• Maxillofacial Plastic and Reconstructive Surgery
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• 제19권3호
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• pp.265-286
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• 1997

Bone morphogenetic proteins(BMPs) are a group of transforming growth factor beta(TGF-${\beta}$)-related factors and multifunctional proteins, especially the only known biologic factors capable of inducing endochondral bone formation at an extraskeletal site. This study was performed to investigate the effect of the partially purified porcine BMP(pBMP) at an ectopic site. PBMP was partially purified from porcine bone matrix and its activity was monitored by an in vivo bioassay. The purification method utilized extraction of the bone-inducing activity with 4M guanidine, followed by chromatography on heparin-Sepharose. Active fractions were assayed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. And the fractions were reconstituted with inactive insoluble collagenous bone matrix from rats, acid soluble type I collagen from rat tail and chondroitin-6-sulfate sodium salt and implanted into the pectroralis muscle pouches of Sprague-Dawley rats. And the carrier complex was implanted on the opposite side as control. The rats were sacrificed at the day of 1st, 3rd, 5th, 7th, 11th, 14th and 21st after implantation and examined histologically, radiologically and biochemically. And alkaline phosphatase activity and calcium content were used as indices of bone formation. The results were as follows ; 1. Active fractions were localized in a zone between 31 and 40 KDa on SDS-PAGE. 2. The implanted 3.0mg of the partially purified pBMP induced cartilage and bone in the muscle tissue of rats through an endochondral ossification process. 3. Inactive insoluble bone matrix, type I collagen and chondroitin-6-sulfate have functioned as carriers for pBMP, but revealed some foreign body reactions. 4. Soft X-ray didn't reveal significant change between the experimental and the control group. 5. The alkaline phosphatase activities in the experimental group of 5th, 7th, 11th, 14th and 21st were increased significantly compared with control (p<0.01) with the peak in the group of 11th day. 6. With time, the calcium content of the experimental group increased. And the calcium contents in the experimental group of 11th, 14th and 21st were increased significantly compared with control (p<0.01).

• Journal of Periodontal and Implant Science
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• 제31권1호
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• pp.1-23
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• 2001

Chitosan is biodegradable natural polymer that has been demonstrated its ability to improve wound healing, and calcium metaphosphate(CMP) is a unique class of phosphate minerals having a polymeric structure. In this study, chitosan/CMP and platelet derived growth factor(PDGF-BB) loaded chitosan/CMP sponges were developed, and the effect of the sponges on bone regeneration and their possibility as scaffolds for bone formation by three-dimensional osteoblast culture were examined. PDGF-BB loaded chitosan/CMP sponges were prepared by freeze-drying of a mixture of chitosan solution and CMP powder, and soaking in a PDGF-BB solution. Fabricated sponge retained its 3-dimensional porous structure with $100-200\;{\mu}m$ pores. The release kinetics of PDGF-BB loaded onto the sponge were measured in vitro with $^{125}I-labeled$ PDGF-BB. In order to examine their possibility as scaffolds for bone formation, fetal rat calvarial osteoblastic cells were isolated, cultured, and seeded into the sponges. The cell-sponge constructs were cultured for 28 days. Cell proliferation, alkaline phosphatase activity were measured at 1, 7, 14 and 28 days, and histologic examination was performed. In order to examine the effect on the healing of bone defect, the sponges were implanted into rat calvarial defects. Rats were sacrificed 2 and 4 weeks after implantation and histologic and histomorphometrical examination were performed. An effective therapeutic concentration of PDGF-BB following a high initial burst release was maintained throughout the examination period. PDGF-BB loaded chitosan/CMP sponges supported the proliferation of seeded osteoblastic cells as well as their differentiation as indicated by high alkaline phosphatase activities. Histologic findings indicated that seeded osteoblastic cells well attached to sponge matrices and proliferated in a multi-layer fashion. In the experiments of implantation in rat calvarial defects, histologic and histomorphometric examination revealed that chitosan/CMP sponge promoted osseous healing as compared to controls. PDGF-BB loaded chitosan/CMP sponge further echanced bone regeneration. These results suggested that PDGF-BB loaded chitosan/CMP sponge was a feasable scaffolding material to grow osteoblast in a three-dimentional structure for transplantation into a site for bone regeneration.

