콜라겐하이드로젤/나노수산화인회석/2형골형성단백질 복합체 코팅이 임플란트 골유착에 미치는 영향

학위논문 (박사)-- 서울대학교 대학원 : 치의학과 구강악안면외과학 전공, 2013. 8. 이종호.연구배경 및 목적: 본 연구의 목적은 콜라겐 하이드로젤 (Col)/나노하이드록시 아파타이트 (nHAp)/ 2형골형성단백질 (BMP-2) (Col/nHAp/BMP-2) 복합체를 제작하여 그 효과를 검증하고, 이 복합체를 타이타늄 표면에 코팅했을 때의 골유도 효과와 임플란트 표면에 코팅했을 때 생체 내 골융합능을 확인하는 것이다. 재료 및 방법: 1형아텔로콜라겐 파우더, 콘드로이틴-6-설페이트, 나노수산화인회석, 2형골형성단백질을 0.001N의 염산에 용해시켜 Col/nHAp/BMP-2 복합체를 제작하였다. 마우스 피하에 Col/nHAp/BMP-2 복합체를 주입하고 4주 후에 희생하여 골형성 마커의 발현을 관찰하였고, 이 복합체가 코팅된 타이타늄 디스크의 표면 거칠기와 표면 친수성, BMP-2의 방출정도를 측정하였다. 또한 코팅된 디스크에 골수유래중간엽줄기세포를 배양하여 골형성 마커의 발현을 분석하였고, Col/nHAp/BMP-2복합체를 타이타늄 임플란트에 코팅하여 토끼 양쪽 경골에 식립하고, 4주 후 골-임플란트 접촉율, 신생골 형성면적, 제거토크를 평가하였다. 결과: 마우스 피하 주입 실험에서 Col/nHAp/BMP-2 복합체는 osteonectin과 CD31의 증가된 발현을 보였다. 복합체를 코팅한 타이타늄 디스크는 친수성이 증가하고 BMP-2의 방출을 5일간 지속시켰다. BM-MSC를 배양했을 때, 코팅한 표면에 있던 중간엽줄기세포가 줄기세포 특성을 크게 상실하였고, 가장 높은 골형성세포 마커의 발현을 보였다. 토끼 경골 임플란트 식립 모델에서 Col/nHAp/BMP-2 복합체를 코팅한 임플란트는 유의할 만한 신생골 형성의 증가를 보였으며, 골-임플란트 접촉율과 제거토크를 향상시켰다. 결론: 본 연구를 통하여 콜라겐하이드로젤/나노하이드록시아파타이트/BMP-2 복합체는 골형성 마커의 발현을 유도하고, 타이타늄 표면 특성을 개선시키고, 주변 세포의 골모세포로의 분화를 유도하였다. 이 복합체를 임플란트 표면에 코팅 하였을 때, 전반적으로 골유착과 관련된 수치의 증가를 보여주었으며, 특히 유의하게 증가된 신생골형성능을 보여주었다. 콜라겐하이드로젤/나노하이드록시아파타이트/BMP-2 복합체를 이용한 치과 임플란트 표면 코팅 기술은 골유착을 개선시킬 수 있는 가능성이 있다고 하겠다.Purpose: The purpose of this study was to evaluate the osteoinductivity of collagen hydrogel (Col) / nanohydroxyapatite (nHAp) / bone morphogenetic protein (BMP) -2 (Col/nHAp/BMP-2) complex and to investigate whether the titanium surface coated with Col/nHAp/BMP2 complex can enhance osseointegration effectively. Materials and Methods: A type I atelocollagen powder, chondroitin-6-sulfate, nHAp, and BMP-2 were dissolved in 0.001 N HCl to fabricate the Col/nHAp/BMP-2 complex. Expression of osteogenic markers were evaluated using mouse subcutaneous model with injecting Col, Col/nHAp or Col/nHAp/BMP-2. To investigate osteogenic potential of bone marrow mesenchymal stem cell (BM-MSC) on coated titanium disc with Col/nHAp/BMP-2 complex, cell culture study and the measuring of the amount of released BMP-2 were evaluated. Finally, the osseointegration potential of titanium implants coated with Col/nHAp/BMP-2 complex was evaluated in rabbit tibia model for 4 weeks by comparing bone-implant contact, new bone formation and removal torque. Results: Mouse subcutaneous pocket injected with Col/nHAp/BMP-2 complex expressed osteonectin and CD31. Titanium discs coated with complex increased the hydrophilicity and the release of BMP-2 from Col/nHA/BMP-2 was maintained for 5 days. Culturing of BM-MSC on discs induced the loss of stemness and increased the expression of alkaline phosphatase activity, glycosaminogrlycan, osteopontin, osteocalcin, osteonectin and osteoprotegrin. Col/nHAp/BMP-2 coated implants in rabbit tibias showed significantly increased new bone formation compared with non-coated implants. Conclusions: Col/nHAp/BMP-2 complex induced the expression of osteogenic markers, increased the surface characteristics when coated on a titanium surface and induced the osteoblastic differentiation of the BM-MSC. Implants coated with Col/nHAp/BMP2 complex showed increased osseointegration values in general with significant improvement in new bone area. These results suggest that surface coating with Col/nHAp/BMP-2 complex has the potential to improve the osseointegration of dental implants.I. Introduction II. Materials and Methods 1. Col/nHAp/BMP2 complex 2. Titanium coated with Col/nHAp/BMP2 complex 3. Statistics III. Results 1. Col/nHAp/BMP2 complex 2. Titanium coated with Col/nHAp/BMP2 complex IV. Discussion V. Conclusions References Table Figures and legends Abstract in KoreanDocto

