Inflammation as an orchestrator of cutaneous scar formation: a review of the literature

Traci A. Wilgus

Plastic and Aesthetic Research ›› 2020, Vol. 7 ›› Issue (1) : 54

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Plastic and Aesthetic Research ›› 2020, Vol. 7 ›› Issue (1) :54 DOI: 10.20517/2347-9264.2020.150
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Inflammation as an orchestrator of cutaneous scar formation: a review of the literature

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Abstract

Inflammation is a key phase in the cutaneous wound repair process. The activation of inflammatory cells is critical for preventing infection in contaminated wounds and results in the release of an array of mediators, some of which stimulate the activity of keratinocytes, endothelial cells, and fibroblasts to aid in the repair process. However, there is an abundance of data suggesting that the strength of the inflammatory response early in the healing process correlates directly with the amount of scar tissue that will eventually form. This review will summarize the literature related to inflammation and cutaneous scar formation, highlight recent discoveries, and discuss potential treatment modalities that target inflammation to minimize scarring.

Keywords

Inflammation / scar / skin / wound healing / macrophage / mast cell / neutrophil

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Traci A. Wilgus. Inflammation as an orchestrator of cutaneous scar formation: a review of the literature. Plastic and Aesthetic Research, 2020, 7(1): 54 DOI:10.20517/2347-9264.2020.150

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References

[1]

Eming SA,Tomic-Canic M.Wound repair and regeneration: mechanisms, signaling, and translation..Sci Transl Med2014;6:265sr6 PMCID:PMC4973620

[2]

Gurtner GC,Barrandon Y.Wound repair and regeneration..Nature2008;453:314-21

[3]

Martin P.Wound healing--aiming for perfect skin regeneration..Science1997;276:75-81

[4]

Aarabi S,Gurtner GC.Hypertrophic scar formation following burns and trauma: new approaches to treatment..PLoS Med2007;4:e234 PMCID:PMC1961631

[5]

Corr DT,Shrive NG.Biomechanical behavior of scar tissue and uninjured skin in a porcine model..Wound Repair Regen2009;17:250-9

[6]

Dunn MG,Swann DA.Mechanical analysis of hypertrophic scar tissue: structural basis for apparent increased rigidity..J Invest Dermatol1985;84:9-13

[7]

Brown BC,Siddhi K,Bayat A.The hidden cost of skin scars: quality of life after skin scarring..J Plast Reconstr Aesthet Surg2008;61:1049-58

[8]

Wilgus TA.Immune cells in the healing skin wound: influential players at each stage of repair..Pharmacol Res2008;58:112-6

[9]

Carlsson AH,Fletcher JL,Leung KP.Antecedent thermal injury worsens split-thickness skin graft quality: a clinically relevant porcine model of full-thickness burn, excision and grafting..Burns2017;43:223-31

[10]

Jabeen S,Thomlinson AM,Ferguson MWJ.Partial thickness wound: does mechanism of injury influence healing?.Burns2019;45:531-42

[11]

Morris MW Jr,Herdrich BJ,Zgheib C.Modulation of the inflammatory response by increasing fetal wound size or interleukin-10 overexpression determines wound phenotype and scar formation..Wound Repair Regen2014;22:406-14

[12]

Dunkin CS,Gillespie PH,Roberts AH.Scarring occurs at a critical depth of skin injury: precise measurement in a graduated dermal scratch in human volunteers..Plast Reconstr Surg2007;119:1722-32discussion 1733-4

[13]

Qian LW,Yamane K,Chan RK.Exacerbated and prolonged inflammation impairs wound healing and increases scarring..Wound Repair Regen2016;24:26-34

[14]

Zhang Q,Kelly AP,Wang S.Tumor-like stem cells derived from human keloid are governed by the inflammatory niche driven by IL-17/IL-6 axis..PLoS One2009;4:e7798 PMCID:PMC2771422

[15]

Zhang M,Liu Y,Zhao P.Chemokine-like factor 1 (CKLF-1) is overexpressed in keloid patients: a potential indicating factor for keloid-predisposed individuals..Medicine (Baltimore)2016;95:e3082 PMCID:PMC4839923

[16]

Jumper N,Paus R.Site-specific gene expression profiling as a novel strategy for unravelling keloid disease pathobiology..PLoS One2017;12:e0172955 PMCID:PMC5336271

[17]

Dong X,Ma S.Mast cell chymase in keloid induces profibrotic response via transforming growth factor-beta1/Smad activation in keloid fibroblasts..Int J Clin Exp Pathol2014;7:3596-607 PMCID:PMC4128972

[18]

