Research and development concept of barrier membranes based on “ immune microenvironment regulation” / 口腔疾病防治

@#Guided bone regeneration technology applied in alveolar bone defect regeneration is based on the barrier function and space maintenance of the barrier membrane. Therefore, traditional development strategies for barrier membranes focus on their physical barrier function, degradation characteristics and biocompatibility to avoid immunogenicity. However, not only does the barrier membrane passively block connective tissue, it is recognized as a “foreign body”that triggers a persistent host immune response, known as a foreign body reaction. The theories of osteoimmunology reveal a close relationship between the immune system and bone system and emphasize the role of immune cells in bone tissue-related pathophysiological processes. Based on these findings, we propose a novel development strategy for barrier membranes based on immune microenvironment regulation: by manipulating mechanical properties, surface properties and physiochemical properties, barrier membranes are endowed with an improved immunomodulation ability, which helps to regulate immune cell reactions to induce a favorable local immune microenvironment, thus coordinating osteogenesis and osteoclastogenesis as well as barrier membrane degradation to increase the efficiency of barrier membranes in GBR applications. In this paper, we review the development of barrier membranes and their close relationship to the immune microenvironment concerning bone regeneration and membrane degradation. Additionally, the outcomes of research on barrier membranes based on the regulation of the immune microenvironment have been summarized to improve the osteogenesis efficiency of barrier membranes and solve the problem of the regeneration and repair of bone defects, especially alveolar bone defects.

New progress in the clinical application of GBR membrane materials / 口腔疾病防治

@#Guided bone regeneration (GBR) barrier membranes are of great significance for the reconstruction of the health and function of different periodontal tissues. Biocompatibility, spatial maintenance, closure, controllability and biological activation are the main criteria that should be met by these membranes. Artificial barrier membrane biomaterials can be divided into synthetic polymer materials, natural polymer materials and metals. According to their degradation characteristics, these membranes can be divided into two categories, absorbable and nonabsorbable membranes. GBR used for horizontal bone increments can be used to treat various types of bone defects, including the treatment of bone fenestration and bone cracking. The use of a non-absorbable e-PTFE membrane or absorbable collagen membrane can achieve the expected effect. However, for incremental or vertical bone growth at the alveolar crest, the use of this membrane is very challenging and requires good strength to maintain the osteogenic space. This space can be enhanced with e-PTFE or d-PTFE membranes with stable morphology, or absorbable membranes can be covered with titanium plates or meshes to achieve vertical bone increments. Currently, bioactive membranes, digital 3D-printed titanium membranes and piezoelectric active biological membranes are research hotspots. In future research, the biological activation of these membranes will be further improved, which will promote the development of artificial membranes in the next stage.

Preparation and characteristics of drug loaded PLGA chitosan/nano-hydroxyapatite membrane for guided periodontal tissue regeneration in surgical implanting / 第二军医大学学报

Objective To prepare the porous drug-conlaining membrane by poly (ladic-co-glycolic acid) (PLGA)/ chitosan (CS)/nano-hydroxyapatitc for guided periodontal tissue regeneration in surgery, and lo evaluate its performance in vitro. Methods The samples were divided into four groups by different mass ratios of the PLGA lo CS (100: 0, 90: 10, 80: 20 and 70: 30). The PLGA/CS/nano-hydroxyapatitcporous films were prepared by freeze-drying process, wilh polyvinylpyrrolidone (PVP) used as porogcn. The best ratio was chosen by detecting the porosity, water absorption, mechanical properties and degradation of the films; and then il was used as drug carrier lo prepare membrane material for clindamycin controlled release. The morphology of membrane was observed by scan electronmicroscope, (he porosity was detected by anhydrous ethanol liquid displacement method, water absorption was determined by ratio of wet to dry weight of the film, (he wel mechanical performance was tested by electronic universal material testing, (he degradation was determined by weight loss and swelling degree, and the release character was investigated by ultraviolet spcctrophotometric method. In the in vitro experiments, periodontal ligament fibroblast cells (PLFs) were cultured in the membrane for 1-7 days, and cell proliferation was measured by CCK-8. Results The optimal porosity and degradation were found when the mass ratio of PLGA lo CS was 90: 10, wilh the porosity being (28. 66il. 35)%, water absorption being (108. 65 ± 2. 27) %, tensile strength being (2. 36 ± 0. 04) MPa, elongation at break of films being (203.64±3. 89)%, breaking power being (45. 98 ± 2. 46) N, and degradation being (17. 60 ± 0. 86)%. The maximum drug release was 150 μg • mL-1 • d-1, and the effective drug release concentration lasted for 15 d, which could promote the proliferation of PLFs. Conclusion The porous PLGA/CS/nano-hydroxyapatite film prepared in the present study has optimal porosity, its degradation in vitro fit well with the tissue growth, and can create and maintain a specific space for guided periodontal tissue regeneration, allowing for steady drug release for a certain period of time.

