Platelet-Enriched Fibrin Glue and Platelet-rich Plasma in the Repair of Bone Defects Adjacent to Titanium Dental Implants

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1 Pltelet-Enriched Firin Glue nd Pltelet-rich Plsm in the Repir of Bone Defects Adjcent to Titnium Dentl Implnts Te-Min You, DDS 1 /Byung-Ho Choi, DDS, PhD 2 /Shi-Jing Zhu, MD 3 /Je-Hyung Jung, DDS 1 / Seoung-Ho Lee, DDS, PhD 4 /Jin-Young Huh, DDS 1 /Hyun-Jung Lee, DDS 1 /Jingxu Li, DDS 3 Purpose: The im of this study ws to compre the effects of pltelet-enriched firin glue nd plteletrich plsm (PRP) on the repir of one defects djcent to titnium dentl implnts. Mterils nd Methods: In 6 mongrel dogs, 3 screw-shped titnium dentl implnts per dog were plced into the osteotomy sites in the tii. Before implnttion, stndrdized gp (2.0 mm) ws creted etween the implnt surfce nd the surrounding one wlls. Six gps were left empty (control group), 6 gps were filled with utogenous prticulte one mixed with PRP (PRP group), nd 6 gps were filled with utogenous prticulte one mixed with pltelet-enriched firin glue (firin glue group). Results: After 6 weeks, the one-implnt contct ws 59.7% in the firin glue group, 29.2% in the PRP group, nd 10.2% in the control defects; this difference ws sttisticlly significnt (P <.05). Discussion nd Conclusion: Greter one-implnt contct ws chieved with pltelet-enriched firin glue thn with PRP. The results indicte tht pltelet-enriched firin glue cn induce stronger peri-implnt one rection thn PRP in the tretment of one defects djcent to titnium dentl implnts. INT J ORAL MAXILLOFAC IMPLANTS 2007;22: Key words: one grfting, one regenertion, dentl implnts, firin glue, pltelet-rich plsm 1 Grdute Student, Deprtment of Orl & Mxillofcil Surgery, College of Dentistry, Yonsei University, Seoul, South Kore. 2 Professor, Deprtment of Orl & Mxillofcil Surgery, College of Dentistry, Yonsei University (Brin Kore 21 Project for Medicl Sciences), Seoul, South Kore. 3 Reserch Assistnt, Deprtment of Dentistry, Yonsei University Wonju College of Medicine, Wonju, South Kore. 4 Associte Professor, Deprtment of Periodontology, Ewh Womns University, Seoul, South Kore. Correspondence to: Prof Byung-Ho Choi, Deprtment of Orl & Mxillofcil Surgery, College of Dentistry, Yonsei University, 134 Shinchon-dong, Seodemun-gu, Seoul, South Kore. Fx: E-mil: choih@yonsei.c.kr Bone resorption fter tooth extrction reduces the height nd width of the lveolr crest, hindering the use of dentl implnts. 1,2 The plcement of dentl implnt immeditely fter tooth extrction hs een recommended s mens to minimize one loss nd shorten the time of the prosthetic tretment. 3,4 Immedite implnttion into fresh extrction sockets is often ssocited with residul one defect etween the implnt neck nd the residul one wlls. As hs een reported, 5,6 lrge gps my jeoprdize the success of immedite implnt procedures. Such gps my cuse cell migrtion from the connective nd epithelil tissue into the gp, which my prevent osseointegrtion. Vrious techniques, including the use of rrier memrnes nd grfting mteril, 7 hve een proposed for the mngement of these defects. In prticulr, grfting mteril mixed with pltelet-rich plsm (PRP) hs een reported to enhnce the osseointegrtion of dentl implnts, 8,9 s it contins lrge numers of pltelets which relese significnt quntities of growth fctors known to promote wound heling. 9,10 The ide of using pltelet-enriched firin glue to fill one defects is ttrctive ecuse this glue contins mny more pltelets thn PRP. 11 In ddition, the high concentrtions of firinogen in firin glue cn produce dense firin clot with sufficient dhesive strength to hold prticulte one in configurtion. For these resons, pltelet-enriched firin glue ws considered for use in one defects djcent to titnium dentl implnts. The im of this study ws to compre the effects of oth pltelet-enriched firin glue nd PRP on one defect repir djcent to tit- The Interntionl Journl of Orl & Mxillofcil Implnts 417

