• Maxillofacial Plastic and Reconstructive Surgery
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• 제30권3호
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• pp.217-224
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• 2008

Angiogenesis plays an important role in bone development and postnatal bone fracture repair. Vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptors (VEGFRs) have been thought to be primarily involved in promoting angiogenesis. It is well known that VEGF and its receptors have been reported to play an important role in the regulation of the interaction between angiogenesis and osteogenesis during bone repair processes. Dexamethasone, a potent synthetic glucocorticoid, promotes phenotype markers of osteoblast differentiation, such as ALP and osteocalcin. It stimulates in vitro osteogenesis of human bone marrow osteogenic stromal cells. Dexamethasone has been reported to suppress VEGF gene expression in some cells. However, our previous study demonstrated VEGF quantification increased in a time-dependent manner in periosteal-derived osteogenesis under dexamethasone. So, the purpose of this study was to examine the angiogenic phenotypes in cultured human periosteal-derived cells under high-dose dexamethasone. Periosteal-derived cells were cultured using a technique previously described. After passage 3, the periosteal-derived cells were further cultured for 28 days in an osteogenic inductive culture medium containing ascorbic acid, ${\beta}$-glycerophosphate and high-dose dexamethasone, We evaluated the expression of VEGF isoforms, VEGFR-1, VEGFR-2, and neuropilin-1, ALL VEGF isoforms ($VEGF_{121},\;VEGF_{165},\;VEGF_{189}$, and $VEGF_{206}$) expression was observed by RT-PCR analysis. VEGFR-1, VEGFR-2 and neuropilin-1 expression increased up to day 14, particularly during the early stage of mineralization. Our results suggest the involvement of direct VEGFs/VEGFRs system on periosteal-derived cells during early mineralization phase under high-dose of dexamethasone. These also suggest that VEGF might act as an autocrine growth molecule during osteoblastic differentiation of cultured human periosteal-derived cells.

• Journal of Korean Neurosurgical Society
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• 제64권4호
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• pp.562-574
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• 2021

Objective : This study is to evaluate the efficacy and safety of demineralized bone matrix (DBM) gel versus DBM gel with recombinant human bone morphogenetic protein-2 (rhBMP-2) used in transforaminal lumbar interbody fusion (TLIF). Methods : This study was designed as a prospective, multi-center, double-blind method, randomized study. All randomized subjects underwent TLIF with DBM gel with rhBMP-2 group (40 patients) as an experimental group or DBM gel group (36 patients) as a control group. Post-operative observations were performed at 12, 24, and 48 weeks. The spinal fusion rate on computed tomography scans and X-rays films, Visual analog scale pain scores, Oswestry disability index and SF-36 quality of life (QOL) scores were used for the efficacy evaluation. The incidence rate of adverse device effects (ADEs) and serious adverse device effects (SADEs) were used for safety evaluation. Results : The spinal fusion rate at 12 weeks for the DBM gel with rhBMP-2 group was higher with 73.68% compared to 58.82% for the DBM gel group. The 24 and 48 weeks were 72.22% and 82.86% for the DBM gel with rhBMP-2 group and 78.79% and 78.13%, respectively, for the DBM gel group. However, there were no significant differences between two groups in the spinal fusion rate at 12, 24, and 48 weeks post-treatment (p=0.1817, p=0.5272, p=0.6247). There was no significant difference between the two groups in the incidence rate of ADEs (p=0.3836). For ADEs in the experimental group, 'Pyrexia' (5.00%) was the most common ADE, followed by 'Hypesthesia', 'Paresthesia', 'Transient peripheral paralysis', 'Spondylitis' and 'Insomnia' (2.50%, respectively). ADEs reported in control group included 'Pyrexia', 'Chest discomfort', 'Pain', 'Osteoarthritis', 'Nephropathy toxic', 'Neurogenic bladder', 'Liver function analyses' and 'Urticaria' (2.86%, respectively). There was no significant difference between the two groups in the incidence rate of SADEs (p=0.6594). For SADE in the experimental group, ''Pyrexia' and 'Spondylitis' were 2.50%. SADE reported in the control group included 'Chest discomfort', 'Osteoarthritis' and 'Neurogenic bladder'. All SADEs described above were resolved after medical treatment. Conclusion : This study demonstrated that the spinal fusion rates of DBM gel group and DBM gel with rhBMP-2 group were not significantly different. But, this study provides knowledge regarding the earlier postoperative effect of rhBMP-2 containing DBM gel and also supports the idea that the longer term follow-up results are essential to confirm the safety and effectiveness.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제38권
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• pp.2.1-2.9
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• 2016

