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Objective: To examine the association between 3D patellar shape and 1) isolated magnetic resonance imaging (MRI)-based patellofemoral osteoarthritis (PFOA), 2) the morphological features of PFOA, and 3) the clinical symptoms of PFOA. Design: MRI data from 66 women with isolated MRI-based PFOA and 66 age- and BMI-matched healthy women were selected from a cohort study. The patellae were manually segmented from MRI scans and used to create a 3D statistical shape model (SSM) of the patella. Structural abnormalities were semi-standardized scored on MRI using MRI osteoarthritis knee score (MOAKS). Regression analyses were applied to determine the associations between the shape parameters retrieved from the SSM, group status, clinical symptoms, and structural abnormalities. Results: Four shape variants showed a statistically significant (Conclusions: Patellar shape is associated with the prevalence of MRI-based PFOA in women. Some shape variants were also associated with clinical symptoms. Interestingly, one particular shape variant associated with the presence of MRI-based PFOA was earlier shown to be associated with structural abnormalities associated with OA in a population aged under 40. This may suggest that patellar shape may be an early detectable risk factor for PFOA.

We studied the three-dimensional (3-D) shape variations and symmetry of the lunate to evaluate whether a contralateral shape-based approach to design patient-specific implants for treatment of Kienböck’s disease is accurate. A 3-D statistical shape model of the lunate was built using the computed tomography scans of 54 lunate pairs and shape symmetry was evaluated based on an intraclass correlation analysis. The lunate shape was not bilaterally symmetrical in (1) the angle scaphoid surface – radius-ulna surface, (2) the dorsal side and the length of the side adjacent to the triquetrum, (3) the orientation of the volar surface, (4) the width of the side adjacent to the scaphoid, (5) the skewness in the coronal plane and (6) the curvature of bone articulating with the hamate and capitate. These findings suggest that using the contralateral lunate to design patient-specific lunate implants may not be as accurate as it is intended.

The treatment of femoral nonunion with large segmental bone defect is still challenging. Although magnesium alloys have been considered potential materials for such a treatment, their application is limited by their fast degradation. Adding bioceramic particles into magnesium to form Mg-matrix composites is a promising strategy to adjust their biodegradation rates and to improve their mechanical properties and cytocompatibility further. Here, we developed an extrusion-based additive manufacturing technique to fabricate biodegradable Mg-Zn/bioceramic composite scaffolds ex-situ. Inks carrying a Mg-Zn powder and 5, 10 and 15% β-tricalcium phosphate (TCP) powder particles were investigated regarding the dispersion of β-TCP particles in the inks and viscoelastic properties. Optimally formulated inks were then employed for subsequent 3D printing of porous composite scaffolds. The in vitro biodegradation rate of the scaffolds containing 5% β-TCP decreased to 0.5 mm/y, which falls within the range desired for critical-sized bone substitution. As compared to the monolithic Mg-Zn scaffolds, the elastic moduli and yield strengths of the composite scaffolds were much enhanced, which remained in the range of the cancellous bone properties even after 28 d of in vitro degradation. The Mg-Zn/5TCP and Mg-Zn/10TCP scaffolds also exhibited improved biocompatibility when cultured with preosteoblasts, as compared to Mg-Zn scaffolds. In addition, the ALP activity and mineralization level of the composite scaffolds were much enhanced in the extracts of the composite scaffolds. Taken together, this research marks a great breakthrough in fabricating porous Mg-matrix composite scaffolds that meet several design criteria in terms of appropriate biodegradation rate, mechanical properties, and bioactivity. Statement of significance: The treatment of posttraumatic femoral nonunion with large segmental bone defect is still challenging. In this study, we developed a multi-material extrusion-based additive technique to fabricate porous Mg/bioceramic composite scaffolds for such a treatment. The technique allowed for the fine-tuning of printable inks to optimize the dispersion of micro-sized particles. The relative densities of the struts of the fabricated composite scaffolds reached 99%. The added bioceramic particles (β-TCP) exhibited proper interfacial bonding with the Mg alloy matrix. The porous Mg-based composite possessed desired biodegradability, bone-mimicking mechanical properties throughout the in vitro biodegradation period and improved bioactivity to bone cells. These results demonstrated great prospects of extrusion-based 3D printed porous Mg materials to be developed further as ideal biodegradable bone-substituting materials.

