ISSN Implantology 2015; 19(1): 16~25 1-ethyl-3-(3-dimethyl aminopropyl) Carbodiimide 로가교화된제 1 형콜라겐차폐막의골유도재생효과 : 증례보고 이재홍, 유훈, 김유경, 신현기, 임현창,

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1 ISSN Implantology 2015; 19(1): 16~25 1-ethyl-3-(3-dimethyl aminopropyl) Carbodiimide 로가교화된제 1 형콜라겐차폐막의골유도재생효과 : 증례보고 이재홍, 유훈, 김유경, 신현기, 임현창, 김영택, 이중석, 정의원, 최성호 연세대학교치과대학치주과학교실, 치주조직재생연구소 Guided Bone Regeneration Using Type-I Collagen Membrane Cross-Linked by 1-ethyl-3-(3-dimethyl aminopropyl) Carbodiimide in Two Implant Dehiscence Cases Jae-Hong Lee, Hoon You, You-Kyung Kim, Hyun-Ki Shin, Hyun-Chang Lim, Young-Taek Kim, Jung-Seok Lee, Ui-Won Jung, Seong-Ho Choi Department of Periodontology, Research Institute for Periodontal Regeneration, Yonsei University College of Dentistry, Seoul, Korea Abstract The purpose of this study was to evaluate the guided bone regeneration, using 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC), cross-linked type-i collagen membrane in bony defects around the installation site of the implant. In two case studies, presented buccal and palatal dehiscence defects were solved using EDC collagen membrane. Defects were measured clinically at the time of the 1st surgery and were compared with defects at the 2nd surgery. No clinical complication was observed. EDC collagen membrane improved the ability of space maintenance and showed biocompatibility and low cytotoxicity. In conclusion, using an implant with EDC collagen membrane has satisfactory results with regard to esthetic and functional aspects. Key Words: case report, collagen membrane, dental implant, guided bone regeneration Reprint requests: Seong-Ho Choi Department of Periodontology, Yonsei University College of Dentistry, 50, Yonsei-ro, Seodaemun-gu, Seoul , Korea Tel: , Fax: shchoi726@yuhs.ac Received for publication: March 10, 2015 Accepted for publication: March 14, 2015 교신저자 : 최성호 ( ) 서울시서대문구연세로 50 연세대학교치과대학치주과학교실 Tel: , Fax: shchoi726@yuhs.ac 원고접수일 : 2015 년 3 월 10 일게재확정일 : 2015 년 3 월 14 일 Copyright The Korean Academy of Oral & Maxillofacial Implantology This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 16 Implantology Vol. 19 No. 1, 2015

2 I 서론 조직유도재생술은긴상피접합과같은원하지않는조직의이주를막고, 상실되거나소실된치주조직및치조골의재생을주요한목적으로한다 1. 조직유도재생술에사용되는비흡수성차폐막과흡수성차폐막이결손된치주조직의치유기간동안골열개, 골천공, 수평및수직적인형태의골결손에임상적으로성공적으로사용되어왔다. 초기에는 expanded-polytetrafluoroethylene (e-ptfe) 와같은비흡수성차폐막이주로사용되었는데, 세포의이동을막고공간을유지, 형성하는데이상적인재료로사용되어왔다 1. 그러나차폐막을제거하는데추가적인술식이필요하고, 치유기간동안차폐막의노출이빈번하였다. Trombelli 등 2 은골결손에서의 e-ptfe 차폐막의노출빈도를 66% 로보고하였다. 이러한의도하지않은차폐막의노출은세균의감염을통한염증반응을일으키고궁극적으로는조직재생의실패를가져올수있다 3. 이에반해, 흡수성콜라겐차폐막은이차수술이필요하지않으며, 많은연구에서비흡수성차폐막에뒤지지않는임상결과를보여주고있다 4,5. 그러나흡수성콜라겐차폐막은분해되는과정에서주변조직에불필요한염증반응을야기할수있으며, 낮은강도로인한붕괴와효소및세균에의한빠른흡수가단점으로지적되고있다 6. 따라서중등도이상의넓은결손에서는차폐막의붕괴를막기위하여결손부를지지해줄수있는골이식재를사용하며, 다양한방법 (ultraviolet radiation, hexamethylene diisocyanate, combined glutaraldehyde and irradiation, diphenylphosphoryl-azide, 1-ethyl-3-[3- dimethyl aminopropyl] carbodiimide [EDC]) 으로가교화 하여분해속도를늦춘콜라겐차폐막들이임상에서성공적으로사용되고있다 7,8. 이중, EDC로가교화된콜라겐차폐막은수용성 carbodiimide 계통으로, glutaraldehyde 나 polyepoxides와는달리 linkage의일부분으로남지않고세포독성이낮은수용성요소유도체로변화되어제거가쉬우며높은생체친화성을가지고있다 7,9. 또한, 반응효율성을증가시키고수화를지연시키기위하여 N-hydroxysuccinimde 를추가하여 EDC로가교화된콜라겐차폐막은 glutaraldehyde 로가교화한차폐막과유사하게늦은분해속도를갖는다 9. 본연구에사용한 EDC로가교화된제1형콜라겐차폐막은 porcine 피부에서추출한순도 99.83% 의아텔로콜라겐으로제작되었으며, 세포차단효과및효소저항성이높고골형성을위한충분한흡수지연시간을가지고있는것으로알려져있다. 따라서, 협측열개결손을가진상악전치부와상악동골이식술이동반된구개측열개결손을가진구치부에 EDC로가교화된콜라겐차폐막을적용한단일치임플란트의증례를통하여본차폐막의임상적유용성을평가해보고자한다. II 증례보고 1. Case 1 23세남자환자가외상으로인해상악우측중절치가부러졌다는주소로본원에내원하여응급으로치수절단술시행하였다 (Fig. 1). 다음내원시구개측파절선이치은연하로깊게존재하여지대치로써예후가불량할것으로판단되어즉시임플란트식립을계획하였으나, 발치와협측결손이발견되어구개상피를이용한발치와보존술을시행하였다 (Fig. 2). 연조직의치유가이루어진 1달후골유도재생술을동반한조기임플란트식립을결 대한구강악안면임프란트학회지 19 권 1 호,

