• Journal of Periodontal and Implant Science
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• v.37 no.3
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• pp.543-551
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• 2007

When clinicians faced with an insufficient volume of supporting bone on ideally esthetic and bio-mechanical position for dental implantation, guided bone regeneration(GBR) was indicated. Although GBR has wide application at clinic, proper time of membrane removal remains qustionable in using non-resorbable membrane, such as non-expanded polytetrafluoroethylene(PTFE), The aim of this study was to compare the effect of maintenance period of PTFE membrane on bone regeneration in rabbit calvarial defects. Eight adult New Zealand white female rabbits were used in this study. Four defects were surgically made in their calvaria. Using a trephine bur, 4 'through and through' defects were created and classified into 3 groups, which were consisted of control group(no graft), experimental group 1(autogenous bone)and experimental group 2(deproteinized bovine bone; $OCS-B^{(R)}$). The defects were covered with PTFE membrane($Cytoplast^{(R)}$). Membranes were removed after 1, 2, 4 and 8 weeks post-GBR procedure in 2 rabbits repectively, All rabbits were sacrificed after 8 week post-GBR procedure. Specimens were harvested and observed histologically. The results were as follow; 1) The use of graft material and membrane was necessary in GBR procedure. 2) When PTFE membranes were removed early, the most favorable bone regeneration was revealed in experimental group T, followed by experimental group II and control group. 3) On GBR, it is recommended that membrane should maintain for 4 weeks with autogenous graft. As well, the use of xenograft need longer maintenance period than autogenous bone. Further evaluations will be needed, such as histomorphologic research, more species and different kinds of graft materials. And on the basis of these studies, clinical researches would be required.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.37
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• pp.16.1-16.7
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• 2015

Background: This study aimed to investigate new bone formation using recombinant human bone morphogenetic protein 2 (rhBMP-2) and locally applied bisphosphonate in rat calvarial defects. Methods: Thirty-six rats were studied. Two circular 5 mm diameter bony defect were formed in the calvaria using a trephine bur. The bony defect were grafted with $Bio-Oss^{(R)}$ only (group 1, n = 9), $Bio-Oss^{(R)}$ wetted with rhBMP-2 (group 2, n = 9), $Bio-Oss^{(R)}$ wetted with rhBMP-2 and 1 mM alendronate (group 3, n = 9) and $Bio-Oss^{(R)}$ wetted with rhBMP-2 and 10 mM alendronate (group 4, n = 9). In each group, three animals were euthanized at 2, 4 and 8 weeks after surgery, respectively. The specimens were then analyzed by histology, histomorphometry and immunohistochemistry analysis. Results: There were significant decrease of bone formation area (p < 0.05) between group 4 and group 2, 3. Group 3 showed increase of new bone formation compared to group 2. In immunohistochemistry, collagen type I and osteoprotegerin (OPG) didn't show any difference. However, receptor activator of nuclear factor ${\kappa}B$ ligand (RANKL) decreased with time dependent except group 4. Conclusion: Low concentration bisphosphonate and rhBMP-2 have synergic effect on bone regeneration and this is result from the decreased activity of RANKL of osteoblast.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.34 no.6
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• pp.377-383
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• 2012

Purpose: The aim of this study was to evaluate the effect of 4-hexylresorcinol and hydroxyapatite combination graft on bone regeneration in the rabbit calvarial defect model. Methods: Ten New Zealand white rabbits were used for this study. Bilateral round shaped defects (diameter: 8.0 mm) were created on the parietal bone. 4-hexylresorcinol and hydroxyapatite combination graft material was grafted into the right parietal bone defect area (experimental). The left bone defect area was not filled with anything (control). The animals were sacrificed at 4 weeks and 8 weeks after grafting. A micro-computerized tomography of each specimen was taken, and the specimens were stained for histological analysis. Results: The average value of bone mineral density (BMD) and Bone volume (BV) was higher in the experimental group than in the control group at 4 weeks and 8 weeks after surgery. However, the difference was not statistically significant (P>0.05) at 8 weeks after grafting. The BMD and BV in the experimental group at 4 weeks after surgery was significantly higher than those in the control group (P<0.05). Conclusion: 4-hexylresorcinol and hydroxyapatite combination graft material showed higher initial bone formation than the control, however, there was no difference at 8weeks after operation.

• Archives of Craniofacial Surgery
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• v.16 no.1
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• pp.11-16
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• 2015

Background: Source material used to fill calvarial defects includes autologous bones and synthetic alternatives. While autologous bone is preferable to synthetic material, autologous reconstruction is not always feasible due to defect size, unacceptable donor-site morbidity, and other issues. Today, advanced three-dimensional (3D) printing techniques allow for fabrication of titanium implants customized to the exact need of individual patients with calvarial defects. In this report, we present three cases of calvarial reconstructions using 3D-printed porous titanium implants. Methods: From 2013 through 2014, three calvarial defects were repaired using custom-made 3D porous titanium implants. The defects were due either to traumatic subdural hematoma or to meningioma and were located in parieto-occipital, fronto-temporo-parietal, and parieto-temporal areas. The implants were prepared using individual 3D computed tomography (CT) data, Mimics software, and an electron beam melting machine. For each patient, several designs of the implant were evaluated against 3D-printed skull models. All three cases had a custom-made 3D porous titanium implant laid on the defect and rigid fixation was done with 8 mm screws. Results: The custom-made 3D implants fit each patient's skull defect precisely without any dead space. The operative site healed without any specific complications. Postoperative CTs revealed the implants to be in correct position. Conclusion: An autologous graft is not a feasible option in the reconstruction of large calvarial defects. Ideally, synthetic materials for calvarial reconstruction should be easily applicable, durable, and strong. In these aspects, a 3D titanium implant can be an optimal source material in calvarial reconstruction.

