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Variations in bone regeneration adjacent to implants augmented with barrier membranes alone or with demineralized freeze-dried bone or autologous grafts: a study in dogs.

A study was performed in two large hound dogs to evaluate the bone-induction potential of demineralized freeze-dried bone (DFDBA) placed into defects adjacent to implants that were placed into extraction sockets. Two implants were untreated controls, two implants received only Gore-Tex Augmentation Membrane (GTAM), two implants received GTAM and autologous bone, and six sites received GTAM and DFDBA. DFDBA was prepared from the long bones of a dog of the same breed as the experimental dogs. P2, P3, and P4 were extracted bilaterally, and buccal defects were created and measured. Twelve commercially pure titanium Brånemark implants were placed. At 12 weeks, clinical measurements were taken and the dogs were sacrificed. The untreated control defects had a mean clinical bone fill of 1.75 mm (37%). Sites treated with autologous bone had a mean of 5.0 mm (95%) of clinical bone fill within the original defects. Sites treated with DFDBA and barriers had 3.8 mm (75%) of bone fill, while sites treated with membranes alone had a mean of 4.2 mm (80%) of bone fill. Histologic evaluation revealed that DFDBA sites had retained nonviable bone chips in 45.4% of the bone matrix, and only 8.3% was lamellar bone. Autologous graft sites had 26.2% retained bone chips within the bone matrix, and 61% percent of the matrix consisted of lamellar bone. For GTAM-only sites, 70.2% of the matrix was lamellar bone and 29.8% was woven bone. Retained DFDBA bone chips were nonviable, occasionally surrounded by woven bone, and appeared to break up and then remineralize without the presence of osteoclastic or osteoblastic activity. Retained autologous bone chips were surrounded and incorporated by the host bone. The autologous bone grafts and DFDBA implants were considered to be osteoconductive. For the three treatment groups, within the defects there were sparse bone-implant contacts. The results indicate that GTAM barriers alone or with autologous bone grafts produced the best clinical and histologic results. DFDBA did not appear to induce bone formation in any of the evaluated specimens.

Alveolar Process↗

Evaluation of a tissue-engineered membrane-cell construct for guided bone regeneration.

PURPOSE: Currently, a number of bioresorbable and biodegradable membranes used for guided bone regeneration lead to incomplete tissue regeneration. Poor mechanical properties, short degradation time, and the lack of integrated biologic components result in the inability to create and maintain an appropriate environment and to actively support tissue remodeling. In the present study, the osteogenic potential of human calvarial periosteal cells in combination with ultrathin polycaprolactone (pc2) membranes of a slow biodegradation rate was investigated. MATERIALS AND METHODS: In vitro and in vivo analyses of the tissue-engineered constructs were conducted using imaging techniques, immunohistochemistry, and histology. Two types of membranes were investigated. Group 1 consisted of a plain membrane, and in group 2 membranes were treated with sodium hydroxide. RESULTS: In vitro results showed that osteoblast-like cells attached and proliferated on the membranes with the formation of extracellular matrix. Sodium hydroxide-treated membranes showed enhanced cell attachment and proliferation kinetics, resulting in a dense cellular layer after 2 weeks in culture. In vivo mineralized tissue formation in association with vascularization was observed. Extracellular matrix calcification with nodule formation was detected via histology as well as scanning electron microscopy. DISCUSSION: PCL membranes support the attachment, growth, and osteogenic differentiation of human primary osteoblast-like cells. Sodium hydroxide-treated membranes demonstrated increased cell attachment resulting from increased hydrophilicity. CONCLUSION: These findings have potential application in the development of a new generation of osteoconductive membranes.

Absorbable Implants↗

Reduced gap strains induce changes in bone regeneration during distraction.

A bilateral New Zealand white rabbit model of distraction osteogenesis (DO) was used to investigate the relationship between strain environment and bone regeneration during limb lengthening. In seven (n = 7) rabbits, a stiffener was applied to the fixator on one side to reduce strains within the gap tissue after lengthening was completed. Animals were euthanized six days later and their distraction zones were harvested and analyzed for changes in new bone volume and architecture. Nonlinear finite element analyses (FEA) were performed to predict changes in the gap strain environment. FEA results predicted a nearly uniform sevenfold decrease in average strain measures within the distraction zone. No change in total average new bone volume and significant decreases in both bone volume fraction (BV/TV) and trabecular thickness (Tb.Th) were observed in tibiae in which gap strains were reduced experimentally, compared to contralateral controls. These results suggest that fixator stiffening influenced the architecture but not the amount of newly formed bone. This animal model of distraction might be used to study the mechanisms by which strain fields affect events in bone repair and regeneration, such as cell proliferation, precursor tissue differentiation, and altered growth factor and nutrient delivery to tissues.

