Wound healing: an overview of acute, fibrotic and delayed healing
Open accessAbstract
Acute wounds normally heal in a very orderly and efficient manner characterized by four distinct, but overlapping phases: hemostasis, inflammation, proliferation and remodeling. Specific biological markers characterize healing of acute wounds. Likewise, unique biologic markers also characterize pathologic responses resulting in fibrosis and chronic non-healing ulcers. This review describes the major biological processes associated with both normal and pathologic healing. The normal healing response begins the moment the tissue is injured. As the blood components spill into the site of injury, the platelets come into contact with exposed collagen and other elements of the extracellular matrix. This contact triggers the platelets to release clotting factors as well as essential growth factors and cytokines such as platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF-beta). Following hemostasis, the neutrophils then enter the wound site and begin the critical task of phagocytosis to remove foreign materials, bacteria and damaged tissue. As part of this inflammatory phase, the macrophages appear and continue the process of phagocytosis as well as releasing more PDGF and TGF beta. Once the wound site is cleaned out, fibroblasts migrate in to begin the proliferative phase and deposit new extracellular matrix. The new collagen matrix then becomes cross-linked and organized during the final remodeling phase. In order for this efficient and highly controlled repair process to take place, there are numerous cell-signaling events that are required. In pathologic conditions such as non-healing pressure ulcers, this efficient and orderly process is lost and the ulcers are locked into a state of chronic inflammation characterized by abundant neutrophil infiltration with associated reactive oxygen species and destructive enzymes. Healing proceeds only after the inflammation is controlled. On the opposite end of the spectrum, fibrosis is characterized by excessive matrix deposition and reduced remodeling. Often fibrotic lesions are associated with increased densities of mast cells. By understanding the functional relationships of these biological processes of normal compared to abnormal wound healing, hopefully new strategies can be designed to treat the pathological conditions.
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The default response to tissue injury occurs in four stages: hemostasis, inflammation, proliferation, and remodeling.
“The default response to tissue injury has been described as occurring in four stages: hemostasis, inflammation, proliferation, and remodeling [86].”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [86]
The default mammalian host response to tissue injury typically results in deposition of dense fibrous connective tissue (scar tissue) at the injury site.
“The default mammalian host response following tissue injury is a well-documented series of events that typically result in the deposition of dense fibrous connective tissue (i.e., scar tissue) within the site of injury [85–87].”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [86]
Cytokines involved in the proliferative phase include EGF, b-FGF, TGF-α, TGF-β, VEGF, and others depending on the injured tissue.
“These cytokines include EGF, b-FGF, TGF-α, TGF-β, VEGF, and others depending on the nature of the injured tissue [86].”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [86]
The remodeling phase begins after deposition of significant ECM (mainly collagens I and III) and is characterized by MMP- and TIMP-mediated degradation and remodeling of new collagen, generally resulting in scar tissue formation or maturation.
“Following the deposition of significant amounts of ECM (predominantly collagens type I and III) during the proliferative phase, the remodeling phase of wound healing begins. This phase is characterized by MMP- and tissue inhibitor of metalloproteinase (TIMP)-mediated degradation and remodeling of the newly deposited collagen, generally resulting in scar tissue formation/maturation [86,100].”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [86]
Prolonged inflammation and remodeling can lead to fibrosis or hypertrophic scar formation due to dysregulation of the default healing process.
“In some cases, as will be discussed in further detail, prolonged inflammation and remodeling leading to fibrosis or hypertrophic scar formation may occur due to dysregulation of the default healing process [32,86,101,102].”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [86]
Neutrophils and monocytes are recruited into the wound environment by PDGF and TGF-β to initiate the inflammatory response.
“So, neutrophils and monocytes are recruited into the wound environment by PDGF and TGF-β, which is to initiate the inflammatory response [15, 44].”
From The role of the extracellular matrix components in cutaneous wound healing (2014) · cites this paper as [15]
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 [15]
Platelets are early modulators of the healing process.
“The platelets are early modulators of the healing process [15].”
From The role of the extracellular matrix components in cutaneous wound healing (2014) · cites this paper as [15]
The absence of neutrophils and reduced amount of macrophages in the wound environment indicates that the inflammatory phase ends and the proliferation phase starts.
