How to Obtain the Maximum Properties Flexibility of 3D Printed Ketoprofen Tablets Using Only One Drug-Loaded Filament?

The flexibility of dose and dosage forms makes 3D printing a very interesting tool for personalized medicine, with fused deposition modeling being the most promising and intensively developed method. In our research, we analyzed how various types of disintegrants and drug loading in poly(vinyl alcohol)-based filaments affect their mechanical properties and printability. We also assessed the effect of drug dosage and tablet spatial structure on the dissolution profiles. Given that the development of a method that allows the production of dosage forms with different properties from a single drug-loaded filament is desirable, we developed a method of printing ketoprofen tablets with different dose and dissolution profiles from a single feedstock filament. We optimized the filament preparation by hot-melt extrusion and characterized them. Then, we printed single, bi-, and tri-layer tablets varying with dose, infill density, internal structure, and composition. We analyzed the reproducibility of a spatial structure, phase, and degree of molecular order of ketoprofen in the tablets, and the dissolution profiles. We have printed tablets with immediate- and sustained-release characteristics using one drug-loaded filament, which demonstrates that a single filament can serve as a versatile source for the manufacturing of tablets exhibiting various release characteristics.

A 3D model of the renal vasculature - a joined result of the corrosion casting technique, micro-CT imaging and rapid prototyping technology.

Three-dimensional (3D) printed model of the renal vasculature shows a high level of accuracy of subsequent divisions of both the arterial and the venous tree. However, minor artifacts appeared in the form of oval endings to the terminal branches of the vascular tree, contrary to the anticipated sharply pointed segments. Unfortunately, selective laser sintering process does not currently permit to present the arterial, venous and urinary systems in distinct colors, hence topographic relationship between the vascular and the pelvicalyceal systems is difficult to attain. Nonetheless, the 3D printed model can be used for educational purposes to demonstrate the vast renal vasculature and may also serve as a reference model whilst evaluating morphological anomalies of the intrarenal vasculature in a surgical setting.

An original micro-CT study and meta-analysis of the internal and external anatomy of maxillary molars-implications for endodontic treatment.

The aim of this work was to conduct a radiological micro-CT study and meta-analysis to determine the morphological features of the root canal anatomy of the maxillary molars. The radiological study included micro-CT scans of 110 maxillary first molars and 98 maxillary second molars. To identify articles eligible for inclusion in our meta-analysis, PubMed, Embase, and Web of Science were search comprehensively. The following data were extracted: study type (cadaveric, intraoperative or imaging), Vertucci types of canal configuration, presence/number of canals, roots, apical foramina, apical deltas, and inter-canal communications. The mesiobuccal root was the most variable with respect to canal configuration, type I being the most common configuration followed by type II and type IV. Type I was the most common canal configuration in the distobuccal and palatal root. Regarding the number of canals in the maxillary first and second molars, one canal was most prevalent in all roots of the three molars, except for the mesiobuccal root of maxillary first molar, in which two canals were most prevalent. The most prevalent number of roots in all maxillary molars was three. Knowledge of endodontic anatomy determines the parameters of root canal treatment and significantly affects the probability of success. It is therefore especially important to know the morphology of the root canal system in order to perform endodontic treatment correctly. Clin. Anat. 31:838-853, 2018. © 2018 Wiley Periodicals, Inc.

Stenotic Bicuspid and Tricuspid Aortic Valves　- Micro-Computed Tomography and Biological Indices of Calcification.

BACKGROUND: Valve calcification is well estimated by ex-vivo micro-computed tomography (micro-CT). The objective of this study was to investigate the associations between micro-CT findings and biological indices of calcification in aortic stenosis (AS), as well as differences between bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV).Methods and Results:Aortic valves and plasma were obtained from patients undergoing valve surgery. Valves were dissected and underwent micro-CT, genetic analyses, and calcium content assessment. Plasma levels of calcification markers were measured. Forty-two patients with isolated severe AS, including 22 with BAV, were studied. BAV patients had a lower median CT value (140.0 [130.0-152.0] vs. 157.0 [147.0-176.0], P=0.002) and high-density calcification (HDC) fraction (9.3 [5.7-23.3] % vs. 21.3 [14.3-31.2] %, P=0.01), as compared with TAV. Calcification fraction (CF) correlated with AS severity (measured as maximal transvalvular pressure gradient [r=0.34, P=0.03], maximal flow velocity [r=0.38, P=0.02], and indexed aortic valve area [r=-0.37, P=0.02]). For TAV patients only, mRNA expression of integrin-binding sialoprotein correlated with CF (r=0.45, P=0.048), and the receptor activator of the nuclear factor κ-B ligand transcript correlated with HDC corrugation (r=0.54, P=0.01). CONCLUSIONS: TAV patients with AS present more mineralized calcifications in micro-CT than BAV subjects. The relative volume of calcifications increases with the AS severity. In TAV patients, upregulated expression of genes involved in osteoblastogenesis in AS correlates with leaflet mineralization in micro-CT.