Additively manufactured (AM) biodegradable magnesium (Mg) scaffolds with precisely controlled and fully interconnected porous structures offer unprecedented potential as temporary bone substitutes and for bone regeneration in critical-sized bone defects. However, current attempts to apply AM techniques, mainly powder bed fusion AM, for the preparation of Mg scaffolds, have encountered some crucial difficulties related to safety in AM operations and severe oxidation during AM processes. To avoid these difficulties, extrusion-based 3D printing has been recently developed to prepare porous Mg scaffolds with highly interconnected structures. However, limited bioactivity and a too high rate of biodegradation remain the major challenges that need to be addressed. Here, we present a new generation of extrusion-based 3D printed porous Mg scaffolds that are coated with MgF

Recently, lattice titanium manufactured by additive manufacturing (AM) techniques has been utilized in various applications, including biomedical. The effects of topological design and processing parameters on the fatigue behaviour of such meta-biomaterials have been studied before. Most studies show that the fatigue life of additively manufactured lattice structures is limited. Post-processing techniques could play a major role in improving the fatigue of these promising biomaterials. This study aims to provide an in-depth investigation into the effects of heat treatments, hot isostatic pressing (HIP), sand blasting, and chemical etching on the microstructure, surface morphology, strength and fatigue resistance of selective laser melted titanium meta-biomaterials. It was found that the combination of microstructural design and surface engineering, induced by HIP and sand blasting respectively, allows to increase the endurance limit of these lattice meta-biomaterials by a factor of two. HIP treatment substantially decreased the internal porosity and transformed the microstructure to a more ductile mixture of α + β phases. Sand blasting allowed to eliminate surface imperfections and induced favourable compressive stress in the surface layer of the struts. Statement of Significance Additively manufactured metallic meta-biomaterials are progressively being used as bone replacement orthopedic implants. While there is a great amount of research related to topological designs and their effect on mechanical (e.g. stiffness), physical (e.g. mass transport), and biological (e.g. osseointegration) properties, fatigue lifetime of such structures remains limited. This study provides fundamental investigation into the combined effect of microstructural design and surface engineering of titanium meta-biomaterial, enabled through various post treatment methods ranging from heat treatments to physical and chemical surface modifications. The findings show that fatigue life is significantly improved by applying developed herein novel method, which effortlessly can be used on other bone-mimicking metallic meta-biomaterials.

The reconstruction of large mandibular defects with optimal aesthetic and functional outcomes remains a major challenge for maxillofacial surgeons. The aim of this study was to design patient-specific mandibular reconstruction implants through a semi-automated digital workflow and to assess the effects of topology optimization on the biomechanical performance of the designed implants. By using the proposed workflow, a fully porous implant (LA-implant) and a topology-optimized implant (TO-implant) both made of Ti–6Al–4V ELI were designed and additively manufactured using selective laser melting. The mechanical performance of the implants was predicted by performing finite element analysis (FEA) and was experimentally assessed by conducting quasi-static and cyclic biomechanical tests. Digital image correlation (DIC) was used to validate the FE model by comparing the principal strains predicted by the FEM model with the measured distribution of the same type of strain. The numerical predictions were in good agreement with the DIC measurements and the predicted locations of specimen failure matched the actual ones. No statistically significant differences (p < 0.05) in the mean stiffness, mean ultimate load, or mean ultimate displacement were detected between the LA- and TO-implant groups. No implant failures were observed during quasi-static or cyclic testing under masticatory loads that were substantially higher (>1000 N) than the average maximum biting force of healthy individuals. Given its relatively lower weight (16.5%), higher porosity (17.4%), and much shorter design time (633.3%), the LA-implant is preferred for clinical application. This study clearly demonstrates the capability of the proposed workflow to develop patient-specific implants with high precision and superior mechanical performance, which will greatly facilitate cost- and time-effective pre-surgical planning and is expected to improve the surgical outcome.

International audience; The design of advanced functional devices often requires the use of intrinsically curved geometries that belong to the realm of non-Euclidean geometry and remain a challenge for traditional engineering approaches. Here, it is shown how the simple deflection of thick meta-plates based on hexagonal cellular mesostructures can be used to achieve a wide range of intrinsic (i.e., Gaussian) curvatures, including dome-like and saddle-like shapes. Depending on the unit cell structure, non-auxetic (i.e., positive Poisson ratio) or auxetic (i.e., negative Poisson ratio) plates can be obtained, leading to a negative or positive value of the Gaussian curvature upon bending, respectively. It is found that bending such meta-plates along their longitudinal direction induces a curvature along their transverse direction. Experimentally and numerically, it is shown how the amplitude of this induced curvature is related to the longitudinal bending and the geometry of the meta-plate. The approach proposed here constitutes a general route for the rational design of advanced functional devices with intrinsically curved geometries. To demonstrate the merits of this approach, a scaling relationship is presented, and its validity is demonstrated by applying it to 3D-printed microscale meta-plates. Several applications for adaptive optical devices with adjustable focal length and soft wearable robotics are presented.

