Warkar da rauni

**Warkar da rauni** na nufin maye gurbin kwayoyin halitta mai rai na nama da aka lalata ko lalacewa ta sabon nama da aka samar.

A cikin fata mara lahani, epidermis (surface, epithelial Layer) da dermis (mai zurfi, haɗin haɗin gwiwa ) suna samar da shinge mai kariya daga yanayin waje. Lokacin da shingen ya karye, ana saita tsarin abubuwan da suka faru na sinadarai don motsawa don gyara lalacewa. Wannan tsari ya kasu kashi kashi-kashi mai tsinkaya: zubar jini ( hemostasis ), kumburi, ci gaban nama ( yaduwa tantanin halitta ), da gyaran gyare-gyaren nama (maturation da bambancin tantanin halitta ). Za a iya ɗaukar zubar jini a matsayin wani ɓangare na matakin kumburi maimakon wani mataki daban.  
## Mataki
Hemostasis (blotting jini): A cikin ƴan mintuna na farko na rauni, platelets a cikin jini sun fara mannewa wurin da aka ji rauni.  Suna canzawa zuwa siffar amorphous, mafi dacewa da ƙwanƙwasa, kuma suna sakin siginar sinadarai don inganta jini. Wannan yana haifar da kunna fibrin, wanda ke samar da raga kuma yana aiki a matsayin "manne" don ɗaure platelets da juna. Wannan yana haifar da gudan jini wanda ke yin aiki don toshe karyewar a cikin magudanar jini, yana rage gudu/hana ƙarin zubar jini. Kumburi: A wannan lokaci, ƙwayoyin da suka lalace da matattu suna fitar da su, tare da ƙwayoyin cuta da sauran ƙwayoyin cuta ko tarkace.  Wannan yana faruwa ta hanyar phagocytosis, inda fararen jinin jini ke mamaye tarkace kuma su lalata shi.  An saki abubuwan haɓakar da aka samu na platelet a cikin rauni wanda ke haifar da ƙaura da rarrabuwar sel yayin lokacin haɓaka. Yaduwa (ci gaban sabon nama): A cikin wannan lokaci, angiogenesis, ƙaddamar da collagen, granulation tissue formation, epithelialization, da raunin rauni yana faruwa.  A cikin angiogenesis, sel endothelial na jijiyoyin jini suna haifar da sabbin hanyoyin jini.  A cikin fibroplasia da granulation nama samuwar, fibroblasts girma da kuma samar da wani sabon, wucin gadi extracellular matrix (ECM) ta excreting collagen da fibronectin. A lokaci guda, sake dawo da epithelial na epidermis yana faruwa, wanda kwayoyin epithelial ke yaduwa kuma suna 'rarrafe' a saman gadon rauni, suna ba da sutura ga sabon nama. A cikin raunin rauni, myofibroblasts suna rage girman raunin ta hanyar kama gefuna na rauni da yin kwangila ta amfani da hanyar da ta yi kama da ita a cikin ƙwayoyin tsoka mai santsi. Lokacin da ayyukan sel ya kusa ƙarewa, ƙwayoyin da ba a buƙata ba suna fuskantar apoptosis.Maturation (gyare-gyare): A lokacin girma da gyare-gyare, collagen yana daidaitawa tare da layin tashin hankali, kuma kwayoyin da ba a buƙatar su ana cire su ta hanyar mutuwar kwayar halitta, ko apoptosis.

## Lokaci da sake dawo da epithelialization
Lokaci yana da mahimmanci don warkar da rauni. Mahimmanci, lokacin sake dawo da rauni na iya yanke shawarar sakamakon waraka. Idan epitheliation na nama a kan wani yanki da aka lalata ya yi sannu a hankali, tabo zai haifar da makonni masu yawa, ko watanni;

## Farko/lokacin salula
Micrograph mai kyalli na sel a cikin Drosophila larvae waraka bayan raunin huda. Kibiya tana nuni ne ga sel waɗanda suka gauraya don samar da syncytia, sannan kibiya tana nuni zuwa ga sel waɗanda ke fuskantar rauni. Warkar da rauni ya kasu kashi na al'ada zuwa hemostasis, kumburi, yaduwa, da sake gyarawa. Ko da yake ginannen fa'ida ne, wannan ƙirar tana ɗaukar babban juzu'i a tsakanin matakai guda ɗaya. An yi bayanin ƙarin samfuri kwanan nan inda yawancin abubuwan da ke warkar da rauni sun fi fayyace a sarari.  Muhimmancin wannan sabon samfurin ya zama mafi bayyana ta hanyar amfani da shi a cikin fagagen maganin farfadowa da injiniyan nama (duba Sashen Bincike da ci gaba a ƙasa). A cikin wannan ginin, tsarin warkar da rauni ya kasu kashi biyu manyan matakai: farkon lokaci da lokacin salula: Sashe na farko, wanda ke farawa nan da nan bayan raunin fata, ya ƙunshi cascading kwayoyin halitta da abubuwan da ke faruwa na salula wanda ke haifar da hemostasis da samuwar farkon, matrix extracellular matrix wanda ke ba da tsarin tsari don haɗin salula da haɓakar salon salula na gaba.
Tsarin salon salula ya ƙunshi nau'ikan ƙwayoyin sel da yawa waɗanda ke aiki tare don haɓaka amsa mai kumburi, haɗa nama na granulation, da dawo da layin epithelial. Rarraba matakin salula sune:
Macrophages da abubuwan kumburi (a cikin kwanaki 1-2) Epithelial-mesenchymal hulda: sake-epithelialization (phenotype canji a cikin sa'o'i, hijira fara a rana 1 ko 2)
Fibroblasts da myofibroblasts: daidaitawar ci gaba, samar da collagen, da ƙanƙantar matrix (tsakanin ranar 4 da ranar 14)
Kwayoyin endothelial da angiogenesis (farawa a ranar 4)
Dermal matrix: abubuwa na ƙirƙira (farawa a ranar 4, makwanni 2 masu dorewa) da gyare-gyare / gyare-gyare (farawa bayan mako 2, makonni masu ƙarewa zuwa watanni-dangane da girman rauni).

## Yanayin kumburi
Kafin a fara aikin kumburin kumburin, ɗigon jini yana faruwa don a sami ciwon jini, ko kuma dakatar da asarar jini ta hanyar ɗigon fibrin. Bayan haka, ana fitar da abubuwa daban-daban masu narkewa (ciki har da chemokines da cytokines) don jawo hankalin sel waɗanda ke lalata tarkace, ƙwayoyin cuta, da nama da suka lalace, baya ga sakin ƙwayoyin sigina waɗanda ke fara haɓaka lokacin warkar da rauni.
### Clotting cascade
Lokacin da nama ya fara rauni, jini yana haɗuwa da collagen, yana haifar da platelets na jini don fara ɓoye abubuwan kumburi. Platelets kuma suna bayyana manne glycoproteins akan membranes na tantanin halitta wanda ke ba su damar haɗuwa, suna yin taro. Fibrin da fibronectin suna haye-haɗe tare kuma su samar da wani toshe wanda ke kama sunadaran sunadarai da barbashi kuma yana hana ƙarin zubar jini. Wannan fibrin-fibronectin kuma shine babban tallafi na tsarin don raunin har sai an adana collagen. Kwayoyin ƙaura suna amfani da wannan filogi azaman matrix don rarrafe, kuma platelets suna manne da shi kuma suna ɓoye abubuwa. A ƙarshe ana lysed da gudan jini da kuma maye gurbinsu da granulation tissue sa'an nan kuma daga baya da collagen. Platelets, kwayoyin da ke cikin adadi mafi girma jim kadan bayan rauni ya faru, suna saki masu shiga cikin jini, ciki har da cytokines da abubuwan girma. Abubuwan haɓaka suna ƙarfafa sel don saurin rabonsu. Platelets suna sakin wasu abubuwan da ke haifar da kumburi kamar serotonin, bradykinin, prostaglandins, prostacyclins, thromboxane, da histamine, waɗanda ke ba da dalilai da yawa, gami da haɓaka haɓakar tantanin halitta da ƙaura zuwa yankin da haifar da jijiyoyin jini su zama dilated da porous. A hanyoyi da yawa, ƙananan platelets a cikin rauni suna yin irin wannan aiki ga macrophages nama da ƙwayoyin mast da aka fallasa su ga sa hannu na kwayoyin halitta a cikin kamuwa da cuta: sun zama masu aiki, kuma suna ɓoye masu shiga tsakani - amines vasoactive, eicosanoids, da cytokines - wanda ya fara aiwatar da kumburi.

