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PubMed2003

Bone regeneration in critical size defects by cell-mediated BMP-2 gene transfer: a comparison of adenoviral vectors and liposomes.

Large bone defects resulting from nonunion fractures or tumour resections are common clinical problems. Recent studies have shown bone morphogenetic protein-2 (BMP-2) gene transfer using adenoviral vectors to be a promising new therapeutic approach. However, comparative studies of different vectors are required to identify the optimal system for possible clinical trials. This study compares the use of liposome-mediated and adenoviral gene transfer for the generation of autologous BMP-2-producing bone marrow stromal cells (BMSC). Primary BMSC isolated from the rat femur were treated ex vivo with either an adenovirus or a liposome carrying human BMP-2 cDNA. The genetically modified cells were evaluated in vitro and transplanted into critical size defects in the rat mandible in vivo. BMSC treated with a reporter gene vector or untreated BMSC served as controls. The newly formed tissue was analysed by in situ hybridization, radiography and immunohistochemistry. Both groups of genetically modified cells produced BMP-2 for at least 2 weeks, and markers of new bone matrix such as osteopontin and osteocalcin were observed within 2 weeks following gene transfer. In the liposome group, the critical size defects were found completely healed at 6 weeks after the gene transfer, whereas the more efficient adenoviral gene transfer allowed for complete bone healing within 4 weeks. None of the three control groups showed bone healing, not even after 8 weeks. Thus, both liposome-mediated and adenoviral BMP-2 gene transfer to primary BMSC are suitable methods to achieve the healing of critical size bone defects in rats. As liposomes have proven sufficient for this purpose and offer several advantages over any other vector, such as ease of preparation, theoretically no limitation of the size of the DNA, and less immunological and safety problems, they may represent the best vector system for future clinical trials of bone regeneration by BMP-2 gene therapy.

Adenoviridae↗
PubMed1976

The effect of systematic plaque control on bone regeneration in infrabony pockets.

A clinical trial was undertaken to test the hypothesis that periodontitis can be cured and that bone regeneration occurs in infrabony pockets in patients maintained on an optimal standard of oral hygiene. The material comprised 24 patients with advanced periodontal disease. After an initial examination, the patients were randomly distributed into one test group and one control group. All the patients were given instruction and practice in a proper oral hygiene technique, and then subjected to periodontal surgery using the modified Widman flap procedure. Following treatment, during a 2-year period the patients of the test group were recalled once every second week for professional tooth cleaning. The control patients were recalled once every 12 months for prophylaxis. The results showed that all osseous defects of the patients of the test group were refilled with bone. The control patients, on the other hand, could not maintain a high standard of oral hygiene, and exhibited a progressive deterioration of the periodontal tissues during the postsurgical observation time.

Adult↗
PubMed1998

The effects of guided bone regeneration and grafting on implants placed into immediate extraction sockets. An experimental study in dogs.

Guided bone regeneration (gbr) for the treatment of insufficient bone volume around implants can be performed using membranes with or without grafting materials (i.e., autogenous, allogenous, xenogenous, or alloplastic grafts). A possible way to evaluate the quality of implant osseointegration is the torque necessary to remove implants from their bony housing. The aim of this study was to compare the torques necessary to remove dental implants from implant beds reconstructed with different bone substitutes and GBR or GBR alone in 6 adult mongrel dogs. All mandibular premolars were extracted and 3 extraction sockets on each side were enlarged using a trephine bur. A 13 mm titanium screw-type dental implant (3.75 mm diameter) was placed in each enlarged extraction socket so that only the apical 3 to 4 mm were engaged in bone. The 3 defects were then randomly treated with either 1) canine demineralized freeze-dried bone allograft (DFDBA) plus GBR using an expanded polytetrafluoroethylene membrane (DFDBA+GTAM); 2) bioabsorbable hydroxyapatite and GBR (HA+GTAM); or 3) GBR (GTAM alone). After 6 months, the torque to remove the implants was measured in 4 animals and analyzed using ANOVA. There were no statistically significant differences between the 3 groups (GTAM alone: 46.37+/-16.41 Ncm; HA+GTAM: 46.00+/-16.59 Ncm; DFDBA+ GTAM: 52.15+/-29.24 Ncm). In addition, the influence of early removal of barriers on the torque values was evaluated with the t-test. Comparing exposed versus retained membranes by treatment modality, the only statistically significant difference was found in the DFDBA+GTAM group. When the torque values of all implants with exposed and retrieved membranes were compared to all those with retained membranes a significant difference could be detected. Histologic sections were prepared from the 2 dogs not included in the removal torque testing. In the histometric analysis the GTAM alone group showed a mean mineralized bone-to-implant-contact of 27.1%, the DFDBA+GTAM group of 34.6%, and the HA+GTAM of 39.3%. The mineralized bone-to-implant-contact of the HA+GTAM group was significantly higher than that of the GTAM alone group. In addition, the mineralized bone-to-implant-contact was divided into an apical and coronal part using the apical seventh thread as the dividing landmark. In the apical region, there was no significant difference between the groups regarding mineralized bone-to-implant-contact. In the coronal part the mineralized bone-to-implant-contact of the GTAM alone group was significantly lower compared to the other 2 groups. Within the limits of this investigation, it can be concluded that the type of grafting material will not influence torque removal values, but that early membrane exposure and removal will negatively influence the torque measurements. The combination of GBR with a bone substitute increased the mineralized bone-to-implant contact.

