www.bjorl.org
Brazilian
Journal
of
OTORHINOLARYNGOLOGY
ORIGINAL
ARTICLE
Endoscopic
observation
of
different
repair
patterns
in
human
traumatic
tympanic
membrane
perforations
夽
Peng
Huang
a,
Shujun
Zhang
b,
Xinhong
Gong
a,
Xuesong
Wang
a,
Zi-Han
Lou
c,∗aBinzhouCentreHospital,DepartmentofOtorhinolary,Shandong,China bBinzhouCentreHospital,DepartmentofPhysiatry,Shandong,China cXinxiangMedicalUniversity,DepartmentofClinicalMedicine,Henan,China
Received4March2017;accepted30June2017 Availableonline3August2017
KEYWORDS Tympanicmembrane perforation; Trauma; Epithelialcell; Granulationtissue; Endoscope Abstract
Introduction:Inthelastdecade,therehasbeenanincreasinguseofbiomaterialpatchesinthe regenerationoftraumatictympanicmembraneperforations.Themajoradvantagesof bioma-terialpatchesaretoprovisionallyrestorethephysiologicalfunctionofthemiddleear,thereby immediatelyimprovingearsymptoms,andactasascaffoldforepitheliummigration.However, whetherthereareadditionalbiologicaleffectsoneardrumregenerationisunclearforbiological materialpatchingintheclinic.
Objective: Thisstudyevaluatedthehealing responsefor differentrepairpatternsinhuman traumatictympanicmembraneperforationsbyendoscopicobservation.
Methods:Intotal,114patientswithtraumatictympanicmembraneperforationswereallocated sequentiallytotwogroups:thespontaneoushealinggroup(n=57)andGelfoampatch-treated group(n=57).Theclosurerate,closuretime,andrateofotorrheawerecomparedbetween thegroupsat3months.
Results:Ultimately,107patientswereanalyzedinthetwogroups(52patientsinthe sponta-neoushealinggroupvs.55patientsintheGelfoampatch-treatedgroup).Theoverallclosure rateattheendofthe3monthfollow-upperiodwas90.4%inthespontaneoushealinggroup and94.5%intheGelfoampatch-treatedgroup;thedifferencewasnotstatisticallysignificant (p>0.05).However,thetotalaverageclosuretimewassignificantlydifferentbetweenthetwo groups (26.8±9.1daysinthespontaneoushealing groupvs.14.7±9.1daysintheGelfoam patch-treated group,p<0.01). In addition,the closure ratewas not significantly different
夽 Pleasecitethisarticleas:HuangP,ZhangS,GongX,WangX,LouZ-H.Endoscopicobservationofdifferentrepairpatternsinhuman
traumatictympanicmembraneperforations.BrazJOtorhinolaryngol.2018;84:545---52.
∗Correspondingauthor.
E-mail:yiwulouzihan@126.com(Z.Lou).
PeerReviewundertheresponsibilityofAssociac¸ãoBrasileiradeOtorrinolaringologiaeCirurgiaCérvico-Facial.
https://doi.org/10.1016/j.bjorl.2017.06.011
1808-8694/©2017Associac¸˜aoBrasileiradeOtorrinolaringologiaeCirurgiaC´ervico-Facial.PublishedbyElsevierEditoraLtda.Thisisanopen accessarticleundertheCCBYlicense(http://creativecommons.org/licenses/by/4.0/).
between thespontaneoushealing groupandGelfoampatch-treated groupregardlessofthe perforationsize.TheclosuretimeintheGelfoampatch-treatedgroupwassignificantlyshorter thanthatinthespontaneoushealinggroupregardlessoftheperforationsize(smallperforations: 7.1±1.6daysvs.12.6±3.9,medium-sizedperforations:13.3±2.2daysvs.21.8±4.2days, andlargeperforations:21.2±4.7daysvs.38.4±5.7days;p<0.01).
Conclusion:Intheregenerationoftraumatictympanicmembraneperforations,Gelfoam patch-ing not only plays a scaffolding role for epithelial migration, it also promotes edema and hyperplasia of granulationtissue at the edges ofthe perforation andaccelerates eardrum healing.