### Vasoconstriction da vasodilation
Nan da nan bayan an karya magudanar jini, ɓangarorin sel da suka fashe suna fitar da abubuwa masu kumburi kamar thromboxanes da prostaglandins waɗanda ke sa jirgin ya fashe don hana zubar jini da tattara ƙwayoyin kumburi da abubuwan da ke cikin wurin.  Wannan vasoconstriction yana ɗaukar minti biyar zuwa goma kuma yana biye da vasodilation, fadada hanyoyin jini, wanda yakan kai kusan mintuna 20 bayan rauni.  Vasodilation shine sakamakon abubuwan da platelets da sauran sel suka fitar.  Babban abin da ke haifar da vasodilation shine histamine. Increased porosity of blood vessels also facilitates the entry of inflammatory cells like leukocytes into the wound site from the bloodstream.  Har ila yau, histamine yana haifar da jijiyoyi na jini su zama poro, yana barin nama ya zama edematous saboda sunadaran da ke fitowa daga jini suna zub da jini zuwa sararin samaniya, wanda ke kara nauyin osmolar kuma yana jawo ruwa zuwa cikin wurin. Ƙara porosity na jini kuma yana sauƙaƙe shigar da ƙwayoyin kumburi kamar leukocytes cikin wurin rauni daga jini.

### Polymorphonuclear neutrophils
A cikin sa'a guda na rauni, polymorphonuclear neutrophils (PMNs) sun isa wurin da aka ji rauni kuma su zama manyan sel a cikin rauni na kwanaki biyu na farko bayan raunin ya faru, tare da adadi mai yawa a rana ta biyu. Suna janyo hankalin su zuwa shafin ta hanyar fibronectin, abubuwan girma, da abubuwa kamar kinins. Neutrophils phagocytise tarkace kuma suna kashe kwayoyin cuta ta hanyar sakin radicals kyauta a cikin abin da ake kira fashewar numfashi. Har ila yau, suna wanke raunin ta hanyar ɓoye ƙwayoyin cuta masu karya lalacewa.  Neutrophils masu aiki a wurin raunin kawai suna da tsawon rayuwa na kusan kwanaki biyu, don haka yawanci suna fuskantar apoptosis da zarar sun kammala ayyukansu kuma an lalata su da macrophages Sauran leukocytes don shiga yankin sun haɗa da sel T masu taimako, waɗanda ke ɓoye cytokines don haifar da ƙarin ƙwayoyin T don rarrabawa da haɓaka kumburi da haɓaka vasodilation da haɓakar jirgin ruwa.  Kwayoyin T kuma suna haɓaka ayyukan macrophages.

### Macrophages
Ɗaya daga cikin ayyukan macrophages shine phagocytize sauran phagocytes da aka kashe,  kwayoyin cuta da nama mai lalacewa, kuma suna lalata nama mai lalacewa ta hanyar sakin proteases. Macrophages suna aiki a cikin sabuntawa kuma suna da mahimmanci don warkar da rauni.  Ƙananan abubuwan da ke kewaye da su suna motsa su don samar da abubuwan da ke haifar da saurin angiogenesis kuma suna motsa ƙwayoyin da ke sake dawo da rauni, haifar da ƙwayar granulation, da kuma shimfiɗa sabon matrix extracellular.  Ta hanyar ɓoye waɗannan abubuwan, macrophages suna ba da gudummawar tura tsarin warkar da rauni zuwa lokaci na gaba.  Suna maye gurbin PMNs a matsayin manyan ƙwayoyin cuta a cikin rauni da kwanaki biyu bayan rauni. Sabo ya ƙunshi rabin monocytes na jiki a ajiye a shirye don a tura shi zuwa nama da suka ji rauni. An jawo hankalin wurin raunin ta hanyar haɓakar abubuwan da ke fitowa daga platelets da sauran sel, monocytes daga jini suna shiga wurin ta bangon jijiyoyin jini.  Adadin monocytes a cikin raunin yakan kai kwana ɗaya zuwa ɗaya da rabi bayan raunin ya faru. Da zarar sun kasance a cikin wurin rauni, monocytes suna girma zuwa macrophages.  Macrophages kuma suna ɓoye abubuwa da yawa kamar abubuwan haɓaka da sauran cytokines, musamman a cikin kwanaki na uku da na huɗu bayan rauni.  Wadannan abubuwan suna jawo hankalin sel masu shiga cikin matakan yaduwar waraka zuwa yankin. A cikin warkar da rauni wanda ke haifar da gyare-gyaren da ba a cika ba, tabo yana faruwa, yana kawo nau'i daban-daban na lahani na tsari, nakasu da matsaloli tare da sassauci.  Macrophages na iya hana lokacin naƙuda.  Masana kimiyya sun ba da rahoton cewa cire macrophages daga salamander ya haifar da gazawar amsawar sabuntawa ta yau da kullun (sakewar hannu), maimakon kawo amsawar gyara (tabo).

### Ragewar lokaci mai kumburi
Yayin da kumburi ya mutu, ƙananan abubuwan kumburi suna ɓoye, waɗanda suke da su sun lalace, kuma adadin neutrophils da macrophages suna raguwa a wurin rauni.  Wadannan canje-canjen suna nuna cewa lokaci mai kumburi yana ƙarewa kuma lokacin haɓaka yana gudana.[19]  Shaidar in vitro, wanda aka samu ta amfani da samfurin daidai da dermal, yana nuna cewa kasancewar macrophages a zahiri yana jinkirta raunin rauni kuma don haka bacewar macrophages daga rauni na iya zama mahimmanci don abubuwan da suka biyo baya su faru.[27]
Saboda kumburi yana taka rawa wajen yaƙar kamuwa da cuta, kawar da tarkace da haifar da lokacin yaduwa, yana da mahimmanci na waraka.  Sai dai kumburi na iya haifar da lalacewar nama idan ya dade da yawa.[7]  Don haka raguwar kumburi akai-akai shine manufa a cikin saitunan warkewa.  Kumburi yana dawwama muddin akwai tarkace a cikin rauni.  Don haka, idan tsarin garkuwar jikin mutum ya lalace kuma ba zai iya kawar da tarkace daga rauni da / ko kuma idan wuce kima detritus, devitalized nama, ko microbial biofilm yana cikin rauni, waɗannan abubuwan na iya haifar da tsawan lokaci mai kumburi da hana rauni.  daga yadda ya kamata ya fara yaduwar lokaci na waraka.  Wannan zai iya haifar da rauni na kullum.

## Lokacin Yaduwa
Kimanin kwanaki biyu ko uku bayan raunin da ya faru, fibroblasts sun fara shiga wurin rauni, wanda ke nuna farkon lokacin yaduwa tun kafin lokacin kumburi ya ƙare.[35].  Kamar yadda yake a cikin sauran matakan warkar da rauni, matakan da ake samu a lokacin yaɗuwar ba sa faruwa a cikin jeri amma a ɗan lokaci su zo kan lokaci.
## Angiogenesis
Har ila yau ana kiransa neovascularization, tsarin angiogenesis yana faruwa a lokaci guda tare da yaduwar fibroblast lokacin da kwayoyin endothelial suka yi ƙaura zuwa yankin rauni.[36].  Saboda ayyukan fibroblasts da ƙwayoyin epithelial suna buƙatar oxygen da abinci mai gina jiki, angiogenesis yana da mahimmanci ga sauran matakai a cikin raunin rauni, kamar ƙaura na epidermal da fibroblast.  Nama wanda angiogenesis ya faru yawanci yayi kama da ja (mai erythematous) saboda kasancewar capillaries.[36]
Angiogenesis yana faruwa a cikin matakai masu haɗuwa don amsawa ga kumburi:
Latent period: A lokacin haemostatic da kumburi lokaci na rauni waraka tsari, vasodilation da permeabilisation damar leukocyte extravasation da phagocytic debridement da decontamination na rauni yankin.  kumburin nama yana taimakawa daga baya angiogenesis ta hanyar faɗaɗawa da sassauta matrix ɗin collagenous na waje.
