MEMBRANE VERSUS AMNIOTIC MEMBRANE IN TREATING MILLER’S CLASS I AND II GINGIVAL RECESSION: A COMPARATIVE STUDY
A Dissertation submitted
in partial fulfilment of the requirements for the degree of
MASTER OF DENTAL SURGERY BRANCH – II
PERIODONTOLOGY
THE TAMIL NADU DR.M.G.R. MEDICAL UNIVERSITY CHENNAI – 600032.
2017-2020.
ADHI PAR ASAK THI D ENT AL CO LL E GE & HOSPI TAL M ELM ARUVA THUR - 60331 9
DEPAR TM ENT O F PE RIO DON TOLOG Y CER TI FICA TE
This is t o cert ify t hat D r. M .A.M EJALL A , Po st Graduat e st udent (2017 - 2020) in t he Dep art me nt o f Per io do nt ic s, Ad hip ara sakt hi D e nt a l Co lle ge a nd Ho sp it a l, Me lmar u vat hur – 603319, has done this dissertation t it led
“EVALUATION OF CORONALLY ADVANCED FLAP WITH COLLAGEN M EM B RANE VERSUS AM NIOT IC M E M B RANE IN TRE AT ING M IL LER’S CLASS I AND I I GI NGI VAL RE CES SION: A COM PARA TI VE S TUDY ” und er o ur d irect gu ida nce a nd sup erv isio n in part ia l fu lfilme nt o f t he re gu lat io ns la id do w n by t he Ta milna du Dr. M.G.R Med ic a l U niver s it y, C he nna i – 6000 32 fo r MDS., (Bra nc h-II) Dep art me nt o f Per io do nt ic s Degre e Exa minat io n.
Co -Gu ide Gu id e
D r. M . EB ENEZER., M DS Dr. T. RAM AK RISHNAN., M DS
Read er Pro fes so r and H OD
Depart me nt o f Per io do nt ic s . Depart me nt o f Per io do nt ic s .
Pr inc ip a l
D r. A. VASANTHA K UM ARI., M DS Pro fe sso r a nd Head,
Depart me nt o f Pedo do nt ics.
I t hank THE LO RD ALM IGH TY fo r my past , prese nt and fut ure.
I t hank o ur Manag ing D ir ect o r Dr. T. Ra me sh M D., fo r h is vit a l sup po rt a nd a llo w ing u s t o ut iliz e a ll t he fac ilit ie s pro vid ed.
I a m t ha nk fu l t o Dr. A.Vasantha K uma ri M .D.S., o ur be lo ved Pr inc ip a l, Ad h ipara sakt hi De nt a l Co lle ge a nd Ho sp it al, M e lmaru vat hur fo r pro vid ing w it h t he o ppo rt unit y t o ut iliz e t he fac ilit ie s o f t he co lleg e.
I ava il t h is o ppo rt unit y t o expre ss my grat it ude and re vere nce t o my be lo ved Tea c her D r. T. Rama kri sh nan M .D.S., Pro fe sso r and Head, Depart me nt o f Per io do nt o lo g y, Ad hip ar asakt h i De nt a l Co lleg e a nd Ho sp it a l Me lmaru vat hur. H is pur su it fo r per fect io n and imme ns e sup po rt were a so urce o f co nst a nt insp irat io n t o me a nd w it ho ut whic h suc h a n e nde a vo ur wo u ld ne ver had mat er ia liz ed.
It is my dut y t o expres s my t ha nk s t o my Co - gu id e D r. M . Ebene ze r, M .D.S., Reader fo r his va lua b le sug ge st io ns a nd e nco urage me nt s t hro ug h o ut t he co mp let io n o f my d is s ert at io n.
I expre ss my grat it ude to my t eac her s Dr. P. Siva ranjani , M .D.S., Read er , D r. P. Shobana, M.D.S., Lect urer and D r. Priyan ka Pa mpani, M .D.S., Lect urer. I wo uld like t o t ha nk D r. Vidy a Sekh a r, M .D.S , Dr. M ani Sund ar, M .D.S, and Dr. M . M anoj, M .D.S fo r t he ir g u ida nce dur ing t he dur at io n o f t he d iss ert at io n.
I t ha nk M r. M avee ran Libr ar ia n a nd lib rar y st a ff, M r. K . Selva ku ma r.
B .A., Ad hip aras akt hi D e nt a l Co lleg e a nd Ho sp it a l Me lma ru vat hur fo r t he fa vo rs rend ered.
I a lso w is h t o t hank my Co -Pg Dr. E. R amnath, a nd my se nio r s D r. R.
I rudhaya Ni rma la, D r. R. Dhivya, D r. P. In dumathi, a nd I war mly ack no w ledg e my ju nio rs D r. K . Sathish K umar, D r. K . Priyadu rga , D r.N.K owsa lya and D r.M .K.Vigneshwa ran.
I o we my grat it ude t o my pare nt s M r. M . Ama la Dhas , M rs. S. Helan Da s a nd my bro t her M r. M .A. Jose Jera ld D as w ho sacr ific ed so muc h fo r me a nd t he so le re aso n fo r what I a m t o da y.
Dr. M. A.MEJ ALLA POST GR ADU ATE STUDENT
TITLE OF THE DISSERTATION
EVALU ATIO N O F C OR ON ALLY AD V ANCE D FLAP WITH CO LLAGEN MEMB R ANE VERSUS
AMNIOTIC MEMB R ANE IN TR EATING
MILLER’S CLASS I AND II GINGIVAL RECESSION: A CO MP AR ATIVE STUDY
PLACE O F THE STUDY Ad h ipara sakt hi De nt a l Co lleg e a nd H o sp it a l, Me lmaru vat hur -603 319.
DUR ATION O F THE COURSE 3 Years
N AME O F THE GUIDE Dr.T.Ra ma kr is hna n, MDS.
N AME OF CO -GUIDE Dr. M.Ebe nezer, M DS.
I here by d ec lar e t hat no part o f t he d iss ert at io n w ill be ut ilize d fo r ga in ing fina nc ia l a s s ist a nc e o r any pro mo t io n w it ho ut o bt aining pr io r per mis s io n o f t he P r inc ip a l, Ad hip ara sakt hi De nt a l co lle ge a nd Ho sp it a l, Me lmaru vat hur -60 3319. I n ad d it io n, I de c lare t hat no part o f t his wo rk w ill be pub lis hed e it her in pr int o r in e lect ro nic med ia w it ho ut t he gu ide s ’ k no w ledg e who ha ve bee n act ive ly in vo lved in d is sert at io n. The aut ho r has t he r ig ht to reser ve fo r p u blis h wo rk so le ly w it h t he per mis s io n o f t he pr inc ipa l, Ad h ipara sakt hi De nt a l co lleg e a nd Ho sp it a l, M e lmaru vat hur -60331 9.
Co-guide Guide & Head of Depa rtment
Signature of c andidate
EVALUATION OF CORONALLY ADVANCED FLAP WITH COLLAGEN MEMBRANE VERSUS AMNIOTIC MEMBRANE IN TREATING MILLER’S CLASS I
AND II GINGIVAL RECESSION: A COMPARATIVE STUDY ABSTRACT
BACKGROUND:
By clinical definition, gingival recession is exposure of root surface by an apical shift in the position of the gingiva. It may result in sensitivity, unaesthetic appearance and root caries. Root coverage procedures aim to restore the gingival margin coronal to the CEJ along with periodontal regeneration. Various procedures such as free gingival graft, lateral pedicle flap, connective tissue graft, coronally displaced flap and double papilla have produced predictable root coverage; however healing almost always occurs by formation of long junctional epithelium. GTR is one of the techniques used for recession coverage. The membranes used for root coverage have evolved. Recently amniotic membrane is being used as an adjunct for treating recession defects. Amniotic tissue contains growth factors and fetal mesenchymal stem cells which may aid in periodontal regeneration.
AIM:
The aim of the study is to compare clinically the outcome of root coverage done using coronally advanced flap with collagen membrane and coronally advanced flap with amniotic membrane in treating Miller’s class I and II gingival recession.
MATERIALS AND METHODS:
Fifteen bilateral recession sites with Miller’s Class I and II gingival recessions in the maxillary arch were included in this study. Recessions were randomly treated according to split mouth design by coronally advanced flap with collagen membrane on the control site and amniotic membrane on the test site.
RESULTS:
The mean root coverage was 88% in the control group and 91% in the test group at the end of three months. No statistical significance was found between the two groups in terms of recession height (RH), recession width (RW), probing depth (PD), width of keratinized tissue (WKT) and clinical attachment level (CAL) at third month.
CONCLUSION:
This study suggests that amniotic membrane can be used as an alternative to collagen membrane in treating Miller’s class I and II gingival recessions using coronally advanced flap.
S.NO. TITLE PAGE NO.
1. INTRODUCTION 1
2. AIM AND OBJECTIVES 3
3. GENERAL REVIEW 4
4. REVIEW OF LITERATURE 18
5. MATERIALS AND METHODS 35
6. RESULTS 52
7. DISCUSSION 66
8. CONCLUSION 76
9. REFERENCES 78
10. ANNEXURE i-viii
LIST OF FIGURE S
S.NO. FIG URE D ESCR I PT ION PAG E NO.
