Keiko Matsui

Synthetic Octacalcium Phosphate Augments Bone Regeneration Correlated with Its Content in Collagen Scaffold

Previous studies have shown that synthetic octacalcium phosphate (OCP) facilitates in vitro osteoblastic cell differentiation in an OCP dose-dependent manner and that a complex of OCP and collagen (OCP/collagen) enhances critical-sized rat calvaria defects more than OCP alone. The present study was designed to investigate whether the bone regenerative properties of OCP/collagen are augmented in an OCP dose-dependent manner, thereby establishing a suitable composition of this composite as a bone substitute material. OCP/collagens with a wide range of mixing ratios from 23:77 to 83:17, including the previously examined composition (77:23), were prepared by blending granules of OCP with atelocollagen and molded into a disk as an implant. A critical-sized defect was made in rat calvaria, and each disk was implanted into the defect for 4 or 12 weeks and then examined radiographically, histologically, and histomorphometrically. Mouse bone marrow-derived stromal ST-2 cells were cultured in dishes pre-coated with OCP/collagen or OCP alone with different OCP contents to determine the capacity of cell attachment and proliferation up to 14 days. Histological and radiographic examinations showed that newly formed bone was observed in relation to OCP granules within the collagen matrix. Histomorphometric analysis confirmed that increasing the amount of OCP in collagen matrices resulted in progressive enhancement of bone regeneration and that the ratio 83:17 generated the maximum repair level of approximately 64% of the defect at 12 weeks. OCP/collagen promoted the proliferation and attachment of ST-2 cells more than OCP alone regardless of OCP content. Fourier transform infrared spectroscopy analysis of the coatings after the incubation indicated that OCP tended to convert to apatite regardless of the presence of collagen. The present study demonstrated that the osteoconductive characteristics of OCP/collagen can be displayed in an OCP dose-dependent manner. The results suggest that collagen promotes the proliferation and attachment of host osteoblastic cells on OCP/collagen composite implants.

Clinical study on eruption of permanent canines after secondary alveolar bone grafting

Objective Eruption of cleft-associated permanent canines was studied in 190 patients with unilateral cleft lip/palate and whose permanent canines had not erupted at the time of alveolar bone grafting. In 162 of these patients, width of bone defect was compared between patients who underwent surgical exposure of canines and those whose canines erupted naturally. Results Cleft-associated canines naturally erupted after bone grafting in 150 patients (78.9%) and required surgical exposure in 36 patients (18.9%). Cleft-associated canines had not yet erupted in two patients. Two patients were lost to follow-up. Nasal-side bone defects were significantly wider in patients who underwent surgical exposure of cleft-associated permanent canines than in those whose cleft-associated permanent canines erupted naturally. Conclusions The present results suggest that nasal-side cleft width is related to the need for surgical exposure of permanent canines in children with cleft lip/palate.

Octacalcium phosphate (OCP) collagen composites enhance bone healing in a dog tooth extraction socket model.

The authors have reported that a scaffold constructed of synthetic octacalcium phosphate (OCP) and porcine atelocollagen sponge (OCP/Col) enhanced bone regeneration more than sintered beta-tricalcium phosphate collagen composite or sintered hydroxyapatite collagen composite with a rat calvarial defect model. To aim for clinical application, the present study investigated whether OCP/Col would enhance bone healing in a dog tooth extraction socket model. Six adult, male, beagle dogs were used. The tooth extraction socket model was made by extracting bilateral third maxillary incisors and the subsequent removal of buccal bone. Disks of OCP/Col were implanted into one side of the model and the other side was untreated. The specimens were fixed 1 or 3 months after implantation. In radiographic analysis, the OCP/Col-treated group showed a wider range of radiopacity than the untreated control. Histologically, the OCP/Col-treated group showed more abundant newly formed bone than untreated control, and the implanted OCP was gradually resorbed. In morphometrical analysis, enlargement of the buccal alveolus in the OCP/Col group was significantly greater than in the untreated control. This study showed that implanted OCP/Col would be replaced by newly formed bone and OCP/Col implantation would enhance bone healing in a tooth socket model.