Kunna endothelial: Yayin da macrophages raunuka ke canzawa daga kumburi zuwa yanayin warkarwa, yana fara ɓoye ƙwayoyin cuta na endothelial da abubuwan haɓaka don jawo hankalin sel na endothelial kusa.  Kwayoyin endothelial da aka kunna suna amsawa ta hanyar ja da baya da rage mahaɗar tantanin halitta, suna kwance kansu daga endothelium ɗin da ke ciki.  A haƙiƙa, ƙwayoyin ƙwanƙwasa da aka kunna suna nuna girman nucleoli.
Lalacewar membrane ginshiki na endothelial: raunin macrophages, ƙwayoyin mast da sel na endothelial da kansu suna ɓoye proteases don rushe basal lamina na jijiyoyin jini.
Bugawar jijiyoyin jini: Tare da rushewar membrane na ginshiki na endothelial, sel na endothelial da aka ware daga capillaries da suka kasance da su da kuma venules na baya-bayan nan na iya rarraba kuma suyi ƙaura ta hanyar chemotactically zuwa ga rauni, shimfiɗa sabbin tasoshin a cikin tsari.  Za'a iya taimakawa tsirowar jini ta hanyar hypoxia na yanayi da acidosis a cikin yanayin rauni, kamar yadda hypoxia ke motsa ƙwayar endothelial transcription factor, hypoxia inducible factor (HIF) don kunna kwayoyin angiogenic kamar VEGF da GLUT1.  Tasoshin da suka tsiro suna iya haɗa kansu zuwa yanayin yanayin haske, kuma haɗuwar tashoshi makafi yana haifar da sabbin hanyoyin sadarwa na capillary.
Balagagge na jijiyoyi: endothelium na tasoshin suna girma ta hanyar shimfida sabon matrix na endothelial na waje, sannan kuma samuwar basal lamina.  A ƙarshe, jirgin yana kafa Layer pericyte.
Kwayoyin da suka samo asali daga sassan jini marasa rauni, suna haɓaka pseudopodia kuma suna tura ta cikin ECM zuwa wurin rauni don kafa sababbin hanyoyin jini.[20].
Kwayoyin endothelial suna janyo hankalin zuwa wurin rauni ta hanyar fibronectin da aka samo akan fibrin scab da chemotactically ta hanyar abubuwan angiogenic da wasu sel suka saki, [37] misali.  daga macrophages da platelets lokacin da suke cikin yanayin ƙarancin oxygen.  Ci gaban endothelial da yaduwa shima yana motsa kai tsaye ta hanyar hypoxia, da kasancewar lactic acid a cikin rauni.[35]  Alal misali, hypoxia yana ƙarfafa ma'anar rubutun endothelial, hypoxia-inducible factor (HIF) don ƙaddamar da saitin kwayoyin halitta masu yaduwa ciki har da vascular endothelial growth factor (VEGF) da glucose transporter 1 (GLUT1).
Don yin ƙaura, ƙwayoyin endothelial suna buƙatar collagenases da plasminogen activator don ƙasƙantar da gudan jini da ɓangaren ECM.[3][19]  Metalloproteinases masu dogara da Zinc suna narkar da membrane na ginshiki da ECM don ba da izinin ƙaura ta tantanin halitta, yaduwa da angiogenesis.[38]
Lokacin da macrophages da sauran sel masu haɓaka abubuwan haɓaka ba su kasance cikin yanayin hypoxic, cike da lactic acid ba, sun daina samar da abubuwan angiogenic.[20]  Don haka, lokacin da nama ya cika sosai, ƙaura da yaɗuwar sel na endothelial yana raguwa.  Daga qarshe magudanar jinin da ba a buqata su ke mutuwa ta hanyar apoptosis.[37]
### Fibroplasia and granulation tissue formation
A lokaci guda tare da angiogenesis, fibroblasts sun fara tarawa a cikin wurin rauni.  Fibroblasts sun fara shiga wurin da aka samu rauni kwana biyu zuwa biyar bayan rauni yayin da lokacin kumburin ke ƙarewa, kuma adadinsu yana ƙaruwa a cikin makonni ɗaya zuwa biyu bayan rauni.[19].  A ƙarshen mako na farko, fibroblasts sune manyan ƙwayoyin cuta a cikin rauni.  Fibroplasia yana ƙare makonni biyu zuwa hudu bayan rauni.
A matsayin misali tsarin fibroplasia na iya zama mai ma'ana a matsayin tsari mai kama da angiogenesis (duba sama) - kawai nau'in tantanin halitta da ke tattare da fibroblasts maimakon sel endothelial.  Da farko akwai wani ɓoyayyen lokaci inda raunin ya sha exudation na plasma, lalatawar kumburi da lalata.  Edema yana ƙara samun dama ga raunin tarihi don ƙaura na fibroplastic daga baya.  Na biyu, yayin da kumburi ya kusa ƙarewa, macrophage da ƙwayoyin mast sun saki ci gaban fibroblast da abubuwan chemotactic don kunna fibroblasts daga nama kusa.  Fibroblasts a wannan matakin suna kwance kansu daga ƙwayoyin da ke kewaye da ECM.  Phagocytes sun kara sakin proteases waɗanda ke rushe ECM na nama maƙwabta, suna 'yantar da fibroblasts da aka kunna don yaduwa da ƙaura zuwa rauni.  Bambanci tsakanin tsirowar jijiyoyin jini da haɓakar fibroblast shine cewa tsohon yana haɓaka ta hypoxia, yayin da ƙarshen ya hana ta hypoxia.  Ajiyayyen nama mai haɗawa da fibroblastic yana girma ta hanyar ɓoye ECM cikin sararin samaniya, yana samar da nama na granulation (duba ƙasa).  A ƙarshe ana saka collagen cikin ECM.
A cikin kwanaki biyu ko uku na farko bayan rauni, fibroblasts galibi suna ƙaura kuma suna yaduwa, yayin da daga baya, su ne manyan ƙwayoyin da ke kwance matrix collagen a wurin rauni.[3]  Asalin waɗannan fibroblasts ana tsammanin su kasance daga nama mara lahani da ke kusa (ko da yake sababbin shaidu sun nuna cewa wasu an samo su ne daga jini, wanda ke zagayawa da ƙwayoyin tsofaffin ƙwayoyin cuta / precursors).[39].  Da farko fibroblasts suna amfani da fibrin da ke haɗa fibers (wanda aka kirkira ta ƙarshen lokacin kumburi) don yin ƙaura zuwa cikin rauni, daga baya kuma suna manne da fibronectin.[37]  Fibroblasts daga nan sai su sanya wani abu na ƙasa a cikin gadon rauni, daga baya kuma collagen, wanda za su iya riko da shi don ƙaura.[15].
Granulation nama yana aiki azaman nama mai rudimentary, kuma ya fara bayyana a cikin raunin riga a lokacin lokacin kumburi, kwana biyu zuwa biyar bayan rauni, kuma yana ci gaba da girma har sai an rufe gadon rauni.  Granulation nama ya ƙunshi sababbin hanyoyin jini, fibroblasts, ƙwayoyin kumburi, ƙwayoyin endothelial, myofibroblasts, da abubuwan da ke cikin sabon matrix extracellular na wucin gadi (ECM).  ECM na wucin gadi ya bambanta da abun da ke ciki daga ECM a cikin nama na al'ada kuma abubuwan da ke tattare da su sun samo asali ne daga fibroblasts.[28]  Irin waɗannan abubuwan sun haɗa da fibronectin, collagen, glycosaminoglycans, elastin, glycoproteins da proteoglycans.[37]  Babban abubuwan da ke tattare da shi shine fibronectin da hyaluronan, wanda ke haifar da matrix mai ruwa sosai kuma yana sauƙaƙe ƙaura ta tantanin halitta.[31]  Daga baya an maye gurbin wannan matrix na wucin gadi da ECM wanda yafi kama da wanda aka samu a cikin nama mara rauni.
Abubuwan haɓaka (PDGF, TGF-β) da fibronectin suna ƙarfafa haɓakawa, ƙaura zuwa gadon rauni, da samar da kwayoyin ECM ta fibroblasts.  Fibroblasts kuma suna ɓoye abubuwan haɓaka waɗanda ke jawo sel epithelial zuwa wurin rauni.  Har ila yau, Hypoxia yana ba da gudummawa ga yaduwar fibroblast da kuma fitar da abubuwan haɓaka, kodayake ƙananan iskar oxygen zai hana ci gaban su da ƙaddamar da abubuwan ECM, kuma zai iya haifar da wuce kima, fibrotic scarring.