© 2017 Associac¸˜ao Brasileira de Otorrinolaringologia e Cirurgia C´ervico-Facial. Published by Elsevier Editora Ltda. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/). PALAVRAS-CHAVE Perfurac¸ãoda membranatimpânica; Trauma; Célulaepitelial; Tecidodegranulac¸ão; Endoscópio
Observac¸ãoendoscópicadediferentespadrõesdereparoemperfurac¸õeshumanas traumáticasdamembranatimpânica
Resumo
Introduc¸ão:Naúltimadécada,houveumusocrescentedeplacasbiomateriaisnaregenerac¸ão deperfurac¸õestraumáticasdamembranatimpânica.Asprincipaisvantagensdasplacasde bio-materiaissãorestaurarprovisoriamenteafunc¸ãofisiológicadaorelhamédia,assimmelhoram imediatamenteossintomasdaorelhaeatuamcomoumsuporteparaamigrac¸ãodoepitélio. Noentanto,nãosesabeseháefeitosclínicosadicionaisnaregenerac¸ãodotímpanoemrelac¸ão aofragmentodematerialbiológico.
Objetivo:Avaliararespostadecicatrizac¸ãoparadiferentespadrõesdereparoemperfurac¸ões demembranatimpânicatraumáticashumanaspormeiodeobservac¸ãoendoscópica.
Método: Foramalocados114pacientescomperfurac¸õesdemembranatimpânicatraumáticas sequencialmenteparadoisgrupos:odecicatrizac¸ãoespontânea(n=57)eotratadocomesponja deGelfoam(n=57).Avelocidadedefechamento,otempodefechamentoeataxadeotorreia foramcomparadosentreosgruposaostrêsmeses.
Resultados: Foramanalisados107pacientesnosdoisgrupos(52nodecicatrizac¸ãoespontânea e 55 notratado comesponja de Gelfoam). A velocidade global de fechamentono finaldo períododeseguimentodetrêsmesesfoide90,4%nogrupodecicatrizac¸ãoespontâneaede 94,5% nogrupo tratadocom esponjade Gelfoam;adiferenc¸a não foiestatisticamente sig-nificativa (p>0,05). Noentanto,otempo total médiodefechamento foisignificativamente diferenteentreosdoisgrupos(26,8±9,1diasnodecicatrizac¸ãoespontâneaversus14,7±9,1 diasnotratadocomesponjadeGelfoam,p<0,01).Alémdisso,avelocidadedefechamento não foi significativamente diferente entre o grupo de cicatrizac¸ão espontânea e o grupo tratadocomesponja deGelfoam,independentementedotamanhodaperfurac¸ão.Otempo defechamentonogrupotratadocomesponjasdeGelfoamfoisignificativamentemenordoque nogrupodecicatrizac¸ãoespontânea,independentementedotamanhodaperfurac¸ão (peque-nasperfurac¸ões:7,1±1,6diasvs.12,6±3,9,perfurac¸õesdetamanhomédio:13,3±2,2dias vs.21,8±4,2diasegrandesperfurac¸ões:21,2±4,7diasvs.38,4±5,7dias;p<0,01).
Conclusão:Naregenerac¸ãodePMTtraumáticas,aesponjadeGelfoamnãosódesempenhaum papeldeestruturaàmigrac¸ãoepitelial,mastambémpromoveedemaehiperplasiadetecido degranulac¸ãonasbordasdaperfurac¸ãoeaceleraacicatrizac¸ãodotímpano.
© 2017 Associac¸˜ao Brasileira de Otorrinolaringologia e Cirurgia C´ervico-Facial. Publicado por Elsevier Editora Ltda. Este ´e um artigo Open Access sob uma licenc¸a CC BY (http:// creativecommons.org/licenses/by/4.0/).
Introduction
Traumatictympanicmembraneperforations(TMPs)tendto
healspontaneously;thehealingtimeformostTMPsis1---3
months.Many studies have shown that a biological patch
couldshortentheclosuretimeoftraumaticTMPsandeven
improvetheclosurerate.1---10Previousauthorsreportedthat
a keyfeatureof biologicalpatcheswastoprovidea
scaf-foldfor epithelial cellmigrationtoaid therepair process
onexperimental histologic examinations.4,7,8,11,12 Whether
thereare additional biologicaleffects on eardrum
regen-eration is unclear for biological material patching in the
clinic.Theobjectiveofthisstudywastoobservetherepair
processfor differentrepair patterns(spontaneoushealing
vs. Gelfoam patching) in human traumatic TMPs through
dynamicendoscopicobservationfromamorphologic
view-point.
