Editing Scar (section)

== Pathophysiology ==
[[File:Key processes contributing to the quasi-neoplastic expression of keloid pathobiology.jpg|thumb|Key processes contributing to the quasi-neoplastic expression of keloid pathobiology.]]

A scar is the product of the body's repair mechanism after tissue injury. If a wound heals quickly within two weeks with new formation of skin, minimal collagen will be deposited and no scar will form.<ref name=bursurg>{{Cite web| title = POST BURN SCAR RELATIVE TO RE-EPITHELIALIZATION| publisher = eplasty.com| year = 2011| url = http://eplasty.com/images/PDF/ManageBurnWound-part4.pdf| quote = Healing in 2 weeks – minimal to no scar; Healing in 3 weeks – minimal to no scar except in high risk scar formers;Healing in 4 weeks or more – hypertrophic in more than 50% of patients| access-date = 6 February 2016| archive-date = 5 October 2016| archive-url = https://web.archive.org/web/20161005230211/http://eplasty.com/images/PDF/ManageBurnWound-part4.pdf| url-status = dead}}</ref> When the extracellular matrix senses elevated mechanical stress loading, tissue will scar,<ref name=scarStress2011/> and scars can be limited by stress shielding wounds.<ref name=scarStress2011>{{cite journal |doi=10.1038/jid.2011.212 |pmid=21776006 |title=Pushing Back: Wound Mechanotransduction in Repair and Regeneration |journal=Journal of Investigative Dermatology |volume=131 |issue=11 |pages=2186–2196 |year=2011 |last1=Wong |first1=Victor W. |last2=Akaishi |first2=Satoshi |last3=Longaker |first3=Michael T. |last4=Gurtner |first4=Geoffrey C. |doi-access=free }}</ref> Small full thickness wounds under 2mm reepithelize fast and heal scar free.<ref name=pmid17586870/><ref name=smallWound>{{cite journal |last1=Tam |first1=Joshua |last2=Wang |first2=Ying |last3=Vuong |first3=Linh N. |last4=Fisher |first4=Jeremy M. |last5=Farinelli |first5=William A. |last6=Anderson |first6=R. Rox |title=Reconstitution of full-thickness skin by microcolumn grafting |journal=Journal of Tissue Engineering and Regenerative Medicine |date=2016 |doi=10.1002/term.2174 |pmid=27296503 |pmc=5697650 |volume=11 |issue=10 |pages=2796–2805}}</ref> Deep second-degree burns heal with scarring and [[hair loss]].<ref name="Kraftlynde">{{cite web |last1=Kraft |first1=John |last2=Lynde |first2=Charles |title=Giving Burns the First, Second and Third Degree - Classification of burns |url=http://www.skincareguide.ca/articles/general_skin_care/gen_skin_care_art_3.html |access-date=31 January 2012 |publisher=skincareguide.ca |quote=Formation of a thick eschar, slow healing (>1month), Obvious scarring, hair loss.}}</ref> Sweat glands do not form in scar tissue, which impairs the regulation of body temperature.<ref name="sweatgland">{{cite journal | vauthors = Fu XB, Sun TZ, Li XK, Sheng ZY | title = Morphological and distribution characteristics of sweat glands in hypertrophic scar and their possible effects on sweat gland regeneration | journal = Chinese Medical Journal | volume = 118 | issue = 3 | pages = 186–91 | date = February 2005 | pmid = 15740645 | url = http://cmj.yiigle.com/CN112154200503/1023825.htm | quote = In hypertrophic scar tissue, no sweet gland and hair follicle exist usually because of the dermal and epidermal damage in extensive thermal skin injury, thus impairing regulation of body temperature }}</ref> Elastic fibers are generally not detected in scar tissue younger than 3 months old.<ref name=eFibers1996>{{cite journal| title = Elastic fibers in scar tissue.| last = Roten SV1, Bhat S, Bhawan J.| date = February 1996| journal = Journal of Cutaneous Pathology| pmid=8720985| volume=23| issue = 1| pages=37–42| doi=10.1111/j.1600-0560.1996.tb00775.x| s2cid = 37823718}}</ref> In scars, [[rete pegs]] are lost;<ref name=rPegs/> through a lack of rete pegs, scars tend to shear easier than normal tissue.<ref name=rPegs>{{cite book | last = Ira D. Papel | title = Facial Plastic and Reconstructive Surgery | publisher = Thieme Medical Publishers | edition = Third | date = 2011 | location = USA | pages = 7 | language = en | url = https://books.google.com/books?id=k6tyROvsZY4C&q=Facial+Plastic+and+Reconstructive+Surgery+7 | isbn = 9781588905154}}</ref>