1 Bas ic Ar ma me nt ar iu m 44
2 Preo perat ive p ict ures o f co nt ro l sit e – co ro na lly ad va nced flap w it h co llage n me mbra ne
44
3 Co llag e n me mbra ne 46
4 Int rao perat ive p ict ures o f co nt ro l sit e – co ro na lly ad va nced flap w it h co llage n me mbra ne
46
5 Preo perat ive p ict ures o f t est sit e – co ro nally ad va nced flap w it h a mn io t ic me mbr a ne
47
6 Amn io t ic me mbr a ne 49
7 Int rao perat ive p ict ures o f t est sit e – co ro na lly ad va nced flap w it h a mn io t ic me mbr a ne
49
8 Po sto perat ive p ict ure s o f co nt ro l sit e – co ro na lly ad va nced flap w it h co llage n me mbra ne
50
9 Po sto perat ive p ict ure s o f t est sit e – co ro na lly ad va nced flap w it h a mn io t ic me mbr a ne
51
S.NO. TAB LE PAG E NO.
1
Co mpar iso n o f Me a n Preo perat ive Va lu es o f Var io u s C lin ic a l P ara met ers bet wee n Co nt ro l a nd Test Sit e
53
2
Co mpar iso n o f Me a n Preo perat ive a nd Po sto perat ive Va lue s o f V ar io u s C lin ic a l P ara met ers in Co nt ro l S it e
56
3
Co mpar iso n o f Me a n Preo perat ive a nd Po sto perat ive Va lue s O f V ar io u s C lin ic a l Para met ers I n Test Sit e
59
4
Co mpar iso n o f Me a n Po sto perat ive Va lu es o f Var io u s C lin ic a l P ara met ers bet wee n Co nt ro l And Test Sit e
62
LIST OF CHARTS
S.NO. CHART PAG E NO.
1
Co mpar iso n o f M ea n Preo perat ive Va lu es o f Var io us C lin ic a l Para met ers bet wee n Co nt ro l a nd Test S it e
55
2
Co mpar iso n o f M ea n Preo perat ive a nd Po sto perat ive Va lu e s o f Var io us C lin ic a l P ara met ers in Co nt ro l S it e
58
3
Co mpar iso n o f M ea n Preo perat ive a nd Po sto perat ive Va lu e s o f Var io us C lin ic a l P ara met ers in Test S it e
61
4
Co mpar iso n o f Mea n Po st o perat ive Va lu es o f V ar io us C lin ica l Para met ers bet wee n Co nt ro l a nd Test S it e
64
5
Co mpar iso n o f Me a n Ro ot Co verage Perce nt age bet wee n Co nt ro l a nd Test S it e
65
AM - Amnion membrane
ACM - Amnion chorion membrane AMSC - Amniotic mesenchymal stem cell bFGF - Basic fibroblast growth factors CAF - Coronally advanced flap
CEJ - Cementoenamel junction
CM - Collagen membrane
CPD - Clinical probing depth
DFDBA - Demineralized freeze dried bone allograft DMSO - Dimethyl sulphoxide
EDGF - Epidermal derived growth factor
GR - Gingival recession
GBR - Guided bone regeneration GTR - Guided tissue regeneration HAE - Human amniotic epithelial cells HAM - Human amniotic mesenchymal cells
HLA - Human leukocyte antigen HNF-3β - Hepatocytes nuclear factor-3β IGF - Insulin derived growth factor ILT - Immunoglobulin-like transcript
IFN - Interferon
KGF - Keratinocyte growth factor MGJ - Mucogingival junction MMP - Matrix metalloproteinases MSC - Mesenchymal stem cell NGF - Nidogen growth factor
OCT - Octamer-binding transcription factor PRC - Percentage of root coverage
PRF - Platelet rich fibrin PDL - Periodontal ligament
PDLSC - Periodontal ligament stem cell
RH - Recession height
RW - Recession width
SCTG - Subepithelial connective tissue graft SLPI - Secretary leukocyte proteinase inhibitor TNF-α - Tumor Necrosis Factor alpha
TGF-β - Transforming growth factor-beta VEGF - Vascular endothelial growth factor WKT - Width of keratinized tissue.
Introduction
1
INTRODUCTION
G ing iva l rece s s io n is c hara ct er iz ed by t he d is p lac e me nt o f t he g ing iva l mar g in ap ica lly fro m t he ce me nt o e na me l ju nct io n, o r CEJ, o r fro m t he fo r mer lo cat io n o f t he CEJ in w hic h r est o rat io ns ha ve d ist o rt ed t he lo cat io n o r appeara nce o f t he CEJ.1 T he re su lt ing ro ot expo sure is no t est het ica lly p le as ing a nd ma y le ad t o se nsit iv it y a nd ro ot car ie s.2 G ing iva l rec es sio n e it her lo c a lize d o r gener a lize d, is o ne o f t he c lin ica l feat ures o f per io do nt al d is e as e a nd is fre que nt ly a s so c iat ed w it h c lin ic a l pro ble ms su c h as ro ot sur fac e hyper se ns it iv it y, ro ot caries, cer vica l ro o t abras io ns, ero sio ns, p laque ret e nt io n a nd ae st het ic d is - sat isfact io n.3 , 4
Var io us t reat me nt o pt io ns had bee n sug gest ed in t he ma nage me nt o f g ing iva l recess io n. T he se inc lu de fre e g ing iva l gr a ft , lat era l p ed ic le fla p, su bep it he lia l co nne ct ive t is sue gra ft , co ro na lly d is p laced fla p a nd do u ble pap illa. T he s e t echniqu es ha ve s ho wn pre d ict a ble re su lt s o ver t he ye ars. Ho we ver, he a ling a lmo st a lwa ys o ccurs by t he fo r mat io n o f lo ng ju nct i o na l ep it he liu m w it h mino r a mo u nt s o f co nnect ive t is sue at t achme nt w it h lit t le o r no new ce me nt u m o r bo ne fo r mat io n.5
T int i a nd V ince nt i u se d t he pr inc ip le o f gu id ed t is sue reg e nerat io n (GTR) to o bt a in co vera ge o f t he de nude d root sur fac e a lo ng w it h rege n erat io n o f t he e nt ire at t achme nt apparat us.6 The me mbra nes u sed in gu ide d t is sue rege nerat io n has e vo lved t hro ugh t he ye ars. To da y, the co nce pt o f e xc lud ing t he g ing iva l ep it he liu m w it h t he mere use o f bar r ier me mbra ne s has e vo lved t o t he
Introduction
2
inco rpo rat io n o f t he co rrect s ig na ling mo le cu le s like t he gro wt h fa ct o rs and t he prese nce o f co rrect ce ll po pu lat io n lik e t he st e m c e lls, fibro bla st , and ce me nt o bla st d irect ly int o t he wo und t o pro mo t e regenerat io n. Me se nc h yma l st e m ce lls (MS Cs) ar e o ne o f t he ma jo r c e lls po pu lat io n t hat p la y a n impo rt ant ro le in me d iat ing ea c h p has e o f t he wo und he a ling pro ces s: Infla mmat o r y, pro lifer at ive, a nd re mo d e ling.
Rec e nt ly a mn io t ic me mbr a ne ha s bee n us ed in gu ide d t issu e rege ner at io n. The c lin ica l app licat io n o f a mn io t ic me mbr a ne fo r GTR, while fu lfilling t he curre nt me c ha nic a l co ncept o f GTR, a me nd s it w it h t he mo der n co nc ept o f bio lo g ic a l GTR.6
There fo r e, t his st ud y hypo t he s ize d t hat a mn io t ic me mbr a ne p la ced a lo ng w it h C AF ma y be a n e ffic ie nt t reat me nt o pt io n in t he ma nage me nt o f M ille r’s c la s s I a nd II g ing iva l rec es s io n. T he purp o se o f t he prese nt st ud y wa s t o co mpar e t he c lin ica l e ffe ct o f co llag e n me mbr a ne a lo ng w it h C AF co mpared t o a mnio t ic me mbr a ne a lo ng w it h C AF in t reat ing g in g iva l r ece s s io n.
Aim and objectives
Aim and objectives
3
AIM AND OBJECTIVES AIM
The a im o f t he st ud y is t o co mpare c lin ic a lly t he o ut co me o f ro o t co verage do ne us ing co ro na lly ad va nced fla p w it h co lla ge n me mbr a ne a nd co ro na lly ad va nce d flap w it h a mn io t ic me mbra ne.
OB JECT IVES
1. To eva luat e t he e ffect ive ne ss o f co ro nally a d va nced flap in ma nag in g Miller’s class I and II gingival recessio n.
2. To eva luat e t he e ffect ive nes s o f a mn iot ic me mbr a ne w it h co ro na lly ad va nced flap in ma nag ing g ing iva l rec es s io n .
3. To eva lu at e and co mp are t he cha nge s in t he g ing iva l d ime ns io ns dur ing t he use o f co lla ge n me mbra ne a nd a mn io t ic me mbra ne a lo ng w it h co ro na lly ad va nc ed flap.