Patients
and
methods
SubjectsA prospective, sequential allocation and controlled
clin-ical study was conducted at Otorhinolaryngology, Head
and Neck Surgery department. The protocol of study had
been approved by our Ethics of Research Committee (n◦
20141201).Theinvestigatorshadobtainedwrittenconsent
from each participant or their guardians. It included 107
patientswithtraumatic TMP,fromJanuary2015 andJune
2016.
Inclusioncriteria
Cases that met the following inclusion criteriawere
ana-lyzed:(i)a slap-or fist-induced TMPwithin7 daysof the
injuries;(ii)age≥16yearsand(iii)dryTMPs.
Exclusioncriteria
(i)A wetor moistTMP withbloody, watery,and/or
puru-lentotorrhea at thefirst hospitalvisit;(ii) severevertigo
orossiculardisruptionsuspecteduponphysicalexamination
or imaging; (iii) blast injury, watersport injury,or direct
penetratinginjury;and(iv)ahistoryofpreviousmiddleear
disease,atrophiceardrum,ormyringosclerosis.
The tympanicmembrane wasexaminedusingan
endo-scope after removing cerumen or blood clots from the
external auditory canal (EAC) using a cotton bud soaked
in povidone-iodinesolution.The tympanicmembrane was
simultaneouslyphotographedusingadigitalvideocamera,
andthe size of theperforation wasanalyzed using Image
Jsoftware(NIH,Bethesda,MD,USA).Eachperforationwas
assignedtooneof threecategories basedontheaffected
portionoftheeardrum:small<1/8;medium1/8to1/4;and
large>1/4.9Age,sex, dateof injury,presenceor absence
ofotorrhea,andassociatedclinicalfindings,including
hear-ingloss,vertigo,andtinnitus,wererecordedateachvisit.
Sinceperforationhealingisassociatedwithsuccessful
clo-sureoftheair-bonegap,audiometricexaminationwasnot
performedinthisstudy.5,6,13
Treatmentallocation
The 114subjects wereallocated intotwogroups:
sponta-neoushealing (n=57) andGelfoam patching (n=57). This
wasperformedby theprincipalinvestigator withthehelp
ofaregisterednurseusingasequentialallocationmethod.
Specifically,consecutive subjectswhobothmetthe
inclu-sioncriteriaandsignedtheconsentformwerealternately
allocatedtothetwogroupsbasedontheorderoftheir
ini-tialhospitalvisit,perforationsize,anddateofreturningthe
signedconsentform.
Treatments
Spontaneoushealinggroup
Patientsin thisgroup receivednointerventionbut
under-wentregularfollow-up.
Gelfoampatch-treatedgroup
The external ear canal was cleaned with a cotton bud
soaked in a povidone-iodine solution. None of the
perfo-rationedgesunderwenttrimming.Amodifiedandpressed
Gelfoamsheet,largerthantheperforation,wassoakedin
0.5%chlortetracyclineointment andthenplaced ontothe
tympanicmembraneremnant(i.e.,onlaytechnique),
com-pletelycoveringtheperforatedareasothatat least2mm
oftheGelfoampatchoverlappedthemargin.
Follow-up
Oral amoxicillin was given to all subjects for 1 week.
Follow-up was scheduled twice a week following the
ini-tiationoftreatment. Thereafter,follow-up wasscheduled
onceaweekuntilcompleteclosureoftheperforationwas
achieved,or forupto3months.The tympanicmembrane
was examined repeatedly by endoscopy at all follow-up
visits.The initialGelfoampatchwasremoved andafresh
pieceofGelfoamwasplacedontothetympanicmembrane
ateachvisitintheGelfoamgroup.Toreduceclinicianbias,
clinicalevents suchastympanicmembraneclosure orthe
presence of otorrheawere photo-documented using color
slides. Ifa patienthad severevertigo, signs of perilymph
leakagewereevaluatedandthepatientwasexcludedfrom
thestudy.Perforationclosurewasconfirmedbyendoscopic
examination. Demographic data and outcome measures
were expressed as the mean±SD and analyzed using a
paired Chi-Squaredtest or t-testwithSPSS software(ver.
