PRIMENA PLAZME BOGATE TROMBOCITIMA U REKONSTRUKTIVNOJ MUKOGINGIVNOJ HIRURGIJI
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1 RADOVI BIBLID: , 136(2008) 3-4, p UDC: : PRIMENA PLAZME BOGATE TROMBOCITIMA U REKONSTRUKTIVNOJ MUKOGINGIVNOJ HIRURGIJI Zoran ALEKSIĆ 1, Saša JANKOVIĆ 1, Božidar DIMITRIJEVIĆ 1, Ana PUCAR 1, Vojkan LAZIĆ 2, Vojislav LEKOVIĆ 1 1 Klinika za parodontologiju i oralnu medicinu, Stomatološki fakultet, Univerzitet u Beogradu, Beograd; 2 Klinika za stomatološki protetiku, Stomatološki fakultet, Univerzitet u Beogradu, Beograd KRATAK SADRŽAJ Uvod Re ce si ja gin gi ve je je dan od naj s lo že ni jih pro ble ma sa vre me ne s to ma to lo gi je. Iznalažewe no vih te ra pij skih me to da za re ša va we ovog pro ble ma je zna ča jan seg ment is tra ži va wa u pa ro don to lo gi ji. Ciq rada Ciq ra da je bio da se pro ce ne kli nič ki efek ti pri me ne pla zme bo ga te trom bo ci ti ma (PBT ) u kom bi na ciji sa tran splan tatom ve ziv nog tki va (TVT) u le če wu re ce si je gin gi ve. Metod rada Istraživawe je ob u hva ti lo 15 bo le sni ka s obo stra nim re ce si ja ma gin gi ve kla se II i III po Mi le ru (Miller). Me to do lo ški kon cept se za sni vao na me to du po de qe nih usta. U le če wu 15 re ce si ja pri me wen je TVT u kom bi na ciji sa ko ro nar no po zi ci o ni ra nim re žwem uz pri me nu ak ti vi ra nog kon cen tra ta trom bo ci ta (PBT gru pa). Isti broj rece si ja na su prot noj stra ni vi li ce zbri wa van je auto tran splan tatom ve ziv nog tki va i pe ri o sta u kom bi na ci ji sa koro nar no po zi ci o ni ra nim re žwem (TVT gru pa). Za pro ce nu sta wa pa ro don ci ju ma i efi ka sno sti pri me we nih hi rurških po stu pa ka ko ri šće ni su sle de ći kli nič ki pa ra me tri: ver ti kal na du bi na re ce si je (VDR), ni vo pri poj nog epite la i ši ri na ke ra ti ni zo va ne gin gi ve. Ni vo oral ne hi gi je ne je u tvr đi van plak- in dek som po Sil nes Lou ( Sil ness Löu), a sta we gin gi ve gin giv nim in dek som po Lou Sil ne su (Löu Sil ness). Rezultati Na osno vu ana li ze sred we vred nos t za du bi nu re ce si je (VDR), us ta no v qe no je s ta ti s tič ki zna čaj no smawe we vred no sti ovog pa ra me tra šest me se ci po sle tret ma na u PBT gru pi (sa 4,93±0,86 mm na 0,60±0,37 mm; p<0,01). U TVT gru pi, u ko joj je vred nost VDR pre le če wa bi la 4,76±0,74 mm, po sle šest me se ci do bi je na je vred nost od 0,63±0,29 mm (p<0,01). U PBT gru pi je po s le op ser va ci o nog pe ri o da za be le že no pro ši re we zo ne ke ra ti ni zo va nog tki va za 2,90 mm, dok je u istom pe ri o du vred nost ovog pa ra me tra u TVT gru pi bi la 2,25 mm. Po re đe wem pro seč ne pro me ne vredno sti kli nič kih pa ra me ta ra u okvi ru obe eks pe ri men tal ne gru pe, sa mo je kod pro me ne ši ri ne ke ra ti ni zo va nog tkiva za be le že na sta ti stič ka zna čaj nost ( p<0,05). Zakqučak Re zul ta ti ove k li nič ke s t u di je uka zu ju na iz u zet nu efi ka snos t oba pri me we na po s t up ka u le če wu re ce si je gin gi ve. Kqučne reči: recesija gingive; plazma bogata trombocitima; transplantat vezivnog tkiva; regeneracija tkiva UVOD Recesija gingive s epidemiološkog, socijalnog i etiopatogenetskog aspekta predstavqa jedan od najsloženijih problema savremene parodontologije. Istovremeno, s terapijskog aspekta, to je jedan od najatraktivnijih izazova iz domena rekonstruktivne plastične mukogingivne hirurgije. Iznalažewe novih terapijskih postupaka rekonstrukcije izgubqenih tkiva u okviru recesije gingive predstavqa značajan segment istraživawa u parodontologiji. Imajući u vidu etiopatogenetski značaj, kao i prevalenciju gingivnih recesija, mukogingivni hirurški zahvati koji se primewuju u rešavawu problema razvili su se u složene plastičnohirurške postupke. Mukogingivnim hirurškim postupcima moguće je otkloniti nastale estetske nedostatke, rešiti problem preosetqivosti izloženog korena zuba, sprečiti nastanak karijesa cementa korena i, što je najznačajnije, obezbediti uslove za efikasniju kontrolu plaka. Na ovaj način se obezbeđuju preduslovi za uspostavqawe zdravqa parodoncijuma i remisiju bolesti u dugom vremenskom periodu. Radi postizawa ovakvih efekata u lečewu recesije gingive, razvijeni su mnogi hirurški postupci. Prvi pokušaji prekrivawa izloženog korena lateralno pomerenim režwem potiču iz godine [1]. Nešto kasnije dolazi do pokušaja prekrivawa