제대 중간엽줄기세포 및 제대혈 중간엽줄기세포 이식을 이용한 백서 좌골 신경 결손부 재생

Thesis(masters) --서울대학교 대학원 :치의학과 (구강악연면외과학전공),2009.2.Maste

Diagnostic aids for the detection of oral cancer

구강암은 8번째로 호발하는 악성 종양으로, 남성에서는 모든 악성 종양 중 4.5%를, 여성에서는 3.5%를 차지한다. 그중에서 구강편평상피세포암(oral squamous cell carcinoma; OSCC)은 전체 구강암 중 90% 정도를 차지하는데, 치료방법이 발전했음에도 20여년간 이환된 환자의 5년 생존률은 50% 수준에서 별다른 진전을 보이지 못하고 있다. 조기 발견된 구강편평상피세포암 환자의 생존률은 80%에 달하고 기능 유지 등의 예후가 좋기 때문에 구강암의 조기발견에 대한 필요성이 대두되고 있다. 지금까지 구강암 및 그 전암병소를 조기에 발견할 수 있는 선별검사(screening test)는 대부분 시진이나 촉진에 의존해왔다. 그러나 이미 초기 구강암이 조직병리학적으로 확진된 병소 중 25% 가량은 맹검 하의 시진 검사상 정상 점막으로 진단되었다는 사실과, 구강암으로 진단받은 환자의 1/3이 3년 이내에 시진에 의한 구강암 선별검사를 했었는데도 불구하고 이를 발견해내지 못했다는 사실로 미루어, 일반적인 시진/촉진은 구강암 및 구강내 전암병소의 선별검사 방법으로써 매우 제한적인 능력을 갖는다고 결론 내릴 수 있다. 이에 따라 임상적이고 분자적 수준에서 구강암을 조기에 발견할 수 있는 진단 방법을 개발하기 위한 연구들이 행해지고있다. 구강암 진단의 표준은 조직 생검을 하여 병리학적인 검사를 하는 것이지만, 이는 훈련된 의료진이 필요하며 침습적이고 통증이 있으며, 비용이 들고 시간이 소요되기에 자궁경부암에서 사용되는 Papanicolaou smear(Pap smear)와 같은 조직생검을 대체 할 수 있는 검사들에 대한 연구가 진행되고 있다. 임상적으로 구강암의 조기 발견을 위해 개발된것에는 toluidine blue염색법, Oral CDx brush biopsy kit, 타액을 이용한 진단법, Velscope, ViziLite같은 image device가 있다. 현재까지, 위의 방법들이 조직검사에 비해 우월하다는 결과를 보여주고 있지는 않지만, 구강암의 간편 진단 방법을 위해 문헌 조사와 함께 저자가 시행하고 있는 VELscope 및 Vizilite를 이용한 검사에 대해 소개하겠다.N

