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1 20 동종골 SureFuse TM 를이용한골결손부의치험례 * 한스바이오메드, ** 가톨릭대학교대전성모병원구강외과, # 청주다인치과보철과, *** 을지대학교정형외과, 서석진 *, 김진 **, 임헌송 #, 이광원 ***, 김수용 *, 김태운 *, 송석범 *, 김진영 *, 안재형 *, 채지화 *, 황호찬 *, 강계원 * I. 서론동종골은사람의사체에서얻어지는이식재로서공신력이있는조직은행에서획득되어관리되며엄격한공정과정을거쳐공급되어지고있다. 동종골이식재에있어서안정성의중요한이유는후천성면역결핍증 (HIV) 기타치명적인병등의전파가문제가될수있기때문이다. 따라서, 골내잔존및면역학적거부반응, 사전에환자에게 informed consent를받는것이필요하고, 안정성이검증된공신력있는조직은행의제품을쓰는것이중요하다. 동종골의사용개념은동종골의골유도성과골전도성이다. FDBA (Freeze-Dried Bone Allograft) 는 mineral 성분이있기때문에 Scaffold ( 비계 ) 역할을주로하여골전도를통하여골형성을한다. Meffert에의하면 DFDBA (Demineralized Freeze-Dried Bone Allograft) 를이용하여상악동에골이식을할경우 6개월후에연골성물질이관찰되었고, 골과유사한단단한경조직이나타났다고하였다. DFDBA는 demineralization 과정을통하여 bone matrix의 BMP(Bone Morphogenetic Protein) 를노출시켜골유도를통하여골형성을한다고알려져있다. DFDBA는골유도성의이론적근거하에개발초기에치주치료에널리사용되었다. Pinholt 등과 Nevins & Mellonig 그리고 Mellonig 등의초기의연구들은주로 DFDBA의골유도능력을입증하는결과를발표하였고또다른 Aspenberg 등과 Buser 등은 DFDBA의골유도능력에대해의문을제기하고있다. Fugazzoto 등과 Stentz 등의연구에서는 DFDBA를이용하여차폐막의붕괴를막아주기위한재료로이용하였다. Tatum은방사선조사된망상골도이식재로서사용보고하였다. Price 등의조직형태학적연구에의하면상악동거상술시 irradiated cancellous bone이가장좋은이식재라고주장하고있으며 Manual Chanavaz의 1979년부터 2000년까지의상악동골이식경험을정리한보고에의하면이기간동안 irradiated cancellous bone을전체이식재중 22% 를사용하였는데가장효과적이었다. 동종골은공여를위한수술이불필요하고부가적인수술없이많은양을얻을수있는장점이있기때문에필요에따라차폐막을지지하는골이식재로서또한골유도물질로서사용되면좋은결과를얻을수있다. 본증례는여러동종골이식재중 SureFuse TM (Hansbiomed Corp. Korea) 를이용하여하악구치부발치와의골결손부에사용한증례에서시간경과후이식부의조직소견과함께동종골로서의기능등에관해살펴보았다. II. 증례보고 1) 환자 ; 김 OO (F/52) 2) 주소 ; 하악우측제 2대구치의동통과동요 3) 진단및치료계획 ; 하악우측제 1대구치원심부치근단농양개인치과몇군데로부터발치후보철치료를권유받고찾아오신분으로발치를전제로 SureFuse TM 이식에 본연구는산업자원부솔 젤하이브리드생체재료및응용기술개발 ( ) 에의해지원되었으며이에감사드립니다.

21 의한치료를진행하기로하고시행하였다. 4) 치료 ; 거주지거리상 3~4개월에한번씩검사만시행하였다.

SureFuse TM 를처리하기전과후를비교하여 X-ray 검사를시행하였다 ( 그림 1). 골결손부를 SureFuse TM gel 0.5cc 로수복시행하였다.