The [[endometrium]], the inner lining of the uterus, is the only adult tissue to undergo rapid cyclic shedding and regeneration without scarring, shedding and restoring roughly inside a 7-day window on a monthly basis.<ref name=Scrrpr2012918>{{cite web| title = Endometrial repair| quote = Importantly, the endometrium is the only adult tissue to undergo rapid cyclic repair without scarring.| publisher = princehenrys.org| date = 18 September 2012 | url = http://www.princehenrys.org/endometrial-repair-menstruation| access-date = 30 June 2013| archive-url =https://web.archive.org/web/20090914010721/http://www.princehenrys.org/endometrial-repair-menstruation| url-status = dead| archive-date =2009-09-14}}</ref> All other adult tissues, upon rapid shedding or injury, can scar.

Prolonged [[inflammation]], as well as the [[fibroblast]] proliferation,<ref name="Fibroblast"/> can occur. Redness that often follows an injury to the skin is not a scar and is generally not permanent (see [[wound healing]]). The time it takes for this redness to dissipate may, however, range from a few days to, in some serious and rare cases, a few years.<ref>{{cite journal | vauthors = Bayat A, McGrouther DA, Barton JJ, Ferguson MW | title = Skin scarring | journal = BMJ (Clinical Research Ed.) | publisher 
 = The BMJ | date = 11 January 2003 | volume = 326 | issue = 7380 | pages = 88–92 | doi = 10.1136/bmj.326.7380.88 | pmid = 12521975| pmc = 5398751 }}</ref>{{Citation needed|date=August 2010}}

Scars form differently based on the location of the injury on the body and the age of the person who was injured.{{Citation needed|date=August 2010}}

The worse the initial damage is, the worse the scar will generally be. {{Citation needed|date=August 2010}}

Skin scars occur when the [[dermis]] (the deep, thick layer of skin) is damaged. Most skin scars are flat and leave a trace of the original [[injury]] that caused them.{{Citation needed|date=August 2010}}

Wounds allowed to heal secondarily tend to scar worse than wounds from primary closure.<ref name=secinten201104>{{Cite web | title = Practical Plastic Surgery for Nonsurgeons - Secondary Wound Closure - Scarring | quote = Wounds that are allowed to heal secondarily tend to have larger and more noticeable scars than the scars that results from primary closure. Secondary healing also has a greater tendency for hypertrophic scar/keloid formation. (page 86) | url = http://www.practicalplasticsurgery.org/docs/Practical_10.pdf | access-date = 2017-01-11 | archive-url = https://web.archive.org/web/20160826074024/http://www.practicalplasticsurgery.org/docs/Practical_10.pdf | archive-date = 2016-08-26}}</ref>

===Collagen synthesis===
An injury does not become a scar until the wound has completely healed; this can take many months, or years in the worst pathological cases, such as keloids. To begin to patch the damage, a [[clot]] is created; this clot is the beginning process that results in a provisional matrix. In the process, the first layer is a provisional matrix and is not a scar. Over time, the wounded body tissue overexpresses [[collagen]] inside the provisional matrix to create a collagen matrix. This collagen overexpression continues and crosslinks the fiber arrangement inside the collagen matrix, making the collagen dense. This densely packed collagen, morphing into an inelastic whitish collagen<ref name="Fibroblast"/> scar wall, blocks off cell communication and regeneration; as a result, the new tissue generated will have a different texture and quality than the surrounding unwounded tissue. This prolonged collagen-producing process results in a fortuna scar.