Craig SS,Schwartz LB.Mast cells in human keloid, small intestine, and lung by an immunoperoxidase technique using a murine monoclonal antibody against tryptase..Am J Pathol1986;124:427-35 PMCID:PMC1888358

[19]

Boyce DE,Ruge F,Harding KG.Inflammatory-cell subpopulations in keloid scars..Br J Plast Surg2001;54:511-6

[20]

Jiao H,Cai J,Yan L.Analysis of characteristics similar to autoimmune disease in keloid patients..Aesthetic Plast Surg2015;39:818-25

[21]

Shaker SA,Hajrah NH.Cell talk: a phenomenon observed in the keloid scar by immunohistochemical study..Appl Immunohistochem Mol Morphol2011;19:153-9

[22]

Arbi S,Oberholzer HM,Bester MJ.Premature collagen fibril formation, fibroblast-mast cell interactions and mast cell-mediated phagocytosis of collagen in keloids..Ultrastruct Pathol2015;39:95-103

[23]

Bagabir R,Chaudhry IH,Paus R.Site-specific immunophenotyping of keloid disease demonstrates immune upregulation and the presence of lymphoid aggregates..Br J Dermatol2012;167:1053-66

[24]

Novak ML.Macrophage phenotypes during tissue repair..J Leukoc Biol2013;93:875-81 PMCID:PMC3656331

[25]

Theoret CL,Parnell LK.Equine exuberant granulation tissue and human keloids: a comparative histopathologic study..Vet Surg2013;42:783-9

[26]

Gaber MA,Ehsan NA.Mast cells and angiogenesis in wound healing..Anal Quant Cytopathol Histpathol2014;36:32-40

[27]

Hellström M,Engström-Laurent A.The structure of the basement membrane zone differs between keloids, hypertrophic scars and normal skin: a possible background to an impaired function..J Plast Reconstr Aesthet Surg2014;67:1564-72

[28]

Aarabi S,Shi Y,Chang EI.Mechanical load initiates hypertrophic scar formation through decreased cellular apoptosis..FASEB J2007;21:3250-61

[29]

Wong VW,Sorkin M,Levi K.Mechanical force prolongs acute inflammation via T-cell-dependent pathways during scar formation..FASEB J2011;25:4498-510

[30]

Wang J,Jiao H,Momtazi M.Human hypertrophic scar-like nude mouse model: characterization of the molecular and cellular biology of the scar process..Wound Repair Regen2011;19:274-85

[31]

Zhu Z,Ma Z,Tredget EE.The natural behavior of mononuclear phagocytes in HTS formation..Wound Repair Regen2016;24:14-25

[32]

Ibrahim MM,Bergeron A,Ehanire T.A novel immune competent murine hypertrophic scar contracture model: a tool to elucidate disease mechanism and develop new therapies..Wound Repair Regen2014;22:755-64 PMCID:PMC4304906

[33]

Harunari N,Armendariz RT,Muangman P.Histology of the thick scar on the female, red Duroc pig: final similarities to human hypertrophic scar..Burns2006;32:669-77 PMCID:PMC2878281

[34]

Kischer CW,Shetlah MR.Mast cell analyses in hypertrophic scars, hypertrophic scars treated with pressure and mature scars..J Invest Dermatol1978;70:355-7

[35]

Beer TW,West L,Wright DH.Mast cells in pathological and surgical scars..Br J Ophthalmol1998;82:691-4 PMCID:PMC1722623

[36]

Niessen FB,Vos H.Hypertrophic scar formation is associated with an increased number of epidermal Langerhans cells..J Pathol2004;202:121-9

[37]

van den Broek LJ,de Jong EH,Niessen FB.Suppressed inflammatory gene expression during human hypertrophic scar compared to normotrophic scar formation..Exp Dermatol2015;24:623-9

[38]

Butzelaar L,Soykan EA,Ulrich MM.Inhibited early immunologic response is associated with hypertrophic scarring..Exp Dermatol2016;25:797-804

[39]

Moore AL,Barnes LA,Ransom RC.Scarless wound healing: transitioning from fetal research to regenerative healing..Wiley Interdiscip Rev Dev Biol2018;7:e309 PMCID:PMC6485243

[40]

Wilgus TA.Regenerative healing in fetal skin: a review of the literature..Ostomy Wound Manage2007;53:16-31

[41]

Wilgus TA.Bagchi D,Roy S.Fetal wound healing..Wound healing, tissue repair, and regeneration in diabetes.2020;Cambridge, MAAcademic Press579-91

[42]

