• Journal of Life Science
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• v.26 no.3
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• pp.331-337
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• 2016

Although fibroblast growth factor 23 (FGF23) is exclusively produced in osteoblasts and osteocytes, its main target is the kidney, where it decreases phosphate reabsorption by suppressing Na-phosphate cotransporters. Independently of its action on phosphate homeostasis, FGF23 also inhibits bone formation in vivo. In a calvarial osteoblastic cell model, FGF23 was shown to negatively affect extracellular matrix mineralization. This study investigated whether FGF23 had similar effects on osteoblast maturation, including differentiation and mineralization of bone marrow-derived mesenchymal stem cells (MSCs). D1 MSCs were cultured in an osteogenic medium containing β-glycerophosphate, ascorbic acid, and dexamethazone. Osteoblastic differentiation was evaluated by alkaline phosphatase (Alp) staining, and matrix mineralization was evaluated by alizarin red staining and calcium deposition. The expression of differentiation-stimulating genes Runx2, Alp, and osteocalcin and mineralization-inhibiting genes Enpp1 and Ank was analyzed using semiquantitative RT-PCR. Supraphysiological doses of FGF23 did not stimulate proliferation or osteoblastic differentiation of MSCs. Matrix mineralization 1, 2, and 3 weeks after the FGF23 treatment did not vary between control and FGF23 groups, although time-dependent enhancement of mineralization was obvious. Calcium deposition was also unchanged after the FGF23 treatment. mRNA expression levels of differentiation- and mineralization-related genes were also similar between the groups. Despite these negative findings, FGF23 signaling through FGF receptors seemed to function normally, with phosphorylation of the Erk protein more evident in the FGF23 group than in controls. These findings suggest that unlike calvarial osteoblasts, FGF23 is not likely to affect osteoblastic differentiation and mineralization of MSCs.

• Journal of Periodontal and Implant Science
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• v.27 no.1
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• pp.129-150
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• 1997

The purpose of this study was to evaluate the effects of tetracycline(TC}, flurbiprofen, and PDGF-BB loaded biodegradable membranes on the cell-attachment, the activity of loaded PDGF-BB, in vivo release kinetics, and guided bone regenerative potentials. To evaluate the cell attachment to membranes, the number of gingival fibroblasts attached to each membrane(10% TC, 10% flurbiprofen, $200ng/cm^2$ PDGF-BB loaded membranes, drug-unloaded membrane) was counted by coulter counter and the morphologic pattern of attached cells was examined under SEM. To determine whether the activity of loaded PDGF-BB is sustained, the cellular growth and survival rate of gingival fibroblasts was used for both standard PDGF-BB and loaded PDGF-BB. For evaluation of in vivo release kinetics, drug-loaded membranes were implanted on the dorsal skin of the rats. On 1, 3, 7, 10, 14, 21, and 28 days after implantation, the amount of remaining drugs were measured by HPLC assay for TC and flurbiprofen, and by ${\gamma}-scintillation$ counter for $PDGF-BB^{1125}$. For evaluation of guided regenerative potential, the amount of new bone in the calvarial defect(5mm in diameter) of the rat was measured by histomorphometry 1 and 2 weeks after implantation of membranes. The number of cells attached to the PDGF-BB loaded membrane was largest as compared with the other mernbranes.(p< 0.05) The activity of loaded PDGF-BB was not significantly different from the activity of standard PDGF-BB.(p<0.05) After initial burst release of drug during the first 24 hours, drugs were gradually released for 4 weeks. Especially the release rate of PDGF-BB was nearly constant during 4 weeks. PDGF-BB loaded membranes(200, $400ng/cm^2$) were effective in guided bone regeneration as compared with drug-unloaded membrane. These results implicate that drug-loaded biodegradable membranes might be a useful for guided bone regeneration.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.33 no.4
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• pp.293-300
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• 2011

Purpose: Substance P is a well known neurotransmitter and has been known to mediate pain. Recently, it has been unveiled that substance P is involved in the recruitment of mesenchymal stem cells to wound sites. The purpose of this study was to exam bone formation when a combination of substance P and silk fibroin was used in a bone defect model. Methods: Twenty rabbits were used and 40 calvarial defects were formed. They were divided as 4 groups (unfilled control, silk only, silk+$10{\mu}g$/ml substance P; Sub10, and silk+$100{\mu}g$/ml substance P; Sub100). All animals were humanely sacrificed 4 or 8 weeks after grafting. The specimens were analyzed by micro-computerized tomography and histological analysis. Results: When compared to the unfilled control to silk only group, there was significant difference in bone mineral density (BMD) and the attenuation coefficient (AC) at 4 weeks ($p$=0.037 and 0.038, respectively). When compared Sub10 group to Sub100 group, there was significant difference in BMD and AC at 8 weeks ($p$=0.004 for all). Residual graft amounts were $52.1{\pm}15.8$%, $15.2{\pm}9.2$% and $9.0{\pm}3.3$% for silk only, Sub10, and Sub100 groups, respectively. When comparing the residual graft amount of silk only to sub10 or sub100, the differences were statistically significant ($p$ <0.001). Conclusion: The silk fibroin scaffold showed higher BMD and AC than the unfilled control. The combination graft with substance P and silk fibroin scaffold showed a faster graft degradation than with a silk fibroin scaffold only.

