• Journal of Korean Dental Science
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• v.15 no.1
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• pp.51-60
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• 2022

Purpose: The aim of this study was to evaluate the bio-durability and bone regeneration capacity of the non-cross-linked collagen membrane in rabbit calvarial defect models. Materials and Methods: Four circular defects with 8 mm diameter were made in each of calvarium of 10 male rabbits. The following groups was randomly assigned to each defect - 1) Control, 2) membrane group containing non-cross-linked collagen membrane only (M), 3) bone graft group (B), 4) bone graft with membrane group (B+M). Animals were sacrificed and samples were harvested at 2 weeks (n=5) and 8 weeks (n=5). Histologic sections were prepared and histomorphometric analysis was performed. Result: Histologic results showed well adaptation of the non-cross-linked membrane on each defect and normal healing response at 2 weeks. At 8 weeks, the membranes were partially biodegraded. Histomorphometrically, B and B+M group showed the significantly greater total augmented area (B+M group, 10.44±1.49, P=0.016; B group, 9.13±0.53, P=0.032) and new bone formation (B+M group, 2.89±0.93, P=0.008; B group, 2.85±1.15, P=0.008) compared to control group. Collapsing of the central portion of the membrane, membrane group showed greater value in new bone formation at 8 weeks (1.78±0.68, P=0.032). Conclusion: Within the limitations of this study, the non-cross-linked collagen membrane fabricated using the improved decellularized method was shown to be effective for the regeneration of calvarial bone defects. In addition, prolonged barrier function might be provided using this collagen membrane.

• The Journal of the Korean dental association
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• v.56 no.12
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• pp.667-685
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• 2018

Objectives: Aim of this study was to evaluate bone regenerative efficacy of a chemically cross-linked porcine collagen membrane (CM) when used in combination with highly soluble biphasic calcium phosphate (BCP). Materials and methods: Physiochemical properties of the experimental collagen membrane were analyzed. Four circumferential defects with diameter of 8 mm were created in each calvarium of New Zealand white rabbits (n = 10). Defects were randomly allocated to one of following 4 groups: 1) BCP-CM (BCP (20% hydroxyapatite/80% ${\beta}$-tricalcium phosphate) covered with the prepared collagen membrane), 2) BCP (only BCP used), 3) CM (only the prepared collagen membrane used), and 4) C (control; only blood clot). After 2 weeks (n = 5) and 8 weeks (n = 5), histologic and histomorphometric analyses were performed. Results: The experimental collagen membrane exhibited dense and compact structure, relatively high tensile strength and lower degradability. Histologic analyses revealed that new bone increased rapidly at 2 weeks, while defect was preserved at 8 weeks. Histomorphometric analyses revealed that the new bone areas increased in the BCP-grafted groups over 8 weeks, with BCP-CM exhibiting greater total augmented area than that of BCP group both at 2 weeks ($27.12{\pm}3.99$ versus $21.97{\pm}2.27mm^2$) and 8 weeks ($25.75{\pm}1.82$ versus $22.48{\pm}1.10mm^2$) (P < 0.05). Conclusions: The experimental collagen membrane successfully preserved localized defect for 8 weeks despite early rapid resorption of BCP. Within the study limitations, combined use of the chemically cross-linked porcine collagen membrane and highly soluble BCP aided localized bone regeneration.

• Journal of Periodontal and Implant Science
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• v.45 no.6
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• pp.229-237
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• 2015

Purpose: The aim of this study was to determine the clinical feasibility of using dehydrothermally cross-linked collagen membrane (DCM) for bone regeneration around peri-implant dehiscence defects, and compare it with non-cross-linked native collagen membrane (NCM). Methods: Dehiscence defects were investigated in twenty-eight patients. Defect width and height were measured by periodontal probe immediately following implant placement (baseline) and 16 weeks afterward. Membrane manipulation and maintenance were clinically assessed by means of the visual analogue scale score at baseline. Changes in horizontal thickness at 1 mm, 2 mm, and 3 mm below the top of the implant platform and the average bone density were assessed by cone-beam computed tomography at 16 weeks. Degradation of membrane was histologically observed in the soft tissue around the implant prior to re-entry surgery. Results: Five defect sites (two sites in the NCM group and three sites in the DCM group) showed soft-tissue dehiscence defects and membrane exposure during the early healing period, but there were no symptoms or signs of severe complications during the experimental postoperative period. Significant clinical and radiological improvements were found in all parameters with both types of collagen membrane. Partially resorbed membrane leaflets were only observed histologically in the DCM group. Conclusions: These findings suggest that, compared with NCM, DCM has a similar clinical expediency and possesses more stable maintenance properties. Therefore, it could be used effectively in guided bone regeneration around dehiscence-type defects.