“The absence of neutrophils as well as the reduced amount of macrophages in the wound environment indicates that the inflammatory phase comes to an end and the proliferation phase starts [15].”
From The role of the extracellular matrix components in cutaneous wound healing (2014) · cites this paper as [15]
PDGF stimulates the expression of collagenase, while TGF-β regulates the accumulation of ECM components.
“The first of the mentioned growth factors, originating mainly from blood platelets and macrophages, stimulates also the expression of collagenase, while the second one, which is also secreted by blood platelets and macrophages, regulates the accumulation of ECM components [15].”
From The role of the extracellular matrix components in cutaneous wound healing (2014) · cites this paper as [15]
Macrophages secrete TGF-β, PDGF, TGF-α, bFGF, HB-EGF, IL-1, IL-6, and TGF-α.
“Moreover, they are the source of TGF-β also secreting PDGF, TGF-α, bFGF, HB-EGF, IL-1, IL-6, and TGF-α [15, 50].”
From The role of the extracellular matrix components in cutaneous wound healing (2014) · cites this paper as [15]
The tensile strength of a wound freshly covered with epithelium equals 25% relative to the dermis.
“The tensile strength, in the case of the wound freshly covered with epithelium, equals 25% related to the dermis”
From The role of the extracellular matrix components in cutaneous wound healing (2014) · cites this paper as [15]
After many months of reconstruction, the tensile strength equals 80% relative to unchanged tissue.
“after many months of reconstruction, the strength equals 80% related to the unchanged tissue”
From The role of the extracellular matrix components in cutaneous wound healing (2014) · cites this paper as [15]
The maturation process of the granulation tissue comprises lowering the content of glycosaminoglycans and proteoglycans.
“lowering the content of glycosaminoglycans and proteoglycans”
From The role of the extracellular matrix components in cutaneous wound healing (2014) · cites this paper as [15]
Epithelialization comprises cellular detachment, migration to the wound area, proliferation, and differentiation.
“The process in question comprises cellular detachment, their migration to the wound area, proliferation, and differentiation [15].”
From The role of the extracellular matrix components in cutaneous wound healing (2014) · cites this paper as [15]
Epithelialization is a multiphase process that reconstructs the epithelium after injury.
“Epithelialization is a multiphase process which is about reconstructing the epithelium after the injury [15].”
From The role of the extracellular matrix components in cutaneous wound healing (2014) · cites this paper as [15]
Epithelialization is a clinical symptom of healing but is not a sign of the end of the healing process.
“Epithelialization is a clinical symptom of healing; however, it is not a sign of the end of this process.”
From The role of the extracellular matrix components in cutaneous wound healing (2014) · cites this paper as [15]
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Cites
Myofibroblasts and mechano-regulation of connective tissue remodelling
Tomasek, J. J., Gabbiani, G., Hinz, B., Chaponnier, C., & Brown, R. A. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm809 · Cited by 4,290 · see citing works
Tonnesen, M. G., Feng, X., & Clark, R. A. F. (2000) · Journal of Investigative Dermatology Symposium Proceedings · doi:10.1046/j.1087-0024.2000.00014.x · Cited by 1,463 · see citing works
Yager, D. R., Zhang, L.-Y., Liang, H.-X., Diegelmann, R. F., & Cohen, I. K. (1996) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12365637 · Cited by 389 · see citing works
Peterkofsky, B. (1991) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/54.6.1135s · Cited by 383 · see citing works
MMP-8 Is the Predominant Collagenase in Healing Wounds and Nonhealing Ulcers
Nwomeh, B. C., Liang, H.-X., Cohen, I. K., & Yager, D. R. (1999) · Journal of Surgical Research · doi:10.1006/jsre.1998.5495 · Cited by 357 · cited 1× · see citing works
“The neutrophils release significant amounts of enzymes such as collagenase (matrix metalloproteinase8) that is responsible for destruction of the connective tissue matrix (57, 58).”
