Immunology of Wound Healing
Open accessAbstract
PURPOSE OF REVIEW: Chronic wounds are a tremendous burden on the healthcare system and lead to significant patient morbidity and mortality. Normal cutaneous wound healing occurs through an intricate and delicate interplay between the immune system, keratinocytes, and dermal cells. Each cell type contributes signals that drive the normal phases of wound healing: hemostasis, inflammation, proliferation, and remodeling. This paper reviews how various immunological cell types and signaling molecules influence the way wounds develop, persist, and heal. RECENT FINDINGS: Concurrent with the achievement of hemostasis, neutrophils are the first cells to migrate to the wound bed, brought in by pro-inflammatory signals including IL-8. Their apoptosis and engulfment by macrophages (efferocytosis) provides a key signal to the local immune milieu, including macrophages, to transition to an anti-inflammatory, pro-repair state, where angiogenesis occurs and granulation tissue is laid down. Myofibroblasts, activated through contractile forces and signaling molecules, then drive remodeling, where granulation tissue becomes scar. Unchecked inflammation at this stage can result in abnormal scar formation. SUMMARY: Although the derangement of immune signals at any stage can result in impaired wound healing, recent research has shown that the key transition point lies between the inflammatory and the proliferative phases. This review summarizes the events that facilitate this transition and discusses how this process can be disrupted, leading to chronic, non-healing wounds.
AI snapshot
Written from the paper’s full text.
TL;DR
This review summarizes immune mechanisms across hemostasis, inflammation, proliferation, and remodeling, arguing that the critical transition from the inflammatory to the proliferative phase often fails in chronic wounds. It highlights neutrophil apoptosis/efferocytosis and macrophage polarization as key drivers of repair.
Key findings
- Chronic wounds in the USA afflict approximately 6.5 million individuals and cost the healthcare system over 25 billion dollars annually; their mortality effect has been reported as comparable to cancer.
- Normal wound healing is divided into hemostasis (minutes to hours), inflammation (days 1–3), proliferation and repair (days 4–21), and remodeling (days 21–365); the key inflammatory-to-proliferative transition occurs around days 2–5 and often fails in chronic wounds.
- Neutrophils are early responders recruited by IL-8/CXCL8; their apoptosis and macrophage engulfment (efferocytosis) signal a shift to anti-inflammatory, pro-repair macrophages. Persistent neutrophils, NETs, proteases/MMPs, reactive oxygen species, and elevated CXCL8 contribute to chronic, non-healing wounds.
- Anti-inflammatory macrophages promote angiogenesis, granulation tissue, and re-epithelialization via VEGF, TGF-β, PDGF, EGF, KGF, and other signals; impaired pro- to anti-inflammatory macrophage transition—seen with iron overload, hyperglycemia, and hypoxia—stalls healing. Mature scars regain only 80% of initial tensile strength.
Methods
- Narrative review of the literature; no primary data, sample, or statistical analysis are reported.
- Synthesizes immune cell and signaling pathways across the four phases of wound healing, focusing on the inflammatory-to-proliferative transition and chronic wounds.
- Draws on cited animal models, in vitro studies, and human wound observations; no systematic search or meta-analysis is described.
Limitations
- The paper states no limitations.
- Evident from the text: it is a narrative review without systematic search, inclusion criteria, or quality appraisal.
- Evident from the text: many mechanistic conclusions rely on mouse models and in vitro findings, with limited direct human chronic wound data; no original experiments or quantitative synthesis are presented.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
0 of 81 cited sources checked · 0 supported · 0 flagged
- Premisecitation
In impaired models of wound healing such as diabetes, where infection risk is higher, neutrophils are clearly required.
“In impaired models of wound healing, such as diabetes, where infection risk is higher, neutrophils are clearly required [28].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [28] Wilgus TA, Roy S, McDaniel JC. Neutrophils and wound repair: positive actions and negative reactions. Adv Wound Care. 2013;2(7):379–88. https://doi.org/10.1089/wound.2012.0383 . source
Not checked in the free run.
- Rests on an assumption: Findings from mouse models of wound healing can be generalized to human wound healing and chronic wounds.
- Premisecitation
Neutrophil influx into a wound is mediated by chemical signals including IL-8/CXCL8.
“Their influx is mediated by a number of chemical signals, including IL-8, or CXCL8, as mentioned above, and neutrophils have over 30 different receptors that mitigate their migration and activation response [24].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [24] Futosi K, Fodor S, Mocsai A. Neutrophil cell surface receptors and their intracellular signal transduction pathways. Int Immunopharmacol. 2013;17(3):638–50. https://doi.org/10.1016/j.intimp.2013.06.034 . source
Not checked in the free run.
- Premisecitation
Normal wound healing can generally be broken down into four overlapping but distinct steps: hemostasis, inflammation, proliferation and repair, and wound remodeling.
“normal wound healing can generally be broken down into four over-lapping but distinct steps (Fig. 1). These steps include hemostasis (minutes to hours after injury), inflammation (days 1–3), proliferation and repair (days 4–21), and lastly, wound remodeling (days 21–365) [8, 9].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [8] Morton LM, Phillips TJ. Wound healing and treating wounds: differential diagnosis and evaluation of chronic wounds. J Am Acad Dermatol. 2016;74(4):589–605; quiz −6. https://doi.org/10.1016/j.jaad.2015.08.068 . source
Not checked in the free run.
- cites [9] Reinke JM, Sorg H. Wound repair and regeneration. Eur Surg Res. 2012;49(1):35–43. https://doi.org/10.1159/000339613 . source
Not checked in the free run.
- Premisecitation
Chronic wounds demonstrate significantly increased levels of the potent neutrophil chemoattractant CXCL8.
“chronic wounds demonstrate significantly increased levels of the potent neutrophil chemoattractant, CXCL8 [58].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [58] Fivenson DP, Faria DT, Nickoloff BJ, Poverini PJ, Kunkel S, Burdick M, et al. Chemokine and inflammatory cytokine changes during chronic wound healing. Wound Repair Regen. 1997;5(4):310–22. https://doi.org/10.1046/j.1524-475X.1997.50405.x . source
Not checked in the free run.
- Premisereasoning
Platelet activation releases growth factors such as PDGF and immune mediators responsible for activation of the immune system and transition to the inflammatory phase.
“Platelet activation not only results in hemostasis, but also in the release of growth factors such as platelet-derived growth factor (PDGF) as well as immune mediators that are responsible for activation of the immune system and transition to the inflammatory phase of wound healing.”
Quote in the paperNot a substantial claim
- Premisecitation
In non-aged, non-impaired mouse models, neutrophil depletion does not negatively affect wound healing as profoundly as macrophage deletion.
“mouse models of wound healing have shown that in non-aged, non-impaired models, neutrophil depletion does not negatively affect wound healing as profoundly as macrophage deletion [25–27].”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [25] Leibovich SJ, Ross R. The role of the macrophage in wound repair. A study with hydrocortisone and antimacrophage serum. Am J Pathol. 1975;78(1):71–100.
Not checked in the free run.
- cites [26] Pinhal-Enfield G, Ramanathan M, Hasko G, Vogel SN, Salzman AL, Boons GJ, et al. An angiogenic switch in macrophages involving synergy between Toll-like receptors 2, 4, 7, and 9 and adenosine A(2A) receptors. Am J Pathol. 2003;163(2):711–21. https://doi.org/10.1016/s0002-9440(10)63698-x . source
Not checked in the free run.
- cites [27] Simpson DM, Ross R. The neutrophilic leukocyte in wound repair a study with antineutrophil serum. J Clin Invest. 1972;51(8):2009–23. https://doi.org/10.1172/jci107007 . source
Not checked in the free run.
- Rests on an assumption: Findings from mouse models of wound healing can be generalized to human wound healing and chronic wounds.
- Interpretationnone given
Chronic wounds fail to shift from the inflammatory to the proliferative phase of wound healing.
“New research has illustrated that chronic wounds fail to shift from the inflammatory to the proliferative phase of wound healing”
Quote in the paperSubstantial claim - Interpretationnone given
The key transition point in wound healing lies between the inflammatory and the proliferative phases.
“recent research has shown that the key transition point lies between the inflammatory and the proliferative phases.”
- Also stated in: § Conclusions · plain
“Recent research has shown that the key transition point in wound healing lies between the inflammatory and the proliferative phases.”
Quote in the paperNot a substantial claim - Also stated in: § Conclusions · plain
- Premisecitation
The immune system plays a substantial role in wound repair mechanisms.
“the immune system has been found to play a substantial role due to its impact on several repair mechanisms [6, 7].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [6] MA S, MJ N. The innate immune system in acute and chronic wounds. Adv Wound Care. 2016;5(2):65–78. https://doi.org/10.1089/wound.2014.0608 . source
Not checked in the free run.
- cites [7] Strbo N, Yin N, Stojadinovic O. Innate and adaptive immune responses in wound epithelialization. Adv Wound Care. 2014;3(7):492–501. https://doi.org/10.1089/wound.2012.0435 . source
Not checked in the free run.
- Premisenone given
Myofibroblasts, activated through contractile forces and signaling molecules, drive remodeling, where granulation tissue becomes scar.
“Myofibroblasts, activated through contractile forces and signaling molecules, then drive remodeling, where granulation tissue becomes scar.”
Quote in the paperNot a substantial claim - Interpretationreasoning
The sustained and inappropriate presence of neutrophils at the site of injury is a major contributing factor in non-healing wounds.
“In sum, the sustained and inappropriate presence of neutrophils at the site of injury is a major contributing factor in non-healing wounds.”
Quote in the paperSubstantial claim - Premisecitation
Apoptosis and engulfment of neutrophils by macrophages provides a key signal to the local immune milieu to transition to an anti-inflammatory, pro-repair state.
“Their apoptosis and engulfment by macrophages (efferocytosis) provides a key signal to the local immune milieu, including macrophages, to transition to an anti-inflammatory, pro-repair state”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [47] Fadok VA, Bratton DL, Konowal A, Freed PW, Westcott JY, Henson PM. Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF. J Clin Invest. 1998;101(4):890–8. https://doi.org/10.1172/jci1112 . source
Not checked in the free run.
- cites [48] Serhan CN, Chiang N, Van Dyke TE. Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol. 2008;8(5):349–61. https://doi.org/10.1038/nri2294 . source
Not checked in the free run.
- cites [49] Widgerow AD. Cellular resolution of inflammation—catabasis. Wound Repair Regen. 2012;20(1):2–7. https://doi.org/10.1111/j.1524-475X.2011.00754.x . source
Not checked in the free run.
- Premisecitation
Derangement of immune signals at any stage can result in impaired wound healing.
“Although the derangement of immune signals at any stage can result in impaired wound healing, recent research has shown that the key transition point lies between the inflammatory and the proliferative phases.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [10••]
Not checked in the free run.
- Premisenone given
Persistence of neutrophils is associated with delayed wound healing and chronic wounds.
“their persistence, as will be discussed in detail below, has been associated with delayed wound healing and chronic wounds.”
Quote in the paperNot a substantial claim - Premisenone given
Unchecked inflammation at the remodeling stage can result in abnormal scar formation.
“Unchecked inflammation at this stage can result in abnormal scar formation.”
Quote in the paperSubstantial claim - Premisecitation
In physiologic wound repair, neutrophil apoptosis followed by local macrophage uptake of apoptotic neutrophils triggers a transition out of the inflammatory phase.
“In physiologic wound repair, neutrophils undergo apoptosis after carrying out their various functions at the site of injury. Local macrophage uptake of apoptotic neutrophils then triggers a transition out of inflammatory phase [47–49].”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [47] Fadok VA, Bratton DL, Konowal A, Freed PW, Westcott JY, Henson PM. Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF. J Clin Invest. 1998;101(4):890–8. https://doi.org/10.1172/jci1112 . source
Not checked in the free run.
- cites [48] Serhan CN, Chiang N, Van Dyke TE. Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol. 2008;8(5):349–61. https://doi.org/10.1038/nri2294 . source
Not checked in the free run.
- cites [49] Widgerow AD. Cellular resolution of inflammation—catabasis. Wound Repair Regen. 2012;20(1):2–7. https://doi.org/10.1111/j.1524-475X.2011.00754.x . source
Not checked in the free run.
- Premisecitation
Hemostasis is achieved within the first minutes to hours of injury through a series of serine protease events designed to prevent blood loss.
“The initial events following injury are designed to achieve hemostasis within the first minutes to hours of injury based on a series of serine protease events designed to prevent blood loss [11].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [11] Smith SA, Travers RJ, Morrissey JH. How it all starts: initiation of the clotting cascade. Crit Rev Biochem Mol Biol. 2015;50(4):326–36. https://doi.org/10.3109/10409238.2015.1050550 . source
Not checked in the free run.
