[Role of oxidative metabolism in the bioenergetics of regenerating bone tissue].
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Normal tissue defects in the tibiae of 16 sheep were filled with gelatine, collagen or a mixture of both. Comparable rates of new bone formation occurred after observation periods of 6 and 12 weeks. The difference is not statistically significant. In our experiment collagen and gelatine showed neither a positive nor a negative influence on new bone formation.
OBJECTIVE: To understand bone regeneration process after tooth extraction could be a clue to develop a new strategy for alveolar bone reconstruction. Recently, accumulated evidences support that connective tissue growth factor (CTGF) is implicated in tissue repair of many tissues. In this study, we investigated the spatial and temporal expression of CTGF in the rat tooth extraction sockets. DESIGN: Five weeks old wild type male rats (weighing 120 g) were used for this experiment. Expression of CTGF was determined by immunohistochemistry and in situ hybridization in the rat upper molar tooth extraction sockets at 2, 4, 7, 10 and 14 days after tooth extraction. RESULTS: CTGF was expressed strongly in the endothelial cells migrating into the granulation tissue at the bottom of the sockets during 4 days after tooth extraction. During the reparative process, no apparent chondrocyte-like cell appeared in the sockets, while osteoblast-like cells proliferated in the sockets with low CTGF expression at 7, 10, 14 days after extraction. As expected, no staining was observed with the preimmune rabbit IgG and CTGF sense probe. CTGF may play an important role in angiogenesis and granulation tissue formation specifically at early healing stage after tooth extraction to initiate alveolar bone repair. CONCLUSION: CTGF was expressed at early healing stage of the rat tooth extraction wound.
The effect of the pure-phase beta-tricalcium phosphate (beta-TCP) Cerasorb on bone regeneration was evaluated in hollow titanium cylinders implanted in the posterior jaws of five volunteers. Beta-TCP particles were inserted inside the cylinders and harvested 6 months after placement. The density of the newly formed bone inside the bone-growing chambers measured 27.84% +/- 24.67% in test and 17.90% +/- 4.28% in control subjects, without a statistically significant difference. Analysis of the histologic specimens revealed that the density of the regenerated bone was related to the density of the surrounding bone. The present study demonstrates the spontaneous healing of infrabony artificial defects, 2.5 mm diameter, in the jaw. The pure beta-TCP was resorbed simultaneously with new bone formation, without interference with the bone matrix formation.
Gene therapy represents a promising approach for delivering regenerative molecules to specific tissues including bone. Several laboratories have shown that virus-based BMP expression vectors can stimulate osteoblast differentiation and bone formation in vivo. Both in vivo and ex vivo transduction of cells can induce bone formation at ectopic and orthotopic sites. Adenovirus and direct DNA delivery of genes encoding regenerative molecules can heal critical-sized defects of cranial and long bones. Although osteogenic activity can be demonstrated for individual BMP vectors, substantial synergies may be achieved using combinatorial gene therapy to express complimentary osteogenic signals including specific combinations of BMPs or BMPs and transcription factors. Further control of the bone regeneration process may also be achieved through the use of inducible promoters that can be used to control the timing and magnitude of expression for a particular gene. Using these types of approaches, it should be possible to mimic natural processes of bone development and fracture repair and, in so doing, be able to precisely control both the amount and type of bone regenerated.
The aim of the present study was to evaluate the effect of natural deproteinized bone mineral on the temporal and spatial pattern of bone formation in a guided bone regeneration model system while using a bioresorbable membrane device. A periosteal skin flap was raised uncovering the calvaria of 20 rabbits. A stiff hemispherical dome made of polylactic acid was placed onto the roughened calvaria and anchored by screws. Prior to placement, the dome was either filled with peripheral blood (control group, 8 rabbits) or with blood and OsteoGraf/N-300 (test group, 12 rabbits). At 1 month, histologic sections revealed bone regeneration in both test and control domes to various degrees. In the test domes, bone height reached 78% (67-83) and bone volume was 11% (6-17), while in the control domes, bone height was 45% (14-67) and bone volume 6% (1-11). At 2 months, bone height was unchanged in the test group at 70% (67-83) and bone volume had only slightly increased to 16% (11-21). In the controls, height increased to 86% (60-100) and volume to 20% (9-27). Thus, in this model system, natural bone mineral fill contributed to accelerate initial bone neogenesis, while it did not contribute to increasing bone volume or bone height at later observation stages.