$fractured by trauma.$ (A) Anterior view. (B) Occlusal view.

3 Case Report Fig. 1. Preoperative intraoral photographs. A maxillary right central incisor fractured by trauma. (A) Anterior view. (B) Occlusal view. (C) Periapical radiograph. Fig. 2. Photographs of a socket seal technique. (A) Buccal bone is not intact and immediate implantation is not possible. (B) Taking a soft tissue punch from the palatal donor site. (C) Socket closure with soft tissue graft. Fig. 3. Clinical situation after 4 weeks. (A) Biologically well integrated and clinically healthy gingiva in the area where the implant will later be placed. (B, C) Intraoperative view at the time of implant insertion. 18 Implantology Vol. 19 No. 1, 2015

Fig. 4. Intraoral photographs of implant placement.

(A) After implant insertion in the correct position, autologous bone is placed into the

(B) Filling the buccal gap between the alveolar wall and the implant with Osteon (Dentium)

정하였다. 수직및수평절개를가한후전층판막으로박리하였으며, 6 mm의협측열개골결손을관찰할수있었다 (Fig. 3).

1 12 mm; Straumann, Waldenburg, Switzerland) 매식체를 20 N으로식립하였다 (Fig. 4).

5 cc 및 Rapi-Gide (Dalim Tissen, Seoul, Korea) 를사용하는샌드위치테크닉을사용하여골유도재생술을시행하였다 10 (Fig. 5).

4 Fig. 4. Intraoral photographs of implant placement. (A, B) Correct positioning of the implant. (C) After implant placement. Fig. 5. (A) After implant insertion in the correct position, autologous bone is placed into the buccal defect. (B) Filling the buccal gap between the alveolar wall and the implant with Osteon (Dentium) granules. (C) Bone graft materials are covered with a Rapi-Gide (Dalim Tissen) membrane. 정하였다. 수직및수평절개를가한후전층판막으로박리하였으며, 6 mm의협측열개골결손을관찰할수있었다 (Fig. 3). Lekholm-Zarb 분류에따른골질과골량은 D3/B로판단하였고 Regular CrossFit (diameter mm; Straumann, Waldenburg, Switzerland) 매식체를 20 N으로식립하였다 (Fig. 4). 자가골을먼저매식체위에이식한후 Osteon (Dentium, Seoul, Korea) 0.5 cc 및 Rapi-Gide (Dalim Tissen, Seoul, Korea) 를사용하는샌드위치테크닉을사용하여골유도재생술을시행하였다 10 (Fig. 5). 봉합후 1~2 mm 가량의연조직열개및차폐막의노출이관찰되었다 (Fig. 6). 1주일뒤임시 치아를인접자연치를이용하여접착하였으며, 수술 2주뒤발사를시행하였다. 3개월뒤이차수술을시행하였으며, 부족한협측연조직을보강하기위하여구개에서채득한상피하결합조직을이식하였다 (Fig. 7). 이차수술당시 perio-test value 는 -2였으며, 술후 4개월뒤보철을완료하였다. 수술후관찰기간동안특별한합병증은발생하지않았으며, Nordland-Tarnow 분류에따라 class I의치간유두의소실이관찰되지만협측연조직은잘유지되었으며, 보철물주위치은형태화교합은양호하였다 (Fig. 8). 대한구강악안면임프란트학회지 19 권 1 호,

A small portion of the membrane was still exposed.

