Novel membrane for guided bone regeneration

Membranes have been clinically used for guided tissue and bone regeneration for decades, but their use in every day clinical practice is rather limited. We developed a biodegradable membrane (InionGTR) composed of polylactide, polyglycolide and trimethylene carbonate aiming to improve the properties of membrane. Before application the membrane is treated with N-methyl-pyrrolidone (NMP) to achieve a rubber like consistency, to allow easy handling and manageability in the clinical setting. After placing the membrane NMP diffuses out from the polymer phase into the water phase. The loss of NMP in the polymer stiffens the membrane up and allows space maintenance in the defect area. In addition the influx and efflux of NMP creates a porous surface on the membrane leading to an improved integration of tissues into the porous surface layers of the InionGTR membrane. Therefore, the use of NMP improves the handling in the clinical setting, and allows tissue integration and space maintenance, both important for the outcome of the treatment.     

Collagen-silica xerogel nanohybrid membrane for guided bone regeneration

A collagen-silica xerogel hybrid membrane was fabricated by a sol-gel process for guided bone regeneration (GBR). The silica xerogel synthesized by the sol-gel method was distributed uniformly within the collagen matrix in the form of nanoparticles. The hybridization of the silica xerogel with collagen improved the biological properties of the membrane significantly. Preosteoblast cells were observed to adhere well and grow much more actively on the hybrid membrane than on the pure collagen membrane. In particular, the hybrid membrane containing 30% of the silica xerogel showed the highest level of osteoblast differentiation. Moreover, the GBR ability, as assessed by the in vivo animal test, was superior to that of the pure collagen membrane. These findings suggest that the collagen-silica xerogel hybrid can be used as a GBR membrane.     

Haversian remodeling in guided bone regeneration with calcium alginate film in circular bone defect model of rabbit

The objective of this study is to investigate the effect of bioabsorbable Calcium alginate film in guided bone regeneration by the study of Haversian remodeling. Circular bone defects of 5 mm diameter were created in the corners of mandibles in 35 rabbits. The defects were covered with calcium alginate film (CAF) served as the experimental group, or collagen membrane (CM) as the control group, respectively. Healing condition was analyzed with gross, histological and immunohistochemical studies after 1, 2, 4, 6 and 8 weeks. The experimental group appeared more and earlier Haversian remodeling and osteoinductive factors leading to better bone regeneration. The control group showed more macrophages, less and later Haversian remodeling, absorbed slowly, while collected fewer osteoinductive factors in the early stage. Calcium alginate film, which is a relatively cheaper material, provides better effect than the collagen membrane in bone regeneration, Haversian remodeling and quantity of osteoinductive factors.     

Self-setting barrier membrane for guided tissue regeneration method: initial evaluation of alginate membrane made with sodium alginate and calcium chloride aqueous solutions.

Alginate membrane was proposed as a self-setting barrier membrane that can be used for guided tissue regeneration (GTR). The alginate membrane can be prepared and placed at the bone defect during the surgical procedure. The procedure consists of two simple steps. First, the bone defect is filled with sodium alginate (Na-Alg) aqueous solution. Then calcium chloride aqueous solution is dropped on the surface of the Na-Alg aqueous solution. An alginate membrane is formed on the bone defect, keeping the inside of the bone defect filled with unreacted Na-Alg aqueous solution. In this investigation, a preliminary animal study was conducted for an initial evaluation as to whether or not the alginate membrane can be used as a barrier membrane for the GTR method. Bone defects were made in the tibiae of 15-week-old rats. The alginate membrane was made on the surface of existing bone by filling the defect with Na-Alg aqueous solution and then dropping calcium chloride aqueous solution onto the surface of the Na-Alg solution. Four weeks after surgery, the bone defect was found to be reconstructed with new bone when the defect had been covered with alginate membrane whereas the bone defect was filled only with connective tissue when it had been kept open. We concluded, therefore, that this alginate membrane may be a useful barrier membrane when the GTR method is employed.     

