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Guided bone regeneration in calvarial bone defects using polytetrafluoroethylene membranes.

Guided bone regeneration is defined as controlled stimulation of new bone formation in a bony defect, either by osteogenesis, osteoinduction, or osteoconduction, re-establishing both structural and functional characteristics. Bony defects may be found as a result of congenital anomalies, trauma, neoplasms, or infectious conditions. Such conditions are often associated with severe functional and esthetic problems. Corrective treatment is often complicated by limitations in tissue adaptations. The aim of the investigation was to compare histologically the amount of bone formed in an experimentally created parietal bone defect protected with one or two polytetrafluoroethylene membranes with a contralateral control defect. A bony defect was created bilaterally in the parietal bone lateral to the sagittal suture in 29 6-month-old male Wistar rats. The animals were divided into two groups: (1) In the double membrane group (n = 9), the left experimental bone defect was protected by an outer polytetrafluoroethylene membrane under the periosteum and parietal muscles and an inner membrane between the dura mater and the parietal bone. (2) In the single membrane group (n = 20), only the outer membrane was placed. The right defect was not covered with any membrane and served as control. The animals were killed after 30 days. None of the control defects demonstrated complete or partial bone regeneration. In the single membrane group, the experimental site did not regenerate in 15 animals, partially in four, and completely in one. In the double membrane group, six of the experimental defects had complete closure with bone, two had partial closure, and one no closure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of platelet-rich plasma on bone regeneration in autogenous bone graft.

In this study, we evaluated the effect of platelet-rich plasma (PRP) on bone regeneration in an autogenous bone graft in a canine model. The mandibular premolar teeth had been bilaterally extracted previously, and the ridges had been allowed to heal for 3 months. After this period, continuity resection was performed on both sides of the mandible. One defect (the PRP group) was reconstructed with the original particulate bone mixed with PRP. As a control, the contralateral defect (non-PRP group) was reconstructed with the original particulate bone alone. Biopsies after 6 weeks showed lower levels of bone formation in the PRP group than in the non-PRP group, and fluorescence microscopy revealed a delay in the remodelling of grafts loaded with PRP. These findings suggest that the addition of PRP does not appear to enhance new bone formation in autogenous bone grafts.

Animals↗

Recombinant human acidic fibroblast growth factor and fibrin carrier regenerates bone.

Bone regeneration promoted by acidic recombinant human fibroblast growth factor (rhFGF-1), rabbit demineralized bone matrix (rDBM), and a fibrin (f) delivery system was measured in critical-sized defects in rabbits' radii. A unilateral segmental defect 20 mm in length was prepared in radii of 48 skeletally mature New Zealand White rabbits divided equally between 4- and 8-week cohorts. The temporal cohorts were divided equally among four treatment groups: rDBM, rDBM/f, rDBM/rhFGF-1/f, and rhFGF-1/f. Data for the fifth group, untreated critical-sized defects, were exploited from previous published reports from this laboratory. In response to experimental treatments, radiomorphometric and histomorphometric methods were used to derive quantitative outcome data that were tested by analysis of variance and post hoc multiple comparison tests (significance p </= 0.05). Radiomorphometric data (percentage of radiopacity of defect) were acquired at the day of the operation and every 2 weeks thereafter, whereas histomorphometric data (square millimeters of new bone formation) were determined at term. The objective for the study was to develop candidate bone regenerative therapies. Therefore, the hypotheses were that experimental treatments would promote bone formation within critical-sized defects and that one treatment would be superior to the rest. Testing hypotheses was achieved with quantitative methodology, and data were subjected to statistical models. Radiopacity at each 2-week period was greater in treated defects than in untreated critical-sized defects. The amount of radiopacity promoted by rDBM/f and rhFGF-1/f at 8 weeks was equivalent and was greater than antecedent times. Histomorphometric data analyses indicated that rDBM/f and rDBM evoked the same quantity of new bone formation at 4 weeks; by 8 weeks, all treatments except rDBM/f had more new bone within the critical-sized defects in comparison to untreated defects. That rDBM/f promoted less new bone than rDBM alone may suggest fibrin decreases bone formation, perhaps by impeding local solubility of endogenous and rDBM-containing signaling molecules. However, rhFGF-1/f promoted a significant and unexpected increase in bone formation response that could refute the previous notion. In conclusion, the combination of rDBM/rhFGF-1/f may represent a significant, new osteogenic therapeutic regimen. Additional assessments in higher order species must be accomplished to corroborate efficacy.