Absorbable Implants↗
PubMed2004

Titanium oxide nanotubes for bone regeneration.

Titanium oxide nanotubes with Ca ions on their surfaces were prepared as 2 mm cylindrical inserts and placed into surgically created bone defects in the femurs of Wistar rats. On day 3, fibroblast-like cells were present on the surface of the nanotube inserts and fibers were observed by scanning electron microscopy (SEM). On day 7, cells with alkaline phosphatase activity were present and identified as osteoblasts by SEM and transmission electron microscopy. New bone matrices were observed in and around the porous nanotube inserts by light microscopy. Compared with clinically used hydroxyapatite and tricalcium phosphate, beta-titanium oxide nanotubes promote faster acquisition and development of osteoblasts and bone tissues and have better bone regenerating ability after one week.

Alkaline Phosphatase↗
PubMed2000

Pliable polylactide plates for guided bone regeneration: manufacturing and in vitro.

Three different types of pliable and bioabsorbable plates, 0.4 mm thick, were developed for guided bone regeneration to cover cranial defects. The processing (extrusion, melt-spinning, knitting and heat pressing) and in vitro degradation of the materials were studied. Materials used were poly-L,DL-lactide with an L/DL ratio of 70/30 (PLA70) and poly-L,D-lactide with an L/D ratio of 96/4 (PLA96). The initial tensile strengths of gamma-sterilized PLA96, PLA70 and the PLA70-PLA96 composite plates were 45.7 +/- 3.8, 51.2 +/- 3.6 and 24.7 +/- 5.1 MPa respectively. The composite plates were the stiffest and lasted for more than 24 weeks. The glass transition temperature (Tg) of both polymers decreased in vitro. The crystallinity of PLA96 increased tenfold within 18 weeks. For initially amorphous PLA70 the highest melting enthalpy was 89 J/g at 60 weeks. PLA70 became partially crystalline and the plates changed from transparent to white and swollen. Extrusion and sterilization decreased the initially different molecular weight (Mw) values to the same level. After 18 weeks of hydrolysis, Mw was 15,000 Da for PLA96 and 12,000 Da for PLA70. For the components of the composite plate Mw was 15,000 Da for the PLA70 plate and 27,000 Da for the PLA96 mesh. Morphologically, all the hydrolysed plates retained, for a long period, a solid surface layer under which a porous structure formed. Crystalline branches and some single crystals were seen. The composite plates had the slowest degradation rate and they remained intact the longest.

Absorbable Implants↗
PubMed1995

Guided bone regeneration in the treatment of a large periapical lesion: a case report.

A large (19 mm x 24 mm) periapical lesion associated with tooth #10, perforating both the labial and palatal cortical plates, was treated with decalcified freeze-dried bone allograft and guided bone regeneration. The membranes were removed after a seven-month healing period. Complete osseous reconstruction of the cortical plates was noted. Biopsies demonstrated healing with mature bone and hemopoietic marrow. Few particles of decalcified freeze-dried bone could be observed. Graft particles that remained were surrounded by new bone. The learning objective of this article is to present the regeneration procedure utilized along with the histologic biopsy results to the clinician.