korena slobodnim mukoznim autotransplantatom (SMAT) [2]. Oba metoda su pokazala mnoge nedostatke. Pravi pomak u rešavawu ovog problema dešava se primenom autotransplantata vezivnog tkiva (TVT), koji se beleži početkom osamdesetih godina prošlog veka [3]. Kasnije dolazi do modifikacije ove tehnike i u literaturi se pojavquje rad koji opisuje modifikovanu envelop-tehniku, koja se takođe izvodi uz primenu TVT [4]. Ova tehnika se pokazala kao efikasan postupak u rešavawu plitkih i uskih recesija. Potreba za obezbeđewem adekvatne ishrane TVT kao preduslova za postizawe odgovarajućih terapijskih rezultata uslovila je nastavak istraživawa i razvoj hirurške tehnike kojom bi se prevazišli uočeni problemi. Objavquje se studija u okviru koje se problem recesije gingive efektno rešava korišćewem TVT potpuno prekrivenim koronarno pomerenim režwem [5]. Kod plitkog vestibuluma i izrazito dubokih recesija, gde primena koronarno pomerenog režwa nije indikovana, veoma uspešno se primewuje tehnika TVT u kombinaciji s lateralno pomerenim režwem od dve papile [6]. 95
2 Početkom devedesetih godina prošlog veka uvodi se postupak usmerene regeneracije parodoncijuma (GTR) radi rešavawa problema recesije gingive, najpre korišćewem neresorptivne politetrafluoretilenske membrane (ep TFE) potpuno prekrivene koronarno pozicioniranim režwem pune debqine [7], a zatim i resorptivne membrane od polilaktičke kiseline [8, 9]. Kao vid resorptivne membrane upotrebqena je i kolagena membrana [10, 11]. Ono što je zajedničko za ove postupke jesu visok stepen nepredvidqivosti pozitivnog rezultata i izuzetno nizak nivo proširewa keratinizovanog tkiva u regionu tretirane recesije. Efikasnost rešavawa složenog problema recesije gingive direktno je povezana s regeneracijom tkiva. Dokazano je da prekrivawe ogolićenog korena zuba može biti dugotrajno i kvalitetno rešewe samo ako je podržano odgovarajućom regeneracijom izgubqenih dubqih parodontnih tkiva u zoni recesije (vestibularne kostne lamele, periodoncijuma i regionalnog cementnog tkiva). Rezultati kliničkih istraživawa su suvereno na tron postavili primenu transplantata vezivnog tkiva kao najkvalitetniju rekonstruktivnu tehniku u rešavawu problema recesije gingive. Međutim, histološka procena ukazuje na nedovoqnu regeneraciju alveolarne kosti, cementa i periodoncijuma u žeqenom regionu [12, 13]. Ujedno se zapaža problem dugačkog pripojnog epitela kod velikog broja bolesnika. Očigledno je da je za obnavqawe dubqih parodontnih tkiva potrebna dodatna aktivna stimulacija. Potrebno je sa pasivnih regenerativnih postupaka preći na poqe biomimetike i aktivne regeneracije. Naravno, reč je o primeni specifičnih bioaktivnih, polipeptidnih molekula poznatih kao faktori rasta. Faktor rasta koji potiče iz trombocita (PDGF) i trombocitni faktor rasta β (TGF-β) predstavqaju sigurno najvažnije stimulatore i koordinatore regeneracije tkiva. Neke studije su potvrdile wihovu presudnu ulogu u hemotaksi, proliferaciji i diferencijaciji ćelija zasluženih za obnovu parodontnih tkiva [14, 15]. PDGF, TGF-β, kao i mnogi drugi mawe eksponirani bioaktivni molekuli nađeni su u ά granulama trombocita. Međutim, za pokretawe regeneracije dubqih parodontnih tkiva potrebna je i visoka koncentracija faktora rasta. Plazma bogata trombocitima (PBT) je deo plazme u kojoj se posebnim tehnološkim postupkom postiže mnogostruko veća koncentracija trombocita (do 400%) nego u normalnoj plazmi [16]. Značaj ovako obrađene plazme jeste u dobijawu ogromnih koncentracija PDGF i TGF-β (450% više u odnosu na nekoncentrovanu plazmu), koji se tog kvantiteta i kvaliteta mogu koristiti za pojačavawe regeneracije tkiva. CIQ RADA Ciq istraživawa je bio da se procene klinički efekti primene plazme bogate trombocitima kao stimulatora regenerativnih procesa u okviru hirurškog postupka korišćewa autotransplantata vezivnog tkiva i periosta u rešavawu problema izolovane recesije gingive. METOD RADA U istraživawe je ukqučeno 15 bolesnika lečenih na Klinici za parodontologiju i oralnu medicinu Stomatološkog fakulteta Univerziteta u Beogradu. Istraživawe je odobrio Etički komitet ovog fakulteta, a svi bolesnici su potpisali pisani pristanak za ukqučivawe u istraživawe. Ispitanici su u proseku bili stari 35,8 godina i svi su bili nepušači. Kod bolesnika su dijagnostikovane obostrano izražene recesije II i III klase (Slika 1), koje su po tipu i veličini bile slične [17]. Recesije su se nalazile u interkaninom i premolarnom regionu gorwe ili dowe vilice. Metodološki koncept je zasnovan na tzv. metodu podeqenih usta. Prema navedenom konceptu, u lečewu jedne recesije je primewen metod koronarno pomerenog režwa (Slika 2) uz korišćewe auto SLIKA 1. Gingivna recesija od 5 mm u regiji zuba 13. FIGURE 1. Gingival recession of 5 mm in tooth #13. SLIKA 2. Podignuti režaw pune debqine u regiji recesije. FIGURE 2. A full thickness flap with mesial and distal releasing incisions was elevated. 96