Tetracyclines (TTC) have been used both systemically and locally during periodontal bone grafting procedures, but previous work regarding the effect of TTC on new bone formation has been contradictory. The purpose of this study was to determine if the use of locally applied TTC in combination with freeze-dried bone allografts (FDBA) would enhance bone regeneration in an experimental alveolar bone osseous defect grafting system. Pre-weighed freeze-dried bone allograft particles (300-500 mu diameter) were placed in nylon mesh chambers (250 mu pore size) and rehydrated with either 10 micrograms/ml aqueous TTC or sterile distilled water. Empty chambers were used as further controls. The chambers were placed in the posterior mandible of baboons in surgically created windows. After 3 and 5 weeks, the chambers were retrieved, processed histologically, and analyzed histometrically for new bone formation. The TTC-rehydrated FDBA demonstrated much greater (greater than 5x) new bone formation than the water rehydrated FDBA. These results strongly suggest that locally-applied TTC in combination with FDBA enhances new bone formation in experimental alveolar bone defects.
The aim of this study was to develop platelet-derived growth factor (PDGF-BB) loaded moldable porous poly (L-lactide) (PLLA)-tricalcium phosphate (TCP) membranes for guided bone regeneration (GBR) therapy. The membranes were designed to fit various types of bone defect sites. PDGF-BB-dissolved PLLA-TCP in methylene chloride-ethyl acetate solution was cast on a dome shaped metallic mold to fabricate a model membrane. The release rate of PDGF-BB, the osteoblast attachment test, and guided bone regeneration potential were evaluated with PDGF-BB-loaded PLLA-TCP membranes. Regular pores were generated throughout the membrane mainly due to phase inversion of PLLA-methylene chloride-ethyl acetate solution. A therapeutic amount of PDGF-BB was released from the membrane. The release rate could be controlled by varying the initial loading content of PDGF-BB. A significant amount of cells attached onto the PDGF-BB-loaded membrane rather than onto the unloaded membrane. Dome shaped bone formation was achieved in rabbit calvaria at 4 weeks. This indicated that restoration of bone defects to the bone's original shape can be made possible by using molded membranes, which guide bone regeneration along with providing sufficient spaces. Bone forming efficiency was increased remarkably due to PDGF-BB release from PLLA-TCP membranes. These results suggested that the PDGF-BB releasing molded PLLA-TCP membrane may potentially improve GBR efficiency in various types of bone defects.
PURPOSE: This study evaluated the spontaneous bone healing after enucleation of large mandibular cysts subjectively and with a computed analysis of postoperative panoramic radiographs. PATIENTS AND METHODS: Twenty-nine patients had large mandibular cysts treated by surgical enucleation. Postoperative clinical and radiographic examinations were performed at 6, 12, and 24 months in 27 patients. Bone regeneration and reduction of the residual cavities and bone density were evaluated with a computed analysis of preoperative and postoperative panoramic radiographs. A subjective and clinical radiographic evaluation of the healing process also was performed. RESULTS: Uneventful healing and spontaneous filling of the residual cavities was obtained in all cases. The computed analysis of the postoperative radiographs showed mean values of reduction in size of the residual cavity of 12.34% after 6 months, 43.46% after 12 months, and 81.30% after 24 months. The increase in bone density was 37% after 6 months, 48.27% after 12 months, and 91.01% after 24 months. CONCLUSION: Spontaneous bone regeneration can occur in large mandibular cysts without the aid of any filling materials. This simplifies the surgical procedure, decreases the economic and biologic costs, and reduces the risk of postoperative complications.
AIM: The purpose of the present study was to evaluate the effects of resorbable and non-resorbable membranes, and calcium sulphate on bone regeneration in osseous defects in conjunction with apicectomy. METHODOLOGY: The mandibular third and fourth premolars of 12 beagle dogs were root treated, and apicectomies were performed. The osseous defects were divided randomly into five groups. In groups A, B and C the osseous defects were covered with e-PTFE membranes, PLGA membranes, and collagen membranes, respectively. In group D, defects were filled with calcium sulphate. Nothing was used in group E, which served as controls. The dogs were sacrificed 4, 8, and 16 weeks after the surgery. Undemineralized sections were obtained and evaluated histomorphometrically. RESULTS: Newly formed cortical bone had closed the defect in the cortical plate in all groups at 16 weeks. The degree of concavity of the new cortical bone at 16 weeks in groups A and D was significantly less than in group B (P < 0.01). The percentage of regenerated bone in group A was significantly greater than in groups B (P < 0.01), C (P < 0.05) and E (P < 0.05). In group D, it was significantly greater than in groups B (P < 0.01) and E (P < 0.05). CONCLUSIONS: The data suggests that e-PTFE membrane is more effective compared to resorbable membranes and controls for bone regeneration after apicectomy, and that calcium sulphate could be substituted for e-PTFE membrane.
