Additive Manufactured Scaffolds for Bone Tissue Engineering: Physical Characterization of Thermoplastic Composites with Functional Fillers

Thermoplastic polymer–filler composites are excellent materials for bone tissue engineering (TE) scaffolds, combining the functionality of fillers with suitable load-bearing ability, biodegradability, and additive manufacturing (AM) compatibility of the polymer. Two key determinants of their utility are their rheological behavior in the molten state, determining AM processability and their mechanical load-bearing properties. We report here the characterization of both these physical properties for four bone TE relevant composite formulations with poly(ethylene oxide terephthalate)/poly(butylene terephthalate (PEOT/PBT) as a base polymer, which is often used to fabricate TE scaffolds. The fillers used were reduced graphene oxide (rGO), hydroxyapatite (HA), gentamicin intercalated in zirconium phosphate (ZrP-GTM) and ciprofloxacin intercalated in MgAl layered double hydroxide (MgAl-CFX). The rheological assessment showed that generally the viscous behavior dominated the elastic behavior (G″ > G′) for the studied composites, at empirically determined extrusion temperatures. Coupled rheological–thermal characterization of ZrP-GTM and HA composites showed that the fillers increased the solidification temperatures of the polymer melts during cooling. Both these findings have implications for the required extrusion temperatures and bonding between layers. Mechanical tests showed that the fillers generally not only made the polymer stiffer but more brittle in proportion to the filler fractions. Furthermore, the elastic moduli of scaffolds did not directly correlate with the corresponding bulk material properties, implying composite-specific AM processing effects on the mechanical properties. Finally, we show computational models to predict multimaterial scaffold elastic moduli using measured single material scaffold and bulk moduli. The reported characterizations are essential for assessing the AM processability and ultimately the suitability of the manufactured scaffolds for the envisioned bone regeneration application.The work was supported by a Horizon 2020 Research and Innovation Programme grant from the European Union, called the FAST project (grant no. 685825, project website: http:// project-fast.eu). The authors acknowledge the support of the FAST project consortium for the various aspects of this wor

Development of model tumor in vitro using bacterial nanocellulose

The aim of this work was to study the behavior of FaDu cells in contact with 2D substrates (pellicles) of BNC and to develop a 3D method to create a model of hypopharyngeal squamous carcinoma by means of BNC/alginate porous sponges. In this perspective, cells were seeded on uncoated scaffolds either as cell suspension or embedded in a 1:1 mixture of medium and Matrigel, and on scaffold pre-coated with collagen I. Nanocellulose was used also in the form of hollow tubes, filled with cell suspension and Matrigel and cultured in a stirrer flask. To create a model better resembling reality, the FaDu cells were also co-cultured with Human Umbilical Vein Endothelial Cells (HUVECs), with the expectation to observe angigogenic effects on these. The sponges seeded with Matrigel showed a higher number of cells grown inside them compared to the other seeding techniques and the gel gave good results also with the cellulose tubes. On the other hand, the co-culture gave results not as great as expected but the experiment can be improved by culturing the two cell type together for a longer time. This study shows that BNC can be used to grow in vitro 3D tumor to be used in screening of cancer therapie

Metodi della bioingegneria e studio del diabete: misura non invasiva del glucosio e tecniche di simulazione per modelli dell'omeostasi del glucosio

Vengono illustrate alcune applicazioni della bioingegneria al metabolismo del glucosio, specificatamente: esperienze di laboratorio di misure di impedenza di soluzioni fisiologiche contenenti glucosio per lo sviluppo di un metodo di misura non invasivo e simulazioni di modelli fisiologici per lo studio del metabolism

Additive Manufacturing Using Melt Extruded Thermoplastics for Tissue Engineering

Melt extrusion of thermoplastic materials is an important technique for fabricating tissue engineering scaffolds by additive manufacturing methods. Scaffold manufacturing is commonly achieved by one of the following extrusion-based techniques: fused deposition modelling (FDM), 3D-fiber deposition (3DF), and bioextrusion. FDM needs the input material to be strictly in the form of a filament, whereas 3DF and bioextrusion can be used to process input material in several forms, such as pellets or powder. This chapter outlines a common workflow for all these methods, going from the material to a scaffold, while highlighting the special requirements of particular methods. A few ways of characterizing the scaffolds are also briefly described