Micro-CT study of the dehiscences of the tympanic segment of the facial canal.

PURPOSE: To depict the anatomy of the tympanic segment of the facial canal using a 3D visualization technique, to detect dehiscences, and to evaluate their frequency, location, shape, and size. METHODS: Research included 36 human temporal bones (18 infant and 18 adult samples) which were scanned using a Nanotom 180N device. The final resolution of the reconstructed object was 18 µm. Obtained micro-CT data were subsequently processed by the volume rendering software. RESULTS: The micro-CT study allowed for the 3D visualization of the tympanic segment of the facial canal and detects dehiscences in the studied material in both infants and adults. Most of the dehiscences (66.7 %) involved the inferior wall of the tympanic segment in infants as well as in adults, and were located above and backward to the oval window. The most frequent dehiscence shape was elliptic (66.7 % in infants; 50 % in adults). Furthermore, we observed dehiscences of fusiform and trapezoidal shape in infants. Length of the dehiscences in most cases ranged from 0.5 to 1.4 mm (50 % in infants; 75 % in adults). CONCLUSIONS: Volumetric reconstructions demonstrated the course of the tympanic segment of the facial canal and its relationship with the tympanic cavity. Knowledge about the size and location of any dehiscence within the tympanic segment of the facial canal is necessary due to the surgical significance of this region. If a dehiscence occurs, there is an increased risk of injury to the facial nerve during the operations or spread of inflammation from the middle ear.

Visual perception of the osseous labyrinth rendered from micro-CT scans of the petrous bone.

Grayscale images comparing to the color images may have less of visual information necessary for easy recognition of the anatomical structures. Although micro-CT scanners deliver images of ultra-high resolution, application of false-colors to the rendered structures enhance their visual perception and allow for quick delineation between them and surrounding bony matrix. This paper presents differences of imaging of the osseous structures of the inner ear labyrinth using pseudo-color volume rendering in contrast to grayscale volume rendering of the micro-CT data. Applied procedures of image processing improved significantly delineation between the bony matrix surrounding the cochlea and vestibule rendered in the pseudo-colors than in grayscale.

3D visualization of the intratemporal course of the facial canal using computed micro-tomography.

The current study presents high resolution reconstructions showing the course of the facial canal within the temporal bone and visualizes the spatial orientation of the subsequent segments of the facial canal. 3D reconstructions of the facial canal were created from micro-CT data obtained from the right and left human temporal bones of an adult individual of the male sex. For this purpose, volume and surface rendering was applied. 3D models of the facial canal and adjacent osseous structures comprehensively revealed its intricate course and depicted the spatial orientation of its subsequent segments: labyrinthine, tympanic and mastoid. The labyrinthine segment of the facial canal was clearly displayed in the horizontal plane whereas the tympanic and mastoid segments were entirely visible in the sagittal plane, which lines up along the long axis of the petrous part of the temporal bone.

Comparison of volumetric reconstructions obtained from CT and micro-CT scans of the petrous bone.

is study presents effects of volumetric reconstructions of the petrous bone anatomy obtained from image data delivered by the medical CT scanner (Optima CT 660) and micro-CT scanner (Nanotom 180N) used in biological and technical applications. Although most of the osseous structures of the ear were visible in the subsequent serial CT scans delivered by the computed tomography system (Optima CT 660), their composition into volume was not satisfactory for viewing as a three-dimensional reconstruction. Micro-CT imaging of the anatomical structures of the petrous bone performed by the Nanotom 180N device was considerably superior to the medical computed tomography and the reconstructed anatomical structures presented a high level of accuracy and very realistic appearance.

Volume rendering of the tympanic cavity from micro-CT data.

The current study presents volumetric reconstruction of the tympanic cavity obtained from micro-CT scans which pixel size was 18 µm. Thanks to this, osseous components of the tympanic cavity were shown in high optical resolution, causing that their morphological appearance was clearly demonstrated. Particular attention was paid on imaging the medial wall of the tympanic cavity, because its structures are of clinical importance. In this respect we showed spatial relationship between the promontory, the oval window, the round window and other minute structures like the pyramidal eminence, subiculum and ponticulus. Hence, application of the microcomputed tomography allowed to visualize abnormal osseous formation located within the tympanic cavity, which potentially could interrupt normal movement of the auditory ossicles.

