Naohisa Miyatake

Effect of partial hydrolysis of octacalcium phosphate on its osteoconductive characteristics.

The present study was designed to investigate whether the stoichiometry of octacalcium phosphate OCP affects its osteoconductive and immune response characteristics in rat bone marrow. Those characteristics of synthetic, well-grown OCP but with a non-stoichiometric composition were compared with those of a slightly hydrolyzed OCP (low crystalline OCP: LC-OCP), the fully hydrolyzed apatitic product of OCP or biodegradable beta-tricalcium phosphate (beta-TCP) ceramic, by their implantation in rat tibia for 56 days. The physicochemical aspect of implants and biological responses were analyzed by X-ray diffraction, histomorphometry, immunohistochemistry and expression of mRNA around the implants. The remarkable findings were that: (1) the highest bone formation rate was obtained for beta-TCP whereas the lowest for LC-OCP at Day 14; (2) the rates were reversed and reached the highest for LC-OCP until Day 56; (3) the early expression of ostoeoclast markers TRAP and cathepsin-K was suppressed with LC-OCP; (4) the expression of inflammatory markers IL-beta1 and TNF-alpha was suppressed with LC-OCP. The results confirmed that the partially hydrolyzed OCP with Ca/P molar ratio 1.37 (LC-OCP) enhances bone formation most, suppressing early osteoclast activity and reducing inflammation.

Effect of addition of hyaluronic acids on the osteoconductivity and biodegradability of synthetic octacalcium phosphate.

The present study was designed to investigate whether three sodium hyaluronic acid (HyA) medical products, Artz(®), Suvenyl(®) and a chemically modified derivative of sodium HyA Synvisc(®), can be used as suitable vehicles for an osteoconductive octacalcium phosphate (OCP). OCP granules (300-500 μm diameter) were mixed with these sodium HyAs with molecular weights of 90 × 10(4) (Artz(®)), 190 × 10(4) (Suvenyl(®)) and 600 × 10(4) (Synvisc(®)) (referred to as HyA90, HyA190 and HyA600, respectively). OCP-HyA composites were injected using a syringe into a polytetrafluoroethylene ring, placed on the subperiosteal region of mouse calvaria for 3 and 6 weeks, and then bone formation was assessed by histomorphometry. The capacity of the HyAs for osteoclast formation from RAW264 cells with RANKL was examined by TRAP staining in vitro. Bone formation was enhanced by the OCP composites with HyA90 and HyA600, compared to OCP alone, through enhanced osteoclastic resorption of OCP. HyA90 and HyA600 facilitated in vitro osteoclast formation. The results suggest that the osteoconductive property of OCP was accelerated by the HyAs-associated osteoclastic resorption of OCP, and therefore that HyA/OCP composites are attractive bone substitutes which are injectable and bioactive materials.

Effect of resorption rate and osteoconductivity of biodegradable calcium phosphate materials on the acquisition of natural bone strength in the repaired bone

The purpose of this study was to compare the biodegradation rate and quality of regenerated bone among four materials. A short time period of 8 weeks was chosen to examine early bone healing. The rod-shaped implants of commercially available two β-tricalcium phosphate (β-TCP) ceramics with porosity 60% and 71-80%, respectively, laboratory prepared octacalcium phosphate/gelatin composite (OCP/Gel), which has been proven to have a highly osteoconductive and biodegradable property in rat calvarial defect, and gelatin sponge (Gelatin) were implanted in rabbit tibia defect of 6 mm diameter and 7 mm depth for 2, 4 and 8 weeks. Analyses by μCT, histomorphometry and push-in test were carried out to evaluate the extent of the tissue regeneration and the material biodegradation in the long bone. OCP/Gel and Gelatin were completely resorbed but only OCP/Gel induced cortical bone bridge until 8 weeks that has strength compatible to that of the natural bone. β-TCP (71%-80%) and β-TCP (60%) were not completely resorbed and never induced the amount of new bone formation beyond that by OCP/Gel. The results indicate that the new bone having enough strength could be regenerated if the material shows not only higher biodegradation rate but also higher osteoconductivity.

Facet cyst haematoma in the lumbar spine: a report of four cases

We present 4 cases of facet cyst haematoma in the ligamentum flavum of the lumbar spine. All patients presented with a one-to-3-month history of back pain or numbness in the legs, and sudden neurological deterioration. One also developed cauda equina syndrome and another developed radiculopathy. In all cases, magnetic resonance imaging showed a mass with high signal intensity on both T1- and T2-weighted images. Facet arthrography and computed tomography revealed communication between the mass and the neighbouring facet joint. The haematomas were removed en bloc with the ligamentum flavum. They were surrounded by the ligament and contained degenerated and lacerated elastic fibres but no synovial lining cells. Facet cyst haematoma is so-named because of bleeding from tissue adjacent to the facet joint into a pre-existing facet cyst.