2 nium dentl implnts in the dog tii.the experimentl model used ws designed to simulte immedite implnttion into fresh tooth extrction sockets. MATERIALS AND METHODS Fig 1 Experimentl design. () The control defect remined empty. () The corticl defect ws filled with utogenous prticulte one mixed with PRP. (c) The corticl defect ws filled with utogenous prticulte one mixed with pltelet-enriched firin glue. Animl Model Six dult femle mongrel dogs weighing more thn 15 kg were used in this experiment. Approvl ws otined from our niml cre committee of Yonsei Medicl Center, Seoul, Kore. PRP Preprtion The PRP ws prepred using technique descried previously. 12 Briefly, 20 ml of utologous lood withdrwn from ech dog ws initilly centrifuged t 2,400 rpm for 10 minutes to seprte the PRP nd pltelet-poor plsm (PPP) portions from the red lood cells. The PRP nd PPP were gin centrifuged t 3,600 rpm for 15 minutes to seprte PRP from PPP. Pltelet counts were then done for ech dog, yielding men PRP pltelet count of 1,490,000 (rnge, 1,020,000 to 2,140,000). The PRP ws ctivted just efore ppliction with 10% clcium chloride solution nd 5,000 units of ovine thromin to form gel. Pltelet-Enriched Firin Glue Preprtion Pltelet-enriched firin glue ws prepred using previously descried technique. 11 Briefly, 20 ml of utologous lood withdrwn from ech dog ws treted using the forementioned technique to seprte PRP from the lood. The firinogen solution ws susequently prepred using the PRP. To 7.5 ml c of PRP, 240 µl of trnsexmic cid nd 900 µl of ethnol were dded. This mixture ws incuted in n ice-wter th for 20 to 30 minutes. The precipitted firinogen ws seprted y centrifugtion t 3000 x g for 8 minutes t 0 C to 4 C. After discrding the superntnt, the firinogen precipitte ws redissolved t 37 C nd diluted to 50% with 0.9% sodium chloride (NCl). A thromin solution ws then prepred using the remining PRP. Briefly, 2.5 ml of PRP ws dded to 22.5 ml of citric cid, nd the mixture ws then centrifuged t 3000 x g for 5 minutes t 4 C. After discrding the superntnt, the precipitte ws dissolved in 150 µl clcium chloride (CCl 2 ; 0.1 mol/l), nd the ph ws djusted to 7 y dding 100 µl of sodium hydrogen cronte (NHCO 3 ). After clot formtion, the thromin solution ws collected nd diluted to 10% with 0.05 mol/l CCl 2. The firin glue ws formed y mixing the firinogen nd thromin solutions in 3:1 (vol/vol) rtio. Thorn et l 11 reported tht utologous firin glue prepred y this technique contins high concentrtions of pltelets nd firinogen. Surgicl Procedure All surgicl procedures were performed under systemic nesthesi (5 mg/kg ketmine nd 2 mg/kg intrmusculr xylzine) s well s locl nesthesi (2% lidocine with 1:80,000 epinephrine). The one surfce of the tii ws exposed y n incision mde on the internl side of the tii. Before implnttion, corticocncellous one grfts were hrvested from 3 implnt recipient sites using trephine ur of 6.0 mm. Bone defects of 6.1 mm were creted t ech site y enlrging the upper spect of the osteotomy site using round ur. Implnts 15 mm in length nd 4.1 mm in dimeter were then plced through oth the defect nd the lower corticl one so tht stndrdized gp of 2.0 mm ws creted etween the ony wlls nd the implnt neck. In ll, 18 implnts (Osstem, Seoul, Kore) were plced (3 in ech tii). Susequently, the otined corticocncellous one ws ground in one mill (Stryker Leiinger, Freiurg, Germny) to uniform prticle size. This prticulte one ws then used to fill the gp from which the one hd een otined. The one gps were treted with 1 of the following 3 tretment modlities: (1) no tretment (control group), (2) grfting with prticulte one mixed with PRP (PRP group), or (3) grfting with prticulte one mixed with pltelet-enriched firin glue (firin glue group) (Fig 1). All experimentl res were covered with the soft tissue flp fter removl of the periosteum. Cefzolin (Choing Kun Dng, Seoul, South Kore) ws dministered 1 hour efore surgery nd once dily for 2 dys following surgery. 418 Volume 22, Numer 3, 2007