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Flagged first, then by citations
Research works printed but not linked: 55
- Lawrence, W. T., and Diegelmann, R. F., Growth factors in wound healing, Clin Dermatol, 12, 157 (1994)
- Ross, R., Wound healing, Sci Am, 220, 40 (1969)
- Prockop, D. J., and Kivirikko, K. I., Collagens: molecular biology, diseases, and potentials for therapy, Annu Rev Biochem, 64, 403 (1995)
- Lazarus, G. S., Cooper, D. M., Knighton, D. R., Margolis, D. J., Pecoraro, R. E., Rodeheaver, G., and Robson, M. C., Definitions and guidelines for assessment of wounds and evaluation of healing, Arch Dermatol, 130, 489 (1994)
- Kim, W. J., Gittes, G. K., and Longaker, M. T., Signal transduction in wound pharmacology, Arch Pharm Res, 21, 487 (1998)
- Gillitzer, R., and Goebeler, M., Chemokines in cutaneous wound healing, J Leukoc Biol, 69, 513 (2001)
- Friesel, R. E., and Maciag, T., Molecular mechanisms of angiogenesis: fibroblast growth factor signal transduction, Faseb J, 9, 919 (1995)
- Ito, Y., Bringas, P., Jr., Mogharei, A., Zhao, J., Deng, C., and Chai, Y., Receptor-regulated and inhibitory Smads are critical in regulating transforming growth factor beta- mediated Meckel's cartilage development, Dev Dyn, 224, 69 (2002)
- van Zuijlen, P. P., Angeles, A. P., Kreis, R. W., Bos, K. E., and Middelkoop, E., Scar assessment tools: implications for current research, Plast Reconstr Surg, 109, 1108 (2002)
- Bock, O., and Mrowietz, U., Keloids. A fibroproliferative disorder of unknown etiology, Hautarzt, 53, 515 (2002)
- Rahban, S. R., and Garner, W. L., Fibroproliferative scars, Clin Plast Surg, 30, 77 (2003)
- Nedelec, B., Ghahary, A., Scott, P. G., and Tredget, E. E., Control of wound contraction. Basic and clinical features, Hand Clin, 16, 289 (2000)
- Krummel, T. M., Nelson, J. M., Diegelmann, R. F., Lindblad, W. J., Salzberg, A. M., Greenfield, L. J., and Cohen, I. K., Fetal response to injury in the rabbit, J Pediatr Surg, 22, 640 (1987)
- Summers, B. K., and Siegle, R. J., Facial cutaneous reconstructive surgery: general aesthetic principles, J Am Acad Dermatol, 29, 669 (1993)
- Iocono, J. A., Colleran, K. R., Remick, D. G., Gillespie, B. W., Ehrlich, H. P., and Garner, W. L., Interleukin-8 levels and activity in delayed-healing human thermal wounds, Wound Repair Regen, 8, 216 (2000)
- Stenn, K. S., Epibolin: a protein of human plasma that supports epithelial cell movement, Proc Natl Acad Sci U S A, 78, 6907 (1981)
- Clark, R. A., Fibrin and wound healing, Ann N Y Acad Sci, 936, 355 (2001)
- Hart, J., Inflammation. 1: Its role in the healing of acute wounds, J Wound Care, 11, 205 (2002)
- Sylvia, C. J., The role of neutrophil apoptosis in influencing tissue repair, J Wound Care, 12, 13 (2003)
- Tschaikowsky, K., Sittl, R., Braun, G. G., Hering, W., and Rugheimer, E., Increased fMet-Leu-Phe receptor expression and altered superoxide production of neutrophil granulocytes in septic and posttraumatic patients, Clin Investig, 72, 18 (1993)
- Thurston, A. J., Of blood, inflammation and gunshot wounds: the history of the control of sepsis, Aust N Z J Surg, 70, 855 (2000)
- Artuc, M., Hermes, B., Steckelings, U. M., Grutzkau, A., and Henz, B. M., Mast cells and their mediators in cutaneous wound healing--active participants or innocent bystanders?, Exp Dermatol, 8, 1 (1999)
- Diegelmann, R. F., Cohen, I. K., and Kaplan, A. M., The role of macrophages in wound repair: a review, Plast Reconstr Surg, 68, 107 (1981)
- Leibovich, S. J., and Ross, R., The role of the macrophage in wound repair. A study with hydrocortisone and antimacrophage serum, Am J Pathol, 78, 71 (1975)