• Journal of Korean Neurosurgical Society
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• v.29 no.5
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• pp.701-705
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• 2000

Solitary plasmacytomas are rare and account for 5-10% of all plasma cell disorders. These tumors are categorized as solitary plasmacytomas of bone(osseous) or extramedullary plasmacytomas(non-osseous). About a half of solitary plasmacytomas of bone occur in the spine but rarely in the skull. We report a case of solitary plasmacytoma of the skull presented with a painless palpable left parietal calvarial mass in an otherwise asymptomatic 38- year-old man. Skull radiographs showed a large radiolucent lesion with well defined non-sclerotic margins. Computed tomograph scan demonstrated a markedly enhancing mass extending from the epidural to the subcutaneous space. The patient underwent surgery and tumor was completely excised. Pathological examination showed tumor to be a plasmacytoma synthesizing IgG. Postoperatively, the patient received radiotherapy. There was no evidence of systemic involvement on postoperative laboratory wokups. Our recommended treatment is a complete surgical excision combined with postoperative radiation therapy. The patient should be follwed carefully for more than 10 years because of either local recurrence or possible progression to multiple myeloma.

• Journal of International Society for Simulation Surgery
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• v.1 no.2
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• pp.99-102
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• 2014

The skull defect can be made after the trauma, oncologic problems or neurosurgery. The skull reconstruction has been the challenging issue in craniofacial fields for a long time. So far the skull reconstruction with autogenous bone would be the standard. Although the autogenous bone would be the ideal one for skull reconstruction, donor site morbidity would be the inevitable problem in many cases. Meanwhile various types of allogenic and alloplastic materials have been also used. However, skull reconstruction with many alloplastic material have produced no less complications including infection, exposure, and delayed wound healing. Because the 3D printing technique evolved so fast that 3D printed titanium implant were possible recently. The aim of this trial is to try to restore the original skull anatomy as possible using the 3D printed titanium implant, based on the mirrored three dimensional CT images based on the computer simulation. Preoperative computed tomography (CT) data were processed for the patient and a rapid prototyping (RP) model was produced. At the same time, the uninjured side was mirrored and superimposed onto the traumatized side, to create a mirror-image of the RP model. And we fabricated Titanium implant to reconstruct three-dimensional orbital structure in advance, using the 3D printer. This prefabricated Titanium-implant was then inserted onto the defected skull and fixed. Three dimensional printing technique of titanium material based on the computer simulation turned out to be very successful in this patient. Individualized approach for each patient could be an ideal way to manage the traumatic patients in near future.

• Archives of Plastic Surgery
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• v.34 no.4
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• pp.448-454
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• 2007

Purpose: The objective of this study was to evaluate the outcomes of using the free flap in the reconstruction of maxillary defects. Methods: 27 consecutive cases of maxillary reconstruction with free flap were reviewed. All clinical data were analyzed, including ideal selection of flap, time of reconstruction, recurrence of cancer, postoperative complications, flap design, and follow-up results. The main operative functional items, including speech, oral diet, mastication, eye globe position and function, respiration, and aesthetic results were evaluated. Results: Among the 24 patients who underwent maxillary reconstruction with the free flap, 14 patients underwent immediate reconstruction after maxillary cancer ablation, and 10 patients underwent delayed reconstruction. There occurred 1 flap loss. Recurrences of the cancer after the reconstruction happened in 2 cases. Postoperative complications were 3 cases of gravitational ptosis of the flap, 2 cases of the nasal obstruction, and 1 case of fistula formation. Out of 27 free flaps, there were 15 latissimus dorsi myocutaneous flaps, 5 radial forearm, 4 rectus abdominis myocutaneous flaps, 1 scapular flap, 2 fibula osteocutaneous flap, respectively. Flaps were designed such as 1 lobe in 9 cases, 2 lobes in 9 cases, and 3 lobes in 5 cases. Among the 14 patients who had intraoral defect or who had palatal resection surgery, 2 patients complained the inaccuracy of the pronunciation due to the ptosis of the flap. It was corrected by the reconstruction of the maxillary buttress and hung the sling to the upper direction. All of the 14 patients were able to take unrestricted diets. In 6 patients who had reconstruction of inferior orbital wall with rib bone graft, they preserved normal vision. Aesthetically, most of the patients were satisfied with the result. Conclusion: LD free flap is suggested in uni-maxilla defect as the 1st choice, and fibular osteocutaneous flap and calvarial bone graft to cover the larger defect in bi-maxilla defect.