### Shigar collagen
Daya daga cikin muhimman ayyukan fibroblasts shine samar da collagen.[36]
Shigar da collagen yana da mahimmanci saboda yana ƙara ƙarfin rauni;  kafin a kwantar da shi, kawai abin da ke riƙe da rauni shine ƙwayar fibrin-fibronectin, wanda baya ba da juriya ga rauni mai rauni.[20]  Har ila yau, ƙwayoyin da ke cikin kumburi, angiogenesis, da ginin nama mai haɗawa suna haɗawa, girma da bambanta akan matrix collagen da fibroblasts suka shimfida.[40].
Nau'in collagen na III da fibronectin gabaɗaya ana fara samarwa cikin ƙima a wani wuri tsakanin kamar sa'o'i 10 [41] da kwanaki 3, [37] ya danganta da girman rauni.  Ajiyensu yana kai kololuwar mako ɗaya zuwa uku.[28]  Su ne manyan abubuwan da ke da ƙarfi har zuwa ƙarshen zamani na maturation, wanda aka maye gurbinsu da nau'in collagen mafi ƙarfi.
Ko da kamar yadda fibroblasts ke samar da sabon collagen, collagenases da sauran abubuwa suna lalata shi.  Ba da daɗewa ba bayan raunin da ya faru, haɗuwa ya wuce lalacewa don haka matakan collagen a cikin rauni ya tashi, amma daga baya samarwa da lalata sun zama daidai don haka babu wani riba na collagen.[20].  Wannan homeostasis yana nuna alamar farkon lokacin maturation na baya.  Granulation sannu a hankali ya daina kuma fibroblasts suna raguwa a lamba a cikin rauni da zarar aikinsu ya yi.[42]  A ƙarshen lokacin granulation, fibroblasts sun fara yin apoptosis, suna canza nama na granulation daga yanayin da ke da wadata a cikin sel zuwa wanda ya ƙunshi galibi na collagen.[3].
### Epithelialization
Samar da nama na granulation a cikin rauni mai buɗewa yana ba da damar lokacin sake dawowa, yayin da ƙwayoyin epithelial ke ƙaura zuwa cikin sabon nama don samar da shinge tsakanin rauni da muhalli.[37]  Basal keratinocytes daga gefen raunuka da dermal appendages kamar gashin follicles, gumi glands da sebaceous (man) gland shine babban sel da alhakin epithelialization lokaci na warkar rauni.[42]  Suna ci gaba a cikin takarda a kan wurin rauni kuma suna yaduwa a gefuna, suna daina motsi lokacin da suka hadu a tsakiya.  A cikin warkaswa wanda ke haifar da tabo, glandon gumi, gashin gashi[43] [44] da jijiyoyi ba sa tasowa.  Tare da rashin gashin gashi, jijiyoyi da glandar gumi, rauni, da tabon warkarwa, suna ba da ƙalubale ga jiki game da kula da yanayin zafi[44].
Keratinocytes suna ƙaura ba tare da fara yaduwa ba.[45]  Hijira na iya farawa da wuri kamar 'yan sa'o'i bayan rauni.  Duk da haka, ƙwayoyin epithelial suna buƙatar nama mai ƙarfi don yin ƙaura, don haka idan raunin yana da zurfi dole ne a fara cika shi da ƙwayar granulation.[46]  Don haka lokacin ƙaura yana canzawa kuma yana iya faruwa kusan kwana ɗaya bayan rauni[47].  Kwayoyin da ke gefen rauni suna yaduwa a rana ta biyu da ta uku bayan raunin da ya faru don samar da ƙarin sel don ƙaura.[28]
Idan ba a keta membrane na ginshiƙi ba, ana maye gurbin ƙwayoyin epithelial a cikin kwanaki uku ta hanyar rarrabuwa da ƙaura zuwa sama na sel a cikin stratum basale kamar yadda yake faruwa a cikin fata mara rauni.[37]  Duk da haka, idan murfin ƙasa ya lalace a wurin da aka samu rauni, sake dawowa dole ne ya faru daga gefen raunin da kuma daga abubuwan da ke cikin fata irin su gashin gashi da gumi da glandan mai da ke shiga cikin dermis wanda ke dauke da keratinocytes masu dacewa.[28].  Idan raunin yana da zurfi sosai, kayan aikin fata kuma na iya lalacewa kuma ƙaura na iya fitowa daga gefuna kawai.[46]
Hijira na keratinocytes a kan wurin rauni yana motsawa ta hanyar rashin hana haɗuwa da kuma ta hanyar sinadarai irin su nitric oxide.[48]  Kafin su fara yin ƙaura, dole ne sel su narkar da desmosomes da hemidesmosomes, waɗanda galibi suna ƙulla sel ta hanyar filaments masu tsaka-tsaki a cikin cytoskeleton zuwa wasu sel zuwa ECM.[23].  Sunadaran masu karɓa na transmembrane da ake kira integrins, waɗanda aka yi da glycoproteins kuma yawanci suna ɗaure tantanin halitta zuwa membrane na ginshiƙi ta hanyar cytoskeleton, ana fitar da su daga tsaka-tsakin filaments na tantanin halitta kuma suna ƙaura zuwa actin filaments don zama haɗe-haɗe ga ECM don pseudopodia yayin ƙaura.[23]  ]  Don haka keratinocytes ke cirewa daga jikin membrane kuma suna iya shiga cikin gadon rauni.[35]
Kafin su fara ƙaura, keratinocytes suna canza siffar, suna zama tsayi kuma suna da kyau kuma suna fadada tsarin salula kamar lamellipodia da kuma matakai masu fadi da suke kama da ruffles.[31]  Actin filaments da nau'in pseudopodia.[35]  A lokacin ƙaura, integrins akan pseudopod suna haɗe zuwa ECM, kuma actin filaments a cikin tsinkaya suna jan tantanin halitta tare.[23].  Yin hulɗa tare da kwayoyin halitta a cikin ECM ta hanyar integrins yana kara inganta samuwar actin filaments, lamellipodia, da filopodia.[23].
Kwayoyin epithelial suna hawa kan juna don yin hijira[42].  Wannan takarda mai girma na sel epithelial ana kiransa da harshen epithelial.[45]  Kwayoyin farko don haɗawa da membrane na ginshiƙi suna samar da stratum basale.  Wadannan sel basal suna ci gaba da yin ƙaura a kan gadon rauni, kuma ƙwayoyin epithelial a samansu suna zamewa tare.[45]  Da zarar wannan hijirar ta yi sauri, to za a samu raguwar tabo.[49]
Fibrin, collagen, da fibronectin a cikin ECM na iya ƙara siginar sel don rarraba da ƙaura.  Kamar fibroblasts, keratinocytes masu ƙaura suna amfani da fibronectin giciye tare da fibrin wanda aka ajiye a cikin kumburi a matsayin wurin da aka makala don rarrafe.[25][31][42]
Yayin da keratinocytes ke ƙaura, suna motsawa sama da nama na granulation amma suna zama ƙarƙashin scab, ta haka ne ke raba scab daga nama mai tushe.[42][47]  Kwayoyin Epithelial suna da ikon yin phagocytize tarkace kamar matattun nama da ƙwayoyin cuta waɗanda ba za su hana hanyarsu ba.  Domin dole ne su narkar da duk wani scab da ke tasowa, ƙaura na keratinocyte ya fi inganta ta wurin daɗaɗɗen yanayi, tun da busassun yana haifar da mafi girma, mafi tsanani.  Don yin hanyarsu tare da nama, keratinocytes dole ne su narkar da gudan jini, tarkace, da sassan ECM don shiga.[47][51]  Suna ɓoye plasminogen activator, wanda ke kunna plasminogen, yana juya shi zuwa plasmin don narkar da scab.  Kwayoyin suna iya yin ƙaura ne kawai akan nama mai rai, [42] don haka dole ne su fitar da collagenases da proteases kamar matrix metalloproteinases (MMPs) don narkar da ɓarna na ECM ta hanyarsu, musamman a gaban takardar ƙaura.[47]  Keratinocytes kuma suna narkar da membrane na ginshiki, ta yin amfani da sabon ECM da fibroblasts suka shimfida don rarrafe.[23]
Yayin da keratinocytes ke ci gaba da ƙaura, dole ne a samar da sababbin ƙwayoyin epithelial a gefen raunuka don maye gurbin su kuma don samar da ƙarin sel don takardar ci gaba.[25]  Yaduwar keratinocytes masu ƙaura yakan fara ƴan kwanaki bayan rauni [46] kuma yana faruwa a cikin adadin da ya ninka sau 17 mafi girma a wannan mataki na epithelialization fiye da na kyallen takarda na al'ada.[25].  Har sai duk wurin da aka samu rauni ya taso, sel epithelial daya tilo don yaduwa suna a gefuna na rauni.[45]
Abubuwan haɓaka, waɗanda ke motsa su ta integrins da MMPs, suna haifar da sel don yaduwa a gefuna masu rauni.  Keratinocytes da kansu kuma suna samar da abubuwan ɓoye, gami da abubuwan haɓakawa da sunadaran membrane na ƙasa, waɗanda ke taimakawa duka a cikin epithelialization da sauran matakan warkarwa.[52]  Har ila yau, abubuwan haɓaka suna da mahimmanci don kare kariya na asali na raunin fata ta hanyar ƙarfafa samar da peptides na antimicrobial da neutrophil chemotactic cytokines a cikin keratinocytes.