Additively manufactured (AM) biodegradable magnesium (Mg) scaffolds with precisely controlled and fully interconnected porous structures offer unprecedented potential as temporary bone substitutes and for bone regeneration in critical-sized bone defects. However, current attempts to apply AM techniques, mainly powder bed fusion AM, for the preparation of Mg scaffolds, have encountered some crucial difficulties related to safety in AM operations and severe oxidation during AM processes. To avoid these difficulties, extrusion-based 3D printing has been recently developed to prepare porous Mg scaffolds with highly interconnected structures. However, limited bioactivity and a too high rate of biodegradation remain the major challenges that need to be addressed. Here, we present a new generation of extrusion-based 3D printed porous Mg scaffolds that are coated with MgF2 and MgF2-CaP to improve their corrosion resistance and biocompatibility, thereby bringing the AM scaffolds closer to meeting the clinical requirements for bone substitutes. The mechanical properties, in vitro biodegradation behavior, electrochemical response, and biocompatibility of the 3D printed Mg scaffolds with a macroporosity of 55% and a strut density of 92% were evaluated. Furthermore, comparisons were made between the bare scaffolds and the scaffolds with coatings. The coating not only covered the struts but also infiltrated the struts through micropores, resulting in decreases in both macro- and micro-porosity. The bare Mg scaffolds exhibited poor corrosion resistance due to the highly interconnected porous structure, while the MgF2-CaP coatings remarkably improved the corrosion resistance, lowering the biodegradation rate of the scaffolds down to 0.2 mm y-1. The compressive mechanical properties of the bare and coated Mg scaffolds before and during in vitro immersion tests for up to 7 days were both in the range of the values reported for the trabecular bone. Moreover, direct culture of MC3T3-E1 preosteoblasts on the coated Mg scaffolds confirmed their good biocompatibility. Overall, this study clearly demonstrated the great potential of MgF2-CaP coated porous Mg prepared by extrusion-based 3D printing for further development as a bone substitute. This journal is

Additive manufacturing (AM) offers great design freedom that enables objects with desired unique and complex geometry and topology to be readily and cost-effectively fabricated. The overall benefits of AM are well known, such as increased material and resource efficiency, enhanced design and production flexibility, the ability to create porous structures and on-demand manufacturing. When AM is applied to medical devices, these benefits are naturally assumed. However, hard clinical evidence collected from clinical trials and studies seems to be lacking and, as a result, systematic assessment is yet difficult. In the present work, we have reviewed 23 studies on the clinical use of AM patient-specific surgical guides (PSGs) for the mandible surgeries (n = 17) and temporomandibular joint (TMJ) patient-specific implants (PSIs) (n = 6) with respect to expected clinical outcomes. It is concluded that the data published on these AM medical devices are often lacking in comprehensive evaluation of clinical outcomes. A complete set of clinical data, including those on time management, costs, clinical outcomes, range of motion, accuracy of the placement with respect to the pre-operative planning, and extra complications, as well as manufacturing data are needed to demonstrate the real benefits gained from applying AM to these medical devices and to satisfy regulatory requirements.

Recent progress in nano-/micro-fabrication techniques has paved the way for the emergence of synthetic bactericidal patterned surfaces that are capable of killing the bacteria via mechanical mechanisms. Different design parameters are known to affect the bactericidal activity of nanopatterns. Evaluating the effects of each parameter, isolated from the others, requires systematic studies. Here, we systematically assessed the effects of the interspacing and disordered arrangement of nanopillars on the bactericidal properties of nanopatterned surfaces. Electron beam induced deposition (EBID) was used to additively manufacture nanopatterns with precisely controlled dimensions (i.e., a height of 190 nm, a diameter of 80 nm, and interspaces of 100, 170, 300, and 500 nm) as well as disordered versions of them. The killing efficiency of the nanopatterns against Gram-positive Staphylococcus aureus bacteria increased by decreasing the interspace, achieving the highest efficiency of 62 ± 23% on the nanopatterns with 100 nm interspacing. By comparison, the disordered nanopatterns did not influence the killing efficiency significantly, as compared to their ordered correspondents. Direct penetration of nanopatterns into the bacterial cell wall was identified as the killing mechanism according to cross-sectional views, which is consistent with previous studies. The findings indicate that future studies aimed at optimizing the design of nanopatterns should focus on the interspacing as an important parameter affecting the bactericidal properties. In combination with controlled disorder, nanopatterns with contrary effects on bacterial and mammalian cells may be developed.