- Premisecitation
Neutrophils can eliminate organisms residing in the extracellular environment through the deployment of neutrophil extracellular traps (NETs).
“More recent evidence indicates that neutrophils can also eliminate organisms residing in the extracellular environment through the deployment of neutrophil extracellular traps (NETs).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [41] Papayannopoulos V, Zychlinsky A. NETs: a new strategy for using old weapons. Trends Immunol. 2009;30(11):513–21. https://doi.org/10.1016/j.it.2009.07.011 . source
Not checked in the free run.
- cites [42] Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, et al. Neutrophil extracellular traps kill bacteria. Science. 2004;303(5663):1532–5. https://doi.org/10.1126/science.1092385 . source
Not checked in the free run.
- Premisecitation
Neutrophils defend against wound infection by phagocytosing pathogens and killing them through release of reactive oxygen species, proteases, or antimicrobial proteins.
“neutrophils defend against wound infection by phagocytosing pathogens then killing them through release of reactive oxygen species, proteases, or antimicrobial proteins [28].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [28] Wilgus TA, Roy S, McDaniel JC. Neutrophils and wound repair: positive actions and negative reactions. Adv Wound Care. 2013;2(7):379–88. https://doi.org/10.1089/wound.2012.0383 . source
Not checked in the free run.
- Premisereasoning
Prolonged presence of neutrophils and their associated inflammatory mediators in the wound milieu contributes to the formation and persistence of chronic wounds.
“Many studies suggest that the prolonged presence of neutrophils and their associated inflammatory mediators in the wound milieu contributes to the formation and persistence of chronic wounds.”
Quote in the paperSubstantial claim - Premisecitation
The remodeling phase is largely driven by myofibroblasts.
“This remodeling phase is largely driven by myofibroblasts, which develop from fibroblasts in response to both mechanical tension and TGF-β signaling and are responsible for contraction of the wound [94].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [94] Yannas IV, Tzeranis DS, So PTC. Regeneration of injured skin and peripheral nerves requires control of wound contraction, not scar formation. Wound Repair Regen. 2017;25(2):177–91. https://doi.org/10.1111/wrr.12516 . source
Not checked in the free run.
- Premisecitation
In a mouse model of iron overload, local wound macrophages persisted in a pro-inflammatory state with excess production of iNOS, IL-12, TNF-α, and free radicals, leading to impaired wound healing.
“in a mouse model of iron overload, local wound macrophages persisted in a pro-inflammatory state with excess production of inducible nitric oxide synthase (iNOS), IL-12, and TNF-α, in addition to free radicals, leading to impaired wound healing [81].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [81] Sindrilaru A, Peters T, Wieschalka S, Baican C, Baican A, Peter H, et al. An unrestrained proinflammatory M1 macrophage population induced by iron impairs wound healing in humans and mice. J Clin Investig. 2011;121(3):985–97. https://doi.org/10.1172/jci44490 . source
Not checked in the free run.
- Rests on an assumption: Findings from mouse models of wound healing can be generalized to human wound healing and chronic wounds.
- Premisecitation
Myofibroblast-induced fibrosis can be over-activated by Th2-derived cytokines IL-4 and IL-13.
“Recent evidence indicates that myofibroblast-induced fibrosis can be over-activated, not only in the setting of signaling through TGF-β, but also in the setting of Th2-derived cytokines IL-4 and IL-13; Th1 cytokines, such as IFN-γ, attenuate excessive scar formation [100, 101].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [100] Wynn TA. Fibrotic disease and the T(H)1/T(H)2 paradigm. Nat Rev Immunol. 2004;4(8):583–94. https://doi.org/10.1038/nri1412 . source
Not checked in the free run.
- cites [101] Hinz B. The role of myofibroblasts in wound healing. Curr Res Transl Med. 2016;64(4):171–7. https://doi.org/10.1016/j.retram.2016.09.003 . source
Not checked in the free run.
- Premisecitation
Myofibroblast-induced fibrosis can be over-activated by signaling through TGF-β.
“Recent evidence indicates that myofibroblast-induced fibrosis can be over-activated, not only in the setting of signaling through TGF-β, but also in the setting of Th2-derived cytokines IL-4 and IL-13; Th1 cytokines, such as IFN-γ, attenuate excessive scar formation [100, 101].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [100] Wynn TA. Fibrotic disease and the T(H)1/T(H)2 paradigm. Nat Rev Immunol. 2004;4(8):583–94. https://doi.org/10.1038/nri1412 . source
Not checked in the free run.
- cites [101] Hinz B. The role of myofibroblasts in wound healing. Curr Res Transl Med. 2016;64(4):171–7. https://doi.org/10.1016/j.retram.2016.09.003 . source
Not checked in the free run.
- Premisecitation
Myofibroblasts contribute to remodeling by releasing MMPs that degrade collagen laid down during granulation tissue formation.
“In addition to contraction of wound beds and generation of collagen, myofibroblasts contribute to remodeling by release of MMPs that degrade collagen laid down during granulation tissue formation [96, 97].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [96] Darby IA, Laverdet B, Bonte F, Desmouliere A. Fibroblasts and myofibroblasts in wound healing. Clin Cosmet Investig Dermatol. 2014;7:301–11. https://doi.org/10.2147/ccid.s50046 . source
Not checked in the free run.
- cites [97] Van De Water L, Varney S, Tomasek JJ. Mechanoregulation of the myofibroblast in wound contraction, scarring, and fibrosis: opportunities for new therapeutic intervention. Adv Wound Care. 2013;2(4):122–41. https://doi.org/10.1089/wound.2012.0393 . source
Not checked in the free run.
- Premisecitation
Myofibroblasts are responsible for contraction of the wound.
“This remodeling phase is largely driven by myofibroblasts, which develop from fibroblasts in response to both mechanical tension and TGF-β signaling and are responsible for contraction of the wound [94].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [94] Yannas IV, Tzeranis DS, So PTC. Regeneration of injured skin and peripheral nerves requires control of wound contraction, not scar formation. Wound Repair Regen. 2017;25(2):177–91. https://doi.org/10.1111/wrr.12516 . source
Not checked in the free run.
- Premisecitation
Myofibroblasts express smooth muscle actin (SMA).
“Myofibroblasts express smooth muscle actin (SMA), which is responsible for generating the contractile force attributed to this cell type [94, 95].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [94] Yannas IV, Tzeranis DS, So PTC. Regeneration of injured skin and peripheral nerves requires control of wound contraction, not scar formation. Wound Repair Regen. 2017;25(2):177–91. https://doi.org/10.1111/wrr.12516 . source
Not checked in the free run.
- cites [95] Hinz B, Phan SH, Thannickal VJ, Prunotto M, Desmouliere A, Varga J, et al. Recent developments in myofibroblast biology: paradigms for connective tissue remodeling. Am J Pathol. 2012;180(4):1340–55. https://doi.org/10.1016/j.ajpath.2012.02.004 . source
Not checked in the free run.
- Premisecitation
The differentiation of myofibroblasts into fat cells is dependent upon neogenic hair follicles, which lead to BMP signaling and activation of adipocyte transcription factors.
“This process is dependent upon neogenic hair follicles, which lead to bone morphogenic protein (BMP) signaling and activation of adipocyte transcription factors [98••].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites 98••
Not checked in the free run.
- Premisecitation
Hypertrophic scars tend to arise in areas of high tension.
“Hypertrophic scars arise within 1–2 months of injury, and tend to arise in areas of high tension.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [99] Gauglitz GG, Korting HC, Pavicic T, Ruzicka T, Jeschke MG. Hypertrophic scarring and keloids: pathomechanisms and current and emerging treatment strategies. Mol Med. 2011;17(1–2):113–25. https://doi.org/10.2119/molmed.2009.00153 . source
Not checked in the free run.
- Premisecitation
Normally, myofibroblasts coordinate the breakdown of granulation tissue and its replacement with long-lasting type I collagen.
“Normally, myofibroblasts carefully coordinate the breakdown of granulation tissue and replacement with long-lasting type I collagen [100].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [100] Wynn TA. Fibrotic disease and the T(H)1/T(H)2 paradigm. Nat Rev Immunol. 2004;4(8):583–94. https://doi.org/10.1038/nri1412 . source
Not checked in the free run.
- Interpretationnone given
Cutaneous wound healing occurs through an interplay between the immune system, keratinocytes, and dermal cells such as platelets, fibroblasts, and myofibroblasts.
“Cutaneous wound healing occurs through an intricate and delicate interplay between the immune system, keratinocytes, and dermal cells such as platelets, fibroblasts, and myofibroblasts.”
Quote in the paperSubstantial claim - Premisecitation
Efferocytosis of apoptotic neutrophils induces macrophages to transition from a pro-inflammatory phenotype to an anti-inflammatory phenotype.
“Macrophages in the wound site are responsible for phagocytosis of apoptotic neutrophils, a process known as efferocytosis [73••]. This action itself induces macrophages to transition from a pro-inflammatory phenotype, to an anti-inflammatory phenotype”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [73••]
Not checked in the free run.
- cites [47] Fadok VA, Bratton DL, Konowal A, Freed PW, Westcott JY, Henson PM. Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF. J Clin Invest. 1998;101(4):890–8. https://doi.org/10.1172/jci1112 . source
Not checked in the free run.
- Premisecitation
Keloid scars can occur at any point post-injury.
“Keloid scars can occur at any point post-injury, do not tend to occur in areas of high tension, and may grow beyond the borders of the initial scar [99].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [99] Gauglitz GG, Korting HC, Pavicic T, Ruzicka T, Jeschke MG. Hypertrophic scarring and keloids: pathomechanisms and current and emerging treatment strategies. Mol Med. 2011;17(1–2):113–25. https://doi.org/10.2119/molmed.2009.00153 . source
Not checked in the free run.
- Premisecitation
In macrophage-deficient models, angiogenesis is impaired.
“in macrophage-deficient models, angiogenesis is impaired [85].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [85] Fantin A, Vieira JM, Gestri G, Denti L, Schwarz Q, Prykhozhij S, et al. Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction. Blood. 2010;116(5):829–40. https://doi.org/10.1182/blood-2009-12-257832 . source
Not checked in the free run.
- Rests on an assumption: Findings from mouse models of wound healing can be generalized to human wound healing and chronic wounds.
- Premisecitation
Macrophages from patients with chronic, non-healing wounds have been shown to have higher levels of iron based on Prussian blue staining.
“Macrophages from patients with chronic, non-healing, wounds have been shown to have higher levels of iron, based on Prussian blue staining [82, 83].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [82] Zamboni P, Izzo M, Tognazzo S, Carandina S, De Palma M, Catozzi L, et al. The overlapping of local iron overload and HFE mutation in venous leg ulcer pathogenesis. Free Radic Biol Med. 2006;40(10):1869–73. https://doi.org/10.1016/j.freeradbiomed.2006.01.026 . source
Not checked in the free run.
- cites [83] Zamboni P, Tognazzo S, Izzo M, Pancaldi F, Scapoli GL, Liboni A, et al. Hemochromatosis C282Y gene mutation increases the risk of venous leg ulceration. J Vasc Surg. 2005;42(2):309–14. https://doi.org/10.1016/j.jvs.2005.04.003 . source
Not checked in the free run.
- Premisecitation
DAMPs and PAMPs, as well as interferon-γ released from natural killer cells, polarize macrophages into a pro-inflammatory phenotype.
“DAMPs and PAMPs (released from necrotic tissue and pathogens, respectively), as well as interferon-γ [(IFN-γ), released from natural killer cells] polarize macrophages into a pro-inflammatory phenotype [64].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [64] Adams DO. Molecular interactions in macrophage activation. Immunol Today. 1989;10(2):33–5. https://doi.org/10.1016/0167-5699(89)90298-3 . source
Not checked in the free run.
- Interpretationcitation
Transitioning from a pro-inflammatory macrophage-dominant wound to an anti-inflammatory macrophage-dominant milieu is essential in resolving inflammation and preparing the wound for effective repair.
“Transitioning from a pro-inflammatory macrophage-dominant wound to an anti-inflammatory macrophage-dominant milieu is essential in resolving inflammation and preparing the wound for effective repair [72].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [72] Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol. 2008;8(12):958–69. https://doi.org/10.1038/nri2448 . source
Not checked in the free run.
- Premisecitation
Iron overload, commonly seen in the skin in the setting of venous stasis, is a signal known to prolong the presence of pro-inflammatory macrophages.
“Certain signals are known to prolong the presence of pro-inflammatory macrophages, including iron overload, which is commonly seen in the skin in the setting of venous stasis [81, 82].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [81] Sindrilaru A, Peters T, Wieschalka S, Baican C, Baican A, Peter H, et al. An unrestrained proinflammatory M1 macrophage population induced by iron impairs wound healing in humans and mice. J Clin Investig. 2011;121(3):985–97. https://doi.org/10.1172/jci44490 . source
Not checked in the free run.
