Mansho Itokazu

Synthesis of antibiotic-loaded interporous hydroxyapatite blocks by vacuum method and in vitro drug release testing.

Interporous hydroxyapatite ceramic (Ca10(PO4)6(OH)2) has excellent bio-compatibility and interlinked pore structure, antibiotics could be loaded into pores in vacuum system. To confirm penetration of the agent to the HAb (2 cm3 cubic block), the aminoglycoside antibiotic (Isepamicin Sulfate; ISP) dissolved in eosin dye at various vacuum pressures. In ISP slow release study, the blocks were placed in 5 ml of PBS at a temperature of 37 degrees C. The PBS was replaced every 48 h and samples containing released ISP were stored until assay. All were found to release the drug maintaining a mean concentration of 0.41 microg ml(-1) even after 18 days of nine exchanges. This concentration of antibiotic exceeded the minimum inhibitory concentration against the common causative organisms of osteomyelitis. The results suggest that HAb impregnated with antibiotics using a simple vacuum system may serve as a valuable new method of administering local chemotherapy, primarily when used as a strut graft for bone defects.

Development of porous apatite ceramic for local delivery of chemotherapeutic agents

An experimental study was conducted on a drug delivery system (DDS), using porous apatite ceramics (PAC): hydroxyapatite block (HAb) [Ca10(PO4)6(OH)2] having a porosity of 35-48% and pore size range of 50-300 microm, and beta-tricalcium phosphate block (TCP) [Ca3(PO4)2] having a porosity of 75-80% and pore size range of 100-400 microm, for sustained release of a chemotherapeutic agent. Methotrexate (MTX) was loaded in the pores of PAC blocks by centrifuging the blocks in MTX solution. Impregnation of MTX in PAC blocks (1 cm3) was confirmed by a magnetic resonance imaging (MRI) study using Gadolinium-DTPA enhancement. The MRI showed high signal intensity in the PAC, which was confirmed by dye loading into the pores. To estimate the MTX-releasing capability of the PAC, the blocks were stored in 3 mL of phosphate-buffered saline (PBS) at 37 degrees C and the PBS was replaced every 48 h. The amount of MTX released was assayed by high-performance liquid chromatography. This study showed that MTX-impregnated PAC (0.63-2.25 mg/block) released the drug in a steady manner and maintained its concentration (0.1-1.0 microg/mL) up to 12 days. This concentration is high enough to be effective against tumor cells. Chemotherapeutic agent-impregnated PAC, prepared by simple centrifugation, could be a valuable form of local chemotherapy when used as a strut graft to repair bone defects. This new DDS material could also be used as an adjuvant to extended curettage and provide a means to reduce the recurrence of tumors without risk of systemic toxicity.

Arthroscopic restoration of depressed tibial plateau fractures using bone and hydroxyapatite grafts

Depressed tibial plateau fractures in 13 patients were treated under arthroscopic control. In 3 patients, bone autograft was used; in the remaining 10, hydroxyapatite (HAP) grafts were used. The depression of the articular surface was managed by elevation of the subchondral plate through a small window. Assisted by fluoroscopy, we corrected and performed the grafting under arthroscopic control. Follow-up periods averaged 5 years 6 months for the autograft and 18 months for the HAP grafts. At the conclusion of the follow-up period, x-ray radiographs and computed tomography (CT) scan showed no evidence of arthrosis and knee motion was normal. There were no significant differences between the two groups. The interporous spaces showed new bone formation on closed biopsy 6 months postoperatively.

Use of arthroscopy and interporous hydroxyapatite as a bone graft substitute in tibial plateau fractures

Tibial plateau fractures in 17 patients were managed arthroscopically, using interporous hydroxypatite (HA) as a bone graft substitute. Soft-tissue repair and intra-articular lavages were carried out arthroscopically, and depression of the articular surface was done by elevation of the subchondral plate by the bone compactor through a small window under image intensification and filling with HA through the tibial outer rim. Follow-up periods averaged 2 years and 6 months. According to roentgenograms and computed tomograms no development of arthrosis could be found. All of the patients have been followed to fracture union and have returned to their previous activity levels.