Biodegradable porous magnesium (Mg) scaffolds are promising for application in the regeneration of critical-sized bone defects. Although additive manufacturing (AM) carries the promise of offering unique opportunities to fabricate porous Mg scaffolds, current attempts to apply the AM approach to fabricating Mg scaffolds have encountered some crucial issues, such as those related to safety in operation and to the difficulties in composition control. In this paper, we present a room-temperature extrusion-based AM method for the fabrication of topologically ordered porous Mg scaffolds. It is composed of three steps, namely (i) preparing a Mg powder loaded ink with desired rheological properties, (ii) solvent-cast 3D printing (SC-3DP) of the ink to form scaffolds with 0 °/ 90 °/ 0 ° layers, and (iii) debinding and sintering to remove the binder in the ink and then get Mg powder particles bonded by applying a liquid-phase sintering strategy. A rheological analysis of the prepared inks with 54, 58 and 62 vol% Mg powder loading was performed to reveal their viscoelastic properties. Thermal-gravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), carbon/sulfur analysis and scanning electron microscopy (SEM) indicated the possibilities of debinding and sintering at one single step for fabricating pure Mg scaffolds with high fidelity and densification. The resulting scaffolds with high porosity contained hierarchical and interconnected pores. This study, for the first time, demonstrated that the SC-3DP technique presents unprecedented possibilities to fabricate Mg-based porous scaffolds that have the potential to be used as a bone-substituting material. Statement of Significance: Biodegradable porous magnesium scaffolds are promising for application in the regeneration of critical-sized bone defects. Although additive manufacturing (AM) carries the promise of offering unique opportunities to fabricate porous magnesium scaffolds, current attempts to apply the AM approach to fabricating magnesium scaffolds still have some crucial limitations. This study demonstrated that the solvent-cast 3D printing technique presents unprecedented possibilities to fabricate Mg-based porous scaffolds. The judicious chosen of formulated binder system allowed for the negligible binder residue after debinding and the short-time liquid-phase sintering strategy led to a great success in sintering pure magnesium scaffolds. The resulting scaffolds with hierarchical and interconnected pores have great potential to be used as a bone-substituting material.

Magnesium and its alloys have the intrinsic capability of degrading over time in vivo without leaving toxic degradation products. They are therefore suitable for use as biodegradable scaffolds that are replaced by the regenerated tissues. One of the main concerns for such applications, particularly in load-bearing areas, is the sufficient mechanical integrity of the scaffold before sufficient volumes of de novo tissue is generated. In the majority of the previous studies on the effects of biodegradation on the mechanical properties of porous biomaterials, the change in the elastic modulus has been studied. In this study, variations in the static and fatigue mechanical behavior of porous structures made of two different Mg alloys (AZ63 and M2) over different dissolution times ( 6, 12, and 24 h) have been investigated. The results showed an increase in the mechanical properties obtained from stress-strain curve (elastic modulus, yield stress, plateau stress, and energy absorption) after 6-12 h and a sharp decrease after 24 h. The initial increase in the mechanical properties may be attributed to the accumulation of corrosion products in the pores of the porous structure before degradation has considerably proceeded. The effects of mineral deposition was more pronounced for the elastic modulus as compared to other mechanical properties. That may be due to insufficient integration of the deposited particles in the structure of the magnesium alloys. While the bonding of the parts being combined in a composite-like material is of great importance in determining its yield stress, the effects of bonding strength of both parts is much lower in determining the elastic modulus. The results of the current study also showed that the dissolution rates of the studied Mg alloys were too high for direct use in human body. © 2018 Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1798-1811, 2018.

Bone shapes, particularly those defining the subtalar joint (STJ), have not received much attention yet as a risk factor for developing chronic ankle instability (CAI) after sustaining a lateral ankle sprain (LAS). This study aimed to compare three‐dimensional (3D) shape variations in the STJ bones within individuals with CAI and healthy controls. 3D statistical shape models (SSMs) of the STJ bones were built to describe the bone shape variations observed within a population consisting of 26 individuals with unilateral CAI and 26 healthy controls. Using the SSMs and analysis of covariance test, age‐ and gender‐adjusted shape variations in the bones were compared within individuals with CAI and healthy controls. The mean age of the CAI patients (14 males and 12 females) and healthy controls (12 males and 14 females) was 29 (standard deviation [SD] = 11) and 36 years (SD = 11), respectively. Tali and calcanei did not significantly vary between ipsilateral CAI and their contralateral ankle. Two shape modes, one for the talus (p = 0.015, variations in the curvature of the talar lateral process and the inclination angle of the talar neck relative to the body) and one for the calcaneus (p = 0.003, variations in the medial and lateral tuberosities, and the contour of the anterior articular surface), described significant shape differences between the CAI patients and healthy controls. The CAI patients generally had flatter talar joint surfaces and a flattened calcaneal ground‐contact surface. These findings suggest that specific bone shapes may increase the risk of developing CAI after sustaining a LAS. © 2019 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 37:1892–1902, 2019

Development of synthetic bactericidal surfaces is a drug-free route to the prevention of implant-associated infections. Surface nanotopographies with specific dimensions have been shown to kill various types of bacterial strains through a mechanical mechanism, while regulating stem cell differentiation and tissue regeneration. The effective ranges of dimensions required to simultaneously achieve both aims are in the