Rubber dam as a barrier membrane in the treatment of periodontal osseous defect.

Background: Barrier membrane helps in periodontal regeneration by preventing the migration of epithelial cells and cells from the gingival connective tissue onto the root surface. Different types of membranes have been used to regenerate periodontal tissues. There are very few documented reports where rubber dam has been used as a barrier membrane for regeneration of periodontal defects. Case Description: A female patient aged 20 years with localized aggressive periodontal disease participated in this clinical report. Infrabony defect in the lower anterior region was selected for surgical treatment. Rubber dam was trimmed to cover the defect. Orthodontic treatment was done for the realignment of malpositioned teeth 1 year after the surgery and patient was followed up for a period of 3 years after surgery. Results: Rubber barrier membrane did not result in any untoward side effects. Patient did not show any sign of inflammation or recurrence of probing depth at 3-year follow-up period. Clinical Implications: Rubber dam as barrier membrane yields good results.

Biomaterial development for oral and maxillofacial bone regeneration

Many oral and maxillofacial bone defects are not self-healing. Guided bone regeneration (GBR), which uses a barrier membrane to prevent the soft tissues from invading the defect to enable slower-growing bone cells to penetrate the area, was developed as a therapy in the 1980s. Although there has been some success with GBR in some clinical situations, better treatments are needed. This review discusses the concept of GBR focusing on bioactive membranes that incorporate osteoconductive materials, growth factors and cells for improved oral and maxillofacial bone regeneration.

Use of periosteal membrane as a barrier membrane for the treatment of buccal Grade II furcation defects in lower molars: A novel technique.

Objective : To use the periosteum as a barrier in treatment of buccal Grade II furcation defects of lower molars. Materials and Methods : This technique was performed on 12 patients with bilateral buccal Grade II furcation defects of lower molars. On a random basis, one furcation defect of each pair was selected for the control group and other for the experimental group. Debridement was done in the defect area in both groups. In the control group, after debridement, mucoperiosteal flap was sutured back. In the experimental group, after reflection of the mucoperiosteal flap, a portion of the periosteum along with a layer of connective tissue (periosteal membrane) was incised and mobilized in the defect area for defect coverage as a barrier, and then the periosteal membrane and mucoperiosteal flap were fixed with suture, respectively. Horizontal dimension of the furcation defect was the primary outcome measure. Gingival index, probing attachment level (PAL), and vertical dimension of furcation defect were the secondary outcome measures. Clinical parameters were registered at baseline and at 6 months. Results : Every clinical parameter was improved by surgery. Significant gain in PAL as well as horizontal and vertical dimensions of the furcation defects was found. Conclusion: This periosteum displacement technique is effective for the treatment of buccal Grade II furcation defects of lower molars.