A histological evaluation for guided bone regeneration induced by a collagenous membrane

This study was designed to evaluate the histological changes during ossification and cellular events including osteogenic differentiation responding to collagenous bioresorbable membranes utilized for GBR. Standardized artificial bony defects were prepared at rat maxillae, and covered with a collagenous bioresorbable membrane. These animals were sacrificed at 1, 2, 3 and 4 weeks after the GBR-operation. The paraffin sections were subject to tartrate resistant acid phosphatase (TRAP) enzyme histochemistry and immunohistochemistry for alkaline phosphatase (ALP), osteopontin (OP) and osteocalcin (OC). In the first week of the experimental group, woven bone with ALP-positive osteoblasts occupied the lower half of the cavity. The collagenous membrane included numerous ALP-negative cells and OP-immunoreactive extracellular matrices. At 2 weeks, the ALP-, OP- and OC-immunoreactivity came to be recognizable in the region of collagenous membrane. Since ALP-negative soft tissue separated the collagenous membrane and the new bone originating from the cavity bottom, the collagenous membrane appeared to induce osteogenesis in situ. At 3 weeks, numerous collagen fibers of the membrane were embedded in the adjacent bone matrix. At 4 weeks, the membrane-associated and the cavity-derived bones had completely integrated, showing the same height of the periosteal ridge as the surrounding alveolar bones. The collagen fibers of a GBR-membrane appear to participate in osteogenic differentiation.     

Asymmetrically porous PLGA/Pluronic F127 membrane for effective guided bone regeneration

Porous guided bone regeneration (GBR) membranes with selective permeability, hydrophilicity and adhesiveness to bone were prepared with PLGA and Pluronic F127 using an immersion precipitation method. The porous PLGA/Pluronic F127 membranes were fabricated by immersing the PLGA/Pluronic F127 mixture solution (in tetraglycol) in a mold into water. The PLGA/Pluronic F127 mixture was precipitated in water by the diffusion of water into PLGA/Pluronic F127 mixture solution. It was observed that the membrane has an asymmetric column-shape porous structure. The top surface of the membrane (water contact side) had nano-size pores (approx. 50 nm) which can effectively prevent from fibrous connective tissue invasion but permeate nutrients, while the bottom surface (mold contact size) had micro-size pores (approx. 40 μm) which can improve adhesiveness with bone. From the investigations of mechanical property, water absorbability, model nutrient permeability and preliminary in vivo bone regeneration, the hydrophilized porous PLGA/F127 (5 wt%) membrane seems to be a good candidate as a GBR membrane for the effective permeation of nutrients and osteoconductivity, as well as good mechanical strength to maintain a secluded space for bone regeneration.     

Asymmetrically porous PLGA/Pluronic F127 membrane for effective guided bone regeneration

Porous guided bone regeneration (GBR) membranes with selective permeability, hydrophilicity and adhesiveness to bone were prepared with PLGA and Pluronic F127 using an immersion precipitation method. The porous PLGA/Pluronic F127 membranes were fabricated by immersing the PLGA/Pluronic F127 mixture solution (in tetraglycol) in a mold into water. The PLGA/Pluronic F127 mixture was precipitated in water by the diffusion of water into PLGA/Pluronic F127 mixture solution. It was observed that the membrane has an asymmetric column-shape porous structure. The top surface of the membrane (water contact side) had nano-size pores (approx. 50 nm) which can effectively prevent from fibrous connective tissue invasion but permeate nutrients, while the bottom surface (mold contact size) had micro-size pores (approx. 40 microm) which can improve adhesiveness with bone. From the investigations of mechanical property, water absorbability, model nutrient permeability and preliminary in vivo bone regeneration, the hydrophilized porous PLGA/F127 (5 wt%) membrane seems to be a good candidate as a GBR membrane for the effective permeation of nutrients and osteoconductivity, as well as good mechanical strength to maintain a secluded space for bone regeneration.     

Prefabrication of vascularized bone graft using guided bone regeneration

This article describes the prefabrication of a vascularized bone graft composed of autologous particulate cancellous bone and marrow (PCBM), a vessel bundle, and a biodegradable membrane. The PCBM was placed around the saphenous vessel bundle of rats and rolled with a biodegradable membrane of L-lactide-epsilon-caprolactone copolymer to prepare the prefabricated vascularized bone graft (group A). As controls, combinations of PCBM and membrane (group B), vessel bundle and membrane (group C), and PCBM and vessel bundle (group D) were prepared. A radiographic study revealed radio-opacity in the implantation site of group A 1 week later, in contrast to the other groups. Newly formed bone in the membrane roll was histologically confirmed, and neomicrovasculature circulating from the vessel bundle through the newly formed bone tissue was observed. The increase in alkaline phosphatase activity and osteocalcin content was significant for the group A preparation compared with the other groups. We concluded that the combination of autologous PCBM, a vessel bundle, and a biodegradable membrane was promising in the prefabrication of vascularized bone with good blood circulation.     

