Mass customization of medical devices and implants: state of the art and future directions

The medical field is one in which the need for customization can be clear cut, as providing tailored devices and implants for unique physiologies can provide for a better overall treatment than the use of 'off the shelf' devices and implants. Customization in the production of medical products can be roughly divided into consideration of medical devices, and of implantable parts or systems. The present paper outlines the current state of the art in both of these areas, presents details of projects that are ongoing at the University of Leeds and outlines future research directions.     

Immunohistochemical study of epithelioid hemangioendothelioma in the leg: a case report

Epithelioid hemangioendothelioma is a relatively rare lesion. Although its histogenesis has been well described, its immunohistochemical characteristics remain controversial. A case of epithelioid hemangioendothelioma of the soft tissue of the right leg in a 67-year-old Chinese woman is reported. Histologic findings of intracytoplasmic lumina in the tumor cells and positive immunostaining for vimentin, factor VIII-related antigen. CD34 and Ulex europaeus agglutinin 1 (UEA-1) were obtained, demonstrating differentiation of the tumor cells to endothelial cells, although staining for antibodies to cytokeratins AE1/AE3 and CAM5.2 was weak. CD34 as well as Factor VIII-related antigen is a useful marker of endothelial differentiation in this tumor. A review of the literature is also presented.     

Non‐cooperative game‐based packet ferry forwarding for sparse mobile wireless networks

In sparse mobile wireless networks, normally, the mobile nodes are carried by people, and the moving activity of nodes always happens in a specific area, which corresponds to some specific community. Between the isolated communities, there is no stable communication link. Therefore, it is difficult to ensure the effective packet transmission among communities, which leads to the higher packet delivery delay and lower successful delivery ratio. Recently, an additional ferry node was introduced to forward packets between the isolated communities. However, most of the existing algorithms are working on how to control the trajectory of only one ferry work in the network. In this paper, we consider multiple ferries working in the network scenario and put our main focus on the optimal packet selection strategy, under the condition of mutual influence between the ferries and the buffer limitation. We introduce a non‐cooperative Bayesian game to achieve the optimal packet selection strategy. By maximizing the individual income of a ferry, we optimize the network performance on packet delivery delay and successful delivery ratio. Simulation results show that our proposed packet selection strategy improves the network performance on packet delivery delay and successful delivery ratio. Copyright © 2013 John Wiley & Sons, Ltd.     

Thermoreversible behavior of κ-carrageenan and its apatite-forming ability in simulated body fluid

Osteoconductive materials with self-setting ability have received much attention because their properties allow developing injectable materials for bone defects. Thermosensitive hydrogel with ability of bone-like apatite formation in a body environment is a candidate of injectable bone fillers with osteoconductivity because the apatite formation on materials is an essential to show osteoconduction. The present study focused on the development of a thermosensitive hydrogel through modifications of the sulphonic groups of the polysaccharide, κ-carrageenan, with potassium chloride (KCl) and calcium chloride (CaCl₂). We found that the gelation temperature of κ-carrageenan solutions increased with increasing amounts of K⁺ ions. Apatite formation was observed on the gel after exposure to simulated body fluid for 0.5 day when the gel was prepared with a molar ratio of Ca²⁺/sulfonic groups = 1.5. These results indicate that a thermosensitive κ-carrageenan hydrogel with apatite-forming ability was obtained through the incorporation of K⁺ and Ca²⁺ ions into the solution.     

Enhancement of bonding strength by graded structure at interface between apatite layer and bioactive tantalum metal

Tantalum metal is a candidate for use as an implant material in high load-bearing bony defects, due to its attractive features such as high fracture toughness and high workability. This metal, however, does not have bone-bonding ability, i.e. bioactivity, and therefore the development of bioactive tantalum metal is highly desirable. It is known that the essential prerequisite for an artificial material to show bioactivity is to form a bonelike apatite layer on its surface in the body environment. The same type of apatite layer is formed in a simulated body fluid (SBF) with inorganic ion concentrations nearly equal to those of human blood plasma. The present authors previously showed that the apatite formation on tantalum metal in SBF was remarkably accelerated by treatment with 0.5 M-NaOH aqueous solution and subsequent firing at 300 °C, while untreated tantalum metal spontaneously formed the same apatite after a long soaking period. In the present study, the bonding strength of the apatite layer to the substrate was quantitatively evaluated in comparison with that to the untreated tantalum metal. Adhesive strength was measured as an estimation of bonding strength, and the surface microstructure of both the substrates was characterized in order to discuss the difference in the bonding strength in terms of surface structure. The apatite layer formed on the NaOH- and heat-treated tantalum metal shows higher adhesive strength than that formed on the untreated metal. The amorphous sodium tantalate layer formed on the tantalum metal by NaOH and heat treatments, has a smooth graded structure where its concentration gradually changes from the surface into the interior metal. Smooth graded structure with complex of apatite is constructed after soaking in SBF. The higher bonding strength of the apatite layer formed on the treated metal is attributed to its smooth graded structure.     