• Journal of Chest Surgery
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• 제35권2호
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• pp.94-101
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• 2002

배경: 모든 조직판막은 면역학적인 불활성화 및 내구성 강화를 위하여 이식 전 터치를 필요로 한다. 그러나 조직 판막은 이식 후 점차적인 석회화 과정을 보이며, 결국 판막의 기능을 상실하게 된다. 최근 석회화 과정의 병리기전에 관한 연구에서는 이식된 조직판막의 석회화 부위에서 정상 골성석회화에 관련하는 결합단백이 검출되기에 이르렀다. 본 실험은 이러한 결합단백의 공통 결합부인 RGD(Arg-Gly-Asp)를 갖는 RGDStetrapeptide를 이식 전 조직에 처치하여 이식 후 숙주의 골성석회화 관련 결합단백의 결합을 억제하는 것이 석회화과정에 영향을 줄 수 있는가를 확인하기 위하여 계획되었다. 대상 및 방법: 실험은 소 심낭을 0.6%글루타알데하이드에 처치한 후 이를 작은 절편으로 나누어 1군은 생리식염수에서 60분간 처리, 2 군은 RGDS와 같은 분자량을 갖는 0.5% GRSD tetrapeptide에서 60분간 처리, 3군은 0.5% RGDS에서 30분간 처리, 4군은 0.5% RGDS에서 60분간 처리, 5군은 0.5% RGDS에서 120분간 처리하였다. 이렇게 처리된 소 심낭절편을 흰쥐의 복부 피하에 이식하였으며, 30일 후 채취하여 방사선 검사와 생화학적 검사 및 조직학적 검사를 시행하여 이식절편의 석회화 정도를 판정하였다. 결과: 이식절편을 방사선 촬영 후, 측정한 음영도는 3, 4, 5군에서 48.00$\pm$3.57, 43.67$\pm$2.31, 42.58$\pm$2.47로 1, 2군의 68.42$\pm$3.06, 64.25+5.58과 통계학적인 차이를 보였다(p<7.05). 1군과 2군간의 유의한 차이는 없었다(p=0.105). 생화학적 검사에서 이식절편의 칼슘 총량은 1군 33.09$\pm$6.59mg, 2군 28.12+5.5mg,, 3군 25.42+7.67mg,, 4군 20.51$\pm$5.11mg, 5군 15.43$\pm$4.25mg을 보여, 5군이 1, 2, 3군에 비하여 통계적으로 유의하게 석회화 정도가 감소되어 있었다(<0.05). 1군과 2군간에 유의한 차이는 없었다(p=0.388). 조직학적 검사에서는 1, 2군에서 현저한 칼슘침착을 확인할 수 있었으며 3, 4군은 적은 양의 칼슘침착을 보여주는 반면, 5군에서는 뚜렷할 칼슘 침착 부를 확인할 수 없었다. 결론: 이상의 결과에서 이식 전 RGDS tetrapeptide를 처치하는 것이 흰쥐의 똑부 피하에 이식된 소 심낭절편의 석회화를 억제하는 효과가 있음을 확인할 수 있었다.

• Journal of Chest Surgery
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• 제44권2호
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• pp.115-122
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• 2011