Background: We reviewed the biological and mechanical properties of porous hydroxyapatite (HA) compared to other synthetic materials. Computer-aided design/computer-aided manufacturing (CAD/CAM) was also evaluated to estimate its efficacy with clinical and radiological assessments. Method: A systematic search of the electronic literature database of the National Library of Medicine (PubMed-MEDLINE) was performed for articles published in English between January 1985 and September 2013. The inclusion criteria were (1) histological evaluation of the biocompatibility and osteoconductivity of porous HA in vivo and in vitro, (2) evaluation of the mechanical properties of HA in relation to its porosity, (3) comparison of the biological and mechanical properties between several biomaterials, and (4) clinical and radiological evaluation of the precision of CAD/CAM techniques. Results: HA had excellent osteoconductivity and biocompatibility in vitro and in vivo compared to other biomaterials. HA grafts are suitable for milling and finishing, depending on the design. In computed tomography, porous HA is a more resorbable and more osteoconductive material than dense HA; however, its strength decreases exponentially with an increase in porosity. Conclusions: Mechanical tests showed that HA scaffolds with pore diameters ranging from 400 to $1200{\mu}m$ had compressive moduli and strength within the range of the human craniofacial trabecular bone. In conclusion, using CAD/CAM techniques for preparing HA scaffolds may increase graft stability and reduce surgical operating time.

• Biomolecules & Therapeutics
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• 제23권5호
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• pp.449-457
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• 2015

The present study was aimed to investigate the effects of MB12662, a synthetic dunnione compound, on cisplatin-induced vomiting reflexes and intestinal, renal, immune system, and hematopoietic toxicities in ferrets and mice, respectively. Male ICR mice were orally administered MB12662 (5, 10, 25 or 50 mg/kg) for 10 days, during which intraperitoneally challenged with cisplatin (3.5 mg/kg) from day 4 to 7, and sacrificed on day 10 for the pathological examination. Male ferrets were orally administered MB12662 (25, 50 or 100 mg/kg) for 7 days, subcutaneously challenged with cisplatin (5 mg/kg), and monitored for vomiting reflexes and survival of the animals. Four-day injection of cisplatin (3.5 mg/kg) to mice caused body weight loss and degeneration and atrophy of intestinal villi, reducing villi/crypt ratio to a half level of control animals. Cisplatin also induced renal and hepatic toxicities, and depletion of splenocytes and bone marrow progenitor cells. The systemic toxicities including decreased villi/crypt ratio, immune system atrophy, splenocyte depletion, and decreased cellularity in bone marrow were improved by MB12662. Cisplatin (5 mg/kg) induced retching and emetic responses of ferrets, which were remarkably attenuated by MB12662 in a dose-dependent manner. All the ferrets pretreated with MB12662 survived the challenge of cisplatin, in comparison with 40% mortality in vehicle-treated animals, and blood parameters of nephrotoxicity and hepatotoxicity were markedly recovered. It is expected that MB12662 could be a candidate for the body protection against burden, including emesis, of chemotherapeutic agents.