The role of rhFGF-2 soaked polymer membrane for enhancement of guided bone regeneration

Abstract

The purposes of this study are to confirm the role of Fibroblast Growth Factor-2 (FGF-2) in bone regeneration by adding various concentrations of FGF-2 to the collagen membrane and applying it to the Biphasic Calcium Phosphate (BCP) bone graft site for guided bone regeneration, to explore the potential of collagen membrane as FGF-2 carrier, and to determine the optimum FGF concentration for enhancement of bone regeneration. Four bone defects of 8 mm in diameter were created in 18 New Zealand rabbit calvaria. After BCP bone graft, graft material was covered with collagen membranes adding various concentration of FGF-2. The concentration of FGF-2 was set at 1.0, 0.5, 0.1 mg/ml, and same amount of saline was used in the control group. To confirm the bone regeneration over time, six New Zealand rabbits were sacrificed each at 2, 4, and 12 weeks, and the amounts of new bone and residual bone graft material were analyzed by histologic and histomorphometric analysis. Qualitative analyses are also conducted through immunohistochemistry, Tetrate-resistant acid phosphatase (TRAP) stain and Russell-Movat pentachrome stain. As the healing period increased, the formation of new bone increased and the amount of residual graft material decreased in all experimental groups. Immunohistochemistry, TRAP staining and pentachrome staining further showed that the addition of FGF-2 promoted bone regeneration in all experimental groups. It was also confirmed that polymer collagen membrane can be used as a useful carrier of FGF-2 when enhanced early stage of new bone formation is required.     

Effect of biological/physical stimulation on guided bone regeneration through asymmetrically porous membrane

Asymmetrically porous polycaprolactone (PCL)/Pluronic F127 guided bone regeneration (GBR) membranes were fabricated. The top surface of the membrane had nanosize pores (～10 nm) which can effectively prevent invasion by fibrous connective tissue but permeate nutrients, whereas the bottom surface had microsize pores (～200 μm) which can enhance the adhesiveness with bone tissue. Ultrasound was applied to a bone morphogenetic protein (BMP-2)-immobilized PCL/F127 GBR membrane to investigate the feasibility of using dual biological (BMP-2) and physical (ultrasound) stimulation for enhancing bone regeneration through the membrane. In an animal study using SD rats (cranial defect model), the bone regeneration behavior that occurred when using BMP-2-loaded GBR membranes with ultrasound treatment (GBR/BMP-2/US) was much faster than when the same GBR membrane was used without the ultrasound treatment (GBR/BMP-2), as well as when GBR membranes were used without stimulations (GBR). The enhanced bone regeneration of the GBR/BMP-2/US group can be interpreted as resulting from the synergistic or additive effect of the asymmetrically porous PCL/F127 membrane with unique properties (selective permeability, hydrophilicity, and osteoconductivity) and the stimulatory effects of BMP-2 and ultrasound (osteoinductivity). The asymmetrically porous GBR membrane with dual BMP-2 and ultrasound stimulation may be promising for the clinical treatment of delayed and insufficient bone healing.     

A composite polymer/tricalcium phosphate membrane for guided bone regeneration in maxillofacial surgery

The aim of the study was the development of a resorbable membrane for guided bone regeneration (GBR) with improved biocompatibility, which should be stiff enough to avoid membrane collapse during bone healing. Combining a bioactive ceramic with a resorbable polymer may improve the biocompatibility and osteoconductivity of resorbable devices. The present article describes the preparation, the mechanical properties, and the in vitro degradation characteristic of a composite membrane made of poly(L, DL-lactide) and alpha-tricalcium phosphate in comparison to a membrane made of pure poly(L, DL-lactide). The tensile strength and the elastic modulus as well as the molecular weight of the membranes were measured after in vitro degradation in buffer at 37 degrees C up to 28 weeks. The initial tensile strength of the composite and the polymer membrane was 37.3 +/- 2.4 MPa and 27.7 +/- 2.3 MPa and the elastic modulus 3106 +/- 108 MPa and 3101 +/- 104 MPa, respectively. The mechanical properties remained constant up to 8 weeks and then decreased slowly until week 28. The molecular weight of both membranes decreased steadily from 170,000 D to 30,000 D. It was concluded that the mechanical requirements for a membrane for GBR were fulfilled by the composite membrane.     

Collagen-apatite nanocomposite membranes for guided bone regeneration

Collagen-apatite nanocomposite is regarded as a potential biomaterial because of its composition and structure, which are similar to those of human hard tissues. However, there have been few investigations of its mechanical and biological benefits in direct comparison with a collagen equivalent. Herein, we successfully produced a biomedical membrane made of a nanocomposite, and systemically evaluated the mechanical, chemical, and biological properties of the nanocomposite in comparison with those of pure collagen. The results showed that significant improvements were achieved by the nanocomposite approach, particularly in terms of the mechanical strength and chemical stability. The present findings point to the potential usefulness of the collagen-apatite nanocomposite membrane in the field of guided bone regeneration (GBR).     