• Journal of Periodontal and Implant Science
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• v.50 no.4
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• pp.238-250
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• 2020

Purpose: This study aimed to evaluate the biocompatibility and the mechanical properties of ultraviolet (UV) cross-linked and biphasic calcium phosphate (BCP)-added collagen membranes and to compare the clinical results of ridge preservation to those obtained using chemically cross-linked collagen membranes. Methods: The study comprised an in vitro test and a clinical trial for membrane evaluation. BCP-added collagen membranes with UV cross-linking were prepared. In the in vitro test, scanning electron microscopy, a collagenase assay, and a tensile strength test were performed. The clinical trial involved 14 patients undergoing a ridge preservation procedure. All participants were randomly divided into the test group, which received UV cross-linked membranes (n=7), and the control group, which received chemically cross-linked membranes (n=7). BCP bone substitutes were used for both the test group and the control group. Cone-beam computed tomography (CBCT) scans were performed and alginate impressions were taken 1 week and 3 months after surgery. The casts were scanned via an optical scanner to measure the volumetric changes. The results were analyzed using the nonparametric Mann-Whitney U test. Results: The fastest degradation rate was found in the collagen membranes without the addition of BCP. The highest enzyme resistance and the highest tensile strength were found when the collagen-to-BCP ratio was 1:1. There was no significant difference in dimensional changes in the 3-dimensional modeling or CBCT scans between the test and control groups in the clinical trial (P>0.05). Conclusions: The addition of BCP and UV cross-linking improved the biocompatibility and the mechanical strength of the membranes. Within the limits of the clinical trial, the sites grafted using BCP in combination with UV cross-linked and BCP-added collagen membranes (test group) did not show any statistically significant difference in terms of dimensional change compared with the control group.

• Journal of Korean Dental Science
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• v.14 no.1
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• pp.12-25
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• 2021

Purpose: (i) To evaluate the biologic properties of a bi-layered 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride-cross-linked collagen membrane (CCM) in vitro. (ii) To assess the efficacy of CCM for localized bone regeneration in vivo. Materials and Methods: Biodegradation of CCM compared to a native collagen membrane (NCM) was assessed in vitro. In vivo, twelve male New Zealand White rabbits were used. Four calvarial, circular defects (diameter 8 mm) were created in each animal. The sites were randomly allocated to i) CCM+biphasic calcium phosphate (BCP) (CCM-BCP group), ii) CCM alone (CCM), iii) BCP alone (BCP) and, iv) negative control (control). Animals were sacrificed at 2 (n=6) and 8 weeks (n=6). Outcome measures included: micro-computed tomography (μCT) analysis (total augmented volume [TAV], new bone volume) and histomorphometry (total augmented area [TAA], newly formed bone, remaining membrane thickness [RMT]). Result: CCM was more resistant to degradation than NCM. μCT analysis showed CCM-BCP (196.43±25.30 mm³) and BCP (206.23±39.13 mm³) groups had significantly (P<0.01) larger TAV than the control (149.72±12.28 mm³) after 8 weeks. Histomorphometrically, CCM-BCP group (17.75±5.97 mm²) had significantly (P<0.01) greater TAA compared to the CCM group (7.74±2.25 mm²) and the control (8.13±1.81 mm²) after 8 weeks. After 8 weeks, RMT was reduced by 67%. Conclusion: CCM can be a favorable choice of barrier membrane when performing guided bone regeneration (GBR) in localized bone defects. CCM has better resistance to degradation than the natural collagen membrane, in vitro. In vivo, CCM provides an advantageous integration of prolonged barrier function and biocompatibility for GBR.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.33 no.2
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• pp.112-119
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• 2011