Animals↗

Resorbable versus nonresorbable membranes in combination with Bio-Oss for guided bone regeneration.

The purpose of this clinical investigation was to compare the new resorbable collagen membrane, Bio-Gide, to the conventional expanded polytetrafluoroethylene material (Gore-Tex) for guided bone regeneration in situations involving exposed implant surfaces. Over a 2-year period, 25 split-mouth patients were treated randomly: one defect site was treated with Bio-Gide and the other defect site with Gore-Tex; all 84 defects were filled with Bio-Oss and covered with the respective membrane. The defect types, their dimensions, and their morphology were measured in detail initially and at re-entry to allow for calculation of the exposed implant surface. Changes in defect surface for both types of membranes were statistically significant (P < .0001); however, no statistical significance (P > .94) could be detected between the two membranes. The mean average percentage of bone fill was 92% for Bio-Gide and 78% for Gore-Tex sites. In the latter group, 44% wound dehiscences and/or premature membrane removal occurred. The resorbable membrane, Bio-Gide, in combination with a bone graft, can be a useful alternative to the well-established expanded polytetrafluoroethylene membranes.

Absorption↗

Demineralized Bone Matrix-stimulated Bone Regeneration in Rats Enhanced by an Angiogenic Dipeptide Derivate.

A lysyl-proline derivate (LP) known to stimulate angiogenesis and formation of granulation tissue was tested as a local additive to allogeneic demineralized bone matrix (DBM) using a rat craniotomy model. Peracetic-acid sterilized DBM (10 mg/defect) was implanted into three groups of 45 animals each with 0, 6 and 20 microg LP. Subsequent evaluation was done by descriptive histology, histomorphometry, and determination of the calcium content of the explants 7, 14, 28, 42 and 84 days post-implantation. Grafting with DBM alone resulted in defect bridging by newly formed bone with incorporated DBM residues on day 84. Addition of LP to the implants caused an enhanced capillarization on day 14 and 28 as well as an enhanced mineralization on day 14, 28, 42 and 84. Both effects were dose-dependent. These data suggest that the local application of a synthetic angiogenic factor significantly improve bone regeneration in DBM-grafted trephine defects in rats. Thereby, they reinforce the opinion that early angiogenesis is crucial for a number of subsequent events in the bone regeneration process.

Journal Article↗

Cortical bone regeneration with a synthetic cell-binding peptide: a histologic and histomorphometric pilot study.

PepGen P-15 is a combination natural anorganic bovine-derived hydroxyapatite matrix (ABM) coupled with a synthetic cell-binding peptide (P-15). This material has been reported to enhance bone formation in periodontal osseous defects. The aim of this study was to assess the effect of ABM/P-15 on the healing of cortical bone defects in rabbits. Five New Zealand rabbits were used. Two 8-mm bone defects were created in each tibia. Eight defects were filled with PepGen P-15, 8 defects with PepGen P-15 Flow, and 4 defects were used as a control group. A total of 20 defects were created. All rabbits were killed at 4 weeks. Block sections containing the defects were retrieved and the specimens processed for light microscopy examination. Newly formed bone was present in both test groups, whereas, in the control-group, only a scarce quantity of newly formed bone was present and the cortical defects had not been filled by the regenerated bone. Statistical evaluation showed that there were statistically significant differences between control sites and sites treated with P-15 and P-15 Flow (P = 0.0001), and also between sites treated with P-15 and P-15 Flow (P = 0.0001), respectively. No acute inflammatory infiltrate cells were visible in both of these groups. Both PepGen P-15 and PepGen P-15 Flow enhanced new bone formation in the cortical drilled defects, whereas control defects showed very little newly formed bone.

Animals↗

[Calcium metabolism and the level of active metabolites of vitamin D3 in the rat serum during bone regeneration].