- cites [82] Zamboni P, Izzo M, Tognazzo S, Carandina S, De Palma M, Catozzi L, et al. The overlapping of local iron overload and HFE mutation in venous leg ulcer pathogenesis. Free Radic Biol Med. 2006;40(10):1869–73. https://doi.org/10.1016/j.freeradbiomed.2006.01.026 . source
Not checked in the free run.
- Premisecitation
Wound bed myofibroblasts may further differentiate into fat cells, replenishing subcutaneous adipose tissue.
“However, exciting new research indicates that these wound bed myofibroblasts may further differentiate into fat cells, replenishing subcutaneous adipose tissue.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites 98••
Not checked in the free run.
- Premisecitation
SMA is responsible for generating the contractile force attributed to myofibroblasts.
“Myofibroblasts express smooth muscle actin (SMA), which is responsible for generating the contractile force attributed to this cell type [94, 95].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [94] Yannas IV, Tzeranis DS, So PTC. Regeneration of injured skin and peripheral nerves requires control of wound contraction, not scar formation. Wound Repair Regen. 2017;25(2):177–91. https://doi.org/10.1111/wrr.12516 . source
Not checked in the free run.
- cites [95] Hinz B, Phan SH, Thannickal VJ, Prunotto M, Desmouliere A, Varga J, et al. Recent developments in myofibroblast biology: paradigms for connective tissue remodeling. Am J Pathol. 2012;180(4):1340–55. https://doi.org/10.1016/j.ajpath.2012.02.004 . source
Not checked in the free run.
- Interpretationreasoning
Each cell type contributes proteins and molecular signals that transition the cycle through the normal phases of wound healing (hemostasis, inflammatory, proliferative, and remodeling).
“Each cell type contributes proteins and molecular signals that transition the cycle through the normal phases of wound healing, including the hemostasis, inflammatory, proliferative, and remodeling phases.”
Quote in the paperSubstantial claim - Premisecitation
Myofibroblasts develop from fibroblasts in response to mechanical tension and TGF-β signaling.
“This remodeling phase is largely driven by myofibroblasts, which develop from fibroblasts in response to both mechanical tension and TGF-β signaling and are responsible for contraction of the wound [94].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [94] Yannas IV, Tzeranis DS, So PTC. Regeneration of injured skin and peripheral nerves requires control of wound contraction, not scar formation. Wound Repair Regen. 2017;25(2):177–91. https://doi.org/10.1111/wrr.12516 . source
Not checked in the free run.
- Premisecitation
In vitro studies have shown that blocking signaling of IL-10 in fibroblasts may decrease keloid scar formation.
“A role for these therapies in cutaneous fibrosis remains to be explored, though in vitro studies have shown that blocking signaling of the related cytokine IL-10 in fibroblasts may decrease keloid scar formation [102].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [102] Shi J, Li J, Guan H, Cai W, Bai X, Fang X, et al. Anti-fibrotic actions of interleukin-10 against hypertrophic scarring by activation of PI3K/AKT and STAT3 signaling pathways in scar-forming fibroblasts. PLoS One. 2014;9(5):e98228. https://doi.org/10.1371/journal.pone.0098228 . source
Not checked in the free run.
- Premisecitation
Angiogenesis occurs in a two-step process: vessel sprouting, followed by vessel anastomosis.
“New blood vessel formation, referred to as angiogenesis, occurs in a two-step process: vessel sprouting, followed by vessel anastomosis [85].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [85] Fantin A, Vieira JM, Gestri G, Denti L, Schwarz Q, Prykhozhij S, et al. Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction. Blood. 2010;116(5):829–40. https://doi.org/10.1182/blood-2009-12-257832 . source
Not checked in the free run.
- Premisecitation
Keratinocytes activate fibroblasts in a feedback loop through the production of fibronectin, tenascin C, and laminin 332.
“Keratinocytes themselves further activate fibroblasts in a feedback loop through the production of fibronectin, tenascin C, and laminin 332 (Fig. 2) [93].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [93] Iorio V, Troughton LD, Hamill KJ. Laminins: roles and utility in wound repair. Adv Wound Care. 2015;4(4):250–63. https://doi.org/10.1089/wound.2014.0533 . source
Not checked in the free run.
- Premisecitation
Re-epithelialization is initiated by EGF, KGF, and TGF-α, which are produced by platelets, keratinocytes, and activated pro-repair, anti-inflammatory macrophages.
“Re-epithelialization is initiated by epidermal growth factor (EGF), keratinocyte growth factor (KGF), and transforming growth factor-α (TGF-α), which are produced by platelets, keratinocytes, and activated pro-repair, anti-inflammatory macrophages [92].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [92] Schultz G, Rotatori DS, Clark W. EGF and TGF-alpha in wound healing and repair. J Cell Biochem. 1991;45(4):346–52. https://doi.org/10.1002/jcb.240450407 . source
Not checked in the free run.
- Premisecitation
Hypertrophic scars arise within 1-2 months of injury.
“Hypertrophic scars arise within 1–2 months of injury, and tend to arise in areas of high tension.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [99] Gauglitz GG, Korting HC, Pavicic T, Ruzicka T, Jeschke MG. Hypertrophic scarring and keloids: pathomechanisms and current and emerging treatment strategies. Mol Med. 2011;17(1–2):113–25. https://doi.org/10.2119/molmed.2009.00153 . source
Not checked in the free run.
- Premisecitation
Keloid scars may grow beyond the borders of the initial scar.
“Keloid scars can occur at any point post-injury, do not tend to occur in areas of high tension, and may grow beyond the borders of the initial scar [99].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [99] Gauglitz GG, Korting HC, Pavicic T, Ruzicka T, Jeschke MG. Hypertrophic scarring and keloids: pathomechanisms and current and emerging treatment strategies. Mol Med. 2011;17(1–2):113–25. https://doi.org/10.2119/molmed.2009.00153 . source
Not checked in the free run.
- Premisecitation
Th1 cytokines, such as IFN-γ, attenuate excessive scar formation.
“Recent evidence indicates that myofibroblast-induced fibrosis can be over-activated, not only in the setting of signaling through TGF-β, but also in the setting of Th2-derived cytokines IL-4 and IL-13; Th1 cytokines, such as IFN-γ, attenuate excessive scar formation [100, 101].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [100] Wynn TA. Fibrotic disease and the T(H)1/T(H)2 paradigm. Nat Rev Immunol. 2004;4(8):583–94. https://doi.org/10.1038/nri1412 . source
Not checked in the free run.
- cites [101] Hinz B. The role of myofibroblasts in wound healing. Curr Res Transl Med. 2016;64(4):171–7. https://doi.org/10.1016/j.retram.2016.09.003 . source
Not checked in the free run.
- Premisecitation
Keloid scars do not tend to occur in areas of high tension.
“Keloid scars can occur at any point post-injury, do not tend to occur in areas of high tension, and may grow beyond the borders of the initial scar [99].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [99] Gauglitz GG, Korting HC, Pavicic T, Ruzicka T, Jeschke MG. Hypertrophic scarring and keloids: pathomechanisms and current and emerging treatment strategies. Mol Med. 2011;17(1–2):113–25. https://doi.org/10.2119/molmed.2009.00153 . source
Not checked in the free run.
- Interpretationreasoning
Alteration of normal signals at any stage can result in impaired wound healing, with non-healing wounds or excessive scar formation.
“Alteration of normal signals at any stage can result in impaired wound healing, with non-healing wounds or excessive scar formation, at great cost to both patients and the healthcare system.”
Quote in the paperSubstantial claim
- May combine two claims. 15
May combine two claims.
PremisecitationNeutrophils are the first cells to migrate to the wound bed, brought in by pro-inflammatory signals including IL-8.
“Concurrent with the achievement of hemostasis, neutrophils are the first cells to migrate to the wound bed, brought in by pro-inflammatory signals including IL-8.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [31] Baggiolini M, Loetscher P, Moser B. Interleukin-8 and the chemokine family. Int J Immunopharmacol. 1995;17(2):103–8. source
Not checked in the free run.
May combine two claims.
PremisecitationNeutrophils are the most abundant inflammatory cells to infiltrate a new wound and function mainly to remove debris and prevent infection.
“Neutrophils represent the most abundant inflammatory cells to infiltrate a new wound and function mainly to remove debris and prevent infection [22, 23].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [22] Engelhardt E, Toksoy A, Goebeler M, Debus S, Brocker EB, Gillitzer R. Chemokines IL-8, GROalpha, MCP-1, IP-10, and Mig are sequentially and differentially expressed during phase-specific infiltration of leukocyte subsets in human wound healing. Am J Pathol. 1998;153(6):1849–60. source
Not checked in the free run.
- cites [23] de Oliveira S, Rosowski EE, Huttenlocher A. Neutrophil migration in infection and wound repair: going forward in reverse. Nat Rev Immunol. 2016;16(6):378–91. https://doi.org/10.1038/nri.2016.49 . source
Not checked in the free run.
May combine two claims.
PremisecitationNETs are detected in excess in diabetic foot wounds and delay healing, and inhibition of NETosis and NET function in mouse models of delayed wound healing improves outcomes.
“NETs have also been detected in excess in diabetic foot wounds and have been shown to delay healing, and inhibition of NETosis and NET function in mouse models of delayed wound healing improves outcomes [59•].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [59•]
Not checked in the free run.
- Rests on an assumption: Findings from mouse models of wound healing can be generalized to human wound healing and chronic wounds.
May combine two claims.
PremisecitationMacrophages play a critical role in wound healing, including in angiogenesis, fibroplasia, cell proliferation, and transition out of the inflammatory phase.
“Macrophages play a critical role in wound healing, and their roles in angiogenesis, fibroplasia, cell proliferation, and transition out of the inflammatory phase is clear (Fig. 2) [25–27, 60].”
Quote in the paperNot a substantial claim0 of 4 sources checked- cites [25] Leibovich SJ, Ross R. The role of the macrophage in wound repair. A study with hydrocortisone and antimacrophage serum. Am J Pathol. 1975;78(1):71–100.
Not checked in the free run.
- cites [26] Pinhal-Enfield G, Ramanathan M, Hasko G, Vogel SN, Salzman AL, Boons GJ, et al. An angiogenic switch in macrophages involving synergy between Toll-like receptors 2, 4, 7, and 9 and adenosine A(2A) receptors. Am J Pathol. 2003;163(2):711–21. https://doi.org/10.1016/s0002-9440(10)63698-x . source
Not checked in the free run.
- cites [27] Simpson DM, Ross R. The neutrophilic leukocyte in wound repair a study with antineutrophil serum. J Clin Invest. 1972;51(8):2009–23. https://doi.org/10.1172/jci107007 . source
Not checked in the free run.
- cites [60] Koh TJ, DiPietro LA. Inflammation and wound healing: the role of the macrophage. Expert Rev Mol Med. 2011;13:e23. https://doi.org/10.1017/s1462399411001943 . source
Not checked in the free run.
May combine two claims.
PremisecitationThe inflammatory phase overlaps considerably with initial hemostasis and occurs during the first 72 h after tissue injury.
“The inflammatory phase overlaps considerably with initial hemostasis, occurring during the first 72 h after tissue injury [16].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [16] Eming SA, Martin P, Tomic-Canic M. Wound repair and regeneration: mechanisms, signaling, and translation. Sci Transl Med. 2014;6(265):265sr6. https://doi.org/10.1126/scitranslmed.3009337 . source
Not checked in the free run.
May combine two claims.
PremisecitationHistamine released by the activated complement cascade causes capillary dilation and leakage, accelerating migration of inflammatory cells and full transition to the inflammatory phase.
“After hemostasis is achieved, histamine released by the activated complement cascade causes capillary dilation and leakage, accelerating migration of inflammatory cells into the wound bed and full transition to the inflammatory phase of wound healing [15].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [15] Sinno H, Prakash S. Complements and the wound healing cascade: an updated review. Plast Surg Int. 2013;2013:146764–7. https://doi.org/10.1155/2013/146764 . source
Not checked in the free run.
May combine two claims.
PremisecitationNeutrophil-derived proteases such as elastase and matrix metalloproteinases can degrade healthy extracellular matrix, and increased levels of these proteases have been repeatedly detected in chronic wounds.
“neutrophil-derived proteases, such as elastase and matrix metalloproteinases (MMPs), can degrade healthy extracellular matrix (ECM), and increased levels of these proteases have been repeatedly detected in chronic wounds [52–56].”
Quote in the paperSubstantial claim0 of 5 sources checked- cites [52] Briggaman RA, Schechter NM, Fraki J, Lazarus GS. Degradation of the epidermal-dermal junction by proteolytic enzymes from human skin and human polymorphonuclear leukocytes. J Exp Med. 1984;160(4):1027–42. source
Not checked in the free run.