The sustained release of antibiotic from freeze-dried fibrin-antibiotic compound and efficacies in a rat model of osteomyelitis

SummaryThe kinetics of drug release from fibrin adhesive agent (consisting of fibrinogen, factor 8, thrombin, aportinin and calcium chloride)-antibiotic compound and efficacy on rat experimental osteomyelitis were studied. To enhance the slow release activities of antibiotic, a mixture of fibrin clots was freeze-dried. Effects of freeze-drying were to make a fibrin clot an interlinked pore and to increase crosslinking rate containing an antibiotic. A diffusion test from aminoglycoside (Arbekacin Sulfate: 200 mg) compound was carried out.In vitro study freeze-dried antibiotic compound (FFAC: 1 cm3) was placed in saline (3 ml). The saline was replaced every 48 h and the previous solution was stored at −45°C until assay. The result was that a concentration of 0.4 mg/l, sufficiently high to controlStaphylococcus aureus strain IM2-42, was maintained within nine exchanges of saline after 18 days.In vivo animal experiments, FFAC (2×2×3 mm) were tested in rats with establishedStaphylococcus aureus osteomyelitis in the proximal tibia. The animals were observed for radiographic signs of infection and tissue was examined histopathologically. Bacterial counts by bone cultures were statistically lower in rats implanted with FFAC than in those only given a drug-free FFC and curettage. Radiographical and histological observations also showed beneficial effects of the FFAC. The results suggest that the FFAC provide a simple drug delivery system, and may be a promising alternative treatment for osteomyelitis.The kinetics of drug release from fibrin adhesive agent (consisting of fibrinogen, factor 8, thrombin, aportinin and calcium chloride)-antibiotic compound and efficacy on rat experimental osteomyelitis were studied. To enhance the slow release activities of antibiotic, a mixture of fibrin clots was freeze-dried. Effects of freeze-drying were to make a fibrin clot an interlinked pore and to increase crosslinking rate containing an antibiotic. A diffusion test from aminoglycoside (Arbekacin Sulfate: 200 mg) compound was carried out.In vitro study freeze-dried antibiotic compound (FFAC: 1 cm3) was placed in saline (3 ml). The saline was replaced every 48 h and the previous solution was stored at −45°C until assay. The result was that a concentration of 0.4 mg/l, sufficiently high to controlStaphylococcus aureus strain IM2-42, was maintained within nine exchanges of saline after 18 days.In vivo animal experiments, FFAC (2×2×3 mm) were tested in rats with establishedStaphylococcus aureus osteomyelitis in the proximal tibia. The animals were observed for radiographic signs of infection and tissue was examined histopathologically. Bacterial counts by bone cultures were statistically lower in rats implanted with FFAC than in those only given a drug-free FFC and curettage. Radiographical and histological observations also showed beneficial effects of the FFAC. The results suggest that the FFAC provide a simple drug delivery system, and may be a promising alternative treatment for osteomyelitis.

Local drug delivery system using ceramics: vacuum method for impregnating a chemotherapeutic agent into a porous hydroxyapatite block.

We performed an experimental study on a new drug delivery system that employs a porous hydroxyapatite block (HAb) (composition: Ca10 (PO4)6 (OH)2) to conduct sustained release of a chemotherapeutic agent. To confirm penetration of the agent into the HAb (2 cm3), an aqueous solution containing eosin dye was used at various vacuum pressures. To estimate the storage capacity of the HAb, blocks were weighed before and after being impregnated with the aqueous dye solutions, and the capacity of the block was calculated from the increase in weight after vacuum. In this slow-release study using vacuum, the anti-cancer drug methotrexate (MTX) was used in vitro. Four HAb (1 cm3) containing different concentrations of MTX, ranging from 1.22 to 2.38 mg per block, were studied. All were found to release the drug, maintaining a mean concentration of 0.22 to 0.32 μg/ml even after twelve days. This concentration is high enough to be effective against tumor cells. The results suggest that HAb impregnated with a chemotherapeutic agent using a simple vacuum system may serve as a valuable new method of administering local chemotherapy, primarily when used as a strut graft for bone defects. This new drug delivery system can also be used as an adjuvant material in extended curettage, which can also discourage recurrence of benign tumors without any risk of systemic toxicity.