3 transplantata vezivnog tkiva i periosta. Ova grupa recesija je lečena plazmom bogatom trombocitima (PBT) ili, preciznije, aktiviranim koncentratom trombocita (PBT grupa). PBT frakcija je dobijena tehnološkim postupkom kroz dve rotacije (dou ble spin). Prvom rotacijom uzete krvi na 2400 rpm tokom 10 minuta odvojena je frakcija eritrocita od plazme (Slika 3). Drugim centrifugirawem na 3600 rpm 15 minuta odvojena je PBT od plazme siromašne trombocitima (Slika 4). U lečewu izolovanih recesija gingive u obe eksperimentalne grupe primewena je hirurška tehnika koju je opisao Alen (Al len) [5]. Posle anestezirawa hirurškog regiona, izvođene su odgovarajuće incizije u zoni recesije. Kosim i vertikalnim incizijama koje polaze od gleđnocementne granice ka alveolarnoj mukozi s obe strane recesije i koje su spojene sulkusnom incizijom omogućeno je odizawe trapezoidnog režwa pune debqine (Slika 2). Na ovaj način postignuto je potpuno izlagawe ogolelog korena zuba i oštećewa alveolarne kosti. Potom je izvođena ciqna obostrana deepitelizacija vestibularnih papila međuzubne gingive. Radi mobilizacije mukoperiostnog režwa i stvarawa uslova za wegovo koro narno pozicionirawe (bez pritiska) u apeksnoj zoni režwa, urađeno je presecawe periosta. Izložena površina korena zuba mehanički je obrađena, kako bi se uklonio nekrotički cement i poravnala i uglačala izložena površina korena zuba. Transplantat vezivnog tkiva uziman je sa nepca u regionu premolara tzv. tehnikom trap do or (Slika 5). U PBT grupi, neposredno po uzimawu transplantata vezivnog tkiva, on se u potpunosti potapao u dobijenu plazmu bogatu trombocitima (Slika 6). Plazma je aktivirana svežom krvqu bolesnika, pri čemu je dobijen koncentrovani koktel citokina. Izloženi koren i okolna alveolarna kost u tretiranom regionu su takođe natopqeni dobijenom aktivnom frakcijom plazme, posle čega je u potpunosti prekriven koronarno pozicioniranim režwem (Slike 7, 8 i 9). U lečewu kontralateralne recesije (TVT grupa) korišćen je istovetni hirurški postupak uz primenu transplantata vezivnog tkiva sa periostom u kombinaciji sa koronarno pozicioniranim režwem, ali bez primene PBT (kontrolna grupa ispitanika). Transplantat je potpunoprekrivan koronarno pozicioniranim režwem pune debqine. SLIKA 3. Odvajawe plazme (2400 rpm tokom 10 minuta). FIGURE 3. Separation of plasma (spin 2400 rpm during 10 minutes). SLIKA 5. Uzimawe transplantata vezivnog tkiva iz premolarnog regiona. FIGURE 5. Harvesting of the connective tissue graft from the palate of premolar region. SLIKA 4. Odvajawe plazme bogate trombocitima od plazme siromašne trombocitima (3600 rpm tokom 15 minuta). FIGURE 4. Separation of platelet-rich plasma from platelet-poor plasma (spin 3600 rpm during 15 minutes). SLIKA 6. Transplantat vezivnog tkiva kondicioniran plazmom bogatom trombocitima. FIGURE 6. Connective tissue graft conditioned with platelet-rich plasma. 97
4 Oporavak posle hirurškog lečewa je obuhvatao odgovarajuće higijensko-dijetetske mere uz primenu 0,12% rastvora hlorheksidin-glukonata za ispirawe usta (dva-tri puta dnevno od drugog dana posle operacije). Analgetici su prepisani po potrebi. Hirurški šavovi su uklawani posle deset dana. Predviđeni higijensko-dijetetski režim i ispirawe usta preporučivani su do tridesetog dana od operacije. Procena stawa parodontnih tkiva, obima i tipa recesije izvedena je utvrđivawem vertikalne dimenzije recesije (VDR), širine keratinizovane gingive, nivoa pripojnog epitela i gingivnog indeksa po Lou Silnesu (Löu Sil ness). Nivo oralne higijene je potvrđen primenom plak-indeksa po Silnes Louu (Sil ness Löu). Primenom navedenih kliničkih parametara utvrđivano je stawe parodontnih tkiva, kao i nivo oralne higijene pre hirurškog zahvata i šest meseci od lečewa, kada je izvedena konačna procena (Slika 10). Dobijene vrednosti za sve