11.0forWindows;SPSSInc.,Chicago,IL,USA).Differences
wereconsideredstatisticallysignificantatp<0.05.
Results
Patientdemographics
Intotal,114casesmettheinclusioncriteriaandwere
ana-lyzed. Of these cases, loss of follow-up occurred in four
patientsinthespontaneoushealinggroupandtwopatients
intheGelfoampatch-treatedgroup.Inaddition,one
mid-dleearinfectionwasseeninthespontaneoushealinggroup;
however,nomiddleearinfectionswereseenintheGelfoam
patch-treated group. Thus, 107 patients were ultimately
analyzedinthetwogroups(52inthespontaneoushealing
groupvs. 55in theGelfoam patch-treatedgroup). Ofthe
52patientsinthespontaneoushealinggroup,the
perfora-tionsizewassmallin14patients,medium in21patients,
andlargein17patients.Ofthe55patientsintheGelfoam
Table1 DemographiccharacteristicofspontaneoushealingandGelfoampatchinggroup.
Group Spontaneoushealing Gelfoampatching pvalue
No. 52 55 ---Age(Y) 36.4±5.2 37.1±4.8 0.486a Sex(M:F) 11:41 17:38 0.472b Size(S:M:L) 14:21:17 12:24:19 0.516b Duration(days) 3.7±2.1 3.2±1.8 0.553a Sideofear(L:R) 46:6 47:8 0.847b
Foldededge(with:without) 12:5 16:3 0.378b
p<0.05wasconsideredstatisticallysignificant.
attest. b 2test.
patients,mediumin24patients, andlarge in19patients.
InlargeTMP,folded edgewasseenin12 patientsin
spon-taneoushealinggroup while in16 patentsin theGelfoam
patch-treatedgroup.Thedemographicdataforthepatients
inthetwogroupsarepresentedinTable1.Theaverageage,
male-to-femalepatientratio,sizeof theperforation,size
oftheear,foldededge,andaverageelapsedtimebetween
injuryandthehospitalvisitweresimilarinthetwogroups
(p>0.05).
Healingoutcome
Thepatientswerefollowedforatotalof3monthsoruntil
completeclosureof theperforation.Thehealingoutcome
is summarized in Table2. The overall closurerate at the
end of the 3 month follow-up period was 90.4% in the
spontaneoushealinggroupand94.5%intheGelfoam
patch-treatedgroup;thedifferencewasnotstatisticallysignificant
(p>0.05).However,thetotalaverageclosuretimewas
sig-nificantlydifferentbetweenthetwogroups(26.8±9.1days
inthespontaneoushealinggroupvs.14.7±9.1daysinthe
Gelfoampatch-treatedgroup;p<0.01).
Thehealingoutcomebasedontheperforationsize
clas-sificationafter3 monthsoffollow-up isshown inTable2.
The closure rate was not significantly different between
the spontaneous healing group and the Gelfoam
patch-treatedgroupregardlessoftheperforationsize.However,
theclosure timein the Gelfoampatch-treated group was
significantly shorter than that in the spontaneous healing
groupregardlessoftheperforationsize(smallperforations:
7.1±1.6 days vs. 12.6±3.9; medium-sized perforations:
13.3±2.2daysvs.21.8±4.2days,andlargeperforations:
21.2±4.7daysvs.38.4±5.7days;p<0.01).