• Archives of Plastic Surgery
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• v.50 no.1
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• pp.54-58
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• 2023

Patients with Crouzon syndrome have increased risks of cerebrospinal fluid rhinorrhea and meningoencephalocele after LeFort III osteotomy. We report a rare case of meningoencephalocele following LeFort III midface advancement in a patient with Crouzon syndrome. Over 10 years since it was incidentally found during transnasal endoscopic orbital decompression, the untreated meningoencephalocele eventually led to intermittent clear nasal discharge, frontal headache, and seizure. Computed tomography and magnetic resonance imaging demonstrated meningoencephalocele in the left frontal-ethmoid-maxillary sinus through a focal defect of the anterior cranial base. Through bifrontal craniotomy, the meningoencephalocele was removed and the anterior cranial base was reconstructed with a pericranial flap and split calvarial bone graft. Secondary frontal advancement was concurrently performed to relieve suspicious increased intracranial pressure, limit visual deterioration, and improve the forehead shape. Surgeons should be aware that patients with Crouzon syndrome have the potential for an unrecognized dural injury during LeFort III osteotomy due to anatomical differences such as inferior displacement and thinning of the anterior cranial base.

• Journal of Periodontal and Implant Science
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• v.27 no.4
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• pp.867-882
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• 1997

Safflower(Carthamus tinctorius $Linn\acute{e}$ has been traditionally used for the treatment of blood stasis, and Dipsasi Radix has been used as a drug for fracture in Chinese medicine. The purpose of present study was to examine the biologic effects of safflower extract and Disasi radix extracts on the periodontal. ligament cells and osteoblastic cells and on the wound healing of rat calvarial defect. The ethanolic extract of safflower blossom, safflower seed and Dipsasi Radix(125, 250, and 500 ${\mu}g/ml$) were prepared as test group, and PDGF-BB(lOng/ml) and unsafonifiable fraction of Zea Mays L.(125, 250, and 500 ${\mu}g/ml$) were employed as positive control. The effects of each agents on the growth and survival, ALPase activity, expression of PDGF-BB receptor, chemotactic response of PDL cell and ATCC human osteosarcoma MG63 cells in vitro were examined. The tissue regenerative effect of each extracts was evaluated by histomorphometric measuring of newly formed bone on the 8mm defect in rat calvaria after oral administration of 3 different dosages groups : 0.02, 0.1 and 0.35g/kg, per day. It was also employed the same dosages of unsaponifiable fraction of Zea Mays L. as positive controls. Safflower blossom extract, safflower seed extract, and Dipsasi Radix extract stimulate the cellular activity of MG63 cells in concentration range of $125-500{\mu}g/ml$, and safflower bolssom extract and safflower seed extract stimulate also the cellular activity of periodontal ligament cells in concentration range of $250-500{\mu}g/ml$. In activity of ALPase, $250-500{\mu}g/ml$ of safflower blossom extracts showed significant stimulating effects on MG63 cells, and the same concentration range of safflower seed extracts showed significant effect on periodontal ligament cells. In the recovery on PDGF-BB receptor expression which was depressed by $IL-1{\beta}$, $125-250{\mu}g/ml$ of safflower blossom extracts and $250-500{\mu}g/ml$ of safflower seed extracts showed significant increasing effect on MG63 cells, and $500{\mu}g/ml$ of safflower blossom extract and $250-500{\mu}g/ml$ of safflower seed extracts showed significant effect on periodontal ligament cells. In chemotactic response, among all tested group, safflower seed extracts only were chemotactic to MG63 cells and periodontal ligament cells in concentration range of $125-500{\mu}g/ml$. Also in the view of bone regeneration in rat calvarial defect model, the only group that was orally administrated 0.35g/kg, day of safflower seed extract showed significant new bone formation. These results suggested that safflower extracts might have a potential possibilities as an useful drug for adjunct to treatment for regeneration of periodontal defect.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.34 no.1
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• pp.1-11
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• 2012