Sustained release of adriamycin from implanted hydroxyapatite blocks for the treatment of experimental osteogenic sarcoma in mice

A sustained-release drug delivery system was developed using a hydroxyapatite (HA) block loaded with adriamycin (ADR) by cenrifugation. Release of ADR was sustained for 66 days in vitro and for 4 weeks in vivo following intramuscular implantation in mice. ADR concentrations in plasma, liver, and kidney were from 0.25% to 10% of that at the implantation site. ADR-HA blocks implanted into osteogenic sarcomas in mice markedly inhibited tumor growth. This drug delivery system provides sustained release of the cancer chemotherapeutic agent and may prove useful for treating malignant tumours while minimising systemic side effects.

Treatment of osteomyelitis by antibiotic impregnated porous hydroxyapatite block

A novel drug delivery system was developed for osteomyelitis using porous hydroxyapatite blocks (HA-b) that were impregnated with antibiotics by a centrifuge method. For the experimental study, a 10 mm3 HA-b was placed in a container, mixed with an antibiotic solution and centrifuged at 1500 rpm for 15 min for the purpose of impregnating antibiotics into the pores. The slow release activity of antibiotic (Arbekacin sulfate [1-N-(S)-4 amino-2-hydroxybutyryl dibekacin]) from the HA-b was tested. An evaluation was made of the slow-releasing capabilities of the ABK from HA-b which was still maintained at 0.5 microgram/ml within 21 exchanges of PBS after 42 days. Consequently, seven patients with osteomyelitis, including one with tuberculosis and two with infected hip arthroplasty, have been treated. On a follow-up study, all of the foci had completely healed by the end of the follow-up period without complications. This new method is simple and can be performed safety as a one-stage operation.

Ankle arthroplasty by excision of the talar body: subtotal talectomy.

We carried out the ankle arthroplasty by excision of the talar body (subtotal talectomy) on 10 ankles of nine patients with talar body tumor, paralytic talipes equinovarus, talipes varus due to spinal injury, or comminuted fracture of the talar body. Talar body excision was initiated by lateral incision and subsequent osteotomy of the fibula. The fibula was everted, leaving the lateral ligament (calcaneofibular ligament) intact. After the talus was exposed, the talar body was excised, leaving about 1.5 cm of head unresected. Subsequently, the fibula was shortened slightly, and the tibia was pulled down to the level of the calcaneus to form a joint, instead of arthrodesis being performed. After surgery, the joint formed by the tibia and calcaneus was mobile in seven of the 10 feet and immobile (arthrodesis) in the remaining three feet. The average follow-up period was 6 years. Although postoperative x-ray revealed slight osteoarthritic changes of Choparts joint and the tibiocalcaneal joint, none of the patients showed ankle pain that impaired activities of daily living. Subtotal talectomy allows correction of talipes equinus without Achilles tendon lengthening.

Influence of anteroposterior and mediolateral instability on range of motion after total knee arthroplasty: an ultrasonographic study.

Ultrasonographically, the femoral component and the tibial plate of total knee prostheses are strongly echogenic, while the high-density polyethylene insert is hypoechoic. This study evaluated the influence of mediolateral and anteroposterior stability after total knee arthroplasty (TKA) on range of motion using real-time monitoring with ultrasound. Mediolateral stress translation, which is increased by horizontal resection of more bone at the ends of the femur or tibia for easy prosthesis implantation, was examined on coronal scans at the level of the collateral ligaments. Anteroposterior drawer was examined on sagittal scans at the level of the patellar tendon. Mediolateral translation (0-10 mm; mean 2.24 mm) did not correlate with range of motion, while anteroposterior drawer (2-10 mm, mean 5.05 mm) correlated well with range of motion. These ultrasonographic findings suggest that horizontal over-resection of the ends of the femur and tibia contributed to joint laxity, which would not result in better ROM. Rollback and sliding of the femoral component on the tibia, which is believed to be correlated with anteroposterior drawer, may be important in achieving better range of motion and obtaining excellent results in TKA.