Guided bone regeneration using two types of non-resorbable barrier membranes

INTRODUCTION: Guided bone regeneration (GBR) is a common procedure for the treatment of bone defects and bone augmentation. The non-resorbable barriers are well-documented barriers for GBR because of their stability and malleability. However, few GBR studies have focused on the different types of non-resorbable barriers. Therefore, this study examined the clinical results of different non-resorbable barriers for GBR; expanded polytetrafluoroethylene (e-PTFE) (TR-Gore Tex, Flagstaff, AZ, USA), and high-density polytetrafluoroethylene (d-PTFE) (Cytoplast membrane, Oraltronics, Bremen, Germany). MATERIALS AND METHODS: The analysis was performed on patients treated with GBR and implant placement from January 2007 to October 2007 in the department of the Seoul National University Bundang Hospital. The patients were divided into two groups based on the type of non-resorbable barrier used, and the amount of bone regeneration, marginal bone resorption after prosthetics, implant survival rate and surgical complication in both groups were evaluated. RESULTS: The implants in both groups showed high survival rates, and the implant-supported prostheses functioned stably during the follow-up period. During the second surgery of the implant, all horizontal defects were filled with new bone, and there was no significant difference in the amount of vertical bone defect. CONCLUSION: In bone defect areas, GBR with non-resorbable barriers can produce favorable results with adequate postoperative management. There was no significant difference in bone regeneration between e-PTFE and d-PTFE.

Effects of Recombinant Human Bone Morphogenetic Protein-2 loaded Acellular Dermal Matrix on Bone Formation / 대한치주과학회지

INTRODUCTION: The purpose of this study was to evaluate the possibility of the acellular dermal matrix (ADM) as a barrier membrane for bone regeneration, and to evaluate the osteogenic effect of ADM as a carrier system for rhBMP-2 in the rat calvarial defect model. MATERIALS AND METHODS: An 8-mm, calvarial, critical-size osteotomy defect was created in each of 60 male Spraque-Dawley rats(weight 250~300g). Three groups of 20 animals, each received either rhBMP-2(0.025mg/ml) in an ADM carrier, ADM only, or negative surgical control. And each group was divided i nto 2- and 8 -weeks healing intervals. The groups were evaluated by histologic and histomorphometric parameters(10 animals/group/healing intervals). Data were expressed as means+/-standard deviations(m+/-SD). Comparisons between experimental and control groups were made using two-way ANOVA and post hoc t-test. Comparisons between 2 weeks and 8 weeks were made using paired t-test. The level of statistical difference was defined as P< 0.05. RESULTS: The ADM group and rhBMP-2/ADM group results in enhanced local bone formation in the rat calvarial defect at both 2 and 8 weeks. The amount of defect closure and new bone formation were significantly greater in the rhBMP-2/ADM group relative to ADM group(P<0.05). At 8 weeks, the majority of ADM in the defect was contracted, and integrated with surrounding host tissues. In addition, host cell infiltration and neovascularization of the ADM in the absence of an inflammatory response were observed, and the newly formed bone around ADM showed a continuous remodeling and consolidation. CONCLUSION: The results of the present study indicated that ADM may be used as a barrier membrane for bone regeneration and that may be employed as a delivery system for BMPs.

Comparison of the Proliferation pattern of Cultured Rat Calvaria Cell on the Resorbable Barrier Membrane / 대한치주과학회지