Purpose: Collagen membranes are used extensively as bioabsorbable barriers in guided bone regeneration. However, collagen has different effects on tissue restoration depending on the type, structure, degree of cross-linking and chemical treatment. The purpose of this study was to evaluate the inflammatory reaction, bone formation, and degradation of dehydrothermal treated porcine type I atelocollagen (CollaGuide$^{(R)}$) compared to of the non-crosslinked porcine type I, III collagen (BioGide$^{(R)}$) and the glutaldehyde cross-linked bovine type I collagen (BioMend$^{(R)}$) in surgically created bone defects in rat mandible. Methods: Bone defect model was based upon 3 mm sized full-thickness transcortical bone defects in the mandibular ramus of Sprague-Dawley rats. The defects were covered bucolingually with CollaGuide$^{(R)}$, BioMend$^{(R)}$, or BioGide$^{(R)}$ (n=12). For control, the defects were not covered by any membrane. Lymphocyte, multinucleated giant cell infiltration, bone formation over the defect area and membrane absorption were evaluated at 4 weeks postimplantation. For comparison of the membrane effect over the bone augmentation, rats received a bone graft plus different covering of membrane. A $3{\times}4$ mm sized block graft was harvested from the mandibular angle and was laid and stabilized with a microscrew on the naturally existing curvature of mandibular inferior border. After 10 weeks postimplantation, same histologic analysis were done. Results: In the defect model at 4 weeks post-implantation, the amount of new bone formed in defects was similar for all types of membrane. Bio-Gide$^{(R)}$ membranes induced significantly greater inflammatory response and membrane resorption than other two membranes; characterized by lymphocytes and multinucleated giant cells. At 10 weeks postoperatively, all membranes were completely resorbed. Conclusion: Dehydrotheramal treated cross-linked collagen was safe and effective in guiding bone regeneration in alveolar ridge defects and bone augmentation in rats, similar to BioGide$^{(R)}$ and BioMend$^{(R)}$, thus, could be clinically useful.

• The Journal of Advanced Prosthodontics
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• v.7 no.6
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• pp.484-495
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• 2015

PURPOSE. This study was to evaluate the effects of bacterial cellulose (BC) membranes as a barrier membrane on guided bone regeneration (GBR) in comparison with those of the resorbable collagen membranes. MATERIALS AND METHODS. BC membranes were fabricated using biomimetic technology. Surface properties were analyzed, Mechanical properties were measured, in vitro cell proliferation test were performed with NIH3T3 cells and in vivo study were performed with rat calvarial defect and histomorphometric analysis was done. The Mann-Whitney U test and the Wilcoxon signed rank test was used (${\alpha}<.05$). RESULTS. BC membrane showed significantly higher mechanical properties such as wet tensile strength than collagen membrane and represented a three-dimensional multilayered structure cross-linked by nano-fibers with 60 % porosity. In vitro study, cell adhesion and proliferation were observed on BC membrane. However, morphology of the cells was found to be less differentiated, and the cell proliferation rate was lower than those of the cells on collagen membrane. In vivo study, the grafted BC membrane did not induce inflammatory response, and maintained adequate space for bone regeneration. An amount of new bone formation in defect region loaded with BC membrane was significantly similar to that of collagen membrane application. CONCLUSION. BC membrane has potential to be used as a barrier membrane, and efficacy of the membrane on GBR is comparable to that of collagen membrane.

• Journal of Periodontal and Implant Science
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• v.50 no.5
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• pp.327-339
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• 2020