The bones forming the talocrural joint (TCJ) and subtalar joint (STJ) are often assumed to be bilaterally symmetric. Therefore, the contralateral limb (i.e. the fibula, tibia, calcaneus and talus) is used as a template or an intra-subject control in clinical and research practice. However, the validity of the symmetry assumption is controversial, because insufficient information is available on the shape variations and bilateral (a)symmetry of the fibula, tibia, calcaneus and talus. Using three-dimensional spatially dense sampled representations of bone shapes extracted from bilateral computed tomography scans of 66 individuals (55 male, mean age: 61 ± 10 years; 11 female, mean age: 53 ± 15 years), we analyzed whether: (i) similar shape patterns exist in the left and right bones of the same type; (ii) gender has an effect on bone shape variations; (iii) intra-subject shape variation is smaller than that of inter-subject for a given shape variance direction. For the first set of analyses, all left and right instances of the same type of bone were considered as two separate groups, and statistically compared with each other on multiple aspects including group location (central tendency), variance-covariance scale (dispersion) and orientation (covariance structure) using distance-based permutational tests. For the second and third sets of analyses, all left and right bones of the same type were pooled into one group, and shape variations in the TCJ and STJ bones were extracted using principal component analysis. The effects of gender on age-adjusted bone shape differences were assessed using an analysis of covariance. Moreover, intra-class correlation was employed to evaluate intra- and inter-subject bone shape variations. For each bone type, both sides had similar shape patterns (Ppermutational-values > 0.05). After Bonferroni adjustment, gender led to shape differences, which were mainly in the lateral and medial condyles of the tibia (P = 0.003), the length and height of the calcaneus (P < 0.001), the posterior and anterior talar articular surfaces of the calcaneus (P = 0.001), and in the posterior aspect of the talus (P = 0.001). Intra-subject shape variations in the tibial tuberosity together with the diameter of the tibia, and the curvature of the fibula shaft and the diameter of the fibula were as high as those of inter-subject. This result suggests that the shape symmetry assumption could be violated for some specific shape variations in the fibula and tibia.

Origami-inspired folding methods present novel pathways to fabricate three-dimensional (3D) structures from 2D sheets. A key advantage of this approach is that planar printing and patterning processes could be used prior to folding, affording enhanced surface functionality to the folded structures. This is particularly useful for 3D lattices, possessing very large internal surface areas. While folding polyhedral strut-based lattices has already been demonstrated, more complex, curved sheet-based lattices have not yet been folded due to inherent developability constraints of conventional origami. Here, a novel folding strategy is presented to fold flat sheets into topologically complex cellular materials based on triply periodic minimal surfaces (TPMS), which are attractive geometries for many applications. The approach differs from traditional origami by employing material stretching to accommodate non-developability. Our method leverages the inherent hyperbolic symmetries of TPMS to assemble complex 3D structures from a net of self-foldable patches. We also demonstrate that attaching 3D-printed foldable frames to pre-strained elastomer sheets enables self-folding and self-guided minimal surface shape adaption upon release of the pre-strain. This approach effectively bridges the Euclidean nature of origami with the hyperbolic nature of TPMS, offering novel avenues in the 2D-to-3D fabrication paradigm and the design of architected materials with enhanced functionality.

Nanopillar arrays that are bactericidal but not cytotoxic against the host cells could be used in implantable medical devices to prevent implant-associated infections. It is, however, unclear what heights, widths, interspacing, and shape should be used for the nanopillars to achieve the desired antibacterial effects while not hampering the integration of the device in the body. Here, we present an in-silico approach based on finite element modeling of the interactions between Staphylococcus aureus and nanopatterns on the one hand and osteoblasts and nanopatterns on the other hand to find the best design parameters. We found that while the height of the nanopillars seems to have little impact on the bactericidal behavior, shorter widths and larger interspacings substantially increase the bactericidal effects. The same combination of parameters could, however, also cause cytotoxicity. Our results suggest that a specific combination of height (120 nm), width (50 nm), and interspacing (300 nm) offers the bactericidal effects without cytotoxicity.

A rigid surface&ndash, volume registration scheme is presented in this study to register computed tomography (CT) and free-hand tracked ultrasound (US) images of the talocrural joint. Prior to registration, bone surfaces expected to be visible in US are extracted from the CT volume and bone contours in 2D US data are enhanced based on monogenic signal representation of 2D US images. A 3D monogenic signal data is reconstructed from the 2D data using the position of the US probe recorded with an optical tracking system. When registering the surface extracted from the CT scan to the monogenic signal feature volume, six transformation parameters are estimated so as to optimize the sum of monogenic signal features over the transformed surface. The robustness of the registration algorithm was tested on a dataset collected from 12 cadaveric ankles. The proposed method was used in a clinical case study to investigate the potential of US imaging for pre-operative planning of arthroscopic access to talar (osteo)chondral defects (OCDs). The results suggest that registrations with a registration error of 2 mm and less is achievable, and US has the potential to be used in assessment of an OCD&rsquo, arthroscopic accessibility, given the fact that 51% of the talar surface could be visualized.

