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[Significance of synthetic calcium phosphate ceramics as a bone replacement material].

With reference to the chemical and crystallographic differences, the line is drawn against bone substitute material produced from biological material. Extensive animal experiments demonstrated the good healing properties when using calcium phosphate ceramics in bony defects. In the long term, there was more new bone formed after filling up the defect with calcium phosphate ceramics than when using autologous bone grafts. Clinically, there is an indication for using this material to fill up bone cysts and defects if there is enough time for biodegradation; in other cases, a mixture using an autologous spongoid graft is necessary.

Animals↗

Preparation and characterization of porous apatite ceramics coated with beta-tricalcium phosphate.

Hydroxyapatite (Ca10(PO4)6(OH)2; HA) is one of the most biocompatible materials with bones, and porous HA is promising bone substitute materials for clinical applications. While there are reports that beta-tricalcium phosphate (Ca3(PO4)2; TCP) has higher resorbability than HA when the material is implanted in a bone defect. In the present study, porous HA coated with beta-TCP was prepared by our unique method. The porous HA of about 60% porosity with interconnecting pore structure was soaked in diammonium hydrogen phosphate solution, and then the HA was sintered at 900 degrees C for 3 h. beta-TCP was revealed by X-ray diffractometry on the surface of porous HA. It was possible to control the content of surface-formed beta-TCP arbitrary by varying the concentration of the solution. The obtained HA coated with 33 wt% beta-TCP (33TCP) had about 60% open porosity with the pore size from 150 to 400 microns. The average compressive strength of this porous ceramics was 17.5 MPa. Surface coated HA with beta-TCP deprived of the brittleness in handling. The weight of HA implanted into muscles was increased obviously at 4 weeks because of formation of carbonate hydroxyapatite on the surface of HA. The weight of 33TCP was scarcely changed up to 12 weeks, but the weight tended to increase at 24 weeks. The carbonate hydroxyapatite was not formed on 33TCP at 4 weeks, but formed on it at 24 weeks. Therefore beta-TCP coated porous HA behaved like beta-TCP initially after implantation, and then behaved like HA.

Animals↗

Ultrastructural evidence in vitro of osteoclast-induced degradation of calcium phosphate ceramic by simultaneous resorption and phagocytosis mechanisms.

Osteoclasts are physiological polykaryons specialized in the resorption of calcified tissue. In the context of the clinical use of calcium-phosphate (CaP) ceramics as bone substitutes, this study used transmission electron microscopy to investigate the in vitro mechanisms of CaP ceramic degradation by osteoclastic cell types. Osteoclasts cultured on CaP ceramic developed typical ultrastructural features of bone osteoclasts, such as a polarized dome shape, a clear zone and a ruffled border. Modification of the shape and density of CaP crystals under the ruffled border indicated an acidic microenvironment. Moreover, osteoclasts were able to degrade ceramic by simultaneous resorption and phagocytosis mechanisms. Phagocytosis did not alter the ability of osteoclasts to resorb CaP ceramic. The phagocytosis mechanism consisted of three steps: crystal phagocytosis, disappearance of the endophagosome envelope membrane and fragmentation of phagocytosed crystals within the cytoplasm. The common mechanism of phagocytosis described here is similar to that observed with the monocyte/macrophage lineage, confirming that osteoclasts are part of the mononuclear phagocyte system. Osteoclasts are thus clearly involved in CaP degradation by means of resorption and phagocytosis.

Animals↗

Trabecular bone response to injectable calcium phosphate (Ca-P) cement.