General Review
General review
4
GENE RAL R EV IEW
There are t wo wa ys in w hic h a muco g ing iva l p ro ble m pres e nt s it s e lf. T he y co u ld e it her be a po cket fo r mat io n du e t o a c lo se d isru pt io n o f t he mu co g ing iva l co mp le x o r as g ing iva l c le ft s a nd r ece ss io n due t o o pen d isrupt io n o f t he mu co g ing iva l co mp le x.7 The t er m g ing iva l re ce ss io n ca n be used t o charact er iz e t he ap ica l s hift o f t he marg ina l g ing iva fr o m it s no r ma l po s it io n o n t he cro wn o f t he toot h to t he le ve ls o n t he root sur fac e be yo nd t he ce me nt o -ena me l ju nct io n.8 Est het ic s ma y be co me a co ncer n in g ing iva l rece s s io n in ca se o f a nt er io r t eet h invo lve me nt a nd fear fo r pro gress io n o f the d ise as e lead ing t o bo ne lo s s. It ma y a lso be as so c iat ed w it h de nt in hyper se ns it iv it y, root caries, a bras io n a nd/o r cer vica l w ear, ero s io n becau se o f e xpo sure o f t he root surface t o t he o ra l e nviro nme nt a nd a n incre as e in acc u mu lat io n o f de nt a l p laqu e.9
The et io lo g y o f g ing iva l re ce ss io n re ma ins t o be mu lt ifa ct o ria l. Ot her t ha n t he pat ho lo g ica l cau se s le ad ing t o g ing iva l re ce ss io n, i t ha s be e n fo u nd t hat inc ide nce o f g ing iva l re ce ss io n increa se s w it h age. Ano t her et io lo g ic fa ct o r t hat ma y be as so c iat ed w it h g ing iva l rec essio n is a pr io r lack o f a lveo lar bo ne at t he s it e.1 0 No rma lly fe ne st rat io n, de hisce nce , abno r ma l t o ot h po sit io n, c ha ng e in pat h o f erupt io n a nd t oot h s hape ma y be co ns ider ed t he a nat o mic a l fact o rs re lat ed to g ing iva l re ce ss io n.1 1 P hys io lo g ic a lly, g ing iva l rec es s io n ma y a lso be caused by g ing iva l de his c e nce c aused b y mo ve me nt o f t he toot h o rt ho do nt ic a ll y to po sit io ns o ut s id e t he la b ia l a nd ling ua l a lveo lar p lat e.1 2 Rece ss io n ma y a lso be cau se d due t o vigo ro us toot hbrus h in g, aberra nt fre na l at t achme nt , t o bacco c hew ing, o cc lu sa l in jur y a nd o perat ive pro cedures. Aberra nt fre na l at t achme nt
5
a lso ha s be e n me nt io ned a s a cau se o f lo ca liz ed rece s s io n, but t he e vid e nc e is no t o verw he lming.2
Var io us c la s s ific at io ns o f g ing iva l re ce ssio ns ha ve bee n us ed fo r d iag no st ic purposes. The most commo n and widely used amo ng them is the Miller’s c las s ific at io n1 3 w hic h w as pro po sed in 19 85 .
C la ss I—M arg ina l t iss ue rece s sio n t hat do es no t ext end t o t he muco g ing iva l ju nct io n ( MG J), w it h no per io do nt a l lo ss in t he int erd e nt a l area ; t he t oot h is we ll a lig ned in t he arc h. O ne hu ndred per ce nt root co verage c a n be a nt ic ipat ed.
C la ss II —Marg ina l t is sue rec es s io n t hat e xt end s be yo nd o r upto t he MGJ, w it h no per io do nt a l lo ss in t he int erd e nt a l area ; t he t oot h is we ll - a lig ne d in t he arc h.
One hu ndred p erce nt root co verag e ca n be ant ic ipat ed.
C la ss III —Marg ina l t is su e rece ss io n t hat e xt end s be yo nd o r upto t he M GJ ; bo ne o r so ft t is sue lo s s in t he int erde nt a l area ; ma l-po s it io ning o f t he t eet h. Part ia l root co verag e ca n be e xpect ed.
C la ss IV— Marg ina l t is su e rece ss io n t hat e xt end s be yo nd o r upto t he MG J ; bo ne o r so ft t issu e lo s s in t he int erd e nt a l ar ea a nd/o r ma lpo s it io ning o f t he t eet h is so se ver e t hat root co verage s ho u ld no t be att empt ed.
Pro per underst a nd ing o n t he et io lo g y a nd d iag no s is o f g ing iva l re ce ss io n he lp s in p la nning t he des ired t reat me nt o pt io n. The var io us t reat me nt mo da lit ie s inc lud ing t he fr ee g ing iva l gra ft , su be p it he lia l co nne ct ive t is sue gra ft , lat era l
General review
6
ped ic le flap, do uble pa p illa fla p a nd t he co ro na lly ad va nce d flap ha s s ho w n goo d resu lt s.
Co ro na lly ad va nc ed fla p (C AF) is a s u it a ble t echn ique t hat pro duces goo d resu lt s in t reat ing g ing iv a l re ce ssio n w it h adequ at e ap ica l kerat iniz ed t is sue.
Alle n, Miller, Zuc c he lli, a nd De Sa nct is are so me o f t he p io neer s w ho ha ve pro po sed d iffer e nt CAF t ec hniqu es . I n t he t echniq ue a s de mo nst rat ed by Alle n a nd Mille r, t he st art ing po int o f t he lat era l inc is io ns w as no t ind ic at ed prec is e ly.
The t rapezo ida l C AF wa s int ro duced by d e Sanct is a nd Zu cc he lli t hat resu lt ed in adequ at e ro ot co verage in ma n y ca se s. Re lat ive ly re ce nt ly, Zucc he lli et al. descr ibed a mo d ifie d C AF w it h a tr ia ngu lar des ig n a nd co mpare d it s e ffe ct ive nes s w it h t he t rapezo ida l C AF. 1 4
The co mmo nly e mp lo yed ro ot co verag e o f CAF w as g ive n by Alle n a nd M ille r in 1989. The C AF is a ro ot co verage surger y t hat do es no t invo lve a pa lat a l do no r s it e, a nd it w as de mo nst rat ed to be a sa fe and pr ed ict a ble ap pro ach. T he C AF is t he fir st cho ic e fo r pat ie nt s w it h hig h e s t het ic co ncer ns. It is per fo r me d w he n t here is adequ at e kerat iniz ed t issue ap ic a l t o t he root expo sure. The est het ic resu lt is mo re s at is fact o ry in t his appro ac h s ince t he ro ot co ve rag e is s imilar in co lo r, t ext ure and t hic k ne ss.1 5
The u se o f p la ce nt a l t is sue fo r t he t reatme nt o f wo und st art ed in 1910 w he n Da vis first used t he se fet a l me mbra nes as sk in su bst it ut es fo r t reat ing o pe n wo und s.1 6 Sabe lla a nd St er n in 191 3 de scr ibed it s u s e fo r bur nt a nd u lc erat ed sk in sur fac es. T he y e va lu at ed t he a cce ler at ive e ffe ct o f t he me mbra ne o n
7
ep it he lia lizat io n a nd t he reduct io n in pa in in t he wo und. In 1940, De Röt h first repo rt ed use o f fet a l me mbra nes in t he o cu lar sur face. He us ed fre s h a mn io n a nd c ho r io n as a bio lo g ica l dre s sing mat eria l fo r ma nag e m e nt o f co nju nct iva l de fect s.1 7
The u se o f t hes e me mbra ne s wa s ver y limit ed at t hat t ime o w ing t o t he lack o f id ea l a nd pract ica l me a ns o f preparat io n, st er iliz at io n a nd st o rage ava ila b le.
Kim a nd Tse ng in 1995 g a ve t he pre ser vat io n met ho d fo r ma xima l ma int e na nc e o f bio lo g ic pro pert ies o f me mbra ne s. It was de mo nst rat ed fo r t he fir st t ime b y D ino et al. in 1965 t hat a mnio t ic me mbr a ne co u ld be sep arat ed, st eriliz ed a nd sa fe ly u sed at a lat er dat e. Sin c e t he n a lo t o f rese arc h ha s be e n in it iat ed t o und erst a nd t he t rue rege nerat ive po t ent ia l o f t his me mbra ne.1 8
The ut ilizat io n of amniot ic me mbrane waned in the early 1980’s because o f incr ea se in t he co mmu n ica ble d isea se s s uc h a s H.I.V./A.I.D.S., Hepat it is, et c.
Amn io n re-ap peare d in t he cr yo pre ser ve d fo r m fo r t he t reat me nt o f o p ht ha lmic wo und s in t he lat e 1990’s a nd ear ly 200 0’s . The a mn io t ic me mbr a ne wa s fir st st ud ie d by Law so n in 198 5 a lo ng w it h pect o ralis ma jo r mu sc le fo r o ra l ca vit y reco nst ruct io n. H e co nc lu ded t hat p la ce me nt o f a mn io n o ver t he d eep a spe ct o f t he mu sc le t hat is e xpo sed t o t he o ra l c a vit y r esu lt ed in a mo re rap id de ve lo p me nt o f mu co sa. Whe n musc le wa s used w it ho ut a mnio t ic me mbra ne, t he hea ling pro ce ss u sua lly t oo k t wice a s lo ng. Also , w he n a mn io n w as no t used, it s ho wed a s ig nific a nt a mo u nt o f wo und co nt ract ure.