Molecular dynamic simulation of heterogeneity and chemical states of fluorine in amorphous alkaline earth silicate systems

Chemical states of fluorine in fluorosilicate glasses in the system MF₂-MO-SiO₂ (M = Ca, Sr and Ba; SiO₂ content < 60 mol%) have been investigated by molecular dynamic (MD) simulations with a perfect ionic two-body potential. Comparison of the results with those derived by X-ray photoelectron spectra of the actual glasses demonstrates that MD simulations reproduce well the bonding states of fluorine in the systems as well as the formation of M-F clusters. The MD generated structure of imaginary glasses, or glasses not obtained by the conventional melt-quench technique, with 70 mol% SiO₂ indicates that an acidic environment induces a greater amount of F---Si bonds. Their M-F pair correlation functions plotted against normalized M-F distances suggest that relative ion positions in the clusters are very similar.     

Evidence for a central substructure in a Lumbricus terrestris hemoglobin obtained with STEM low-dose and digital processing techniques

Applications of scanning transmission electron microscope (STEM) low-dose and digital image processing techniques to the annelid extracellular hemoglobin of Lumbricus terrestris have shown the existence of a central substructure. The techniques involve low-dose STEM images of less than 2 e/A2 irradiation. Many such low-dose images were then aligned in their symmetry, N-fold averaged, and summed. The central substructure appears to be supported by spokes which are connected to a surrounding hexagonal bilayer of 12 subunits. In comparison to the summed image of Nephtys hombergii hemoglobin which is known to possess a central substructure, the morphology of both central mass and spokes were very similar. This finding of a central substructure is consistent with the report of a small angle X-ray scattering study (Pilz et al., 1980, Int. J. Biol. Macromol. 2, 279-283) which predicted the possible existence of substructure in the center of the molecule.     

Development of bioactive PMMA-based cement by modification with alkoxysilane and calcium salt

Poly (methyl methacylate) (PMMA) bone cement is one of the popular bone-repairing materials for fixation of artificial hip joints. Significant problems on the PMMA bone cement are caused by loosening at the interface between bone and the cement, since the cement does not show bone-bonding, i.e. bioactivity. Development of PMMA bone cement capable of bone-bonding has been therefore long desired. The prerequisite for an artificial material to show bone-bonding is the formation of a biologically active bone-like apatite layer on its surface when implanted in the body. The same type of apatite formation can be observed on bioactive materials even in a simulated body fluid (Kokubo solution) with ion concentrations nearly equal to those of human blood plasma. Fundamental researches for bioactive glasses and glass-ceramics revealed that the apatite deposition is initiated by release of Ca2+ ions from the material into the body fluid, and by catalytic effect of Si-OH groups formed on the surface of the material. These findings lead an idea that novel bioactive cement can be designed by incorporation of Si-OH groups and Ca2+ ion into PMMA bone cement. In the present study, PMMA bone cement is modified with 20 mass % of various kinds of alkoxysilanes and calcium salts, and its apatite-forming ability was evaluated in Kokubo solution. The apatite formation was observed on the surface of the modified cements containing 20 mass % of CaCl2, irrespective of the kind of the examined alkoxysilane. On the other hand, the apatite formation was observed on the cement containing CaCl2, Ca(CH3COO)2 or Ca(OH)2, but not on the cement containing CaCO3 or beta-Ca3(PO4)2, even when the cement contains 3-methacryloxypropyltrimethoxysilane (MPS). The results indicate that modification with alkoxysilane and calcium salts showing high water-solubility is effective for providing PMMA bone cement with bioactivity.     

Acceleration of calcium phosphate formation on bioactive PMMA-based bone cement by controlling spatial design

Polymethylmethacrylate (PMMA)-based bone cement is widely used for the fixation of artificial joints. However, it is not considered a bioactive material because it lacks the ability to induce a direct bond with bone. In order to improve the long-term stability of cemented fixations, the development of bioactive bone cements is desirable. An essential requirement of a bioactive material includes the induction of bone-like apatite on its surface within the in vivo environment. Previously, we prepared bioactive PMMA-based bone cements by a modification with water-soluble calcium salts and alkoxysilane. Because spatial design may enhance apatite formation on bioactive material surfaces in vivo, we aimed to evaluate the effect of spatial design on apatite formation on modified PMMA-based bone cements in simulated body fluid (SBF). We found that an appropriate spatial design shortened the induction period for the apatite deposition on the modified bone cements. It is expected that osteoconduction would be enhanced in spontaneously created gap between the cement and the host bone leading to tight integration.