The aim of this study was to investigate the physicochemical, biological, and handling properties of a new developed calcium phosphate (Ca-P) cement when implanted in trabecular bone. Ca-P cement consisting of a powder and a liquid phase was implanted as a paste into femoral trabecular bone of goats for 3 days and 2, 8, 16, and 24 weeks. The cement was tested using three clinically relevant liquid-to-powder ratios. Polymethylmethacrylate bone cement, routinely used in orthopedics, was used as a control. The Ca-P cement was easy to handle and was fast setting with good cohesion when in contact with body fluids. X-ray diffraction at the different implantation periods showed that the cement had set as an apatite and remained stable over time. Histological evaluation after 2 weeks, performed on 10 microm un-decalcified sections, showed abundant bone apposition on the cement surface without any inflammatory reaction or fibrous encapsulation. At later time points, the Ca-P cement implants were totally covered by a thin layer of bone. Osteoclast-like cells, as present at the interface, had resorbed parts of the cement mass. At locations where Ca-P cement was resorbed, new bone was formed without loss of integrity between the bone bed and the cement. This demonstrated the osteotransductive property of the cement, i.e., resorption of the material by osteoclast-like cells, directly followed by the formation of new bone. Histological and histomorphometrical evaluation did not show any significant differences between the Ca-P cement implanted at the three different liquid/powder ratios. The results indicate that the investigated Ca-P cement is biocompatible, osteoconductive, as well as osteotransductive and is a candidate material for use as a bone substitute.

Animals↗

Comparison of inorganic bovine bone mineral particles with porous hydroxyapatite granules and cranial bone dust in the reconstruction of full-thickness skull defect.

Twenty adult rabbits were used to evaluate the biocompatibility and osteoconductivity of Bio-Oss, an inorganic bovine bone mineral, in the reconstruction of full-thickness skull defects. Skull defects were treated with either autogenous bone dust, porous hydroxyapatite granules, Bio-Oss particles, or were left untreated as controls. Histological examination of decalcified sections showed incorporation of Bio-Oss into the host tissue without a significant inflammatory reaction. Measurement of the profile area occupied by the bone revealed that Bio-Oss, hydroxyapatite, and the control had the same amount of bone ingrowth, whereas autogenous bone dust produced a greater amount of bone (p < 0.01). We conclude that Bio-Oss, like porous hydroxyapatite, has sufficient osteoconductive properties and can also be used as a bone substitute material.

Animals↗

Reconstruction of a large congenital cranioorbital defect with a species-specific demineralized bone implant.

Bone grafting is one of the most common operative procedures in craniofacial surgery today. Almost all surgical defects have to be closed with a graft, and all stabilized segments require bone grafts for stabilization prior to fixation. In certain circumstances, however, lack of availability of large grafts necessitates the use of bone substitutes. In the patient presented, a large defect--which is larger than a critical size defect--did not close on its own, even though neonates have a very high potential for forming bone around the dura. The defect was closed with demineralized bone implantation and showed complete filling of the defect through the bone induction principle.

Abnormalities, Multiple↗

Posterolateral and anterior interbody spinal fusion models in the sheep.

Posterolateral and anterior interbody spinal arthrodesis is a frequent procedure, but high nonunion rates are reported and harvesting autologous bone graft from the iliac crest significantly increases morbidity. Bone graft substitutes are an alternative, but to date clinical results are not conclusive. Bone substitutes can be organic or inorganic, biologic or synthetic. They can have osteoconductive properties, inductive properties or both. Animal experiments are essential to investigating bone substitutes using biomechanical and histologic methods not available in clinical studies. Few authors reported on instrumented anterior fusion models, but none used the sheep model. In the current study posterolateral and anterior interbody fusion models in sheep are described. Both models used instrumented fusions, applying porous mineral scaffolds, alone or mixed with bone. The surgical techniques are described step-by-step and potential difficulties are highlighted. Preliminary results are reported for the posterolateral fusion model using coralline graft substitutes. The coral granules mixed with locally harvested bone had fusion outcomes similar to pure autologous bone. The graft substitute showed marked resorption between 12 and 20 weeks. All fusions had bone cortex and good trabecular connectivity. Histologic evaluation suggests after 20 weeks nearly the entire surface of the substitute is covered with new bone. Porous mineral bone substitutes mixed with locally harvested autologous bone are thought to be a valid alternative for posterolateral fusions.