====Fibroblasts====
The scarring is created by [[fibroblast]] proliferation,<ref name="Fibroblast"/> a process that begins with a reaction to the clot.<ref name=pmid18086923>{{cite journal |doi=10.1083/jcb.200704042 |pmid=18086923 |pmc=2140013 |title=Myofibroblast contraction activates latent TGF-β1 from the extracellular matrix |journal=The Journal of Cell Biology |volume=179 |issue=6 |pages=1311–1323 |year=2007 |last1=Wipff |first1=Pierre-Jean |last2=Rifkin |first2=Daniel B. |last3=Meister |first3=Jean-Jacques |last4=Hinz |first4=Boris }}</ref> To mend the damage, fibroblasts slowly form the [[collagen]] scar. The fibroblast proliferation is circular<ref name=pmid18086923/> and cyclically, the fibroblast proliferation lays down thick, whitish collagen<ref name="Fibroblast"/> inside the provisional and collagen matrix, resulting in the abundant production of packed collagen on the fibers<ref name="Fibroblast">{{cite encyclopedia  | title = Facts about fibroblast: scar tissue formation| quote = As part of the healing process, specialized cells called fibroblasts in adjacent areas of skin produce a fibrous connective tissue made up of collagen. The bundles formed by these whitish, rather inelastic fibres make up the bulk of the scar tissue...| encyclopedia = Britannica.com| url = http://www.britannica.com/facts/5/264152/fibroblast-as-discussed-in-scar-biology| access-date = 19 April 2010}}</ref><ref name=pmid18086923/> giving scars their uneven texture. Over time, the fibroblasts continue to crawl around the matrix, adjusting more fibers and, in the process, the scarring settles and becomes stiff.<ref name=pmid18086923/> This fibroblast proliferation also contracts the tissue.<ref name=pmid18086923/> In unwounded tissue, these fibers are not overexpressed with thick collagen and do not contract.

EPF and ENF fibroblasts have been genetically traced with the [[EN1 (gene)|Engrailed-1]] genetic marker.<ref name=EPFsENFs/> EPFs are the primary contributors to all fibrotic outcomes after wounding.<ref name=EPFsENFs/> ENFs do not contribute to fibrotic outcomes.<ref name=EPFsENFs>{{Citation| last1 = Jiang| first1 = D| last2 = Rinkevich| first2 = Y | title = Scars or Regeneration?—Dermal Fibroblasts as Drivers of Diverse Skin Wound Responses| journal = International Journal of Molecular Sciences| year = 2020| volume = 21| issue = 2| page = 617| doi = 10.3390/ijms21020617| pmid = 31963533| pmc = 7014275| language = English| doi-access = free}}</ref><ref name=EngrailedEPFsENFs>{{Citation| last = Rinkevich| first = Y| title = Skin fibrosis. Identification and isolation of a dermal lineage with intrinsic fibrogenic potential| journal = Science| year = 2015| volume = 348| issue = 6232| pages = aaa2151| doi = 10.1126/science.aaa2151| pmid = 25883361| pmc = 5088503| language = English}}</ref>

====Myofibroblast====
Mammalian wounds that involve the dermis of the skin heal by repair, not regeneration (except in 1st trimester inter-uterine wounds and in the regeneration of deer antlers). Full-thickness wounds heal by a combination of [[wound contracture]] and edge re-epitheliasation. Partial thickness wounds heal by edge re-epithelialisation and epidermal migration from [[Skin appendage|adnexal]] structures (hair follicles, sweat glands and sebaceous glands). The site of [[keratinocyte]] stem cells remains unknown but stem cells are likely to reside in the [[Stratum basale|basal layer]] of the [[epidermis]] and below the bulge area of hair follicles.

