• Journal of the korean academy of Pediatric Dentistry
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• v.26 no.4
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• pp.652-663
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• 1999

Craniosynostosis, the premature fusion of cranial sutures, presumably involves disturbance of the interactions between different tissues within the cranial sutures. Interestingly, point mutaions in the genes encoding for the fibroblast growth factor receptors(FGFRs), especially FGFR2, cause various types of human craniosynostosis syndromes. To elucidate the function of these genes in the early morphogenesis of mouse cranial sutures, we first analyzed by in situ hybridization the expression of FGFR2(BEK) and osteopontin, an early marker of osteogenic differentiation, in the sagittal suture of calvaria during embryonic(E15-E18) and postnatal stage(P1-P3). FGFR2(BEK) was intensely expressed in the osteogenic fronts, whose cells undergo differentiation into osteoprogenitor cells that ultimately lay down the bone matrix. Osteopontin was expressed throughout the parietal bones excluding the osteogenic fronts, the periphery of the parietal bones. To further examine the role of FGF-mediated FGFR signaling in cranial suture, we did in vitro experiments in E15.5 mouse calvarial explants. Interestingly, implantation of FGF2 soaked beads onto both the osteogenic fronts and mid-mesenchyme of sagittal suture after 36 hours organ culture resulted in the increase of the tissue thickness and cell number around FGF2 beads, moreover FGF4-soaked beads implanted onto the osteogenic fronts stimulated suture closure due to an accelerated bone growth, compared to FGF4 beads placed onto mid-mesenchyme of sagittal suture and BSA control beads. In addition FGF2 induced the ectopic expression of osteopontin and Msx1 genes. Taken together, these data indicate that FGF-mediated FGFR signaling has a important role in regulating the cranial bone growth and maintenance of cranial suture, and suggest that FGF-mediated FGFR signaling is involved in regulating the balance between the cell proliferation and differentiation through inducing the expression of osteopontin and Msx1 genes.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.36 no.5
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• pp.353-359
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• 2010

Introduction: This study examined the effect of cyclosporine A (CsA) on the allogenic cranial bone graft in the mice. Materials and Methods: Twenty eight 12-week-old male ICR mice weighing 40 g were used. The experimental group was injected subcutaneously with CsA (10 mg/kg/day) diluted in Caster oil for 7 days prior to the graft until sacrifice. The control group was injected with the same solution without CsA. Two full-thickness bone defects with a diameter of 3 mm were made with a trephine bur in the parietal bone lateral to the sagittal suture. A calvarial defect of a mouse was grafted with allogenic calvarial bone disc from another mouse. The experimental and control groups were injected with CsA and the solution without CsA in the same manner before surgery, respectively. The mice were sacrificed at 1 week, 2 weeks and 4 weeks after the bone graft, respectively. Results: In the experimental group, fibrous connective tissues and small amounts of inflammatory cells were observed. At 2 weeks after the allograft in the experimental group, new bone formation in fibrous collagenous tissue and around the allogenic bone was noted. At 4 weeks after the allograft, new bone formation was active along and at the periphery of the mature allogenic bone. The proliferation of blood vessels increased in bone marrow. In the control group, fibrous tissues and inflammatory cells were observed around the allogenic bone and existing bone at 1 week. At 2 weeks after the allograft, the proliferation of blood vessels accompanied by inflammatory cells were scattered in the fibrous connective tissues. New bone formation around the allogenic and existing bone could be observed. At 4 weeks after the allograft, inflammatory cells were severely infiltrated around the allogenic bone. Osteoclasts were scattered along the allogenic bone and induced bone resorption. Conclusion: These results suggest that the daily administration of CsA (10 mg/kg/day) induces efficient immunosuppression without serious complications, and this protocol might be useful for the experimental model of allogenic bone grafts.

• Journal of Korean Dental Science
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• v.4 no.1
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• pp.6-13
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• 2011

Purpose: Craniosynostosis (CS), one of the most common congenital craniofacial deformities, is the premature closure of cranial sutures. NELL-1 is a novel molecule overexpressed during premature cranial suture closure in human CS. From a functional perspective, NELL-1 has been reported to accelerate chondrocyte maturation and modulate calvarial osteoblast differentiation and apoptosis pathways. The mechanism through which NELL-1 induces these phenomena, however, remains unclear. The purpose of this study is to identify the NELL-1 binding protein(s) through which the biologic mechanism of NELL-1 can be further investigated. Materials and Methods: Far-Western and Immunoprecipitation (IP) assays were performed, independently and in sequence, followed by mass spectrometry to identify the NELL-1 binding proteins. Reverse IP was used to verify and confirm candidate binding protein. Results: The only confirmative protein from current experimentation was vimentin. Vimentin is the major structural component of the intermediate filaments. Conclusion: The present study identified and confirmed vimentin as a NELL-1 binding protein, which opened up a new window to mechanistically facilitate studies on this CS-associated molecule.

