TiO2 nanotubes with customized diameters for local drug delivery systems.

In this study, we evaluated the drug release behavior of diameter customized TiO2 nanotube layers fabricated by anodization with various applied voltage sequences: conventional constant applied potentials of 20 V (45 nm) and 60 V (80 nm), a 20/60 V stepped potential (50 nm [two-diameter]), and a 20-60 V swept potential (49 nm [full-tapered]) (values in parentheses indicate the inner tube diameter at the top part of nanotube layers). The structures of the 50 nm (two-diameter) and 49 nm (full-tapered) samples had smaller inner diameters at the top part of nanotube layers than that of the 80 nm sample, while the outer diameters at the bottom part of nanotube layers were almost the same size as the 80 nm sample. The 80 nm sample, which had the largest nanotube diameter and length, exhibited the greatest burst release, followed by the 50 nm (two-diameter), 49 nm (full-tapered), and 45 nm samples. The initial burst released drug amounts and release rates from the 50 nm (two-diameter) and 49 nm (full-tapered) samples were significantly suppressed by the smaller tube top. On the other hand, the largest proportion of the slow released drug amount to the total released drug amount was observed for the 50 nm (two-diameter) sample. Thus, 50 nm (two-diameter) achieved suppressed initial burst release and large storage capacity. Therefore, this study has, for the first time, applied TiO2 nanotube layers with modulated diameters (two-diameter and full-tapered) to the realization of a localized drug delivery system (LDDS) with customized drug release properties.

Corrosion Generation and Cleaning Effect on Surgical Instruments with Attached Radiofrequency Identification Tags in Long-Term Usage.

Background: Faulty cleaning of surgical instruments may lead to corrosion damage and a higher risk of surgical site infection. We have developed a method in which each instrument has an attached radiofrequency identification (RFID) tag for individual management. However, because of the structure of the instruments, a risk of corrosion from poor cleaning exists; therefore, observation during long-term usage is necessary. Methods: The cleaning effect at the jig of the RFID tag was verified by the amount of residual protein left by various cleaning methods. In our investigation of long-term usage, we examined 94 surgical instruments with RFID tags used in the operating room for 50 months employing a microscope to identify any corrosion at the jig. Results: The method using a washer disinfector (WD) was found to be highly effective. From observation after long-term usage, friction by the RFID tag occurred in about 70% of the jigs. However, no pitting or general corrosion was seen. Conclusions: When WD is used properly, there is only a minor risk of residual protein, and corrosion does not occur even with long-term use. By using surgical instruments with RFID tags, it is possible to determine the number of uses and the history at the individual level. This facilitates operation of safe surgical instruments by limiting the number of times a particular instrument is used.

Osteoporosis Changes Collagen/Apatite Orientation and Young's Modulus in Vertebral Cortical Bone of Rat.

This study revealed the distinguished changes of preferential orientation of collagen and apatite and Young's modulus in two different types of osteoporotic bones compared with the normal bone. Little is known about the bone material properties of osteoporotic bones; therefore, we aimed to assess material properties in osteoporotic bones. 66 female Sprague-Dawley rats were used. We analyzed the volumetric bone mineral density, collagen/apatite orientation, and Young's modulus of fifth lumbar vertebral cortex for osteoporotic rats caused by ovariectomy (OVX), administration of low calcium and phosphate content (LCaP) diet, and their combination (OVX + LCaP), as well as sham-operated control. Osteocyte conditions were assessed by hematoxylin and eosin and immunohistochemical (matrix extracellular phosphoglycoprotein (MEPE) and dentin matrix protein 1 (DMP1)) staining. All osteoporotic animals showed bone loss compared with the sham-operated control. OVX improved craniocaudal Young's modulus by enhancing collagen/apatite orientation along the craniocaudal axis, likely in response to the elevated stress due to osteoporotic bone loss. Conversely, LCaP-fed animals showed either significant bone loss or degraded collagen/apatite orientation and Young's modulus. Osteocytes in LCaP and OVX + LCaP groups showed atypical appearance and MEPE- and DMP1-negative phenotype, whereas those in the OVX group showed similarity with osteocytes in the control group. This suggests that osteocytes are possibly involved in the osteoporotic changes in collagen/apatite orientation and Young's modulus. This study is the first to demonstrate that osteoporosis changes collagen/apatite orientation and Young's modulus in an opposite manner depending on the cause of osteoporosis in spite of common bone loss.