The impact of the parameters of the constitutive model on the distribution of strain in the femoral head.

The rapid spread of the finite element method has caused that it has become, among other methods, the standard tool for pre-clinical estimates of bone properties. This paper presents an application of this method for the calculation and prediction of strain and stress fields in the femoral head. The aim of the work is to study the influence of the considered anisotropy and heterogeneity of the modeled bone on the mechanical fields during a typical gait cycle. Three material models were tested with different properties of porous bone carried out in literature: a homogeneous isotropic model, a heterogeneous isotropic model, and a heterogeneous anisotropic model. In three cases studied, the elastic properties of the bone were determined basing on the Zysset-Curnier approach. The tensor of elastic constants defining the local properties of porous bone is correlated with a local porosity and a second order fabric tensor describing the bone microstructure. In the calculations, a model of the femoral head generated from high-resolution tomographic scans was used. Experimental data were drawn from publicly available database "Osteoporotic Virtual Physiological Human Project." To realistically reflect the load on the femoral head, main muscles were considered, and their contraction forces were determined based on inverse kinematics. For this purpose, the results from OpenSim packet were used. The simulations demonstrated that differences between the results predicted by these material models are significant. Only the anisotropic model allowed for the plausible distribution of stresses along the main trabecular groups. The outcomes also showed that the precise evaluation of the mechanical fields is critical in the context of bone tissue remodeling under mechanical stimulations.

An Insight into the Defects-Driven Plasticity in Ductile Cast Irons.

The microstructure and tensile behavior of two heavy section castings that had chemical compositions typical of GJS400 were investigated. Conventional metallography, fractography, and micro-Computer Tomography (µ-CT) were employed, enabling the quantification of the volume fractions of eutectic cells with degenerated Chunky Graphite (CHG), which was identified as the major defect in the castings. The Voce equation approach was exploited to evaluate the tensile behaviors of the defective castings for integrity assessment. The results demonstrated that the Defects-Driven Plasticity (DDP) phenomenon, which refers to an unexpected regular plastic behavior related to defects and metallurgical discontinuities, was consistent with the observed tensile behavior. This resulted in a linearity of Voce parameters in the Matrix Assessment Diagram (MAD), which contradicts the physical meaning of the Voce equation. The findings suggest that the defects, such as CHG, contribute to the linear distribution of Voce parameters in the MAD. Furthermore, it is reported that the linearity in the MAD of Voce parameters for a defective casting is equivalent to the existence of a pivotal point in the differential data of the tensile strain hardening data. This pivotal point was exploited to propose a new material quality index assessing the integrity of castings.

Simple anisotropic model of Bone Adaptation - SAMBA.

Bone presents the ability to adapt itself to the evolving mechanical environment. A simple anisotropic model for bone adaptation allowing reproducing the evolution of the elastic properties and the reorientation of the anisotropy frame is proposed is this work. The elastic properties are related to the value of the bone apparent density. The evolution law of the density is described via two functions reflecting the activities of the osteoclast and osteoblast cells. The anisotropy of the elastic properties of the bone is assumed evolving continuously between those of trabecular and compact tissues. The existence of a target material frame is assumed to describe its reorientation. The rate of rotation or spin of the material frame is supposed to be proportional to the target orientation angle and to the activity of the osteoclasts and osteoblasts. The mechanical stimulus governing the evolution of the apparent density is defined as the ratio between the current strain energy density and its critical value corresponding to the initiation of bone damage. The simulations showed that this simple model can reproduce some essential phenomena observed during bone adaptation process.

Investigation of Molten Metal Infiltration into Micropore Carbon Refractory Materials Using X-ray Computed Tomography.

The lifetime of a blast furnace (BF), and, consequently, the price of steel, strongly depends on the degradation of micropore carbon refractory materials used as lining materials in the BF hearth. One of the major degradation mechanisms in the BF hearth is related to the infiltration and dissolution of refractory materials in molten metal. To design new and more resilient materials, we need to know more about degradation mechanisms, which can be achieved using laboratory tests. In this work, we present a new investigation method of refractory materials infiltration resistance. The designed method combines a standard degradation test (hot metal penetration test) with X-ray computed tomography (XCT) measurements. Application of XCT measurements before and after molten metal infiltration allows observing changes in the micropore carbon refractory material's microstructure and identifying the elements of the open pore structure that are crucial in molten metal infiltration.

Decoding Rocks: An Assessment of Geomaterial Microstructure Using X-ray Microtomography, Image Analysis and Multivariate Statistics.