ispitivane parametre obrađene su primenom odgovarajućih statističkih modela, sredwe vrednosti, prosečne promene vrednosti, standardne devijacije i Studentovog t-testa. REZULTATI SLIKA 7. Transplantat vezivnog tkiva fiksiran na žeqenom mestu. FIGURE 7. Connective tissue graft placed and stabilized on the recipient site. SLIKA 8. Aktivacija plazme bogate trombocitima u regionu recesije. FIGURE 8. Additional application of activated platelet-rich plasma on the recipient site. Postoperacioni period je kod svih 15 bolesnika protekao bez komplikacija. U PBT grupi vrednost za VDR u zoni recesije pre operacije bila je 4,93±0,86 mm (Slika 11), a šest meseci posle hirurškog lečewa 0,60±0,37 mm, sa statistički značajnom razlikom (Tabela 1, Slika 12). Razlika sredwih vrednosti za VDR od 4,56 mm ukazuje na obim postignutog prekrivawa izloženog korena zuba (90,9%). U TVT grupi, u kojoj su u lečewu recesije gingive korišćeni autotransplantat vezivnog tkiva sa periostom i koronarno pomereni režaw bez primene PBT, prosečna vrednost za VDR od 4,76±0,74 mm pre operacije (Slika 13) jasno ukazuje na izraženost recesije gingive kod ispitanika ove grupe. Šest meseci po primewenoj terapiji vrednost ovog parametra od 0,63±0,29 mm potvrđuje efekte izvedene terapije (Slika 14, Tabela 2). Postignuto prekrivawe bilo je 4,13 mm, odnosno 89,9% površine ogolelog korena zuba. Efekti primewenog lečewa su se odrazili i na širinu keratinizovane gingive. Prosečna širina SLIKA 9. Koronarno pozicionirani režaw fiksiran tako da potpuno pokriva region recesije. FIGURE 9. Coronally advanced flap sutured over connective tissue graft. SLIKA 10. Izgled lečenog regiona šest meseci posle hirurške intervencije. FIGURE 10. Six months postoperatively full root coverage was obtained. 98
5 keratinizovane gingive pre operacije u PBT grupi bila je 0,88±0,30 mm. Posle lečewa recesije gingive prosečna vrednost ovog parametra bila je 3,78±0,49 mm. Na ovaj način je postignuto prosečno nominalno proširewe zone keratinizovane gingive od 2,90 mm. Vrednost širine keratinizovane gingive je statistički visoko značajno različita u odnosu na nivo pre hirurškog lečewa (Tabela 1). Kod ispitanika TVT grupe prosečna vrednost keratinizovane gingi ve pre operacije bila je 0,90±0,34 mm, dok je postoperacioni nivo od 3,15±0,41 mm pokazao proširewe ove zone za 2,25 mm (Tabela 2). U eksperimentalnoj grupi prosečna vrednost nivoa pripojnog epitela pre operacije bila je 6,28±0,78 mm, dok je šest meseci posle izvedene hirurške terapije vrednost ovog parametra bila 1,63±0,40 mm (Tabela 1). U kontrolnoj grupi nivo pripojnog epitela se sa 6,17±0,82 mm smawio na 1,73±0,46 mm (Ta SLIKA 11. Izgled gingivne recesije zuba 13 pre hirurške intervencije. FIGURE 11. Preoperative view on the gingival recession tooth #13. SLIKA 13. Izgled gingivne recesije zuba 23 pre hirurške intervencije. FIGURE 13. Preoperative view on the gingival recession tooth #23. TABELA 1. Rezultati grupe ispitanika lečenih transplantatom vezivnog tkiva uz primenu plazme bogate trombocitima. TABLE 1. Clinical results of group treated with connective tissue graft and platelet-rich plasma. Parametar Parameter Vertikalna dimenzija recesije Recession depth Širina keratinizovane gingive Keratinized tissue width Nivo pripojnog epitela Clinical attachment level p<0.01 Pre lečewa Baseline Posle šest meseci After six months 4.93±0.86 mm 0.60±0.37 mm 0.88±0.30 mm 3.78±0.49 mm 6.28±0.78 mm 1.63±0.40 mm SLIKA 14. Izgled gingivne recesije tretirane transplantatom vezivnog tkiva posle hirurške intervencije. Uočava se značajno mawa augmentacija keratinizovanog tkiva u odnosu na lečewe plazmom bogatom trombocitima i transplantatom vezivnog tkiva. FIGURE 14. Postoperative view on outcome of gingival recession treatment with connective tissue graft. Focus on appreciably smaller gain of keratinized tissue in comparison with gingival recession treated with platelets-rich plasma and conncetive tissue graft. TABELA 2. Rezultati grupe ispitanika lečenih transplantatom vezivnog tkiva bez primene plazme bogate trombocitima. TABELA 2. Clinical results of group treated with connective tissue graft without platelet-rich plasma. SLIKA 12. Izgled gingivne recesije tretirane plazmom bogatom trombocitima i transplantatom vezivnog tkiva posle hirurške intervencije. Obratiti pažwu na značajno proširewe širine keratinizovanog tkiva. FIGURE 12. Postoperative view on outcome of gingival recession treatment with platelet-rich plasma and connective tissue graft. Pay attention on significant increase of keratinized tissue width. Parametar Parameter Vertikalna dimenzija recesije Recession depth Širina keratinizovane gingive Keratinized tissue width Nivo pripojnog epitela Clinical attachment level p<0.01 Pre lečewa Baseline Posle šest meseci After six months 4.76±0.74 mm 0.63±0.29 mm 0.90±0.34 mm 3.15±0.41 mm 6.17±0.82 mm 1.73±0.46 mm 99