(A) Good healing of hard and soft tissue 4 months postoperatively.

(C) Insertion of a healing abutment and sutured. 2.

스텐트를이용한 cone-beam computed tomography 촬영영상을바탕으로구개부의 2 mm 열개및 4 mm의높이가부족할것으로판단하였으며,

수술부위전층판막을거상후제조자의가이드라인에따라골삭제를진행하였으며, 치조정접근법을통해 6 mm의상악동거상을포함 한골이식술을시행후 TS III

5 Case Report Fig. 6. (A, B) Flaps are sutured to allow soft and hard tissue healing and maturation. A small portion of the membrane was still exposed. (C) Postoperative periapical radiograph. Fig. 7. (A) Good healing of hard and soft tissue 4 months postoperatively. (B) Subepithelial connective tissue graft was harvested from the palatal donor site. (C) Insertion of a healing abutment and sutured. 2. Case 2 46세여자환자가상실된상악좌측제1대구치수복을주소로내원하였다. 발치는 2개월전에시행되었으며, 특이할만한전신적병력은없었다 (Fig. 9). 스텐트를이용한 cone-beam computed tomography 촬영영상을바탕으로구개부의 2 mm 열개및 4 mm의높이가부족할것으로판단하였으며, 오스테오톰을이용한상악동거상술을계획하였다 (Fig. 10). 수술부위전층판막을거상후제조자의가이드라인에따라골삭제를진행하였으며, 치조정접근법을통해 6 mm의상악동거상을포함 한골이식술을시행후 TS III (diameter mm; Osstem, Seoul, Korea) 매식체를식립하였다 (Fig. 11). Lekholm-Zarb 분류에따른골질과골량은 D2/C로판단하였고최종식립토크는 30 N이었다. 상악동골이식재와구개부열개에 Bio-Oss (Geistlich Biomaterials, Bern, Switzerland) 를 0.5 g 사용하였으며, 구개부열개에는골이식후흡수성콜라겐차폐막 Rapi-Gide 를사용하여골유도재생술을시행한후일차봉합하였다 (Fig. 12). 3개월뒤이차수술을시행하였으며, 임상적으로확인하였을때 2 mm의구개측열개결손은회복되었고 20 Implantology Vol. 19 No. 1, 2015

placement. (A) Anterior view. (B) Occlusal view.

: Guided Bone Regeneration Using Type-I Collagen

aminopropyl) Carbodiimide in Two Implant

Cone-beam computed tomography pre-implant

6 A B Fig. 8. Intraoral photographs 6 months after implant placement. (A) Anterior view. (B) Occlusal view. Fig. 9. Preoperative intraoral photographs. (A) Anterior view. (B) Occlusal view. A B Jae-Hong Lee et al. : Guided Bone Regeneration Using Type-I Collagen Membrane Cross-Linked by 1-ethyl-3-(3-dimethyl aminopropyl) Carbodiimide in Two Implant Dehiscence Fig. 10. Cone-beam computed tomography pre-implant assessment. (A) Axial view. (B) Sagittal view. (C) Coronal view. Jae-Hong Lee et al. : Guided Bone Regeneration Using Type-I Collagen Membrane Cross-Linked by 1-ethyl-3-(3-dimethyl aminopropyl) Carbodiimide in Two Implant Dehiscence 대한구강악안면임프란트학회지 19 권 1 호,

Case Report A B Fig. 11. Intraoral photographs of implant placement.

