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PubMed2001

Mineralization dynamics of regenerate bone during mandibular osteodistraction.

Distraction osteogenesis offers an alternative approach for the correction of craniofacial deformities, yet little substantive data is available regarding mineralization of the forming regenerate. The purpose of this study was to evaluate, by plain film radiography and digital subtraction radiography, the mineralization dynamics of regenerate bone during osteodistraction. Thirteen skeletally mature male beagle dogs underwent 10 mm of bilateral mandibular distraction osteogenesis, at which time the bone was allowed to consolidate for either 4, 6, or 8 weeks. The tissues were then evaluated clinically and radiographically. The results demonstrate that several different types of regenerate are evident during mineralization of the distraction gap. A classification system is presented based on the length, width, and density of the mineralizing regenerate, as well as the presence or absence of an interzone. It appears that important factors for determining regenerate stability are the presence or absence of an interzone, as well as the width of the regenerate relative to the host bone segments. Finally, in cases where an interzone is present, subtraction radiography may provide a means of evaluating the level of mineralization within the interzone as well as the dynamics of mineralization over the course of distraction and consolidation.

Animals↗
PubMed2003

Combination of local and systemic parathyroid hormone enhances bone regeneration.

Parathyroid hormone is one of the most promising therapeutic agents for osteoporosis, but its use to facilitate bone regeneration in osseous defects is less clear. The purpose of the current study was to determine the effects of combining systematic parathyroid hormone and a local parathyroid hormone gene therapy in a critical-sized osteotomy model. Rats received bilateral femoral osteotomies followed by implantation of a gene-activated matrix encoding parathyroid hormone (1-34) on one side and a control gene-activated matrix on te opposite side. Systematic parathyroid hormone (1-34) or vehicle was injected daily and rats were sacrificed 6 weeks later. Systematic parathyroid hormone increased bone mineral density and bone mineral content measured by dual-energy xray absorptiometry analysis of tibias and vertebrae, and increased serum osteocalcin levels during healing of osteotomies. Furthermore, comparing osteotomy sites that received the same gene-activated matrices as vehicle-injected rats, parathyroid hormone-injected rats showed trends of greater bone areas via histomorphometric and microradiographic analyses and higher osteocalcin messenger ribonucleic acid expression via Northern blot analyses. The combination of systemic and local parathyroid hormone led to higher bone mineral density, bone mineral content, and bone area, a trend for greater radiographic-detected bone area and higher expression of osteocalcin in osteotomy sites when compared with the individual treatment or control groups. Local parathyroid hormone gene therapy enhanced the anabolic effect of systemic parathyroid hormone during osteotomy healing. This study supports the concept of a combined local and systemic approach for enhancing the repair of a fracture at risk for nonunion.

Absorptiometry, Photon↗
PubMed2002

Biomechanical properties of regenerated bone by mandibular distraction osteogenesis.

OBJECTIVE: To study the biomechanical properties of the new bone generated by mandibular distraction osteogenesis (DO). METHODS: A total of 11 healthy adult goats were randomly divided into 2 groups, the experimental group (n=9) and the control group (n=2). For the goats in the experimental group, the bilateral mandibles were gradually lengthened for 10 mm with distraction appliances. Three goats were sacrificed respectively at 2, 4 and 8 weeks after completion of distraction. Compressive, three-point bending and shearing tests were conducted on the standard regenerated bone samples and the whole unilateral mandibular specimens. For the goats in the cont rol group, no operation was made and the whole unilateral mandible was taken as the test specimen. RESULTS: The compressive strength and bending stiffness of the new bone reached the normal level at 4 and 8 weeks after completion of distraction, respectively. But the shearing strength remained significantly weaker than that of the controls at 8 weeks after distraction. CONCLUSIONS: The distraction appliance can be removed and the lengthened mandible should be exposed to adaptive functional exercise at 8 weeks after completion of distraction.

Animals↗
PubMed1997

Assessment of cell proliferation in regenerating bone during distraction osteogenesis at different distraction rates.

An experimental model of lengthening of the lower limb was used to study the morphology and cellular proliferation of regenerating bone tissue after 20% lengthening at four rates of distraction. Groups of rabbits were killed at different times 1-8 weeks after surgery. The regenerated area was divided into three zones: fibrous, primary mineralization front, and new bone. As the rate of distraction increased, the size of the fibrous zone increased and that of the new bone zone decreased. Necrosis, formation of cysts, and cartilage were found in the regenerated area at the higher distraction rates. Cell proliferation was assessed by in vivo labelling with bromodeoxyuridine, and the positive staining index for anti-bromodeoxyuridine antibody was calculated in the zones of the regenerated tissue. The index values for the fibrous zones and the new bone zones did not differ significantly in any of the groups. The value increased significantly (p < 0.05) in the primary mineralization front as the rate of distraction increased from 0.3 to 0.7 mm/day, but there was no further significant increase at higher distraction rates. In conclusion, cell proliferation was increased at all of the higher rates (more than 0.3 mm/day) of distraction studied. Higher rates of distraction caused tissue damage. A distraction rate of 0.7 mm/day appeared optimal for cell proliferation and histological characteristics.