The fibroblast involved in scarring and contraction is the [[myofibroblast]],<ref name="myo201103" /> which is a specialized contractile fibroblast.<ref name="myo2011033" /> These cells express α-smooth muscle actin (α-SMA).<ref name="pmid17586870">{{cite journal |pmid=17586870 |url=https://www.o-wm.com/content/regenerative-healing-fetal-skin-a-review-literature?page=0,11 |year=2007 |last1=Wilgus |first1=T. A. |title=Regenerative healing in fetal skin: A review of the literature |journal=Ostomy/Wound Management |volume=53 |issue=6 |pages=16–31; quiz 32–3 }}</ref> 
The myofibroblasts are absent in the first trimester in the embryonic stage where damage heals scar-free;<ref name=pmid17586870/>  in small incisional or excision wounds less than 2&nbsp;mm that also heal without scarring;<ref name=pmid17586870/> and in adult unwounded tissues where the fibroblast in itself is arrested; however, the myofibroblast is found in massive numbers in adult wound healing which heals with a scar.<ref name=myo2011033/>

The myofibroblasts make up a high proportion of the fibroblasts proliferating in the postembryonic wound at the onset of healing. In the rat model, for instance, myofibroblasts can constitute up to 70% of the fibroblasts,<ref name=myo201103>{{Cite web |author=Linge, Claire (Harrow, GB), Mackie, Ian Paul (Sheffield, GB) | title = Method of preventing or reducing scarring of human skin | quote = myofibroblasts become differentiated from other cells in the wound within a few days after the onset of healing, and in the rat model can reach a peak where about 70% of the fibroblastic cells present are of the myofibroblast phenotype. | publisher = freepatentsonline.com | url = http://www.freepatentsonline.com/y2005/0054608.html| access-date = 26 March 2010}}</ref> and is responsible for fibrosis on tissue.{{needs source|date=October 2024}} Generally, the myofibroblasts disappear from the wound within 30 days,<ref name=myo2011032/> but can remain in pathological cases in [[hypertrophy]], such as keloids.<ref name=myo2011033>{{Cite web |author=Linge, Claire (Harrow, GB), Mackie, Ian Paul (Sheffield, GB) | title = Method of preventing or reducing scarring of human skin| quote = These cells, which differentiate from the unwounded tissue cell type (fibroblasts), are responsible for laying down scar tissue. Indeed, myofibroblasts remain present in hypertrophic scars up to four years after the original wounding event. An in vitro assay was accordingly developed to identify actives which prevent or reduce myofibroblast formation and thus identify actives which are effective in reducing and/or preventing scar tissue formation. | publisher = freepatentsonline.com | url = http://www.freepatentsonline.com/y2005/0054608.html| access-date = 26 March 2010}}</ref><ref name=myo2011032>{{Cite web |author=Linge, Claire (Harrow, GB), Mackie, Ian Paul (Sheffield, GB) | title = Method of preventing or reducing scarring of human skin | quote = the number of myofibroblasts present in the forming scar tissue begins to reduce via apoptosis, until by about 30 days no myofibroblasts are obvious within the scar.| publisher = freepatentsonline.com | url = http://www.freepatentsonline.com/y2005/0054608.html| access-date = 26 March 2010}}</ref> Myofibroblasts have plasticity and in mice can be transformed into fat cells, instead of scar tissue, via the regeneration of hair follicles.<ref name=hairFatMyo>{{cite journal | title = Regeneration of fat cells from myofibroblasts during wound healing | last = Plikus |display-authors=etal | date = 5 January 2017 | journal = Science | pmid=28059714 | doi=10.1126/science.aai8792 | volume=355 | issue = 6326 | pmc=5464786 | pages=748–752| bibcode = 2017Sci...355..748P }}</ref><ref name=MyoFatRegen2017>{{cite journal | title = Repeal and Replace: Adipocyte Regeneration in Wound Repair. | last = Horsley, Watt | date = 6 April 2017 | journal = Cell Stem Cell | pmid=28388424 | doi=10.1016/j.stem.2017.03.015 | volume=20 | issue = 4 | pages=424–426| url = https://kclpure.kcl.ac.uk/portal/en/publications/repeal-and-replace-adipocyte-regeneration-in-wound-repair(bd32d20d-cd1f-4336-a20d-df4f2cda095b).html | type = Submitted manuscript | doi-access = free }}</ref>