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Amn io t ic me mbr a ne ( AM) is no w used s ucce ss fu lly in t he t reat me nt o f burns ; creat io n o f bio lo g ic surg ic a l dre ssing ; rec o nst ruct io n o f t he o ra l ca vit y, bla dder, a nd vag ina ; t ymp a no p last y; art hro p last y; a bdo mina l surger y; a nd co rnea l t ransp la nt at io n. It has a lso bee n int ro duc ed as a su it a ble me mbr a ne fo r p last ic surger ie s in de nt ist r y.
STRUC TUR E AND COM POS I TION O F HUM AN AM NIOTIC M EM B RANE The a mn io t ic me mbra ne ( AM) e nca se s t he a mn io t ic flu id a nd fet us, a nd is hig h ly fle xib le bec aus e o f w hic h it ca n eas ily be s eparat ed fro m t he c ho r io n.
AM is co mpo se d o f a mn io n ep it he lia l c e lls der ive d fro m e mbr yo nic e ct o der m a nd a mn io n me se nc h yma l ce lls fro m e mbr yo n ic meso der m. A M is a t hin, to u gh, t ransp are nt and a va scu lar co mpo sit e me mbra ne . It is co mpo s ed o f t hree ma jo r la yers: a s ing le ep it he lia l la yer, a t hick base me nt me mbra ne, a nd a n a vas cu lar me se nc hyme co ns ist ing ma i n ly o f co lla ge n.
The a mn io t ic ep it he liu m is a s ing le la yer o f flat , cub o ida l a nd co lu mnar c e lls . The ep it he lia l ce lls ar e in d ir ect co nt act w it h t he a mnio t ic flu id. It is fro m t his la yer t hat amnio t ic MSC ( AMS C) are iso lat ed a nd st o red to be u sed fo r rege nerat ing t is su es. T he ep it he lia l ce lls secret e co lla ge n t ype III a nd IV a nd no n co llage no us g lyco pro t eins like la min ins, nido ge n, fibro ne ct in a nd vit ro nect in w it hin t he ba se me nt me mb rane t hat ser ve a s ad hes io n liga nd s t rans mit t ing s ig na ls a nd int era ct i ng at ce ll sur fa ce rec ept o rs. The a mn io t ic me mbr a ne is de vo id o f ner ve s, mus c le s and lymp hat ic s. Thes e hu ma n a mn io t ic ep it he lia l a nd me se nc h yma l c e lls (H AE & HAM ce lls) e xpre ss p lur ipo t enc y a nd
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are po t ent st em c e lls r eser vo ir s. The re is a sp ec ia lize d arra nge me nt o f intracellular cytoskeletal filaments such as act in, α -act inin, spectrin, ezrin, c yt o kerat ins, vime nt in, a nd de s mo p la k in . The y p la y a ro le in t he st ruct ura l int egr it y a nd mo du lat io n o f ce ll s hap e o f t he he a ling t iss ue.1 9 The a mn io t ic me so der m la yer co ns ist s o f macro p hag es a nd fibro bla st - lik e mes e nc h yma l ce lls . The ba se me nt me mbra ne o f t he a mn io n is ver y s imila r to t he ba se me nt me mbr a ne fo u nd in t he o t her p art s o f t he bo d y lik e t he co n ju nct iva o r g ing iva.2 0 Co llag e n t yp e IV a nd VII, la min in 1 a nd 5, fibro nect in, a nd ba s ic fibr o bla st gro wt h fact o r (bFG F) are co mpo ne nt s o f t he ba se me nt me mbra ne . La min in-5 be ing t he mo st preva le nt in t he a mn io n me mbr a ne he lps in c e llu lar a d he s io n o f g ing iva l ce lls , inva s ive gro wt h o f fibro bla st s a nd a ng io ge nes is in t he e ar ly phas es o f wo und hea ling.1 6 T he s id e o f a mn io t ic t is sue w ho se su bc ha ins are id e nt ified as ha ving co nju nct io n o f co lla ge n IV w it h la min in is e spe c ia ll y e ffe ct ive in fac ilit at ing ep it he lia l c e ll adhes io n. T he ba sa l la mina o f AM co nt a ins a la rge a mo u nt o f pro t eo glyc a ns lik e hep ara n su lfat e t hat is o ne o f t he ma jo r prot eo glyc a n in t he g ing iva.1 6
The AM st ro ma co nt a ins mit o ge nic fact o rs, ant ia ng io ge nic fact o rs, ant i - in fla mmat o r y pro t e ins, a nd nat ura l pr ot ease inh ib it o rs a nd a nt i s carr ing pro pert ie s t hat a llo w t he wo u nd t o hea l in a mu c h fa st er and e ffic ie nt wa y. The mat r ix o f hu ma n AM co nt a ins a bu nda nt gro wt h fact o rs like kerat ino c yt e gro wt h fa ct o r (KG F), ba s ic - fibro bla st gro wt h fa ct o r (b -FG F), t rans fo r ming gro wt h fa ct o r-bet a (TGF-β), n ido ge n gro wt h fact o r (NGF), and ep ider ma l d er ive d gro wt h fact o r (EDGF) w hic h pro mo t e pe r io do nt a l reg e nerat io n. I nt egr in a6/ b4
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prese nt in t he bas e me nt me mbra ne a s t he ma in lig a nd s part ic ipat es in t he co nst ruct io n o f t he he mide s mo so me like st ruct ure and fa vo urs t he adhe s io n a nd a nc ho r ing o f ESC s t o t he he a ling wo u nd. This fac ilit at es migrat io n o f ep it he lia l ce lls, re in fo rc es ad he s io n o f ba sa l ep it he lia l ce lls , pro mo t es ep it he lia l d iffere nt iat io n, a nd pre ve nt s apo pt o sis . Var io us st e m ce ll mark ers su c h as o ct amer - bind ing t ranscr ipt io n fact o r (OCT) - 4, hepat o c yt es nuc le ar fact o r -3β (HNF-3 β), nest in a nd na no g w hic h are spe c ific st e m c e lls mar kers ar e a lso fo und in t he a mn io n me mbra ne. The st e m ce ll mark ers lik e ep id er ma l mark er C A12 5 a nd ge ner a l ep it he lia l mark ers s uc h a s c yto kerat ins a nd vime nt in are pre se nt in larg e a mo u nt in t he a mn io t ic ep it he lia l ce lls. T he se MSC s ha ve t he a bilit y t o acce le rat e t he in fla mmat o r y p hase t o wards t he pro lifer at ive p has e w hic h is cr it ica l fo r t reat ing c hro nic wo unds like p er io do nt it is.
PRO PE RT IES
ANT I IN FL AM M ATORY
The Me se nc hyma l St e m Ce lls (MS Cs) in t he AM d ecre as e t he s ecret io n o f pro infla mmat o ry c yt o k ines lik e Tu mo r Necro s is Fact o r a lp ha (TN F -α) a nd Int er fero n (IFN) w hile incr ea s ing t he pro duct io n o f a nt i - in fla mmat o r y c yt o k ine s int er leuk in-1 0 a nd int er le uk in -4. T he pro infla mmat o r y me d iat o rs, int er leuk in -1α a nd int er le uk in -1 β, are a lso su ppre ss e d b y mat r ix o f st ro ma o f a mn io t ic me mbr a ne. T he inh ib it o rs o f mat r ix met a llo pro t einas es fo u nd in t he a mn io t ic me mbr a ne de crea se s mat r ix met a llo pro t einase s (M MPs) re lea se d by in filt rat ing neut ro phils a nd ma cro phage s.1 7 Var io us t issue inh ib it o rs o f met a llo pro t eina se s
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1,2,3 and 4, int er le uk in -10, a nd int er leuk in -1 rec ept o r ant ago nist s a nd e ndo st at in w hic h inh ib it e ndo t he lia l c e ll pro lifer at io n, a ng io g e ne s is, a nd t u mo r gro wt h are a lso e xpre s sed by hu ma n a mn io t ic ep it h e lia l a nd me se nc hyma l ce lls.2 1 AM a lso redu ce s t he recru it me n t o f var io u s o t her infla mmat o r y ce lls inc lud ing po lymo rp ho nuc le ar c e lls, CD3 ce lls, CD4 T c e lls a nd CD1 1 b c e lls t o t he in jured s it e t here by red uc ing t he infla mmat io n.2 0
ANGIOG EN ESIS
The c e lls o f t he AM e nha nce t he pro du ct io n o f Va scu lar E ndo t he lia l Gro wt h Fa ct o r (VEGF) by act ivat ing t he V EGF rece pt o rs 1 and 2. Ext ens iv e neo va scu la r izat io n a ft er t he app lic at io n o f AM is due t o t he re lea se o f a ng io ge n ic fact o r lik e insu lin d er ived gro wt h fa ct o r (IGF) t hat pro mo t es granu lat io n t is sue fo r mat io n a nd ep it he lia lizat io n.1 6 The inc rea sed cap illa r y blo o d flo w t o t he lyo p hiliz ed a mn io t ic me mbr a ne s w he n u sed as gra ft mat er ia l in ve st ibu lo p la st y pro mo t es he a ling.2 2
IM M UNOM ODULATOR Y
The AM is u nsu sc ept ible t o mat erna l immu ne at t ack t hro ugh it s u niq ue mo le cu lar s ur face arc hit ect ure and bio c he mic a l pro pert ies t hat is der ive d fro m t he la yer o f t ro pho bla st ce lls. The no n -po lymo rp hic, no n-c la s s ic a l hu ma n le uko c yt e a nt ige n (H LA-G) is e xpre s sed by t he a mn io t ic ep it he lia l ce lls ( AEC s) but lack t he po lymo rp hic a nt ige ns H LA - A, B (C la s s I A) a nd H LA-DR ( C la ss II) o n t he ir s ur face s. The c la s s I a nt ige n is s ee n in a lmo st a ll c e lls o f t he a mn io t ic me mbr a ne u n like t he c la ss II a nt ige n w hic h is o nly prese nt in so me fibro b last s.