The purpose of this study is to evaluate the phenomenon of attachment and spreading of the cultured rat calvarial cell inoculated on their surface of different kinds of biodegradable membrane which had been used on tissue regeneration on periodontal defects by using scanning electron microscope. In this experiment 30 Sprague-Dawley male rats (mean BW 150gm) were used to harvest abundant number of cell in the short period. The rats were sacrificed by decapitatioan to obtain the calvaria for bone cell culture. Calvarial cells were cultured with Dulbecco's Modified Essential Medium contained with 10% Fetal Bovine Serum under the conventional conditions. Biodegradable barrier membrane were collected with collagen type, and were divided into 3 different kind of surface such as scattered, polarized and fine-net type as their surface texture. Microcover plate which usually used for cell cuture was used as control for smooth surface. All the membrane were seeded with cultured calvarial cell on their surface. The number of cell inoculated on the membrane were 1x106 Cells/ml. After the culture as designed time, all the membrane were washed with 0.1 M Phosphate Buffered saline and fixed with 2.5% Glutaraldehyde. And all specimen were treated with OsO4, and Tannic acid before drying the cell for coating the cell with gold. Scanning Electron Microscope was used to observation. The following results were obtained. 1. During the whole period of experiment, the phenomenon of cell attachment and spreading were revealed similar pattern to compare with smooth surface culture plate and ordinary culture dish. 2. The shape of cell attchment and spreading on the surface of barrier membrane were observed no remaked difference pattern between smooth surface culture plate and ordinary culture dish. 3. The cytoplasmic process of cultured calvaria cell extent to the deep portion of barrier membrane like as their own proper shape. 4. There were no remarkable relationships between the degree of cultured cell spreading and surface structure of barrier membrane. 5. Slight starified layer of cultured calvaria cell were observed on the scattered type of resorbable membrane. Conclusively, this study thus suggest that cultured bone cell inoculated onto the biodegradable barrier membrane may have an important role of carrier for many cell which could be used as new tissue regeneration, and those tissue engeering technique may become an new method in the approach to the repair of bone defects.

Clinical Study on Therapeutic Effects of Biodegradable membrane Biomesh(R) and autogenous bone grafts in infrabony defects / 대한치주과학회지

The ultimate goal of periodontal disease therapy is to promote the regeneration of lost periodontal tissue, there has been many attempts to develop a method to achieve this goal, but none of them was completely successful. This study was designed to compare the effects of treatment using resorbable barrier membrane(Biomesh?) in combination with autogenous bone graft material with control treated by only modified Widman flap. 22 infrabony defecs from 10 patients with chronic periodontitis were used for this study, 10 sites of them were treated with resorbable barrier membrane and autogenous bone graft material as experimental group and 12 site were treated by only modified Widman flap as control group. Clinical parameters including probing depth, gingival recession, bone probing depth and loss of attachment were recorded at 6-8 months later, and the significance of the changes was statistically analyzed. The results are as follows : 1. Probing depth of the two group was reduced with statistically significance(P<0.05), but this changes were not different between the two experiment, control group with statistically significance. 2. Gingival recession showed statistically significant increase in control group(P<0.05), but not in experimental group, and initial values of the two group were in statistically significant difference(P<0.05). 3. Bone probing depth showed statistically significant decrease in experimental group(P<0.05), but not in control group, and this changes were different between the two experiment, control group with statistically significance(P<0.05). 4. Loss of attachment showed statistically significant decrease in experimental group(P<0.05), but not in control group, and this changes were different between the two experiment, control group with statistically significance(P<0.05) On the basis of these results, treatment using resorbable barrier membrane in combination with autogenous bone graft material improve the probing depth, bone probing depth and loss of attachment in infrabony defects.

Experimental study on bioactive membrane for guided bone regeneration in alveolar cleft / 实用口腔医学杂志

Objective: To evaluate the effect of barrier m em brane on guided bone regeneration(GBR) in alveolar cleft. Methods: The alveolar cleft of animal model was established in the maxilla in 10 rabbi ts. The artificial alveolar clefts were treated immediately with following mater ials respectively: (1) PLA+collagen+rhBMP-2 membrane, (2)PLA membrane, (3)colla ge membrane, (4) blank control. All the membranes were fixed by PLA pin and mini -titanium pin. The animals were sacrificed 2 weeks, 1,2,3 and 6 months after su rgery respectively. Samples were studied through macroscopic observation, X-rad iography, histomorphology and enzyme histochemistry analysis. Results: In the clefts covered with the 3 kinds of membrane more bone fromation wa s observed. The compound membrane of PLA+collagen+rhBMP-2 showed the best bone regeneration effects. Conclusion: The GBR technique can be used to repair the bone defect of alveolar cleft.