Mechanical properties and apatite forming ability of TiO<Subscript>2</Subscript> nanoparticles/high density polyethylene composite: Effect of filler content

Composite materials consisting of TiO₂ nanoparticles and high-density polyethylene (HDPE), designated hereafter as TiO₂/HDPE, were prepared by a kneading and forming process. The effect of TiO₂ content on the mechanical properties and apatite forming ability of these materials was studied. Increased TiO₂ content resulted in an increase in bending strength, yield strength, Young’s modulus and compressive strength (bending strength = 68 MPa, yield strength = 54 MPa, Young’s modulus = 7 GPa, and compressive strength = 82 MPa) at 50 vol% TiO₂. The composite with 50 vol% TiO₂ shows a similar strength and Young’s modulus to human cortical bone. The TiO₂/HDPE composites with different TiO₂ contents were soaked at 36.5°C for up to 14 days in a simulated body fluid (SBF) whose ion concentrations were nearly equal to those of human blood plasma. The apatite forming ability, which is indicative of bioactivity, increased with TiO₂ content. Little apatite formation was observed for the TiO₂/HDPE composite with 20 vol% content. However, in the case of 40 vol% TiO₂ content and higher, the apatite layers were formed on the surface of the composites within 7 days. The most potent TiO₂ content for a bone-repairing material was 50 vol%, judging from the mechanical and biological results. This kind of bioactive material with similar mechanical properties to human cortical bone is expected to be useful as a load bearing bone substitute in areas such as the vertebra and cranium.     

Prediction of osteoconductive activity of modified potassium fluorrichterite glass-ceramics by immersion in simulated body fluid

Potassium fluorrichterite (KNaCaMg₅Si₈O₂₂F₂) glass-ceramics were modified by either increasing the concentration of calcium (GC5) or by the addition of P₂O₅ (GP2). The stoichiometric composition (GST), GC5 and GP2 were soaked in simulated body fluid (SBF) along with 45S5-type bioglass as a control. After immersion, surface analyses were performed using thin-film X-ray diffraction (TF-XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and Fourier-transform infrared (reflection) spectroscopy (FT-IR). All compositions showed the formation of a calcium phosphate rich surface layer in SBF; GST, GP2 and the bioglass control within 7 days of immersion and GC5 after 14 days. It was concluded that all compositions were likely to be osteoconductive in vivo, with GP2 providing the best performance in terms of the combination of rapid formation of the surface layer and superior mechanical properties. This glass-ceramic system has potential as a load bearing bioceramic for fabrication of medical devices intended for skeletal tissue repair.     

Apatite–organic polymer composites prepared by a biomimetic process: improvement in adhesion of the apatite layer to the substrate by ultraviolet irradiation

A dense and uniform layer of highly bioactive apatite can be formed in arbitrary thickness on any kind and shape of organic polymer substrates by the following biomimetic process. The substrate is first placed in contact with granular particles of CaO, SiO2-based glass soaked in a simulated body fluid with ion concentrations nearly equal to those of human blood plasma for forming apatite nuclei, and then soaked in another fluid highly supersaturated with respect to the apatite for making the apatite nuclei grow. In the present study, the polymer substrates were pretreated with ultraviolet (UV) light, and then subjected to the biomimetic process described above. By UV irradiation, the induction period for the apatite nucleation of poly(ethylene terephthalate) (PET), poly-ether sulphone (PESF), polyethylene (PE), poly(methyl methacrylate) (PMMA) and polyamide 6 (N6) substrates were reduced form 24 h to 10 h. The adhesive strengths of the apatite layer to the substrates increased from 2.5–3.2 MPa to 4.5–6.0 MPa for PET, PESF and PMMA, and from about 1.0 MPa to 4.0–6.5 MPa for PE and N6 substrates. These results have been explained by assuming that silicate ions, which induce apatite nucleation, are easily adsorbed on the substrates due to the formation of polar groups, with an improved hydrophilic nature, on the polymer surfaces by UV irradiation. © 1998 Chapman & Hall     

Effect of Ca contamination on apatite formation in a Ti metal subjected to NaOH and heat treatments