Purpose: The purpose of this study was to evaluate the bone regeneration capacity of silk fibroin (SF) when combined with beta tricalcium phosphate (${\beta}$-tricalcium phosphate [TCP]) and rh-bone morphogenetic protein (BMP) in vivo by micro-computed tomography (CT), soft x-ray, and histological analysis. Methods: A total of 56 critical size defects formed by a trephine bur made on 28 adult female Spague-Dawley rats were used for this study and the defect size was 5.0 mm in diameter. The defects were transplanted with (1) no graft material (raw defect), (2) autogenous bone, (3) SF ($10{\mu}g$), (4) SF-BMP ($10{\mu}g$, $0.8{\mu}g$ each), and (5) SF+${\beta}$-TCP ($10{\mu}g$). At 4 and 8 weeks after operation, the experimental animals were sacrificed. Samples were evaluated with soft x-ray, histological examinations and 3-dimensional micro-CT analysis. Results: In the 3-dimensional micro-CT evaluation, bone volume and bone surface data were higher in the SF-BMP ($12.8{\pm}1.5$, $138.6{\pm}45.0$ each) (P<0.05) and SF-TCP ($12.3{\pm}1.5$, $144.9{\pm}30.9$ each) group than in the SF group ($6.1{\pm}3.3$, $77.2{\pm}37.3$ each) (P<0.05), except for the autogenous group ($15.0{\pm}3.0$, $190.7{\pm}41.4$ each) at 4 weeks. At 8 weeks, SF-BMP ($16.8{\pm}3.5$, $173.9{\pm}34.2$ each) still revealed higher (P<0.05) bone volum and surface, but SF-TCP ($11.3{\pm}1.5$, $1132.9{\pm}52.1$ each) (P=0.5, P=0.2) revealed the same or lower amount compared with the SF group ($13.8{\pm}2.7$, $127.5{\pm}44.8$ each). The % of bone area determined by radiodensity was higher in the SF-TCP ($31.4{\pm}9.1%$) and SF-BMP ($36.2{\pm}16.2%$) groups than in the SF ($19.0{\pm}10.4$) group at the period of 4 weeks. Also, in the histological evaluation, the SF-BMP group revealed lower inflammation reaction, lower foreign body reaction and higher bone healing than the SF group at postoperative 4 weeks and 8 weeks. The SF-TCP group revealed lower inflammation at 4 weeks, but accordingly, as the TCP membrane was absorbed, inflammatory and foreign body reaction are increased at 8 weeks. Conclusion: The current study provides evidence that the silk fibrin can be used as an effective grafted material for tissue engineering bone generation through a combination of growth factor or surface treatment.

• Journal of Periodontal and Implant Science
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• v.27 no.1
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• pp.165-177
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• 1997

The purpose of this study was to perform on the biological activity of Magnolia and Zizyphi fructus extract mixtures on the wound healing of defected rat calvaria. For the determination of the mixture ratio of two extracts for oral administration, preliminary experiments were performed with the mixture combination of 2000 and $3000{\mu}g/ml$ of Magnolia extract, and also 20, 30, 200, 300, 2000 and $3000{\mu}g/ml$ of Zizyphi fructus extract, respectively and divided into 6 groups. The combination of extracts mixture were tested on the enhancing effect of cellular activity. The effect of the extracts mixture on the cellular activity was evaluated using MTT method and measured on the results with optical density by ELISA reader. The ability to tissue regeneration of the extracts mixture was performed by measuring new bone and new connective tissue regeneration on the 5mm defected rat calvaria for 1, 2 and 3 weeks after oral administration of 2 different dosages groups : 10:1(0.1g/kg) and 10:1(0.5g/kg). It was employed the same dosages of unsaponifiable fraction of Zea Mays L as positive controls. Each group of rat was sacrificed and en bloc section for histological examination. The effect on the cellular activity of each mixture ratio showed significantly higher in $2000{\mu}g/ml$ of Magnolia extract and $200{\mu}g/ml$ of Zizyphi fructus extract group to compare with other groups. These preliminary results showed that appropriate mixture ratio of two extracts was 10:1 of Magnolia and Zizyphi fructus extract. Histological examination on the activity of tissue regeneration of each group showed that 2weeks and 3weeks specimens of 0.5g/kg of 10:1 extract mixture of Magnolia and Ziziphi fructus administrated rat calvaria revealed significantly more osteoid and new bone formation of defected calvaria with unification of defected area than the specimens of any other negative and positive controls. Even though the specimen administrated the same dosages of unsaponifiable fraction of Zea Mays L, positive controls, showed the trend that they promote significantly the repair of calvarial defect, their bone reparative activities were less inductive than the same dosages of Magnolia and Ziziphi fructus extract mixture. These results implicated that the mixture of Magnolia and Zizyphi fructus extracts should be highly effective on the wound healing of bony defected site and might have potential possibilities as an useful drug to promote periodontal tissue regeneration.