Animals↗
PubMedDate not supplied

Effects of osteopromotive and anti-infective membranes on bone regeneration: an experimental study in rat mandibular defects.

PURPOSE: Reconstructive surgical treatment with osteopromotive membranes has become an integral part of implant dentistry. Nevertheless, there are still instances in which this technique alone is of limited or no benefit. The aim of the present study was to determine whether a combination of titanium membranes coated with transforming growth factor beta1 (TGF-beta1) and insulin-like growth factor I (IGF-I) is of value in the regeneration of so-called critical-size defects in the rat model. An analysis was made of whether or not locally administered antibiotics are deleterious to bone regeneration. MATERIALS AND METHODS: A total of 24 rats were included in the study and were divided into 4 groups, each with 6 animals. Critical-size defects were created bilaterally and covered by titanium membranes coated with (1) polylactide, (2) polylactide and clindamycin, (3) polylactide and growth factors, or (4) polylactide, clindamycin, and growth factors. All 24 contralateral defects were covered by titanium membranes without any substrate (controls). Four weeks after treatment the animals were sacrificed. RESULTS: In groups 3 and 4, most defects showed thin but almost complete bridging of the defects with new bone formation. In particular, clindamycin had no inhibitory effect on the regeneration of bone. Nevertheless, after 28 days, there was no significant difference between the individual groups (including controls) with respect to the total amount of newly formed bone. DISCUSSION AND CONCLUSION: These results support the hypothesis that coating titanium membranes with TGF-beta1/IGF-I leads to almost complete bony bridging of critical-size defects without voluminous carrier materials. Moreover, simultaneous administration of clindamycin seems possible.

Animals↗
PubMed2002

Healing patterns in calvarial bone defects following guided bone regeneration in rats. A micro-CT scan analysis.

OBJECTIVE: The objective of this study was to evaluate healing patterns of critical-size calvarial bone defects treated according to principles of guided bone regeneration using micro-CT scan analysis. Specifically, the contribution of bone, periosteum and dura mater to the amount and mineralization of newly formed bone was evaluated. MATERIAL AND METHODS: Surgically induced, critical-size calvarial bone defects in 48 adult male Wistar rats received the following: an occlusive expanded polytetrafluoroethylene (ePTFE) membrane at the exo- and endocranial aspect (OO; n = 12); an occlusive membrane at the exocranial and a perforated membrane at the endocranial aspect (OP; n = 12); a perforated membrane at the exocranial and an occlusive membrane at the endocranial aspect (PO; n = 12); and a perforated membrane at the exo- and endocranial aspect (PP; n = 12). The animals were euthanized at 4 weeks for quantitative analysis of bone volume fraction and mineralization in the region of interest (ROI) as well as in the external, middle and central area of the defect using micro-CT. RESULTS: Bone volume fraction ranged from 31.4% (OP) to 24.5% (PP). No differences were found among the groups. Bone volume fraction and mineralization in the middle area were significantly greater in group OP than in group PP, and in the central area in group OO and PO than in group PP. CONCLUSIONS: The results of this study suggest that use of occlusive ePTFE membranes enhances bone formation and maturation in the calvarial skeleton. When occlusion of endo- and exocranial tissues was compromised by membrane perforation, impaired bone formation and mineralization were observed.

Analysis of Variance↗
PubMed2006

Guided bone regeneration of a pronounced gingivo-alveolar cleft due to orthodontic space closure.

BACKGROUND: Gingival invagination is a relatively common occurrence following orthodontic closure of extraction sites. The present paper reports a combined periodontal and orthodontic treatment in a patient with a severe gingivo-alveolar cleft due to orthodontic closure of maxillary central incisor extraction space. METHODS: A definite interdental gingival cleft, extending 8 mm into the alveolar bone, required the correction of the gingival deformity as a first step, followed by guided bone regeneration (GBR). The GBR approach included the emptying of the incisive foramen to approximately 5 mm in depth followed by the insertion of bioabsorbable hydroxyapatite and covering with a bioabsorbable barrier membrane. Six months afterward, the orthodontic therapy was resumed. RESULTS: Radiographs and clinical examination 4 years after the completion of therapy indicates functionally and aesthetically satisfactory and stable results. CONCLUSION: The present paper illustrates an additional application for the guided bone regeneration technique.

Adolescent↗
PubMedDate not supplied

Histologic evaluation of the effect of nicotine administration on bone regeneration. A study in dogs.

