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The use of guided tissue regeneration in conjunction with implants is a routine procedure in oral implant reconstruction. Three patient reports of the staged approach are presented and discussed. Implants were placed in regenerated bone 9 months after augmentation. Barrier membranes, with and without supporting screws, were used in different types of extraction site defects and followed for 2 years postoperatively.
Guided bone regeneration is a well-established technique used for augmentation of deficient alveolar ridges. Predictable regeneration requires both a high level of technical skill and a thorough understanding of underlying principles of wound healing. This article describes the 4 major biologic principles (i.e., PASS) necessary for predictable bone regeneration: primary wound closure to ensure undisturbed and uninterrupted wound healing, angiogenesis to provide necessary blood supply and undifferentiated mesenchymal cells, space maintenance/creation to facilitate adequate space for bone ingrowth, and stability of wound and implant to induce blood clot formation and uneventful healing events. In addition, a novel flap design and clinical cases using this principle are presented.
A new method was developed in this study for testing excised sheep mandibles as a cantilever. The method was used to determine the strength and stiffness of sheep hemi-mandibles including a 35 mm defect bridged by regenerated bone. Recombinant human bone morphogenetic protein-7 (rhBMP-7) in a bovine collagen type-I carrier was used for the bone regeneration. Initial tests on ten intact sheep mandibles confirmed that the strength, stiffness and area beneath the load-deformation curves of the right and left hemi-mandibles were not significantly different, confirming the validity of using the contra-lateral hemi-mandible as a control side. Complete bone regeneration occurred in six hemi-mandibles treated with rhBMP, but the quality and mechanical properties of the bone were very variable. The new bone in three samples contained fibrous tissue and was weaker and less stiff than the contra-lateral side (strength, 10-20 per cent; stiffness, 6-15 per cent). The other half had better-quality bone and was significantly stiffer and stronger (p < 0.05), with strength 45-63 per cent and stiffness 35-46 per cent of the contra-lateral side. Hemi-mandibles treated with collagen alone had no regenerated bone bridge suggesting that 35 mm is a critical-size bone defect.
The aim of this study was to delineate the pattern of bone regeneration from cortical bone segments during distraction lengthening. The lengthening procedure was applied for various periods through the Ilizarov system on the forearms of mature dogs. Bone was sectioned either by corticotomy, preserving the nutrient artery integrity, or by osteotomy. When an osteotomy was performed, the marrow cavity was in some cases plugged with either resorbable bone wax or nonresorbable material. Under distraction, both periosteal and medullary callus on either side of the gap gave rise to new bone trabeculae. The trabeculae on either side were oriented along the direction of distraction and progressively approached one another. This striated callus emerging from both sides was the most characteristic pattern of bone regeneration subsequent to distraction lengthening. Fusion was achieved approximately four weeks after the end of the lengthening period. Most of the new bone was formed by membranous ossification; some cartilaginous nodules developed. Corticalization of the bone trabeculae that had begun at three months was not fully achieved at five months after the lengthening period. There were no differences found in the pattern of bone healing and the amount of newly formed bone after corticotomy or osteotomy with or without resorbable bone wax plugging.
The objective of this study was to evaluate the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) dose on alveolar ridge augmentation and dental implant osseointegration. Bilateral, 5 mm supraalveolar, peri-implant defects were surgically created in 6 beagle dogs. rhBMP-2 (0.05, 0.1 or 0.2 mg/ml) in an absorbable collagen sponge (ACS) carrier was molded around the fixtures and wounds were closed. Treatment variations were alternated between animals (incomplete block design). Animals were sacrificed at week 8 postsurgery. Nine of twelve jaw quadrants healed uneventfully. Two jaw quadrants exhibited wound failure by week 4 and one by week 8 postsurgery. Radiographic bone regeneration was observed in defects without wound failure from week 4 postsurgery. Radiolucent voids of variable size and shape were observed and regressed over time. In weeks 6 through 8, there was an apparent increase in bone density and trabecular structure, while bone height and volume decreased. Histometric analysis revealed limited differences in bone regeneration between experimental conditions. Bone regeneration area averaged (+/- SD) 1.0 +/- 0.5, 3.5 +/- 1.4 and 2.3 +/- 0.4 mm2 for the 0.05, 0.1 and 0.2 mg/ml dose, respectively. There were no significant differences in osseointegration. Osseointegration in newly formed bone averaged 19 +/- 4%, 18 +/- 10% and 21 +/- 6% for the 0.05, 0.1 and 0.2 mg/ml rhBMP-2 sites, respectively. Collectively, the data suggest that there are no dramatic differences in bone induction and osseointegration within the selected dose and observation interval.