Keratinocytes suna ci gaba da yin ƙaura a kan gadon rauni har sai sel daga kowane bangare sun hadu a tsakiya, a lokacin hana haɗuwa ya sa su daina ƙaura.[31]  Lokacin da suka gama ƙaura, keratinocytes suna ɓoye sunadaran da ke haifar da sabon membrane na ƙasa.[31]  Kwayoyin suna juyar da sauye-sauyen yanayin halittar da suka yi don fara ƙaura;  sun sake kafa desmosomes da hemidesmosomes kuma sun sake komawa cikin membrane na kasa.[23]  Kwayoyin Basal sun fara rarrabuwa da bambancewa kamar yadda suke yi a cikin fata na yau da kullun don sake kafa nau'in da aka samu a cikin fata mai sake dawowa[31].
### Hankali
Matsala shine muhimmin lokaci na warkar da rauni tare da gyarawa.  Idan ciwon ya ci gaba na tsawon lokaci, zai iya haifar da lalacewa da asarar aiki.[32]  Don haka akwai babban sha'awar fahimtar ilimin halitta na raunin rauni, wanda za'a iya tsara shi a cikin vitro ta hanyar amfani da collagen gel contraction assay ko kwatankwacin samfurin dermal.[27][53].
Kwangila yana farawa kamar mako guda bayan rauni, lokacin da fibroblasts ya bambanta zuwa myofibroblasts.[54]  A cikin cikakkun raunukan da ke cikin kauri, raguwa yana kaiwa kwanaki 5 zuwa 15 bayan rauni.[37]  Kwangila na iya ɗaukar makonni da yawa[46] kuma yana ci gaba ko da bayan an sake dawo da raunin gaba ɗaya.[3]  Babban rauni na iya zama 40 zuwa 80% karami bayan anguwa[31][42].  Raunuka na iya yin mugunyar gudu har zuwa milimita 0.75 a kowace rana, ya danganta da yadda naman da ke wurin da aka ji rauni ke kwance.[37]  Kwangila yawanci ba ya faruwa daidai gwargwado;  maimakon mafi yawan raunuka suna da 'axis of contraction' wanda ke ba da damar haɓaka mafi girma da daidaitawar sel tare da collagen.[54]
Da farko, ƙanƙancewa yana faruwa ba tare da shigar da myofibroblast ba.[55]  Daga baya, fibroblasts, wanda aka haɓaka ta hanyar abubuwan haɓaka, sun bambanta cikin myofibroblasts.  Myofibroblasts, waɗanda suke kama da ƙwayoyin tsoka masu santsi, suna da alhakin ƙaddamarwa.[55]  Myofibroblasts sun ƙunshi nau'in actin iri ɗaya kamar wanda aka samo a cikin ƙwayoyin tsoka mai santsi.[32]
Myofibroblasts suna jawo hankalin fibronectin da abubuwan haɓaka kuma suna tafiya tare da fibronectin da ke da alaƙa da fibrin a cikin ECM na wucin gadi don isa ga gefuna na rauni.[25].  Suna samar da haɗin kai zuwa ECM a gefen raunuka, kuma suna haɗawa da juna da kuma gefen raunin ta hanyar desmosomes.  Har ila yau, a manne da ake kira fibronexus, actin a cikin myofibroblast yana da alaƙa a cikin membrane na tantanin halitta zuwa kwayoyin halitta a cikin matrix na extracellular kamar fibronectin da collagen.[55].  Myofibroblasts suna da irin wannan mannewa da yawa, wanda ke ba su damar cire ECM lokacin da suka yi kwangila, yana rage girman rauni.[32]  A cikin wannan ɓangaren ƙanƙara, rufewa yana faruwa da sauri fiye da na farko, ɓangaren myofibroblast mai zaman kansa.[55]
Yayin da actin a cikin myofibroblasts ke yin kwangila, ana jan gefuna na rauni tare.  Fibroblasts suna kwantar da collagen don ƙarfafa rauni yayin kwangilar myofibroblasts.[3]  Matsayin raguwa a cikin yaduwa yana ƙare yayin da myofibroblasts suka daina yin kwangila kuma suna yin apoptosis.[32]  Rushewar matrix na wucin gadi yana haifar da raguwar hyaluronic acid da karuwa a cikin chondroitin sulfate, wanda a hankali yana haifar da fibroblasts don dakatar da ƙaura da haɓaka.[19]  Waɗannan abubuwan suna nuna alamar farkon matakin balaga na warkar da rauni.
## Balaga da gyarawa
Lokacin da matakan samar da collagen da lalata suka daidaita, an ce lokacin maturation na gyaran nama ya fara.[20]  A lokacin balaga, nau'in collagen na III, wanda ke yaduwa yayin yaduwa, ana maye gurbinsa da nau'in collagen I.[17].  Asalin ɓarkewar zaruruwan collagen an sake tsara su, an haɗa su da juna, da kuma daidaita su tare da layukan tashin hankali.[31]  Farkon lokacin balaga na iya bambanta da yawa, ya danganta da girman raunin da kuma ko an rufe shi da farko ko kuma an bar shi a buɗe, [28] daga kusan kwanaki uku[41] zuwa makonni uku.[56].  Lokacin balaga na iya ɗaukar shekara ɗaya ko fiye, haka ma ya danganta da nau'in rauni.[28]
Yayin da lokaci ya ci gaba, ƙarfin raunin rauni yana ƙaruwa.[28]  Collagen zai kai kusan kashi 20% na ƙarfin ƙarfinsa bayan makonni uku, yana ƙaruwa zuwa 80% bayan watanni 12.  Matsakaicin ƙarfin tabo shine kashi 80% na fatar da ba ta samu rauni ba.[57]  Tun lokacin da aka rage yawan aiki a wurin rauni, tabon yana rasa jajayen kamanninsa saboda ana cire magudanar jinin da ba a buƙata ta hanyar apoptosis.[20]
Hanyoyin warkar da rauni suna ci gaba a cikin abin da ake iya faɗi, akan lokaci;  idan ba haka ba, warkaswa na iya ci gaba da rashin dacewa zuwa ko dai wani rauni na yau da kullun[7] kamar ciwon jijiyoyi ko tabo kamar tabon keloid.[58][59]
## Abubuwan da ke shafar rauni
Abubuwa da yawa da ke sarrafa inganci, saurin gudu, da kuma yadda ake warkar da raunuka suna faɗuwa ƙarƙashin nau'i biyu: abubuwan gida da na tsari.[2]
### Abubuwan gida
Danshi;  Rike rauni da ɗanshi maimakon bushewa yana sa raunin waraka cikin sauri kuma tare da ƙarancin zafi da ƙarancin tabo[60]
Abubuwan inji
edema
Ionizing radiation
Rashin dabarar rufe rauni
Ischemia da necrosis
Kasashen waje.  Kaifi, ƙananan jikin waje na iya shiga cikin fata ya bar rauni kaɗan amma yana haifar da rauni na ciki da zubar jini na ciki.  Ga jikin baƙon gilashi, "sau da yawa, raunin fata marar laifi yana canza yanayin raunin da ke ƙarƙashinsa"[61].  Raunin jijiya na matakin farko yana buƙatar sa'o'i kaɗan zuwa wasu makonni don murmurewa.[62]  Idan jikin waje ya wuce ta jijiyoyi kuma ya haifar da raunin jijiya na farko a lokacin shigarwa, to, jin dadin jikin waje ko jin zafi saboda raunin ciki na iya jinkirta da 'yan sa'o'i zuwa wasu makonni bayan shigarwa.  Ƙaruwa kwatsam a cikin ƴan makonnin farko na warkar da rauni na iya zama alamar jijiyar da aka dawo da ita tana ba da rahoton raunin ciki maimakon sabon kamuwa da cuta.