The objective of this study was to investigate the histometric impact of nicotine on bone regeneration of surgically created alveolar ridge defects in dogs. Sixteen mongrel dogs were used. One defect was surgically created unilaterally in the mandible, and left to heal spontaneously. The animals were randomly assigned to one of the following groups: Group 1--control (n = 8) and Group 2--subcutaneous nicotine administration (2 mg/kg) twice a day (n = 8). After 4 months, the animals were sacrificed and the specimens routinely processed for semi-serial decalcified sections. Bone height (BH), bone width (BW), bone density (BD), and bone area (BA) of the newly-formed bone were evaluated. Intergroup analysis (Mann-Whitney rank sum test) showed that regardless of the presence of nicotine, no significant differences were observed regarding bone width (BW), bone area (BA) and bone height (BH) (p > 0.05). On the other hand, it was demonstrated that nicotine administration significantly influenced the proportion of mineralized tissue within the limits of the newly-formed bone (BD) (p < 0.001). Within the limits of the present study, it can be concluded that nicotine might affect but not prevent bone healing in defects left to heal spontaneously.

Alveolar Process↗
PubMed1991

[Bone regeneration in implantology. The use of Gore-Tex membranes: GTAM].

The use of expanded polytetrafluorethylene membranes to attain bone regeneration around dental implants is described. Membranes discourage "non-desirable" cells form colonizing the healing site. These cells are essentially derived from gingival epithelium and gingival connective tissue. It is suggested that this procedure could be employed directly after tooth extraction.

Bone Regeneration↗
PubMed2006

Experimental studies on the effect of osteotomy technique on the bone regeneration in distraction osteogenesis.

The objective of the experiment was to study the effect of osteotomy technique on the course of bone regeneration in distraction osteogenesis in sheep. Thirty five merino sheep were divided into 5 groups of 7 sheep each, depending on the osteotomy technique: subcutaneous corticotomy, open corticotomy, Cattaneo corticotomy, open osteotomy and osteoclasia. Formation of regenerate and its remodeling was assessed, based on roentgenograms and morphological examination (bone sections, histological evaluation, SEM, superficial X-ray analysis). Irrespective from the osteotomy technique applied, in all experimental groups, regenerates filling the distraction gap were obtained. Analysis of bone sections and histological slides indicated the most advanced osteogenesis processes in the osteoclasia group. SEM examination and X-ray microanalysis confirmed not only the presence of mature bone tissue structures in this group, but also showed a mineralization close to that of a healthy bone. Osteogenesis was the slowest in the group of subcutaneous corticotomy. The observed histological picture and analysis of elemental composition indicate a normal course of distraction osteogenesis in this group, but its consecutive phases proceed with a certain delay, compared to the remaining groups. With a good deal of caution, it can be assumed that the delay of osteogenesis in the group of subcutaneous corticotomy in the 14th post-operative week was ca. 3 weeks compared to the osteoclasia group. In all experimental groups, few cartilaginous nodules were observed in regenerates 5 weeks and, in few cases, 9 weeks old. Ossification in such places was indirect, cartilage-based. In the remaining regions direct, membrane-based ossification prevailed. Direct apposition bone lamellae on islands of fibrous bone tissue was observed in regenerates aged 9 and 14 weeks, especially in periosteal regions. The intensity and rate of formation of new bone tissue varied between the experimental groups, based on roentgenological analysis and histological evaluation. Complex morphological studies on the course of regeneration in sheep showed the most advanced remodeling and mineralization of bone tissue in animals subject to osteoclasia.

Animals↗
PubMed1993

Temporal changes during bone regeneration in the calvarium induced by osteogenin.

Repair of rat craniotomy defects, 8 mm in diameter, was compared with that of defects treated with either rat insoluble collagenous bone matrix (ICBM) or partially purified bovine osteogenin, a bone-inductive protein, reconstituted with ICBM (OG/ICBM). Repair of all defects was similar histologically throughout the first 3 days, characterized by acute, then chronic inflammation and granulation tissue formation. In defects treated with OG/ICBM, cartilage and osteoblasts were present at day 5. By day 9, cartilage and osteoid production were active. New bone showed hematopoietic tissue by day 11; a complete bone bridge was established by day 21. By day 42, fatty marrow was present. Defects treated with ICBM alone showed islands of cartilage and bone embedded in connective tissue at day 9, which reached peak maturity by day 14. In these and in untreated defects, significant osteoblastic and osteoclastic activity, located primarily at the margins of the defects, subsided by day 28. Untreated defects gradually filed in with fibrous connective tissue which matured throughout 156 days. Radiopacity, quantified by computerized image analysis, increased significantly between days 9 and 11 in OG/ICBM-treated defects, and remained greater (P < 0.05) than that of the ICBM-treated defects. There was a more gradual increase in radiopacity in ICBM-treated defects. The sequence of morphologic events during calvarial bone regeneration was very similar to that described previously for heterotopic bone formation induced by demineralized bone matrix.