OBJECTIVE: In the concept of guided tissue regeneration (GTR), a space is created for selected cells to differentiate, proliferate and repair the defect at last by implanting a membrane around the defect area, which serves as a physiologic barrier. This experiment was designed to test GTR in long bone, namely, guided bone regeneration (GBR). METHODS: Ten New Zealand rabbits were used in this experiment. A piece of silicone membrane sutured as a tube was used to bridge a 10-mm defect on radius. 10-mm defects were also produced on the control sides. Radiography of forelimbs was taken weekly until 12 weeks. Gross sample examination, 3-point bending test and histology were involved in evaluating bone regeneration. RESULTS: By the 12th week, seven of 10 experimental sides were healed, 2 were healed with a connective cartilage zone, and I was not healed. None of the control was healed but the defect was occupied by soft tissue. CONCLUSIONS: The results of this preliminary study showed that GBR is present in long bone of rabbits. The following points relate to the mechanism of GBR; providing a space for bone regeneration; preventing surrounding tissue from the defect; increasing the density of osteogenic precursor cells and concentration of bone morphogenetic protein (BMPs); and maintaining a complete blood clot to bridge the fracture ends in the tube, which provides a structure for osteogenic cells ingrowth.
This study was conducted to observe bone regeneration guided by poly-DL-latic acid (PDLLA) membrane in rabbit radii bone defects and to explore the mechanism of the membrane guided bone regeneration (MGBR). The animal models of bony and periosteous defects were established in both radii of 40 adult New Zealand white rabbits. The left defect as the experimental side was bridged with PDLLA membrane tube, the right side as the controlled side was untreated. The specimens were collected at 2, 4, 8 and 12 weeks postoperatively. General observation, X-ray, histological observation and biomechanical examination were applied to the repair of the models of MGBR in both groups. Two weeks after operation, with much new bony callus formed outside the tube at both fragments, the membrane tube covered with connective tissues was filled with haematoma and fibrous callus. Twelve weeks after operation, the PDLLA membrane became white and its tube shape was still maintained. However, new bone callus outside the tube almost completely disappeared, and inside the tubes all radii bone defects were successfully repaired with bony union. On the controlled sides, bone defects were filled with connective tissues 2 weeks postoperatively. And 12 weeks after operation, the typical nonunion that had been formed after bone marrow canals were sealed with cortical bone. On the experimental side, the strength of the newly formed bone at the 12th week was higher than that at the 8th week (P<0.05), whereas the biomechanical examination could not be done on the controlled side. Therefore, these findings suggested that the bone regeneration could be successfully guided by PDLLA membrane, and this MGBR technique might be generally used in the treatment of bone defects and nonunion.
Fragmented embryonic bone tissue stimulates bone regeneration. Bone formation starts not from implanted embryonic fragments, but in intact periosteum and endosteum containing cambial cells of the osteodifferon. In rabbits, recovery of damaged radial bone after implantation of fragmented embryonic bone tissue into bone defect was associated with a pronounced periosteal reaction and focal resorption of intact ulnar bone. Consolidation of damaged radial bone without implantation of fragmented embryonic bone tissue was incomplete in all experimental animals.
Prompted by severe problems in autogeneic and allogeneic bone transplantation, intensive efforts were made to find sufficient substitutes. A main demand on these materials, especially in healing of osseous defects, is to achieve results comparable to those of auto- or allografts. These must be related to their biomechanical and particularly to their biological properties, i.e. the ability to form new bone, osseous integration and physiological remodeling. Within different trials in the tibiae of sheep we investigated bone substitutes like hydroxyapatite ceramics (HA) or partially demineralized bone matrix (pDBM) and compared them to the gold standards of autogeneic and allogeneic bone transplantation. Therefore we used two different models: the drill hole model with small size defects of 6 mm in diameter and the shaft defect model as a true-to-life defect with a 5 cm large diaphyseal defect. Evaluation was done by X-rays, histology, microradiography, fluorescent microscopy and morphometry of the small size defects. HA showed only small effects on new bone formation and works merely as an osteoconductor. However, excellent new bone formation was regularly achieved by pDBM in the small defects, whereas it was limited in the large size defects. But considering their mechanism of action, it is possible to bridge large bone defects by pDBM.