Adult↗
PubMed2003

Guided bone regeneration using an absorbable membrane combined with a one-stage implant into a recent extraction site: a case report.

Guided bone regeneration using an absorbable membrane combined with one-stage implants was used to treat a 45-year-old woman. Two months following tooth extraction, two implants were placed--one in the extraction site and one in a healed site. An absorbable membrane was applied to cover the bony defect in this recent extraction site. After a 24-month follow-up, probing depths were normal, increased radiopacity was seen in the extraction site, and the implant was still clinically stable.

Absorbable Implants↗
PubMed1991

[Effects of benzofurocaine, etaden and xanthinol nicotinate on reparative bone regeneration in animal experiments].

In the process of treatment of experimental close fractures of radius in rats by intramuscular administration of benzofurocaine (60 mg/kg), the regeneration processes of the bone tissue were activated to a greater degree than in case of administration of etadene (20 mg/kg) or xanthinol nicotinate (30 mg/kg). Under the influence of benzofurocaine, beginning on the 10-20-th day of the experiment, there have been noted the reorganization of young callus into the mature laminal bone. The preparations of comparison have demonstrated less expressed analogous action.

Adenine↗
PubMed1995

Guided bone regeneration around an immediate transmucosal implant for single tooth replacement: a case report.

This case report describes the procedure of guided bone regeneration around an endosseous dental implant, placed into an extraction alveolus in the absence of total soft tissue coverage, ie, in a transmucosal condition. The technique presented permits an immediate placement of the implant after the extraction of the maxillary right lateral incisor. A nonresorbable barrier membrane was used, and strict chemical plaque control was maintained during osseointegration. After an uneventful healing period of 6 months, the membrane was removed in a second-stage surgery. Two months later, the fixed single tooth prosthesis was placed. The learning objective of this article is to explain the immediate transmucosal implant surgery technique, using a case report to illustrate the procedure.

Adult↗
PubMed2001

Effects of implant design and surface on bone regeneration and implant stability: an experimental study in the dog mandible.

BACKGROUND: Previous experimental studies have shown a higher degree of bone-implant contact for surface-enlarged implants compared with machined implants. Yet, there is insufficient evidence that such implants show higher stability and an increased survival rate. PURPOSE: The purpose of this investigation was to study the integration and stability of grit-blasted implants with retention elements on the implant neck, with and without marginal bone defects, compared with machined implants without retention elements. MATERIALS AND METHODS: After tooth extraction of the mandibular premolars in six dogs, two grit-blasted, partly microthreaded Astra Tech implants and one standard Brånemark implant were bilaterally placed in each dog. On one side, 3 x 3 mm large buccal defects were created, to expose three to four implant threads. The contralateral side served as control, and no defects were made. The animals were sacrificed after 4 months of healing. Implant stability was measured using resonance frequency analysis at implant installation and after 4 months of healing. Histologic and histomorphometric evaluation was made after 4 months of healing. RESULTS: Resonance frequency analysis indicated that all implants in the test and control groups were osseointegrated after 4 months, with a tendency toward higher implant stability for the Astra Tech implants. There was a statistically significant higher increase in resonance frequency for the Astra test implants compared with their corresponding controls. Histology and histomorphometry showed well-integrated implants with varying degrees of bone repair at the defect sites. The greater bone-implant contact for the Astra implants was statistically significant. No significant difference between the implants in amount of bone filling the threads was recorded. CONCLUSIONS: The Astra Tech implants tested showed a higher degree of bone-implant contact and higher level of bone regenerated at defect sites compared with the Brånemark implants. Resonance frequency analysis demonstrated a significantly higher increase in the Astra test implants compared with their control groups than did the Brånemark test implants versus their controls.

Alveolar Bone Loss↗
PubMed1985

Bone regeneration pattern and ankylosis in experimental furcation defects in dogs.

This study reports on the pattern of interradicular bone formation and the frequency and localization of ankylosis following regenerative surgery of experimentally-induced furcation defects in 12 beagle dogs. Observations were made in 39 specimens showing healing with connective tissue attachment in the full circumference of the furcation. The findings indicate that bone regeneration first occurs adjacent to the root surfaces, followed by a subsequent fill of the central portion of the interradicular area. Ankylosis, observed in 24 of the 39 specimens, was more frequent in large defects than in small defects. The incidence of ankylosis increased with increased distance from the base of the original wound. These findings suggest that coronal bone apposition may require or be facilitated by the presence of a root surface, and that undisturbed coronal regeneration may be dependent upon cellular or some other activity from the intact periodontal ligament.