그림 1에서는 SureFuse TM 을처리전 (a) 과후 (b) 에따라서 X-ray 결과가달라짐을알수있다.

2 Histological pictures at three months after treatment with SureFuse TM ; (a) H&E and (b)

2 21 의한치료를진행하기로하고시행하였다. 4) 치료 ; 거주지거리상 3~4개월에한번씩검사만시행하였다. 이후 1년경과후무통, 무동요등의개선양상을보이고보철치료를원하여근관치료중인상태이다. SureFuse TM 를처리하기전과후를비교하여 X-ray 검사를시행하였다 ( 그림 1). 골결손부를 SureFuse TM gel 0.5cc 로수복시행하였다. 처리부위의골조직을채취하여조직검사로 HE와 MT 염색을시행하였다 ( 그림 2). 그림 1에서는 SureFuse TM 을처리전 (a) 과후 (b) 에따라서 X-ray 결과가달라짐을알수있다. 또한그림 2의조직검사에서는화살표에서보이는바와같이 3개월후에 osteocyte가형성됨을알수있었다. (a) (a) (b) Fig. 2 Histological pictures at three months after treatment with SureFuse TM ; (a) H&E and (b) MT staining. III. 총괄및고찰 (b) Fig. 1 Radiographic finding of (a) before and (b) after treatment with SureFuse TM. implant 주위골결손을치료하기위해서임상적으로골재생술식이성공적으로이루어지고있다. 긍정적인결과는장기간의임상연구와막이흡수성인지비흡수성인지그리고막의사용여부, 그리고막의흡수성혹은비흡수성에따라확실히결정된다. 발치후골결손부에식립시골결손을치료하기위해서여러가지방법이제안되었다. 자가골혹은 DFDBA의사용시에는합성생체재료막혹은천연콜

3 22 라겐이혼합되거나흡수성혹은비흡수성막을같이사용하기도한다. 환상형혹은 3벽성골내결손은골재생이가장잘일어나며작은특별한골재생술식이필요하지않다. implant와골벽사이의거리가 1.5~2mm 보다큰경우에는생체재료 (bio material) 나자가골을빈공간에채워넣는것을추천한다. 자가골의사용시에는 200~400rpm 의저속으로큰회전 (45NCm) 을사용하여 implant 부위에서골삭제를시행하는동안에쉽게얻을수있다. 선택된골재생물질과그와관련된재료들은다음에쉽게다루기위해 dappen dish에올려놓고증류수를몇방울떨어뜨려서수화시킨다. 열개 (dehisences) 와천공 (fenestration) 은자가골치유능력이있음에도불구하고골재생술식이필요하다. 3벽성골결손에서이미언급한자가골과생체재료 (biomaterial) 를혼합한섬유소봉합제 (fibrin sealant) 를골결손과임플란트계면사이에서안정성을위해사용되기도한다. 큰결손부의경우일반적으로 1차연조직치유를얻은후다양한골이식재를이용한이식법이추천되나때론생체재료 (biomaterials) 와섬유소봉합제 (fibrin sealant) 의혼합물을사용하기도한다. 발치후골결손부가보인경우에는발치와의기저부와구개측벽의변연부사이의열개부를식립후 1차고정을치근단과구개측벽에서얻기위해골삭제술을시행하고단백직을제거한뼈의미네랄과섬유소를혼합해서결손부에채워넣는다. 봉합제 (sealant) 가굳기를기다린후에판막을치관부로위치시킨다. 이것은 1차치유를얻기위해봉합하는것이다. 6개월후 implant를노출시켜보면완전한골재생이보인다. 골활성이란말은일반적으로사용되어지지않았었다. 이와유사한개념으로는 1971년 Urist가 osteoinduction 이란말을쓴것에서유래한다. Osteoinduction이란말이처음나올때는골기질내에존재하는단백질인 BMP에대한것이었는데, 최근에와서는골기질내의 BMP 외에도다른곳에존재하는 growth factor나합성물중에도골의생성을촉진하 는여러물질이있기때문에보다포괄적인의미에서 osteoactive 란말을쓰게되었다. 골유도능은약리적인작용으로이식재료에포함된 BMP의농도에의존하다. BMP를포함한재료로는자가골, 동종골, rhbmp-2, rhbmp-7이있다. rhbmp-2와 rhbmp-7은그자신에의해골형성을일으키지만, 특히 BMP-2를콜라겐에포함시켜사용한경우에는신속한골형성이생긴다. 골유도능을갖는이식재료를사용한경우에는신속한골형성이생긴다. 그러나여러가지이식재료가어떻게혈관신생과골신생, 화골, osseointegration, remodeling에관여하고있는지를명확하게이해하려면앞으로의연구가더욱필요하다. 또한이러한명확한연구가치유기전과최적의이식재료를결정할수있고치유의판정에도도움된다. 다른이식재료라도성공률에차이는없고또많은요인이관여하고있으므로한종류의이식재료와수술방법이뛰어나다고는말할수없었다. REFERENCES Ashok Sethi, Thomas Kaus (2005) Practical implant dentistry diagnostic, surgical, restorative and technical aspects of aesthetic and functional harmaony. Ch. 15 p , Quintessence Publishing Co. Ltd. Printed in Germany. Aspenberg P, Kalebo P & Albrekssen T (1988) Rapid bone healing delayed by bone matrix implantation. International Journal of Oral & Maxillofacial implants. 3;p123~127 Becker W, Urist MR, Tucker LM, Becker BE, and Ochsenbein C. (1995) Human demineralized freeze-dried bone: inadequate induced bone formation in athymic mice. A preliminary report. J Periodontol 66: p Bo Han, Baowei Tang, Marcel E. Nimni (2003) Quantitative and sensitive in vitro assay for