Hydrophilized polycaprolactone nanofiber mesh-embedded poly(glycolic-co-lactic acid) membrane for effective guided bone regeneration

A novel guided bone regeneration (GBR) membrane was fabricated by an immersion precipitation of poly (glycolic-co-lactic acid) (PLGA)/Pluronic F127 solution impregnated in an electrospun polycaprolactone (PCL)/Tween 80 nanofiber mesh. The prepared PCL/Tween 80 nanofiber mesh-embedded PLGA/Pluronic F127 membrane (hydrophilized PCL/PLGA hybrid membrane) had nano-size pores on the top side (which can prevent from fibrous connective tissue infiltration but allow permeation of oxygen and nutrients) and micro-size pores on the bottom side (which can improve adhesiveness with bone). From the comparisons of mechanical properties (tensile and suture pullout strengths), model nutrient (FITC-labeled bovine serum albumin) permeability, and bone regeneration behavior using a rat model (skull bone defect) of the hybrid membrane with those of PLGA/Pluronic F127 membrane (asymmetrically porous, hydrophilized PLGA membrane), PCL/Tween 80 nanofiber mesh (electrospun, hydrophilized PCL nanofiber mesh), and a commercialized GBR membrane, Bio-Gide (collagen type I/III membrane), it was observed that the PCL/PLGA hybrid membrane seems to be highly desirable as a GBR membrane for the selective permeability caused by its unique morphology and osteoconductivity provided by several tens micro-size pores of the bottom side as well as the excellent mechanical strengths by the hybridization of porous PLGA membrane and PCL nanofiber mesh.     

Development of guided bone regeneration membrane composed of beta-tricalcium phosphate and poly (L-lactide-co-glycolide-co-epsilon-caprolactone) composites

To create biodegradable and thermoplastic materials for guided bone regeneration, GBR, and guided tissue regeneration, GTR, membranes, composites of beta-tricalcium phosphate, TCP, and biodegradable polyesters, poly (L-lactide-co-glycolide-co-epsilon-caprolactone), PLGC, and poly (L-lactide-co-epsilon-caprolactone), PLCL, were prepared by a heat-kneading method. The composites maintained thermoplasticity and mechanical strength by formation of a chemical interaction between Ca on TCP and C=O on the lactide segment of PLGC or PLCL. The composites also indicated composite effects in pH auto-regulation property and elongation of biodegradation period, e.g., the composites maintained their mechanical strength up to 12 weeks after soaking in both physiological and phosphate-buffered saline, and the period was sufficient time to use for GBR and GTR membranes. Animal tests for GBR indicated that the present composite membrane successfully regenerated beagles' mandible defects 10 x 10 x 10 mm3 in size. These results suggested that the TCP/PLGC bioresorbable composites could be utilized for GBR and GTR therapy.     

Bioabsorbable scaffolds for guided bone regeneration and generation

Several different bioabsorbable scaffolds designed and manufactured for guided bone regeneration and generation have been developed. In order to enhance the bioactivity and potential osteoconductivity of the scaffolds, different bioabsorbable polymers, composites of polymer and bioactive glass, and textured surface structures of the manufactured devices and composites were investigated in in vitro studies and experimental animal models. Solid, self-reinforced polyglycolide (SR-PGA) rods and self-reinforced poly L-lactide (SR-PLLA) rods were successfully used as scaffolds for bone formation in muscle by free tibial periosteal grafts in animal experiments. In an experimental maxillary cleft model, a bioabsorbable composite membrane of epsilon-caprolactone and L-lactic acid 50/50 copolymer (PCL/LLA) film and mesh and poly 96L,4D-lactide (PLA96) mesh were found to be suitable materials for guiding bone regeneration in the cleft defect area. The idea of solid layer and porous layer combined together was also transferred to stiff composite of poly 70L,30DL-lactide (PLA70) plate and PLA96 mesh which structure is introduced. The osteoconductivity of several different biodegradable composites of polymers and bioactive glass (BG) was shown by apatite formation in vitro. Three composites studied were self-reinforced composite of PLA70 and bioactive glass (SR-(PLA70 + BG)), SR-PLA70 plate coated with BG spheres, and Polyactive with BG.     