Background: The intramural coronary artery has been known as a risk factor for early death after an arterial switch operation (ASO). We reviewed the morphological characteristics and evaluated the early and mid-term results of ASO for patients with an intramural coronary artery. Materials and Methods: From March 1994 to September 15th 2010, 158 patients underwent ASO at Dong-A and Pusan National University Hospitals for repair of transposition of the great arteries and double outlet right ventricle. Among these patients, 14 patients (8.9%) had an intramural coronary artery. Mean age at operation was $13.4{\pm}10.2$ days (4 to 39 days) and mean body weight was $3.48{\pm}0.33$ kg (2.88 to 3.88 kg). All patients except one were male. Eight patients had TGA/IVS and 4 patients had an aortic arch anomaly. Two patients (14.3%) had side-by-side great artery relation, of whom one had an intramural right coronary artery and the other had an intramural left anterior descending coronary artery. Twelve patients had anterior-posterior relation, all of whom had an intramural left coronary artery (LCA). The aortocoronary flap technique was used in coronary transfer in 8 patients, of whom one patient required a switch to the individual coronary button technique 2 days after operation because of myocardial ischemia. An individual coronary button implantation technique was adopted in 6, of whom 2 patients required left subclavian artery free graft to LCA during the same operation due to LCA injury during coronary button mobilization and LCA torsion. Results: There was 1 operative death (7.1%), which occurred in the first patient in our series. This patient underwent an aortocoronary flap procedure for coronary transfer combining aortic arch repair. Overall operative mortality for 144 patients without an intramural coronary artery was 13.2% (19/144). There was no statistical difference in operative mortality between the patients with and without an intramural coronary artery (p>0.1). There was no late death. The mean follow-up duration was $52.1{\pm}43.0$ months (0.5 to 132 months). One patient who had a subclavian artery free graft required LCA stenting 6.5 years after surgery for LCA anastomotic site stenosis. No other surviving patient needed any intervention for coronary problems. All patients had normal ventricular function at latest echocardiography and were in NYHA class 1. Conclusion: The arterial switch operation in Transposition of Great Arteries or Double Outlet Right Ventricle patients with intramural coronary can be performed with low mortality; however, there is a high incidence of intraoperative or postoperative coronary problems, which can be managed with conversion to the individual coronary button technique and a bypass procedure using a left subclavian free graft. Both aortocoronary flap and individual coronary button implantation techniques for coronary transfer have excellent mid-term results.

• Clinical and Experimental Reproductive Medicine
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• 제23권3호
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• pp.247-268
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• 1996