• Journal of Korean Neurosurgical Society
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• v.59 no.3
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• pp.242-246
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• 2016

Craniosynostosis is the premature fusion of calvarial sutures, resulting in deformed craniofacial appearance. Hence, for a long time, it has been considered an aesthetic disorder. Fused sutures restrict growth adjacent to the suture, but compensatory skull growth occurs to accommodate the growing brain. The primary goal for the management of this craniofacial deformity has been to release the constricted skull and reform the distorted shape of the skull vault. However, the intellectual and behavioral prognosis of affected children has also been taken into consideration since the beginning of the modern era of surgical management of craniosynostosis. A growing body of literature indicates that extensive surgery, such as the whole-vault cranioplasty approach, would result in better outcomes. In addition, the age at treatment is becoming a major concern for optimal outcome in terms of cosmetic results as well as neurodevelopment. This review will discuss major concerns regarding neurodevelopmental issues and related factors.

• Journal of Periodontal and Implant Science
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• v.30 no.4
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• pp.851-870
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• 2000

The major goals of periodontal therapy is the functional regeneration of periodontal supporting structures already destructed by periodontal disease as well as the reduction of signs and symptoms of progressive periodontal disease. There have been many efforts to develop materials and therapeutic methods to promote periodontal wound healing. There have been increasing interest on the chitosan made by chitin. Chitin is second only to cellulose as the most abundant natural biopolymer. It is a structural component of the exoskeleton of invertebrates(e.g., shrimp, crabs, lobsters), of the cell wall of fungi, and of the cuticle of insects. Chitosan is a derivative of chitin made by deacetylation of side chains. Many experiments using chitosan in various animal models have proven its beneficial effects. The aim of this study is to evaluate the osteogenesis of chitosan on the calvarial critical size defect in Sprague Dawley rats. An 8 mm surgical defect was produced with a trephine bur in the area of the midsagittal suture. The rats were divided into two groups: Untreated control group versus experimental group with 50mg of soluble chitosan gel. The animals were sacrificed at 2, 4 and 8 weeks after surgical procedure. The specimens were examined by histologic, histomorphometric and radiodensitometric analyses. The results are as follows: 1. The length of newly formed bone in the defects was $102.91{\pm}25.46{\mu}m$, $219.46{\pm}97.81{\mu}m$ at the 2 weeks, $130.95{\pm}39.24{\mu}m$, $212.39{\pm}89.22{\mu}m$ at the 4 weeks, $181.53{\pm}76.35{\mu}m$ and $257.12{\pm}51.22{\mu}m$ at the 8 weeks in the control group and experimental group respectively. At all periods, the means of experimental group was greater than those of control group. But, there was no statistically significant difference between the two groups. 2. The area of newly formed bone in the defects was $2962.06{\pm}1284.48{\mu}m^2$, $5194.88{\pm}1247.88{\mu}m^2$ at the 2 weeks, $5103.25{\pm}1375.88{\mu}m^2$, $7751.43{\pm}2228.20{\mu}m^2$ at the 4 weeks and $8046.20{\pm}818.99{\mu}m^2$, $15578.57{\pm}5606.55{\mu}m^2$ at the 8 weeks in the control group and experimental group respectively. At all periods, the means of experimental group was greater than those of control group. The experimental group showed statistically significant difference to the control group at the 2 and 8 weeks. 3. The density of newly formed bone in the defects was $14.26{\pm}6.33%$, $27.91{\pm}6.65%$ at the 2 weeks, $20.06{\pm}9.07%$, $27.86{\pm}8.20%$ at the 4 weeks and $22.99{\pm}3.76%$, $32.17{\pm}6.38%$ at the 8 weeks in the control group and experimental group respectively. At all periods, the means of experimental group was greater than those of control group. The experimental group showed statistically significant difference to the control group at the 2 and 8 weeks. These results suggest that the use of chitosan on the calvarial defects in rats has significant effect on the regeneration of bone tissue in itself

• Journal of Periodontal and Implant Science
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• v.33 no.1
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• pp.61-77
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• 2003