: Guided Bone Regeneration Using Type-I Collagen Membrane Cross-Linked by

alveolar wall and the implant with Bio-Oss (Geistlich Biomaterials)

(B) Bone graft materials are covered with a Rapi-Gide (Dalim Tissen)

7 Case Report A B Fig. 11. Intraoral photographs of implant placement. (A, B) Correct positioning of the implant. Jae-Hong Lee et al. : Guided Bone Regeneration Using Type-I Collagen Membrane Cross-Linked by 1-ethyl-3-(3-dimethyl aminopropyl) Carbodiimide in Two Implant Dehiscence Fig. 12. (A) After implant insertion, filling the palatal defect between the alveolar wall and the implant with Bio-Oss (Geistlich Biomaterials) granules. (B) Bone graft materials are covered with a Rapi-Gide (Dalim Tissen) membrane. (C) Postoperative periapical radiograph. perio-test value 는 -5였다. 치근단방사선사진상돔형태의골이식부가방사선불투과상을보였으며, 약 5 mm 의높이를유지하고있는것을확인할수있었다. 1개월뒤보철을진행하였으며, 특별한합병증의발생없이전 반적으로양호한치은의형태및치조제폭을유지하였다 (Fig. 13). 22 Implantology Vol. 19 No. 1, 2015

Fig. 13. Good healing of hard and soft tissue 4 months postoperatively. (A) Anterior view. (B) Occlusal view. (C) Periapical radiograph.

일차수술당시연조직열개없는일차봉합을이루었다면더늦은차폐막의흡수와골결손부의이상적인회복을기대할수있었을것으로고려된다. 이차수술을시행하며협측연조직의증대를위하여상피하결합조직이식술을동반함으로써만족스러운협측외형을얻을수있었다.

콜라겐은생체적합성을지니고상처치유및혈관화를촉진시키며, 가교화를통하여생체내분화정도를조절할수있다는장점을가지고있다 8,11,12. 가교화되지않은콜라겐차폐막은 2주후에약 69% 의흡수가일어나는반면에, 가교화된콜라겐차폐막은 4주후에 28.5% 의흡수를보인다고보고되었다 13. 따라서다양한화학적가교화방법들이콜라겐의단백질분해활성에저항을높이는방향으로연구되어왔다.

8 Fig. 13. Good healing of hard and soft tissue 4 months postoperatively. (A) Anterior view. (B) Occlusal view. (C) Periapical radiograph. III 총괄및고찰 첫번째증례에서 6 mm의협측열개결손봉합후연조직열개및차폐막의노출이관찰되었으나특이할만한염증반응없이빠른치유양상을보였으며, 1주일뒤 ovate pontic type의임시치아를이용하여자연스러운치간유두형성을유도할수있었다. 3개월뒤, 이차수술시행시차폐막은모두흡수되었으며임플란트협측 1 mm의열개결손만남아있었다. 일차수술당시연조직열개없는일차봉합을이루었다면더늦은차폐막의흡수와골결손부의이상적인회복을기대할수있었을것으로고려된다. 이차수술을시행하며협측연조직의증대를위하여상피하결합조직이식술을동반함으로써만족스러운협측외형을얻을수있었다. 두번째증례에서는 2 mm의구개측열개결손및 4 mm 높이의골량이부족하여치조정접근법을통하여 6 mm의높이증대및 2 mm의구개측열개결손의완전한회복을얻을수있었다. 일차봉합후, 창상열개없이빠른연조직의회복과만족스러운치조제의외형을얻을수있었다. 콜라겐은생체적합성을지니고상처치유및혈관화를촉진시키며, 가교화를통하여생체내분화정도를조절할수있다는장점을가지고있다 8,11,12. 가교화되지않은콜라겐차폐막은 2주후에약 69% 의흡수가일어나는반면에, 가교화된콜라겐차폐막은 4주후에 28.5% 의흡수를보인다고보고되었다 13. 따라서다양한화학적가교화방법들이콜라겐의단백질분해활성에저항을높이는방향으로연구되어왔다. 특히, 치과영역에서화학적가교화방법으로널리이용되고있는 glutaraldehyde 나 hexamethylene diisocyanate와같은 bifunctional agents 가충분한골생성을위한차폐막의느린흡수를목적으로널리사용되고있다. 하지만이렇게가교화된차폐막은 oligomeric bridges의분해과정중에독성물질을배출하고석회화를유도하는등의단점이존재한다 14. 이에반하여, EDC 가교결합법은 1 nm 이내의결합구조를가지고있기때문에트로포콜라겐분자사이의결합을강화시키며, 효소분해시험에서 EDC로가교화된차폐막은 0.625% glutaraldehyde 로가교화된차폐막에비하여높은저항성을가지고있는것으로보고되었다 15. 또한이러한구조의차폐막은석회화를감소시키고세포차단효과및효소저항성을높여서골형성가능성을높 대한구강악안면임프란트학회지 19 권 1 호,