PRELAMINATED FREE FLAP FOR THE RECONSTRUCTION OF MAXILLARY DEFECTS

Background In contrast to defects of the mandible and mouth floor region, in the defect of maxilla, the availability of firmly attached oral and nasal mucosal linings is needed. In addition to it, in consider of operation field, operating convenience, and esthetics, reconstruction using prelaminated flap is strongly recommended. Therefore we consider the prelaminated flap through the cases that is reconstructed using prelaminated forearm flap and prelaminated scapular flap. Patients and Methods From 2001 to 2008, in OMFS SNUDH, there were 6 cases that had reconstruction using prelaminated forearm free flap and other 3 cases that had reconstruction using prelaminated scapular flap of maxilla. The average age of patients that were reconstructed using prelaminated forearm free flap was 47.5 years, the average prelaminated period (after 1st operation ~ until 2nd operation) was 51.8 days and the average follow-up period after 2nd operation was 35.3 months. As well, the average age of patients that were reconstructed using prelaminated scapular free flap was 37 years, the average prelaminated period (after 1st operation ~ until 2nd operation) was 57 days and the average follow-up period after 2nd operation was 42.3 months. Results Except 1 case that were reconstructed using prelaminated scapular flap, we could get firmly attached oral and nasal stable skin(mucosal like) lining, more adequate thickness flap than any other flap and improved esthetic and functional results in the other 8 cases that were reconstructed using prelaminated flap. The complications of the prelaminated forearm flap cases were inconvenient swallowing, sputum, limitation of mouth opening and difficult mastication. It came from flap shrinkage of the flap in some aspect, as well as other combined operations such as mass resection or RND. The difficult point of the reconstruction of prelaminated scapular flap was the possibility of vascular damage at preparation of flap in 2nd surgery. The damage could cause the failure of the prelaminated scapular flap. And the skin-lining of the prelaminated flap had limitations, so it is needed to study about the cultured oral epithelium-lining flap instead of the skin-lining flap. Conclusion We considered about advantages, complications and notable things of prelaminated flap through maxillary reconstruction cases using prelaminated forearm flap and prelaminated scapular flap so far. Furthermore, we should go on studying for functional reconstruction of prelaminated fasciomucosal flap using cultured oral epithelium.N

LITERATURE REVIEW OF ANTIBIOTICS PRESCRIPTION IN GENERAL DENTAL AND ORAL-MAXILLOFACIAL SURGICAL PRACTICE

Objectives : Administration methods of antibiotics implements a variety for indications and diseases. Therefore, it is impossible to produce a single guideline. Many antibiotics have been prescribed without specific index, by practicians for a long period of time. In general dental practice and oral and maxillofacial surgical practice, there is not a guidelines for antibiotics. Therefore, there is a dependency on pre-existent methods rather than following an exact guideline. Consequently, a controversy was issued that prescription of antibiotics tend to be misused or abused. And it is also direct relation to the tolerance of antibiotics as well. Moving forward, in this review we will be analyzing the exact usage and indication of antibiotics in dental treatment. Materials and Methods : 29 published articles of both domestic and international were researched through Pubmed and Kormed, and the review from these articles were performed accordingly. We examined the administration of antibiotics through the objective usage, that classified prophylactic and therapeutic. Results : For therapeutic usage, empirical prescription is mandatory for the first step. Next is to moderate the empirical prescription depending upon the result of its culture. Administration of antibiotics must be kept for 2days after the symptoms disappear. For a prophylactic use, we can generally pr escribe antibiotics to prevent local infection or systemic infection. Although the method of prescription and neccessity of antibiotics to prevent local in fection are controversial, exact guidelines of antibiotics to prevent systemic infection are established by AHA. Conclusion : Most crucial concept for prescript antibiotics is to determine if it is adequately suitable for all circumstances. In this decision making, a guideline for prescription of antibiotics in various dental surgical practice is necessary. This guideline can reduce the misusage and disusage of a ntibiotics in general dental practices and oral and maxillofacial surgical practices.N

Absorbable Guided Bone Regeneration Membrane Fabricated from Dehydrothermal Treated Porcine Collagen