Endoscopicobservation
Inthe52patientsinthespontaneoushealinggroup,
hyper-emiaandedemaattheperforationedgeswereseenwithin
48h, andvarious degrees of proliferationof the thin and
transparent epithelium occurred and formed a few areas
of regenerated eardrum at 3---4 days. Edema at the
per-forationedgesdecreasedgradually,andturbidityoccurred
immediatelyfollowingregenerationoftheeardrumat 4---5
days. Thereafter, the epithelium accumulated gradually
andmigrated toward thecenter oftheperforation at the
edge. Seven small-sized perforations achieved complete
closure within1 week. The epithelium continuedto grow
andmigrated toward thecenter oftheperforation at the
edgesofunhealedperforationsuntiltheywerecompletely
closed(Fig.1).However,theincreasingepitheliumcaused
anabnormalityinthecenteroftheperforationandoutward
migrationinonesmall-sizedperforationandtwolarge-sized
perforations.Theoutwardlymigratingepitheliumgradually
formed a crust and did not close the perforation within
3 months. The epithelium didnot continue to grow after
about 6 weeks to 2 months and failed to close within 3
months in two large-sized perforations. In addition,
tur-bidityoftheregeneratedeardrumdidnotoccur,andonly
the atrophic regenerated eardrum closed the perforation
in a small-sized perforation. The folded edges gradually
became necrosis and formed curst over time, eventually
migrated to EAC after perforation closure and did not
affect the healing process in 11 large perforations with
folded edge. Of the 47 healed TMPs, the morphology of
the regenerated eardrum wasnormal in 46 patients, and
the regenerated eardrumwas atrophic in one small-sized
perforation.
Table2 HealingoutcomeofdifferentsizeperforationsofspontaneoushealingandGelfoampatchinggroup.
Group Perforationsize No Closurerate(%) Averageclosuretime
Spontaneous healing
Small-sized 14 13(92.85) 12.6±3.9
Medium-sized 21 21(100.4) 21.8±4.2
Large-sized 17 13(76.5) 38.4±5.7
Gelfoampatch Small-sized 12 12(100.0) 7.1±1.6
Medium-sized 24 23(95.8) 13.3±2.2
Figure1 Spontaneoushealingprocessofsmallperforation:(A---C)wasthe1day,5daysand8daysfollowingperforation.Red indicatedepitheliumproliferationattheedge.
Figure2 ThehealingprocessofperforationafterGelfoampatching:(A)3daysafterGelfoampatchingtreatment;(B)4days afterGelfoampatchingtreatment.Blackarrowsindicategranulationtissue,edema,andexudateatthemargin.
Among the 55 patients in the Gelfoam patch-treated
group,edema,reddishgranularhyperplastictissue,and exu-dation wasseenat the perforationedges within2---3 days
after Gelfoam patching in 48 patients. The regenerated
tissuewasthick,reddishgranulartissuethatincreased grad-ually andmigrated toward thecenter of theperforation.
Subsequently,epithelizationfollowedonthesurfaceofthe granulartissue,andfinallythereddishgranulartissueclosed theperforation. Significant edema and hyperplasiaof the granulartissueoccurredandgraduallybecamedominantat theedgesinfourlarge-sizedperforations.Fourlarge-sized perforationscompletelyclosedat9---12days(Figs.2and3).
Figure3 ThehealingprocessofperforationafterGelfoampatching:(A)1stfollowingperforation;(B---E)2,4,7,and9days,and 2weeksafterGelfoampatching.Blackarrowsindicategranulationtissue,edema,andexudateatthemargin.
The folded edges graduallybecameedema anddissolved,
the proliferation of red granulation tissue or proliferous
eardrumwasseenandgraduallyincreasedover timein14
largeperforationswithfoldededge.However,edema,
red-dishgranular hyperplastic tissue,andexudation werenot
seenduringthefollow-upperiodinonesmall-sized
perfora-tionandtwolarge-sizedperforations,andthesethreeTMPs
failedtoclosewithin3months.Ofthe52healedeardrums
in the Gelfoam patch-treated group, the healedeardrum
wasthickerthantheuninjuredeardrum,butthethickness
ofthehealedeardrumbecamenormalabout3---7daysafter
healing.
Discussion
There are at least two advantages to biological material
patching in the regeneration of traumatic TMPs1---3,5,6,9,10:
(1)a biological materialpatch of similarthicknesstothe
eardrumcoverstheperforationandcanprovisionallyrestore
thephysiologicalfunctionofthemiddleear,thereby
imme-diately improving ear symptoms (e.g., tinnitus and ear
fullness);and(2)abiologicalmaterialpatchactsasa
scaf-foldforepitheliummigrationandshortenstheclosuretime
oftraumaticTMPs.Thisstudyalsosuggeststhattheclosure
timeof theGelfoampatch-treatedgroupwassignificantly
shorterthanthatofthespontaneoushealinggroup
regard-lessoftheperforationsize.However,thetherapeuticeffect
ofabiologicalmaterialpatchontraumaticTMPsisnot
com-pletelyunderstood.