Animals↗

Tissue reaction to collagen-coated porous hydroxyapatite.

To give tenacity to high porosity (80%-90%) hydroxyapatite (HA) and to make a stronger bone substitute, a collagen-coated porous HA (C-HA) was prepared, and its compressive strength was examined. By implanting C-HA into the femoral condyle of adult rabbits, the capacity for new bone formation and foreign-body reactivity were quantitatively compared with those of HA alone. The compressive strength of C-HA was 4.3 times greater than HA. At four weeks after implantation, the mean areal ratio of the newly formed bone in the C-HA block in each rabbit was 9.9%, which was somewhat less than the 13.7% in the HA block; the mean number of multinucleated giant cells (MGC) per visual field at x25 in the C-HA-implanted specimens in each rabbit was 14.4, significantly larger than the 6.1 in the HA specimens. However, 12 weeks after C-HA implantation, the areal ratio of new bone increased to 32.7%, the number of MGC decreased to 9.4, and the differences compared to the values in HA cases, 31.5% and 6.8, disappeared. These results showed that C-HA is mechanically stronger than HA and that there is no difference between HA and C-HA in capacity for new bone formation or foreign-body reaction.

Animals↗

[Osteogenic potential of three kinds of calcium phosphate ceramics as carriers for recombinant human morphogenetic protein-2 in vivo].

OBJECTIVE: To investigate and compare the osteogenic potential of three kinds of calcium phosphate ceramic as carriers for recombinant human bone morphogenetic protein-2(rhBMP-2) in vivo. METHODS: BCP ceramics (HA, TCP, HA/TCP) impregnated with rhBMP-2 (experimental groups) and without rhBMP-2(control groups) were implanted into 6 muscles pockets on the dorsum of 3-month-old Wistar rabbits. The rabbits were sacrificed 2, 4 and 8 weeks after implantation and bone induction was estimated by alkaline phosphatase (ALP) activity measurement. The implants were also examined histologically and histomorphometrically by HE staining and computerized graphical analysis. RESULTS: The ALP activity of implants with rhBMP-2 was higher than that of control groups (P < 0.05), but there was no difference between 2 and 4 weeks in experimental groups. In all experimental groups, the implants exhibited that new bone formation increased with the lapse of time. The amount of new bone formation is more in HA/rhBMP-2 group than in the other two group in the 2nd and 4th weeks, but there was no difference between them (P > 0.05). In the 8th week, the amount of bone formation was most in HA/TCP with rhBMP-2, and was more than that in the 2nd and 4th weeks. Whereas in control groups, there was only fibrous connective tissue. CONCLUSION: HA/TCP is a good carriers of rhBMP-2 and can be used as bone substitutes clinically.

Animals↗

[Bone transplantation in diaphyseal defects of the long bones].

The treatment of large diaphyseal defects has remained in the domain of autologous bone transplantation, but has been substantially complemented by the Ilazarow technique. Bone formation following transplantation or segmental transport is controlled by three interacting mechanisms involving osteoregeneration, osteovascularization and osteostabilization. All three components are equally important in the healing process of large cortical defects. Osteoregeneration is inseparably linked to an intact bone matrix. Therefore, entirely inorganic bone substitutes are not suitable for difficult conditions such as is the case diaphyseal defects.

Adolescent↗

Bone formation in the goat maxillary sinus induced by absorbable collagen sponge implants impregnated with recombinant human bone morphogenetic protein-2.