The major goals of periodontal therapy are the functional regeneration of periodontal supporting structures already destructed by periodontal disease as well as the reduction of signs and symptoms of progressive periodontal disease. There have been many efforts to develop materials and therapeutic methods to promote periodontal wound healing. Bone graft & guided tissue are being used for the regeneration of destroyed periodontium these days. Non-resorbable membranes were used for Guided tissue regeneration in early days, however more researches are focused on resorbable membranes these days. The aim of this study is to evaluate the osteogenesis of paradioxanone membrane on the calvarial critical size defect in Sprague Dawley rats. An 8 mm diameter surgical defect was produced with a trephine bur in the area of the midsagittal suture. The rats were divided into three groups: Untreated control group, Biomesh(R) group and paradioxanone group. The animals were sacrificed at 4, 8 and 12 weeks after surgical procedure. The specimens were examined by histologic, histomorphometric analyses. The results are as follows: 1. In histological view on Biomesh(R), no visible signs of resorption was observed at 4 weeks but progressive resorption was observed at 8 weeks through 12 weeks. Paradioxanone membrane expanded at 4 weeks, and rapid resorption was observed at 8 weeks. In both the membranes, inflammatory cells were observed around them. Inflammatory cells decreased with time but were still present at 12 weeks. More inflammatory cells were observed in paradioxanone membranes than in Biomesh(R) membrane. 2. The area of newly formed bone in the defects were 0.001${\pm}$0.001, 0.006${\pm}$0.005, 0.002${\pm}$0.003 at the 4 weeks, 0.021${\pm}$0.020, 0.133${\pm}$0.073, 0.118${\pm}$0.070 at the 8 weeks and 0.163${\pm}$0.067, 0.500${\pm}$0.197, 0.487${\pm}$0.214 at the 12 weeks in the control group, Biomesh(R) group and experimental group respectively. Compared to the control group, Biomesh(R) group displayed significant differences at 4,8, and 12 weeks and the paradioxanone group at 8 and 12 weeks.(P<0.05)

• Archives of Craniofacial Surgery
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• v.9 no.2
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• pp.85-89
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• 2008

Purpose: Unicoronal synostosis is the craniofacial anomaly caused by premature fusion of unilateral coronal suture. Ipsilateral flattening of the frontal and parietal bones, temporal retrusion with elevation and recession of the supraorbital rim are main clinical features. Compensatory contralateral frontal bossing and deviation of the nasal root and/or chin can also occur. There is a controversy about techniques for surgical correction, however, bilateral approach technique is more effective for correction of deformity. Methods: A 4-year-old patient with unicoronal synostosis had undergone unilateral suturectomy at 28-month-old but fronto-facial deformity had remained and aggravated as she grew older. She had both fronto-facial and endocranial asymmetry. We performed coronal cranial approach and fully exposed affected cranium including supraorbital rim. Anterior 2/3 calvarial reconstruction with bilateral frontal bone osteotomy and fronto-orbital bandeau advancement was performed. Results: Fronto-facial symmetry including fronto-orbital contour, nasal devation was improved. Endocranial twisting was also improved from $158^{\circ}$ to $162^{\circ}$ in CSO(crista gallisella turcica-opisthion) degree. There was no postoperative complications and no need for revision, and facial asymmetry improved at the period of 2 years of follow-up. Conclusion: Bilateral approach with fronto-orbital bandeau remodeling in surgery of unicoronal synostosis looked superior to unilateral approach in achieving better symmetry and preventing recurrence of asymmetry. Remodeling surgery should be tried in patients even at an older age to correct fronto-facial asymmetry.

• Archives of Plastic Surgery
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• v.40 no.4
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• pp.341-347
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• 2013

Background Intractable chronic scalp ulcers with cranial bone exposure can occur along the incision after cranioplasty, posing challenges for clinicians. They occur as a result of severe scarring, poor blood circulation of the scalp, and focal osteomyelitis. We successfully repaired these scalp ulcers using a vascularized bipedicled pericranial flap after complete debridement. Methods Six patients who underwent cranioplasty had chronic ulcers where the cranial bone, with or without the metal plate, was exposed along the incision line. After completely excising the ulcer and the adjacent scar tissue, subgaleal dissection was performed. We removed the osteomyelitic calvarial bone, the exposed metal plate, and granulation tissue. A bipedicled pericranial flap was elevated to cover the defect between the bone graft or prosthesis and the normal cranial bone. It was transposed to the defect site and fixed using an absorbable suture. Scalp flaps were bilaterally advanced after relaxation incisions on the galea, and were closed without tension. Results All the surgical wounds were completely healed with an improved aesthetic outcome, and there were no notable complications during a mean follow-up period of seven months. Conclusions A bipedicled pericranial flap is vascularized, prompting wound healing without donor site morbidity. This may be an effective modality for treating chronic scalp ulcer accompanied by the exposure of the cranial bone after cranioplasty.