6 TABELA 3. Rezultati plak-indeksa (PI) i gingivnog indeksa (GI) u obe eksperimentalne grupe. TABLE 3. Plaque Index (PI) and Gingival Index (GI) results in both experimental groups. Grupa Group PBT PRP TVT CTG p<0.01 Parametar Parameter Pre lečewa Baseline Posle šest meseci After six months PI 1.73± ±0.23 GI 1.32± ±0.14 PI 1.41± ±0.18 GI 1.45± ±0.20 bela 2). Statistističkom analizom vrednosti za nivo pripojnog epitela utvrđena je statistički visoko značajna razlika u obe grupe ispitanika. Primewena terapija, čiji je ciq bilo prekrivawe ogolelog korena zuba i postizawe normalnih anatomomorfoloških i topografskih odnosa, odrazila se i na stvarawe povoqnih uslova za održavawe higijene usta i zuba, te na oslobađawe preosetqivosti korena na termičke i mehaničke nadražaje. Vrednost plak-indeksa pre operacije od 1,73±0,15 u PBT grupi i 1,41±0,23 u TVT grupi značajno se smawila na 0,41±0,23, odnosno na 0,36±0,18 posle lečewa (Tabela 3). Ovakvi efekti primewenog lečewa u pogledu nivoa oralne higijene direktno su imali uticaja i na jačinu zapaqewa gingive. Vrednost gingivnog indeksa pre operacije od 1,32±0,17 u eksperimentalnoj grupi značajno se smawila posle hirurškog lečewa (0,35±0,14; p<0,01). Sličan nalaz je zabeležen i kod ispitanika kontrolne grupe, gde se vrednost gingivnog indeksa smawio sa 1,45±0,16 na 0,30±0,20 (Tabela 3). Pomoću statističkog metoda poređewa prosečnih promena vrednosti za određene parametre u dve ispitivane grupe utvrđeno je da su rezultati u PBT grupi koji se odnose na proširewe zone keratinizovanog tkiva statistički značajno boqi (2,90 mm) od rezultata dobijenih u TVT grupi (2,25 mm) (p<0,05). Primenom statističkog metoda poređewa prosečnih PBT TV T Δ VDR Δ DP Δ NPE Δ KG GRAFIKON 1. Poređewe prosečnih promena vrednosti ispitivanih parametara u obe eksperimentalne grupe posle godinu dana. GRAPH 1. Comparison of mean changes in experimental groups after one year follow-up period. promena vrednosti za druge ispitivane kliničke parametre, nije uočena statistička značajnost razlika (Grafikon 1). DISKUSIJA Recesija gingive s izloženim korenom zuba je čest problem koji se javqa u svakodnevnoj stomatološkoj praksi. Prvi pokušaji rešavawa ovog problema potiču iz godine, kada su Grup (Gr up e) i Voren (War re n) [1] opisali tehniku lateralno pomerenog režwa. Međutim, utvrđeno je da se ovim postupkom obezbeđuje prekrivawe korena od najviše 65%. Nedostatak hirurškog postupka su relativno uske indikacije i visok stepen nepredvidqivosti. Saliven (Su li van) i Etkins (At kins) [2] su godine objavili studiju u kojoj za prekrivawe ogolićenih korenova koristi slobodni mukozni autotransplantat (SMAT). Nažalost, dokazano je da neodgovarajuća ishrana dela transplantata iznad eksponirane površine korena uslovqava mali procenat uspešnosti ovog postupka (do 50%). Langer (Lan ger) i Kalawa (Ca lag na) [3] godine u mukogingivnu hirurgiju uvode novi pristup rešavawa problema recesije gingive primenom TVT. Prema datoj metodologiji vezivnotkivnim transplantatom se izloženi koren prekriva uz delimično prekrivawe transplantata repozicioniranim režwem poludebqine. Recke (Ra et zke) [4] godine predlaže modifikovanu envelop-tehniku, takođe uz primenu TVT. Ova tehnika se pokazala kao efikasna u rešavawu recesije gingive, ali samo kod plitkih (do 4 mm) i uskih recesija. Kod dubqih recesija rezultati su značajno nepovoqniji. Ovakav ishod bio je uslovqen ugroženom ishranom dela transplantata u zoni izložene površine korena. Alen [5] pokušava da reši problem tako što TVT potpuno prekriva koronarno pomerenim režwem. Kod plitkog vestibuluma i dubokih recesija, kada nije indikovano koronarno pomerawe režwa, može se primeniti tehnika TVT u kombinaciji s lateralno pomerenim režwem dve papile. Ovaj metod je opisao Nelson (Nel s on) [6] godine. U okviru ove tehnike preporučuje se režaw pune debqine. Uspešnu modifikaciju Nelsonove tehnike opisao je Haris (Har ris) [18] godine primewujući režaw poludebqine. Tinti (Tin ti) i Vinčenci (Vin cen zi) [7] godine problem recesije gingive rešavaju tako što prvi uvode postupak usmerene regeneracije parodoncijuma (GTR). Kao promotera regenerativnih procesa u parodoncijumu, oni koriste neresorptivnu ep TFE membranu potpuno prekrivenu koronarno pozicioniranim režwem pune debqine. Pini Prato (Pi ni Pra to) i Kortelini (C or tel li ni) i [8] i Haris [9] izolovanu recesiju gingive eliminišu primenom GTR uz korišćewe resorptivne mem 100