This study assessed the efficacy, safety, and technical feasibility of inducing bone formation in an animal model of maxillary sinus floor augmentation using recombinant human bone morphogenetic protein-2 (rhBMP-2) impregnated on an absorbable collagen sponge (ACS). Bilateral antral maxillary sinus floor elevation procedures were surgically performed in six adult female Alpine-Saanen goats. Bone formation in response to the implant was evaluated using sequential radiographs, computerized tomography, and gross pathologic and histologic analysis performed at necropsy. Computerized tomographic scans documented nonosseous radiopacity in both sinuses postimplantation. Sinuses implanted with the rhBMP-2/ACS subsequently demonstrated increasing radiopacity local to the implant site, while radiopacity of the negative control sinuses remained unchanged or decreased. The results demonstrated the ability of an rhBMP-2/ACS implant to induce substantive new bone formation within the maxillary sinus of goats without adverse sequelae. The rhBMP-2/ACS composite implant may represent an acceptable alternative to traditional bone grafts and bone substitutes for maxillary sinus floor augmentation procedures in humans.

Animals↗

[Bone augmentation at present and in the near future].

Autologous bone graft is a gold standard for bone augmentation and is routinely applied. As methods for bone augmentation in the dental field, GBR, distraction osteogenesis, bone substitutes of calcium-phosphate materials and PRP have already been applied clinically. Furthermore, clinical results of the applications of recombinant proteins of BMP and various growth factors, and the applications of the cells from bone marrow and periostium have been reported. A new method for bone augmentation is thus likely to appear. Society accepts medical treatments that are "effective", "safe", "simple" and "economical". Taking the initials of these words, this paper proposes the concept of "2E2S". Based on recent studies of bone augmentation from the viewpoint of "2E2S", the author will predict bone augmentation in the near future.

Bone Regeneration↗

[Clinical study of immediate implant].

OBJECTIVE: To evaluate the clinical result of immediate implant. METHODS: 32 cases underwent immediate implant surgery for 59 implants simultaneously when the teeth or roots extracted. 55 implants were placed with bone grafts or bone substitutes. The second stage operation were performed in the sixth month and ceramic crown were fixed in the seventh to eighth month postoperatively, the follow up were mean 39 months. RESULTS: One implant was lost. Bone resorption of alveolar crest was observed in 4 implants. Mean resorption was 2 mm. CONCLUSIONS: The result of immediate implant is predictable, the advantages are avoiding the alveolar bone resorption after teeth extraction, implant could be placed in an ideal position; less operation trauma, good esthetics results.

Adult↗

[High tibial open-wedge osteotomy using a tricalcium phosphate substitute: 70 cases with 18 months mean follow-up].

PURPOSE OF THE STUDY: We report our experience with a B tricalcium phosphate ceramic to fill open-wedge tibial osteotomy gaps. MATERIAL AND METHODS: Seventy high tibial open-wedge osteotomies were performed in 70 patients (47 men and 23 women). Ostotomy was performed for osteoarthritis in 56 knees, Ahlback classification stage I (n = 18), stage II (n = 32), stage III (n = 6) and for congenital varus in 14. Mean patient age was 45.2 years (16-69). We used a wedge-shaped piece of ceramic with an appropriate angle, which was associated with granulated material to complete the gap filling for the last 20 cases. One or two staples were used for fixation. Clinical and radiological outcome was assessed at 6 weeks, 3 months, 6 months, and at last follow-up. Mean follow-up was 18 months. RESULTS: There were no biological or clinical complications related to biomaterial intolerance. Tolerance to the osteosynthesis material was mediocre since we observed one infection and 12 cases of pain related to the staples which required material removal in 8 patients. Bone healing was achieved in 98.5%. Final correction was between 3 degrees and 6 degrees valgus in 80.5%. There was a loss of correction angle between the postoperative film and the bone healing film. Factors related to sustained correction were: non-fractured wedge, intact lateral tibial cortical, osteosynthesis with two staples. Osteointegration was good and rapid in 96%. We found two complete lucent lines at last follow-up but with variable resorption depending on the shape of the bone substitute. CONCLUSION: Use of a ceramic wedge to fill high tibial medial open-wedge osteotomy gap is a reliable reproducible technique providing correction without formation of a malalignment callus. Bone healing is achieved in 98.5% of the cases at about three months. Osteointegration is good in 96%. Resorption is complete and rapid when the substitute is implanted in granular form in a cancellous zone and is partial and slow when implanted as a massive wedge.