- cites [53] Grinnell F, Zhu M. Fibronectin degradation in chronic wounds depends on the relative levels of elastase, alpha1-proteinase inhibitor, and alpha2-macroglobulin. J Invest Dermatol. 1996;106(2):335–41. source
Not checked in the free run.
- cites [54] Herrick S, Ashcroft G, Ireland G, Horan M, McCollum C, Ferguson M. Up-regulation of elastase in acute wounds of healthy aged humans and chronic venous leg ulcers are associated with matrix degradation. Lab Invest. 1997;77(3):281–8.
Not checked in the free run.
- cites [55] Nwomeh BC, Liang HX, Cohen IK, Yager DR. MMP-8 is the predominant collagenase in healing wounds and nonhealing ulcers. J Surg Res. 1999;81(2):189–95. https://doi.org/10.1006/jsre.1998.5495 . source
Not checked in the free run.
- cites [56] Pirila E, Korpi JT, Korkiamaki T, Jahkola T, Gutierrez-Fernandez A, Lopez-Otin C, et al. Collagenase-2 (MMP-8) and matrilysin-2 (MMP-26) expression in human wounds of different etiologies. Wound Repair Regen. 2007;15(1):47–57. https://doi.org/10.1111/j.1524-475X.2006.00184.x . source
Not checked in the free run.
May combine two claims.
PremisecitationPlatelet degranulation releases inflammatory mediators including IL-8/CXCL8, IL-1α, IL-1β, IL-6, and TNF-α, and activates the complement cascade.
“Platelet degranulation also leads to the release of inflammatory mediators such as interleukin (IL)-8, or CXCL8 (a potent neutrophil chemoattractant), in addition to IL-1α, IL-1β, IL-6, and tumor necrosis factor (TNF)-α, and activates the complement cascade [9, 14].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [9] Reinke JM, Sorg H. Wound repair and regeneration. Eur Surg Res. 2012;49(1):35–43. https://doi.org/10.1159/000339613 . source
Not checked in the free run.
- cites [14] Bjork J, Hugli TE, Smedegard G. Microvascular effects of anaphylatoxins C3a and C5a. J Immunol. 1985;134(2):1115–9. source
Not checked in the free run.
May combine two claims.
PremisecitationDysregulation of hemostasis, inflammation, proliferation, or remodeling can result in delayed wound healing and the potential to form chronic ulcers and/or excessive scarring.
“Dysregulation of any of these events can result in delayed wound healing and the potential to form chronic ulcers and/or excessive scarring [10••].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [10••]
Not checked in the free run.
May combine two claims.
PremisecitationAnti-inflammatory, pro-repair macrophages produce VEGF, which promotes vessel sprouting, and express two transmembrane proteins that promote vascular anastomosis.
“Not only do anti-inflammatory, pro-repair macrophages produce VEGF, which promotes vessel sprouting, they also express two transmembrane proteins that have been shown to promote vascular anastomosis [80, 85, 86].”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [80] Brancato SK, Albina JE. Wound macrophages as key regulators of repair: origin, phenotype, and function. Am J Pathol. 2011;178(1):19–25. https://doi.org/10.1016/j.ajpath.2010.08.003 . source
Not checked in the free run.
- cites [85] Fantin A, Vieira JM, Gestri G, Denti L, Schwarz Q, Prykhozhij S, et al. Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction. Blood. 2010;116(5):829–40. https://doi.org/10.1182/blood-2009-12-257832 . source
Not checked in the free run.
- cites [86] Affolter M, Zeller R, Caussinus E. Tissue remodelling through branching morphogenesis. Nat Rev Mol Cell Biol. 2009;10:831–42. https://doi.org/10.1038/nrm2797 . source
Not checked in the free run.
May combine two claims.
PremisecitationWounds without IL-6 lack an appropriate inflammatory response and demonstrate stunted angiogenesis, collagen accumulation, and re-epithelialization.
“Wounds without IL-6 lack an appropriate inflammatory response and demonstrate stunted angiogenesis, collagen accumulation, and re-epithelialization [89].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [89] Lin ZQ, Kondo T, Ishida Y, Takayasu T, Mukaida N. Essential involvement of IL-6 in the skin wound-healing process as evidenced by delayed wound healing in IL-6-deficient mice. J Leukoc Biol. 2003;73(6):713–21. source
Not checked in the free run.
May combine two claims.
InterpretationcitationWhen the transition from a pro-inflammatory to an anti-inflammatory macrophage phenotype is impaired, wound healing stalls in the inflammatory phase and a chronic wound results.
“When the transition from a pro- to an anti-inflammatory macrophage phenotype is impaired, wound healing stalls in the inflammatory phase and a chronic wound results [10••].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [10••]
Not checked in the free run.
May combine two claims.
Premisenone givenHyperglycemia in diabetes, hypoxia in arterial or venous insufficiency, or secondary infection likely also contribute to the persistence of pro-inflammatory macrophages.
“Additional signals, such as hyperglycemia in the setting of diabetes, hypoxia in the setting of arterial or venous insufficiency, or secondary infection likely also contribute to the persistence of pro-inflammatory macrophages.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationreasoningIf wounds fail to transition from the inflammatory phase, pro-inflammatory macrophages persist and non-healing wounds develop.
“If wounds fail to transition from the inflammatory phase, pro-inflammatory macrophages persist and non-healing wounds develop.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationnone givenNumerous signals are responsible for the transition between the inflammatory and proliferative phases, most notably the apoptosis and phagocytosis of wound-bed resident neutrophils (efferocytosis).
“Numerous signals are responsible for the transition, most notably the apoptosis and phagocytosis of wound-bed resident neutrophils (efferocytosis).”
Quote in the paperNot a substantial claim
The paper relies on this without support.
Findings from mouse models of wound healing can be generalized to human wound healing and chronic wounds.
“mouse models of wound healing have shown that in non-aged, non-impaired models, neutrophil depletion does not negatively affect wound healing as profoundly as macrophage deletion [25–27].”
“in a mouse model of iron overload, local wound macrophages persisted in a pro-inflammatory state with excess production of inducible nitric oxide synthase (iNOS), IL-12, and TNF-α, in addition to free radicals, leading to impaired wound healing [81].”
“inhibition of NETosis and NET function in mouse models of delayed wound healing improves outcomes [59•].”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
These cells are known to be irreplaceable partners in a successful wound healing.
“Indeed, these cells are known to be irreplaceable partners in a successful wound healing70.”
From Platelets induce increased estrogen production through NF-κB and TGF-β1 signaling pathways in endometriotic stromal cells (2020) · cites this paper as [70]
The absence or over-abundance of any of these cell types would derail the normal healing process, leading healing astray and causing pathological healing such as fibrosis.
“The absence or over-abundance of any of these cell types would derail the normal healing process, leading healing astray and causing pathological healing such as fibrosis70.”
From Platelets induce increased estrogen production through NF-κB and TGF-β1 signaling pathways in endometriotic stromal cells (2020) · cites this paper as [70]
Cites
Neutrophil Extracellular Traps Kill Bacteria
Brinkmann, V., Reichard, U., Goosmann, C., Fauler, B., Uhlemann, Y., Weiss, D. S., Weinrauch, Y., & Zychlinsky, A. (2004) · Science · doi:10.1126/science.1092385 · Cited by 10,268 · see citing works
Exploring the full spectrum of macrophage activation
Mosser, D. M., & Edwards, J. P. (2008) · Nature Reviews Immunology · doi:10.1038/nri2448 · Cited by 9,144 · see citing works
Pattern Recognition Receptors and Inflammation
Takeuchi, O., & Akira, S. (2010) · Cell · doi:10.1016/j.cell.2010.01.022 · Cited by 8,895 · see citing works
Mizgerd, J. P., Kubo, H., Kutkoski, G. J., Bhagwan, S. D., Scharffetter-Kochanek, K., Beaudet, A. L., & Doerschuk, C. M. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.186.8.1357 · Cited by 7,332 · see citing works
The chemokine system in diverse forms of macrophage activation and polarization
MANTOVANI, A., SICA, A., SOZZANI, S., ALLAVENA, P., VECCHI, A., & LOCATI, M. (2004) · Trends in Immunology · doi:10.1016/j.it.2004.09.015 · Cited by 6,534 · see citing works
Macrophage plasticity and polarization: in vivo veritas
Sica, A., & Mantovani, A. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59643 · Cited by 6,335 · see citing works
MANTOVANI, A., SOZZANI, S., LOCATI, M., ALLAVENA, P., & SICA, A. (2002) · Trends in Immunology · doi:10.1016/s1471-4906(02)02302-5 · Cited by 5,528 · see citing works
Neutrophil recruitment and function in health and inflammation
Kolaczkowska, E., & Kubes, P. (2013) · Nature Reviews Immunology · doi:10.1038/nri3399 · Cited by 5,472 · see citing works
Monocyte and macrophage heterogeneity
Gordon, S., & Taylor, P. R. (2005) · Nature Reviews Immunology · doi:10.1038/nri1733 · Cited by 5,190 · see citing works
Wound repair and regeneration: Mechanisms, signaling, and translation
Eming, S. A., Martin, P., & Tomic-Canic, M. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3009337 · Cited by 3,562 · see citing works
Fadok, V. A., Bratton, D. L., Konowal, A., Freed, P. W., Westcott, J. Y., & Henson, P. M. (1998) · Journal of Clinical Investigation · doi:10.1172/jci1112 · Cited by 3,166 · see citing works
Macrophage activation and polarization
Martinez, F. O. (2008) · Frontiers in Bioscience · doi:10.2741/2692 · Cited by 3,160 · see citing works
Neutrophils and immunity: challenges and opportunities
Nathan, C. (2006) · Nature reviews. Immunology · doi:10.1038/nri1785 · Cited by 2,971 · see citing works
Human skin wounds: A major and snowballing threat to public health and the economy
Sen, C. K., Gordillo, G. M., Roy, S., Kirsner, R., Lambert, L., Hunt, T. K., Gottrup, F., Gurtner, G. C., & Longaker, M. T. (2009) · Wound Repair and Regeneration · doi:10.1111/j.1524-475x.2009.00543.x · Cited by 2,965 · see citing works
Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators
Serhan, C. N., Chiang, N., & Van Dyke, T. E. (2008) · Nature Reviews Immunology · doi:10.1038/nri2294 · Cited by 2,932 · see citing works
Transition from inflammation to proliferation: a critical step during wound healing
Landén, N. X., Li, D., & Ståhle, M. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2268-0 · Cited by 1,980 · see citing works
Reinke, J. M., & Sorg, H. (2012) · European Surgical Research · doi:10.1159/000339613 · Cited by 1,898 · see citing works
Fibrotic disease and the TH1/TH2 paradigm
Wynn, T. A. (2004) · Nature Reviews Immunology · doi:10.1038/nri1412 · Cited by 1,765 · see citing works
How dying cells alert the immune system to danger
Kono, H., & Rock, K. L. (2008) · Nature Reviews Immunology · doi:10.1038/nri2215 · Cited by 1,737 · see citing works
Inflammation and wound healing: the role of the macrophage
Koh, T. J., & DiPietro, L. A. (2011) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399411001943 · Cited by 1,667 · see citing works
Neutrophils, from marrow to microbes.
Borregaard, N. (2010) · Immunity · doi:10.1016/j.immuni.2010.11.011 · Cited by 1,550 · see citing works
Hypertrophic Scarring and Keloids: Pathomechanisms and Current and Emerging Treatment Strategies
Gauglitz, G. G., Korting, H. C., Pavicic, T., Ruzicka, T., & Jeschke, M. G. (2011) · Molecular Medicine · doi:10.2119/molmed.2009.00153 · Cited by 1,462 · see citing works
The role of the macrophage in wound repair. A study with hydrocortisone and antimacrophage serum.