Low oxygen tashin hankali
Perfusion
### Matsalolin tsarin
Kumburi
Ciwon sukari - Mutanen da ke da ciwon sukari suna nuna raguwar iyawa wajen warkar da raunuka masu tsanani.  Bugu da ƙari, masu ciwon sukari suna da saurin kamuwa da ciwon ƙafar ƙafar ciwon sukari na yau da kullun, wani mummunan rikitarwa na ciwon sukari wanda ke shafar kashi 15% na masu ciwon sukari kuma yana da kashi 84% na duk yanke ƙafafu masu alaƙa da ciwon sukari [63].  Rashin iyawar warkarwa na masu ciwon sukari tare da ciwon ƙafar ƙafar masu ciwon sukari da/ko raunuka masu tsanani sun haɗa da hanyoyin ilimin halittar jiki da yawa.[64]  Wannan raunin warkarwa ya haɗa da hypoxia, fibroblast da epidermal cell dysfunction, rashin lafiyan angiogenesis da neovascularization, manyan matakan metalloproteases, lalacewa daga nau'in oxygen mai amsawa da AGEs (ci gaban glycation ƙarshen samfurori), rage yawan juriya na rigakafi, da kuma neuropathy.
Abubuwan gina jiki - Rashin abinci mai gina jiki ko ƙarancin abinci mai gina jiki yana da tasirin da za a iya gane shi kan warkar da rauni bayan rauni ko aikin tiyata.[65]  Abubuwan gina jiki da suka haɗa da sunadaran, carbohydrates, arginine, glutamine, polyunsaturated fatty acids, bitamin A, bitamin C, bitamin E, magnesium, jan karfe, zinc da baƙin ƙarfe duk suna taka muhimmiyar rawa wajen warkar da raunuka.[64]  Fats da carbohydrates suna ba da mafi yawan kuzarin da ake buƙata don warkar da rauni.  Glucose shine mafi shahararren tushen man fetur kuma ana amfani dashi don ƙirƙirar ATP ta salula, yana samar da makamashi don angiogenesis da shigar da sababbin kyallen takarda.[64].  Kamar yadda buƙatun abinci na kowane majiyyaci da raunin da ke tattare da su yana da sarƙaƙiya, ana ba da shawarar cewa tallafin abinci mai gina jiki da aka keɓance zai amfana da warkar da rauni mai tsanani da na yau da kullun.[64]
Cututtuka masu narkewa
Immunosuppression
Rashin haɗin nama
Shan taba - Shan taba yana haifar da jinkiri a cikin saurin gyaran rauni musamman a cikin matakan haɓakawa da kumburi.  Hakanan yana ƙara yuwuwar wasu rikice-rikice kamar fashewar rauni, rauni da necrosis flap, raguwar ƙarfin raunin rauni da kamuwa da cuta.[64]  Hakanan shan taba sigari yana lalata tsarin warkar da rauni mai kyau.[66]
Shekaru - Ƙarar shekaru (sama da shekaru 60) abu ne mai haɗari don raunin raunin rauni.[64]  An san cewa, a cikin tsofaffi na in ba haka ba lafiya gabaɗaya, sakamakon tsufa yana haifar da jinkiri na ɗan lokaci a cikin warkarwa, amma babu wani babban lahani game da ingancin waraka.[67]  Jinkirin warkar da rauni a cikin marasa lafiya na haɓaka shekaru yana da alaƙa da canjin kumburi;  misali jinkirta shigar T-cell na rauni tare da sauye-sauye a cikin samar da chemokines, da rage karfin macrophage phagocytic.[68]
Barasa - Shaye-shaye yana lalata raunin rauni kuma yana ƙara haɗarin kamuwa da cuta.  Barasa yana rinjayar lokacin yaduwa na waraka.  Raka'a ɗaya na barasa yana haifar da mummunan tasiri akan sake dawo da epithelialization, ƙulli rauni, samar da collagen da angiogenesis.[64]
A cikin 2000s an sami samfuran lissafin farko na tsarin warkaswa, dangane da sauƙaƙan zato da kuma tsarin bambance-bambancen daidaitawa da aka warware ta hanyar MATLAB.  Samfuran sun nuna cewa "yawan tsarin warkarwa" ya bayyana yana da tasiri sosai ta hanyar aiki da girman raunin da kansa da kuma aikin wakili na warkaswa "[69].
## Bincike da haɓakawa
Har zuwa kusan shekara ta 2000, ba a taɓa fuskantar ƙalubale mai tsanani ba.  Tun daga wannan lokacin, ra'ayin manyan ƙwayoyin ƙwayoyin cuta suna da filastik ta salula ko kuma ikon bambancewa zuwa ƙwayoyin da ba na asali ba ya fito a matsayin madadin bayani.[1]  Don zama ƙayyadaddun ƙayyadaddun ƙwayoyin ƙwayoyin ƙwayoyin cuta na hematopoietic (waɗanda ke haifar da sel masu girma a cikin jini) na iya samun ikon rarrabuwar kawuna zuwa cikin sel na hematopoietic da / ko canzawa zuwa sel waɗanda ba na asali ba, kamar fibroblasts.[39]
### Kwayoyin kara da filastik ta salula
Kwayoyin kararrakin manya masu ƙarfi suna da ikon sabunta kansu kuma suna haifar da nau'ikan tantanin halitta daban-daban.  Kwayoyin sel suna haifar da sel masu tasowa, waɗanda sel waɗanda ba su sabunta kansu ba, amma suna iya haifar da nau'ikan sel da yawa.  Matsakaicin shigar da kwayar cutar ta jiki a cikin cututtukan fata (fata) yana da rikitarwa kuma ba a fahimta sosai ba.
Ana tunanin cewa epidermis da dermis an sake gina su ta hanyar ƙwayoyin ƙwayoyin ƙwayoyin cuta masu aiki waɗanda ke zaune a koli na rete ridges (basal stem cell ko BSC), kumburin gashin gashi (hair follicular stem cell ko HFSC), da kuma papillary dermis (  dermal stem cell).[1]  Bugu da ƙari, maƙarƙashiyar ƙashi na iya ƙunsar ƙananan ƙwayoyin cuta waɗanda ke taka muhimmiyar rawa wajen warkar da rauni na cuta.[39]
A cikin yanayi da ba kasafai ba, irin su babban rauni na cuta, yawan sabunta kai a cikin kasusuwan kasusuwa ana haifar da su don shiga cikin tsarin warkaswa, ta yadda suke haifar da sel masu ɓoye collagen waɗanda da alama suna taka rawa yayin gyaran rauni.[1]  Waɗannan ƙaƙƙarfan yawan sabuntawar kansu guda biyu sune (1) ƙwararrun ƙwararrun ƙasusuwan ƙashi (MSC) da (2) ƙwayoyin sel na hematopoietic (HSC).  Har ila yau, kasusuwa na kasusuwa yana dauke da yawan jama'a na asali ( endothelial progenitor cells ko EPC ) wanda, a cikin nau'i ɗaya, ana tattara su don taimakawa wajen sake gina hanyoyin jini.[39]  Bugu da ƙari, ana tunanin cewa babban rauni ga fata kuma yana haɓaka farkon fataucin wani yanki na musamman na leukocytes (waɗanda fibrocytes) zuwa yankin da suka ji rauni, inda suke yin ayyuka daban-daban da suka shafi warkar da rauni.[1]
### Gyaran raunuka da farfadowa
Raunin shine katsewar ilimin halittar jiki da/ko aikin wani nama da aka bayar.  Bayan rauni, nama mai tsari yana warkarwa tare da rashin cikawa ko cikakkiyar sabuntawa.[71][72]  Nama ba tare da katsewa ga ilimin halittar jiki kusan ko da yaushe gaba daya sabunta.  Misali na cikakkiyar sabuntawa ba tare da katsewar ilimin halittar jiki ba shine nama mara rauni, kamar fata.[73]  Fatar da ba ta yi rauni ba tana da ci gaba da maye gurbinsu da sake haifuwa na sel wanda koyaushe yana haifar da cikakkiyar farfadowa.[73]
Akwai bambanci tsakanin 'gyara' da 'sabuntawa'.[1][71][72]  Gyarawa yana nufin rashin cikawa.[71]  Gyarawa ko rashin cikar sabuntawa, yana nufin daidaitawar jiki na gabobin jiki bayan rauni a ƙoƙarin sake tabbatar da ci gaba ba tare da la'akari da ainihin maye gurbin nama da ya ɓace ba.[71]  Farfaɗowar nama na gaskiya ko cikakkiyar sabuntawa, [72] yana nufin maye gurbin nama da aka ɓata/lalacewa tare da kwafin 'daidai', wanda duka biyun ilimin halittar jiki da ayyuka sun dawo gaba ɗaya.[72]  Ko da yake bayan rauni dabbobi masu shayarwa na iya sake farfadowa gaba ɗaya ba tare da bata lokaci ba, yawanci ba su sake farfadowa gaba ɗaya ba.  Misali na nama yana sake farfadowa gaba daya bayan katsewar ilimin halittar jiki shine endometrium;  endometrium bayan aikin rushewa ta hanyar hawan haila yana warkarwa tare da cikakkiyar farfadowa.[73].