Bone regeneration by octacalcium phosphate collagen composites in a dog alveolar cleft model

Octacalcium phosphate (OCP) and porcine atelocollagen sponge composites (OCP/Col) markedly enhanced bone regeneration in a rat cranial defect model. To assess clinical application, the authors examined whether OCP/Col would enhance bone regeneration in an alveolar cleft model in an adult dog, which was assumed to reflect patients with alveolar cleft. Disks of OCP/Col or collagen were implanted into the defect and bone regeneration by OCP/Col or collagen was investigated 4 months after implantation. Macroscopically, the OCP/Col-treated alveolus was obviously augmented and occupied by radio-opacity, and the border between the original bone and the defect was indistinguishable. Histological analysis revealed it was filled and bridged with newly formed bone; a small quantity of the remaining implanted OCP was observed. X-ray diffraction patterns of the area of implanted OCP/Col indicated no difference from those of dog bone. In the collagen-treated alveolus, the hollowed alveolus was mainly filled with fibrous connective tissue, and a small amount of new bone was observed at the defect margin. These results suggest that bone was obviously repaired when OCP/Col was implanted into the alveolar cleft model in a dog, and OCP/Col would be a significant bone regenerative material to substitute for autogeneous bone.

Reconstruction of Critical-Sized Bone Defect in Dog Skull by Octacalcium Phosphate Combined with Collagen

PURPOSE The present study was designed to investigate whether synthetic octacalcium phosphate (OCP) combined with collagen (OCP/collagen) can repair a critical-sized defect in dog skull. OCP/collagen has been shown to biodegrade and to tend to be replaced by newly formed bone if implanted in rat calvaria defects. MATERIALS AND METHODS An OCP/collagen disk was prepared from pepsin-digested atelocollagen isolated from porcine dermis and synthetic OCP. Two critical-sized defects (20 mm in diameter) were made in a dog skull. Ten disks of OCP/collagen or collagen (control) were implanted in the bone defects and resected with surrounding tissues at 3, 6, or 12 months after the implantation. The specimens were analyzed radiographically, crystallographically, histologically, and histomorphometrically. RESULTS X-ray diffraction and FTIR analyses showed that OCP tended to convert to a poorly crystallized hydroxyapatite, similar to that of biological apatite, by 3 months. Radiographic and histologic analyses showed that the implantation of OCP/collagen disks initiated new bone formation in the defects at 3 months after implantation. However, there was no promotion of bone formation by control collagen disks even with prolonged implantation up to 12 months. Histomorphometric analysis revealed that the percentage of newly formed bone in the defect implanted with OCP/collagen increased significantly, from 30.91 ± 6.65 at 3 months to 51.22 ± 5.99 at 12 months, although the value tended to reach a plateau at 6 months (44.49 ± 3.34). On the other hand, the percentage of remaining OCP was estimated at approximately 10% at 3 months and remained nearly unchanged thereafter. CONCLUSION The results suggest that bone regeneration of a critical-sized bone defect of dog calvaria by OCP/collagen can be enhanced for 3 to 6 months and that OCP/collagen holds potential as a bone substitute material.

Dehydrothermal treatment of collagen influences on bone regeneration by octacalcium phosphate (OCP) collagen composites

We have engineered a scaffold constructed of synthetic octacalcium phosphate (OCP) and collagen composites (OCP–collagen) and report that OCP–collagen significantly enhanced bone regeneration more than the implantation of OCP. We hypothesized that the dehydrothermal treatment (DHT) during the fabrication of OCP–collagen might influence bone regeneration by OCP–collagen. To examine this hypothesis, bone regeneration by the implantation of OCP–collagen with DHT [OCP/Col(+)] was compared with that by OCP–collagen without DHT [OCP/Col(−)]. It was confirmed that both OCP/Col(+) and OCP/Col(−) contained the characteristics of OCP structure in X‐ray diffraction. Before implantation, calcium deposition derived from OCP was observed within the collagen of both OCP/Col(+) and OCP/Col(−) by undecalcified histological sections. OCP/Col(+) or OCP/Col(−) was implanted into the critical‐sized defects in rat crania. Radiographic and histological examination was performed and the percentage of newly formed bone (n‐Bone%) in the defect was determined by a histomorphometrical analysis. N‐Bone% treated with OCP/Col(+) was significantly higher than that with OCP/Col(−) at 4 and 12 weeks after implantation, because fast degradation of the implanted collagen of OCP/Col(−) elicited disappearance of the scaffold for bone regeneration. The stiffness of the calcified collagen in OCP–collagen would be more important than the existence of calcified collagen to enhance the bone regeneration by OCP–collagen composites. The present study suggests that the dehydrothermal treatment would influence effective bone regeneration by OCP–collagen. Copyright

Comparison of bone regeneration between octacalcium phosphate/collagen composite and β-tricalcium phosphate in canine calvarial defect

OBJECTIVE The present study evaluated the efficacy of bone regeneration between synthetic octacalcium phosphate (OCP) granules combined with porcine atelocollagen (OCP/Col) and β-tricalcium phosphate (β-TCP). STUDY DESIGN A disk of OCP/Col (20 mm diameter, 2.5 mm thick) or commercially available sintered porous β-TCP was implanted into a critical-sized calvarial defect (20 mm diameter) of adult male canines (n = 10). The newly formed bone in the defect was analyzed radiographically, crystallographically, histologically, and histomorphometrically at 6 months after implantation. RESULTS Histomorphometry showed that there was significantly more newly formed bone in OCP/Col-treated defects than for β-TCP (P < .05). X-Ray diffraction patterns of implanted OCP/Col were similar to those of original bone and different from those of implanted β-TCP. CONCLUSIONS These results suggest that OCP/Col implantation in canine critical-sized defect enhanced bone regeneration more than β-TCP, which is the most commonly used synthetic bone substitutes.