3 Smple Preprtion Animls were scrificed 6 weeks fter surgery, nd one locks with the implnts were excised. Resected one specimens were fixed in 10% uffered formlin nd emedded in methylmethcrylte resin. The locks were cut longitudinlly through the middle plne of the implnts. Histologic sections (40 µm) were prepred using cutting-grinding method nd were stined with toluidine lue. Histomorphometry A morphometric study using n imge nlysis system (IBAS; Contron, Erching, Germny) ws used to quntify the newly formed one round the implnts. The one-implnt contct (BIC), defined s the length of one surfce order in direct contct divided y the implnt perimeter ( 100%), ws then clculted. BIC ws mesured t the upper corticl nd medullry levels. Sttisticl Anlysis The Wilcoxon signed rnk test ws used to clculte sttisticl differences etween the 2 ctive tretments. P vlues less thn.05 were considered significnt. RESULTS No postopertive infections or loose implnts were oserved during the follow-up period. In the control group, firous memrne with fiers prllel to the implnt surfce ws found in contct with the implnt surfce, nd there ws very little direct contct etween the one nd the implnt in the medullry nd trnscorticl portions of the implnt (Fig 2). In the PRP group, the newly formed one ws in contct with the implnt surfce, nd no firous memrne ws oserved. New one ws formed lrgely t the interfce etween the implnt interfce nd the upper corticl one (Fig 3). Compred with the PRP group, the firin glue group showed more newly formed trecule round the implnt in the upper corticl nd medullry portions. These trecule were thicker thn those in the PRP group (Fig 4). The men percentges of direct BIC in the 3 groups re shown in Tle 1. The quntittive morphometric nlysis showed significntly more BIC in the firin glue group (P <.05) thn in the other 2 groups together. The BIC ws 10.2% ± 1.9% for the control group, 29.2% ± 7.8% for the PRP group, nd 59.7% ± 13.8% for the firin glue group. DISCUSSION In recent yers, severl sustnces hve een used to improve peri-implnt one response: PRP, one morphogenetic proteins, 16,17 nd growth fctors The use of PRP is sed on the premise tht the high quntity of pltelets in PRP relese significnt mounts of growth fctors tht id in one grft mturtion. 21 Growth fctors relesed from the pltelets hve een shown to include plteletderived growth fctor, trnsforming growth fctor-, pltelet-derived epiderml growth fctor, plteletderived ngiogenesis fctor, insulin-like growth fctor 1, nd pltelet fctor 4. 9,10 These fctors signl the locl mesenchyml nd epithelil cells to migrte, divide, nd increse collgen nd mtrix synthesis. 22 It hs een suggested tht PRP cn e used to increse the rte of one deposition nd the qulity of one regenertion when ugmenting sites prior to or in conjunction with dentl implnt plcement. 22,23 PRP hs lso een recommended for use lone or in comintion with one grfts in the tretment of peri-implnt defects tht result s consequence of immedite implnt plcement. 8,9 The present study showed tht when comintion of pltelet-enriched firin glue nd one grfts ws used in the tretment of one defects djcent to titnium dentl implnts, the BIC ws significntly higher in the firin glue group thn in the PRP group. This suggests tht the pltelet-enriched firin glue promotes stronger peri-implnt one rection thn PRP, most likely due to the properties of the plteletenriched firin glue. Thorn et l 11 reported tht the concentrtion of firinogen in pltelet-enriched firin glue ws pproximtely 12 times tht found in PRP nd tht the concentrtion of growth fctors (s mesured y pltelet-derived growth fctor) ws pproximtely 8 times tht in PRP. In the present study, pltelet-enriched firin glue with high concentrtions of pltelets nd firinogen ws prepred using the technique descried y Thorn et l. 11 PRP nd pltelet-enriched firin glue mimic the lst steps in the cogultion process (the conversion of firinogen to firin, ided y thromin nd clcium) y helping to cross-link the firin into stle clot. 24 Theoreticlly, the firin clot cn keep the pltelets on loction nd serve s n osteoconductor. 25 The pltelet-enriched firin glue in this study produced denser firin clot thn PRP, with more dhesive strength to hold prticulte one in required configurtion due to its high firinogen concentrtion. Vrious memrne techniques originlly developed for the tretment of one loss due to periodontl disese hve een used to promote one form- The Interntionl Journl of Orl & Mxillofcil Implnts 419