Armstrong JR.Ontogeny of the skin and the transition from scar-free to scarring phenotype during wound healing in the pouch young of a marsupial, Monodelphis domestica..Dev Biol1995;169:242-60

[43]

Kumta S,Hurley JV,Romeo R.Acute inflammation in foetal and adult sheep: the response to subcutaneous injection of turpentine and carrageenan..Br J Plast Surg1994;47:360-8

[44]

Wilgus TA,Tober KL,Mitra S.The impact of cyclooxygenase-2 mediated inflammation on scarless fetal wound healing..Am J Pathol2004;165:753-61 PMCID:PMC1618587

[45]

Liechty KW,Crombleholme TM.Diminished interleukin 6 (IL-6) production during scarless human fetal wound repair..Cytokine2000;12:671-6

[46]

Liechty KW,Cass DL,Adzick NS.Diminished interleukin-8 (IL-8) production in the fetal wound healing response..J Surg Res1998;77:80-4

[47]

Wulff BC,Wilgus TA.Interleukin-33 encourages scar formation in murine fetal skin wounds..Wound Repair Regen2019;27:19-28 PMCID:PMC6448156

[48]

Dardenne AD,Wilgus TA.The alarmin HMGB-1 influences healing outcomes in fetal skin wounds..Wound Repair Regen2013;21:282-91 PMCID:PMC3594575

[49]

Gordon A,Keswani SG,Katz AB.Permissive environment in postnatal wounds induced by adenoviral-mediated overexpression of the anti-inflammatory cytokine interleukin-10 prevents scar formation..Wound Repair Regen2008;16:70-9

[50]

Wulff BC,Parent AE.Novel differences in the expression of inflammation-associated genes between mid- and late-gestational dermal fibroblasts..Wound Repair Regen2013;21:103-12 PMCID:PMC3540136

[51]

Olutoye OO,Carr ME,Yager DR.Aggregatory characteristics and expression of the collagen adhesion receptor in fetal porcine platelets..J Pediatr Surg1995;30:1649-53

[52]

Olutoye O,Cohen I.Lower cytokine release by fetal porcine platelets: a possible explanation for reduced inflammation after fetal wounding..J Pediatr Surg1996;31:91-5

[53]

Wulff BC,Meleski MA,Schrementi ME.Mast cells contribute to scar formation during fetal wound healing..J Invest Dermatol2012;132:458-65 PMCID:PMC3258379

[54]

Wulff BC.Gourdie RG.Examining the role of mast cells in fetal wound healing using cultured cells in vitro..Wound regeneration and repair.2013;TotowaHumana Press495-506

[55]

Cowin A,Holmes T.Endogenous inflammatory response to dermal wound healing in the fetal and adult mouse..Dev Dyn1998;212:385-93

[56]

Hopkinson-Woolley J,Gordon S.Macrophage recruitment during limb development and wound healing in the embryonic and foetal mouse..J Cell Sci1994;107:Pt 51159-67

[57]

Burrington JD.Wound healing in the fetal lamb..J Pediatr Surg1971;6:523-8

[58]

Naik-Mathuria B,Yu L,Smith CW.Fetal wound healing using a genetically modified murine model: the contribution of P-selectin..J Pediatr Surg2008;43:675-82 PMCID:PMC2424112

[59]

Olutoye OO,Cass DL.Neutrophil recruitment by fetal porcine endothelial cells: implications in scarless fetal wound healing..Pediatr Res2005;58:1290-4

[60]

Rowlatt U.Intrauterine wound healing in a 20 week human fetus..Virchows Arch A Pathol Anat Histol1979;381:353-61

[61]

Walraven M,Beelen RH,Ulrich MM.Healthy human second-trimester fetal skin is deficient in leukocytes and associated homing chemokines..Wound Repair Regen2016;24:533-41

[62]

Wong JW,Wiebe C,Hart DA.Wound healing in oral mucosa results in reduced scar formation as compared with skin: evidence from the red Duroc pig model and humans..Wound Repair Regen2009;17:717-29

[63]

Szpaderska AM,DiPietro LA.Differential injury responses in oral mucosal and cutaneous wounds..J Dent Res2003;82:621-6

[64]

Mak K,Gallant-Behm C,Hart DA.Scarless healing of oral mucosa is characterized by faster resolution of inflammation and control of myofibroblast action compared to skin wounds in the red Duroc pig model..J Dermatol Sci2009;56:168-80

[65]

Glim JE,Niessen FB,Ulrich MM.The number of immune cells is lower in healthy oral mucosa compared to skin and does not increase after scarring..Arch Oral Biol2015;60:272-81

[66]

