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Alveolar ridge repair in a canine model using rhTGF-beta 1 with barrier membranes.

In both normal and membrane-assisted situations, healing events are modulated by the activity of endogenous protein molecules known as cytokines. Due to its mitogenic and chemotactic characteristics, the addition of rhTGF-beta 1 should increase the rate of osteogenesis or increase the potential for bone regeneration in oral osseous defects. This study evaluates the effects of an osteoconductive biodegradable matrix incorporating human recombinant transforming growth factor beta 1 (rhTGF-beta 1) in conjunction with barrier membranes on bone regeneration in canine alveolar ridge defects. A matrix of calcium carbonate and hydroxyethyl starch served as the carrier for test concentrations of 2.0 micrograms/0.8 ml and 20.0 micrograms/0.8 ml of rhTGF-beta 1. One surgically prepared site in each of 13 adult male fox-hounds received 1 of 4 experimental treatment regimens, with 6 sites utilizing barrier membranes. Four sites in each of 2 additional animals, two containing carrier matrix only and 2 with the additional barrier membrane, served as controls. Specimens were retrieved after 2 months of healing and processed for routine light microscopy. The quantity and composition of regenerated bone was examined. Analysis of variance revealed a statistically significant increase (P < 0.05) in the development of bone with the use of rhTGF-beta 1. Likewise, a statistically significant increase in regeneration was found in membrane-protected sites over nonmembrane-protected sites. No statistically significant difference was noted between the low and high dose treatments. The authors conclude that the use of rhTGF-beta 1 in conjunction with a barrier membrane greatly enhances bone regeneration in osseous oral defects.

Alveolar Process↗

Guided tissue regeneration enhances bone formation in a rat model of failed osteogenesis.

BACKGROUND: Guided tissue regeneration is a technique that uses barrier materials to enhance tissue regeneration. Although previously demonstrated to be an effective way of enhancing craniofacial osteogenesis in several animal models, the ability of guided tissue regeneration to augment bone formation in the context of distraction osteogenesis is unknown. In the current study, the authors applied the principle of guided tissue regeneration to their rat mandibular distraction osteogenesis model in an attempt to enhance bone regeneration. METHODS: Twelve (n = 6 per group) adult Sprague-Dawley rats underwent routine gradual distraction (5 days' latency, 4-mm distraction over 8 days, 4 to 6 weeks of consolidation) and acute distraction (immediate lengthening to 4 mm, 6 to 8 weeks of consolidation). An additional 10 animals underwent acute distraction followed by application of bioabsorbable Gore Resolut XT membranes (acute distraction plus guided tissue regeneration). Membranes were completely wrapped around the distraction gap. Animals were killed 6 and 8 weeks postoperatively and mandibles analyzed radiographically and histologically. RESULTS: Quantitative histomorphometric analyses were performed to compare relative bone formation between all three groups. Gradual distraction mandibles achieved bony union by 6 weeks with 86 percent bone formation, which increased to 98 percent by 8 weeks. Acute distraction mandibles healed with a fibrous nonunion and only 37 percent bone formation by 8 weeks. In contrast, acute distraction plus guided tissue regeneration-treated mandibles formed significantly more bone than acute distraction mandibles by 6 weeks (57 percent) and achieved bony bridging by 8 weeks, with 88 percent new bone formation. CONCLUSION: The authors' data demonstrate that guided tissue regeneration can significantly enhance bone formation in a fibrous nonunion model of mandibular distraction osteogenesis.

Animals↗

Treatment of exposed implant threads using a synthetic bone graft.

The aim of this study was to evaluate clinically and histologically the use of a synthetic bone graft (Ionogran) alone and in combination with guided bone regeneration (GBR) to facilitate bone regeneration and augmentation around exposed implant threads. Five male Beagle dogs were used in this investigation. Prior to the study all 3rd and 4th premolars were extracted. After 3 months, a flap was elevated and two Brånemark implants were inserted in each quadrant in such a way that two-three threads remained exposed over the alveolar bone. On the control sites the synthetic bone graft was then placed around the exposed threads and the flaps were repositioned and sutured. On the test sites, the same procedure was performed, but an expanded polytetrafluoroethylene barrier was placed to cover the bone graft and implants. Three months after implant placement, the barriers on the test sites were removed, healing abutments were inserted on all implants, and a thrice weekly plaque control regime was initiated. The following clinical parameters were measured at 1, 2, and 3 months: Plaque Index, Gingival Index, Probing Depth and Clinical Attachment Level. Three months after abutment connection the animals were killed and specimens were obtained for histological evaluation. Clinical parameters revealed a significant improvement on the experimental sites compared to control sites during the 3 month loading phase. Histological analyses, however, could not determine a difference in the nature of the implant/tissue interphase between experimental and control sites.