Most scholars believe that a biological material patch
acts only asa scaffold for epithelium migrationand does
notimprovetheclosurerate.2,5,6Inourstudy,the
sponta-neoushealingprocessofhumantraumaticTMPswassimilar
to that in the experimental group; that is, the
perfora-tions were first closed by proliferation of the epidermal
layerof the drumfrom proliferationcenters,followed by
proliferationofthefibrouslayer.14---16Thecentripetal
migra-tionof a single thin and transparent layer (most likelya
proliferatingepithelial layer) was the first event seen by
endoscopy,andthickeningofthislayer(presumablydueto
emergence and growth of the fibrous and mucosal layers
underneath) followed in most traumatic TMPs.
Neverthe-less, outward migration of a single thin epidermal layer
occurredat1---2weeks,graduallyformedthecrust,and
ulti-mately failed to close the perforation in a few patients.
In addition,the epithelium did notcontinue togrow and
turbidityof the regenerated eardrum didnot occur after
about 6 weeks to 2 months. In addition, closure failed
tooccur within3 months in twolarge-sized perforations.
Thus, epithelial cells may deviate from the center of a
perforationandmigrateoutwardduringspontaneous
heal-ing, or hyperplastic epithelial cells may not be sufficient
torepairtheperforation. However,in theGelfoam
patch-treated group, the outward migration and deviation of
regenerated tissue at the perforation edge was not seen
in all patients. Edema, reddish granular hyperplastic
tis-sue, and exudation were seen at the perforation edges
after Gelfoampatching. Reddish granular tissue migrated
centripetallyand firstclosed theperforation, followedby
epithelizationinmostcases.Interestingly,significantedema
andhyperplasiaofgranulationtissueattheedgesresulted
infasterhealinginfourlarge-sizedperforations;inothers,
edemaandreddishgranularhyperplastictissuedidnotoccur
and closure failed. We speculate that the inflammatory
responsetoa biologicalmaterialpatchat the perforation
edge plays a vital role in the regeneration of traumatic
TMPs.
The regeneration of TMPs is a complex biological
pro-cessthatinvolvesepithelialcellproliferationandmigration,
fibroblast hyperplasia, and vascular tissue remodeling.17
Gelfoampatchingpromotededemaandgranulation
hyper-plasiaatperforationedges,andthegranulationtissuewas
rich in neovascularization and fibroblasts, which provided
the necessary oxygen and nutrition for wound healing,18
therebyacceleratingTMPhealing.Alargeamount of
exu-dateattheedgesnotonlyhelpedavoidtissuenecrosisand
adhesion, the wet environment also stimulated the rapid
growthofepithelialcellsandfibroblasts,thereby
facilitat-ingwoundhealing.19,20Althoughchlortetracyclineointment
was a confounding factor in this study, chlortetracycline
ointmentkeeps theeardrum moistandpromotes
granula-tiontissuehyperplasiaatperforationedges,therebyaiding
eardrum healing.21,22 However, the number of patients
receivingchlortetracyclineointmentinourstudywassmall;
the chlortetracycline ointment would dry within a few
days, such that the effects on eardrum healing were
negligible. In clinical studies, an antibiotic ointment is
usually used to secure the patching material (e.g., hen
egg Shell2 and Steri-Strips patch5) and prevent it from
detaching from the eardrum. A clinical study of paper
patchingalonefor traumaticTMPs reporteda92% closure
rate.10
Previousstudiesoveremphasizedthescaffoldfunctionof
patchesand ignoredthe inflammatory responseand
gran-ulation hyperplasia of biological materials at the edges.