An understanding of the microstructure of geomaterials such as rocks is fundamental in the evaluation of their functional properties, as well as the decryption of their geological history. We present a semi-automated statistical protocol for a complex 3D characterization of the microstructure of granular materials, including the clustering of grains and a description of their chemical composition, size, shape, and spatial properties with 44 unique parameters. The approach consists of an X-ray microtomographic image processing procedure, followed by measurements using image analysis and statistical multivariate analysis of its results utilizing freeware and widely available software. The statistical approach proposed was tested out on a sandstone sample with hidden and localized deformational microstructures. The grains were clustered into distinctive groups covering different compositional and geometrical features of the sample's granular framework. The grains are pervasively and evenly distributed within the analysed sample. The spatial arrangement of grains in particular clusters is well organized and shows a directional trend referring to both microstructures. The methodological approach can be applied to any other rock type and enables the tracking of microstructural trends in grains arrangement.

Application of ZnO Nanoparticles in Sn99Ag0.3Cu0.7-Based Composite Solder Alloys.

The properties of Sn99Ag0.3Cu0.7 (SACX0307) solder alloy reinforced with ZnO nanoparticles were investigated. The primary ZnO particle sizes were 50, 100, and 200 nm. They were added to a solder paste at a ratio of 1.0 wt %. The wettability, the void formation, the mechanical strength, and the thermoelectric parameters of the composite solder alloys/joints were investigated. Furthermore, microstructural evaluations were performed using scanning electron and ion microscopy. ZnO nanoparticles decreased the composite solder alloys' wettability, which yielded increased void formation. Nonetheless, the shear strength and the thermoelectric parameters of the composite solder alloy were the same as those of the SACX0307 reference. This could be explained by the refinement effects of ZnO ceramics both on the Sn grains and on the Ag3Sn and Cu6Sn5 intermetallic grains. This could compensate for the adverse impact of lower wettability. After improving the wettability, using more active fluxes, ZnO composite solder alloys are promising for high-power applications.

Micro-CT analysis of the internal acoustic meatus angles as a method of sex estimation in skeletal remains.

The aim of the present study was to verify the lateral angle method for sex estimation by using computed micro-tomography. Two measurements of the anterior lateral angle of the internal acoustic meatus were assessed. The performed analysis revealed that the mean angle at the level of transverse crest of the fundus of the internal acoustic meatus in adults is significantly greater in females (45.58° vs. 39.68°; p < 0.05). A 45° sectioning point was applied, and sex allocation using this measurement was correct in 81.81% of adult samples. In turn, when utilizing the measurement at the level of modiolus of the cochlea, we did not obtain a satisfactory result in sex classification (59.09%). In subadults (male and female samples), the anterior lateral angles were undifferentiated. Thus, the conducted micro-CT analysis shows that the anterior lateral angle measurement method can be used as a preliminary indication of sex in adult individuals.

Characterization of mechanical behaviour of healthy and injured human incus by eigenfrequency evaluation.

The usage of finite element method techniques gives a possibility to replace time-consuming experiments or imitate physical process in the ear by numerical simulation. Especially, the research of spatial motion of ossicular chain in the middle ear is of high interest for the oto-surgeons and engineers. It is known that the most affected bone from the ossicular chain is the incus. After the cholesteatoma operation and tympanoplasty, the affected incus is removed or sacrificed; thus, the possibility of transducing noise lays on the stapes, new titanium or other material prosthesis. In this case, the affected incus was removed because of the cholesteatoma that was lying in front of it in the tympanic cavity. The removed incus with the affected long process passed micro-computed tomography. The computer-aided design systems allowed redesigning a 'healthy' incus with an intact long process. In this way, it was possible to evaluate the influence of damaged long process of incus in the vibrational analysis. This article analyses the problems of mechanical behaviour of injured and healthy human incus. The numerical simulation has demonstrated that the features of healthy incus and analysed injured incus do not differ significantly, especially at low (about 500 Hz) frequencies. It explains why there is no impact of cholesteatoma on hearing for a long time in the audiogram.

Examining the influence of functionalized POSS on the structure and bioactivity of flexible polyurethane foams.