• Journal of Periodontal and Implant Science
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• v.46 no.4
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• pp.220-233
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• 2016

Purpose: The aim of this study was to present new a model that allows the study of the bone healing process, with an emphasis on the biological behavior of different graft-to-host interfaces. A standardized "over-inlay" surgical technique combined with a differential histomorphometric analysis is presented in order to optimize the use of critical-size calvarial defects in pre-clinical testing. Methods: Critical-size defects were created into the parietal bone of 8 male Wistar rats. Deproteinized bovine bone (DBBM) blocks were inserted into the defects, so that part of the block was included within the calvarial thickness and part exceeded the calvarial height (an "over-inlay" graft). All animals were sacrificed at 1 or 3 months. Histomorphometric and immunohistochemical evaluation was carried out within distinct regions of interest (ROIs): the areas adjacent to the native bone (BA), the periosteal area (PA) and the central area (CA). Results: The animals healed without complications. Differential morphometry allowed the examination of the tissue composition within distinct regions: the BA presented consistent amounts of new bone formation (NB), which increased over time ($24.53%{\pm}1.26%$ at 1 month; $37.73%{\pm}0.39%$ at 3 months), thus suggesting that this area makes a substantial contribution toward NB. The PA was mainly composed of fibrous tissue ($71.16%{\pm}8.06%$ and $78.30%{\pm}2.67%$, respectively), while the CA showed high amounts of DBBM at both time points ($78.30%{\pm}2.67%$ and $74.68%{\pm}1.07%$, respectively), demonstrating a slow remodeling process. Blood vessels revealed a progressive migration from the interface with native bone toward the central area of the graft. Osterix-positive cells observed at 1 month within the PA suggested that the periosteum was a source of osteoprogenitor elements. Alkaline phosphatase data on matrix deposition confirmed this observation. Conclusions: The present model allowed for a standardized investigation of distinct graft-to-host interfaces both at vertically augmented and inlay-augmented sites, thus possibly limiting the number of animals required for pre-clinical investigations.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.33 no.6
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• pp.459-466
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• 2011

Purpose: This study evaluated the capability of bone formation with silk fibroin/nano-hydroxyapatite/corn starch composite scaffold as a bone defect replacement matrix when grafted in a calvarial bone defect of rabbits $in$ $vivo$. Methods: Ten New Zealand white rabbits were used for this study and bilateral round-shaped defects were formed in the parietal bone (diameter: 8.0 mm). The silk fibroin 10% nano-hydroxyapatite/30% corn starch/60% composite scaffold was grafted into the right parietal bone (experimental group). The left side (control group) was grafted with a nano-hydroxyapatite (30%)/corn starch (70%) scaffold. The animals were sacrificed at 4 weeks and 8 weeks. A micro-computerized tomography (${\mu}CT$) of each specimen was taken. Subsequently, the specimens were decalcified and stained with Masson's trichrome for histological and histomorphometric analysis. Results: The average ${\mu}CT$ and histomorphometric measures of bone formation were higher in the control group than in the experimental group at 4 weeks and 8 weeks after surgery though not statistically significant ($P$ >0.05). Conclusion: The rabbit calvarial defect was not successfully repaired by silk fibroin/nano-hydroxyapatite/corn starch composite scaffold and may have been due to an inflammatory reaction caused by silk powder. In the future, the development of composite bone graft material based on various components should be performed with caution.

• Archives of Plastic Surgery
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• v.35 no.6
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• pp.631-636
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• 2008

Purpose: Adipose tissue-derived stem cells(ADSC) has an osteoconductive potential and demineralized bone matrix(DBM) is an osteoinductive material. A combination of DBM and ADSC wound probably create osteoinductive properties. The purpose of this study is to determine the effect of the combination of DBM and ADSC mixture on healing of rat calvarial defect. Methods: Thirty adult male Sprague-Dawley rats were randomized into 3 groups(n=10) as 1) Control, 2) DBM alone, 3) DBM with ADSC mixture. DBM with ADSC mixture group has had a 3-day preculture of ADSC from groin fat pad. An 6 mm critical size circular calvarial defect was made in each rat. Defect was implanted with DBM alone or DBM with ADSC mixture. Control defect was left unfilled. 6 and 12 weeks after the implantation, the rats were sacrificed and the defects were evaluated by histomorphometric and radiographical studies. Results: Histomorphometric analysis revealed that DBM with ADSC mixture group showed significantly higher bone formation than DBM alone group(p<0.05). Although radiographs from DBM alone group and DBM with ADSC group revealed similar diffuse radiopaque spots dispersed throughout the defect. Densitometric analysis of calvarial defect revealed DBM with ADSC mixture group significantly higher bone formation than DBM alone(p<0.05). There was correlation of densitometry with new bone formation(Spearman's correlation of coefficient=0.804, 6 weeks, 0.802, 12 weeks). Conclusion: The DBM with ADSC mixture group showed the best healing response and the osteoinductive properties of DBM were accelerated with ADSC mixture. It will be clinically applicable that DBM and ADSC mixture in plastic and reconstructive surgery, such as alveolar cleft and congenital facial deformities that bone graft should be required.