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The se me se nc hyma l st e m ce lls ar e d iffe rent fro m o t her nuc le at ed ma mma lia n ce lls as t he y s ho w lit t le a llo ge nic r e act ivit y w he n ad min ist ered t o MHC unmat c hed ad u lt immu ne co mp et ent re c ip ie nt s.1 6 The ce lls o f AM ne it her e xpres s t he pro gra mme d ce ll deat h rece p t o r 1 (PD1) (an inh ib it o r y re cept o r t hat is no r ma lly e xpres se d o n act ivat ed T and B ce lls), no r it s t wo lig a nd s:
pro gra mmed de at h liga nds 1 a nd 2 (PD -L1 a nd PD-L2) a nd t he immu no g lo bu lin- lik e t rans cr ipt recept o rs 2, 3, and 4 (IL T R-2, ILT R-3, and ILT R-4).2 0 The immu no mo du lat o r y a ct io n o f AM is a lso due t o la ck o f e xpre ss io n o f co - st imu lat o r y ce ll s ur face mo le cu le s suc h as CD80, C D -86, a nd CD-40 in t he prese nce o r abs e nc e o f I nt er fero n -ϒ (IFN-ϒ). Furt her mo re, t he y act ive l y suppre ss T ce ll, de ndr it ic c e ll a nd B ce ll fu nct io n t hat do wn mo du lat e e xu bera nt in fla mmat io n.
ANT IM ICROB I AL AN D ANT IV IRA L
Amn io t ic me mbra ne fir mly ad here s w it h t he wo u nd via fibr in a nd e la st in link age s t hat sea ls t he wo u nd a nd pr e ve nt co nt a minat io n. T his t ig ht ad her e nc e he lps in rest o r ing lymp hat ic int egr it y, prot ect s c ircu lat ing p hago c yt e s fro m e xpo sure a nd a llo ws fast er re mo va l o f sur face de br is a nd bact er ia fro m t he wo und.2 1 The a nt imicro bia l a ct ivit y o f t he MS Cs in AM is med iat ed by t wo me c ha nis ms : d irect ly via t he s ecret io n o f a nt i mic r o bia l fa ct o rs suc h a s LL -37 a nd ind ire ct ly via s ecret io n o f immu no mo du lat ive fa ct o rs whic h w ill upr egu lat e s bact er ia l k illing a nd p hago c yt o sis by immu ne ce lls .2 4 Ma ny bact er ic ida l pro duct s o f pur ine met abo lis m a nd lyso z yme ar e a lso fo u nd in t he AM.
De fe nsins, mo st ly bet a 3 de fe nsins, se cret ar y leu ko c yt e pro t einase inh ib it o r
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(SLPI) and e la fin pre se nt in t he a mn io t ic ce lls a ct as co mpo ne nt s o f t he innat e immu ne s yst e m t o pro vid e prot ect io n fro m in fect io n.1 6 It s ant ivira l pro pert ie s are e xhib it e d by t he p re se nce o f a po werfu l a nt iv ir a l age nt , C yst at in E w hic h is a n a na lo g ue o f c yst e ine pro t e ina se inh ib it o rs.
ANT I SCARR ING
AM s ecret es vas cu lar e ndo t he lia l gro wth fa ct o r (VEGF), he pat o c yt e gro wt h fa ct o r (HGF) t hat ma int a ins a pro per ba la nce bet wee n TG F -1 a nd TG F-3 t hat preve nt s scarr ing. It a lso do wn -regu lat es TGF-bet a a nd it s recept o r expre ss io n by fibro bla st t hat reduces fibro s is at t he sit e. T his a lso mo d u lat es t he he a ling o f a wo und b y pro mo t ing t is sue re co nst ruct io n. Var io us immu ne ce lls like T c e ll, de ndr it ic ce ll a nd B ce ll ar e a lso act ive ly suppre s sed t hat preve nt s pat ho lo g ica l re mo de ling a nd e xc es s ive fibro s is.
PROM OT ION OF E PITH EL IA LIZA TI ON
Aid ing in t he migrat io n o f ep it he lia l ce lls , reinfo r ce me nt o f bas a l c e ll ad he s io n, pro mo t io n o f e p it he lia l d iffere nt iat io n, preve nt io n o f ep it he lia l apo pt o sis a nd pro mo t io n o f e p it he lia liz at io n in t he hea ling o f wo unds are so me o f t he pro pert ie s o f a mn io t ic me mbr a ne. It s pro pert ie s inc lud e t he pro mo t io n o f e xpa nsio n a nd ma int e na nc e o f ep it he lia l pro genit o r ce l ls. It can a lso pro duce e ndo t he lin -1 a nd p arat hyro id ho r mo ne re lat ed prot ein. Bra in nat r iuret ic p ept id e a nd co rt ico t ro phin re le as ing ho r mo ne are a lso pro duced by me mbra ne ep it he lia l ce lls w h ic h p la y ro les in incre asing ce llu lar pro liferat io n a nd ca lc iu m met a bo lis m. The base me nt me mbr a ne is a sa fe a nd su it a b le bed fo r t he gro wt h o f
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ep it he lia l ce lls . Su ffic ie nt o xyge nat io n fo r epit he lia l ce lls is pro vide d by it s goo d per me a bilit y in co nt rast to ot her synt het i c mat er ia ls . A mn io t ic me mbra ne fa c ilit at es t he gro w t h o f ep it he lia l ce lls, he lp ing in t he ir m igr at io n a nd d iffere nt iat io n, t hu s act s as a n id ea l me mbra ne.
REDU CT ION OF PA IN
Amn io n me mbra ne ( AM) reduc es pa in as it d imin is he s infla mmat io n and pro vides a bet t er st at e o f hydrat io n t hat s oot he s t he wo und bed t o pro mo t e fast er hea ling. T he e xpo s ed ner ve e nd ing s are prot ect ed fro m t he e xt erna l irr it a nt b y t he so ft mu co id lin ing t hat he lp t o decrea se p a in s e nsat io n. I ncre as ed e xt race llu lar mat r ix depo s it io n MS Cs d iffere nt iat io n he lp s in re ge ner at ing t he da mage d t is sue a nd regu lat e s t he lo ca l c e llu lar r espo ns es t o injur y b y para cr ine s ig na ling. It he lp s in ce ll s ur viva l, pro liferat io n, migr at io n a nd g e ne e xpr es s io n o f e p it he lia l ce lls , e ndo t he lia l ce lls, kerat ino c yt e s, a nd fibro bla st s. The me se nc hyma l ce lls ma y ac ce ler at e wo und hea ling b y act ing a s a c he mo at t ract ant fo r macro p hage s, e ndo t he lia l c e lls, ep id er ma l k erat ino c yt e s, a nd fibro bla st s . PROC ESSI NG OF AM NIO TI C M EM B RANE
Fo r c lin ic a l u se, a mn io t ic me mbra ne c a n be prep ared in t he fo llo w ing fo r ms:2 0
Fre s h me mbra ne
Dr ie d me mbra ne
Fro ze n me mbra ne
Free ze der ive d irr ad iat ed me mbra ne
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St abilize d a mn io t ic me mbra ne
Cr yo pre ser ved me mbra ne .
Fro zen me mb rane:
Liqu id nit ro ge n at -196°F is us ed fo r freez ing a mn io t ic me mbra ne . Co o lin g pro duces bact er io lo g ic a lly pure a nd immuno lo g ic a lly a lmo st inert mat er ia l. It preser ves t he me mbra ne fo r a lo nger t ime.
C ryop res e rved me mb rane:
Cr yo pre ser vat io n w it h d imet hyl su lp ho xide (DMSO) at -80°C a llo w s ret e nt io n o f c e lls in t he AM at appro ximat e ly 5 0% fo r se vera l mo nt hs. T he se vera l a ng io ge n ic gro wt h fact o rs and c yt o k ine s are re mo ved dur ing cr yo pre ser vat io n o f t he AM. The via b ilit y o f AECs is lo st if t he AM is cr yo pr es er ved in 50%
g lyc ero l. It has be e n no t ed t hat st o rage of t he AM in g lycero l at 4°C re su lt s in imme d iat e ce ll de at h.2 5
Fre e ze d ried i rradi ated (ly ophi li zed)2 6:
The me mbra ne is free ze dr ied at -60°C und er vacu u m (at mo sp her ic pres sur e 102) fo r 48 ho urs in t his pro ce ss. Irrad iat io n is t he n do ne w it h 2.5 mega rad s (25 K Gra y) in a bat ch t ype co ba lt -60 irra d iat o r. B y t he met ho d o f fre eze dr ying t here is s u blimat io n o f liqu id mo ist ure o f me mbra ne t o gaseo us st at e w it ho ut ha ving u ndergo ne t he int er med iat e so lid st age. The me mbra ne ma int a ins it s o rig ina l s iz e a nd s hape w it h min imu m c e ll rupt ure in t his met ho d. This fo r m o f me mbr a ne c a n be use d a ft er so ak ing it in no r ma l sa line fo r 1 minut e.