Immune cell response and subsequent bone formation induced by implantation of octacalcium phosphate in a rat tibia defect

The present study was designed to investigate how octacalcium phosphate (OCP) induces an immune response and whether the response is involved in the biodegradation and subsequent bone formation by OCP implantation in bone defects. Tissue and cellular responses to OCP were compared with those to OCP hydrolyzate (referred to as HL hereafter), which is a Ca-deficient hydroxyapatite (HA) prepared through OCP hydrolysis, by implanting them in rat tibia defects from 5 days to one month. They were also incubated with the macrophage cell line J774.1 for 3 days in vitro. Immunostaining, tartrate-resistant acid phosphatase (TRAP) staining, and histomorphometric analyses indicated that CD68-positive macrophage-like cells, CXCL2-positive cells and TRAP-positive cells accumulated around OCP to a greater extent than HL. In addition, OCP induced more extensive bone formation compared to HL. OCP also enhanced greater IL-6 production and macrophage migration compared to HL. A physicochemical milieu containing calcium ions, which simulates that induced by OCP, also increased macrophage migration. Together, these results suggest that the stimulatory capacity of OCP to induce bone formation can be explained in part by the immune response moderately induced by OCP, which is related to its physicochemical properties.

Dose-dependent enhancement of octacalcium phosphate biodegradation with a gelatin matrix during bone regeneration in a rabbit tibial defect model

The present study was designed to investigate how the dose of granular octacalcium phosphate (OCP) in a gelatin (Gel) matrix affects its bone regenerative and biodegradable properties in a rabbit tibia defect with a depth of 7 mm and diameter of 6 mm made in the cortical bone to bone marrow space. A spongy OCP/Gel rod, which corresponded to the defect shape, was prepared by mixing OCP granules with diameters of 300–500 μm in a gelatin matrix that contained 17–77 wt% OCP. Lyophilization and dehydrothermal treatment were performed to cross-link the materials. OCP/Gel composites were characterized by scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy. At 4 and 6 weeks after the implantation, soft X-ray and micro-CT were taken, followed by histomorphometric analysis using decalcified specimens. The results showed that the composites had a porous structure of up to 500 μm in diameter and maintained the OCP structure regardless of its content in the gelatin matrix. The OCP/Gel composite with a higher OCP content showed greater bone regeneration and tended to undergo faster biodegradation in both cortical bone and bone marrow regions. These results suggest that the biodegradation tendency of the composite could be accelerated by increasing the OCP content. This is likely due to the effect of OCP together with gelatin matrix, which results in higher osteoconductivity.

Autologous morselised bone grafting for medial tibial defects in total knee arthroplasty.

Purpose. To evaluate the outcome of autologous morselised bone grafting for a medial tibial defect of ≥10 mm deep in 45 total knee arthroplasties (TKAs). Methods. 38 patients aged 46 to 85 (mean, 73) years underwent 45 TKAs and autologous morselised bone grafting for a medial tibial defect of ≥10 (range, 10–25) mm in depth by a single surgeon. In the first 19 TKAs, 2 resected subchondral bone plates from the lateral tibial plateau were driven into 2 gutters made on the floor of the medial tibial defect as bony support posts. Morselised cancellous bone grafts were then impacted around these posts. In the remaining 26 TKAs, multiple drill holes were made on the floor of the defect to decrease the remodelling time. Morselised cancellous bone grafts were impacted to fill the defects. The tibial components were fixed with cemented (n=34) or non-cemented (n=11) technique. Internal fixation devices were not used; stem extension was used in only 2 TKAs (in a patient with Charcot joint and a patient undergoing revision TKA). Results. After a mean follow-up duration of 65 (range, 24–174) months, no patient showed gait disturbance. The mean knee flexion angle was 113.8° (range, 90°–130°). No absorption or collapse of the grafted bone, or component loosening were noted on radiographs. The grafted bone completely incorporated into the host bone, with bony trabeculae crossing the interface within 2 years in the first 19 TKAs and within one year in the latter 26 TKAs. The margin of the grafted area resembled bony cortex in 30 TKAs. Conclusion. Autologous morselised bone grafting is a viable option for most medial tibial defects during TKA.

Cortical Bone Tissue Response of Injectable Octacalcium Phosphate-Hyaluronic Acid Complexes

We have previously shown that synthetic octacalcium phosphate (OCP) displays highly osteoconductive and biodegradable characteristics. However, OCP cannot be sintered without thermal decomposition due to the existence of water molecules in the structure. The acquisition of the moldability and the improvement of the handling property in this material are subjects for the clinical use. In the present study, we prepared OCP complex with hyaluronic acid (Hya) that could be used in the injectable form and further examined the bone tissue reaction to cortical bone by placing the complex directly on an 8-weeks-old ICR mouse calvaria in comparison with the placement of OCP granules only. The granule form of OCP (between 300 to 500 μm in diameter) was mixed with sodium hyaluronic acid with molecular weights 90 x 104. The complex revealed an injectable characteristic if it was utilized in a syringe. After polytetrafluoroethylen ring was mounted on mouse calvaria, the inner space of the ring was filled with the complex and left the complex as it is for 6 weeks. Histological examination using the decalcified specimens indicated that the OCP/Hya complex exhibited greater bone formation than OCP granules only group within the ring at 6 weeks. The results suggested that the OCP/Hya complex could be used as an injectable and osteoconductive bone substitute material in many clinical situations.