(1975) · PubMed Central · Cited by 1,437 · see citing works
uPAR: a versatile signalling orchestrator
Blasi, F., & Carmeliet, P. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm977 · Cited by 1,224 · see citing works
Intravascular Danger Signals Guide Neutrophils to Sites of Sterile Inflammation
McDonald, B., Pittman, K., Menezes, G. B., Hirota, S. A., Slaba, I., Waterhouse, C. C. M., Beck, P. L., Muruve, D. A., & Kubes, P. (2010) · Science · doi:10.1126/science.1195491 · Cited by 1,210 · see citing works
Differential Roles of Macrophages in Diverse Phases of Skin Repair
Lucas, T., Waisman, A., Ranjan, R., Roes, J., Krieg, T., Müller, W., Roers, A., & Eming, S. A. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903356 · Cited by 1,205 · see citing works
Recent Developments in Myofibroblast Biology
Hinz, B., Phan, S. H., Thannickal, V. J., Prunotto, M., Desmoulière, A., Varga, J., De Wever, O., Mareel, M., & Gabbiani, G. (2012) · The American Journal of Pathology · doi:10.1016/j.ajpath.2012.02.004 · Cited by 1,193 · see citing works
Fantin, A., Vieira, J. M., Gestri, G., Denti, L., Schwarz, Q., Prykhozhij, S., Peri, F., Wilson, S. W., & Ruhrberg, C. (2010) · Blood · doi:10.1182/blood-2009-12-257832 · Cited by 1,153 · see citing works
Sindrilaru, A., Peters, T., Wieschalka, S., Baican, C., Baican, A., Peter, H., Hainzl, A., Schatz, S., Qi, Y., Schlecht, A., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci44490 · Cited by 1,100 · see citing works
Neutrophil migration in infection and wound repair: going forward in reverse
de Oliveira, S., Rosowski, E. E., & Huttenlocher, A. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.49 · Cited by 1,058 · see citing works
Galli, S. J., Borregaard, N., & Wynn, T. A. (2011) · Nature Immunology · doi:10.1038/ni.2109 · Cited by 1,055 · see citing works
Fibroblasts and myofibroblasts in wound healing
Desmouliere, A., Darby, I. A., Laverdet, B., & Bonté, F. (2014) · Clinical, Cosmetic and Investigational Dermatology · doi:10.2147/ccid.s50046 · Cited by 1,039 · see citing works
Verreck, F. A. W., de Boer, T., Langenberg, D. M. L., Hoeve, M. A., Kramer, M., Vaisberg, E., Kastelein, R., Kolk, A. H. J., Malefyt, R. D. W., & Ottenhoff, T. H. M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400983101 · Cited by 969 · see citing works
Stout, R. D., Jiang, C., Matta, B., Tietzel, I., Watkins, S. K., & Suttles, J. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.1.342 · Cited by 968 · see citing works
Chemokines in cutaneous wound healing
Gillitzer, R., & Goebeler, M. (2001) · Journal of Leukocyte Biology · doi:10.1189/jlb.69.4.513 · Cited by 943 · see citing works
Overview of the coagulation system
Palta, S., Saroa, R., & Palta, A. (2014) · Indian Journal of Anaesthesia · doi:10.4103/0019-5049.144643 · Cited by 903 · see citing works
Toll-like receptor function and signaling
Kaisho, T., & Akira, S. (2006) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2006.02.023 · Cited by 893 · see citing works
Chemokine receptors and their role in inflammation and infectious diseases
Murdoch, C., & Finn, A. H. R. (2000) · Blood · doi:10.1182/blood.v95.10.3032 · Cited by 841 · see citing works
Wound healing and treating wounds
Powers, J. G., Higham, C., Broussard, K. C., & Phillips, T. J. (2016) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2015.08.070 · Cited by 758 · see citing works
The CXCL8/IL-8 chemokine family and its receptors in inflammatory diseases
Russo, R. C., Garcia, C. C., Teixeira, M. M., & Amaral, F. A. (2014) · Expert Review of Clinical Immunology · doi:10.1586/1744666x.2014.894886 · Cited by 652 · see citing works
Neutrophil cell surface receptors and their intracellular signal transduction pathways
Futosi, K., Fodor, S., & Mócsai, A. (2013) · International Immunopharmacology · doi:10.1016/j.intimp.2013.06.034 · Cited by 642 · see citing works
NETs: a new strategy for using old weapons
Papayannopoulos, V., & Zychlinsky, A. (2009) · Trends in Immunology · doi:10.1016/j.it.2009.07.011 · Cited by 634 · see citing works
Neutrophils and Wound Repair: Positive Actions and Negative Reactions
Wilgus, T. A., Roy, S., & McDaniel, J. C. (2013) · Advances in Wound Care · doi:10.1089/wound.2012.0383 · Cited by 616 · see citing works
Lin, Z.-Q., Kondo, T., Ishida, Y., Takayasu, T., & Mukaida, N. (2003) · Journal of Leukocyte Biology · doi:10.1189/jlb.0802397 · Cited by 585 · see citing works
Regeneration of fat cells from myofibroblasts during wound healing
Plikus, M. V., Guerrero-Juarez, C. F., Ito, M., Li, Y. R., Dedhia, P. H., Zheng, Y., Shao, M., Gay, D. L., Ramos, R., Hsi, T.-C., et al. (2017) · Science · doi:10.1126/science.aai8792 · Cited by 584 · see citing works
How it all starts: Initiation of the clotting cascade
Smith, S. A., Travers, R. J., & Morrissey, J. H. (2015) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2015.1050550 · Cited by 529 · see citing works
Wound Macrophages as Key Regulators of Repair
Brancato, S. K., & Albina, J. E. (2011) · The American Journal of Pathology · doi:10.1016/j.ajpath.2010.08.003 · Cited by 508 · see citing works
MacDonald, K. P. A., Palmer, J. S., Cronau, S. L., Seppanen, E. J., Olver, S. D., Raffelt, N. C., Kuns, R. D., Pettit, A. R., Clouston, A. D., Wainwright, B. J., et al. (2010) · Blood · doi:10.1182/blood-2010-02-266296 · Cited by 507 · see citing works
Wound healing and treating wounds
Morton, L. M., & Phillips, T. J. (2016) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2015.08.068 · Cited by 475 · see citing works
Guest Editorial: are diabetes‐related wounds and amputations worse than cancer?
Armstrong, D. G., Wrobel, J., & Robbins, J. M. (2007) · International Wound Journal · doi:10.1111/j.1742-481x.2007.00392.x · Cited by 456 · see citing works
The phenotype of murine wound macrophages
Daley, J. M., Brancato, S. K., Thomay, A. A., Reichner, J. S., & Albina, J. E. (2009) · Journal of Leukocyte Biology · doi:10.1189/jlb.0409236 · Cited by 452 · see citing works
Efferocytosis Signaling in the Regulation of Macrophage Inflammatory Responses
Elliott, M. R., Koster, K. M., & Murphy, P. S. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1601520 · Cited by 440 · see citing works
Engelhardt, E., Toksoy, A., Goebeler, M., Debus, S., Bröcker, E.-B., & Gillitzer, R. (1998) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)65699-4 · Cited by 435 · see citing works
Cutting Edge: Regulatory T Cells Facilitate Cutaneous Wound Healing
Nosbaum, A., Prevel, N., Truong, H.-A., Mehta, P., Ettinger, M., Scharschmidt, T. C., Ali, N. H., Pauli, M. L., Abbas, A. K., & Rosenblum, M. D. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1502139 · Cited by 418 · see citing works
Interleukin-8 and the chemokine family
Baggiolini, M., Loetscher, P., & Moser, B. (1995) · International Journal of Immunopharmacology · doi:10.1016/0192-0561(94)00088-6 · Cited by 400 · see citing works
The neutrophilic leukocyte in wound repair
Simpson, D. M., & Ross, R. (1972) · Journal of Clinical Investigation · doi:10.1172/jci107007 · Cited by 394 · see citing works
EGF and TGF‐α in wound healing and repair
Schultz, G., Clark, W., & Rotatori, D. S. (1991) · Journal of Cellular Biochemistry · doi:10.1002/jcb.240450407 · Cited by 357 · 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 · see citing works
NETosis Delays Diabetic Wound Healing in Mice and Humans
Fadini, G. P., Menegazzo, L., Rigato, M., Scattolini, V., Poncina, N., Bruttocao, A., Ciciliot, S., Mammano, F., Ciubotaru, C. D., Brocco, E., et al. (2016) · Diabetes · doi:10.2337/db15-0863 · Cited by 339 · see citing works
The role of myofibroblasts in wound healing
Hinz, B. (2016) · Current Research in Translational Medicine · doi:10.1016/j.retram.2016.09.003 · Cited by 328 · see citing works
Complements and the Wound Healing Cascade: An Updated Review
Sinno, H., & Prakash, S. (2013) · Plastic Surgery International · doi:10.1155/2013/146764 · Cited by 304 · see citing works
The Innate Immune System in Acute and Chronic Wounds
MacLeod, A. S., & Mansbridge, J. N. (2016) · Advances in Wound Care · doi:10.1089/wound.2014.0608 · Cited by 289 · see citing works
Exploring the role of stem cells in cutaneous wound healing
Lau, K., Paus, R., Tiede, S., Day, P., & Bayat, A. (2009) · Experimental Dermatology · doi:10.1111/j.1600-0625.2009.00942.x · Cited by 279 · see citing works
Pinhal-Enfield, G., Ramanathan, M., Hasko, G., Vogel, S. N., Salzman, A. L., Boons, G.-J., & Leibovich, S. J. (2003) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63698-x · Cited by 278 · see citing works
Kim, M. H., Liu, W., Borjesson, D. L., CURRY, F. E., Miller, L. S., Cheung, A. L., Liu, F., Isseroff, R. R., & Simon, S. I. (2008) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5701223 · Cited by 271 · see citing works
The Inflammation–Fibrosis Link? A Jekyll and Hyde Role for Blood Cells during Wound Repair
Stramer, B. M., Mori, R., & Martin, P. (2007) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700811 · Cited by 251 · see citing works
Van De Water, L., Varney, S., & Tomasek, J. J. (2013) · Advances in Wound Care · doi:10.1089/wound.2012.0393 · Cited by 251 · see citing works
Associations between chronic disease, age and physical and mental health status
Hopman, W. M., Harrison, M. B., Coo, H., Friedberg, E., Buchanan, M., & VanDenKerkhof, E. G. (2009) · Chronic diseases in Canada · doi:10.24095/hpcdp.29.3.03 · Cited by 243 · see citing works
Oxidative stress in chronic venous leg ulcers
Wlaschek, M., & Scharffetter‐Kochanek, K. (2005) · Wound Repair and Regeneration · doi:10.1111/j.1067-1927.2005.00065.x · Cited by 241 · see citing works
Damage-Associated Molecular Patterns Control Neutrophil Recruitment
Pittman, K., & Kubes, P. (2013) · Journal of Innate Immunity · doi:10.1159/000347132 · Cited by 241 · see citing works
Grinnell, F., & Zhu, M. (1996) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12342990 · Cited by 232 · see citing works
Theilgaard‐Mönch, K., Knudsen, S., Follin, P., & Borregaard, N. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.12.7684 · Cited by 226 · see citing works
Petreaca, M. L., Yao, M., Liu, Y., DeFea, K., & Martins‐Green, M. M. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-01-0004 · Cited by 219 · see citing works
Brauchle, M. A., Angermeyer, K., Hübner, G., & Werner, S. (1994) · PubMed · Cited by 203 · see citing works
Innate and Adaptive Immune Responses in Wound Epithelialization
Strbo, N., Yin, N., & Stojadinovic, O. (2014) · Advances in Wound Care · doi:10.1089/wound.2012.0435 · Cited by 200 · see citing works
Briggaman, R. A., Schechter, N. M., Fraki, J., & Lazarus, G. S. (1984) · The Journal of experimental medicine · doi:10.1084/jem.160.4.1027 · Cited by 190 · see citing works
Tissue remodelling through branching morphogenesis
Affolter, M., Zeller, R., & Caussinus, E. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2797 · Cited by 185 · see citing works
Rethinking Regenerative Medicine: A Macrophage-Centered Approach
Brown, B., Sicari, B. M., & Badylak, S. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00510 · Cited by 185 · see citing works
Laminins: Roles and Utility in Wound Repair
Iorio, V., Troughton, L. D., & Hamill, K. J. (2015) · Advances in Wound Care · doi:10.1089/wound.2014.0533 · Cited by 169 · see citing works
Chemokines and Their Receptors Are Key Players in the Orchestra That Regulates Wound Healing
Martins‐Green, M. M., Petreaca, M. L., & Wang, L. (2013) · Advances in Wound Care · doi:10.1089/wound.2012.0380 · Cited by 151 · see citing works
Herrick, S. E., Ashcroft, G. S., Ireland, G. W., Horan, M. A., McCollum, C. N., & Ferguson, M. W. J. (1997) · PubMed · Cited by 146 · see citing works
Growth regulation of skin fibroblasts
Takehara, K. (2000) · Journal of Dermatological Science · doi:10.1016/s0923-1811(00)00144-4 · Cited by 143 · see citing works
Chemokines Have Diverse Abilities to Form Solid Phase Gradients
Patel, D. D., Koopmann, W., Imai, T., Whichard, L. P., Yoshie, O., & Krangel, M. S. (2001) · Clinical Immunology · doi:10.1006/clim.2000.4997 · Cited by 142 · see citing works
The sweet spot: how GAGs help chemokines guide migrating cells
Monneau, Y. R., Arenzana‐Seisdedos, F., & Lortat‐Jacob, H. (2015) · Journal of Leukocyte Biology · doi:10.1189/jlb.3mr0915-440r · Cited by 137 · see citing works
Edwards, H. E., Finlayson, K. J., Courtney, M. D., et al. (2013) · BMC Health Services Research · doi:10.1186/1472-6963-13-86 · Cited by 136 · see citing works
Microvascular effects of anaphylatoxins C3a and C5a.