- Roberts, A. B., and Sporn, M. B., Physiological actions and clinical applications of transforming growth factor-beta (TGF-beta), Growth Factors, 8, 1 (1993)
- Roberts, A. B., McCune, B. K., and Sporn, M. B., TGF-beta: regulation of extracellular matrix, Kidney Int, 41, 557 (1992)
- Hall, M. C., Young, D. A., Waters, J. G., Rowan, A. D., Chantry, A., Edwards, D. R., and Clark, I. M., The comparative role of activator protein 1 and Smad factors in the regulation of Timp-1 and MMP-1 gene expression by transforming growth factor-beta 1, J Biol Chem, 278, 10304 (2003)
- Yates, R. A., Nanney, L. B., Gates, R. E., and King, L. E., Jr., Epidermal growth factor and related growth factors, Int J Dermatol, 30, 687 (1991)
- Schultz, G., Rotatori, D. S., and Clark, W., EGF and TGF-alpha in wound healing and repair, J Cell Biochem, 45, 346 (1991)
- Hunt, T. K., Knighton, D. R., Thakral, K. K., Goodson, W. H., 3rd, and Andrews, W. S., Studies on inflammation and wound healing: angiogenesis and collagen synthesis stimulated in vivo by resident and activated wound macrophages, Surgery, 96, 48 (1984)
- LaVan, F. B., and Hunt, T. K., Oxygen and wound healing, Clin Plast Surg, 17, 463 (1990)
- Knighton, D. R., Hunt, T. K., Scheuenstuhl, H., Halliday, B. J., Werb, Z., and Banda, M. J., Oxygen tension regulates the expression of angiogenesis factor by macrophages, Science, 221, 1283 (1983)
- Battegay, E. J., Angiogenesis: mechanistic insights, neovascular diseases, and therapeutic prospects, J Mol Med, 73, 333 (1995)
- Gerber, H. P., Condorelli, F., Park, J., and Ferrara, N., Differential transcriptional regulation of the two vascular endothelial growth factor receptor genes. Flt-1, but not Flk- 1/KDR, is up-regulated by hypoxia, J Biol Chem, 272, 23659 (1997)
- Blumenkrantz, N., Assad, R., and Peterkofsky, B., Characterization of collagen hydroxylysyl glycosyltransferases as mainly intramembranous microsomal enzymes, J Biol Chem, 259, 854 (1984)
- Prockop, D. J., Sieron, A. L., and Li, S. W., Procollagen N-proteinase and procollagen C-proteinase. Two unusual metalloproteinases that are essential for procollagen processing probably have important roles in development and cell signaling, Matrix Biol, 16, 399 (1998)
- Zanaboni, G., Rossi, A., Onana, A. M., and Tenni, R., Stability and networks of hydrogen bonds of the collagen triple helical structure: influence of pH and chaotropic nature of three anions, Matrix Biol, 19, 511 (2000)
- Woodruff, C. W., Ascorbic acid--scurvy, Prog Food Nutr Sci, 1, 493 (1975)
- Hornstra, I. K., Birge, S., Starcher, B., Bailey, A. J., Mecham, R. P., and Shapiro, S. D., Lysyl oxidase is required for vascular and diaphragmatic development in mice, J Biol Chem, 278, 14387 (2003)
- Pilcher, B. K., Wang, M., Qin, X. J., Parks, W. C., Senior, R. M., and Welgus, H. G., Role of matrix metalloproteinases and their inhibition in cutaneous wound healing and allergic contact hypersensitivity, Ann N Y Acad Sci, 878, 12 (1999)
- Parks, W. C., Matrix metalloproteinases in repair, Wound Repair Regen, 7, 423 (1999)
- Mast, B. A., The Skin, in Wound Healing; Biochemical and Clinical Aspects, Cohen, I. K., Diegelmann, B., and Lindblad, W. J., Eds., W.B. Saunders Company, Philadelphia, pp. 344 (1992)
- Kovacs, E. J., Fibrogenic cytokines: the role of immune mediators in the development of scar tissue, Immunol Today, 12, 17 (1991)
- Shaffer, J. J., Taylor, S. C., and Cook-Bolden, F., Keloidal scars: a review with a critical look at therapeutic options, J Am Acad Dermatol, 46, S63 (2002)