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USE OF AM NIO T IC M EM B RANE IN D ENT IST RY
AM is se mi per me a ble me mbra ne a nd is a n immu no t o lera nt st ruct ure. The AM fu lfills t he curre nt mec ha n ica l co ncept o f GTR whic h a me nd s it w it h t he mo d er n co nce pt o f bio lo g ic a l GTR. B io mec ha nic a l GTR pro po sed here in u s ing a mn io t ic me mbr a ne, no t o nly ma int a ins t he st ruct ural a nd a nat o mic a l co nfigurat io n o f rege nerat ed t is sue s, but a lso co nt rib ut e to t he e nha nce me nt o f hea ling t hro ug h reduct io n o f po st -o perat ive s carr ing a nd su bsequ e nt lo ss o f fu nct io n a nd pro vid ing a r ic h so urce o f st e m c e lls. Amn io t ic me mbra ne e nha nc es g ing iva l wo und hea ling pro pert ie s a nd redu ce s sc arr ing. E xc e lle nt re va scu la r izat io n o f t he a mn io t ic me mbra ne is a no t her fa vo ra ble pro pert y. Amn io t ic me mbra ne w as a pot ent ia l gra ft ing mat er ia l w hic h s ho we d ver y go o d wo und co verage. It sho wed bet t er wo und he a ling , go o d po st -o perat ive fu nct io n a nd e st het ic s w it ho ut an y co mp lic at io ns. Hu ma n a mn io t ic me mbr a ne co u ld be o ne o f t he co ns ider ed o pt io ns in re co nst ruct io n o f o ra l c a vit y de fe ct s as it e nsure s go o d reco nst ruct io n, po st o perat ive fu nct io n a nd est het ics.2 7
An in je ct a ble so lut io n o r to pica l ge l ca n be cr eat ed b y mix ing t he micro nize d de hydrat ed a mn io n o r cho r io n me mbr a ne a llo gra ft w it h sa line . Rec e nt ly t he c lin ica l u se o f a mn io t ic me mbra ne ha s in creased. It can be u sed fo r c hro nic a nd acut e wo und care ma na ge me nt , fo r scar t issu e reduct io n, as a barr ier me mbr a ne, a nd a s a so ft t issu e rege nerat io n gra ft . AM is hig hly us e fu l a nd e ffe ct ive a s a cu lt ure s u bst rat e. The e ffect ive ne ss o f new a mn io t ic me mbra ne - ba sed rege nerat ive t herap y t o o ra l hea lt h care t hro ugh su cce ss fu l prep arat io n o f a cu lt ivat ed o ra l muco sa l ep it he lia l ce ll sheet o n AM a nd t he e st a blish me nt and
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c lin ica l app lic at io n o f a n aut o t ransp la nt at io n t ec hniq ue fo r var io us t ype s o f o ra l mu co sa l de fe ct s in de nt a l o ra l surg er y. The gra ft o f a mn io t ic me mbra ne is a via b le a nd re lia b le met ho d to co ver t he e xpo sed per io st eu m as t he y ser ve as a goo d a lt er nat ive t o muco s a l a nd sk in gra ft s. Co nnect ive t issu e gra ft s c a n be a lt er nat ed w it h a mn io n a llo gr a ft in ro ot co verage pro cedure s a nd to reduce recess io n d ept h. R ece nt ly, t he AM-base d ce ll-cu lt ur e s yst e m t o cu lt ure PDL der ived ce lls fo r rege nerat ive t herap y fo r perio do nt a l t is sue. Thes e ce lls are co ns id ered cap a ble o f pro lifer at io n a nd pot ent ia lly ma int a in ing t he ir PD L - like pro pert ie s e ve n o n AM.2 8
Use o f the amniot ic me mbrane has been successful for oronasal fistula repa ir a nd t he use o f t his mu lt ila yer t ec hniqu e a nd pro t ect ive p lat e ut iliz at io n pre ve nt s t he rupt ure o f t he me mbra ne . Amn io t ic me mbra ne pre ve nt s t he seco ndar y co nt ract io n a ft er ve st ibu lo p la st y a nd t he y a lso ma int a in t he po st o perat ive vest ibu lar dept h, w hic h mak es t he m a via ble a nd re lia ble mat er ia l fo r co ver in g t he raw sur face in ve st ibu lo p la st y. T he a mn io t ic me mbr a ne c a n pro mo t e hea ling a nd pre ve nt ing re la ps e whe n use d in cas es o f vest ibu lo p la st y. It is ea s ily a va ila b le a nd pre ser ved a nd is a co st -e ffe ct ive mat er ia l.2 9
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REV IEW O F L IT ERA TUR E
Shaila V. K othiwale et al., (2009)3 0 condu ct ed a n e va luat io n o f D FD B A w it h a mn io t ic me mbra ne a nd bo vine der ive d xe no gra ft w it h a mn io t ic me mbra ne us ing bo t h c lin ic a l a nd rad io lo g ic a l e va luat io n in hu ma n p er io do nt a l grad e II furcat io n de fect s. It was co nc lud ed t hat at 9 mo nt hs a ft er surger y bo t h t herap ie s resu lt ed in significant PD reduct io ns and CAL gains and significant improve ment was seen in bo ne fill and percentage gain wit h both the material s. T here was no significant difference between both.
Ha rveen Singh et al., (2012)3 1 eva luat ed t he e ffic ie nc y o f bio act ive a mn io n a s a GTR fo r treat me nt o f iso lat ed g ing iva l re cess io n a nd co nc lu ded t hat t here wer e goo d resu lt s in t er ms o f ro ot co verage, increas ed t is su e t hick nes s a nd incr ea se d att ached g ing iva l t iss ue s. The a bilit y o f a mn io n t o se lf ad here e liminat e s t he need fo r sut ures, mak ing t he pro cedure le s s t echn ica lly d e ma nd ing a nd s ig nific a nt ly de crea s ing s urg ica l t ime.
Dan J. Ho lt zc la w et al., (2012)3 2 per fo rme d a ca se ser ie s o n a mn io n –c ho r io n a llo gra ft barr ier u sed fo r g u ided t is sue rege nerat io n t reat me nt o f p er io do nt a l int ra bo ny de fe ct s and co nc lud ed t hat whe n co mp ared t o t radit io na l GT R me mbr a ne s, p lace nt a l barr ier s, suc h a s AC Ms, de mo nst rat e ma ny u niqu e pro pert ie s. ACM do es no t requ ire pr e c is e t rimming fo r adapt at io n. The AC M int imat e ly adapt s t o co nto urs aro und ro ots a nd o ver d e fect s du e t o t he min ima l t hick ne s s o f t his barr ier me mbra ne a nd it s se lf-a d here nt nat ure. AC M ha s a st and ard ize d siz e, sha pe, a nd t hic k ne ss unlik e a mo rp ho us mixed barr ier s a nd
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do es no t requ ire c ha ir -s id e o r in s it u fa br ic at io n. Alt ho ug h AC Ms are new t o de nt ist r y a nd ha ve u niqu e pro pert ie s t ha t differ fro m t rad it io na lly us ed GT R barr iers, t he resu lt s o f t his ret ro spect ive o bser vat io na l repo rt are pro mis ing a nd in line w it h o t her rece nt ly pu blis hed G TR and bo ne gra ft st ud ie s. Lo ng -t er m fo llo w up and add it io na l co nt ro lled st udie s furt her e va luat ing use o f AC M in rege nerat ive pro cedure s are warra nt ed.
Ami r A li re za Rasou li Ghah raudi et a l., (2013)3 3 perfo r med a rando miz ed, do uble- blind ed, co nt ro lle d c lin ic a l t r ia l to co mp are a mn io n a llo gra ft w it h co nne ct ive t is su e gra ft fo r root co verag e pro cedures a nd st at ed t hat a po sit ive s ig nific a nt co rre lat io n was no t ed bet wee n pap illa d ime ns io ns a nd t he a mo u nt o f root co verage. I n mu co g ing iva l surg er ie s, t he int erde nt a l pa p illa is t he mo st co ro na l he mat o lo g ic bed a ft er de-e p it he lia liz at io n to whic h ro ot -co ver ing flap is a nc ho red. Due t o t his, a n incr ease in p ap illa d ime ns io ns mig ht incre as e va scu lar e xc ha nge bet wee n t he he mat o lo g ic bed a nd t he fla p . The sur fa ce o f t he de- ep it he lia lize d po rt io n mig ht be mo re imp o rt ant t ha n t he he ig ht a nd w idt h o f t h e pap illa a lo ne. There fo re, a mn io n a llo gra ft mig ht be a su it a ble a lt er nat ive to su bep it he lia l co nne ct ive t iss ue gra ft .