• Journal of Periodontal and Implant Science
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• v.35 no.4
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• pp.1019-1037
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• 2005

The major goals of periodontal therapy are the functional regeneration of periodontal supporting structures already destructed by periodontal disease as well as the reduction of signs and symptoms of progressive periodontal disease. There have been many efforts to develop materials and therapeutic methods to promote periodontal wound healing. There have been increasing interest on the chitosan made by chtin. Chitosan is a derivative of chitin made by deacetylation of side chains. Chitosan has been widely studied as bone substitution and membrane material in periodontology. Many experiments using chitosan in various animal models have proven its beneficial effects. Tetracycline has been considered for use in the treatment of chronic periodontal disease and gingivitis. The aim of this study is to evlauate the osteogenesis of tetracycline blended chitosan membranes on the calvarial critical size defect in Sprague Dawley rats. An 8mm surgical defect was produced with a trephine bur in the area of the midsagittal suture. The rats were divided into five groups: Untreated control group versus four experimental group. Four types of membranes were made and comparative study was been done. Two types of non-woven membranes were made by immersing non-woven chitosan into either the tetracycline solution or chitosan-tetracycline solution. Other two types of sponge membranes were fabricated by immersing chitosan sponge into the tetracycline solution, and subsequent freeze-drying. The animals were sacrificed at 2 and 8 weeks after surgical procedure. The specimens were examined by histologic analyses. The results are as follows: 1. Clinically the use of tetracycline blended chitosan membrane showed great healing capacity. 2. The new bone formations of all the experimental group, non-woven and sponge type membranes were greater than those of control group. But, there was no significant difference between the experimental groups. 3. Resorption of chitosan membranes were not shown in any groups at 2 weeks and 8 weeks. These results suggest that the use of tetracycline blended chitosan membrane on the calvarial defects in rats has significant effect on the regeneration of bone tissue in itself. And it implicate that tetracycline blended chitosan membrane might be useful for guided tissue regeneration.

• Journal of Periodontal and Implant Science
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• v.36 no.1
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• pp.1-14
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• 2006

The purpose of the present study was to evaluate the histologic results of bone cavities that were surgically created in the calvaria of rabbit and filled with $HA/{\beta}-TCP$ composite powders, which had been developed in Korea (Dentium, Korea). Ten young adult rabbits were used. Four defects were surgically produced in calvaria of each rabbit. Each rabbit was anesthetized with Ketamine-HCI (5 mg/kg, Yuhan Cor. Korea) and Xylazine-HCI (1.5 ml/kg, Yuhan Cor. Korea)). An incision was made to the bony cranium and the periosteum was reflected. Using a trephine bur (external diameter: 8 mm, 3i, USA), 4 'through-and-through' bone defects were created with copious irrigation, and classified into 4 groups: control group: no graft materials, experimental group I: normal saline + graft materials: experimental group II: venous blood + graft materials: experimental group III: graft materials only. The defects were randomly filled with graft materials. The defects were closed with resorbable suture material. At the end of the surgical procedure, all animals received a single intramuscular injection of antibiotics Gentamicin (0.1 mg/kg, Dae Sung Microb. Korea). Rabbits were sacrificed with phentobarbital (100 mg/kg) intravenously at 1-, 2-, 4-, 6- and 8-week after. Specimens were treated with hydrochloric acid decalcifying solution (Fisher Scientific, Tustin, CA) and sectioned by bisecting the 8 mm diameter defects. The histologic specimens were prepared in the general method with H & E staining at 6 ${\mu}m$ in thickness. The results were as follows; 1. New bone formation showed from after 2-week of surgery in defect area. As time lapsed, lots of new bone formation and mature bones showed. 2. Histologically, degree of new bone formation could not be discerned among the experimental groups. But, for experimental group II, lots of cells gathered around graft materials after 1-week of surgery, new bone formed slightly faster and than the others at 1-week after. For experimental group I, a few inflammatory finding showed around graft material at after 1-week and after 2-week of surgery. 3. No bone formation did show for control group. Based on histologic results, the new $HA/{\beta}-TCP$ composite powders appeared to act as a scaffolding material for regeneration of osseous defects.