• Journal of Periodontal and Implant Science
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• v.34 no.3
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• pp.543-549
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• 2004

Chitosan has been widely researched as bone substitution materials and membranes in orthopedic/periodontal applications. Chitosan nanofiber membrane was fabricated by chitosan nanofiber using electrospinning technique. The structure of the membrane is nonwoven, three-dimensional, porous, and nanoscale fiber-based matrix. The aim of this study was to evaluate the biocompatibility of chitosan nanofiber membrane and to evaluate its capacity of bone regeneration in rabbit calvarial defect. Ten mm diameter round cranial defects were made and covered by 2 kinds of membranes (Gore-Tex membrane, chitosan nanofiber membrane) in rabbits. Animals were sacrificed at 4 weeks after surgery. Decalcified specimens were prepared and observed by microscope. Chitosan nanofiber membrane maintained its shape and space at 4 weeks. No inflammatory cells were seen on the surface of the membrane. In calvarial defects, new bone bridges were formed at all defect areas and fused to original old bone. No distortion and resorption was observed in the grafted chitosan nanofiber membrane. However bone bridge formation and new bone formation at the center of the defect could not be seen in Gore-Tex membranes. It is concluded that the novel membrane made of chitosan nanofiber by electrospinning technique may be used as a possible tool for guided bone regeneration.

• Journal of Periodontal and Implant Science
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• v.37 no.4
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• pp.733-742
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• 2007

Bone morphogenetic proteins have been shown to possess significant osteoinSductive potential, but in order to take advantage of this effect for tissue engineering, carrier systems are essential. Successful carrier systems must enable vascular and cellular invasion, allowing BMP to act as a differentiation factor. The carrier should be reproducible, non-immunogenic, moldable, and space-providing, to define the contours of the resulting bone. The purpose of this study was to review available literature, in comparing various carriers of BMP on rat calvarial defect model. The following conclusions were deduced. 1. Bone regeneration of ACS/BMP, ${\beta}-TCP/BMP$, FFSS/BMP, $FFSS/{\beta}-TCP/BMP$, MBCP/BMP group were significantly greater than the control groups. 2. Bone density in the ACS/BMP group was greater than that in ${\beta}-TCP$, FFSS, $FFSS/{\beta}-TCP$ carrier group. 3. Bone regeneration in FFSS/BMP group was less than in ACS/BMP, ${\beta}-TCP/BMP$, MBCP/BMP group. However, New bone area of $FFSS/{\beta}-TCP/BMP$ carrier group were more greater than that of FFSS/BMP group. ACS, ${\beta}-TCP$, FFSS, $FFSS/{\beta}-TCP$, MBCP were used for carrier of BMP. However, an ideal carrier which was reproducible, non-immunogenic, moldable, and space-providing did not exist. Therefore, further investigation are required in developing a new carrier system.

• Journal of Veterinary Clinics
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• v.27 no.4
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• pp.325-329
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• 2010

The osteogenic potential of hydroxyapatite/poly $\varepsilon$-caprolactone composite (HA/PCL) scaffolds with matrigel was evaluated in a rat calvarial defect model. Calvarial defect formation was surgically created in Sprague Dawley rats (n = 18). HA/PCL scaffold was grafted with matrigel (M-HA/PCL group, n = 6) or without matrigel (HA/PCL group, n = 6). A critical defect group (CD group, n = 6) did not received a graft. Four weeks after surgery, bone formation was evaluated with radiography, micro computed tomography (micro CT) scanning, and histologically. No bone tissue formation was radiographically evident in the CD group. Bone tissue was radiographically evident in the HA/PCL and M-HA/PCL groups, however, there was more bone-similar opacity in the M-HA/PCL group. Micro CT analysis revealed that the bone volume of the M-HA/PCL group was higher than the HA/PCL group, however, no significant difference was found between the HA/PCL and M-HA/PCL groups. Bone mineral density in the M-HA/ PCL group was significantly higher than in the HA/PCL group (p < 0.05). Histologically, new bone was formed only from existing bone in the CD group, showing concavity without bone formation in the defect. In the HA/PCL group, new bone formation was only derived from existing bone, while in the M-HA/PCL group the largest bone formation was observed, with new bone tissue forming at the periphery of existing bone and around the HA/PCL scaffold with matrigel. The results indicate that the combination of HA/PCL scaffold with matrigel may be an effective means of enhancing bone formation in critical-sized bone defects.