7 brane od polilaktičke kiseline. Slične rezultate dobili su i De Sanktis (De San ctis) i Cukeli (Zuc cheli) [10] i Haris [11] primenom resorptivne membrane od kolagena. Ono što je zajedničko za ove postupke jesu visok stepen nepredvidqivosti pozitivnog rezultata i izuzetno nizak nivo proširewa keratinizovanog tkiva u regionu tretirane recesije. Rezultati naše studije ukazuju na izuzetnu efikasnost oba primewena specifična hirurška postupka u rešavawu složenih problema lečewa recesije gingive. Analiza dobijenih podataka pokazuje da su kod ispitanika lečenih TVT u kombinaciji sa PBT postignuti boqi rezultati u širini zone keratinizovane gingive nego kod ispitanika TVT grupe posle šestomesečnog perioda nadgledawa. Ova saznawa, kao i rezultati, u saglasnosti su sa nalazima drugih autora [1, 3, 17]. Ovaj nalaz ni na koji način ne umawuje izuzetno pozitivne efekte primene TVT bez primene PBT u rešavawu problema izolovane recesije gingive u parodontopatiji. U prilog ovom stavu govori i čiwenica da je postignuta prosečna prekrivenost izloženih korenova primenom ove tehnike korišćewem samo TVT bila 88,5%. Ipak, treba imati u vidu zavidne efekte koji su postignuti primenom PBT, gde je prosečno prekrivawe korena bilo 90,9%. Zanimqiva su tumačewa postizawa proširewa zone keratinizovane gingive u lečewu recesije gingive. Ovaj fenomen se tumači sposobnošću tkiva regenerisanog iz periodoncijuma i kosti da indukuje keratinizaciju i postoperacionu regresiju nivoa mukogingivne linije na wenu genetski predodređenu lokalizaciju [9, 19]. Proširewe zone keratinizovanog tkiva posle primene TVT i periosta može biti direktna posledica induktivnog delovawa nekih faktora iz mezenhimnog tkiva transplantata na metaplaziju epitela režwa u pravcu keratinizacije [17]. Ovakvom analizom dolazi se do razumevawa fenomena proširewa zone keratinizovanog tkiva kod ispitanika lečenih aktiviranim PBT u odnosu na grupu ispitanika gde on nije korišćen. Očigledno je da je mnogostruko stimulativno dejstvo visokokoncentrovanih citokina, prvenstveno PDGF i TGF-β iz aktivirane PBT frakcije plazme (oslobađawem iz ά granula trombocita), unapredilo regenerativne procese na nivou dubqih parodontnih tkiva. Poznata je wihova uloga na hemotaksi matičnih ćelija, aktivirawu mitotske aktivnosti i diferencijaciji u produktivne ćelijske grupe koje direktno učestvuju u regeneraciji parodontnih tkiva. Smatra se da PDGF i TGF-β, vezujući se za specifične površinske receptore i aktivirajući unutarćelijski mehanizam tirozin-kinaze, imaju posebno snažno dejstvo na nediferencirane mezenhimne ćelije periodontnog i kostnog porekla [20]. U zavisnosti od tipa receptora za koji se vežu, PDGF i TGF-β deluju kao mitogen (proliferacija) ili morfogen (diferencijacija). Potvrđeno je da ove ćelije predstavqaju izvor obnavqawa kostnog, periodontnog i cementnog tkiva. Ujedno, navedeni bioaktivni faktori rasta pojačavaju sintezu kolagena tip I od strane fibroblasta i osteoblasta, koji postoje u tkivu parodoncijuma. Ove dve vrste ćelija imaju osnovnu ulogu u stvarawu novog vanćelijskog matriksa vezivnog i kostnog tkiva, te u stvarawu novog pripoja [20]. PDGF u velikim koncentracijama veoma efektno suprimira proliferaciju epitela, što ima poseban značaj, budući da je u lečewu recesija gingive dugačak pripojni epitel, kao nepovoqni ishod lečewa, histološki zabeležen u većini uzoraka [21]. Klinički boqi rezultati zabeleženi kod ispitanika eksperimentalne grupe lečenih aktiviranom PBT se dodatno mogu objasniti i postojawem efekta tkivnog lepka u regionu rane. U ovom predelu se aktivirawem plazme visokokoncentrovane trombocitima za 30 minuta stvara izuzetno kvalitetan koagulum koji odlikuje i do stotinu puta veća gustina fibrinske mreže u odnosu na spontano formiran koagulum. Ovakav koagulum omogućava dodatnu stabilnost rane. S