OBJECTIVES: An assessment was done of the bone-healing rate after implantation of a polylactide/polyglycolide copolymer (PLA-PGA) 50/50 dispersed in aqueous solution of PGA and dextran, used as bone substitutes in an animal model. STUDY DESIGN: Two groups of 5 rabbits each were used. In both the femoral condyles, a critical size defect of 6x10 mm was made. On the right side PLA/PGA was inserted; the left side remained empty. Thirty and 90 days after surgery the animals were killed. RESULTS: Defects left unfilled showed no spontaneous healing after 30 and 90 days. Sites filled with experimental materials showed new bone ranging between 11.46% and 76.82% after 30 days, and 75.98% and 95.34% after 90 days. Histomorphometry showed an increase in bone maturation between day 30 and 90 in experimental sites. At day 90, no statistical difference was seen as compared to normal bone. CONCLUSION: PLA/PGA copolymer dispersed in hydrosoluble matrix seems to be suitable as osteoconductive material in critical size defects.
OBJECTIVE: The aim of this study was to examine the ability of platelet-enriched fibrin glue to enhance bone formation in critically sized defects in the dog mandible. STUDY DESIGN: Seven adult female mongrel dogs underwent continuity resections on both sides of the mandible; 1 defect was reconstructed with the original particulate bone mixed with platelet-enriched fibrin glue, and as a control the contralateral defect was reconstructed with the original particulate bone alone. RESULTS: Biopsies after 6 weeks showed that the addition of platelet-enriched fibrin glue enhanced new bone formation in the autogenous bone grafts. CONCLUSION: Our data suggest that fibrin nets formed by fibrinogen, in combination with growth factors present in platelet-enriched fibrin glue, might effectively promote bone healing at bone graft sites.
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The effects of recombinant human bone morphogenetic protein (rhBMP)-2 and a novel carrier, PLGA-coated gelatin sponge (PGS), on bone defect repair was examined. A 1.5 cm unilateral segmental bone defect was created in the ulnar diaphysis of a Japanese white rabbit. In an initial study, defects were either treated with PGS impregnated with various concentrations of rhBMP-2 (0, 0.1, 0.4 and 1 mg/cm(3)) or left untreated. Defect healing was assessed by radiographic union rate, and biomechanical properties of regenerated bones were determined at 16 weeks postoperatively. In a second study, defects were implanted with PGS with or without rhBMP-2, and histologically observed at postoperative weeks 8 and 16. Radiographic union rate increased the dose-dependently at an early time point. All defects treated with rhBMP-2 (0.4 and 1 mg/cm(3)) were radiographically repaired. Mechanical properties of regenerated bones were restored in a dose-dependent manner. Neither ulnae left untreated nor implanted PGS alone showed radiographic union. Longitudinal alignment of lamellar structure was observed histologically at 16 weeks, indicating that remodeling of regenerated bone was complete. Implanted PGS was almost completely resorbed by 8 weeks, and no abnormalities were observed in the surrounding soft tissue. These results suggest that PGS is a promising carrier for rhBMP-2.
Information on proteoglycan synthesis by bone cells and tissue is largely limited to studies of developing fetal bone. The present investigation focuses on proteoglycan synthesis during the intramembranous type of bone regeneration seen within avulsive (puncture-type) defects placed in guinea pig tibiae. [35S] Sulfate-labeled proteoglycans were extracted from tissue within regenerating tibial avulsive defects seven days following surgical wounding and also from xiphisternal cartilage utilized as an internal control. Labeled proteoglycans in 4M guanidine HCl extracts of regenerating bone and cartilage were purified by DEAE-Sephacel chromatography and further analyzed by chromatography and appropriate enzyme digestions. Regenerating bone tissue contained a proteoglycan relatively small in size (Kav = 0.56 following chromatography on Sepharose CL-2B) compared to proteoglycan from xiphisternal cartilage (Kav = 0.17). Alkaline borohydride treatment degraded this bone proteoglycan (Kav = 0.4 on Sepharose CL-6B), indicating an average molecular weight of glycosaminoglycan chains approximating 50,000. Enzymatic digestions followed by Sepharose CL-6B chromatography showed that glycosaminoglycan side chains of regenerating bone proteoglycan contained dermatan sulfate, with 60% chondroitinase AC II-resistant but chondroitinase ABC-sensitive material. This bone proteoglycan did not interact with hyaluronic acid to form aggregates under conditions where such aggregates were formed by xiphisternal cartilage proteoglycan. The regenerating bone proteoglycans are therefore similar to other bone proteoglycans in hydrodynamic size and glycosaminoglycan chain size, but differ in the per cent of iduronic acid within glycosaminoglycan side chains. This guinea pig bone proteoglycan may be associated with the large mesenchymal cell population noted histologically within the bone defects at seven days of regeneration.