여포와 난포의 성숙, 배란과 착상, 임신의 유지와 태아의 성장 발달, 분만 및 유선발육과 비유 등 일련의 생식현상에서 있어서 성선자극호르몬과 스테로이드 호르몬의 작용이 중추적인 역할을 한다는 사실은 오래 전부터 알려져왔다. 그러나 이러한 일련의 현상에 고전적인 호르몬 외에도 다수의 성장인자가 관여되고 있음이 최근의 연구 결과 밝혀지고 있다. 생식기관에서 성장인자들은 대부분 autocrine/paracrine mode로 작용하여, 성선자극호르몬과 스테로이드 호르몬의 작용을 매개하거나 이들 호르몬 등과 교호적인 작용(synergy)을 한다. 생식기관 내 insulin-like growth factor(IGF) system은 최근 가장 활발히 연구된 분야 중의 하나로 생식현상의 전반에 걸쳐 중요한 역할을 하고 있음이 밝혀졌다. 본 지면에서는 IGF system에 관한 개괄적인 정보를 소개하고 현재까지 보고된 intrauterine IGF system에 관한 연구를 요약하고자 한다. IGF family는 IGF-I과 IGF-II ligands, 두종류의 IGF receptors(수용체), 그리고 지금까지 발견된 6종류의 IGF-binding proteins(IGFBPs)로 이루어져 있다. IGF-I과 IGF-II는 proinsulin과 상동한 구조를 가진 peptide로서 포도당과 아미노산 운반을 자극하는 등 insulin과 유사한 작용을 한다. 이 외에도 IGFs는 세포분열촉진제(mitogens)로서 여러 형태의 세포에 걸쳐 세포증식을 자극하고, 세포의 분화(differentiation)과 세포기능의 발현에 관여한다. IGFs는 간과 주로 messenchymal cells에서 발현되어 endocrine mode는 물론 autocrine/paracrine mode로 거의 모든 조직에 작용한다. IGF 수용체는 두종류가 알려져 있는데 type I IGF receptor는 tyrosine kinase로서 IGF-I과 IGF-II에 공히 high-affinity를 나타내고, 상기한 대부분의 IGFs의 작용을 매개한다. Type II IGF receptor 혹은 IGF-II/mannose-6-phosphate receptor는 두개의 서로 다른 binding sites를 가지고 있는데 IGF-II binding site는 IGF-II에만 high-affinity를 나타낸다. Type II IGF receptor의 주요 역할은 IGF-II를 lysosomal targeting하여 ligand를 파괴하는데 있다. 체액 속의 IGFs는 대부분 IGFBP에 결합되어 있다. IGFBPs는 IGF의 저장/운반체 혹은 IGF 작용을 조절하는 역할을 하는 것으로 알려져 있으나 개개 IGFBP의 역할에 대해서는 지극히 제한된 정보만이 알려져 있다. IGFBPs의 IGF ligands에의 affinity는 IGF receptors의 IGFs에의 affinity보다 크기 때문에 대부분의 in vitro 상황 하에서 IGFBPs는 IGF 작용을 억제한다. IGFBP에 결합되어 있는 IGF가 어떤 기작에 의해 IGFBP로부터 분리되어 IGF receptor에 도달하는지는 알려지지 않고 있으나, 혈액과 조직액에 들어있는 불특정 IGFBP protease activity는 IGF의 방출과정에서 일역을 하는 것으로 믿어지고 있다. 최근 연구보고에 의하면 특정 in vitro 상황 하에서 IGFBP-1, -3, -5 등은 IGF와 무관한 작용도 있다는 증빙이 있어 IGF system의 또 다른 차원을 예고하고 있다. IGF family members의 mRNAs & proteins는 영장류, 설치류 및 가축의 자궁조직과 수태물(conceptus)에서 발현되어 자궁과 태아의 성장 발달에 중요한 역할을 한다. 자궁조직의 IGF system의 발현은 성선호르몬, 국소 생리조절인자 등에 의해 발현시기와 장소의 특이성이 결정되며, 발현된 IGFs와 IGFBPs는 autocrine/paracrine mode로 자궁조직에 작용하기도 하고, 자궁강에 분비되어 수태물의 성장 발달에 관여한다. 착상을 전후하여 수태물에서도 IGF system이 발현되는데 개개 IGF family member의 발현 시기는 모체로부터 유래된 mRNA의 유무, 수태물 자체의 genetic programming, 모체와의 상호작용 등에 의해 결정되고, IGFs의 작용 부위 역시 시간(생리적 상태)과 장소의 특이성이 있다. 이와같이 conceptus IGF system의 발현이 시간적, 공간적으로 조절되고있다는 사실은 IGFs가 수태물의 성장 발달에 일역을 한다는 가설을 간접적으로 지지해 준다. 자궁조직과 수태물에서 발현된 IGFs는 세포의 증식과 분화, 포도당과 아미노산의 운반과 단백질합성, placental lactogen과 prolactin 등과 같은 유선자극호르몬의 생성을 자극하고 스테로이드 호르몬의 합성에도 관여한다. 태아의 성장 발달에 있어서 IGFs의 역할은 embryo의 IGF-I, IGF-II, 혹은 IGF receptor gene을 homologous recombination technique에 의해 파괴(gene targeting)하여을 때의 결과로써 입증되었다. 생쥐의 IGF and/or IGF-II gene 혹은 IGF receptor gene을 파괴했을 때 출생 전후 모두 성장 발달이 지연되며 출생시 무게는 정상치의 30-60% 수준에 머물고, 특히 type I IGF receptor gene 혹은 IGF-I과 IGF-II genes를 모두 파괴했을 경우에는 출생 후 곧 치사한다. 자궁 내의 IGFBPs는 IGF ligands를 자궁 내에 제한시키거나 IGFs의 receptor binding을 억제하는 negative regulators 역할을 하는 것으로 믿어지고 있다. 그러나 영장류의 자궁에서 IGFBP-I과 같은 특정 IGFBP는 IGFs보다 월등히 많은 양이 발현 분비되고 있는 것으로 추산되고 있으며, 또한 이 단백질은 모체탈락막세포에서 분비되는 주요 단백질 중의 하나라는 점을 감안할 때 IGFBP-I이 IGF과 무관한 작용이 있을 가능성도 배제할 수 없다. 따라서 IGFBPs의 역할 규명은 IGF system을 이해하는데 중요한 부분을 차지하고 있어 향후 이 분야의 연구에 많은 기대와 촛점이 모여지고 있다.