• 한국기계가공학회지
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• 제17권1호
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• pp.108-115
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• 2018

In bone tissue engineering, polycaprolactone (PCL) is one of the most widely used biomaterials to manufacture scaffolds as a synthetic polymer with biodegradability and biocompatibility. The polymer deposition system (PDS) with four axis heads, which can dispense bio-polymers, has been used in scaffold fabrication for tissue engineering applications. A dual-head deposition technology of PDS is an effective technique to fabricate 3D scaffolds. The electrospinning technology has been widely used to fabricate porous and highly interconnected polymer fibers. Thus, PDS can fabricate nanofiber-combined hybrid scaffolds using fused deposition modeling (FDM) and electrospinning methods. This study aims to fabricate nanofiber-combined scaffolds with uniform nanofibers using PDS. The PCL nanofibers were fabricated and evaluated according to the fabrication process parameters. PCL nanofibers were successfully fabricated when the applied voltage, tip-to-collector distance, flow rate, and solution concentration were 5 kV, 1 cm, 0.1 ml/h, and 8 wt%, respectively. The cell proliferation was evaluated according to the electrospinning time. Scanning electron microscopy was used to acquire images of the cross-sectioned hybrid scaffolds. The cell proliferation test of the PCL and nanofiber-combined hybrid scaffolds was performed using a CCK-8 assay according to the electrospinning time. The result of in-vitro cell proliferation using osteosarcoma MG-63 cells shows that the hybrid scaffold has good potential for bone regeneration.

• 대한기계학회논문집A
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• 제39권11호
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• pp.1153-1159
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• 2015

최근 조직 공학 분야에서는 폴리카프로락톤(PCL), 수산화인회석, 삼인산칼슘, 이상인산칼슘(BCP), 지르코니아(Zirconia, $ZrO_2$) 와 같은 합성 생체폴리머와 생체세라믹 등은 다양한 생체 조직 또는 장기를 재생하는데 필요한 대체재로 사용되고 있다. 따라서, 본 연구의 목적은 골 조직 재생을 위한 혼합된 $ZrO_2$/BCP/PCL(ZBP) 인공지지체의 특성을 관찰하기 위함이다. 단선 패터닝 실험의 결과를 토대로 내부연결성 있는 공극을 가지고 $45^{\circ}+135^{\circ}$ 타입과 격자타입의 새로운 복합 공극 패턴을 가지는 혼합된 ZBP 인공지지체는 폴리머 적층시스템에 의해 성공적으로 제작되었다. 뿐만 아니라 기계적 특성에 대한 ZBP 인공지지체의 효과를 분석하였다. 게다가 MG63 세포에 대한 ZBP 인공지지체의 세포 상호작용은 CCK-8 분석을 이용함으로써 평가되었다.

• Journal of Periodontal and Implant Science
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• 제32권2호
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• pp.429-455
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• 2002

There are numerous kind of materials and techniques to regenerate the periodontal tissue which has been lost due to destructive periodontal disease, including bone graft material. Many bone graft materials have been reported and among these materials, synthetic material has been developed fin the long time because of its sufficient supply economically. Calcium sulfate which was evaluated as including much calcium, has been used in the clinical field. In the dental field calcium sulfate has been used as bone graft material and Kim reported that improved bone formation and more amount of new attachment after grafting calcium sulfate. but, because calcium sulfate has the problem that it generates the heat in setting period and resolves fast, we need to evaluate the effect of the improved calcium sulfate on periodontal tissue. The present study evaluates the effect of paste type calcium sulfate on the epithelial migration, alveolar bone regeneration, cementum formation and gingival connective tissue attachment in intrabony defect in dogs. Four millimeter deep and four millimeter wide 3-wall defects were surgically created in the mesial or distal aspects of premolars or molars. the test group received paste-type calcium sulfate with a flap procedure and the control group underwent flap procedure only. Histologic analysis after 8 weeks of healing revealed the following results : 1. The length of epithelial growth(the distance from CEJ to the apical end of JE) was 0.52${\pm}$0.26mm in the control and 0.56${\pm}$0.25mm in the test group. there was no statistically significant difference between the two groups. 2. The length of connective tissue adhesion was 1.74${\pm}$1.06mm in the control and 1.28${\pm}$0.57mm in the test group. there was no statistically significant difference between the two groups. 3. The length of new bone was 2.01${\pm}$0.95mm in the control and 2.62${\pm}$0.81mm in the test group. there was no statistically significant difference between the two groups. 4. The length of new cementum was 1.86${\pm}$0.80mm in the control and 2.77${\pm}$ 0.86mm in the test group. there was a statistically significant difference between the two groups.(P<0.01) These results suggest that the use of paste type calcium sulfate in 3-wall intrabony defects has significant effect on new cementum formation , but doesn't have any significant effect on the prevention of junctional epithelium migration and new bone formation. Finally, the paste type calcium sulfate that is used in this study is suggested to be the material that can have a significant effect on the periodontal healing, if its biocompatibility is improved.