4 Fig 2 A section from the control group t originl mgnifictions of () 5 nd () 100 (toluidine lue). A firous memrne surrounds the implnt surfce, nd no one contcts the implnt. Fig 3 A section from the PRP group t originl mgnifictions of () 5 nd () 100 (toluidine lue). The newly formed one contcts the implnt surfce; no firous memrne is seen. Fig 4 A section from the firin glue group t originl mgnifictions of () 5 nd () 100 (toluidine lue). The new trecule re thicker nd etter formed thn in the PRP group. 420 Volume 22, Numer 3, 2007

5 Tle 1 Percentge of BIC in the Exmined Dog Tiie Dog numer Control group PRP group Firin glue group Men ± SD 10.2 ± ± ± 13.8 tion in the presence of lrge gps (> 2 mm) etween the ony wlls nd the implnt neck. 5 However, inconsistent results hve een chieved. Postopertive infections, memrne exposure to the orl cvity, nd prtil necrosis of the djcent one hve een reported. 26 In this study, nongrfted gps tht did not hve rrier memrne showed firous memrne surrounding the implnt surfce, wheres gps filled with one grft mixed with either PRP or pltelet-enriched firin glue showed one in contct with implnt surfce. Bsed on these results, it is possile tht either pltelet-enriched firin glue or PRP could e used s n lterntive to memrnes to prevent connective nd epithelil cells from migrting into the gps. CONCLUSION Bsed on dt presented in this study, it cn e concluded tht pltelet-enriched firin glue cn induce stronger peri-implnt one rection thn PRP in the tretment of one defects djcent to titnium dentl implnts. ACKNOWLEDGMENT This work ws supported y grnt no. R from the Medicl Science nd Engineering Reserch Progrm of the Koren Science & Engineering Foundtion. REFERENCES 1. Crlsson GE, Persson G. Morphologic chnges of the mndile fter extrction nd wering of the denture. Odontol Rev 1967;18: Atwood D. Postextrction chnges in the dult mndile s illustrted y micrordiogrphs of midsgittl section nd seril cephlometric roentgenogrms. J Prosthet Dent 1963;13: Lng N, Brgger U, Hämmerle C, Sutter F. Immedite trnsmucosl implnts using the principle of guided tissue regenertion. I. Rtionle, clinicl procedures nd 30-month results. Clin Orl Implnts Res 1994;5: Rosenquist B, Grenthe B. Immedite plcement of implnts into extrction sockets: Implnt survivl. Int J Orl Mxillofc Implnts 1996;11: Becker BE, Becker W, Ricci A, Geurs N. A prospective clinicl tril of endosseous screw-shped implnts plced t the time of tooth extrction without ugmenttion. J Periodontol 1998;69: Lndserg CJ. Socket sel surgery comined with immedite implnt plcement: A novel pproch for single tooth replcement. Int J Periodontics Restortive Dent 1997;17: Becker W, Becker B, Hndelsmn M, et l. Bone formtion t dehisced dentl implnt sites treted with implnt ugmenttion mteril: A pilot study in dogs. Int J Periodontics Restortive Dent 1990;10: Kim SG, Kim WK, Prk JC, Kim HJ. A comprtive study of osseointegrtion of Avn implnts in deminerlized freezedried one lone or with pltelet-rich plsm. J Orl Mxillofc Surg 2002;60: Snchez AR, Sheridn PJ, Kupp LI. Is pltelet-rich plsm the perfect enhncement fctor? A current review. Int J Orl Mxillofc Implnts 2003;18: Gnio C,Tenewitz FE, Wilson RC, Mules BG.The tretment of chronic nonheling wounds using utologous plteletderived growth fctors. J Foot Ankle Surg 1993;32: Thorn JJ, Sørensen H, Weis-Fogh U, Andersen M. Autologous firin glue with growth fctors in reconstructive mxillofcil surgery. Int J Orl Mxillofc Surg 2004;33: Okud K, Kwse T, Momose M, et l. Pltelet-rich plsm contins high levels of pltelet-derived growth fctor nd trnsforming growth fctor- nd modultes the prolifertion of periodontlly relted cells in vitro. J Periodontol 2003;74: Zechner W,Tngl S,Tepper G, et l. Influence of pltelet-rich plsm on osseous heling of dentl implnts: A histologic nd histomorphometric study in minipigs. Int J Orl Mxillofc Implnts 2003;18: Jensen TB, Rhek O, Overgrd S, Sølle K. Pltelet rich plsm nd fresh frozen one llogrft s enhncement of implnt fixtion: An experimentl study in dogs. J Orthop Res 2004;22: Weirich G, Hnsen T, Kleis W, Buch R, Hitzler WE. Effect of pltelet concentrtion in pltelet-rich plsm on peri-implnt one regenertion. Bone 2004;34: The Interntionl Journl of Orl & Mxillofcil Implnts 421

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