4 23 osteoinductive activity of demineralized bone matrix. J Orthop Res 21: p Buser D, Bernard JP, Hofmann B, Lussi A, Mettler D & Schenik RK (1998) Evaluation of bone filling materials in membrane protected defects of the mandible. A histomorphometric-study in miniature psigs. Clinical Oral Implants Research 9;p137~150 Cameron M.L. Clokie, Hassan Moghadam, Michael T.Jackson, George K.B. Sandor (2002)Closure of critical sized defects with allogenic and alloplastic bone substitutes vol 13, no. 1, p111~121 Cammisa FP Jr. et al (2004) Two-year fusion rate equivalency between Grafton DBM gel and autograft in posterolateral spine fusion. Spine 29: p Chung-Hung Tsai et al. (2002) A composite Graft Material containing bone particles and collagen in osteoinduction in mouse. J Biomed Mater Res. 63: p65-70 Clokie CML, Hassan Moghadam, Jackson MT, Sandor GKB (2002) Closure of Critical sized defects with allogenic and alloplastic bone substitutes. J Craniofacial Surg 13: Coulson R, Clokie CML, Peel SAF. (1999) Collagen and a thermally reversible poloxamer deliver demineralized bone matrix(dbm) and biologically active proteins to sites of bone regeneration. Portland Bone Symposium. p Georgios Romanos (2005) Immediate loading of endosseous implants in the posterior area of the mandible. Ch. 3 p , Quintessence Publishing Co. Ltd. Printed in Germany. Fugazzoto PA, Shanaman R, Manos T & Shecrtman R (1997) Guided bone regeneration around titanium implants ; report of the treatment of 1,503 sites with clinical reentries. International Journal of Oral & Maxillofacial Implants 17;p293~299 Jortika L, Laitinen M, Wiklund J, Lindholm TS, and Marttinen A. (1998) Use of myoblasts in assaying the osteoinductivity of bone morphogenetic proteins. Life Sciences 62: p Meffert Ra. (1998) Current usage of bone fill as an adjunct in implant dentistry. Dent Implant dentisrty. Dent Implantol Update 9;p9~12 Mellonig JT, Nevins M & Sanchez R (1998) Evaluation of a bioabsorable physical barrier for guided bone regeneration, Part II. Material and a bone replacement graft. International Journal of Periodontics and Restorative dentistry. 19;p139~149 Nevina M, & Mellonig JT (1992) Enhancement of the damaged edentulous ridge to receive dental implants : a combination of allograft and Gore-Tex membrane. International Journal of Periodontics and Restorative dentistry. 12;p97~111 Peel SAF, Clokie CML, Coulson R. (1999) A simple in vitro assay to measure the osteo inductive activity of implants made with human demineralized bone matrix(hdbm). J Bone Mineral Research 14: S218 Pinholt EM, Bang G & Hanaes HR (1990) Alveolar ridge augementation by osteoinduction in rats. Scandinvian Journal of Dental Research 98;p434~441 Shteyer A, Kaban LB, Kao RT. (1990) Effect of demineralized bone powder on osteoblast-like cells in culture. Int J Oral Maxillofac Surg 19: p Stentz WC, Mealey BL, Nummikoski PV, Gunsolley JC & Waldrop TC (1993) Effect of guided bone