Degradation of Ti-6Al-4V alloy under cyclic loading in a simulated body environment with cell culturing.

The present study reports the corrosion fatigue of the Ti-6Al-4V alloy using cyclic deformation test in a simulated body fluid under cell culturing for the first time. Cyclic deformation tests were carried out using three types of specimens to reveal the effects of proteins and cells on the corrosion fatigue of the alloy. For the 1-day-immersed and 1-week-immersed specimens, tensile specimens were soaked in a simulated body fluid for 1 day and 1 week, respectively, before cyclic deformation test, whereas for the cell-cultured specimen, MC3T3-E1 osteoblast-like cells were seeded and then cultured on tensile specimens for 1 week. The incubation period for crack initiation was longer for the cell-cultured and 1-week-immersed specimens compared to that for the 1-day-immersed specimen. On the other hand, crack propagation period for the cell-cultured and 1-week-immersed specimens was shorter than that for the 1-day-immersed specimen. These results indicate that proteins and cells adhered on the alloy surface inhibit metal dissolution at newly created surface emerged by cyclic deformation to suppress crack initiation, whereas they accelerate crack propagation because dissolution at crack tip is accelerated in the occluded space formed under proteins and cells.

The combination therapy with alfacalcidol and risedronate improves the mechanical property in lumbar spine by affecting the material properties in an ovariectomized rat model of osteoporosis.

BACKGROUND: We conducted the present study to investigate the therapeutic effects of a combination treatment of alfacalcidol (ALF) and risedronate (RIS) on the bone mechanical properties of bone and calcium (Ca) metabolism using an ovariectomized (OVX) rat model of osteoporosis. METHODS: Female Wistar rats were OVX- or sham-operated at 40 weeks of age. Twelve weeks post-surgery, rats were randomized into seven groups: 1) sham + vehicle, 2) OVX + vehicle, 3) OVX + ALF 0.025 microg/kg/day, 4) OVX + ALF 0.05 microg, 5) OVX + RIS 0.3 mg, 6) OVX + RIS 3.0 mg, 7) OVX + ALF 0.025 microg + RIS 0.3 mg. Each drug was administered orally five times a week for 12 weeks. After treatment, we evaluated the mechanical properties of the lumbar vertebra and femoral midshaft. In the lumbar vertebra, structural and material analyses were performed using micro-computed tomography (micro-CT) and microbeam X-ray diffraction (micro-XRD), respectively. Biochemical markers in serum and urine were also determined. RESULTS: (1) With respect to improvement in the mechanical strength of the lumbar spine and the femoral midshaft, the combination treatment of ALF and RIS at their sub-therapeutic doses was more effective than each administered as a monotherapy; (2) In the suppression of bone resorption and the amelioration of microstructural parameters, the effects of ALF and RIS were considered to be independent and additive; (3) The improvement of material properties, such as microstructural parameters and the biological apatite (Bap) c-axis orientation, contributed to the reinforcement of spinal strength; and (4) The combination treatment of ALF and RIS normalized urinary Ca excretion, suggesting that this treatment ameliorated the changes in Ca metabolism. CONCLUSION: These results demonstrate that the combination treatment of ALF and RIS at their sub-therapeutic doses can improve the mechanical properties of the spine as well as the femur and ameliorate changes in Ca metabolism in an animal model of osteoporosis, suggesting that the combination treatment of ALF and RIS has a therapeutic advantage over each monotherapy for the treatment of osteoporosis.