9 Case Report 이기때문에골유도재생술에장점을가지고있는것으로보인다. EDC로가교화된차폐막은 84~190 μm 크기의공극과 62%~64% 의다공성을가지고있다 15. 일반적으로팽윤이나친수성정도는가교화될수록줄어들게되나, EDC로가교화된차폐막은가교화되지않은차폐막과유사한정도의팽윤성및친수성을보인다. 98% 까지의높은팽윤성은다공성구조와관련이있으며, 차폐막의임상적용시유리한혈액의접촉성과우수한조작성을보인다 15. 실제로본두증례에서골결손부에적용한차폐막은친수성이높아혈액과자연스럽게혼합되었고임상에적용시우수한조작성을확보할수있었다. 본연구의두증례에서이차수술시, 모두임상적으로만족할만한골재생량을확인할수있었다. 또한첫번째증례의경우차폐막의노출에도불구하고경미한염증반응의발생과건강한연조직형태의재연은 EDC로가교화시킨콜라겐차페막의장점을확인할수있었다. 따라서이러한 EDC로가교화시킨콜라겐차폐막의낮은세포독성과높은생체친화성, 그리고느린흡수속도는임플란트식립시골결손부의골재생유도술식에유용하게사용될수있을것으로고려된다. IV 결론 골결손이존재하는치조제에서의임플란트수복에있어서 EDC로가교화된제1형콜라겐차폐막은기능적으로나심미적으로유용하게사용될수있다. References 1. Buser D, Dula K, Hirt HP, et al. Lateral ridge augmentation using autografts and barrier membranes: a clinical study with 40 partially edentulous patients. J Oral Maxillofac Surg. 1996; 54: Trombelli L, Kim CK, Zimmerman GJ, et al. Retrospective analysis of factors related to clinical outcome of guided tissue regeneration procedures in intrabony defects. J Clin Periodontol. 1997; 24: Ling LJ, Hung SL, Lee CF, et al. The influence of membrane exposure on the outcomes of guided tissue regeneration: clinical and microbiological aspects. J Periodontal Res. 2003; 38: Jung RE, Fenner N, Hämmerle CH, et al. Long-term outcome of implants placed with guided bone regeneration (GBR) using resorbable and non-resorbable membranes after years. Clin Oral Implants Res. 2013; 24: Cortellini P, Pini Prato G, Tonetti MS. Periodontal regeneration of human intrabony defects with bioresorbable membranes. A controlled clinical trial. J Periodontol. 1996; 67: Quteish D, Singrao S, Dolby AE. Light and electron microscopic evaluation of biocompatibility, resorption and penetration characteristics of human collagen graft material. J Clin Periodontol. 1991; 18: Bunyaratavej P, Wang HL. Collagen membranes: a review. J Periodontol. 2001; 72: Charulatha V, Rajaram A. Influence of different crosslinking treatments on the physical properties of collagen membranes. Biomaterials. 2003; 24: Hafemann B, Ghofrani K, Gattner HG, et al. Cross-linking by 1-ethyl-3- (3-dimethylaminopropyl)-carbodiimide (EDC) of a collagen/elastin membrane meant to be used as a dermal substitute: effects on physical, biochemical and biological features in vitro. J Mater Sci Mater Med. 2001; 12: Wang HL, Misch C, Neiva RF. "Sandwich" bone augmentation technique: rationale and report of pilot cases. Int J Periodontics Restorative Dent. 2004; 24: Ghanaati S. Non-cross-linked porcine-based collagen I-III membranes do not require high vascularization rates for their integration within the implantation bed: a paradigm shift. Acta Biomater. 2012; 8: Locci P, Calvitti M, Belcastro S, et al. Phenotype expression of gingival fibroblasts cultured on membranes used in guided tissue regeneration. J 24 Implantology Vol. 19 No. 1, 2015

10 Periodontol. 1997; 68: Lee EU, Cheryl-Yang, Hwang JW, et al. Early healing processes in guided bone regeneration using cross-linked type-i collagen membrane at rabbit calvarial defect. Biomaterials Research. 2012; 16: Simmons DM, Kearney JN. Evaluation of collagen cross-linking techniques for the stabilization of tissue matrices. Biotechnol Appl Biochem. 1993; 17: Park SN, Park JC, Kim HO, et al. Characterization of porous collagen/ hyaluronic acid scaffold modified by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide cross-linking. Biomaterials. 2002; 23: 대한구강악안면임프란트학회지 19 권 1 호,

01)13-2목차1~3

01)13-2목차1~3 Guided bone regeneration on a single tooth with horizontal and vertical bone loss Ji-Eun Song, Ji-Youn Hong, Chang-Sung Kim, Kyoo-Sung Cho, Chong-Kwan Kim, Seong-Ho Choi Department of Periodontology, Research