Fracture of rat femur bone was accompanied by an increase in content of calcium and 25(OH)D3, by a decrease in content of 1,25(OH)2D3 while the 24,25(OH)2D3 level was unaltered in blood serum as well as an augmented absorption of calcium was found in small intestine during formation and mineralization of callus. The elevated consumption of the vitamin D3 active metabolites in small intestine mucose and in bone tissue and/or stimulation of their biosynthesis in these tissues appear to occur in response to transformation of the calcium metabolism and to remodelation of rat bone tissue in fractures.

24,25-Dihydroxyvitamin D 3↗

[Histologic and histomorphometric study of bone regeneration induced by beta-tricalcium phosphate (multicenter study)].

INTRODUCTION: Autogenous bone graft insertion can effectively enhance the regeneration of the debilitated bone. However, bone graft can be harvested only by a second surgery, which is inconvenient for the patient and raises the possibility of many complications. AIMS: The effect of an alloplastic bone-replacing material, beta-tricalcium phosphate and that of the autogenous bone graft were compared. The studies were performed on patients deriving from four European centers. METHODS: In 20 edentulous patients, the alveolar ridge was extremely atrophied, so fixation of the denture was impossible. The base of the maxillary sinus was surgically elevated bilaterally by insertion of Cerasorb (beta-tricalcium phosphate) (experimental side) and by autogenous bone graft (control side). After surgery the recovery was controlled clinically and radiologically. After 6 months bone cylinders were excised from the grafted areas and implants were inserted into their place. 80 bone samples were embedded into resin, and the osteointegration of the grafts was studied histologically. The new bone density was measured by histomorphometry. RESULTS: Beta-tricalcium phosphate proved to be an effective bone replacing material with osteoconductivity, and was capable of gradual disintegration, providing space to the regenerating bone. The new bone density was similar on both sides without significant differences. CONCLUSIONS: After 6 months, insertion of the beta-tricalcium phosphate graft resulted in formation of stable bony bed apt to anchor of dental implants.

Adult↗

Development of beta-tricalcium phosphate/collagen sponge composite for bone regeneration.

Synthetic biomaterials have been developed and used for bone grafting. Here, we developed a biodegradable sponge composite for bone tissue engineering by combining beta-tricalcium phosphate (beta-TCP) and collagen. In addition, we sought to determine the optimal beta-TCP granules/collagen ratio by evaluating and bone formation in vivo. Porous beta-TCP granules were mixed with atelocollagen hydrochloride solution at various ratios--0.02, 0.05, 0.1, and 0.2 g/mL. The resultant mixtures were freeze-dried and subjected to dehydrothermal treatment in vacuo. The final composites obtained were designated beta-TCP/collagen sponge composites (beta-TCP/CS). Through compression testing, it was found that the stress values for beta-TCP/CS (0.2 g/mL) were higher than those of the other three composites over the whole strain range. Histological evaluation at four weeks after implantation revealed that the collagen sponge had degraded and newly formed bone was present on the surface of the beta-TCP granules. At 12 weeks, the beta-TCP granules were completely degraded and remodeling of the lamellar bone was observed.

Animals↗

Studying bone regeneration with the scanning electron microscope.

The interest in bone structure is very old. That is shown in a historical review with special regard to bone fractures and gap healing. The three-dimensional architecture of the supporting tissue corresponds to the strain acting on it. This can only be presented clearly in the SEM, especially by stereoscopical documentation. Three aspects of utmost importance when studying bone formation were taken into consideration: the three-dimensional presentation of the trabeculae, the processing of the vascular system together with the bony trabeculae, and the preservation of the cells and fibres in their natural state which is only guaranteed in a non-dehydrated frozen state. Reliable bone histology requires the preparation of non-decalcified specimens which are processed for light microscopy. Labeling newly formed bone with fluorochromes is a very common method to analyse sequences of bone formation. Studying the same specimens using both fluorescence microscopy and the SEM provides information not obtained using one method alone. Fresh specimens can be processed for the SEM following light microscopical documentation especially in incident fluorescent light; embedded blocks used for light microscopical investigations can also give valuable information in the SEM when the resin has been removed. The combination of the different methods is of special interest for orthopaedic basic research.

