Mechanisms, signaling, and translation (2014) · cites this paper as [29]
These macrophages are predominantly pro-inflammatory and secrete cytokines/chemokines that promote further leukocyte recruitment.
“These cells are of a predominantly pro-inflammatory phenotype and secrete cytokines and chemokines that promote the further recruitment of leukocytes to the site of injury [89,91].”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [89]
ECM components serve as a reservoir and modulator of cytokines and growth factors' action, thereby regulating wound repair activity.
“ECM components serve also as a reservoir and a modulator of cytokines and growth factors' action, thus regulating wound repair activity [5, 15, 22–24].”
From The role of the extracellular matrix components in cutaneous wound healing (2014) · cites this paper as [24]
Fibroblasts are attracted to the wound area according to the chemotactic PDGF, EGF, IGF-1, and TGF-β gradient, proliferate under stimulation by growth factors, and then synthesize ECM components and form granulation tissue.
“The cells in question are “attracted” to the wound area according to the chemotactic PDGF, EGF, IGF-1, and TGF-β gradient where the proliferation of these cells takes place (stimulated by growth factors) and, after that the synthesis of ECM components and formation of “granulation” tissue starts [24, 39, 66, 67].”
From The role of the extracellular matrix components in cutaneous wound healing (2014) · cites this paper as [24]
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- Authors
- Barrientos, S., Stojadinovic, O., Golinko, M. S., Brem, H., & Tomic‐Canic, M.
- Affiliations
- Hospital for Special Surgery (US)
- Columbia University Irving Medical Center (US)
- Corresponding author
- Tomic‐Canic, Marjana
- Venue
- Wound Repair and Regeneration
- Publisher
- Wiley
- Published
- 2008-09
- Volume
- 16
- Issue
- 5
- Pages
- 585-601
- ISSN
- 1067-1927 (ISSN-L)
- 1524-475X
- OpenAlex
- W1949832432
- Cited by
- 3,583
- References
- 4
- Citations by year
- 2026: 177 · 2025: 288 · 2024: 270 · 2023: 222 · 2022: 285 · 2021: 305 · 2020: 282 · 2019: 219 · 2018: 228 · 2017: 214 · 2016: 197 · 2015: 157 · 2014: 164 · 2013: 159 · 2012: 148
- FWCI
- 10.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Wound Repair and Regeneration (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG030673, R21AG030673)
- National Institute of Nursing Research (NR08029, R01NR008029)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK59424, K08DK059424)
- U.S. National Library of Medicine (LM 008443, R01LM008443)
- National Center for Research Resources (UL1RR024996)
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- wound healing, growth factors, cytokines, epidermal growth factor, TGF-beta, fibroblast growth factor, vascular endothelial growth factor, GM-CSF, platelet-derived growth factor, connective tissue growth factor, interleukins, TNF-α, PDGF-BB, basic fibroblast growth factor, growth factor delivery systems, skin barrier restoration, cell proliferation and migration
- MeSH terms
- Animals, Humans, Wound Healing, Cytokines, Intercellular Signaling Peptides and Proteins
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