Evaluation of porous collagen membrane in guided tissue regeneration

Porous collagen membrane was prepared with collagen protein, which was extracted from bovine tendon by enzyme digestion, by freeze-drying method. The animal, clinical experiments of the membrane used in artificial dental implant system were studied. In the animal experiments, pure titanium spiral implants, which were prepared according to Adell etc. method, were implanted in the mandibular dental alveus of adult hybrid dog and covered with collagen membrane. Then the animals were killed after 4, 18 weeks individually. In the clinical research, the implants (phi 3.3 mm) were used in 33 patients of different age groups. The implant was put on the buccal lateral deficiency of implantation cavity wall, and covered with collagen membrane on the buccal lateral, then observed after 3, 6 months individually. The results of animal experiments proved the collagen membrane could guide osseous tissue regeneration around the bone integral implant which was implanted in the fresh tooth extraction fossa, be helpful to repair the fissural bone deficiency produced when implanted the implant, increase the bone content around the implant significantly, and improve the structure of new bone to a certain extent. The results of clinical research proved that collagen membrane was used in the patients with density deficiency, irregularity of alveolar ridge, or artificial dental of shorter tooth extraction, could significantly improved the bone density of artificial implant's shoulder.     

引导骨再生技术在治疗三叉神经痛中的应用

目的：探讨引导骨再生( GBR)技术在治疗三叉神经痛的临床效果。方法选择三叉神经第Ⅱ支眶下神经痛的患者根据治疗方法分成治疗组48例,对照组47例,治疗组在眶下神经切断撕脱的同时采用GBR技术,对照组常规行眶下神经切断撕脱术。结果经术后1~2年随访,应用GBR技术治疗三叉神经有效率明显优于对照组(P<0.01)。结论 GBR技术在治疗三叉神经中疗效确切,可作为治疗三叉神经的优先选择。     

Poly(L-lactide)acid/alginate composite membranes for guided tissue regeneration

The barrier membranes for guided tissue regeneration (GTR) to treat bone defects have to satisfy the criteria of biocompatibility, cell-occlusiveness, space-making, tissue integration and clinical manageability. In this study a system constituted of a poly(L-lactide) acid (PLLA) asymmetric membrane combined with an alginate film was prepared. The PLLA membrane functions to both support the alginate film and separate the soft tissue; the alginate film is intended to act as potential vehicle for the growth factors to promote osteogenesis. The structural, morphological, and mechanical properties of the bilamellar membrane and its stability in culture medium were evaluated. Moreover, the feasibility of using the alginate membranes as controlled-release delivery vehicles of TGF-beta was monitored. Finally, the bacterial adhesion and permeability of Streptococcus mutans, selected for the high adhesive affinity, were monitored. The results showed that the surfaces of the alginate side, to be used in contact with the bone defect, were rougher than PLLA ones. When in contact with complete culture medium, the PLLA-alginate membrane retained its mechanical and structural properties for more than 100 days. Then, the degradation processes occurred but the membrane continued to be stable and manageable for 6 months. Growth factors such as TGF-beta can be incorporated into alginate membranes functioning as drug delivery vehicle, and retain the biological activity when tested in an in vitro model system. The obtained membrane acted as a barrier to the passage of S. mutans bacteria and showed to promote a lower bacterial adhesion with respect to commercial GTR membranes.     

Effects of latex membrane on guided regeneration of long bones

Abstract

Natural latex extracted from Hevea brasiliensis is one of the materials pointed out as potential tissue regenerators. The use of latex-based membranes in bone regeneration might be an alternative to stimulate bone formation. The aim of this study was to evaluate the effects of latex membranes in guided bone regeneration of defects produced in long bones of rats. Sixty rats were equally divided into latex and control groups, and each group was subdivided into two subgroups according to treatment duration of 1 and 4 weeks. Bone defects with 2.5?mm in diameter were surgically made in the left tibia. In the animals of the latex group, a latex membrane was placed over the bone defect. The samples underwent quantitative histological analysis of bone formation and collagen matrix, immunohistochemical analysis of osteogenic protein markers, assessment of bone mechanical properties and bone densitometry, and radiological assessment. The osteocalcin immunostaining data were submitted to the generalized linear model test with two independent factors. For the other data, the multivariate ANOVA with two independent factors was performed. The use of the latex membrane significantly improved (p?<?0.005) the volume of newly formed bone, collagen type I matrix, expression of osteopontin, and bone stiffness, both in the early and late stages of regeneration. In conclusion, the latex membrane was able to promote bone regeneration in long bones.