Animals↗
PubMed2005

Nanoporous delivery system to treat osteomyelitis and regenerate bone: gentamicin release kinetics and bactericidal effect.

Conventional treatment of osteomyelitis involves the repeated surgical removal of dead bone tissue coupled with repeated irrigation of the wound and prolonged systemic administration of antibiotics. Therapy of bone infections could easily last the rest of the patient's life because of the poor accessibility of the infection site by common systemically administered antibiotics. The objective of the present study is to develop a novel bone bioactive resorbable nanocomposite that can serve as a delivery system for antibiotics. We synthesized three different samples of porous bioactive resorbable silica-calcium phosphate nanocomposite (C3S1, C1S1, and C1S3) that has the ability to provide a sustained release of effective dose of gentamicin for 28 days. Porosity measurements showed that the average pore diameter of C3S1, C1S1, and C1S3 samples is 44.8, 54.4, and 70.9 nm, respectively. Moreover, the silica-rich composite (C1S3) is characterized by a significantly higher surface area (155.8 m(2)/g) than the silica-poor samples (C3S1) (42.9 m(2)/g). For all samples, the release profile study showed initial burst release followed by a sustained release of gentamicin. The released gentamicin has a strong inhibitory effect on Staphylococcus aureus bacteria. In addition FTIR analysis showed the formation of a biological apatite layer on the material surface after 24 h of immersion in simulated body fluid. Results of the study suggest that the silica-calcium phosphate nanocomposite can serve as a delivery vehicle for gentamicin to treat osteomyelitis and regenerate bone.

Anti-Bacterial Agents↗
PubMed2005

Prosthetic devices shaped as tubular chambers for the treatment of large diaphyseal defects by guided bone regeneration.

Guided tissue regeneration is based on the hypothesis that the different tissues have unequal abilities to penetrate a wounded area during the healing process. The use of a device acting as a chamber allows the growth of a particular tissue and prevents the ingrowth of other tissues which impair the healing process. At the same time the chamber protects and maintains in situ the intrinsic growth factors so that they may perform their specific activity. Guided tissue regeneration currently plays a well-recognized role mostly in dentistry and peripheral nerve surgery but interesting perspectives have also opened up in orthopedics. Considering the possibility of using guided bone regeneration in the repair of diaphyseal bone defects, this updated survey highlights some critical points and pathways related to the state-of-the-art of this promising procedure, focusing particularly on the properties of the material to make the tubular chamber, the use of osteopromotive factors and the most appropriate animal model to be used for the experimental evaluation.

Animals↗
PubMed2002

Bone regeneration with calcium sulfate: evidence for increased angiogenesis in rabbits.

Autologous bone is the preferred bone graft material because it carries proteins as bone-enhancing substrates, minerals, and vital bone cells. Calcium sulfate (CS) is a well-tolerated, biodegradable, osteoconductive bone graft substitute and is a reasonable alternative to autogenous bone graft. Blood vessels are an important component of bone formation and maintenance. The process of vascular induction is called angiogenesis, and it plays a key role in all regenerative processes. Bone tissue differentiation is related to the local presence of blood vessels. One method to evaluate the presence of blood vessels in a tissue is to count the microvessels to evaluate microvessel density (MVD). The aim of the present study was to conduct a comparative evaluation of microvessel density in sites treated with CS and autologous bone in rabbits, with or without e-PTFE nonresorbable membranes (Gore-Tex, Flagstaff, Ariz). Nine New Zealand rabbits, each weighing about 2.5 kg, were used in this experiment. Three 6-mm wide defects were created in each tibial metaphysis. The defects were filled in a random way. The defects of group 1 (3 rabbits) were filled with CS granules (Surgiplaster, Classimplant, Rome, Italy) and covered with e-PTFE membranes. The defects in group 2 (3 rabbits) were filled with CS granules (Surgiplaster). The defects in group 3 (3 rabbits) were filled with autologous bone. A total of 54 defects were filled (18 with CS and e-PTFE membranes, 18 with CS alone, and 18 with autologous bone). No postoperative deaths or complications occurred. All nine animals were sacrificed at 4 weeks. MVD results were as follows: in the first group, 9.88 +/- 4.613; in the second group, 7.92 +/- 1.998; and in the third group, 5.56 +/- 1.895. P = .000 was highly significant. Statistically significant differences were found between groups 1 and 3, 1 and 2, and 2 and 3. The presence of more blood vessels in the sites treated with CS could help to explain the good results reported in the literature with the use of CS.

Analysis of Variance↗