Chen L,Guo S,Mustoe TA.Positional differences in the wound transcriptome of skin and oral mucosa..BMC Genomics2010;11:471 PMCID:PMC3091667

[67]

Iglesias-Bartolome R,Molinolo AA,Brooks SR.Transcriptional signature primes human oral mucosa for rapid wound healing..Sci Transl Med2018;10:eaap8798 PMCID:PMC6598699

[68]

Seifert AW,Seifert MG,Palmer TM.Skin shedding and tissue regeneration in African spiny mice (Acomys)..Nature2012;489:561-5 PMCID:PMC3480082

[69]

Brant JO,Baker HV,Maden M.A comparative analysis of gene expression profiles during skin regeneration in Mus and Acomys..PLoS One2015;10:e0142931 PMCID:PMC4659537

[70]

Brant JO,Polvadore T,Maden M.Cellular events during scar-free skin regeneration in the spiny mouse, Acomys..Wound Repair Regen2016;24:75-88

[71]

Dabrowski R.The effect of disodium cromoglycate on the skin wound healing and collagen content in the wounds of rats..Acta Physiol Pol1990;41:195-8

[72]

Chen L,Ranzer MJ,DiPietro LA.Blockade of mast cell activation reduces cutaneous scar formation..PLoS One2014;9:e85226 PMCID:PMC3898956

[73]

Gallant-Behm CL,Hart DA.The mast cell stabilizer ketotifen prevents development of excessive skin wound contraction and fibrosis in red Duroc pigs..Wound Repair Regen2008;16:226-33

[74]

Younan GJ,Dastouri P,Xing W.Mast cells are required in the proliferation and remodeling phases of microdeformational wound therapy..Plast Reconstr Surg2011;128:649e-58

[75]

Shiota N,Kakizoe E,Niibayashi T.Pathophysiological role of skin mast cells in wound healing after scald injury: study with mast cell-deficient W/W(V) mice..Int Arch Allergy Immunol2010;151:80-8

[76]

Antsiferova M,Huber M,Förster A.Mast cells are dispensable for normal and activin-promoted wound healing and skin carcinogenesis..J Immunol2013;191:6147-55

[77]

Nauta AC,Montoro DT,Tsai M.Evidence that mast cells are not required for healing of splinted cutaneous excisional wounds in mice..PLoS One2013;8:e59167 PMCID:PMC3609818

[78]

Willenborg S,Brinckmann J,Waisman A.Genetic ablation of mast cells redefines the role of mast cells in skin wound healing and bleomycin-induced fibrosis..J Invest Dermatol2014;134:2005-15

[79]

Wulff BC.Mast cell activity in the healing wound: more than meets the eye?.Exp Dermatol2013;22:507-10 PMCID:PMC3723719

[80]

Martin P,Martin J,Cooper L.Wound healing in the PU.1 null mouse-tissue repair is not dependent on inflammatory cells..Curr Biol2003;13:1122-8

[81]

Chrysanthopoulou A,Apostolidou E,Mikroulis D.Neutrophil extracellular traps promote differentiation and function of fibroblasts..J Pathol2014;233:294-307

[82]

Mirza R,Koh TJ.Selective and specific macrophage ablation is detrimental to wound healing in mice..Am J Pathol2009;175:2454-62 PMCID:PMC2789630

[83]

Lucas T,Ranjan R,Krieg T.Differential roles of macrophages in diverse phases of skin repair..J Immunol2010;184:3964-77

[84]

Rodero MP,Bou-Gharios G.Wound-associated macrophages control collagen 1α2 transcription during the early stages of skin wound healing..Exp Dermatol2013;22:143-5

[85]

Zhu Z,Ma Z,Tredget EE.Systemic depletion of macrophages in the subacute phase of wound healing reduces hypertrophic scar formation..Wound Repair Regen2016;24:644-56

[86]

Shook BA,Rivera-Gonzalez GC,López-Giráldez F.Myofibroblast proliferation and heterogeneity are supported by macrophages during skin repair..Science2018;362:eaar2971 PMCID:PMC6684198

[87]

Sinha M,Singh K,Ghatak S.Direct conversion of injury-site myeloid cells to fibroblast-like cells of granulation tissue..Nat Commun2018;9:936 PMCID:PMC5838200

[88]

Jeong W,Roh TS,Lee JH.Scar prevention and enhanced wound healing induced by polydeoxyribonucleotide in a rat incisional wound-healing model..Int J Mol Sci2017;18:1698 PMCID:PMC5578088

[89]

Wilgus TA,Vittadini E,Oberyszyn TM.Reduction of scar formation in full-thickness wounds with topical celecoxib treatment..Wound Repair Regen2003;11:25-34