Björk, J., Hugli, T. E., & Smedegård, G. (1985) · The Journal of Immunology · doi:10.4049/jimmunol.134.2.1115 · Cited by 134 · see citing works
Proteolytic activity in wound fluids and tissues derived from chronic venous leg ulcers
Moor, A. N., Vachon, D. J., & Gould, L. J. (2009) · Wound Repair and Regeneration · doi:10.1111/j.1524-475x.2009.00547.x · Cited by 126 · see citing works
In vivo restoration of laminin 5 β3 expression and function in junctional epidermolysis bullosa
Robbins, P. B., Lin, Q., Goodnough, J. B., Tian, H., Chen, X., & Khavari, P. A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.091484998 · Cited by 124 · see citing works
Yannas, I. V., Tzeranis, D. S., & So, P. T. C. (2017) · Wound Repair and Regeneration · doi:10.1111/wrr.12516 · Cited by 119 · see citing works
Chemokine and inflammatory cytokine changes during chronic wound healing
Fivenson, D. P., Faria, D. T., Nickoloff, B. J., Poverini, P. J., Kunkel, S., Burdick, M., & Strieter, R. M. (1997) · Wound Repair and Regeneration · doi:10.1046/j.1524-475x.1997.50405.x · Cited by 118 · see citing works
Bianchi, M. E., & Manfredi, A. A. (2009) · Science · doi:10.1126/science.1172794 · Cited by 117 · see citing works
Shi, J., Li, J., Guan, H., Cai, W., Bai, X., Fang, X., Hu, X., Wang, Y., Wang, H., Zheng, Z., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0098228 · Cited by 116 · see citing works
Hemochromatosis C282Y gene mutation increases the risk of venous leg ulceration
Zamboni, P., Tognazzo, S., Izzo, M., Pancaldi, F., Scapoli, G. L., Liboni, A., & Gemmati, D. (2005) · Journal of Vascular Surgery · doi:10.1016/j.jvs.2005.04.003 · Cited by 105 · see citing works
Reduced Il17a Expression Distinguishes a Ly6cloMHCIIhi Macrophage Population Promoting Wound Healing
Rodero, M. P., Hodgson, S. S., Hollier, B., Combadiere, C., & Khosrotehrani, K. (2013) · Journal of Investigative Dermatology · doi:10.1038/jid.2012.368 · Cited by 104 · see citing works
Wound Fluids: A Window Into the Wound Environment?
Yager, D. R., Kulina, R. A., & Gilman, L. A. (2007) · The International Journal of Lower Extremity Wounds · doi:10.1177/1534734607307035 · Cited by 103 · see citing works
Molecular interactions in macrophage activation
Adams, D. O. (1989) · Immunology Today · doi:10.1016/0167-5699(89)90298-3 · Cited by 101 · see citing works
Collagenase‐2 (MMP‐8) and matrilysin‐2 (MMP‐26) expression in human wounds of different etiologies
Pirilä, E., Korpi, J. T., Korkiamäki, T., Jahkola, T., Gutierrez‐Fernandez, A., Lopez‐Otin, C., Saarialho‐Kere, U., Salo, T., & Sorsa, T. (2007) · Wound Repair and Regeneration · doi:10.1111/j.1524-475x.2006.00184.x · Cited by 92 · see citing works
de Oliveira, S., López‐Muñoz, A., Candel, S., Pelegrı́n, P., Calado, Â., & Mulero, V. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1302902 · Cited by 81 · see citing works
The overlapping of local iron overload and HFE mutation in venous leg ulcer pathogenesis
Zamboni, P., Izzo, M., Tognazzo, S., Carandina, S., De Palma, M., Catozzi, L., Caggiati, A., Scapoli, G., & Gemmati, D. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.01.026 · Cited by 76 · see citing works
Chemokine Involvement in Fetal and Adult Wound Healing
Balaji, S., Watson, C. L., Ranjan, R., King, A., Bollyky, P. L., & Keswani, S. G. (2014) · Advances in Wound Care · doi:10.1089/wound.2014.0564 · Cited by 63 · see citing works
In Vivo Imaging Reveals a Pioneer Wave of Monocyte Recruitment into Mouse Skin Wounds
Rodero, M., Licata, F., Poupel, L., Hamon, P., Khosrotehrani, K., Combadière, C., & Boissonnas, A. (2014) · PLoS ONE · doi:10.1371/journal.pone.0108212 · Cited by 55 · see citing works
Cellular resolution of inflammation—catabasis
Widgerow, A. D. (2012) · Wound Repair and Regeneration · doi:10.1111/j.1524-475x.2011.00754.x · Cited by 48 · see citing works
MicroRNAs in skin wound healing
Li, D., & Xu, N. (2017) · European Journal of Dermatology · doi:10.1684/ejd.2017.3040 · Cited by 37 · see citing works
Flagged first, then by citations
2 of the 105 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Immunology of Acute and Chronic Wound Healing
Raziyeva, K., Kim, Y., Zharkinbekov, Z., Kassymbek, K., Jimi, S., & Saparov, A. (2021) · Biomolecules · doi:10.3390/biom11050700 · Cited by 967 · see citing works
Immunoregulation in Diabetic Wound Repair with a Photoenhanced Glycyrrhizic Acid Hydrogel Scaffold
Qian, Y., Zheng, Y., Jin, J., Wu, X., Xu, K., Dai, M., Niu, Q., Zheng, H., He, X., & Shen, J. (2022) · Advanced Materials · doi:10.1002/adma.202200521 · Cited by 762 · see citing works
Rational Design of Immunomodulatory Hydrogels for Chronic Wound Healing
Kharaziha, M., Baidya, A., & Annabi, N. (2021) · Advanced Materials · doi:10.1002/adma.202100176 · Cited by 732 · see citing works
The Dynamics of the Skin’s Immune System
Nguyen, A. V., & Soulika, A. M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20081811 · Cited by 719 · see citing works
“Once initiated, the remodeling phase can continue for at least one year post-injury [81,366].”
BackgroundChouhan, D., Dey, N., Bhardwaj, N., & Mandal, B. B. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2019.119267 · Cited by 524 · see citing works
The Role of the Extracellular Matrix (ECM) in Wound Healing: A Review
Diller, R. B., & Tabor, A. J. (2022) · Biomimetics · doi:10.3390/biomimetics7030087 · Cited by 502 · see citing works
“, days to weeks), while the remodeling phase of the wound healing responses can take up to months (12 months) for completion [45,47].”
BackgroundMarconi, G. D., Fonticoli, L., Rajan, T. S., Pierdomenico, S. D., Trubiani, O., Pizzicannella, J., & Diomede, F. (2021) · Cells · doi:10.3390/cells10071587 · Cited by 423 · see citing works
“The haemostasis phase occurs immediately after injury and results in the formation of a provisional wound matrix [22].”
BackgroundThe Healing Power of Neutrophils.
Phillipson, M., & Kubes, P. (2019) · Trends in immunology · doi:10.1016/j.it.2019.05.001 · Cited by 345 · see citing works
Cheng, H., Shi, Z., Yue, K., Huang, X., Xu, Y., Gao, C., Yao, Z., Zhang, Y. S., & Wang, J. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.02.002 · Cited by 371 · see citing works
Bian, D., Wu, Y., Song, G., Azizi, R., & Zamani, A. (2022) · Stem Cell Research & Therapy · doi:10.1186/s13287-021-02697-9 · Cited by 383 · see citing works
“bed for the founding of novel tissue [48, 49].”
BackgroundMicroenvironment‐Based Diabetic Foot Ulcer Nanomedicine
Huang, F., Lu, X., Yang, Y., Yang, Y., Li, Y., Kuai, L., Li, B., Dong, H., & Shi, J. (2022) · Advanced Science · doi:10.1002/advs.202203308 · Cited by 368 · see citing works
Hydrogels and Wound Healing: Current and Future Prospects
Gounden, V., & Singh, M. (2024) · Gels · doi:10.3390/gels10010043 · Cited by 382 · see citing works
“The granulation tissue undergoes a slow remodeling process, forming scar tissue [21].”
BackgroundChronic Inflammation in Non-Healing Skin Wounds and Promising Natural Bioactive Compounds Treatment
Schilrreff, P., & Alexiev, U. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094928 · Cited by 374 · see citing works
“Besides removing pathogens, neutrophils can upregulate and secrete various pro-inflammatory cytokines such as IL-1α, IL-1β, IL-6, and TNF-α to stimulate monocytes to differentiate into M1 macrophages [31].”
BackgroundRecent advances in molecular mechanisms of skin wound healing and its treatments
Mamun, A. A., Shao, C., Geng, P., Wang, S., & Xiao, J. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1395479 · Cited by 298 · see citing works
“Apoptosis, a regulated form of cell death, serves a critical function in the stages of tissue healing, as shown by its complex involvement in the resolution of these phases (112).”
BackgroundPlasma membrane integrity: implications for health and disease
Ammendolia, D. A., Bement, W. M., & Brumell, J. H. (2021) · BMC Biology · doi:10.1186/s12915-021-00972-y · Cited by 267 · see citing works
“It is convenient to conceptualize the requirements for cell repair by paralleling those of tissue healing, encompassing four complementary stages [115]: hemostasis (sealing off the breach), inflammation (removal of dangerous material that entered the cell), proliferation and migration (replacement of lost or damaged c…”
BackgroundAcute Inflammation in Tissue Healing
Soliman, A. M., & Barreda, D. R. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms24010641 · Cited by 283 · see citing works
Biofilm-Innate Immune Interface: Contribution to Chronic Wound Formation
Versey, Z., Nizer, W. S. D. C., Russell, E., Zigic, S., DeZeeuw, K. G., Marek, J. E., Overhage, J., & Cassol, E. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.648554 · Cited by 268 · see citing works
“During the proliferation phase they also release growth factors, such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor-2 (FGF-2), which promote angiogenesis and keratinocyte and fibroblast proliferation (86, 88, 89, 91, 111).”
BackgroundInfluentialElectrospun nanofibers promote wound healing: theories, techniques, and perspectives
Gao, C., Zhang, L., Wang, J., Jin, M., Tang, Q., Chen, Z., Cheng, Y., Yang, R., & Zhao, G. (2021) · Journal of Materials Chemistry B · doi:10.1039/d1tb00067e · Cited by 246 · see citing works
Applications of Mesenchymal Stem Cells in Skin Regeneration and Rejuvenation
Jo, H., Brito, S., Kwak, B.-M., Park, S., Lee, M., & Bin, B. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052410 · Cited by 231 · see citing works
“Fibroblasts increase the migration and proliferation of keratinocytes via EGF, fibronectin, and keratinocyte growth factor (KGF) [77].”
BackgroundInfluentialWang, T., Bai, J., Lu, M., Huang, C., Geng, D., Chen, G., Wang, L., Qi, J., Cui, W., & Deng, L. (2022) · Nature Communications · doi:10.1038/s41467-021-27816-1 · Cited by 221 · see citing works
“Tissue regeneration involves three indispensable stages: (i) immune action, (ii) cell proliferation and new tissue formation, and (iii) remodeling and maturation 7,8 .”
Mahmoud, N. N., Hamad, K. M., Shibitini, A. A., Juma, S., Sharifi, S., Gould, L., & Mahmoudi, M. (2024) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.3c00336 · Cited by 210 · see citing works
Films for Wound Healing Fabricated Using a Solvent Casting Technique
Borbolla‐Jiménez, F. V., Peña‐Corona, S. I., Farah, S. J., Jiménez-Valdés, M. T., Pineda-Pérez, E., Romero‐Montero, A., Prado-Audelo, M. L. D., Bernal-Chávez, S. A., Magaña, J. J., & Leyva‐Gómez, G. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15071914 · Cited by 227 · see citing works
“Furthermore, this leads to the formation of a fibrin clot, referred to as an eschar, which acts as a plug for the wound, preventing blood loss, providing a scaffold for incoming immune cells, serving as a reservoir for cytokines and growth factors during the early stages of repair, and offering protection against bact…”
BackgroundInfluentialCannabinoid Signaling in the Skin: Therapeutic Potential of the “C(ut)annabinoid” System
Tóth, K. F., Ádám, D., Bı́ró, T., & Oláh, A. (2019) · Molecules · doi:10.3390/molecules24050918 · Cited by 209 · see citing works
Therapeutic Potential of Cannabidiol (CBD) for Skin Health and Disorders
Baswan, S. M., Klosner, A. E., Glynn, K. M., Rajgopal, A., Malik, K. A., Yim, S., & Stern, N. (2020) · Clinical Cosmetic and Investigational Dermatology · doi:10.2147/ccid.s286411 · Cited by 194 · see citing works
Advances in bioactive glass-containing injectable hydrogel biomaterials for tissue regeneration
Zeimaran, E., Pourshahrestani, S., Fathi, A., Razak, N. A. A., Kadri, N. A., Sheikhi, A., & Baino, F. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.09.034 · Cited by 168 · see citing works
The Colorectal Cancer Tumor Microenvironment and Its Impact on Liver and Lung Metastasis
Chandra, R., Karalis, J. D., Liu, C., Murimwa, G. Z., Park, J. V., Heid, C. A., Reznik, S. I., Huang, E. H., Minna, J. D., & Brekken, R. A. (2021) · Cancers · doi:10.3390/cancers13246206 · Cited by 165 · see citing works
Natural polymers used in the dressing materials for wound healing: Past, present and future
Sheokand, B., Vats, M., Kumar, A., Srivastava, C. M., Bahadur, I., & Pathak, S. R. (2023) · Journal of Polymer Science · doi:10.1002/pol.20220734 · Cited by 168 · see citing works
Cai, Y., Chen, K., Liu, C., & Qu, X. (2023) · Bioactive Materials · doi:10.1016/j.bioactmat.2023.04.019 · Cited by 169 · see citing works
“247 initiating re-epithelialization by producing epidermal growth factor (EGF) and keratinocyte growth factor (KGF), M1 macrophages hinder keratinocyte migration with over-expressed TNF-α [60,61].”