- Diegelmann, R. F., Cohen, I. K., and McCoy, B. J., Growth kinetics and collagen synthesis of normal skin, normal scar and keloid fibroblasts in vitro, J Cell Physiol, 98, 341 (1979)
- Babu, M., Diegelmann, R., and Oliver, N., Keloid fibroblasts exhibit an altered response to TGF-beta, J Invest Dermatol, 99, 650 (1992)
- Chin, G. S., Liu, W., Peled, Z., Lee, T. Y., Steinbrech, D. S., Hsu, M., and Longaker, M. T., Differential expression of transforming growth factor-beta receptors I and II and activation of Smad 3 in keloid fibroblasts, Plast Reconstr Surg, 108, 423 (2001)
- Ehrlich, H. P., Desmouliere, A., Diegelmann, R. F., Cohen, I. K., Compton, C. C., Garner, W. L., Kapanci, Y., and Gabbiani, G., Morphological and immunochemical differences between keloid and hypertrophic scar, Am J Pathol, 145, 105 (1994)
- Gruber, B. L., Mast cells in the pathogenesis of fibrosis, Curr Rheumatol Rep, 5, 147 (2003)
- LeRoy, E. C., Trojanowska, M., and Smith, E. A., The pathogenesis of scleroderma (systemic sclerosis, SSc), Clin Exp Rheumatol, 9, 173 (1991)
- Kofford, M. W., Schwartz, L. B., Schechter, N. M., Yager, D. R., Diegelmann, R. F., and Graham, M. F., Cleavage of type I procollagen by human mast cell chymase initiates collagen fibril formation and generates a unique carboxyl-terminal propeptide, J Biol Chem, 272, 7127 (1997)
- Keller, B. P., Wille, J., van Ramshorst, B., and van der Werken, C., Pressure ulcers in intensive care patients: a review of risks and prevention, Intensive Care Med, 28, 1379 (2002)
- Allman, R. M., The impact of pressure ulcers on health care costs and mortality, Adv Wound Care, 11, 2 (1998)
- Wenk, J., Foitzik, A., Achterberg, V., Sabiwalsky, A., Dissemond, J., Meewes, C., Reitz, A., Brenneisen, P., Wlaschek, M., Meyer-Ingold, W., and Scharffetter- Kochanek, K., Selective pick-up of increased iron by deferoxamine-coupled cellulose abrogates the iron-driven induction of matrix-degrading metalloproteinase 1 and lipid peroxidation in human dermal fibroblasts in vitro: a new dressing concept, J Invest Dermatol, 116, 833 (2001)
- Falanga, V., Growth factors and wound healing, Dermatol Clin, 11, 667 (1993)
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“occurring in four stages: hemostasis, inflammation, proliferation, and remodeling [86].”
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- Authors
- Diegelmann, R.
- Venue
- Frontiers in Bioscience
- Publisher
- IMR Press
- Published
- 2004
- Volume
- 9
- Issue
- 1-3
- Pages
- 283
- ISSN
- 1093-4715 (ISSN-L)
- 1093-9946
- DOI
- 10.2741/1184
- OpenAlex
- W2142605112
- Cited by
- 2,147
- References
- 5
- Citations by year
- 2026: 52 · 2025: 91 · 2024: 106 · 2023: 111 · 2022: 119 · 2021: 124 · 2020: 124 · 2019: 117 · 2018: 152 · 2017: 139 · 2016: 158 · 2015: 140 · 2014: 136 · 2013: 126 · 2012: 98
- FWCI
- 6.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Frontiers in bioscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Dermatology › Dermatologic Treatments and Research
- Keywords
- wound healing, acute wounds, fibrosis, chronic non-healing ulcers, pressure ulcers, hemostasis, inflammation, proliferation, remodeling, platelet-derived growth factor, TGF-beta, neutrophils, macrophages, fibroblasts, extracellular matrix, mast cells, chronic inflammation, reactive oxygen species
- MeSH terms
- Animals, Fibrosis, Humans, Ulcer, Wound Healing, Wounds and Injuries, Signal Transduction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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