Animals↗

Maintenance of regenerated bone beneath pontics: preliminary clinical report of 43 sites.

Ridge augmentation was achieved through the use of guided bone regeneration procedures in pontic areas of 43 planned fixed prostheses. Measurements taken through templates, which fit over the final fixed prostheses, at the time of prosthetic placement and a mean of 123 weeks after prosthesis placement demonstrated a change of less than 0.1 mm in buccopalatal dimensions of the regenerated hard tissues.

Adult↗

Bone regeneration after radicular cyst removal with and without guided bone regeneration.

In order to determine the degree of bone regeneration after removal of radicular cysts using guided bone regeneration (GBR), a prospective, controlled and randomized clinical study was performed. Thirty patients with radicular cysts were divided into three groups. One group, the control group (n=10 patients), was treated by enucleation and primary closure. The other two groups were treated by enucleation and primary closure but GBR was used in addition, using a resorbable membrane (n=10) and a nonresorbable membrane (n=10). The membranes were fixed with nonresorbable Memfix System screws. The residual volume and the density of the newly formed tissue was measured by computer-assisted tomography and computer-assisted digital image analysis before enucleation and three and six months postoperatively. No statistical significance was found in density and residual volume between the three treatment groups after six months. These results suggest that GBR using membranes does not contribute to increased bone regeneration.

Adult↗

Enhanced bone regeneration at a segmental bone defect by controlled release of bone morphogenetic protein-2 from a biodegradable hydrogel.

The objective of this study is to investigate the feasibility of a biodegradable hydrogel of gelatin as the controlled release carrier of bone morphogenetic protein-2 (BMP-2) suitable for enhancement of bone regeneration at a segmental bone defect. Hydrogels with three different water contents were prepared through glutaraldehyde crosslinking of gelatin with an isoelectric point of 9.0 under varied reaction conditions. Segmental critical-sized defects (20 mm) were created at the ulnar bone of skeletally mature New Zealand white rabbits, and gelatin hydrogels incorporating BMP-2 (17 microg/hydrogel) were implanted into the defects. When bone regeneration was evaluated by soft x-ray observation and bone mineral density (BMD) measurement, the gelatin hydrogels incorporating BMP- 2 exhibited significantly high osteoinduction activity compared with that of free BMP-2, although the activity depended on the water content of the hydrogels. Significantly higher BMD enhancement was observed in the gelatin hydrogel with a water content of 97.8 wt% than that with the lower or higher water content. We concluded that the biodegradable gelatin hydrogel is a promising controlled release carrier of BMP-2 for bone regeneration at the segmental bone defect.

Absorbable Implants↗

Gene therapy for bone regeneration.

Efficacious bone regeneration could revolutionize the clinical management of many bone and musculoskeletal disorders. Bone has the unique ability to regenerate and continuously remodel itself throughout life. However, clinical situations arise when bone is unable to heal itself, as with segmental bone loss, fracture non-union, and failed spinal fusion. This leads to significant morbidity and mortality. Current attempts at improved bone healing have been met with limited success, fueling the development of improved techniques. Gene therapy in many ways represents an ideal approach for augmenting bone regeneration. Gene therapy allows specific gene products to be delivered to a precise anatomic location. In addition, the level of transgene expression as well as the duration of expression can be regulated with current techniques. For bone regeneration, the gene of interest should be delivered to the fracture site, expressed at appropriate levels, and then deactivated once the fracture has healed. Delivery of biological factors, mostly bone morphogenetic proteins (BMPs), has yielded promising results both in animal and clinical studies. There has also been tremendous work on discovering new growth factors and exploring previously defined ones. Finally, significant advances are being made in the delivery systems of the genes, ranging from viral and non-viral vectors to tissue engineering scaffolds. Despite some public hesitation to gene therapy, its use has great potential to expand our ability to treat a variety of human bone and musculoskeletal disorders. It is conceivable that in the near future gene therapy can be utilized to induce bone formation in virtually any region of the body in a minimally invasive manner. As bone biology and gene therapy research progresses, the goal of successful human gene transfer for augmentation of bone regeneration draws nearer.