Aluminum Silicates↗

A poly(lactide-co-glycolide)/hydroxyapatite composite scaffold with enhanced osteoconductivity.

Biodegradable polymer/ceramic scaffolds can overcome the limitations of conventional ceramic bone substitutes. However, the conventional methods of polymer/ceramic scaffold fabrication often use organic solvents, which might be harmful to cells or tissues. Moreover, scaffolds fabricated with the conventional methods have limited ceramic exposure on the scaffold surface since the polymer solution envelopes the ceramic particles during the fabrication process. In this study, we developed a novel fabrication method for the efficient exposure of ceramic onto the scaffold surface, which would enhance the osteoconductivity and wettability of the scaffold. Poly(D,L-lactide-co-glycolide)/nanohydroxyapatite (PLGA/HA) scaffolds were fabricated by the gas foaming and particulate leaching (GF/PL) method without the use of organic solvents. Selective staining of ceramic particles indicated that HA nanoparticles exposed to the scaffold surface were observed more abundantly in the GF/PL scaffold than in the conventional solvent casting and particulate leaching (SC/PL) scaffold. Both types of scaffolds were implanted to critical size defects in rat skulls for 8 weeks. The GF/PL scaffolds exhibited significantly enhanced bone regeneration when compared with the SC/PL scaffolds. Histological analyses and microcomputed tomography of the regenerated tissues showed that bone formation was more extensive on the GF/PL scaffolds than on the SC/PL scaffolds. Compared with the SC/PL scaffolds, the enhanced bone formation on the GF/PL scaffolds may result from the higher exposure of HA nanoparticles to the scaffold surface. These results show that the biodegradable polymer/ceramic composite scaffolds fabricated with the novel GF/PL method can enhance bone regeneration compared with those fabricated with the conventional SC/PL method.

Absorbable Implants↗

[Repair of tibial defect with tissue-engineered bone graft and radionuclide bone imaging in goats].

OBJECTIVE: To observe the effect of tissue-engineered bone grafts in repairing large tibial defect in goats, and assess the value of radionuclide bone imaging in monitoring the therapeutic effect of this approach. METHODS: Tibial defects measuring 2 cm was artificially made in the left tibia of 27 normal goats that were subsequently divided into 3 groups (9 each) to undergo treatment with tissue-engineered bone grafts, artificial bone grafts or without any grafts (as control group) respectively. The tissue-engineered bone grafts contained bone marrow stroma cells (BMSCs) of the goats and coral hydroxyapatite (CHAP), while the artificial bone grafts were from CHAP only. After the operations, radionuclide bone imaging was used to monitor the therapeutic effects at 2, 4 and 8 postoperative weeks. RESULTS: The 99mTc-MDP uptake of the region of interest (ROI) and the target to non-target ratios (T/NT) of the control group did not indicate any process of revascularization or bone regeneration. An increasing tendency of the revascularization and bone regeneration, in contrast, was observed in goats receiving the artificial bone grafts, a tendency that was far more obvious in the goats with tissue-engineered bone grafts. CONCLUSION: Tissue-engineered bone graft is eligible in repairing large defect in the caprine tibia, and radionuclide bone imaging may accurately monitor the revascularization and bone regeneration after the bone graft implantation.

Animals↗

Effect of cisplatin on bone transport osteogenesis in dogs.