Purpose: The purpose of this study was to examine the local tissue reactions associated with 3 different poly(lactic-co-glycolic acid) (PLGA) prototype membranes and to compare them to the reactions associated with commercially available resorbable membranes in rats. Methods: Seven different membranes-3 synthetic PLGA prototypes (T1, T2, and T3) and 4 commercially available membranes (a PLGA membrane, a poly[lactic acid] membrane, a native collagen membrane, and a cross-linked collagen membrane)-were randomly inserted into 6 unconnected subcutaneous pouches in the backs of 42 rats. The animals were sacrificed at 4, 13, and 26 weeks. Descriptive histologic and histomorphometric assessments were performed to evaluate membrane degradation, visibility, tissue integration, tissue ingrowth, neovascularization, encapsulation, and inflammation. Means and standard deviations were calculated. Results: The histological analysis revealed complete integration and tissue ingrowth of PLGA prototype T1 at 26 weeks. In contrast, the T2 and T3 prototypes displayed slight to moderate integration and tissue ingrowth regardless of time point. The degradation patterns of the 3 synthetic prototypes were similar at 4 and 13 weeks, but differed at 26 weeks. T1 showed marked degradation at 26 weeks, whereas T2 and T3 displayed moderate degradation. Inflammatory cells were present in all 3 prototype membranes at all time points, and these membranes did not meaningfully differ from commercially available membranes with regard to the extent of inflammatory cell infiltration. Conclusions: The 3 PLGA prototypes, particularly T1, induced favorable tissue integration, exhibited a similar degradation rate to native collagen membranes, and elicited a similar inflammatory response to commercially available non-cross-linked resorbable membranes. The intensity of inflammation associated with degradable dental membranes appears to relate to their degradation kinetics, irrespective of their material composition.

• Journal of Periodontal and Implant Science
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• v.50 no.6
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• pp.406-417
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• 2020

Purpose: This study investigated whether the placement of ribose cross-linked collagen (RCLC) membranes without primary soft tissue closure predictably resulted in sufficient alveolar ridge preservation in contained and non-contained extraction sockets. Methods: Membranes were positioned across extraction sockets, undermining full-thickness flaps, and the gingival margins were fixed by double-interrupted sutures without crossed horizontal mattress sutures for 1 week. In non-contained sockets, a bone substitute was used to support the membrane within the bony envelope. Radiographs and clinical images obtained 4 months later were analyzed by ImageJ software using non-parametric tests. Results: In 18 patients, 20 extraction sockets healed uneventfully and all sites received standard-diameter implants (4.1, 4.8, or 5.0 mm) without additional bone augmentation. Soft tissues and the muco-gingival border were well maintained. A retrospective analysis of X-rays and clinical photographs showed non-significant shrinkage in the vertical and horizontal dimensions (P=0.575 and P=0.444, respectively). The new bone contained vital bone cells embedded in mineralized tissues. Conclusions: Within the limitations of this pilot study, open healing of RCLC membranes may result in sufficient bone volume for implant placement without additional bone augmentation in contained and non-contained extraction sockets.

• Clinical and Experimental Pediatrics
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• v.62 no.5
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• pp.193-197
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• 2019

Alport syndrome (ATS) is an inherited glomerular disease caused by mutations in one of the type IV collagen novel chains (${\alpha}3$, ${\alpha}4$, and ${\alpha}5$). ATS is characterized by persistent microscopic hematuria that starts during infancy, eventually leading to either progressive nephritis or end-stage renal disease. There are 3 known genetic forms of ATS, namely X-linked ATS, autosomal recessive ATS, and autosomal dominant ATS. About 80% of patients with ATS have X-linked ATS, which is caused by mutations in the type IV collagen ${\alpha}5$ chain gene, COL4A5. Although an 80% mutation detection rate is observed in men with X-linked ATS, some difficulties do exist in the genetic diagnosis of ATS. Most mutations are point mutations without hotspots in the COL4A3, COL4A4, and COL4A5 genes. Further, there are insufficient data on the detection of COL4A3 and COL4A4 mutations for their comparison between patients with autosomal recessive or dominant ATS. Therefore, diagnosis of ATS in female patients with no apparent family history can be challenging. Therefore, in this study, we used whole-exome sequencing (WES) to identify mutations in type IV collagen in 2 girls with glomerular basement membrane structural changes suspected to be associated with ATS; these patients had no relevant family history. Our results revealed de novo c.4688G>A (p.Arg1563Gln) and c.2714G>A (p.Gly905Asp) mutations in COL4A5. Therefore, we suggest that WES is an effective approach to obtain genetic information in ATS, particularly in female patients without a relevant family history, to detect unexpected DNA variations.