druge strane, proteolitičkom razgradwom fibrina fibroblasti dobijaju značajan gradivni materijal za pojačanu sintezu kolagena. Mora se naglasiti i uloga aktivirane plazme u difuzionoj prehrani transplantata i tkiva režwa u prva dva dana posle intervencije mnogim hranqivim sastojcima. Prosečne vrednosti za nivo pripojnog epitela pre i šest meseci posle hirurškog lečewa pokazuju da se primewenim terapijskim postupkom značajno pospešuje razvoj regenerativnih procesa u parodoncijumu. Na ovo ukazuje i koronarno pomerawe pripojnog epitela. Oslobađawe recesije kod ispitanika obe grupe, uz uspostavqawe povoqnih anatomomorfoloških i topografskih odnosa u tkivu gingive, kao i u mukogingivnom kompleksu parodontnih tkiva, odrazila se na mogućnost adekvatnog održavawa higijene usta i zuba. Stvoreni uslovi za manipulaciju četkicom (proširewe zone keratinizovane gingive, produbqivawe vestibuluma i dr.), ali i postignuta desenzibilizacija korena, obezbedili su efekte u pogledu potrebnog nivoa oralne higijene, na šta ukazuje smawewe vrednosti plak-indeksa i gingivnog indeksa. Idealni ciq svih rekonstruktivnih mukogingivnih hirurških zahvata jeste potpuna rekonstrukcija svih izgubqenih parodontnih tkiva u regionu tretirane gingivne recesije. Ocewujući potvrđene biološke efekte aktiviranog koncentrata trombocita mogu se objasniti boqi klinički rezultati, po svim kliničkim parametrima, postignuti u eksperimentalnoj grupi ispitanika lečenih primenom PBT. Čiwenica da je samo kod proširewa zone keratinizovanog tkiva utvrđena statistički značajna razlika ohrabruje i upućuje na zakqučak o mogućoj intenzivnijoj regeneraciji dubqih parodontnih tkiva (alveolarna kost, cement i periodoncijum) u tretiranim regionima. Međutim, dobijeni pozitivni klinički 101
8 rezultati primenom navedenih hirurških postupaka mogu se potvrditi i objektivizirati jedino kvalitetnom histološkom analizom. ZAKQUČAK Na osnovu dobijenih rezultata istraživawa može se zakqučiti da je primena metoda koronarno pomerenog režwa i transplantata vezivnog tkiva u kombinaciji sa plazmom bogatom trombocitima vrlo efikasna u rešavawu problema recesije gingive. Budućnost regenerativne parodontne terapije, pa i rekonstruktivne mukogingivne hirurgije, leži u aktivnoj regeneraciji i primeni biomimetičkih principa i tehnologija. ZAHVALNICA Rad je finansiralo Ministarstvo nauke i tehnologije Republike Srbije u okviru projekta br , pod nazivom Parodontalna medicina, koncept aktivne regeneracije u parodontologiji i implantologiji. LITERATURA 1. Grupe J, Warren R. Repair of gingival defects by sliding flap operation. J Periodontol 1956; 27: Sulivan HC, Atkins JH. Free autogenous gingival grafts. III Utilization of grafts in the treatment of gingival recession. J Periodontol 1968; 6: Langer B, Calagna L. The subepithelial connective tissue graft. A new approach to enhancement of anterior cosmetics. Int J Periodontics Restorative Dent 1982; 2: Raetzke P. Covering localized areas of root exposure employng the "envelope" technique. J Periodontol 1985; 56: Allen EP. Pedicle flaps, gingival grafts and connective tissue grafts in aesthetics treatment of gingival recessions. Pract Periodontics Aesthet Dent 1993; 5: Nelson S. The subpedicle connective tissue graft. A bilaminar reconstructive procedure for covering of denuded surfaces. J Periodontol 1987; 58: Tinti C, Vincenzi GP, Cortelini P.The treatment of gingival recession with guided tissue regeneration procedures with means of Gore Tex membranes. Quintessence Int 1990; 6: Pini Prato G, Cortellini P. Guided tissue regeneration versus mucogingival surgery in the treatment of human buccal gingival recession. J Periodontol 1992; 63: Harris RJ. A comparative study of root coverage obtained with guided tissue regeneration utilizing a biobsorbable membrane and subepithelial connective tissue graft. J Periodontol 1997; 68: De Sanctis M, Zuccheli G. Guided tissue regeneration with resorbable barrier membrane for the management of buccal recession. Int J Periodontics Restorative Dent 1996; 16: Harris RJ. The connective tissue graft and partial thickness double pedicle graft: A predictable method of obtaining root coverage. J Periodontol 1992; 63: Trombeli L. Periodontal regeneration in gingival recession defects. J Periodontol ; 19: Waterman CA. Guided tissue regeneration using a bioabsorbable membrane in the treatment of