OBJECTIVE: To document effects of cisplatin on regenerate bone formation during the distraction and consolidation phases of bone transport osteogenesis. ANIMALS: 10 skeletally mature hounds. PROCEDURES: Bone transport osteogenesis was performed to reconstruct a 3-cm defect in the radius of each dog. Five dogs were randomly selected to receive cisplatin (70 mg/m2, IV, q 21 d for 4 cycles), and 5 were administered saline (0.9% NaCl) solution. Bone mineral density was measured by use of dual-energy x-ray absorptiometry (DEXA) on days 24, 55, and 90 after surgery. Dogs were euthanatized 90 days after surgery. Histomorphometry was performed on nondecalcified sections of regenerate bone. Bone mineral density and histomorphometric indices of newly formed bone were compared between groups. RESULTS: Densitometric differences in regenerate bone mineral density were not detected between groups at any time period. Cisplatin-treated dogs had decreased mineralized bone volume, decreased percentage of woven bone volume, decreased percentage of osteoblast-covered bone, increased porosity, and increased percentage of osteoblast-covered surfaces, compared with values for control dogs. Lamellar bone volume and osteoid volume did not differ significantly between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Regenerate bone will form and remodel during administration of cisplatin. Results of histomorphometric analysis suggest that bone formation and resorption may be uncoupled in cisplatin-treated regenerate bone as a result of increased osteoclast activity or delayed secondary bone formation during remodeling. These histomorphometric differences were modest in magnitude and did not result in clinically observable complications or decreased bone mineral density as measured by use of DEXA.

Absorptiometry, Photon↗

The use of a slowly resorbable collagen barrier in the regeneration of bone in deep wide defects: a case report.

This paper presents a case in which a resorbable collagen membrane and a collagen-based spacemaker and root surface conditioning were used in a guided tissue regeneration procedure. There was no need to disturb the healing potential of the underlying selected cells with an early reentry procedure. Clinical postoperative findings at the time of surgery and in an 18-month follow-up and the differences in density of the mineralized tissues, as detected by standardized series of juxtagingival radiographs and during surgical reentry, showed encouraging results in bone regeneration and soft tissue management.

Adult↗

Primary hyperparathyroidism: evaluation of different treatments of jaw lesions based on case reports.

On the basis of three case reports, different treatment modalities of primary hyperparathyroidism of the jaws are presented. Surgical intervention made as the result of misdiagnosis in the first case caused an unnecessary bone defect and delayed bone regeneration for several months. Two other cases showed spontaneous regeneration of bone after parathyroidectomy. The second case disproved the earlier opinion that regeneration of the bone lesions could last for several years, and that the normal morphology could be restored. Complete resolution of the central giant-cell lesion was found 6 months after removal of the parathyroid adenoma.

Adenoma↗

A comparative study of barrier membranes as graft protectors in the treatment of localized bone defects. An experimental study in a canine model.

Guided bone regeneration is a predictable and well-documented surgical approach for the treatment of deficient alveolar ridges prior to endosseous implant placement. The purpose of this study was to compare a new resorbable membrane (GORE RESOLUT ADAPT Regenerative Membrane, i.e. 67% glycolide (PGA) : 33% trimethyline carbonate (TMC)) with Bio-Gide, a resorbable collagen membrane. Five canines were used in the study. Three saddle-type osseous defects were created bilaterally in edentulous areas of the mandible. The defects were filled with assayed, canine demineralized freeze-dried bone (DFDB) in a thermoplastic gelatin matrix. Using a randomized block design, four sites were covered with PGA : TMC membranes of four different porosities, one site was covered with a collagen membrane and one site consisted of DFDB alone (control). At 3 months, the animals were euthanized and the mandibles were removed en bloc for laboratory processing. A total of 30 sites were reviewed microradiographically and underwent histomorphometric analysis for bone regeneration, soft tissue presence and remaining graft material. All sites exhibited uneventful healing. A significantly higher percentage of bone regeneration was seen in the sites protected by the PGA : TMC membrane. A higher component of soft tissue was visible beneath the collagen membrane as compared with the PGA : TMC membrane. The control sites exhibited noticeable deformation of the regenerated bone secondary to collapse of the overlying periosteum. The authors conclude that the PGA : TMC membrane protected the DFDB-filled defect and allowed a greater amount of bone regeneration than the defect protected by the collagen membrane or the control.

Absorbable Implants↗

New scaffold for recombinant human bone morphogenetic protein-2.