A histologic study demonstrated that different biological
materialsmaycausevaryingdegreesofinflammation.4,11,12
Clinical studies also found that the repair of traumatic
TMPs was notcompletely dependent onthe scaffold
sup-port; on the contrary, the topical application of certain
agents alone (e.g., growth factors23,24 and ofloxacin ear
drops25)promotedfasterhealingcomparedtoagents
com-bined with biological materials. Similarly, some scholars
overemphasized the role of proliferation and migration
of the epithelium on eardrum healing and
deempha-sized the proliferation ofgranulation tissuein thefibrous
layer at the edges. This and a previous histologic study
found that the proliferation of granulation tissue in the
fibrous layer plays an important role in the healing of
traumatic TMPs.26 Without proliferation of the fibrous
layer, atrophic healing of the eardrum and failure to
healcouldresult.Inourstudy,oneperforation ultimately
formed an atrophic eardrum in the spontaneous healing
group,andtheregeneratedeardrumdidnotsubsequently
become turbid during spontaneous healing of the
per-foration. No reddish granular tissue occurred during the
healing process, and closure failed to occur within 3
months in three patients in the Gelfoam patch-treated
group. A few experimental studies also found that
gran-ulation tissueproliferation in the fibrouslayer closed the
perforation.27,28
OurevaluationofthehealingprocessoftraumaticTMPs
observation.Theabsenceofhistologicevidencehasobvious
drawbacks;however,itisimpossibletoobtainthisevidence
for ethical reasons. Single granulation tissue first closed
the perforation; thus, the synchronous proliferation of
granulation tissue in the fibrous and epithelial layers
in the Gelfoam patch-treated group should be studied
further.Inaddition,perforationswithanatrophiceardrum
and myringosclerosis were excluded from this study; the
therapeutic effectof Gelfoam patching onthesepatients
requiresfurtherstudy.
Conclusions
IntheregenerationoftraumaticTMPs,Gelfoampatchingnot
onlyplaysascaffoldingroleforepithelialmigration,italso
promotes edema and hyperplasia of granulation tissue at
theedgesandaccelerateseardrumhealing.Thus,patching
shouldbeconsideredforlarge-sizedperforations;however,
traumaticTMPshaveanexcellentcapacityforspontaneous
healing.Thus,spontaneoushealingshouldberecommended
first for small- and medium-sized perforations. In
addi-tion,wefoundthatperforationshealedmorerapidlywhen
edema and hyperplasiaof granulation tissue at theedges
becamemoresignificant.Thus,itisimportantthataclinic
seekbiologicalmaterialsthatarenon-ototoxic,produceno
localpain,andcauseastronginflammatoryreactioninthe
future.
Funding
This study was supported by the Science and Technology
Agency of Zhejiang Province, Health & Medicine Agency
of Zhejiang Province,and Scienceand TechnologyAgency
of Yiwu, China (Grants n◦ 2013C33176, 2015KYB420, and
2015-3-06).
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
References
1.SimsekG, Akin I.Earlypaperpatchingversus observation in patients with traumatic eardrum perforations: comparisons of anatomical and functional outcomes. J Craniofac Surg. 2014;25:2030---2.
2.Jun HJ, Oh KH, Yoo J, Han WG, Chang J, Jung HH, et al. Anewpatchmaterialfortympanicmembraneperforationby trauma:themembraneofaheneggshell.ActaOtolaryngol. 2014;134:250---4.
3.SayinI,KayaKH,Ekizo˘gluO,ErdimI,KayhanFT.Aprospective controlledtrial comparing spontaneous closure and Epifilm® patchingin traumatic tympanic membrane perforations. Eur ArchOtorhinolaryngol.2013;270:2857---63.
4.Altuntas¸EE,SümerZ.Biocompatibilityevaluationofcigarette and carbon papers used in repair of traumatic tympanic membraneperforations:experimentalstudy.EurArch Otorhi-nolaryngol.2013;270:81---6.
5.ParkMK,KimKH,LeeJD, LeeBD. Repairoflargetraumatic tympanic membrane perforation with a Steri-Strips patch. OtolaryngolHeadNeckSurg.2011;145:581---5.
6.LouZC,HeJG.Arandomisedcontrolledtrialcomparing spon-taneous healing, Gelfoam patching and edge-approximation plusGelfoampatchingintraumatictympanicmembrane per-foration with inverted or everted edges. Clin Otolaryngol. 2011;36:221---6.
7.KimJH,ChoiSJ,ParkJS,LimKT,ChoungPH,KimSW,etal. Tym-panicmembraneregenerationusinga water-solublechitosan patch.TissueEngPartA.2010;16:225---32.
8.KimJH,BaeJH,LimKT, ChoungPH,ParkJS,ChoiSJ,etal. Development of water-insoluble chitosan patch scaffold to repairtraumatic tympanicmembrane perforations.JBiomed MaterResA.2009;90:446---55.