Animals↗

[Experimental study on stimulation of guided bone regeneration by autogenous bone marrow].

OBJECTIVE: To study the effect of autogenous bone marrow on guided bone regeneration (GBR), and evaluate the repairing ability of GBR in bone defect with autogenous bone marrow. METHODS: Ten mm segmental defects were produced in both radii of 18 rabbits. The defect was bridged with a silicon tube. Autogenous bone marrow was injected into the tube on the experimental group at 0, 2, 4 weeks after operation, and peripheral blood into the control group at the same time. The X-ray, gross, histological and biochemical examinations were observed in various times. RESULTS: The new bone formation of experimental group was prior to that of control group; calcium and alkaline phosphatase of experimental group were higher than those of control group. The experimental group had all been healed at the tenth week, but no one healed in control group. CONCLUSION: It can be conclude that autogenous bone marrow can stimulate bone formation and facilitate GBR in bone defect.

Animals↗

Homogeneous osteogenesis and bone regeneration by demineralized bone matrix loading with collagen-targeting bone morphogenetic protein-2.

Considerable research has been focused on the development of bone morphogenetic protein-2 (BMP-2) delivery system for homologous and efficient bone regeneration. The aim of the present study was to develop a collagen-based targeting bone repair system. A collagen-binding domain (CBD) was added to the N-terminal of native BMP-2 to allow it bind to collagen specifically. We showed that the collagen-binding bone morphogenetic protein-2 (named bone morphogenetic protein2-h, BMP2-h) had maintained the full biological activity as compared to rhBMP2 lacking the CBD. In vitro functional study also demonstrated that collagen matrix could maintain higher bioactivity of BMP2-h than native BMP-2. When demineralized bone matrix (DBM) impregnated with BMP2-h was implanted subcutaneously in rats, homogeneous bone formation was observed. Moreover, in a rabbit mandible defect model, surgical implantation of collagen matrix loaded with BMP2-h exhibited remarkable osteoinductive properties and excellent homogeneous bone formation. Our studies suggested that this novel collagen-based BMP-2 targeting bone repair system induced better bone formation not only in quantity but also in quality. Similar approaches may also be used for the repair of other tissue injuries.

Animals↗

Recovery of alveolar bone by the guided bone regeneration technique.

Bone defects associated with the removal of endosteal implants often create challenging problems for clinicians. The guided bone regeneration (GBR) technique has been recently used in the treatment of such defects, and promising results have been obtained. This report describes the use of Gore-Tex tissue augmentation material (GTAM) membranes after the removal of Bioceram screw implants in two patients who wore the implants for 10 years and seven years, respectively. After removal, the residual bone defects were treated by the GBR technique. Bone regeneration was confirmed in the defects around the newly placed implants, and decreased bone mass was avoided in both patients. In case 1, a free gingival graft was used to increase the area of attached gingiva around the implants, since the status of peri-implant soft tissue is also crucial to the outcome of therapy. This technique was very effective in maintaining an adequate width of attached gingiva.

Adult↗

[Cellular aspects of bone regeneration: role of bone marrow periostium].

Bone regeneration is only possible if stem cells give rise to progenitors of osteoblasts, chondroblasts or chondroidocytes. Stem cells and osteogenic progenitors were evidenced in bone marrow while only progenitors can be found in periosteum. Bone marrow stem cells did show an amazing plasticity and some cells of the bone surrounding tissues such as perivascular cells, adipocytes, muscle cells or even circulating cells are able to transdifferentiate in osteoblasts when submitted to an osteogenic environment. We have shown that the destruction of both bone marrow and periost impairs the bone healing. It indicates that the periost and bone marrow destruction removes the predetermined osteogenic cells and the informative factors able to induce the transdifferenciation of the cells contained in the peri-osseous tissues.

Bone Marrow↗

Bone regeneration by recombinant human bone morphogenetic protein-2 around immediate implants: a pilot study in rats.