Animals↗

[The bone regeneration in cleft palate after surgical repair (a prelimilnary observation)].

OBJECTIVE: To study the bone healing situation of the cleft palate after surgical procedure, and discuss the factors affecting it. METHODS: 20 patients with repaired cleft palate were examined by CT scan coronally. The result of images were observed and the position, shape and quality of bone bridge were measured. RESULTS: Formation of bone bridge was found in 13 cleft gaps out of 20 patients (65%), the sex ratio among patients with bone bridge was 1:1; there was no obvious difference between unilateral and bilateral cleft palate. Considering the operation age with the bone formation, the highest percentage of bone bridge formation fell into the group of 4-6 years old, and the most occurring regions were in premolar and anterior part of molar area. CONCLUSIONS: There can be new bone bridge regeneration in bone gap after palate surgery, and the bone formation may have some relationship with the operation age and surgical technique.

Adolescent↗

Alveolar distraction osteogenesis vs. vertical guided bone regeneration for the correction of vertically deficient edentulous ridges: a 1-3-year prospective study on humans.

The purpose of this prospective study was to compare vertical guided bone regeneration (GBR) and vertical distraction osteogenesis (DO) for their ability in correcting vertically deficient alveolar ridges and their ability in maintaining over time the vertical bone gain obtained before and after implant placement. Eleven patients (group 1) were treated by means of vertical GBR with autogenous bone and e-PTFE membranes, while 10 patients (group 2) were treated by means of DO. In group 1, six patients received implants at the time of GBR (subgroup 1A), while five patients had implants placed at the time of membrane removal (subgroup 1B). In group 2, implants were placed at the time of distraction device removal. A total of 25 implants were placed in group 1 and 34 implants were placed in group 2 patients. Three to 5 months after implant placement, patients were rehabilitated with implant-borne dental prostheses. The following parameters were evaluated: (a) bone resorption of the regenerated ridges before and after implant placement; (b) peri-implant clinical parameters 1, 2, and 3 years after prosthetic loading of implants; (c) survival and success rates of implants. Bone resorption values before and after implant placement were significantly higher in group 1. The results suggested that both techniques may improve the deficit of vertically resorbed edentulous ridges, although distraction osteogenesis seems to be more predictable as far as the long-term prognosis of vertical bone gain is concerned. Implant survival rates as well as peri-implant clinical parameters do not differ significantly between the two groups, whereas the success rate of implants placed in group 2 patients was higher than that obtained in group 1 patients.

Adolescent↗

Membrane-guided bone regeneration. Segmental radius defects studied in the rabbit.

We tested the principle of guided tissue regeneration (GTR) for healing segmental long-bone defects. 7 mm (3 animals) or 10 mm (5 animals) long segmental defects were created in the diaphyses of both radii in 8 rabbits. The defect on one side was covered with a barrier membrane of expanded polytetrafluoroethylene membrane shaped as a tube, while the contralateral side with no membrane served as the control. Healing was followed with radiographs obtained repeatedly during a 13- (n 3) or 27- (n 5) week period. Thereafter, the animals were killed and ground sections of the defect sites were prepared for histologic examination. Radiographically, the control sites showed some early subperiosteal callus formation and nonunion of the defects after 6 weeks. The bone ends were rounded off and sealed with cortical bone. No major changes were noted after 6 weeks. At the test sites, subperiosteal bone formation at the bone ends was first observed radiographically at 2 weeks. At 9 weeks, a thin cortical bone bridged the defect along the inner surface of the membrane. Histologically, an interrupted line of thin, cortical bone was observed along the inner surface of the barrier membrane. Fatty bone marrow occupied the central and largest volume of the defect. We conclude that it seems possible to use the principle of GTR to accomplish bone union of segmental long-bone defects.

Animals↗

Bone regeneration around implants using spherical and granular forms of bioactive glass particles.