Purpose: Collagen membranes are used extensively as bioabsorbable barriers in guided bone regeneration. However, collagen has different effects on tissue restoration depending on the type, structure, degree of cross-linking and chemical treatment. The purpose of this study was to evaluate the inflammatory reaction, bone formation, and degradation of dehydrothermal treated porcine type I atelocollagen (CollaGuide?) compared to of the non-crosslinked porcine type I, III collagen (BioGide?) and the glutaldehyde cross-linked bovine type I collagen (BioMend?) in surgically created bone defects in rat mandible. Methods: Bone defect model was based upon 3 mm sized full-thickness transcortical bone defects in the mandibular ramus of Sprague-Dawley rats. The defects were covered bucolingually with CollaGuide?, BioMend?, or BioGide? (n=12). For control, the defects were not covered by any membrane. Lymphocyte, multinucleated giant cell infiltration, bone formation over the defect area and membrane absorption were evaluated at 4 weeks postimplantation. For comparison of the membrane effect over the bone augmentation, rats received a bone graft plus different covering of membrane. A 3×4 mm sized block graft was harvested from the mandibular angle and was laid and stabilized with a microscrew on the naturally existing curvature of mandibular inferior border. After 10 weeks postimplantation, same histologic analysis were done. 원고접수일 2010년 9월 20일, 게재확정일 2011년 1월 4일책임저자 이종호(110-749) 서울시 종로구 연건동 28번지, 서울대학교 치의학대학원 구강악안면외과학교실Tel: 02-2072-2630, Fax: 02-766-4948, E-mail: [email protected] RECEIVED September 20, 2010, ACCEPTED January 4, 2011Correspondence to Jong-Ho Lee Department of Oral and Maxillofacial Surgery, School of Dentistry, Seoul National University 28, Yeongun-dong, Chongro-gu, Seoul 110-749, Korea Tel: 82-2-2072-2630, Fax: 82-2-766-4948, E-mail: [email protected] CC This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Results: In the defect model at 4 weeks post-implantation, the amount of new bone formed in defects was similar for all types of membrane. Bio-Gide? membranes induced significantly greater inflammatory response and membrane resorption than other two membranes; characterized by lymphocytes and multinucleated giant cells. At 10 weeks postoperatively, all membranes were completely resorbed. Conclusion: Dehydrotheramal treated cross-linked collagen was safe and effective in guiding bone regeneration in alveolar ridge defects and bone augmentation in rats, similar to BioGide? and BioMend?, thus, could be clinically useful.N

GORHAM-STOUT DISEASE OF THE MANDIBLE: A CASE REPORT

Gorham-Stout disease is a rare skeletal disease which is progressive and spontaneous and idiopathic resorption of whole body bone. In the initial stage, the osteolytic site is replaced by histologically benign vascular proliferation without new bone formation and finally by dense fibrous tissues. We encountered with a patient involving the mandible with attention by the clinical, radiographic, scintigraphic, angiographic, and computed tomography. We resected the mandibular lesion which was reconstructed with a fibular free flap. We report literature review with a mandibular lesion involved with Gorham-Stout disease.N

Sinus floor grafting using calcium phosphate nano-crystal coated xenogenic bone and autologous bone

Purpose: Rehabilitation of the edentulous posterior maxilla with dental implants often poses difficulty because of insufficient bone volume caused by pneumatization of the maxillary sinus and by crestal bone resorption. Sinus grafting technique was developed to increase the vertical height to overcome this problem. The present study was designed to evaluate the sinus floor augmentation with anorganic bovine bone (Biocera TM) using histomorphometric and clinical measures. Patients and methods: Thirteen patients were involved in this study and underwent total 14 sinus lift procedures. Residual bone height was ≥2mm and ≤6mm. Lateral window approach was used, with grafting using Bio-cera™ only(n=1) or mixed with autogenous bone from ramus and/or maxillary tuberosity(n=13). After 6 months of healing, implant sites were created with 3mm diameter trephine and biopsies taken for histomorphometric analysis. The parameters assessed were area fraction of new bone, graft material and connective tissue. Immediate and 6 months after grafting surgery, and 6 months after implantation, computed tomography (CT) was taken and the sinus graft was evaluated morphometric analysis. After implant installation at the grafted area, the clinical outcome was checked. Results: Histomorphometry was done in ten patients. Bio-cera™ particles were surrounded by newly formed bone. The graft particles and newly formed bone were surrounded by connective tissue including small capillaries in some fields. Imaging processing revealed 24.86±7.59% of new bone, 38.20±13.19% connective tissue, and 36.92±14.51% of remaining Bio-cera™ particles. All grafted sites received an implant, and in all cases sufficient bone height was achieved to install implants. The increase in ridge height was about 15.9±1.8mm immediately after operation (from 13mm to 19mm). After 6 months operation, ridge height was reduced about 11.5±13.5%. After implant installation, average marginal bone loss after 6 months was 0.3±0.15mm. Conclusion: Bio-cera™ showed new bone formation similar with Bio-Oss histomorphometrically and appeared to be an effective bone substitute in maxillary sinus augmentation procedure with the residual bone height from 2 to 6mm.N