Adolescent↗

The resorption of bone-implanted corals varies with porosity but also with the host reaction.

Three different exoskeletons of coral species Porites asteroides (P), Montastrea annularis (M), and Dichocoenia stokesi (D) were implanted for 2-20 weeks in rabbits. At 2, 4, 8, or 20 weeks, the exoskeletons presented variations in their resorptions depending on the species. To understand the variations in the decreasing speed of the implants despite their similar chemical composition, a study of the surface and architecture of the coral was carried out using scanning electronic microscopy, porosity was evaluated, and growth and differentiation of osteogenic cells cultured in vitro were observed for more than 1 month. At the cellular level, the surface of the implants was identical. Three-dimensional structures of the implants were variable, but the porosity values [P = 42.7%, M = 40.7%, and D = 17.4%] could not completely account for the differences in the resorbing process of the species. Standard histologic studies performed at 2, 4, 8, and 20 weeks after implantation produced the same pattern with P or M, showing aspects of rapid resorption; however, with D there were images resembling those of a foreign-body reaction. It seems that when resorption is not quick enough, a foreign body reaction develops which further slows down the process. This work focuses on the importance of porosity when using coral as bone substitute.

Animals↗

[Cement wedge replacing iliac graft in tibial wedge osteotomy].

The authors report their experience in substituting cement for full-thickness iliac crest wedge in medial tibial wedge osteotomy using buttress plate fixation. A review of 107 osteotomies performed between January 1985 and March 1989, demonstrated that using cement wedge do not expose to any special complication and raise the accuracy of frontal mechanical axes correction. At last, cement wedge seems not to evolve as a stranger corpus able to give long or mean terms complications; it perhaps make unnecessary bone substitute or allografts wedges.

Adult↗

Repair of segmental bone defects using bioactive bone cement: comparison with PMMA bone cement.

We developed a bioactive bone cement (BABC) that consists of apatite and wollastonite containing glass ceramic (AW-GC) powder and bisphenol-A-glycidyl dimethacrylate (Bis-GMA) based resin. In the present study, the effectiveness of the BABC for repair of segmental bone defects under load-bearing conditions was examined using a rabbit tibia model. Polymethylmethacrylate (PMMA) bone cement was used as a control. A 15-mm length of bone was resected from the middle of the shaft of the tibia, and the tibia was fixed by two Kirschner wires. The defects were replaced by cement. Each cement was used in 12 rabbits; six rabbits were sacrificed at 12 and 25 weeks after surgery, and the tibia containing the bone cement was excised and tension tested. At both the intervals studied, the failure loads of the BABC were significantly higher than those of the PMMA cement. The BABC was in direct contact with bone, whereas soft tissue was observed between the cement and bone in all PMMA cement specimens. Results indicated that the BABC was useful as a bone substitute under load-bearing conditions.

Animals↗

Osteopromotion for cranioplasty: an experimental study in rats using acidic fibroblast growth factor.

BACKGROUND: Many growth factors influence the bone healing cascade. Furthermore, the occasional failure of bone repair may in part be due to perturbation in the activation of local growth factors. Local activation of fibroblast growth factors (FGFs) at the fracture site may serve to increase neovascularization, and induce early granulation formation that can affect bone healing. METHODS: We have performed a rat parietal (6 x 3 mm) critical size defect (CSD). Human recombinant acidic fibroblast growth factor (hraFGF) imbided in agarose was topically administered at the craniectomy site. Control animals received agarose alone in the same manner. Three weeks after surgery, osteopromotion was histologically evaluated. RESULTS: hraFGF-treated animals show a continuous bridge of regenerated bone extending from one edge of the defect to the other. None of the parietal defects that had been treated with agarose contained new bone in the central portion. CONCLUSION: Our results suggest an important role of FGFs to promote large cranioplasty repair and support the use of these proteins as an alternative choice for bone grafts and bone substitutes.

Animals↗