Aditi Chop ra et al., (2013)3 4 per fo r me d a review o n Amn io t ic Me mbr a ne: A No ve l Mat er ia l fo r Reg e nerat io n a nd Repa ir a nd co nc lude d t hat t hes e me mbr a ne s are e xt re me ly t hin aro und 3 00 nm in cro s s se ct io na l t hick nes s . The y are u nlike t he o t her co lla ge n me mbra ne s us ed fo r gu id ed t is su e rege nerat io n whic h are aro und 700 - 800 nm. It int imat e ly mo lds a cco rd ing t o t he de fect a nat o my a nd root surface du e t o it s t hin d ia met er. The k no w le dge o n t he
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st abilit y o f t he hyperdr y AM in t he o ra l e nviro nme nt requ ire s f urt her lo ng t er m c lin ica l t r ia l a nd res earc h. It keeps it s st re ngt h a nd mo rp ho lo g y fo r at lea st o ne mo nt h in vit ro whe n so aked in st er iliz e d ph ys io lo g ic sa line so lut io n at roo m t emperat ure. Furt her inve st ig at io n is need ed to eva luat e it s a bilit y w he n u sed a s a barr ier me mbr a ne.
K engo Iwasa ki et al., (2013)3 5 st ud ied per io do nt a l r ege nerat io n u s ing per io do nt a l lig a me nt st e m ce ll-t ra ns fer red a mn io n a nd co nc lud ed t hat t he per io do nt a l re ge ner at io n fo u nd in t his st ud y w as mo st ly der ive d fro m t ra ns ferre d PDLSC s. PD LSC s were s ho w n t o have t he a bilit y t o differe nt iat e int o ce me nt o bla st s t hat fo r m t he ce me nt u m, whic h is a cruc ia l t is sue in per io do nt a l rege nerat io n. Furt her, it was s ho wn t hat PDLSC s fo r m a ce me nt u m - lik e t is su e o n t he sur fac e o f hydro xyl -ap at it e part ic les ect o p ic a lly in nude mic e. Mo reo ver, it ha s bee n d e mo nst rat ed t hat PDLSCs fo r m ce me nt u m - lik e t is sue w he n t he y are t ransp la nt ed o nt o root surface s co at ed wit h de nt in no nco llag e no us prot e ins in vivo . Thes e dat a stro ng ly sugg est t hat PDLSC s ha ve t he a bilit y t o reco gniz e t he ir micro e nviro nme nt ( i.e., dent in su r fac e) and d iffere nt iat e int o ce me nt o bla st s. Our PDLS C -a mn io n a llo w s c lo se co nt act bet wee n PDLS C s a nd t he de nt in sur fac e, wh ic h e na ble s t he int eract io n bet wee n PD LSC s a nd t he ir rege nerat ive micro e nviro nme nt a nd ma y fa vo r per io do nt a l rege nerat io n.
Rucha Sha h et al., (2014)3 6 eva lu at ed t he e ffic ie nc y o f a mn io n a llo gr a ft in co nju nct io n w it h co ro na lly ad va nc ed fla p in t he ma na ge me nt o f g ing iva l recess io n a nd co nc lud ed t hat a ll t he o pt imu m de s ired res u lt s a s a n a llo gra ft fo r root co verage wer e ac hie ved by a mn io n a llo gra ft w it h co mp let e root co verag e,
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a n exce lle nt co lo r mat c h to t he rec ip ie nt s it e, no recurrence o f reces s io n fo r 6 mo nt hs po st -t reat me nt and e nha nce me nt o f g ing iva l bio t yp e. Mo re st ud ie s are requ ir ed t o exp lo re t he po t ent ia l o f t his me mbr a ne.
Ashi sh Aga rw a l et al., (2014)3 7 publis hed a re vie w art ic le o n p le io t ro pic pro pert ie s o f a mn io t ic me mbra ne fo r mo du lat io n o f p er io do nt a l hea ling a nd st at ed t hat hu ma n a mn io t ic me mbr a ne (H AM) is co mpo se d o f in ner mo st la yer s o f p la ce nt a w hic h co mpr ise s o f t he a mn io n a nd c ho r io n. It is w id e ly u sed i n me d ica l fie ld esp ec ia lly in o p ht ha lmo lo g y. It is a co mpo s it e me mbra ne co ns ist ing o f p lur ipo t ent ce llu lar e le me nt e mbe dded in a se mip er mea b le me mbr a no us st ruct ure. The a mn io t ic me mbr a ne ha s a nt iin fla mmat o ry, a nt i - scarr ing, a nt imicro bia l a nd e xc e lle nt re vasc u lar iz at io n pro pert ie s. AM is a e xce lle nt me mbra ne fo r reco nst ruct ive s urger y be cau se it is eas ily a cc es s ib le, et hica lly ac cept a ble, ea s y t o use, a nd e as ily st o red w it ho ut a lt erat io n t o it s t herapeut ic pro pert ie s.
Supriy a M ishra et al., (2014)3 8 researc hed o n hu ma n a mn io t ic me mbra ne a nd co nc lud ed t hat it is a no ve l t is sue e ng ine e red bio mat er ia l t hat is rece nt ly t r ied in fie ld o f med ic ine a nd d e nt ist r y t o regenerat e t he lo st t is sue s a nd ac ce ler at e repa ir. The c lin ic a l app lic at io n o f a mnio t ic me mbr a ne co nt r ibut es t o t he e nha nce me nt o f he a ling t hro ugh reduc t io n o f po st -o perat ive sc arr ing and su bsequ e nt lo ss o f fu nct io n a nd pro vid ing a r ic h so urce o f st e m c e lls in a dd it io n to ma int a in ing t he st ruct ura l a nd a nat o mic a l co nf igur at io n o f reg e nerat ed t iss ues. Ho we ver, furt her res earc h a nd lo ng t er m c lin ica l t r ia ls inve st ig at ing t he
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fu ll po t ent ia l o f t his st e m ce ll res er vo ir ar e st ill warra nt ed to strengt he n t he fact a mn io t ic me mbr a ne is ind eed a s a re ser vo ir fo r rege nerat io n.
Sonali Ch a krabo rth y et al., (2015)3 9 perfo r med a c lin ic a l st ud y o n a mn io n a nd c ho r io n a llo gra ft s in co mbinat io n w it h co ro na lly ad va nc ed flap in t he t reat me nt o f g ing iva l r ece ss io n a nd co nc lud ed t hat r ic h so urce o f st e m ce lls, e nha nc e me nt o f hea ling a nd se l f-ad her ing pro pert y ma k e t he se me mbra ne s a n e ffe ct ive o pt io n fo r root co verage pro cedure s. Ho wever rando mize d co nt ro l t ria ls w it h lo nger fo llo w up per io d ne ed t o be carr ied o ut to asses s t he lo ng t er m be ne fit s o f a mn io n a nd c ho r io n a llo gra ft s.
K ala. S. B hu shan et al., (2015)4 0 review ed a mn io t ic me mbr a ne & it s st ruct ure, fe at ures a nd use s in d e nt ist r y a nd co nc lud ed t hat t he AM has ma n y c haract er ist ics, w hic h ma ke it po t ent ia lly s u it a ble fo r us e in d e nt ist r y. T he ep it he lia l la ye r o f t he AM inc lu de s ce lls t hat have s imilar c haract er ist ics t o st e m ce lls. The a mn io t ic me mbra ne ca n be used a s a sca ffo ld . The ECM co mpo ne nt s o f t he ba se me nt me mbr a ne fro m t he AM inc lu de co lla ge n, fibro nect in, la min in a nd o t her prot eo glyc a ns impo rt ant fo r o ver lying ce l l gro wt h. The se ingr ed ie nt s are t he liga nd s fo r int egr in rec ept o rs. The y ha ve a great ro le in ce ll ad hes io n dur ing t he ce ll seed ing pro to co l. Ot her pro pert ies o f t he AM inc lud e a nt i infla mmat io n, a nt ifibro s is, a nt i - sc arr ing, a nt i- micro b ia l, lo w immu no ge nic it y a nd r ea so na b le me c ha nic a l pro pert y, w hic h are a ll impo rt ant fo r use a s barr ier me mbra n e . Amn io n o bt a ined fro m d is c arded p lace nt a is a n int erest ing so urce o f ce lls fo r regenerat ive med ic ine.
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Rupali M ahajan et al., (2015)4 1 asses sed gu ided t is su e rege nerat io n ba se d t reat me nt o f root co verage us ing p la ce nt a l me mbr a ne a llo gra ft a nd co nc lude d t hat a no ve l a nd versat ile t reat me nt mo da lit y fo r ro ot co verage o f iso lat ed bu cca l g ing iva l rec es s io ns is t he u se o f reso rba b le me mbra nes w it h co ro na ll y ad va nced flap . Ho we ver, a mn io n me mbra ne has cert a in add it ive ad va nt ag es o ver ot her me mbr a ne s a nd ca n be used a s an a lt er nat ive t o co llag e n me mbra ne. R ic h so urce o f st e m c e lls, e nha nc e me nt o f he a ling a nd se lf -ad her ing pro pert y ma ke these membranes an effect ive option for root coverage pro cedure.