Alginate membrane is a new bioabsorbable, guided bone regeneration (GBR) membrane, which is placed directly on the surface of the bone defect. It is designed to drop a calcium chloride aqueous solution into the bone defect, which is filled with sodium alginate aqueous solution. Alginate membrane is an excellent agent for this procedure due to its close assimilation to the surface of the bone. In this study, we evaluated the short-term biocompatibility of alginate membrane in the bone defects of rat tibiae. GBR membrane availability was also examined. Consequently, we found that the healing process in bone defects covered with an alginate membrane was delayed in comparison with that of controls, however, the defect was restored to nearly original condition. In contrast, in the controls, bone defect repairs exhibited partitioning as a result of connective tissue involvement. Furthermore, we observed a relation between the sodium alginate concentration and the rate of absorption of the sodium alginate membrane. Absorption of a 1.5% sodium alginate membrane was slow. As a result, the compound was not absorbed completely and bone repairs resembled an hourglass. Moreover, the inflammatory response was absent surrounding the alginate membrane. The present findings suggested that the alginate membrane functions effectively as a GBR membrane. In addition, the alginate membrane derived from 3% calcium chloride and 1% sodium alginate was most suitable as a GBR membrane.
Diaphyseal segmental defects 10 mm in length in the radii of 36 skeletally mature rabbits were covered with tubular microporous membranes prepared from poly(L/D-lactide) (18 rabbits) and poly(L/DL-lactide) (18 rabbits) to determine whether chemical composition of the membrane affected the bone healing in the defect. The results of a previous study in which similar defects of the rabbits radii were not covered with membranes or covered with poly(L-lactide) membranes were used as controls. The control defects were rapidly filled with overlying muscle and soft tissues, producing a radio-ulnar synostosis. The osseous activity of control defects was limited to the bone ends. The defects covered with membranes were progressively filled with new bone. At 1 year, complete bone regeneration in the defects covered with the poly(L/D-lactide) membrane was found in 16 cases, no regeneration in 1 animal and pseudoarthrosis in 1 animal. For the poly(L/DL-lactide) membrane there was complete bone regeneration in 17 cases (1 animal died during surgery). The quality of the interface between the new bone and the membrane seemed to be affected by the chemical structure of the polylactides used for membranes preparation. For poly(L/D-lactide), the connective tissue layer entirely separated the new bone from the polymeric membrane. This has been observed before for poly(L-lactide) membranes. In the case of poly(L/DL-lactide) the new bone was formed in some places in direct contact with the membrane and the membrane fragments were osteointegrated. The differences in chemical composition of the polylactide membranes did not have an evident effect on the bone regeneration process in segmental defects of the rabbit radii.
Mature solid bone of dogs before an after substitution of diaphyseal defect using monolocal distraction osteosynthesis by Ilizarov as well as the growth zone and the ossified fragments of the regenerate produced were studied. In reparative osteogenesis proteoglycans and sialoproteins participated sequently in the management of calcification, as shown by analysis of specific correlations between mineral (calcium, phosphorus, carbonate and citrate) and organic components (collagen, non-collagenous proteins, hexuronic and sialic acids) in demineralized bone as well as in zones of the primary mineral deposition and crystallization, Solubilization of the complex of non-collagenous proteins and calcium phosphate might be important in demineralization of intact bone tissue of the animals studied.
Spontaneous bone regeneration is an unexpected phenomenon that may take place in large mandibular defects secondary to trauma and tumor resection. One explanation for this unusual healing course is that it may be derived from the mechanism of fracture healing. A review of the literature presents several factors that may influence this process, such as the presence of periosteum and bony fragments, mandibular stabilization, soft tissue protection, the presence of infection, and a young age. Previous reports of spontaneous mandibular regeneration have all taken place in relatively young patients (5-35 years old). This paper reports a case of spontaneous bone regeneration in a 58-year-old woman who sustained an injury to her mandible from an explosive blast, and presents some explanations on how such an event could take place.