• 대한한의학방제학회지
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• 제16권1호
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• pp.65-78
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• 2008

Objectives : this study was to access the effect of Hyeonggaeyeongyotang water extracts, a polyherbal formula has been used as folk medicine, on the fertility and early embryonic development of male and female Wistar rats when administered by oral gavage. Methods : In male rats, Hyeonggaeyeongyotang extract were dosed 4 weeks before pairing and 2 weeks after mating including the mating periods up to termination after necropsy of the majority of the females. In female rats, they were dosed 2 weeks before pairing, and from Day 0 to Day 7 of gestation. This study was conducted in accordance with the recommendations of the KFDA Guideline [2005-60] for Detection of Toxicity to Reproduction for Medicinal Products. Results: 1. No Hyeonggaeyeongyotang extract treatment-related changes on the clinical signs and mortalities, the Food consumptions, the Body weights and gains were demonstrated in all dosed levels tested in this study except for 500ml/kg-dosing male group in which a significant(p<0.05) increase of body gains was detected during day 0-7 after dosing. 2. No Hyeonggaeyeongyotang extract treatment-related changes on the pre-coital intervals, the estrus cycles, the mating index, conception rate and fertility index were demonstrated in all dosed levels tested in this study. 3. No Hyeonggaeyeongyotang extract treatment-related gross findings on reproductive organs, the weights of reproductive organs, histopathological findings on reproductive organs, the corpora lutea number, implantation site number, live fetus number, number of resorpted embryo and pre-and post-implatation loss were demonstrated in all dosed levels tested in this study. Conclusions : Base on the results, it is considered that the NOAEL (No-Observed-Adverse-Effect Level) for fertility and early embryonic development toxicity of Hyeonggaeyeongyotang extract was under 2000ml/kg/day in Wistar male and female rats because there no treatment-related changes on the fertility and early embryonic developmental index were demonstrated in all dosed levels tested.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제11권1호
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• pp.117-129
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• 1989

The commercial availability of processed heterogenous bone has provided the surgeons with almost unlimited supply, avoidance of additional operation and prevention of the postoperative complications. In addition to these merits, unnecessary bone bank, easy availibility and storage have been achieved. The purpose of this study was to compare and examine the healing capacity of Kiel bone, Pyrost and Osteovit which used as the processed heterografts for the reconstruction of bony defect. Twenty rabbits weighing about 1.7-2.0 Kg were selected and divided into two groups. In experimental group A, the left mandibular defect was allowed to fill with blood, and the right defect was filled with Kiel bone. In experimental group B, the left defect was grafted with Pyrost, and the right with Osteovit. The experimental animals were sacrified after 1, 2, 4 and 8 weeks and the grafted site was studied histologically. To evaluate the strength of healed bone, 2 rabbits from each experimental group and a nonoperated control were sacrified at the 6th week after implantation and used for biometric testing on universal testing machine. The results obtained were as follows : 1. It was considered that these heterogenous bone grafts has feeble or absent immunogenicity since all of them appeared to evoke little inflammatory or forign body reaction. 2. In all experimental groups, new bone formation began from the adjacent region of host bone and extended progressively into the defect sites. New bone was partly formed within the intertrabecular space of the implant and gradually united with the bone that formed at the margin of the host bone. 3. With Pyrost bone formation was rapid and prominent comparing with other graft materials. 4. Osteovit was begun to be absorbed from 2 weeks, and Kiel bone from 4 weeks, however Pyrost was remained to be intact until the end of 8 weeks. 5. As the results of tensile test, the mean values of maximum tensile stress were 1.11${\uparrow}$ $Kgf/mm^{2}$ in Pyrost implanted specimens, 0.85 $Kgf/mm^{2}$ in Osteovit, 0.42 $Kgf/mm^{2}$ in Kiel bone, 0.66 $Kgf/mm^{2}$ in blood filled specimens and 1..13 $Kgf/mm^{2}$ in control. These results indicate that heterogenous bones grafted have little antigenicity to the host tissue, and that they mediate effectively osteoconduction by providing the scaffold for the bone formation. Pyrost and Osteovit appeared to be suitable for the clinical use.

• Reproductive and Developmental Biology
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• 제35권3호
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• pp.281-285
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• 2011