An ideal bone substituting material should be bone-mimicking in terms of mechanical properties, present a precisely controlled and fully interconnected porous structure, and degrade in the human body to allow for full regeneration of large bony defects. However, simultaneously satisfying all these three requirements has so far been highly challenging. Here we present topologically ordered porous magnesium (WE43) scaffolds based on the diamond unit cell that were fabricated by selective laser melting (SLM) and satisfy all the requirements. We studied the in vitro biodegradation behavior (up to 4 weeks), mechanical properties and biocompatibility of the developed scaffolds. The mechanical properties of the AM porous WE43 (E = 700–800 MPa) scaffolds were found to fall into the range of the values reported for trabecular bone even after 4 weeks of biodegradation. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), electrochemical tests and µCT revealed a unique biodegradation mechanism that started with uniform corrosion, followed by localized corrosion, particularly in the center of the scaffolds. Biocompatibility tests performed up to 72 h showed level 0 cytotoxicity (according to ISO 10993-5 and -12), except for one time point (i.e., 24 h). Intimate contact between cells (MG-63) and the scaffolds was also observed in SEM images. The study shows for the first time that AM of porous Mg may provide distinct possibilities to adjust biodegradation profile through topological design and open up unprecedented opportunities to develop multifunctional bone substituting materials that mimic bone properties and enable full regeneration of critical-size load-bearing bony defects. Statement of Significance The ideal biomaterials for bone tissue regeneration should be bone-mimicking in terms of mechanical properties, present a fully interconnected porous structure, and exhibit a specific biodegradation behavior to enable full regeneration of bony defects. Recent advances in additive manufacturing have resulted in biomaterials that satisfy the first two requirements but simultaneously satisfying the third requirement has proven challenging so far. Here we present additively manufactured porous magnesium structures that have the potential to satisfy all above-mentioned requirements. Even after 4 weeks of biodegradation, the mechanical properties of the porous structures were found to be within those reported for native bone. Moreover, our comprehensive electrochemical, mechanical, topological, and biological study revealed a unique biodegradation behavior and the limited cytotoxicity of the developed biomaterials.

Magnesium and its alloys have the intrinsic capability of degrading over time in vivo without leaving toxic degradation products. They are therefore suitable for use as biodegradable scaffolds that are replaced by the regenerated tissues. One of the main concerns for such applications, particularly in load-bearing areas, is the sufficient mechanical integrity of the scaffold before sufficient volumes of de novo tissue is generated. In the majority of the previous studies on the effects of biodegradation on the mechanical properties of porous biomaterials, the change in the elastic modulus has been studied. In this study, variations in the static and fatigue mechanical behavior of porous structures made of two different Mg alloys (AZ63 and M2) over different dissolution times ( 6, 12, and 24 h) have been investigated. The results showed an increase in the mechanical properties obtained from stress-strain curve (elastic modulus, yield stress, plateau stress, and energy absorption) after 6-12 h and a sharp decrease after 24 h. The initial increase in the mechanical properties may be attributed to the accumulation of corrosion products in the pores of the porous structure before degradation has considerably proceeded. The effects of mineral deposition was more pronounced for the elastic modulus as compared to other mechanical properties. That may be due to insufficient integration of the deposited particles in the structure of the magnesium alloys. While the bonding of the parts being combined in a composite-like material is of great importance in determining its yield stress, the effects of bonding strength of both parts is much lower in determining the elastic modulus. The results of the current study also showed that the dissolution rates of the studied Mg alloys were too high for direct use in human body. © 2018 Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1798-1811, 2018.

Recent discoveries have shown that nanopatterns with feature sizes ≤100 nm could direct stem cell fate or kill bacteria. These effects could be used to develop orthopedic implants with improved osseointegration and decreased chance of implant-associated infections. The quest for osteogenic and bactericidal nanopatterns is ongoing but no controlled nanopatterns with dual osteogenic and bactericidal functionalities have been found yet. In this study, electron beam induced deposition (EBID) was used for accurate and reproducible decoration of silicon surfaces with four different types of nanopatterns. The features used in the first two nanopatterns (OST1 and OST2) were derived from osteogenic nanopatterns known to induce osteogenic differentiation of stem cells in the absence of osteogenic supplements. Two modifications of these nanopatterns were also included (OST2-SQ, OST2-H90) to study the effects of controlled disorder and lower nanopillar heights. An E. coli K-12 strain was used for probing the response of bacteria to the nanopatterns. Three nanopatterns (OST2, OST2-SQ, and OST2-H90) exhibited clear bactericidal behavior as evidenced by severely damaged cells and disrupted formation of extracellular polymeric substance. These findings indicate that controlled nanopatterns with features derived from osteogenic ones can have bactericidal activity and that EBID represents an enabling nanotechnology to achieve (multi)functional nanopatterns for bone implants.