PURPOSE: Difficulties relating to bone regeneration that complicate immediate implant placement include buccal and/or lingual fenestrations, primary anchorage of the implants, and the need for protection from functional loading during the osseointegration period. The objective of this pilot study was to evaluate bone regeneration by recombinant human bone morphogenetic protein-2 (rhBMP-2) around immediate implants placed in maxillary sockets in rats. MATERIALS AND METHODS: A total of 16 cylindric 0.8 x 1.8-mm commercially pure, solid titanium Implants were placed immediately after gentle extraction of the maxillary first molar teeth of 8 male Wistar rats. The sockets were randomly divided into 3 groups: group 1 (n = 6) received rhBMP-2 with polylactic acid/polyglycolic acid copolymer-coated gelatin sponge carrier; group 2 (n = 5) received only the carrier; and group 3 (n = 5) received no grafting materials following placement The rats were euthanized at 90 days postsurgery for microscopic analysis. RESULTS: In group 1, the implant body remained submerged completely, including the coronal part, which was fully covered by a significant amount (30% of total height) of regenerated cortical bone, even though the implant could easily be pulled out by a tweezer at the time of placement. Close approximation between the implant surface and regenerated bone could also be detected, indicating good bone-to-implant contact. In contrast, only peri-implant bone regeneration occurred in group 2, and an approximate 0.3-mm coronal part of the implant remained exposed. When no grafting materials were used (group 3), almost one third of the total length of the implant was exfoliated out of the socket when no grafting materials were used. DISCUSSION AND CONCLUSIONS: Based on previous study and data from 16 sockets of the present study, it could be concluded that rhBMP-2 facilitated the regeneration of bone around immediate implants. In particular, the bone covering the coronal part could have been regenerated shortly after surgery, which helped to maintain the implant body inside the socket during the integration period in rats.

Animals↗

The importance of periodontal pathogens in guided periodontal tissue regeneration and guided bone regeneration.

Although guided tissue regeneration (GTR) procedures in periodontitis lesions and around endosseous dental implants represent exciting new therapeutic modalities in periodontics, these treatments can fail because of shortcomings in surgical techniques, restriction in the size and shape of the defect, anatomic features interfering with surgery, or infectious complications. Our studies show that optimal tissue regeneration cannot be expected for a nonbioabsorbable barrier membrane placed in a site infected by periodontopathic microorganisms. Our data also indicate that treatment failure is most frequent in patients who harbor high levels of periodontal pathogens and show evidence of severe periodontitis in numerous teeth. To decrease the risk of infection and to ensure proper healing, periodontal therapy should precede insertion of the barrier membrane for GTR. Recently, we have studied the effect of the pathogens on periodontal GTR and guided bone regeneration around dental implants and the results are reviewed in this article.

Biofilms↗

[Experimental observation of origins of osteoblasts in guided bone regeneration in long bone].

OBJECTIVE: To study the origins of osteoblasts in guided bone regeneration (GBR) so as to understand the mechanism of GBR. METHODS: New Zealand rabbits were used. Standard ununited defect models were made in bilateral middle radial shaft of each rabbit. Randomly, one defect enveloped with silicon membrane as test, another without membrane as control. 12 rabbits were selected for X-ray examination weekly after procedure. 30 rabbits were divided into 6 groups, and sacrificed at 3 days, 1, 2, 3, 4, 5 weeks after surgery for histological observation by immunohistochemical staining of BMP, BGP. RESULTS: The sealed spaces were made by silicon membranes in the defects to prevent peripheral tissue ingrowing early. The defect spaces were filled by granulation tissue formed from proliferative endoperiosteal and medullary stromal cells in bone end. Histological characteristics after callus forming showed that there were 2 - 3 layers of osteoblasts in the surface of callus, and granulation tissue in the center of bone defect. The transforming region existed between the extending callus and granulation tissue, which consisted of a few of cells and a lot of stroma. Early proliferative endo-periosteal and medullary stromal cells in the bone end were positive against BMP, BGP. Some cells in the transforming region were positive against BMP, BGP after callus forming. CONCLUSIONS: Osteoblasts derive from endoperiosteum and medullary stroma in the early stage of GBR and from granulation tissue formed by proliferative endo-periosteal and medullary stromal cells in the later stage.

Animals↗

In vitro and in vivo evaluation of e-PTFE and alkali-cellulose membranes for guided bone regeneration.