A bioactive and resorbable scaffold is necessary to exhibit the osteoinductive potency of recombinant human bone morphogenetic protein-2 (rhBMP-2). In a previous study, we found that synthetic octacalcium phosphate (OCP) enhances bone regeneration and is replaced by newly formed bone after it is resorbed. We hypothesized that OCP may be useful as an effective scaffold for rhBMP-2 to enhance bone regeneration. To test this hypothesis, the present study was designed to investigate whether an OCP/BMP composite implant could more effectively enhance bone regeneration. A critical-sized defect was made in a rat calvarium and 1. 15 mg of OCP combined with 10 microg of rhBMP-2 (OCP/BMP 10 microg), 2. 15 mg of OCP combined with 1 microg of rhBMP-2 (OCP/BMP 1 microg), or 3. OCP (OCP alone) was implanted into the defect and fixed at 4 or 8 weeks after implantation. The percentage of newly formed bone (n-Bone%) in the defect was determined by a histomorphometrical analysis. A statistical analysis showed that n-Bone% with OCP/BMP was significantly higher than that with OCP at both time points, whereas the difference in n-Bone% between OCP/BMP 10 microg and OCP/BMP 1 microg was not significant. The present results suggest that OCP can be used as an effective scaffold for rhBMP-2 and this OCP delivery system may be able to reduce the standard effective dose of rhBMP-2, which would be beneficial because low doses (<100 microg/g OCP) of rhBMP-2 enhance bone regeneration.

Absorbable Implants↗

[Computerized tomography aspects of tibial distraction regeneration].

Computer tomography (CT) potentialities in examinations of patients over the course of distraction osteosynthesis and in assessment of the bone regenerate structure of different sites in various periods of its formation and 'maturation' were studied in 25 patients (22 men and 3 women aged 14 to 54, mean age 31.7) in periods from 24 days to 5 years. CT permitted a visual and densitometric assessment of the developing bone regenerate surrounded by metal constructions. The distraction osteogenesis involves the development of bone regenerate copying the anatomical shape and structure of the regenerated tubular bone at the site of its osteotomy. CT helps follow up all the periods of bone regenerate formation and maturation and permits the detection of deviations in this process, if any. This method permits analysis of the bone regenerate ossification time course, that is important for the assessment of the distraction rate and of the time of removing the external fixation apparatus.

Adolescent↗

Regeneration of cranial suture and bone plate lesions in rabbits. Implications for positioning of osteotomies.

The positioning of osteotomies in intramembranous cranial bone was studied by exploring the pattern of bone regeneration in growth areas (the sutural region) as compared to that of the bone plate proper. Trephine defects in the left coronal suture area and the right parietal bone were produced in fifty-nine young rabbits. A pilot study to refine operative and analytical methods comprised 22 animals. The experiments were terminated at one, three, and six weeks after surgery. The bone regenerative response was assessed by x-ray planimetry, plain microscopy, enzyme histochemistry, and fluorescent labelling. Only minor divergences in healing capacity between the two defects were found. No adverse effects on the growth process were indicated. As to clinical management, the findings suggest that osteotomies designed to traverse sutural areas will, under normal circumstances, regenerate in a similar manner and rate to adjoining bone plates.

Acid Phosphatase↗

Histamine-correcting drug pherofunginum and bone tissue regeneration.

It has been shown that a histamine-correcting preparation (Pherofunginum) speeds up bone tissue regeneration. Other histamine correcting preparations behave in a similar way. We conclude that the application of these preparations in traumatology may have beneficial results.

Animals↗

[Effect of various implant materials on cementogenesis].

Various implant materials have been used to stimulate the regeneration of supporting bone lost from periodontal disease. In addition, the histologic features of bone regeneration associated with their implantation have been evaluated. Very little, however, seems to be known about the effect of implant materials on cementum formation. The aim of this study was to determine whether implant materials stimulate the cementogenesis on adjacent planed root surfaces. Twelve monkeys with healthy gingivae were used in this experiment. Following mucoperiosteal flap elevation, "windows" were chiseled in the bone to the proximal root dentin surfaces and adjacent root surfaces were planed. Each of the three implant materials [tricalcium phosphate (TCP), decalcified bone matrix (DBM) and hydroxyapatite (HA)] were then placed in the cuspid and incisor root "windows" before the flap was sutured back into the previous position. Windows with no implantation served as a control. Animals were sacrificed 2, 4 and 8 weeks postoperatively. Biopsy specimens including the tooth and surrounding bone were examined by light and electron microscopy. At 2 weeks, all implant particles were surrounded by fibrous tissue. On the other hand, fibrous tissues filled the control defect. On the planed root surfaces after the implantation of TCP and DBM, furthermore, cementoid tissue appeared. At 4 weeks, a considerable amount of new cementum was deposited on the root surfaces except in the implantation of HA. It was especially pronounced after implantation of TCP and DBM which promoted bone regeneration after resorption. These results suggest that resorbable implant materials such as TCP and DBM not only facilitate the formation of new bone, but also of new cementum.

Animals↗