BackgroundInfluentialAn Updated Review of Hypertrophic Scarring
Mony, M. P., Harmon, K. A., Hess, R., Dorafshar, A. H., & Shafikhani, S. H. (2023) · Cells · doi:10.3390/cells12050678 · Cited by 174 · see citing works
“The primary functions of the inflammation phase during wound healing are to protect wounds against invading pathogens and to jumpstart the subsequent inflammatory and non-inflammatory responses needed for proper healing [26,27].”
BackgroundThe Insights of Microbes’ Roles in Wound Healing: A Comprehensive Review
Thambirajoo, M., Nurul, A. A., & Fauzi, M. B. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13070981 · Cited by 161 · see citing works
“Granulation tissue Normal production [40] Neoangiogeneis, less fibroblasts, low oxygen→ tissue hypoxia Tissue hypoxia—low production of granulation tissue [40]”
BackgroundTopical gel-based biomaterials for the treatment of diabetic foot ulcers
Bardill, J. R., Laughter, M. R., Stager, M. A., Liechty, K. W., Krebs, M. D., & Zgheib, C. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.10.045 · Cited by 168 · see citing works
Anti-inflammation biomaterial platforms for chronic wound healing
Xu, Z., Liang, B., Tian, J., & Wu, J. (2021) · Biomaterials Science · doi:10.1039/d1bm00637a · Cited by 151 · see citing works
Mohsin, F., Javaid, S., Tariq, M., & Mustafa, M. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.112713 · Cited by 153 · see citing works
Heras, K. L., García-Orue, I., Rancan, F., Igartúa, M., Santos‐Vizcaíno, E., & Hernández, R. M. (2024) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2024.115342 · Cited by 142 · see citing works
Bacteria and Antibiotics in Wound Healing
Caldwell, M. D. (2020) · Surgical Clinics of North America · doi:10.1016/j.suc.2020.05.007 · Cited by 136 · see citing works
Chittasupho, C., Manthaisong, A., Okonogi, S., Tadtong, S., & Samee, W. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms23010142 · Cited by 131 · see citing works
“The inflammation occurs where white blood cells such as phagocytic cells, neutrophils and macrophages migrate to the injured site [5].”
BackgroundApplication of stem cells in regeneration medicine
Jin, Y. H., Li, S., Yu, Q., Chen, T., & Liu, D. (2023) · MedComm · doi:10.1002/mco2.291 · Cited by 131 · see citing works
Healing Mechanisms in Cutaneous Wounds: Tipping the Balance
Singer, A. J. (2021) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2021.0114 · Cited by 133 · see citing works
“For more on the role of the immune response in wound healing, see the recent reviews by CañedoDorantes and Cañedo-Ayala and Ellis et al.(45,60) Compared with reparative healing, the inflammatory response in regenerative healing is attenuated.”
BackgroundWound healing and microbiome, an unexpected relationship
Canchy, L., Kérob, D., Demessant‐Flavigny, A., & Amici, J. M. (2023) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/jdv.18854 · Cited by 131 · see citing works
“Moreover, excessive inf lammation is commonly associated with chronicity as it further delays the complete transition to the proliferative phase.(9,10) Besides, it can provide an ideal environment for bacterial infiltration and proliferation, increasing the risk of persistent infection.”
BackgroundDiban, F., Lodovico, S. D., Fermo, P. D., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24021004 · Cited by 122 · see citing works
Hydrogel-Based Skin Regeneration
Arabpour, Z., Abedi, F., Salehi, M., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25041982 · Cited by 120 · see citing works
“These stages involve the interaction of various cell types and matrix components, including hemostasis, inflammation, proliferation, and remodeling, as illustrated in Figure 1 [11].”
BackgroundEpigenetic regulation of macrophage polarization in wound healing
Chen, C., Liu, T., Tang, Y., Luo, G., Liang, G., & He, W. (2023) · Burns & Trauma · doi:10.1093/burnst/tkac057 · Cited by 123 · see citing works
“At an early stage of wound healing, a proinflammatory reaction is conducive to anti-infection activity in injured tissue and a late pro-healing response is beneficial to wound repair [9].”
BackgroundXing, C., Zhu, H., Dou, X., Gao, L., Baddi, S., Zou, Y., Zhao, C., Peng, Y., Fang, Y., & Feng, C. (2023) · ACS Nano · doi:10.1021/acsnano.2c10039 · Cited by 120 · see citing works
Distinct inflammatory and wound healing responses to complex caudal fin injuries of larval zebrafish
Miskolci, V., Squirrell, J. M., Rindy, J., Vincent, W. J. B., Sauer, J., Gibson, A. L. F., Eliceiri, K. W., & Anna Huttenlocher, A. (2019) · eLife · doi:10.7554/elife.45976 · Cited by 114 · see citing works
“We evaluated three aspects of these injuries (Figure 1A), representing key stages of wound healing – new tissue formation, inflammation and remodeling (Ellis et al., 2018).”
MethodBeneficial Effects of Green Tea EGCG on Skin Wound Healing: A Comprehensive Review
Xu, F.-W., Lv, Y.-L., Zhong, Y., Xue, Y., Wang, Y., Zhang, L., Hu, X. M., & Tan, W. (2021) · Molecules · doi:10.3390/molecules26206123 · Cited by 123 · see citing works
“The skin wound healing process has four sequential and overlapping stages, including hemostasis, inflammation, proliferation and tissue remodeling [52], which involves various types of cells (e.”
BackgroundInfluentialPalani, N., Vijayakumar, P., Monisha, P., Ayyadurai, S., & Rajadesingu, S. (2024) · Journal of Nanobiotechnology · doi:10.1186/s12951-024-02491-8 · Cited by 125 · see citing works
Rejuvenation of three germ layers tissues by exchanging old blood plasma with saline-albumin
Mehdipour, M., Skinner, C. M., Wong, N., Lieb, M., Liu, C., Etienne, J., Kato, C., KIPROV, D. D., Conboy, M. J., & Conboy, I. M. (2020) · Aging · doi:10.18632/aging.103418 · Cited by 113 · see citing works
“Immune regulators promote better surveillance and wound clearance in multiple tissues [75, 76].”
BackgroundČoma, M., Fröhlichová, L., Urban, L., Zajíček, R., Urban, T., Szabó, P., Novak, S., Fetissov, V., Dvořánková, B., Smetana, K., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22020897 · Cited by 121 · see citing works
Bacteriophages for Chronic Wound Treatment: From Traditional to Novel Delivery Systems
Pinto, A. M., Cerqueira, M. Â., Bañobre‐López, M., Pastrana, L. M., & Sillankorva, S. (2020) · Viruses · doi:10.3390/v12020235 · Cited by 115 · see citing works
“Fibroblasts that acquire contractile properties can contract the wound edges and the migration and proliferation of keratinocytes, which are responsible for the closure of the lesion [17,27].”
BackgroundInfluentialBacterial Cellulose as a Versatile Biomaterial for Wound Dressing Application
de Amorim, J. D. P., da Silva, C. J. G., de Medeiros, A. D. M., et al. (2022) · Molecules · doi:10.3390/molecules27175580 · Cited by 108 · see citing works
Harrell, C. R., Markovic, B. S., Fellabaum, C., Arsenijevic, N., Djonov, V., & Volarevic, V. (2020) · BioFactors · doi:10.1002/biof.1587 · Cited by 106 · see citing works
“inflammatory M1 macrophages and neutrophils in IFN-γ, IL-17, and IL-22-dependent manner, creating an “autocrine inflammatory loop” that results in a persistent inflammation within the nonhealing wounds.(25) Vander Beken and colleagues recently demonstrated that within the ATP-binding cassette Subfamily B Member 5 (ABC…”
BackgroundLiu, B., Fu, R., Duan, Z., Zhu, C., Deng, J., & Fan, D. (2022) · Composites Part B Engineering · doi:10.1016/j.compositesb.2022.109804 · Cited by 102 · see citing works
Sadat, Z., Farrokhi-Hajiabad, F., Lalebeigi, F., et al. (2022) · Biomaterials Science · doi:10.1039/d2bm01308h · Cited by 101 · see citing works
Kalasin, S., Sangnuang, P., & Surareungchai, W. (2022) · Analytical Chemistry · doi:10.1021/acs.analchem.2c00782 · Cited by 102 · see citing works
Flynn, K., Mahmoud, N. N., Sharifi, S., Gould, L. J., & Mahmoudi, M. (2023) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.3c00030 · Cited by 101 · see citing works
Applications of Nanosized-Lipid-Based Drug Delivery Systems in Wound Care
Matei, A.-M., Căruntu, C., Tampa, M. Ş., Georgescu, S. R., Matei, C., Constantin, M. M., Constantin, T. V., Călina, D. C., Ciubotaru, D. A., Bădărău, I. A., et al. (2021) · Applied Sciences · doi:10.3390/app11114915 · Cited by 94 · see citing works
“It involves activation of the immune system’s cellular components, the coagulation cascade, and the inflammatory pathways, leading to a massive remodeling of all skin compartments [1,2].”
BackgroundMacrophage Phenotypes in Normal and Diabetic Wound Healing and Therapeutic Interventions
Sadoun, H. A. (2022) · Cells · doi:10.3390/cells11152430 · Cited by 95 · see citing works
“C3b mediates bacterial opsonization, and this further stimulates neutrophil recruitment to the wound site [1,16,17] (Figure 1).”
BackgroundKeratinocyte-Macrophage Crosstalk by the Nrf2/Ccl2/EGF Signaling Axis Orchestrates Tissue Repair
VILLARREAL-PONCE, A. P., Tiruneh, M. W., Lee, J., Guerrero‐Juarez, C. F., Kuhn, J. F., David, J. A., Dammeyer, K. L., Kell, R. M., Kwong, J., Rabbani, P. S., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108417 · Cited by 88 · see citing works
“Granulation tissue formation describes an essential component of wound repair that encompasses the production of new connective tissue and blood vessels within the wound bed (Ellis et al., 2018).”
BackgroundZhao, Y., & Jalili, S. (2022) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2022.02.114 · Cited by 85 · see citing works
Multifunctional lipid-based nanoparticles for wound healing and antibacterial applications: A review
Motsoene, F., Abrahamse, H., & Kumar, S. S. D. (2023) · Advances in Colloid and Interface Science · doi:10.1016/j.cis.2023.103002 · Cited by 85 · see citing works
Myofibroblast progeny in wound biology and wound healing studies
Monika, P., Waiker, P. V., Chandraprabha, M. N., Rangarajan, A., & Murthy, K. N. C. (2021) · Wound Repair and Regeneration · doi:10.1111/wrr.12937 · Cited by 88 · see citing works
“hospitalization, loss of mobility, compromising quality of life, requirement of support and sometime increase the risk of nosocomial infection causing burden to health care workers and other patients visiting hospital.(2) Considering the number of diabetic patients, accidents and other events associated with wound, th…”
BackgroundCerium oxide nanoparticles in wound care: a review of mechanisms and therapeutic applications
Chen, S., Wang, Y., Bao, S., Li, Y., Fu, X., Yu, Y., Lyu, H., Pang, H., Guo, S., Zhang, H., et al. (2024) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2024.1404651 · Cited by 84 · see citing works
“These factors play a catalytic role in the wound healing cascade by activating neutrophils, and subsequently macrophages, endothelial cells and fi broblasts (Ellis et al., 2018).”