[90]

Xu W,Zeitchek M,Jia S.Hydration status regulates sodium flux and inflammatory pathways through epithelial sodium channel (ENaC) in the skin..J Invest Dermatol2015;135:796-806

[91]

Zhang J,Liu M,Shi J.IL-17 promotes scar formation by inducing macrophage infiltration..Am J Pathol2018;188:1693-702

[92]

Ferreira AM,Fresco R,Varga J.Diminished induction of skin fibrosis in mice with MCP-1 deficiency..J Invest Dermatol2006;126:1900-8

[93]

Wong VW,Akaishi S,Glotzbach JP.Focal adhesion kinase links mechanical force to skin fibrosis via inflammatory signaling..Nat Med2011;18:148-52 PMCID:PMC4457506

[94]

Cooper L,Burslem F.Wound healing and inflammation genes revealed by array analysis of ‘macrophageless’ PU.1 null mice..Genome Biol2005;6:R5 PMCID:PMC549066

[95]

Mori R,Martin P.Molecular mechanisms linking wound inflammation and fibrosis: knockdown of osteopontin leads to rapid repair and reduced scarring..J Exp Med2008;205:43-51 PMCID:PMC2234383

[96]

Liechty KW,Adzick NS.Fetal wound repair results in scar formation in interleukin-10-deficient mice in a syngeneic murine model of scarless fetal wound repair..J Pediatr Surg2000;35:866-72discussion 872-3

[97]

Kieran I,Bush J,Metcalfe A.Interleukin-10 reduces scar formation in both animal and human cutaneous wounds: results of two preclinical and phase II randomized control studies..Wound Repair Regen2013;21:428-36

[98]

Wise LM,Jones NC,Mercer AA.Orf virus IL-10 and VEGF-E act synergistically to enhance healing of cutaneous wounds in mice..J Clin Med2020;9:1085 PMCID:PMC7231296

[99]

Wise LM,Real NC,Mercer AA.Orf virus IL-10 accelerates wound healing while limiting inflammation and scarring..Wound Repair Regen2014;22:356-67

[100]

Balaji S,Marsh E,Bhattacharya SS.The role of interleukin-10 and hyaluronan in murine fetal fibroblast function in vitro: implications for recapitulating fetal regenerative wound healing..PLoS One2015;10:e0124302 PMCID:PMC4423847

[101]

Balaji S,King A,Bhattacharya SS.Interleukin-10-mediated regenerative postnatal tissue repair is dependent on regulation of hyaluronan metabolism via fibroblast-specific STAT3 signaling..FASEB J2017;31:868-81 PMCID:PMC5295728

[102]

King A,Le LD,Crombleholme TM.Interleukin-10 regulates fetal extracellular matrix hyaluronan production..J Pediatr Surg2013;48:1211-7 PMCID:PMC3959980

[103]

King A,Marsh E,Shaaban AF.Interleukin-10 regulates the fetal hyaluronan-rich extracellular matrix via a STAT3-dependent mechanism..J Surg Res2013;184:671-7 PMCID:PMC3759570

[104]

Caskey RC,Lind RC,Xu J.Lentiviral-mediated over-expression of hyaluronan synthase-1 (HAS-1) decreases the cellular inflammatory response and results in regenerative wound repair..Cell Tissue Res2013;351:117-25

[105]

Estes JM,Harrison MR,Stern R.Hyaluronate metabolism undergoes and ontogenic transition during fetal development: Implications for Scar-free wound healing..J Pediatr Surg1993;28:1227-31

[106]

Longaker MT,Hall JL,Crombleholme TM.Studies in fetal wound healing, VII. Fetal wound healing may be modulated by hyaluronic acid stimulating activity in amniotic fluid..J Pediatr Surg1990;25:430-3

[107]

Longaker MT,Adzick NS,Harrison MR.Studies in fetal wound healing. V. A prolonged presence of hyaluronic acid characterizes fetal wound fluid..Ann Surg1991;213:292-6 PMCID:PMC1358347

[108]

Longaker MT,Harrison MR,Langer JC.Studies in fetal wound healing. IV. Hyaluronic acid-stimulating activity distinguishes fetal wound fluid from adult wound fluid..Ann Surg1989;210:667-72 PMCID:PMC1357805

[109]

Longaker MT,Crombleholme TM,Decker M.Studies in fetal wound healing: I. A factor in fetal serum that stimulates deposition of hyaluronic acid..J Pediatr Surg1989;24:789-92

[110]