Objective: The etiology of osteochondral defects (OCDs), for which the ankle (talocrural) joint is one of the common sites, is not yet fully understood. In this study, we hypothesized that bone shape plays a role in development of OCDs. Therefore, we quantitatively compared the morphology of the talus and the distal tibia between an OCD group and a control group. Methods: The shape variations of the talus and distal tibia were described separately by constructing two statistical shape models (SSMs) based on the segmentation of the bones from ankle computed tomography (CT) scans obtained from control (i.e., 35 CT scans) and OCD (i.e., 37 CT scans) groups. The first five modes of shape variation for the SSM corresponding to each bone were statistically compared between control and OCD groups using an analysis of variance (ANOVA) corrected with the Bonferroni for multiple comparisons. Results: The first five modes of variation in the SSMs respectively represented 49% and 40% of the total variance of talus and tibia. Less than 5% of the variance per mode was described by the higher modes. Mode 5 of the talus (P = 0.004) primarily describing changes in the vertical neck angle and Mode 1 of the tibia (P

Additive manufacturing (AM) techniques enable fabrication of bone-mimicking meta-biomaterials with unprecedented combinations of topological, mechanical, and mass transport properties. The mechanical performance of AM meta-biomaterials is a direct function of their topological design. It is, however, not clear to what extent the material type is important in determining the fatigue behavior of such biomaterials. We therefore aimed to determine the isolated and modulated effects of topological design and material type on the fatigue response of metallic meta-biomaterials fabricated with selective laser melting. Towards that end, we designed and additively manufactured Co-Cr meta-biomaterials with three types of repeating unit cells and three to four porosities per type of repeating unit cell. The AM meta-biomaterials were then mechanically tested to obtain their normalized S-N curves. The obtained S-N curves of Co-Cr meta-biomaterials were compared to those of meta-biomaterials with same topological designs but made from other materials, i.e. Ti-6Al-4V, tantalum, and pure titanium, available from our previous studies. We found the material type to be far more important than the topological design in determining the normalized fatigue strength of our AM metallic meta-biomaterials. This is the opposite of what we have found for the quasi-static mechanical properties of the same meta-biomaterials. The effects of material type, manufacturing imperfections, and topological design were different in the high and low cycle fatigue regions. That is likely because the cyclic response of meta-biomaterials depends not only on the static and fatigue strengths of the bulk material but also on other factors that may include strut roughness, distribution of the micro-pores created inside the struts during the AM process, and plasticity. Statement of significance Meta-biomaterials are a special class of metamaterials with unusual or unprecedented combinations of mechanical, physical (e.g. mass transport), and biological properties. Topologically complex and additively manufactured meta-biomaterials have been shown to improve bone regeneration and osseointegration. The mechanical properties of such biomaterials are directly related to their topological design and material type. However, previous studies of such biomaterials have largely neglected the effects of material type, instead focusing on topological design. We show here that neglecting the effects of material type is unjustified. We studied the isolated and combined effects of topological design and material type on the normalized S-N curves of metallic bone-mimicking biomaterials and found them to be more strongly dependent on the material type than topological design.

Both aging and exercise are associated with alterations in circulating levels of catecholamines. To determine the interactions of age and exercise on tyrosine hydroxylase (TH) activity and TH mRNA, Fischer-344 female rats aged 5 months (young) and 25 months (old) were trained by treadmill running for 10 weeks. The elevation in maximum oxygen consumption in both groups was equivalent following exercise, indicating that training had occurred. In control rats, both TH activity and TH mRNA were greater in the older groups when compared with the younger animals. In young rats, exercise decreased TH activity by 25% and TH mRNA by 27%. In older rats, exercise was not associated with a decrease in TH activity and TH mRNA. Choline acetyltransferase activity (ChAT) was decreased and glutamic acid decarboxylase activity (GAD) was increased by exercise in young rats. The decrease in ChAT activity and increase in GAD activity suggest that transynaptic mechanisms play a role in the exercise-induced alteration of TH gene expression. Neither ChAT nor GAD was altered by exercise in older groups. Our data suggest that the previously reported diminution in catecholamines associated with exercise may be due to a decrease in TH mRNA and a resulting decrease in TH activity. There was no effect of exercise in the old rats, supporting previous observations that the plasticity of the sympathoadrenal system diminishes with age.