9.SaitoH,KazamaY,YazawaY.Simplemaneuverforclosing trau-maticeardrum perforationbymicroporestrip tapepatching. AmJOtol.1990;11:427---30.
10.CamnitzPS,BostWS.Traumaticperforationsofthetympanic membrane:earlyclosurewithpapertapepatching.Otolaryngol HeadNeckSurg.1985;93:220---3.
11.Shen Y, RedmondSL, Teh BM,YanS,Wang Y, ZhouL, et al. Scaffoldsfortympanicmembraneregenerationinrats.Tissue EngPartA.2013;19:657---68.
12.JangCH,AhnS,LeeJW,LeeBH,LeeH,KimG.Mesenchymal stemcell-ladenhybridscaffoldforregeneratingsubacute tym-panicmembraneperforation.MaterSciEngCMaterBiolAppl. 2017;72:456---63.
13.Orji FT, Agu CC. Determinants of spontaneous healing in traumatic perforations of the tympanic membrane. Clin Otolaryngol.2008;33:420---6.
14.JohnsonA,HawkeM.Thefunctionofmigratoryepidermisin thehealingoftympanicmembraneperforationsinguinea-pig. Aphotographicstudy.ActaOtolaryngol.1987;103:81---6.
15.Wang WQ,Wang ZM, Chi FL.Spontaneoushealing ofvarious tympanicmembraneperforationsintherat.ActaOtolaryngol. 2004;124:1141---4.
16.StenforsLE,Carlsöö B,SalénB,Winblad B.Repairof exper-imental tympanic membrane perforations. Acta Otolaryngol. 1980;90:332---41.
17.Gladstone HB, Jackler RK, Varav K. Tympanic membrane woundhealing.Anoverview.OtolaryngolClinNAm.1995;28: 913---32.
18.SteinbrechDS,LongakerMT,MehraraBJ,SaadehPB,ChinGS, GerretsRP,etal.Fibroblastresponsetohypoxia:the relation-shipbetweenangiogenesisandmatrixregulation.JSurgRes. 1999;84:127---33.
19.OkanD,WooK,AyelloEA,SibbaldG.Theroleofmoisture bal-anceinwoundhealing.AdvSkinWoundCare.2007;20:39---53.
20.SvensjöT,PomahacB,YaoF,SlamaJ,ErikssonE.Accelerated healingoffull-thicknessskinwoundsinawetenvironment.Plast ReconstrSurg.2000;106:602---12.
21.Chang J. Does chlortetracycline ointment aid healing of a traumatic tympanicmembrane perforation.ClinOtolaryngol. 2016;41:435---6.
22.Amadasun JE. Anobservationalstudyofthe managementof traumatic tympanicmembraneperforations.JLaryngolOtol. 2002;116:181---4.
23.LouZ.Healinglargetraumaticeardrumperforationsinhumans usingfibroblastgrowthfactorapplieddirectlyorviagelfoam. OtolNeurotol.2012;33:1553---7.
24.Zhengcai-Lou,Zihan-Lou,Yongmei-Tang.Comparativestudyon theeffectsofEGFandbFGFonthehealingofhumanlarge trau-maticperforationsofthetympanicmembrane.Laryngoscope. 2016;126:E23---8.
25.LouZ,LouZ,TangY,XiaoJ.Theeffectofofloxacinoticdrops ontheregenerationofhumantraumatictympanicmembrane perforations.ClinOtolaryngol.2016;41:564---70.
26.SantaMariaPL,RedmondSL,AtlasMD,GhassemifarR.Histology ofthehealingtympanicmembranefollowingperforationinrats. Laryngoscope.2010;120:2061---70.
27.MartiniA,GovoniE,BeghiA,FontanaM,LiniE,MariniP,etal. Spontaneous reparation ofpost-traumatic tympanic perfora-tion:anexperimentalstudyinrats.ActaOtorhinolaryngolItal. 1990;10:559---77.
28.TaylorM,McMinnRM.Cytologyofrepairinexperimental perfo-rationofthetympanicmembraneanditsrelationshiptochronic perforationsinman.TransAmAcadOphthalmolOtolaryngol. 1967;71:802---12.