West DC,Lorenz P,Longaker MT.Fibrotic healing of adult and late gestation fetal wounds correlates with increased hyaluronidase activity and removal of hyaluronan..Int J Biochem Cell Biol1997;29:201-10

[111]

Yates CC,Whaley D,Turner T.Lack of CXC chemokine receptor 3 signaling leads to hypertrophic and hypercellular scarring..Am J Pathol2010;176:1743-55 PMCID:PMC2843466

[112]

Cash JL,Campbell J,Kubes P.Resolution mediator chemerin15 reprograms the wound microenvironment to promote repair and reduce scarring..Curr Biol2014;24:1406-14 PMCID:PMC4064685

[113]

Sidgwick GP,Bayat A.A comprehensive evidence-based review on the role of topicals and dressings in the management of skin scarring..Arch Dermatol Res2015;307:461-77 PMCID:PMC4506744

[114]

Amini-Nik S,Jeschke MG.Scar management in burn injuries using drug delivery and molecular signaling: Current treatments and future directions..Adv Drug Deliv Rev2018;123:135-54 PMCID:PMC5742037

[115]

Ogawa R,Akaishi S,Dohi T.Diagnosis and treatment of keloids and hypertrophic scars-japan scar workshop consensus document 2018..Burns Trauma2019;7:39 PMCID:PMC6933735

[116]

Roques C.The use of corticosteroids to treat keloids: a review..Int J Low Extrem Wounds2008;7:137-45

[117]

Kim DY,Kim SR,Park JH.Effects of a topical angiotensin-converting enzyme inhibitor and a selective COX-2 inhibitor on the prevention of hypertrophic scarring in the skin of a rabbit ear..Wounds2012;24:356-64

[118]

Yuan Z,Chen Y,Cui W.Regulating inflammation using acid-responsive electrospun fibrous scaffolds for skin scarless healing..Mediators Inflamm2014;2014:858045 PMCID:PMC3984856

[119]

Rahmani-Neishaboor E,Hartwell R,Carr N.Topical application of a film-forming emulgel dressing that controls the release of stratifin and acetylsalicylic acid and improves/prevents hypertrophic scarring..Wound Repair Regen2013;21:55-65

[120]

Medina A,Kilani RT.The role of stratifin in fibroblast-keratinocyte interaction..Mol Cell Biochem2007;305:255-64

[121]

Rahmani-Neishaboor E,Jalili R,Ghahary A.Improvement of hypertrophic scarring by using topical anti-fibrogenic/anti-inflammatory factors in a rabbit ear model..Wound Repair Regen2010;18:401-8

[122]

Wilgus TA.Alerting the body to tissue injury: the role of alarmins and DAMPs in cutaneous wound healing..Curr Pathobiol Rep2018;6:55-60 PMCID:PMC5978745

[123]

Wang J,Ding J,Kwan P.Toll-like receptors expressed by dermal fibroblasts contribute to hypertrophic scarring..J Cell Physiol2011;226:1265-73

[124]

Li XP,Li YF,Zeng DS.LPS induces activation of the TLR4 pathway in fibroblasts and promotes skin scar formation through collagen I and TGF-beta in skin lesions..Int J Clin Exp Pathol2019;12:2121-9 PMCID:PMC6949634

[125]

Bhattacharyya S,Wang W,Hoover P.FibronectinEDA promotes chronic cutaneous fibrosis through Toll-like receptor signaling..Sci Transl Med2014;6:232ra50 PMCID:PMC4414050

[126]

Bhattacharyya S,Qin W,Coulup S.TLR4-dependent fibroblast activation drives persistent organ fibrosis in skin and lung..JCI Insight2018;3:98850 PMCID:PMC6124522

[127]

Bhattacharyya S,Tamaki Z,Yeldandi A.Pharmacological inhibition of Toll-like receptor-4 signaling by TAK242 prevents and induces regression of experimental organ fibrosis..Front Immunol2018;9:2434 PMCID:PMC6207051

[128]

Blohm-Mangone K,Tahsin S,Aodah A.Pharmacological TLR4 antagonism using topical resatorvid blocks solar UV-induced skin tumorigenesis in SKH-1 mice..Cancer Prev Res (Phila)2018;11:265-78 PMCID:PMC5932085

[129]

Janda J,Blohm-Mangone K,Curiel-Lewandrowski C.Resatorvid-based pharmacological antagonism of cutaneous TLR4 blocks UV-induced NF-κB and AP-1 signaling in keratinocytes and mouse skin..Photochem Photobiol2016;92:816-25 PMCID:PMC5161657

[130]