Octacalcium phosphate collagen composites with titanium mesh facilitate alveolar augmentation in canine mandibular bone defects.

This study was designed to investigate whether bone regeneration by implantation of octacalcium phosphate and porcine atelocollagen composite (OCP/Col) would be enhanced if mechanical stress to the implanted OCP/Col were alleviated. OCP/Col discs were implanted into an arc-shaped mandibular defect in male adult beagle dogs divided into untreated, OCP/Col, and OCP/Col/Mesh groups. In the OCP/Col/Mesh group, mechanical stress towards the implanted OCP/Col was alleviated by a titanium mesh. Bone regeneration in the three groups was compared after 6 months. Macroscopically, the alveolus in the OCP/Col/Mesh group was augmented vertically more than in the other two groups. Morphometric analysis by micro-CT showed the bone volume in the OCP/Col/Mesh group was significantly greater than in the other two groups. The augmented alveolus in the OCP/Col/Mesh group consisted of outer cortical and inner cancellous structure. Histologically, the OCP/Col/Mesh-treated alveolus was augmented by matured bone tissue along the inside of the titanium mesh. The implanted OCP/Col in the OCP/Col/Mesh and OCP/Col groups had almost disappeared. These results indicated that vertical bone regeneration by OCP/Col was efficient and successful when the mechanical stress to the implanted OCP/Col was alleviated. OCP/Col should be a useful bone substitute with active structural reconstitution.

Long-term follow-up of dental implants placed in a grafted alveolar cleft: evaluation of alveolar bone height

OBJECTIVE The purpose of this study was to evaluate the long-term follow-up of dental implants placed in the grafted alveoli of patients with cleft lip or palate clinically. PATIENTS AND METHODS Sixteen patients (8 males and 8 females) who had dental implants placed in alveoli grafted using particulate cancellous bone and marrow (PCBM) from the iliac crest were evaluated. The marginal bone level around the implant was evaluated radiologically at 1 (stage I), 3 (stage II), and 6 years (stage III) after connecting the abutment. The interdental alveolar bone height (IABH) was also evaluated radiologically for up to 6 years. RESULTS During the follow-up period of an average of 8.6 +/- 0.6 years (range: 7.2 to 9.4 years), only 2 implants were lost in 1 patient, the cumulative survival rate was 90.9%, and the clinical outcome was uneventful in all implants. The marginal bone levels around the implants were 0.29 +/- 0.18, 0.29 +/- 0.19, and 0.28 +/- 0.15 mm at stages I to III, respectively. Moreover, IABH was reduced only in 2 of 16 (12.5%) of the implant-placed grafted alveoli, and was maintained after implant placement for up to 6 years. CONCLUSIONS These findings indicate that the use of dental implants placed in grafted alveoli is beneficial for maintenance of the grafted bone in patients undergoing secondary bone grafting for cleft repair.

Bone graft in alveolar cleft with autogenous particulate cancellous bone

This study was undertaken to estimate the interdental alveolar bone height in regions undergoing bone grafts, and to determine what factors were correlated with the prognosis of the bone graft. A total of 120 alveolar clefts in 107 patients were studied. The alveolar clefts received grafts of autogenous particulate cancellous bone obtained from the iliac bone. The cases were documented by periapical radiographs taken before bone grafting and between 12-18 months after grafting. Successful bone formation (i.e., an interdental alveolar bone height of the grafted portion measuring more than 3/4 of the root length of the upper central incisor adjacent to the cleft), was observed in 70.8% of all clefts. The rate of successful bone formation was significantly higher in the group in which the bone graft was performed at less than ten years old than that in the older group. Unfavorable results were found at a significantly higher rate in cases in which the average width of the alveolar cleft was more than 11 mm. Thus, the age at the time of bone grafting, or the width of the alveolar cleft was definitely shown to affect the prognosis of the bone graft in the alveolar cleft. The eruption stage of the canine on the cleft side, or the cleft type, tended to be related to whether the interdental alveolar bone height was formed successfully or not.