5 24 regeneration around commercially pure titanium and hydroxyapatite-coated dental implants. I. Radiographic analysis. Journal of Periodontology 68;p199~208 Summers RB (1994) A new concept in maxillary implant surgery : The osteotome technique. Compend Contin Educ Dental 15;p698 Tatum H Jr. (1986) Maxillary and sinus implant reconstructions. Dent Clin North Am 30;207 Tatum OJ Jr, Lebowitz MS, Tatum CA, Borgner RA (1993) Sinus augmentation : Rationale, Development, long-term results. NY state Dent J. May;p43~48 Tatum OJ Jr (1996) Osseous grafts in intra-oral sites. J Oral Implantol 22;p51~52 Schwartz Z et al. (1996) Ability of commercial demineralized freeze-dried bone allograft to induce new bone formation. J Periodontol 67: p Wolfinbarger L. (1998) Assessment of Dynagraft TM Putty and Gel(GenSci Regeenration Sciences) versus LifeNet DFDBA. LifeNet Research Report: January Zhang M, Powers RM, Wolfinbarger A. (1997) A quantitative assessment of osteoinductivity of human demineralized bone matrix. J Periodontol 68: p

6 25 Abstract Clinical Case of Alveolar Bone defect using Allograft SureFuse TM Seog-jin Seo *, Jin Kim **, Heon-song Lim #, Kwang-won Lee ***, Soo-yong Kim *, Tae-woon Kim *, Seok-bum Song *, Jin-young Kim *, Jae-hyung Ahn *, Ji-wha Chae *, Ho-chan Hwang *, Ke-won Kang * * Hans Biomed Corp., Korea ** Oral and Maxillofacial Surgery, Deajeon ST. Mary's Hospital, The Catholic University of Korea, Korea # Prosthodontics, Dain Dental Clinic, Korea *** Orthopedic Surgery, Eulji University Hospital, Korea. The purpose of this study was to evaluate the efficacy of allograft SureFuse TM which is an allograft product applicable for alveolar bone defect. SureFuse TM is composed mainly of demineralized human bone matrix that has several advantageous properties compared with other products in biocompatibility and bone inductions. Repair process was examined by radiograph and histological sections. After 3 months of treatments, SureFuse TM showed regenerative effect for alveolar bone defect. We assume the results by release of bone morphogenetic proteins which may play a role of osteoinduction. Key words ; alveolar, bone defect, demineralized bone matrix, allograft

12-3전체

12-3전체 The histologic study of the effect of enamel matrix protein and -tricalcium phosphate in gap defect model in dogs : pilot study Lim Hyun-Chang 1, Yang Jin-Hyuk 1, Chae Gyoung-Joon 1, Kim Sung-Tae 1, Jung