Rice TW,Bernard GR,Angus DC.A randomized, double-blind, placebo-controlled trial of TAK-242 for the treatment of severe sepsis..Crit Care Med2010;38:1685-94

[131]

Ding J,Zhang R,Honardoust D.Stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4 in the formation of postburn hypertrophic scar (HTS)..Wound Repair Regen2011;19:568-78

[132]

Liu H,Ma Z,Shankowsky HA.A novel subpopulation of peripheral blood mononuclear cells presents in major burn patients..Burns2015;41:998-1007

[133]

Shin JU,Kim H,Jin S.TSLP is a potential initiator of collagen synthesis and an activator of CXCR4/SDF-1 axis in keloid pathogenesis..J Invest Dermatol2016;136:507-15

[134]

Hall CL,Leung KP.Pirfenidone reduces profibrotic responses in human dermal myofibroblasts, in vitro..Lab Invest2018;98:640-55

[135]

Saito M,Maeda T,Setoguchi Y.Pirfenidone suppresses keloid fibroblast-embedded collagen gel contraction..Arch Dermatol Res2012;304:217-22

[136]

Wells AR.Pirfenidone attenuates the profibrotic contractile phenotype of differentiated human dermal myofibroblasts..Biochem Biophys Res Commun2020;521:646-51

[137]

Satish L,Geletu E,Supp DM.Pirfenidone inhibits epithelial-mesenchymal transition in keloid keratinocytes..Burns Trauma2020;8:tkz007 PMCID:PMC7175767

[138]

Dorati R,DeLuca PP.Development of a topical 48-H release formulation as an anti-scarring treatment for deep partial-thickness burns..AAPS PharmSciTech2018;19:2264-75

[139]

Medina JL,Fourcaudot AB,Leung KP.Pirfenidone ointment modulates the burn wound bed in c57bl/6 mice by suppressing inflammatory responses..Inflammation2019;42:45-53

[140]

Armendariz-Borunda J,Medina-Preciado D,Martinez-Fong D.A controlled clinical trial with pirfenidone in the treatment of pathological skin scarring caused by burns in pediatric patients..Ann Plast Surg2012;68:22-8

[141]

Afaq F,Ahmad N.Inhibition of ultraviolet B-mediated activation of nuclear factor kappaB in normal human epidermal keratinocytes by green tea Constituent (-)-epigallocatechin-3-gallate..Oncogene2003;22:1035-44

[142]

Elmets CA,Tubesing K,Katiyar S.Cutaneous photoprotection from ultraviolet injury by green tea polyphenols..J Am Acad Dermatol2001;44:425-32

[143]

Gensler HL,Valcic S,Dorr R.Prevention of photocarcinogenesis by topical administration of pure epigallocatechin gallate isolated from green tea..Nutr Cancer1996;26:325-35

[144]

Katiyar SK.Green tea polyphenol (-)-epigallocatechin-3-gallate treatment to mouse skin prevents UVB-induced infiltration of leukocytes, depletion of antigen-presenting cells, and oxidative stress..J Leukoc Biol2001;69:719-26

[145]

Zhang Q,Wang L,Tang X.Green tea extract and (-)-epigallocatechin-3-gallate inhibit mast cell-stimulated type I collagen expression in keloid fibroblasts via blocking PI-3K/AkT signaling pathways..J Invest Dermatol2006;126:2607-13

[146]

Park G,Moon JH,Jun EK.Green tea polyphenol epigallocatechin-3-gallate suppresses collagen production and proliferation in keloid fibroblasts via inhibition of the STAT3-signaling pathway..J Invest Dermatol2008;128:2429-41

[147]

Syed F,Paus R.Ex vivo evaluation of antifibrotic compounds in skin scarring: EGCG and silencing of PAI-1 independently inhibit growth and induce keloid shrinkage..Lab Invest2013;93:946-60

[148]

Ud-Din S,Mazhari M,Baguneid M.A double-blind, randomized trial shows the role of zonal priming and direct topical application of epigallocatechin-3-gallate in the modulation of cutaneous scarring in human skin..J Invest Dermatol2019;139:1680-90.e16

[149]

Soo C,Zhang X,Beanes SR.Differential expression of fibromodulin, a transforming growth factor-β modulator, in fetal skin development and scarless repair..The American Journal of Pathology2000;157:423-33 PMCID:PMC1850122

[150]

Honardoust D,Hori K,Shankowsky HA.Small leucine-rich proteoglycans, decorin and fibromodulin, are reduced in postburn hypertrophic scar..Wound Repair Regen2011;19:368-78

[151]