PURPOSE: It has been reported that previous Biogran (3i Implant Innovations, Inc., Palm Beach Gardens, FL) can be converted in vitro into hydroxyapatite (Biogran II) to accelerate new bone formation. The purpose of this study was to evaluate the bone regeneration around implants placed in critical-sized defects in rabbit tibia using granular and spherical forms of Biogran II in regards to implant contact, bone-to-graft contact, bone graft area, and total bone volume. MATERIALS AND METHODS: Twelve adult New Zealand rabbits were used, offering 24 surgical sites (1 in each tibia), where 6-mm round defects were created allowing the homocentric insertion of a screw type experimental implant with Osseotite (3i Implant Innovations, Inc.) surface. Half of the defects (group A) were filled up with spherical and half (group B) with granular forms of Biogran II. Ossix (3i Implant Innovations, Inc.) membranes covered the surgical sites. RESULTS: The histological evaluation after 8 weeks showed new bone formation in both groups, without any statistically significant differences in regards to bone-to-implant contact, bone-to-graft contact, bone graft area, and bone volume. Both dissolution of the outer shell and inner silica gel of the particles were observed mostly in spherical particles. In addition, new bone formation within the protected pouch interconnected with the surrounding new bone was observed exclusively in spherical particles of Biogran II. CONCLUSION: Faster dissolution of both outer and inner portions of spherical particles of Biogran II led to better integration with the surrounding new bone during an 8-week period of healing.

Animals↗

Management of peri-implant bone loss using guided bone regeneration: a clinical report.

This clinical report presents a patient who developed peri-implant bone loss around 2 maxillary endosseous root-form implants after restoration with cement-retained single crowns. Significant localized bone loss occurred around 1 of the implants due to retained excess cement. Reparative treatment consisted of a guided bone regeneration technique. Following a 9-month period of submerged healing, the implants were re-exposed and restored to complete function.

Adult↗

Non-invasive densitometric and histomorphometric study of the regenerated bone in the distraction gap in rabbits.

The long period of external fixation after the completion of distraction, which is necessary to obtain enough strength for resisting without fixation is a significant disadvantage of distraction osteogenesis. The purpose of this study is to understand the mechanical property of the regenerated bone and try to find an appropriate timing for safely removing the fixation device. An external fixation device was applied to the right tibia in rabbits and transverse osteotomy was performed just below the tibio-fibula junction. The tibiae were lengthened 7.2 mm at 0.72 mm a day for 10 days after surgery. A bone mineral density (BMD) and stress strain index (SSI) analyzed by peripheral quantitative computed tomography showed a significant increase on day 40, but returned to the control level at day 64 after the completion of distraction. Therefore, the newly formed bone between the host cortical bone seemed to be enough to resist the mechanical stress on day 40 during the consolidation period in this study. The present results suggested the possibility of removing the fixation device during the period when the BMD and SSI showed a significantly high level during the consolidation period.

Absorptiometry, Photon↗

Mechanical and radiological assessment of the influence of rhTGFbeta-3 on bone regeneration in a segmental defect in the ovine tibia: pilot study.

Limitations in the use of autologous bone graft, which is the gold standard therapy in bone defect healing, drive the search for alternative treatments. In this study the influence of rhTGFbeta-3 on mechanical and radiological parameters of a healing bone defect in the sheep tibia was assessed. In the sheep, an 18-mm long osteoperiosteal defect in the tibia was treated by rhTGFbeta-3 seeded on a poly(L/DL-lactide) carrier (n = 4). In a second group (n = 4), the defect was treated by the carrier only, in a third group (n = 4) by autologous cancellous bone graft, and in a fourth group (n = 2) the defect remained blank. The healing process of the defect was assessed by weekly in vivo stiffness measurements and radiology as well as by quantitative computed tomographic assessment of bone mineral density (BMD) every 4 weeks. The duration of the experiment was 12 weeks under loading conditions. In the bone graft group, a marginally significant higher increase in stiffness was observed than in the PLA/rhTGFbeta-3 group (p = 0.06) and a significantly higher increase than in the PLA-only group (p = 0.03). The radiographic as well as the computed tomographic evaluation yielded significant differences between the groups (p = 0.03), indicating the bone graft treatment (bone/per area, 83%; BMD, 0.57 g/cm(3)) performing better than the PLA/rhTGFbeta-3 (38%; 0.23 g/cm(3)) and the PLA-only treatment (2.5%; 0.09 g/cm(3)), respectively. Regarding the mechanical and radiological parameters assessed in this study, we conclude that rhTGFbeta-3 has a promoting effect on bone regeneration. However, under the conditions of this study, this effect does not reach the potential of autologous cancellous bone graft transplantation.

Absorbable Implants↗