A wasu lokuta, bayan raunin nama, kamar a cikin fata, ana iya haifar da sabuntawa kusa da cikakkiyar farfadowa ta hanyar amfani da ɓangarorin biodegradable (collagen-glycoaminoglycan).  Waɗannan ɓangarorin suna kwatankwacin tsari da matrix extracellular (ECM) da aka samu a cikin dermis na al'ada/marasa rauni.[74]  Mahimman yanayin da ake buƙata don farfadowar nama sau da yawa suna adawa da yanayin da ke ba da ingantaccen gyaran rauni, gami da hana (1) kunna platelet, (2) amsa mai kumburi, da (3) raunin rauni.[1]  Bugu da ƙari don bayar da tallafi ga fibroblast da ƙwanƙwasa sel na endothelial, ɓangarorin da za su iya hana raunin rauni, ta haka ne ke ba da damar tsarin warkarwa don ci gaba zuwa hanyar da za ta sake farfadowa / rashin lalacewa.  An bincika magungunan magunguna waɗanda za su iya kashe bambancin myofibroblast.[75]
Sabuwar hanyar tunani da aka samo daga ra'ayi cewa heparan sulfates sune mabuɗin mai kunnawa a cikin nama homeostasis: tsarin da ke sa nama ya maye gurbin matattun ƙwayoyin cuta ta sel iri ɗaya.  A cikin wuraren rauni, homeostasis nama yana ɓacewa yayin da heparan sulfates suka lalace suna hana maye gurbin matattun sel ta sel iri ɗaya.  Heparan sulfate analogues ba za a iya wulakanta su da duk sanannun heparanases da glycanases da kuma ɗaure ga free heparin sulfate daure spots a kan ECM, don haka kiyaye al'ada nama homeostasis da kuma hana tabo.[76][77][78]
Gyara ko sabuntawa game da hypoxia-inducible factor 1-alpha (HIF-1a).  A cikin yanayi na al'ada bayan rauni HIF-1a yana raguwa ta hanyar prolyl hydroxylases (PHDs).  Masana kimiyya sun gano cewa sauƙi mai sauƙi na HIF-1a ta hanyar masu hanawa na PHD suna sake farfado da nama da suka ɓace ko lalacewa a cikin dabbobi masu shayarwa waɗanda ke da amsawar gyara;  da kuma ci gaba da ka'idojin Hif-1a yana haifar da warkarwa tare da amsa mai ban tsoro a cikin dabbobi masu shayarwa tare da amsawar farfadowa na baya ga asarar nama.  Ayyukan sarrafa HIF-1a na iya ko dai kashewa, ko kunna maɓallin tsarin farfadowar dabbobi masu shayarwa.[79][80]
## Warkar da rauni mara tabo
Warkar da rauni mara tabo ra'ayi ne dangane da waraka ko gyaran fata (ko wasu nama/gabobin) bayan rauni tare da manufar warkarwa tare da zahiri da ƙarancin tabo fiye da yadda aka saba tsammani.  Warkar da ba ta da tabo wani lokaci tana haɗe tare da manufar warkar da tabo, wanda ke warkar da rauni wanda ke haifar da kwata-kwata babu tabo (ba tare da tabo ba).  Duk da haka su ne daban-daban Concepts.
Juyawa zuwa warkar da rauni mara tabo shine tabo (warkar da rauni zuwa tabo). A tarihi, wasu al'adu suna ɗaukar scarification mai ban sha'awa;[81] duk da haka, wannan ba haka yake ba a cikin al'ummar yammacin zamani na zamani, wanda yawancin marasa lafiya ke juya zuwa asibitocin tiyata na filastik tare da tsammanin rashin gaskiya.  Dangane da nau'in tabo, jiyya na iya zama ɓarna ( injections na intralesional steroid, tiyata) da / ko masu ra'ayin mazan jiya (maganin matsawa, gel silicone gel, brachytherapy, photodynamic far).[82]  Hukuncin asibiti ya zama dole don samun nasarar daidaita yuwuwar fa'idodin jiyya daban-daban da ake samu akan yuwuwar rashin amsa mara kyau da yuwuwar rikitarwa sakamakon waɗannan jiyya.  Yawancin waɗannan jiyya na iya samun tasirin placebo kawai, kuma tushen shaidar amfani da yawancin jiyya na yanzu ba shi da kyau.[83]
Tun daga shekarun 1960, fahimtar ainihin hanyoyin nazarin halittu da ke tattare da gyaran raunuka da sake farfadowar nama sun karu saboda ci gaban ilimin halitta da salon salula.[84]  A halin yanzu, manyan manufofin kula da rauni shine a cimma saurin rufe raunuka tare da nama mai aiki wanda ke da ƙarancin tabo.[85]  Koyaya, babban makasudin ilimin halitta na warkar da rauni shine don haifar da ingantaccen sake gina yankin rauni.  Ciwon rauni mara tabo yana faruwa ne kawai a cikin kyallen jikin tayi na mammalian[86] kuma cikakkiyar farfadowa yana iyakance ga ƙananan kasusuwa, kamar salamanders, da invertebrates.[87].  A cikin mutane balagagge, ana gyara nama da suka ji rauni ta hanyar shigar da collagen, gyaran collagen da kuma samuwar tabo, inda aka yi imani da warkar da raunin tayin ya zama wani tsari na farfadowa tare da ƙananan ko babu tabo.[86]  Don haka, ana iya amfani da warkar da rauni na tayi don samar da samfurin dabbobi masu shayarwa mai isa ga mafi kyawun amsawar warkarwa a cikin kyallen jikin ɗan adam.  Alamun yadda za'a iya samun wannan sun fito ne daga nazarin warkar da raunuka a cikin embryos, inda gyaran yake da sauri da inganci kuma yana haifar da cikakkiyar farfadowa na kowane nau'in nama da ya ɓace.
Etymology na kalmar warkar da rauni mara tabo yana da dogon tarihi. A cikin wallafe-wallafen tsohuwar manufar warkarwa mara tabo an samo asali ne a farkon karni na 20 kuma ta bayyana a cikin wata takarda da aka buga a London Lancet.  Wannan tsari ya haɗa da yanke a cikin sling, maimakon kusurwar dama ...;  An bayyana shi a cikin Jaridu daban-daban.
### Cutar daji
Bayan kumburi, maido da mutuncin nama na al'ada da aiki ana kiyaye shi ta hanyar hulɗar amsawa tsakanin nau'ikan tantanin halitta daban-daban waɗanda ke daidaitawa ta ƙwayoyin mannewa da cytokines masu ɓoye.  Rushewar hanyoyin amsawa na yau da kullun a cikin ciwon daji yana barazana ga amincin nama kuma yana ba da damar ƙwayar cuta mai cutarwa don tserewa tsarin rigakafi. Misali na mahimmancin amsawar warkar da raunuka a cikin ciwace-ciwacen daji an kwatanta shi a cikin aikin Howard Chang da abokan aiki a Jami'ar Stanford suna nazarin ciwon nono.