A ravind K uma r et al., (2015)4 2 per fo r med a ra ndo miz ed c lin ica l t r ia l t o e va luat e t he c lin ica l, a nt i- infla mmat o r y a nd a nt i- in fect ive pro pert ies o f a mn io t ic me mbr a ne u se d fo r gu ided t is sue re ge ner a t io n a nd co nc lud ed t hat t he use o f AM resu lt e d in a n impro ve me nt in per io do nt a l para met er s and ha d a marked a nt i- infla mmatory effect. Newer GTR materials are expected to fulfill t he properties o f bio lo g ic a l GTR in add it io n t o t he bio me c ha nic a l pro pert ies o f co nve nt io na l GTR mat er ia ls. AM ha s t he a bilit y t o funct io n as a barr ier fo r GTR . It ha s var io us u niqu e pro pert ies a sso c iat ed t hat can aug me nt it s pot ent ia l a s a mat r ix fo r per io do nt a l rege nerat io n.
Akan ksha Gupta et al., (2015)4 3 did a rev iew o n a mn io n a nd c ho r io n me mbr a ne s a s a po t ent ia l st e m ce ll reser vo ir w it h w ide app lic at io ns in per io do nt ics a nd co nc lud ed t hat a mn io t ic me mb r a ne s ha ve fo u nd t o be r ic h in co llage n t yp es I, IV, V and VI, prot eo glyc a ns, la min in a nd fibro nect in. C o llag e n is w e ll t o lerat ed a nd b io a bso rba b le st ruct ure. It has he mo st at ic pro pert ies.
Co llag e n he lp s in t he migr at io n o f ad ja c e nt auto geno us co nne ct ive t issu e a nd
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ep it he lia l c e lls o ver it s sur fac e. The var io us pro pert ies o f la min ins inc lud e pro mo t io n o f ce l l at t achme nt , gro wt h, a nd d iffer e nt iat io n o f nu mber o f ce ll t yp es. Fibro ne ct in he lp s in var io us c e llu lar pro cesse s s uc h a s t he t issu e repa ir, blo o d c lo t t ing, c e ll migr at io n, a nd ad he sio n. Amn io t ic me mbra ne is a u niqu e no ve l a nd po t ent ia l bio mat er ia l fo r us e in me d ic ine, t iss ue e ng ineer ing, st e m ce ll r es earc h, repa ir, a nd rege nerat io n du e to it s d ivers e pro pert ie s. The ir us e in Per io do nt ic s is a lso qu ick ly e xpa nd in g w it h w ide ra nge o f app lic at io ns.
Eva lu at io n o f t he e ffic ac y o f t he se me mbra ne s in co mpar iso n w it h curre nt l y a va ila b le a lt er nat ive s in furt her st ud ie s is requ ir ed. Mo re researc h a nd c lin ica l st ud ie s are r equ ired t o st udy t he po t ent ia l o f t his me mbr a ne. T his r es earc h is requ ir ed t o de fine t he ir o ver a ll sco pe a nd furt her app lic at io ns in t he fie ld o f Per io do nt ic s.
Anami ka Sha rma et al., (2015)4 4 co nduct ed a c as e s er ie s us ing a mn io t ic me mbr a ne fo r ro ot co verage a nd co nc lu de d t hat a mn io t ic me mbra ne pro vid es a n e ffe ct ive a lt er nat ive t o auto graft t issue in t he t reat me nt o f mild t o mo derat e Miller’s Class I and II recessio n defects. In addit io n, the self‑adherent nature o f t he a mn io t ic me mbr a ne s ig n ific a nt ly red uced surg ic a l t ime ; ea s ier t o perfo r m re lat ive t o ot her t echnique s. The resu lt s obt a ine d in t his st ud y co u ld be t aken a s ind ir ect evid e nc e o f new at t achme nt fo rmat io n. The impro ve me nt in C AL a nd po cket pro bing dept h co u ld be no t iced up to t he st age at whic h new t issu e fo r mat io n o ccurred , s inc e a lveo lar bo ne a nd p er io do nt a l liga me nt fo r mat io n is a pro cess t hat requ ir es se vera l mo nt hs. Furt her rese arc h a nd lo ng -t er m c lin ic a l t ria ls inve st ig at ing t he fu ll po t ent ia l o f t his po t ent ia l st e m r eser vo ir are st il l
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warra nt ed t o st rengt he n t he fa ct t ha t a mnio t ic me mbr a ne is ind eed a res er vo ir fo r rege nerat io n a nd repa ir.
Vanish ree HS et al., (2016)4 5 asse sse d whet her a mn io t ic me mbra ne co u ld be a bet t er graft and a dres s ing mat er ia l fo r t he root co verage a nd co nc lud ed t hat it s inhe re nt wo und mo du lat ing p ro pert ie s ma y be us ed t o enha nc e per io do nt a l wo und hea ling a nd e na ble g ing iva l t issue rege nerat io n. I n ca se s o f t reat ing g ing iva l r ece ss io ns, a mn io n a llo gra ft ma y pro vid e a n a lt er nat ive t o ot her co nve nt io na l met ho ds . The resu lt s de mo nst rat e t hat t he a mn io n a llo gra ft is we l l to lerat ed by t he g ing iva l t iss ue s a nd resu lt s in e xce lle nt he a ling.
Ruchi Sri vasta va et al., (2016)4 6 perfo rme d a st ud y us ing do uble pap illa gra ft w it h a mnio n me mbra ne fo r root co verag e o f iso lat ed rece ss io n a nd co nc lud ed t hat it is a n e ffect ive t reat me nt mo da lit y fo r t he ma nag e me nt o f iso lat ed recess io n de fe ct . It is a c ha lle ng ing a nd t echn ique s e ns it ive pro cedure to jo in t he t wo delic at e pap illa e a nd t o avo id re cess io n o r bo ne lo s s at t he do no r s it e.
Ho wever, t his surg ic a l t ec hnique sho we d a res u lt o f hig hly sat is fa ct o ry a nd co mp let e root co verage in t he reg io n o f re cess io n d e fect .
M egha Phogat R ana et al., (2016)4 7 revie wed t he hu ma n a mn io t ic me mbra ne : ho pe in per io do nt a l re ge ner at io n a nd c o nc lude d t hat t he us e o f t h is no ve l bio lo g ic a l me mbr a ne is r is ing in var io u s fie ld s o f t is su e eng ineer ing, med ic ine, rege nerat io n bio lo g y a nd st e m ce ll r ese arc h. T he c lin ica l app lic at io n o f a mn io t ic me mbr a ne co nt r ibut es t o t he e nha nc e me nt o f he a ling t hro ug h reduct io n o f po st - o perat ive s carr ing a nd su b s eque nt lo ss o f fu nct io n a nd pro vid ing a r ic h so urce
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o f st e m c e lls in ad d it io n t o ma int a ining t he st ruct ura l a nd a nat o mica l co nfigurat io n o f rege nerat ed t issue s . Ho we ver, furt her re sear c h a nd lo ng t er m c lin ica l t r ia ls inve st ig at ing t he fu ll po t ent ia l o f t his st e m ce ll re ser vo ir are st il l warra nt ed to st rengt he n t he fact a mn io t ic me mbra ne is ind eed a res er vo ir fo r rege nerat io n.
A rde shi r La fzi et al., (2016)4 8 perfo rme d a sp lit mo ut h st ud y t o clin ica ll y co mpare co ro na lly- ad va nced fla p p lu s a mn io t ic me mbra ne o r subep it he lia l connect ive t issue in the treatment of Miller’s class I and II gingiva l recessio ns a nd st at ed t hat SCTG w it h C AF is t he go ld st and ard fo r t he t reat me nt o f M ille r c las s I a nd II g ing iva l re ce ss io n de fe ct s, a nd a mn io t ic me mbra ne w it h C AF ma y be re lat ive ly co mp ara ble w it h go ld st a nd ard. This new a llo gr a ft decre as es t he durat io n o f surg er y a nd mo r bid it y o f t he pat ie nt . Est het ic s at is fa ct io n ha s bee n larg er in c as es w it h a mn io t ic me mbra ne.
Songa Vaj ra M adhu ri (2 016)4 9 re view ed t he me mbra nes u sed in GTR a nd G BR.
The “ide a l” me mbra ne fo r use in per io do nt a l reg e nerat ive t herap y ha s yet be e n de ve lo p ed. B as ed o n a grade d - bio mat er ia ls appro ac h, it is hypo t he s iz ed t hat a bio lo g ic a lly a ct ive a nd s pat ia lly de sig ne d a nd fu nct io na lly graded na no fibro us mat er ia l t hat mimic s c lo se ly t he nat ive ECM co uld succ eed a s t he ne xt - ge nerat io n o f gu id ed reg e ner at io n me mbr a ne s fo r p er io do nt a l t is su e rege nerat io n.
Abis Ami r et al., (2017)5 0 perfo r med a c o mp arat ive eva luat io n o f root co verage in c la ss I recessio n using a mn io n me mbr a ne a nd PRF me mbr a ne a nd co nc lu ded