Honardoust D,Marcoux Y,Tredget EE.Reduced decorin, fibromodulin, and transforming growth factor-β3 in deep dermis leads to hypertrophic scarring..J Burn Care Res2012;33:218-27

[152]

Zheng Z,Zhang X,Hsu C.Fibromodulin-deficiency alters temporospatial expression patterns of transforming growth factor-β ligands and receptors during adult mouse skin wound healing..PLoS One2014;9:e90817 PMCID:PMC3948369

[153]

Zheng Z,Dang C,Chang GX.Fibromodulin is essential for fetal-type scarless cutaneous wound healing..Am J Pathol2016;186:2824-32 PMCID:PMC5222972

[154]

Zheng Z,Zhang X,Wang JZ.Delayed wound closure in fibromodulin-deficient mice is associated with increased TGF-β3 signaling..J Invest Dermatol2011;131:769-78 PMCID:PMC4073663

[155]

Jiang W,Lee S,Song R.Fibromodulin reduces scar size and increases scar tensile strength in normal and excessive-mechanical-loading porcine cutaneous wounds..J Cell Mol Med2018;22:2510-3 PMCID:PMC5867110

[156]

Stoff A,Mathis JM,Banerjee NS.Effect of adenoviral mediated overexpression of fibromodulin on human dermal fibroblasts and scar formation in full-thickness incisional wounds..J Mol Med (Berl)2007;85:481-96

[157]

Pang X,Zheng Z.Small leucine-rich proteoglycans in skin wound healing..Front Pharmacol2019;10:1649 PMCID:PMC6997777

[158]

Breuing K,Liu P.Healing of partial thickness porcine skin wounds in a liquid environment..J Surg Res1992;52:50-8

[159]

Junker JP,Caterson EJ.Clinical impact upon wound healing and inflammation in moist, wet, and dry environments..Adv Wound Care (New Rochelle)2013;2:348-56 PMCID:PMC3842869

[160]

Reish RG,Bergmann J,Koyama T.Modulation of scarring in a liquid environment in the Yorkshire pig..Wound Repair Regen2009;17:806-16

[161]

Mustoe TA.The role of the epidermis and the mechanism of action of occlusive dressings in scarring..Wound Repair Regen.2011;19 Suppl 1:s16-21 PMCID:PMC3725331

[162]

Gallant-Behm CL.Occlusion regulates epidermal cytokine production and inhibits scar formation..Wound Repair Regen2010;18:235-44 PMCID:PMC2860621

[163]

Zhao J,Friedrich EE,Xie P.S100A12 induced in the epidermis by reduced hydration activates dermal fibroblasts and causes dermal fibrosis..J Invest Dermatol2017;137:650-9

[164]

Zhong A,Zhao J,Jia S.S100A8 and S100A9 are induced by decreased hydration in the epidermis and promote fibroblast activation and fibrosis in the dermis..Am J Pathol2016;186:109-22

[165]

O’Shaughnessy KD,Roy NK.Homeostasis of the epidermal barrier layer: a theory of how occlusion reduces hypertrophic scarring..Wound Repair Regen2009;17:700-8

[166]

Gurtner GC,Wong VW,Wu K.Improving cutaneous scar formation by controlling the mechanical environment: large animal and phase I studies..Ann Surg2011;254:217-25

[167]

Dohi T,Akaishi S,Terashima M.The interplay of mechanical stress, strain, and stiffness at the keloid periphery correlates with increased caveolin-1/ROCK signaling and scar progression..Plast Reconstr Surg2019;144:58e-67

[168]

Pakshir P,Wong B,Chen X.Dynamic fibroblast contractions attract remote macrophages in fibrillar collagen matrix..Nat Commun2019;10:1850 PMCID:PMC6478854

[169]

Lim AF,Kaplan EN,Cowley C.The embrace device significantly decreases scarring following scar revision surgery in a randomized controlled trial..Plast Reconstr Surg2014;133:398-405 PMCID:PMC4874339

[170]

Longaker MT,Greenberg L,Wald R.A randomized controlled trial of the embrace advanced scar therapy device to reduce incisional scar formation..Plast Reconstr Surg2014;134:536-46 PMCID:PMC4425293

[171]

Januszyk M,Bhatt KA,Paterno J.Mechanical offloading of incisional wounds is associated with transcriptional downregulation of inflammatory pathways in a large animal model..Organogenesis2014;10:186-93 PMCID:PMC4154952

[172]

Ma K,Padmanabhan J,Trotsyuk AA.Controlled delivery of a focal adhesion kinase inhibitor results in accelerated wound closure with decreased scar formation..J Invest Dermatol2018;138:2452-60

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