Familial Mediterranean fever (FMF) is an autosomal recessive disorder of childhood characterized by attacks of fever and serositis. Renal amyloidosis is the most important complication of the disease that determines the prognosis.Forty-eight Turkish FMF patients with amyloidosis who have been followed at the two hospitals in Ankara were included in this study.All patients with amyloidosis had been symptomatic for FMF at the time of the diagnosis (Phenotype I), none had received regular colchicine therapy and all presented with proteinuria. Ten of them had asymptomatic proteinuria; 38 had nephrotic syndrome and 8 of them had renal insufficiency (CRI) as well, at the time of the diagnosis. Regular colchicine therapy was commenced to all of the patients. At the end of observation period of 4.5 +/- 2.23 years (range 2-12 yrs) on treatment, nephrotic syndrome resolved in 13 patients and proteinuria was lost in 5 of them. None but 2 of the patients who were diagnosed at proteinuric stage progressed to end stage renal failure (ESRF). Seven MEFV mutations (M694V, M680I, V726A, M694I, K695R, R761H, E148Q) were systematically investigated in 32 patients. Six of the seven studied mutations were found in these patients and clinical diagnosis was confirmed by mutation analysis in 24 patients. Eight patients were found to have mutations on one of the alleles.Amyloidosis is the most serious complication of FMF. Colchicine treatment ameliorates the progression of renal disease in the patients who presented with proteinuria and even with nephrotic syndrome. No correlation between the outcome of the patients with nephrotic syndrome and the degree of proteinuria and/or serum albumin levels at the initiation of treatment were noted. Progression to ESRF seems inevitable despite colchicine therapy after the development of CRI in patients with FMF associated amyloidosis.

Familial Mediterranean fever (FMF) is an autosomal recessive disease. It is characterized by recurrent febrile episodes in association with peritonitis, pleuritis, and arthritis. Progressive systemic amyloidosis is the most important complication of FMF that inevitably leads to chronic renal failure. Recently, the gene for FMF, MEFV, has been cloned and four missense mutations have been described: M694V, M680I, V726A, and M694I. Initial studies have suggested that the presence of the M694V mutation carries a significant risk for the development of amyloidosis. In this study, we present seven families, in which at least two individuals have been diagnosed with FMF and at least one with amyloidosis. Among 18 individuals, in whom molecular testing was performed for the four aforementioned mutations, ten had amyloidosis. None of these ten individuals was found to be homozygous for the M694V mutation. In three families, there were two sibs with amyloidosis. None of the sib-pairs with amyloidosis was found to have the same genotype. There were two or more sibs with the same genotype in four families. Only one sib from each family developed amyloidosis in these families. These results provide evidence that FMF patients without the M694V mutation are also at risk for the development of amyloidosis. Particular mutations themselves do not appear to be sufficient to explain the occurrence of amyloidosis in all cases with FMF.

In this study, the clinical, laboratory and histopathological features of 50 children with membranoproliferative glomerulonephritis are reviewed. Age distribution varied from 5 to 15 years. The clinical presentation in the patients was nephrotic syndrome (24%), acute nephritic syndrome (20%) and nephritic/nephrotic syndrome (56%). Hypertension, macroscopic hematuria and hypocomplementemia were present in 40 percent, 58 percent and 34 percent of the patients, respectively. Light microscopic findings were as follows: glomerular lobulation (36%), mesangial sclerosis (20%), tubulointerstitial findings (36%), and crescents (26%). C3 (93%) was the most common immunofluorescence and IgM (86%), the most frequently encountered immunoglobulin. Response to treatment could not be anticipated by the initial clinical and laboratory features. Patients who did not have tubulointerstitial changes tended to have a greater response to therapy.

The effect on growth of long-term treatment with prednisolone was studied in 12 patients with steroid-sensitive nephrotic syndrome. Our patient's heights were found between the 10th and 25th percentile both at the first and last height measurement. There was no statistical difference between the first and last height standard deviation score (Ht SDS) (p greater than 0.05). When compared with chronological age, growth velocity (GV), GV SDS and bone age were found low but within the normal range for this age group. There was not any correlation between the last Ht SDS and relapse number, total doses and duration of daily and alternate-day steroid therapy (p greater than 0.05). Growth hormone (GH) responses to pharmacological stimuli were obtained as severe deficiency in 10 patients, partial deficiency in 1 patient and normal level in 1. There was statistical difference between the pulse number of the overnight GH profile of the patients and control group (p less than 0.05). But no statistical difference was found between GH pulse amplitude and GH concentration in patients and control group (p greater than 0.05).

A nine-year-old girl with renovascular hypertension is presented. The diagnosis of fibromuscular dysplasia was established by selective renal angiography, and percutaneous transluminal renal angioplasty was performed. After successful dilation, the blood pressure returned to normal. The patient has been followed for a year and there is no evidence of hypertension.

In this study 2,591 apparently healthy children aged 1 day-16 years were examined to determine the existence of asymptomatic urinary tract infection. A prevalence of 4% in newborns, 5.2% in infants, 5.8% in preschool children, 4.5% in elementary school children, and of 4.8% in high-school children was found.

Although detailed data on the dynamics of tension in vascular smooth muscle are most pertinent for an exact description of circulatory flow dynamics there are only few quantitative descriptions of the role of the smooth muscle effector in circulatory dynamics (Basar et al., 1968; Basar, 1976; Basar and Eroǧlu, 1976).