This work reports for the first time on a new class of flexible polyurethane foam hybrids (PUFs) synthesized with the use of less toxic aliphatic hexamethylene diisocyanate (HDI), which have been chemically modified by POSS moieties. The flexible polyurethane foam hybrids (PUFs) chemically modified by functionalized polyhedral oligomeric silsesquioxanes: octa(3-hydroxy-3-methylbutyldimethylsiloxy)POSS (OCTA-POSS) and 1,2-propanediolizo-butylPOSS (PHI-POSS), was obtained. The resulting foams, which contain 0 to 15 wt % POSS, were characterized in terms of their structure, morphology, density and compressive strength. The FT-IR results indicate the chemical incorporation of both OCTAPOSS and PHIPOSS into the polyurethane matrix. SEM-EDS analysis showed that both OCTAPOSS and PHIPOSS nanoparticles are distributed homogeneously in the foam structure; at 15 wt % load PHIPOSS characteristic "crosses" are formed. With the increase of PHIPOSS content in the matrix, the formation of agglomerates is observed, as revealed by WAXD spectra. The introduction of POSS compounds reduces the porosity of the polyurethane, with the number of pores increasing as the amount of modifier increases. Mechanical tests - compressive strength - show that the hardness of modified materials (5 wt % POSS) increases compared to the reference material. An incubation was carried out in a simulated physiological fluid (SBF) to pre-assess the bioactivity of the materials obtained. The obtained results confirmed the formation of a hydroxyapatite layer on the PUF-POSS surface. Cytotoxicity, cell cycle and apoptosis of osteoblast cells and fibroblasts were assessed in the presence of the PUF-POSS materials. Test materials have a cytotoxic effect on both established cell lines. PUF-PHIPOSS samples showed better biocompatibility than reference and PUF-OCTAPOSS samples, as they caused lower mortality of the examined cells.

Carbon nanotube/iron oxide hybrid particles and their PCL-based 3D composites for potential bone regeneration.

This study describes the preparation, and evaluates the biocompatibility, of hydroxylated multi-walled carbon nanotubes (fCNTs) functionalized with magnetic iron oxide nanoparticles (IONs) creating hybrid nanoparticles. These nanoparticles were used for preparing a composite porous poly(ε-caprolactone) scaffolds for potential utilization in regenerative medicine. Hybrid fCNT/ION nanoparticles were prepared in two mass ratios - 1:1 (H1) and 1:4 (H4). PCL scaffolds were prepared with various concentrations of the nanoparticles with fixed mass either of the whole nanoparticle hybrid or only of the fCNTs. The hybrid particles were evaluated in terms of morphology, composition and magnetic properties. The cytotoxicity of the hybrid nanoparticles and the pure fCNTs was assessed by exposing the SAOS-2 human cell line to colloids with a concentration range from 0.01 to 1 mg/ml. The results indicate a gradual increase in the cytotoxicity effect with increasing concentration. At low concentrations, interestingly, SAOS-2 metabolic activity was stimulated by the presence of IONs. The PCL scaffolds were characterized in terms of the scaffold architecture, the dispersion of the nanoparticles within the polymer matrix, and subsequently in terms of their thermal, mechanical and magnetic properties. A higher ION content was associated with the presence of larger agglomerates of particles. With exception of the scaffold with the highest content of the H4 nanoparticle hybrid, all composites were superparamagnetic. In vitro tests indicate that both components of the hybrid nanoparticles may have a positive impact on the behavior of SAOS-2 cells cultivated on the PCL composite scaffolds. The presence of fCNTs up to 1 wt% improved the cell attachment to the scaffolds, and a content of IONs below 1 wt% increased the cell metabolic activity.

Biocompatible Nanocomposite Implant with Silver Nanoparticles for Otology-In Vivo Evaluation.

The aim of this work was to investigate of biocompatibility of polymeric implants modified with silver nanoparticles (AgNPs). Middle ear prostheses (otoimplants) made of the (poly)acrylonitrile butadiene styrene (ABS) and ABS modified with silver nanoparticles were prepared through extrusion and injection moulding process. The obtained prostheses were characterized by SEM-EDX, micro-CT and mechanical tests, confirming their proper shape, good AgNPs homogenization and mechanical parameters stability. The biocompatibility of the implants was evaluated in vivo on rats, after 4, 12, 24 and 48 weeks of implantation. The tissue-healing process and cytotoxicity of the implants were evaluated on the basis of microscopic observations of the materials morphology after histochemical staining with cytochrome c oxidase (OCC) and acid phosphatase (AP), as well as via micro-tomography (ex vivo). The in vivo studies confirmed biocompatibility of the implants in the surrounding tissue environment. Both the pure ABS and nanosilver-modified ABS implants exhibited a distinct decrease in the area of granulation tissue which was replaced with the regenerating muscle tissue. Moreover, a slightly smaller area of granulation tissue was observed in the surroundings of the silver-doped prosthesis than in the case of pure ABS prosthesis. The kinetics of silver ions releasing from implants was investigated by ICP-MS spectrometry. The measurement confirmed that concentration of the silver ions increased within the implant's immersion period. Our results showed that middle ear implant with the nanoscale modification is biocompatible and might be used in ossicular reconstruction.