It has long been known that titanium (Ti) metal bonds to living bone through an apatite layer formed on its surface in the living body after it had previously been subjected to NaOH and heat treatments and as a result had formed sodium titanate on its surface. These treatments were applied to a porous Ti metal layer on a total hip joint and the resultant joint has been in clinical use since 2007. It has been also demonstrated that the apatite formation on the treated Ti metal in the living body also occurred in an acelullar simulated body fluid (SBF) with ion concentrations nearly equal to those of the human blood plasma, and hence bone-bonding ability of the treated Ti metal can be evaluated using SBF in vitro. However, it was recently found that certain Ti metals subjected to the same NaOH and heat treatments display apatite formation in SBF which is decreased with the increasing volume of the NaOH solution used in some cases. This indicates that bone-bonding ability of the treated Ti metal varies with the volume of the NaOH solution used. In the present study, this phenomenon was systematically investigated using commercial NaOH reagents and is considered in terms of the structure and composition of the surface layers of the treated Ti metals. It was found that a larger amount of the calcium contamination in the NaOH reagent is concentrated on the surface of the Ti metal during the NaOH treatment with an increasing volume of the NaOH solution, and that this inhibited apatite formation on the Ti metal in SBF by suppressing Na ion release from the sodium titanate into the surrounding fluid. Even a Ca contamination level of 0.0005 % of the NaOH reagent was sufficient to inhibit apatite formation. On the other hand, another NaOH reagent with a nominal purity of just 97 % did not exhibit any such inhibition, since it contained almost no Ca contamination. This indicates that NaOH reagent must be carefully selected for obtaining reliable bone-bonding implants of Ti metal by the NaOH and heat treatments.     

Formation of bioactive functionally graded structure on Ti-6Al-4V alloy by chemical surface treatment

An Al- and V-free sodium titanate hydrogel layer with a graded structure where the sodium titanate gradually decreases toward the interior, was formed on the surface of Ti-6Al-4V alloy, when the alloy was exposed to 5M NaOH solution at 60 °C for 24 h. This gel layer was transformed into an amorphous sodium titanate layer without giving considerable change in the graded structure, except a little increase in the depth of the oxygen distribution by a heat treatment at 600 °C for 1 h. The sodium titanate layer formed Ti-OH groups on its surface by exchanging its Na⁺ ion with H₃O⁺ ion in simulated body fluid when soaked in the fluid, and thus formed Ti-OH groups induced the apatite nucleation. The apatite layer also formed a graded structure toward the substrate. The strong bond of the apatite layer to the substrate was attributed to this graded structure.     

XPS study of the process of apatite formation on bioactive Ti—6Al—4V alloy in simulated body fluid

Bioactive Ti—6Al—4V alloy, which spontaneously forms a bonelike apatite layer on its surface in the body and bonds to living bone through this apatite layer, can be prepared by producing an amorphous sodium titanate on its surface by NaOH and heat treatments. In this study, the process of apatite formation on the bioactive Ti—6Al—4V alloy was investigated in vitro, by analyzing its surface with X-ray photoelectron spectroscopy as a function of soaking time in a simulated body fluid 4SBF). Thin-film X-ray diffractometry of the alloy surface and atomic emission spectroscopy of the fluid were also performed complementarily. It was found that immediately after immersion in the SBF,the alloy exchanged Na¹ ions from the surface sodium titanate with H₃O¹ ions in the fluid to form Ti-OH groups on its surface. The Ti-OH groups, immediately after their formation,incorporated the calcium ions in the fluid to form calcium titanate. The calcium titanate thereafter incorporated the phosphate ions in the fluid to form an amorphous calcium phosphate, which was later crystallized into bonelike apatite. This process of apatite formation on the alloy was the same as on the pure titanium metal, because the alloy formed the sodium titanate free of Al and V by the NaOH and heat treatments. The initial formation of the calcium titanate is proposed to be a consequence of the electrostatic interaction of negatively charged units of titania dissociated from the Ti-OH groups with the positively charged calcium ions in the fluid. The calcium titanate is postulated to gain a positive charge and interact with the negatively charged phosphate ions in the fluid to form amorphous calcium phosphate, which eventually stabilizes into crystalline apatite.     

Printed Circuit Board Design via Organizational-Learning Agents

This paper proposes a novel evolutionary computation model: Organizational-Learning Oriented Classifier System (OCS), and describes its application to Printed Circuit Boards (PCBs) redesign problems in a computer aided design (CAD). Using the conventional CAD systems which explicitly decide the parts' placements by a knowledge base, the systems cannot effectively place the parts as done by human experts. Furthermore, the supports of human experts are intrinsically required to sa tisfy the constraints and to optimize a global objective function. However, in the proposed model OCS, the parts generate and acquire adaptive behaviors for an appropriate placement without explicit control. In OCS, we focus upon emergent processes in which the parts dynamically form an organized group with autonomously generating adaptive behaviors through local interaction among them. Using the model OCS, we have conducted intensive experiments on a practical PCB redesign problem for electric appliances. The experimental results have shown that: (1) it has found the feasible solutions of the same level as the ones by human experts, (2) solutions are locally optimal, and also globally better than the ones by human experts with regard to the total wiring length, and (3) the solutions are more preferable than those in the conventional CAD systems.     