Guided bone regeneration (GBR) is employed to encourage the formation of new bone in osseous defects by restricting the infiltration of soft tissues. While a variety of membranes have been evaluated for this surgical procedure, the non-resorbable material of choice is currently expanded polytetrafluoroethylene (e-PTFE). A new alkali-cellulose membrane produced by a biotechnological process has been developed as an alternative to e-PTFE for GBR. In this study, the biocompatibility of this novel alkali-cellulose membrane and e-PTFE was compared using tissue culture and an in vivo GBR model. In vitro both materials supported the attachment, migration and differentiation of osteoblast-like cells in culture for up to 3 weeks. The in vivo model was based upon full-thickness transcortical bone defects in the mandibular rami of Sprague-Dawley rats. The right rami were used as controls, contralateral defects being covered bucally and lingually with either e-PTFE or alkali-cellulose membranes. Pathological and histomorphometric analysis was undertaken at 4 and 10 weeks post-implantation. Bone regeneration associated with alkali-cellulose membranes was predominantly endochondral in type in contrast to e-PTFE which induced direct bone formation (intramembranous ossification). The amount of new bone formed in defects was similar for both types of membrane, but alkali-cellulose membranes induced significantly greater inflammatory response; characterized by lymphocytes, macrophages and multinucleated giant cells. Degradation and possible exposure of individual cellulose fibres may account for the poor performance of alkali-cellulose membranes in vivo. This animal and in vitro study indicates that when choosing a non-resorbable membrane for GBR, e-PTFE membranes are likely to perform better than those produced from alkali-cellulose.

Alveolar Bone Loss↗

Transient expression of activin betaA mRNA on osteoprogenitor cells in rat bone regeneration after drill-hole injury.

We investigated the expression of activin betaA on osteoprogenitor cells in the regenerating bone and bone marrow of the rat femur after drill-hole injury, by immunocytochemistry and in situ hybridization. The periosteum and endosteum adjacent to the wound region showed marked thickening at day 3 and abundant osteoprogenitor cells, which were immunoreactive for proliferating cell nuclear antigen and showed positive reactions for alkaline phosphatase activity, and existed in the inner layer of the periosteum as well as in the endosteum. During the same period, these osteoprogenitor cells began to exhibit activin betaA immunoreactivity and mRNA expression. However, the latter expression gradually reduced the intensity as the cells started to express osteocalcin mRNA during their differentiation to osteoblasts participating in the periosteal and medullary bone formation from day 5. Immunoreactivity for activin type IB and II receptors was also found on activin betaA-immunoreactive cells between days 3 and 7. The above findings suggest that proliferating osteoprogenitor cells, before their transformation to osteoblasts, transiently produce and release activin A, which may play crucial roles in bone and bone marrow regeneration in a receptor-mediated, autocrine and paracrine fashion.

Animals↗

Supracrestal bone regeneration: a pilot study.

The purpose of this study was to determine the feasibility of regenerating bone in patients with advanced horizontal bone loss. Demineralized freeze-dried bone allografts (DFDBA) in particle, strut, and laminar forms were used in combination with guided tissue regeneration. The cortical struts and strips were processed from long bones and were supplied in different widths and lengths. The strips were prepared in various thicknesses ranging from 100 to 500 microns; the struts ranged from 1 to 3 mm thick. These 2 materials provided structural support for the retention of DFDBA particles supracrestally, and they supported the gingival flap as a space maintainer, preventing the collapse of the tissue onto the roots and existing bone. The results indicated successful supracrestal regeneration of horizontal defects when combining existing techniques and materials. The mean attachment gain for the 7 patients studied ranged from 2.6 to 3.0 mm.

Alveolar Ridge Augmentation↗

Bone regeneration guided by resorbable collagen membranes in rabbits: a pilot study.

Artificial cross-shaped intrabony defects were created in the mandibles of 12 rabbits and the cavities covered with Type I highly cross-linked resorbable collagen membranes for 30 days. Similar cavities were prepared in three control animals and left uncovered for the same time period. Morphological and analytical data were obtained by means of light microscopy, scanning electron microscopy, and x-ray energy-dispersive spectrometry. After the experimental period, the membrane covered cavities were completely filled with regenerated bone. In the control specimens, the artificial cavities were occupied by fibrous connective tissue.

Animals↗