In the present study, we identified differentially methylated region (DMR) upstream of Dnmt1o and Dnmt1s gene in early porcine embryos. Porcine Dnmt1o had at least one DMR which was located between -530 bp to -30 bp upstream from transcription start site of the Dnmt1o gene. DNA methylation analyses of Dnmt1o revealed the DMR to be hypomethylated in oocytes, whereas it was highly methylated in sperm. Moreover, the DMR upstream of Dnmt1o was gradually hypermethylated from oocytes to two cells and dramatically changed in the methylation pattern from four cells to BL stages in an in vivo. In an IVF, the methylation status in the DMR upstream of Dnmt1o was hypermethylated from one cell to eight cells, but demethylated at the Morula and BL stages, indicating that the DNA methylation pattern in the Dnmt1o upstream ultimately changed from stage to stage before the implantation. Next, to elucidate whether DNA methylation status of Dnmt1s upstream is stage-by-stage changed in during porcine early development, we analyzed the dynamics of the DNA methylation status of the Dnmt1s locus in germ cell, or one cell to BL cells. The Dnmt1s upstream was highly methylated in one and eight cells, while less methylated in two, four, morula, and BL cells. Taken together, our data demonstrated that DNA methylation and demethylation events in upstream of Dnmt1o/Dnmt1s during early porcine embryos dramatically occurred, and this change may contribute to the maintenance of genomewide DNA methylation in early embryonic development.

• Journal of Periodontal and Implant Science
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• 제33권1호
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• pp.13-26
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• 2003

Periodontal regeneration therapy with bone-substituting materials has gained favorable clinical efficacy by enhancing osseous regeneration in periodontal bony defect. As bone-substituting materials, bone powder, calcium phosphate ceramic, modified forms of hydroxyapatite, and hard tissue replacement polymer have demonstrated their periodontal bony regenerative potency. Bone-substituting materials should fulfill several requirements such as biocompatibility, osteogenecity, malleability, biodegradability. The purpose of this study was to investigate biocompatibility, osteo-conduction capacity and biodegradability of $Na_2O$, $K_2O$ added calcium metaphosphate(CMP). Beta CMP was obtained by thermal treatment of anhydrous $Ca_2(H_2PO_4)_2$. $Na_2O$ and $K_2O$ were added to CMP. The change of weight of pure CMP, $Na_2O$-CMP, and $K_2O$-CMP in Tris-buffer solution and simulated body fluid for 30 days was measured. Twenty four Newzealand white rabbits were used in negative control, positive control(Bio-Oss), pure CMP group, 5% $Na_2$-CMP group, 10% $Na_2O$-CMP goup, and 5% $K_2O$-CMP group. In each group, graft materials were placed in right and left parietal bone defects(diameter 10mm) of rabbit. The animals were sacrificed at 3 months and 6 months after implantation of the graft materials. Degree of biodegradability of $K_2O$ or $Na_2O$ added CMP was greater than that of pure CMP in experimental condition. All experimental sites were healed with no clinical evidence of inflammatory response to all CMP implants. Histologic observations revealed that all CMP grafts were very biocompatible and osseous conductive, and that in $K_2O$-CMP or $Na_2O$-CMP implanted sites, there was biodegradable pattern, and that in site of new bone formation, there was no significant difference between all CMP group and DPBB(Bio-Oss) group. From this result, it was suggested that all experimental CMP group graft materials were able to use as an available bone substitution.

• 구강회복응용과학지
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• 제26권1호
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• pp.59-68
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• 2010

최근 무치악 부위를 대신하여 광범위하게 식립되고 있는 치과용 임플란트는 높은 임상 성공률을 보이고 있으나 실패 가능성은 늘 존재하며 이는 예기치 않은 경우가 많다. 임플란트의 실패과 관련하여 여러 가지 요인들이 거론되고 있으나, 아직 논란의 여지가 있다. 본연구에서는 서울 보훈병원에서 2005-2006년에 하악 구치부위에 임플란트를 식립한 212명의 환자, 총 358개의 임플란트를 대상으로 환자의 연령, 임플란트 식립 부위, 시스템, 직경과 길이, 골이식 유무에 따른 생존율을 비교하였다. 각 요소에 따른 생존율을 SPSS chi-square test를 이용한 multi-variable analysis를 시행하여 관련성을 검증하였다. 연구 결과 3년간 98.3%의 누적 생존율을 보였으며, 조사한 요인 중 임플란트 직경만이 임플란트 생존율과 관련성이 있는 것으로 나타났다. 이는 넓은 직경의 임플란트가 주로 대체(rescue) 임플란트 혹은 골질이 좋지 않은 부위에 사용되는 경우가 많은 것이 원인으로 작용한 것으로 사료된다. 향후 임플란트의 성공과 관련하여 명확한 지표를 제공할 수 있는 지속적인 연구가 필요할 것이다.