Evaluation of Oil/Water-Type Cyclosporine Gel Ointment with Commercially Available Oral Solution

Oil/water-type cyclosporine (CyA) hydrogel ointment was evaluated as a candidate for the percutaneous application of CyA. The physical properties and the permeation profiles of 2% w/w CyA gel ointment were compared with other CyA ointments. All ointments used in this study were prepared with commercially available CyA (Sandimmune) oral solution, unlike the ointment reported in the publication of by Mizoguchi et al. The gel ointment required a surfactant corresponding to 5-7% w/w to obtain fine uniform particles. Mean diameter of oily particles in the gel ointment was 8.75 μm. The permeation of CyA from the ointments was investigated by using the abdominal skin of hairless rats in vitro. The percutaneous permeation of CyA was observed to be influenced by a variety of ointment bases used and by the presence of a stratum corneum which plays a role as the main barrier. In intact skin, the extent of permeation from the gel ointment was almost equivalent to that from Mizoguchi's ointment, which used the raw CyA. No permeation was observed in ointment bases with either white petrolatum or hydrophilic petrolatum, indicating values under the limit of detection (78 ng/ml) of the high-performance liquid chromatographic method used in this study. On the other hand, in stripped skin, differences in flux value of each ointment were shown. Those values increased in the following order: Mizoguchi's ointment, white petrolatum, hydrogel, hydrophilic petrolatum. From these results, hydrogel ointment seemed to be applicable for various skin diseases which respond to CyA. Of the physical properties, spreadability and consistency showed that gel ointment was superior to Mizoguchi's ointment. In stability tests, the gel ointment was stable with regard to particle size and residual CyA for 4 weeks. These results suggested that the oil/water-type CyA hydrogel ointment prepared in a combination with hydrogel and commercially available oral solution was useful for practical hospital preparations, with good physical properties, permeability, and stability.     

X-ray Photoelectron Spectroscopy Study on the Process of Apatite Formation on a Sodium Silicate Glass in Simulated Body Fluid

The process of apatite formation on the surface of Na₂O–SiO₂ glass in a body environment was investigated, mainly by X-ray photoelectron spectroscopy, as a function of soaking time in a simulated body fluid (SBF). The glass was found to release Na⁺ ions via exchange with H₃O⁺ ions in the SBF to form Si—OH groups on its surface. These Si—OH groups induced apatite formation indirectly, by forming calcium silicate and amorphous calcium phosphate. The formation of the calcium silicate and amorphous calcium phosphate is attributed to electrostatic interactions between the Si—OH groups on the glass surface and the calcium and phosphate ions in the SBF.     

Osteoclastic resorption of bone-like apatite formed on a plastic disk as an in vitro assay system

Congenital diaphragmatic hernia (CDH) is associated with high neonatal mortality from lung hypoplasia and persistent pulmonary hypertension. Pulmonary neuroendocrine cells (PNEC) produce calcitonin gene-related peptide (CGRP), a potent vasodilator. We previously reported altered distribution of CGRP-positive PNEC in full-term rats with CDH, that may lead to an imbalance in vasoactive mediators. In the present study we examined the expression of CGRP-positive PNEC during lung development in rats with CDH induced by 2,4-dichlorophenyl-p-nitrophenylether (Nitrofen). Cesarean sections were performed on Days 16, 18, 20, or 22, and the lungs were immunostained for CGRP and immunoreactive cells were quantitated through image analysis. On Day 16, CGRP-immunoreactive staining was negative; on Day 18, CGRP-immunoreactive cells were found in all controls (not exposed to Nitrofen), whereas in CDH pups, CGRP-positive cells were present in only four of six cases. On Day 20, CGRP immunoreactivity was similar in CDH pups, Nitrofen-exposed pups without CDH, and controls. On Day 22 (term), significantly more CGRP-positive cells (i.e., number of positive cells per surface area [mm2] or lung volume [mm3]) were found in ipsilateral lungs of CDH pups than in controls (P < 0.05). The difference was even more striking in contralateral lungs of CDH pups (P < 0.001), ruling out nonspecific effects of Nitrofen. In CDH lungs, the proportion of immunostained epithelium and the size of the neuroendocrine cell clusters (neuroepithelial bodies [NEB]) were not significantly different from those of controls. On Day 22, supraoptimal dilution immunocytochemistry yielded similar results in CDH pups and controls. We conclude that in CDH, CGRP expression in PNEC and NEB is delayed during early stages of lung development. Because CGRP also exhibits growth factor-like properties for endothelium and epithelial cells, the lack of this factor during a crucial developmental stage (canalicular period) may be causally related to lung hypoplasia.