BackgroundAn Update on Molecular Mechanisms of Scarring—A Narrative Review
Kohlhauser, M., Mayrhofer, M., Kamolz, L., & Smolle, C. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252111579 · Cited by 89 · see citing works
“These cells in turn not only lead to expression of cytokines but also chemokines, which subsequently attract inflammatory cells [6,21,22].”
BackgroundAdvanced Wound Diagnostics: Toward Transforming Wound Care into Precision Medicine
Weigelt, M. A., Lev‐Tov, H. A., Tomic‐Canic, M., Lee, W. D., Williams, R., Strasfeld, D. B., Kirsner, R. S., & Herman, I. M. (2021) · Advances in Wound Care · doi:10.1089/wound.2020.1319 · Cited by 82 · see citing works
“77,78 MMP-2, neutrophil elastase, and CG have highest activity at pH 7–8, which fits in with our understanding of the increased protease activity seen in chronic wounds.”
Recent advancements in bioadhesive self-healing hydrogels for effective chronic wound care
Nezhad‐Mokhtari, P., Hasany, M., Kohestanian, M., Dolatshahi‐Pirouz, A., Milani, M., & Mehrali, M. (2024) · Advances in Colloid and Interface Science · doi:10.1016/j.cis.2024.103306 · Cited by 86 · see citing works
Khalili‐Tanha, G., Radisky, E. S., Radisky, D. C., & Shoari, A. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-06447-w · Cited by 90 · see citing works
“Following injury, platelets create a provisional clot containing fibrinogen and fibronectin, and inflammatory cells clear debris, setting the stage for epithelial cells to migrate over the wound bed [2, 112].”
The role of the host—Neutrophil biology
Chapple, I. L. C., Hirschfeld, J., Kantarci, A., Wilensky, A., & Shapira, L. (2023) · Periodontology 2000 · doi:10.1111/prd.12490 · Cited by 83 · see citing works
Enhancing wound healing dressing development through interdisciplinary collaboration
Hawthorne, B., Simmons, J. K., Stuart, B., Tung, R., Zamierowski, D. S., & Mellott, A. J. (2021) · Journal of Biomedical Materials Research Part B Applied Biomaterials · doi:10.1002/jbm.b.34861 · Cited by 80 · see citing works
“as well as secrete proinflammatory cytokines and chemokines that increase the number of natural killer cells, helper T cells, and macrophages at the site of injury.(13) Some macrophages will differentiate into antiinflammatory and pro-regenerative M2 macrophages.”
BackgroundInfluentialdel Olmo, J. A., Pérez‐Álvarez, L., Sáez‐Martínez, V., Cid, S. B., Ruiz‐Rubio, L., Pérez-González, R., Vilas‐Vilela, J. L., & Alonso, J. M. (2022) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2022.01.193 · Cited by 78 · see citing works
Cutaneous Wound Healing: A Review about Innate Immune Response and Current Therapeutic Applications
Adib, Y., Bensussan, A., & Michel, L. (2022) · Mediators of Inflammation · doi:10.1155/2022/5344085 · Cited by 81 · see citing works
“Different signals can induce the activation of resident innate cells and the recruitment of circulating inflammatory cells into the wound site; they include the release of alarmins, also known as damage-associated molecular patterns or DAMPs by damaged host cells (e.g., uric acid, DNA, RNA, and extracellular matrix co…”
BackgroundInfluentialHybrid-Based Wound Dressings: Combination of Synthetic and Biopolymers
Aderibigbe, B. A. (2022) · Polymers · doi:10.3390/polym14183806 · Cited by 78 · see citing works
“In this phase, neutrophils and monocyte infiltration in the wound bed prevent the invasion of microbes, foreign debris, and tissue damage [27,28].”
BackgroundTumors vs. Chronic Wounds: An Immune Cell's Perspective
Hua, Y., & Bergers, G. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02178 · Cited by 76 · see citing works
“During this inflammation period, neutrophils secrete reactive oxygen species (ROS), nitric oxide (NO), and antimicrobial proteins (AMPs) and deploy web-like extracellular traps (NETs) in order to phagocytose and kill contaminating microorganisms (12, 13).”
BackgroundBacterial cellulose/chitosan composite materials for biomedical applications
Liu, K., Wang, Y., Liu, W., et al. (2024) · Chemical Engineering Journal · doi:10.1016/j.cej.2024.153014 · Cited by 75 · see citing works
MSCs and their exosomes: a rapidly evolving approach in the context of cutaneous wounds therapy
Marofi, F., Alexandrovna, K. I., Margiana, R., Bahramali, M., Suksatan, W., Abdelbasset, W. K., Chupradit, S., Nasimi, M., & Maashi, M. S. (2021) · Stem Cell Research & Therapy · doi:10.1186/s13287-021-02662-6 · Cited by 78 · see citing works
“The inflammatory phase, as the second step of wound healing, concentrates on deteriorating bacteria and eliminating debris, thereby providing the wound bed for the establishment of new tissue [27, 28].”
BackgroundQin, X., He, J., Wang, X., Wang, J., Yang, R., & Chen, X. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1256687 · Cited by 79 · see citing works
Biofilms and Chronic Wounds: Pathogenesis and Treatment Options
Shen, A., Taha, M. R., Ghannoum, M. A., & Tyring, S. K. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14217784 · Cited by 92 · see citing works
“After this, proliferation begins where granulation tissue forms and the keratinocytes undergo epithelialization [30,31].”
Tang, Q., Chen, C., Jiang, Y., et al. (2020) · Journal of Materials Chemistry B · doi:10.1039/d0tb00726a · Cited by 73 · see citing works
Current Progress and Outlook of Nano-Based Hydrogel Dressings for Wound Healing
Zhang, X., Wei, P., Yang, Z., Liu, Y., Yang, K., Cheng, Y., Yao, H., & Zhang, Z. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics15010068 · Cited by 74 · see citing works
Constantino, V. R. L., Figueiredo, M. P., Magri, V. R., Eulálio, D., Cunha, V. R. R., Alcântara, A. C. S., & Perotti, G. F. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15020413 · Cited by 73 · see citing works
Stimuli-responsive hydrogels for skin wound healing and regeneration
Xin, H., Maruf, D. S. A. A., Akin-Ige, F., & Amin, S. (2024) · Emergent Materials · doi:10.1007/s42247-024-00930-8 · Cited by 74 · see citing works
“Granula - tion tissues are also converted to scar at this stage [ 41, 51].”
Tyavambiza, C., Meyer, M., & Meyer, S. (2022) · Bioengineering · doi:10.3390/bioengineering9110712 · Cited by 72 · see citing works
Yang, Y., Suo, D., Xu, T., Zhao, S., Xu, X., Bei, H., Wong, K. K. Y., Li, Q., Zheng, Z., Li, B., et al. (2024) · Science Advances · doi:10.1126/sciadv.ado9479 · Cited by 70 · see citing works
“During hemostasis, the activated platelets could secrete immune mediators (e.g., IL-8 and transforming growth factor– β ) to recruit immune cells (e.g., macrophages) and, thus, to evoke the immune response ( 53 ).”
Applications of mesenchymal stem cell-exosome components in wound infection healing: new insights
Fakouri, A., Razavi, Z.-S., Mohammed, A. T., Hussein, A. H. A., Afkhami, H., & Hooshiar, M. H. (2024) · Burns & Trauma · doi:10.1093/burnst/tkae021 · Cited by 69 · see citing works
“During the advanced phases of wound healing, it has been observed that effector cells undergo apoptosis, collagen III is replaced by collagen I, matrix metalloprotease degradation occurs and the synthesis of other ECM proteins takes place [146].”
BackgroundImmunomodulatory Properties of Host Defence Peptides in Skin Wound Healing
Petkovic, M., Mouritzen, M. V., Mojsoska, B., & Jenssen, H. (2021) · Biomolecules · doi:10.3390/biom11070952 · Cited by 68 · see citing works
“Hemostasis involves various protease cascades leading to the formation of a fibrin cloth to prevent blood loss and seal the wound [61].”
BackgroundDirect and Indirect Roles of Macrophages in Hypertrophic Scar Formation
Feng, Y., Sun, Z., Liu, S., Wu, J., Zhao, B.-H., Lv, G., Du, Y., Yu, S., Yang, M., Yuan, F., et al. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.01101 · Cited by 68 · see citing works
Wójcik, M., Kazimierczak, P., Benko, A., Pałka, K., Vivcharenko, V., & Przekora, A. (2021) · Materials Science and Engineering C · doi:10.1016/j.msec.2021.112068 · Cited by 66 · see citing works
Hasannasab, M., Nourmohammadi, J., Dehghan, M. M., et al. (2021) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2021.121227 · Cited by 67 · see citing works
Clinically relevant experimental rodent models of diabetic foot ulcer
Rai, V., Moellmer, R., & Agrawal, D. K. (2022) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-022-04372-w · Cited by 68 · see citing works
3D scaffolds in the treatment of diabetic foot ulcers: New trends vs conventional approaches
Glover, K., Stratakos, A. C., Váradi, A., & Lamprou, D. A. (2021) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2021.120423 · Cited by 65 · see citing works
Skin γδ T Cells and Their Function in Wound Healing
Hu, W., Shang, R., Yang, J., Chen, C., Liu, Z., Liang, G., He, W., & Luo, G. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.875076 · Cited by 72 · see citing works
Skin immunity in wound healing and cancer
Jakovija, A., & Chtanova, T. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1060258 · Cited by 59 · see citing works
“After sterilizing the wound, neutrophils initiate an apoptotic celldeath pathway which leads to efferocytosis by macrophages (53).”
BackgroundMetal-organic framework-based dressings: Application and opportunities in wound healing
Huang, Q., Chen, Y., Ye, M., Zhuang, S., Zhong, A., Liu, J., Maduraiveeran, G., Peng, Y., & Huang, Y. (2024) · Materials Today Chemistry · doi:10.1016/j.mtchem.2024.102235 · Cited by 68 · see citing works
Eosinophils in wound healing and epithelial remodeling: Is coagulation a missing link?
Coden, M. E., & Berdnikovs, S. (2020) · Journal of Leukocyte Biology · doi:10.1002/jlb.3mr0120-390r · Cited by 62 · see citing works
Masri, S., Mazlan, Z., Zulkiflee, I., Salleh, A., Fadilah, N. I. M., Maarof, M., Wen, A. P. Y., Duman, F., Tabata, Y., Aziz, I. A., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23010476 · Cited by 61 · see citing works
Buck, E., Lee, S., Stone, L. S., & Cerruti, M. (2021) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.0c16509 · Cited by 60 · see citing works
Ding, Y., Ding, X., Zhang, H., Li, S., Yang, P., & Tan, Q. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/9687925 · Cited by 63 · see citing works
“Nonheal-ing wounds in patients with DM negatively a ff ect the quality of life, mortality, and morbidity, and hence, pose a critical clinical challenge and impose an economic burden worldwide [3].”
Lacina, L., Kolář, M., Pfeiferová, L., Gál, P., & Smetana, K. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1403570 · Cited by 65 · see citing works
Zhang, S., Li, Y., Li, Y., et al. (2021) · Bioactive Materials · doi:10.1016/j.bioactmat.2021.03.009 · Cited by 59 · see citing works
Zhang, Y., Luo, J., Zhang, Q., & Deng, T. (2021) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2021.09.210 · Cited by 58 · see citing works
A Photo‐Responsive Hollow Manganese/Carbon Hybrid Nanosphere for Wound Disinfection and Healing
Lu, M., Li, S., Xiong, X., et al. (2022) · Advanced Functional Materials · doi:10.1002/adfm.202208061 · Cited by 58 · see citing works
- Authors
- Ellis, S., Lin, E. J., & Tartar, D.
- Affiliations
- University of California, Davis (US)
- Corresponding author
- Tartar, Danielle
- ORCID
- Tartar, Danielle
- Venue
- Current Dermatology Reports
- Published
- 2018-09-28
- Volume
- 7
- Issue
- 4
- Pages
- 350-358
- ISSN
- 2162-4933 (ISSN-L)
- PMC
- PMC6244748
- OpenAlex
- W2892642834
- Semantic Scholar
- 2db5782e12aeaff45400ab4236b744f21a3178e0
- Cited by
- 625
- References
- 105
- Citations by year
- 2026: 65 · 2025: 114 · 2024: 109 · 2023: 90 · 2022: 96 · 2021: 86 · 2020: 44 · 2019: 21
- FWCI
- 4.74
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Current Dermatology Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Dermatology › Dermatologic Treatments and Research
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- wound healing, chronic wounds, skin wound healing, neutrophils, efferocytosis, macrophages, interleukin-8, inflammation, angiogenesis, granulation tissue, myofibroblasts, scar formation, keratinocytes, dermal cells, immune signaling
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.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.
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 ›
Are you an author, or do you see a problem with this page? Request a review