Animals↗
PubMed2006

Bone regeneration in mandibular distraction osteogenesis combined with compression stimulation.

PURPOSE: This study compared modified distraction osteogenesis (DO) protocol with conventional DO protocol on healing bone formation. Computer simulation was performed to understand the mechanical environment of modified DO protocol, which applies compression during the consolidation period. MATERIALS AND METHODS: Fifty rats were used in this study. Twenty-five rats in the conventional DO (control) group were sacrificed at postoperative days 11, 21, 28, 35, and 49 after osteotomy. In the modified DO (experimental) group, compression was applied on day 7 after distraction (day 18 postoperatively) for 4 days during the early consolidation period and 25 rats were sacrificed on postoperative day 19, 28, 39, 46, and 53. The histologic and radiographic findings were used to compare the 2 groups. Further, computer simulation was used to predict the mechanical environment of healing bone under conventional and modified DO protocol. RESULTS: Radiographic findings showed that the experimental group resulted in denser and wider healing bone. Histologically, the experimental group yielded more mature lamellar bone than the control group. Computer simulation showed that absolute values of tissue strains were nearly double in the control group because of the softer healing tissues. Both the experimental and control groups showed high strains at the ridge crest. Concentrated tensile strain along the distraction direction at the ridge crest might hinder bone formation at the interface, while compressive strain could facilitate the process. CONCLUSION: This study proposed a modified DO protocol of adding compression during the early consolidation period of conventional DO protocol. This new technique appears to provide faster and denser bone regeneration.

Animals↗
PubMed2000

Evaluation of guided bone regeneration in rabbit femur using collagen membranes.

The aim of the study was to evaluate the mechanical performance and the structure of neoformed bone around hydroxyapatite-coated titanium fixtures according to guided bone regeneration techniques. Ten hydroxyapatite-coated titanium fixtures were inserted in the femurs of five rabbits, in which a cortical defect was created and after the insertion of the fixture, covered with a resorbable membrane obtained from bovine Achilles tendon collagen Type I (A implant). In the same femur, a second fixture was inserted in similar cavities without application of the membrane (B implant). After 60 days, the animals were sacrificed, and block sections of the femoral bone containing the implants were embedded in polymethylmetacrylate and subjected to tensile shear-stress at break testing. After the detachment of the implants from the bone, their surfaces were examined with a scanning electron microscope. Tensile shear-stress values for A and B implant specimens were comparable to some extent, but the former had a lower performance. In this regard, scanning electron microscope observations showed that the neoformed cortical bone present cervically around implant A was much thicker than around implant B.

Absorbable Implants↗
PubMed2000

Platelet-derived growth factor/insulin-like growth factor-1 combination and bone regeneration around implants placed into extraction sockets: a histometric study in dogs.

This study evaluated, by histometric analysis, the wound healing process of bone around implants placed into extraction sockets with or without the concurrent application of a combination of platelet-derived growth factor (PDGF) and insulin-like growth factor (IGF-1). Mandibular premolars were removed, and 32 implants were inserted in eight dogs. Before insertion, two implants received a single application of 5 micrograms/mL of PDGF and IGF-1 delivered in 0.10 mL of 4% methylcellulose gel or 0.10 mL of 4% methylcellulose gel only as a control. To label regenerated bone, a 2% calcein green solution was administered by intramuscular injection at 0, 7, 15, 30, 45, 60, and 75 days after implant insertion. Three, 8, and 12 weeks after implant insertion, undecalcified sections were obtained, and the degree of bone contact with the implant surface, the bone area, and the intensity of bone labeling were measured into the limits of the threads of the implant. Greater extension of bone/implant contact (paired t test, P < .05) was observed in test (22.4% +/- 13.7%) than in control (17.2% +/- 13.6%) implants at 3 weeks. One-way ANOVA revealed a higher intensity of bone labeling (P < .05) at 3 weeks than at 12 weeks (127.8 +/- 42.59 and 56.7 +/- 26.34, gray scale values) for test implants. Within the limits of the present study, it was concluded that the combination of PDGF/IGF-I actively took part in the initial phase of bone repair.

Analysis of Variance↗