### Abubuwan kari na collagen na baka
Sakamako na farko yana da alƙawarin ga ɗan gajeren lokaci da kuma dogon lokaci na amfani da kariyar collagen na baka don warkar da rauni da tsufa na fata.  Abubuwan kari na collagen na baka kuma suna kara elasticity na fata, hydration, da dermal collagen density. Ƙarin collagen gabaɗaya ba shi da haɗari ba tare da an ruwaito munanan aukuwa ba.  Ana buƙatar ƙarin nazarin don bayyana amfani da likita a cikin cututtukan fata kamar cututtukan fata na atopic dermatitis da kuma ƙayyade mafi kyawun tsarin allurai.
### Tufafin rauni
Tufafin raunuka na zamani don taimakawa wajen gyara rauni sun sami babban bincike da haɓaka a cikin 'yan shekarun nan. Masana kimiyya sun yi niyyar haɓaka suturar rauni waɗanda ke da halaye kamar haka:
Samar da kariya daga rauni
Cire wuce gona da iri
Kaddarorin antimicrobial
Kula da yanayin danshi
Yana da babban permeability zuwa oxygen
A sauƙaƙe cire daga wurin rauni
Halayen marasa anaphylactic
Tufafin auduga sun kasance ma'aunin kulawa, duk da busassun kaddarorinsu da ke iya mannewa saman rauni da haifar da rashin jin daɗi yayin cirewa. Bincike na baya-bayan nan ya yi nisa don inganta suturar gauze na auduga don kusantar da su a layi don cimma ka'idodin gyaran raunuka na zamani, ta hanyar sanya suturar gauze auduga tare da chitosan/Ag/ZnO nanocomposite. Waɗannan suturar da aka sabunta suna ba da haɓaka shayarwar ruwa da ingantacciyar tasirin ƙwayoyin cuta.
### Wankan rauni
Datti ko ƙura a saman raunin, ƙwayoyin cuta, nama da suka mutu, da ruwa daga rauni na iya tsaftacewa.  Shaidar da ke goyan bayan fasaha mafi mahimmanci ba ta bayyana ba kuma babu isasshen shaida don kammala ko tsaftacewar raunuka yana da amfani don inganta warkarwa ko kuma maganin tsaftacewa na rauni (polyhexamethylene biguanide, oxygen peroxide mai ruwa, da dai sauransu) sun fi kyau fiye da ruwa mai tsabta ko saline mafita ga  yana taimakawa ciwon kafa na jijiyoyi ya warke. Ba shi da tabbas ko zaɓin maganin tsaftacewa ko kuma hanyar yin amfani da shi yana da wani bambanci ga warkar da ciwon ƙafar jijiyoyi.

## Yin kwaikwayon warkar da rauni daga hangen nesa mai girma
An ba da himma sosai don fahimtar alaƙar jiki da ke tafiyar da warkar da raunuka da tabo daga baya, tare da ƙirar lissafi da simintin gyare-gyare don fayyace waɗannan alaƙa.[96]  Girman nama a kusa da wurin rauni shine sakamakon ƙaura na sel da ƙaddamar da collagen ta waɗannan sel.  Daidaitawar collagen yana kwatanta matakin tabo;  Kwandon saƙa na collagen siffa ce ta fata ta al'ada, yayin da madaidaicin zaruruwan collagen ke haifar da tabo mai mahimmanci.[97]  An nuna cewa ana iya sarrafa haɓakar nama da girman samuwar tabo ta hanyar daidaita damuwa a wurin rauni.[98]
Ana iya kwaikwayon haɓakar nama ta amfani da alaƙar da aka ambata daga mahallin sinadarai da sinadarai.  Sinadarai masu aiki da ilimin halitta waɗanda ke taka muhimmiyar rawa wajen warkar da rauni an tsara su tare da yaduwar Fickian don samar da bayanan tattara bayanai.  Ma'auni na ma'auni don buɗe tsarin lokacin yin samfurin warkar da rauni ya haɗa da girma mai yawa saboda ƙaurawar tantanin halitta da yaduwa.  Anan ana amfani da ma'auni mai zuwa:
Dtρ0 = Div (R) + R0,
inda ρ ke wakiltar yawan yawa, R yana wakiltar ɗimbin yawa (daga ƙaurawar tantanin halitta), kuma R0 yana wakiltar tushen taro (daga yaduwar kwayar halitta, rarraba, ko haɓakawa).[99].  Ana iya haɗa alaƙa irin waɗannan a cikin nau'ikan tushen wakili, inda za'a iya gwada hankali ga sigogi guda ɗaya kamar daidaitawar collagen na farko, kaddarorin cytokine, da ƙimar haɓakar tantanin halitta.[100]
## Manufar rufe raunuka
Nasarar warkar da rauni ya dogara ne da nau'ikan tantanin halitta daban-daban, matsakaitan kwayoyin halitta da abubuwan tsari.[101]
### Niyya ta farko
Babban niyya ita ce warkar da rauni mai tsabta ba tare da asarar nama ba.[101]  A cikin wannan tsari, ana haɗa gefuna da raunuka, don haka suna kusa da juna (sake kusantar su).  Ana yin ƙullewar rauni da sutures (stitches), maɗaukaki, ko tef ɗin manne ko manne.
Za a iya aiwatar da niyya ta farko kawai lokacin da raunin ya kasance daidai kuma akwai ƙarancin rushewa ga nama na gida da membrane na ginshiƙan epithelial, misali.  tiyatar tiyata.[102]
Wannan tsari ya fi waraka da niyya ta biyu.[101]  Hakanan akwai ƙarancin tabo da ke da alaƙa da niyya ta farko, saboda babu babban asarar nama da za a cika da nama na granulation, ko da yake wasu naman granulation za su yi.[101]
Misalai na niyya ta farko sun haɗa da: gyare-gyare mai kyau, raguwar karayar kashi, waraka bayan tiyata.
Cire riguna da wuri daga raunuka masu tsabta ko gurɓataccen gurɓataccen rauni yana shafar farkon warkar da raunuka.[103][mafi kyawun tushe da ake bukata].
### Niyya ta biyu
Ana aiwatar da niyya ta biyu lokacin da niyya ta farko ba ta yiwuwa saboda gagarumin lalacewa ko asara, yawanci saboda raunin da ya haifar da babban rauni.[102]
An ba da izinin rauni don granulate.
Likitan fiɗa na iya ɗaukar raunin da gauze ko amfani da tsarin magudanar ruwa.
Granulation yana haifar da babban tabo.
Tsarin warkarwa na iya zama jinkirin saboda kasancewar magudanar ruwa daga kamuwa da cuta.
Dole ne a gudanar da kula da raunuka kowace rana don ƙarfafa cire tarkacen rauni don ba da damar samuwar nama.
Yin amfani da maganin rigakafi ko maganin kashe ƙwayoyin cuta don warkar da rauni ta tiyata ta hanyar niyya ta biyu yana da jayayya.[104]
Misalai: gingivectomy, gingivoplasty, soket na cire hakori, raguwa mara kyau, konewa, lacerations mai tsanani, matsi mai matsa lamba.
Babu isassun shaidun da ke nuna cewa zaɓin sutura ko abubuwan da ake amfani da su na zahiri suna shafar warkar da raunuka na biyu.[105]
Akwai rashin shaida kan tasirin maganin rauni mara kyau a cikin raunin rauni ta hanyar niyya ta biyu.[106]
### Babban niyya
(An jinkirta rufewar farko):
An fara tsabtace raunin, an lalata shi kuma ana lura da shi, yawanci kwanaki 4 ko 5 kafin rufewa.
An bar raunin da gangan a buɗe.
Misalai: warkar da raunuka ta hanyar amfani da nama.
Idan ba a sake kusantar gefen raunin nan da nan ba, jinkirin raunin farko yana faruwa.  Ana iya son irin wannan nau'in waraka idan akwai gurɓatattun raunuka.  A rana ta huɗu, phagocytosis na gurɓataccen kyallen takarda yana gudana da kyau, kuma matakan epitheliation, ƙaddamar da collagen, da maturation suna faruwa.  An rufe kayan waje ta hanyar macrophages waɗanda zasu iya metamorphose cikin sel epithelioid, waɗanda ke kewaye da leukocytes mononuclear, suna kafa granulomas.  Yawancin lokaci raunin yana rufewa ta hanyar tiyata a wannan lokacin, ko kuma a ci scab, kuma idan "tsabta" raunin bai cika ba, kumburi na yau da kullum zai iya faruwa, wanda ya haifar da fitacciyar tabo.
## Manazarta