human gingival recession. A re-entry study. J Periodontol 1997; 68: Lynch SE, Williams RC, Polson AM, et al. A combination of platelet-derived and insulin-like growth factors enhances periodontal regeneration. J Clin Periodontol 1989; 16: Wang H-L, Pappert TD, Castelli WA, Chiego DJ Jr, Shyr Y, Smith BA. The effect of platelet-derived growth factor on the cellular response of the periodontium: An autoradiographic study on dogs. J Periodontol 1994; 65: Marx RE, Carlson ER, Eichstaedt RM, Schimmele SR, Strauss JE, Georgeff KR. Platelet-rich plasma: Growth factor enhancement for bone grafts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998; 85: Miller PD, Alen EP. Coronal positioning of existing gingiva Short term results in the treatment of shallow marginal tissue recession. J Periodontol 1989; 60: Harris RJ. A comparison of 2 root coverage techniques: Guided tissue regeneration with a bioabsorbable matrix style membrane versus connective tissue graft combined with coronally positioned pedicle graft. J Periodontol 1998; 69: Cortelini P, Clauser C. Histologic assessment of new attachment following the treatment of a human buccal recessions by means of guided tissue regeneration procedures. J Periodontol 1993; 64: Pfeifer JA, Heller R. Histologic evaluation of full and partial thickness lateral positioned flaps: A pilot study. J Periodontol 1971; 42: Kawase T, Okuda K, Wolff LF, Yoshie H. Platelet-rich plasmaderived fibrin clot formation stimulates collagen synthesis in periodontal ligament and osteoblastic cells in vitro. J Periodontol 2003; 74: Carnio J, Camargo P, Kenney B. Histological evaluation of 4 cases of root coverage following a connective tissue graft combined with enamel matrix derivate preparation. J Periodontol 2002; 73:
9 CLINICAL IMPACT OF PLATELET RICH PLASMA IN TREATMENT OF GINGIVAL RECESSIONS Zoran ALEKSIĆ 1, Saša JANKOVIĆ 1, Božidar DIMITRIJEVIĆ 1, Ana PUCAR 1, Vojkan LAZIĆ 2, Vojislav LEKOVIĆ 1 1 Clinic for Periodontology and Oral Medicine, School of Dentistry, University of Belgrade, Belgrade; 2 Clinic for Prosthodontics, School of Dentistry, University of Belgrade, Belgrade INTRODUCTION Root coverage supported with complete regeneration of lost periodontal tissues represents the ultimate goal of gingival recession treatment. OBJECTIVE This study was designed to evaluate clinical effectiveness of platelet rich plasma gel (PRP) with connective tissue graft (CTG) in the treatment of gingival recession. METHOD 15 gingival recessions Miller class I or II were treated with CTG and PRP (group PRP). Connective tissue graft was harvested from the premolar region using trap door technique. After elevation of the flap, the regional bone and root surface were smeared with activated PRP gel. CTG was also irrigated with PRP gel before placement over the exposed root surface and local bone. Fixed CTG was covered with a coronally advanced flap. The same number of gingival recessions were treated with CTG in combination with the coronally advanced flap with no PRP gel (group TVT). Clinical recordings included recession depth (RD), probing depth (PD), clinical attachment level (CAL) and keratinized tissue width (KT) before and 1 year after mucogingival surgical treatment. RESULTS Mean value of RD was significantly decreased from 4.93±0.86 mm to 0.60±0.37 (p<0.01) with CTG and PRP and from 4.76±0.74 mm to 0.63±0.29 mm (p<0.01) in CTG group. This difference was not statistically significant. Results of the keratinized tissue width showed significant increase from 0.88± 0.30 mm presurgery to 3.78±0.49 mm (p<0.01) six months after treatment in PRP group and from 0.90±0.34 mm to 3.15±0.41 in TVT group (p<0.01). This difference was statistically significant (p>0.05). No statistically significant differences were observed between treatment groups in CAL and PD. CONCLUSION Clinical results validate both procedures as effective and highly predictable surgical techniques in solving gingival recession problem. Histological evaluation may confirm advantage of PRP use related to regeneration of periodontal tissues. Key words: gingival recession; platelet rich plasma; connective tissue graft; tissue regeneration Zoran ALEKSIĆ Stomatološki fakultet Dr Subotića 4, Beograd Tel.: Faks: draleksic@ptt.yu * Rukopis je dostavqen Uredništvu godine. 103
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