• 대한치과보철학회지
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• 제48권2호
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• pp.158-165
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• 2010

연구목적: 본 연구는 hyaluronic acid (HA)를 poly (D, L-lactic-co-glycolic acid) (PLGA)에 적용하여 새로 개발된 차폐막들을 실험군으로, 차폐막이 사용되지 않은 조건과 시중에 사용 중인 collagen membrane ($Ossix^{TM}$)을 이용한 조건을 대조군으로 하여, 토끼 두개골에 형성된 골 결손부에 4, 8, 12주간 적용하고 조직학적인 관찰을 함으로써 골 재생 능력을 비교 평가하고자 한다. 연구 재료 및 방법: 12마리의 웅성 가토 두개골에, 6 mm 직경의 골 결손부를 4개씩 형성하였다. 각각의 결손부는 5가지 중 하나의 차폐막으로 덮여졌다; No-membrane, Collagen, PLGA, HA-coated-PLGA, HA-PLGA/PLGA. 4주, 8주, 그리고 12주 후 두개골을 절단하여H-E 염색한 후 조직학적 분석을 하였다. 결과: 본 연구에서, 차폐막을 사용하지 않은 군에서 골형성은 12주 후에 나타났으며, 골 결손부를 일부 채우고 있었다. 신생골은 하방의 뇌경막을 따라 형성되었고 결손부의 상부는 결합조직과 지방으로 채워져 있었다. 콜라겐 차폐막인 $Ossix^{TM}$는 4주 후부터 신생골을 보였으며 신생골은 차폐막을 따라 형성되어 있었고 12주 까지 차폐막이 유지되었다. PLGA, HA-coated-PLGA, HA-PLGA/PLGA는 4주 후부터 골 재생을 보이고 8주 후에 결손부를 전반적으로 채우고 있다. 12주에는 기존 골과 구분이 되지 않으며 잘 융합되어 있음을 알 수 있다. 차폐막은 4주 후부터 명확히 구분되지 않고 흡수되어 있었다. 결론:PLGA와 HA-coated-PLGA, HA-PLGA/PLGA는 대조군에 비해 골의 형성이 빠르고 성숙 또한 빠르게 나타났으나, HA의 적용에 따른 차이를 보이지 않았으며 4주 후부터 흡수되어 차폐막으로써 임상에서 사용하기 위해서는 흡수기간을 연장하여 조절 가능하도록 더 많은 연구가 필요할 것으로 생각된다.

• 폴리머
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• 제32권1호
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• pp.26-30
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• 2008

추간판 디스크의 섬유륜(AF)조직 재생에 적합한 다양한 담체를 평가하기 위해 천연재료인 소장점막하조직(SIS)과 탈미네랄화된 골분(DBP)을 폴리(락타이드-글리콜라이드) 공중합체(PLGA)와 혼합하여 담체(PLGA/SIS, PLGA/DBP, PLGA/SIS/DBP)를 제조하였으며, PLGA담체, PGA 메쉬, SIS 스폰지와 비교하였다. 제조된 담체의 압축강도 및 AF 세포를 담체에 파종하여 콜라겐 양과 DNA량을 측정하였으며, 이를 누드마우스 피하에 이식 후 적출하여 육안관찰과 조직학적인 평가를 수행하였다. 압축강도 측정에서 PLGA와 유사하게 PLGA/SIS, PLGA/DBP 에서도 충분한 강도를 나타내었다. DNA 증가량에 따른 콜라겐 양은 PLGA/SIS 에서 가장 높게 나타났고, 면역화학 염색을 통해 PLGA/SIS, PLGA/SIS/DBP 에서 글라이코스아미노글라이칸과 콜라겐 발현량이 높음을 확인하였다.

• 대한치주과학회:학술대회논문집
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• 대한치주과학회 2007년도 제47회 종합학술대회 연제초록
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• pp.45-46
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• 2007