Muscle MRI and functional outcome measures in Becker muscular dystrophy

Abstract Becker muscular dystrophy (BMD) is a neuromuscular disorder allelic to Duchenne muscular dystrophy (DMD), caused by in-frame mutations in the dystrophin gene, and characterized by a clinical progression that is both milder and more heterogeneous than DMD. Muscle magnetic resonance imaging (MRI) has been proposed as biomarker of disease progression in dystrophinopathies. Correlation with clinically meaningful outcome measures such as North Star Ambulatory Assessment (NSAA) and 6 minute walk test (6MWT) is paramount for biomarker qualification. In this study, 51 molecularly confirmed BMD patients (aged 7–69 years) underwent muscle MRI and were evaluated with functional measures (NSAA and 6MWT) at the time of the MRI, and subsequently after one year. We confirmed a pattern of fatty substitution involving mainly the hip extensors and most thigh muscles. Severity of muscle fatty substitution was significantly correlated with specific DMD mutations: in particular, patients with an isolated deletion of exon 48, or deletions bordering exon 51, showed milder involvement. Fat infiltration scores correlated with baseline functional measures, and predicted changes after 1 year. We conclude that in BMD, skeletal muscle MRI not only strongly correlates with motor function, but also helps in predicting functional deterioration within a 12-month time frame

Shaping and properties of thermoplastic scaffolds in tissue regeneration: The effect of thermal history on polymer crystallization, surface characteristics and cell fate

Abstract: Thermoplastic semi-crystalline polymers are excellent candidates for tissue engineering scaffolds thanks to facile processing and tunable properties, employed in melt-based additive manufacturing. Control of crystallization and ultimate crystallinity during processing affect properties like surface stiffness and roughness. These in turn influence cell attachment, proliferation and differentiation. Surface stiffness and roughness are intertwined via crystallinity, but never studied independently. The targeted stiffness range is besides difficult to realize for a single thermoplastic. Via correlation of thermal history, crystallization and ultimate crystallinity of vitamin E plasticized poly(lactide), surface stiffness and roughness are decoupled, disclosing a range of surface mechanics of biological interest. In osteogenic environment, human mesenchymal stromal cells were more responsive to surface roughness than to surface stiffness. Cells were particularly influenced by overall crystal size distribution, not by average roughness. Absence of mold-imposed boundary constrains makes additive manufacturing ideal to spatially control crystallization and henceforward surface roughness of semi-crystalline thermoplastics. Graphic abstract: [Figure not available: see fulltext.

Power-Efficient Computing: Experiences from the COSA Project

Energy consumption is today one of the most relevant issues in operating HPC systems for scientific applications. The use of unconventional computing systems is therefore of great interest for several scientific communities looking for a better tradeoff between time-to-solution and energy-to-solution. In this context, the performance assessment of processors with a high ratio of performance per watt is necessary to understand how to realize energy-efficient computing systems for scientific applications, using this class of processors. Computing On SOC Architecture (COSA) is a three-year project (2015-2017) funded by the Scientific Commission V of the Italian Institute for Nuclear Physics (INFN), which aims to investigate the performance and the total cost of ownership offered by computing systems based on commodity low-power Systems on Chip (SoCs) and high energy-efficient systems based on GP-GPUs. In this work, we present the results of the project analyzing the performance of several scientific applications on several GPU-A nd SoC-based systems. We also describe the methodology we have used to measure energy performance and the tools we have implemented to monitor the power drained by applications while running

Computing on SoC Architecures (COSA)

COSA is a project funded by the Scientific Commission V of the Italian Institute for Nuclear Physics (INFN). The main focus of the project is to investigate the performances, the total cost of ownership and the possibilities offered by computing systems based on commodity low power Systems on Chip (SoC). Computing performances will be measured running real life applications taken from the High Energy Physics (HEP) community belonging to the Institute. The project is building and maintaining three clusters. One is located in Bologna (CNAF department) and will be composed of development boards powered by the state of the art low power SoCs running Linux. Another one, located in Rome (ROME1 department) exploits the last generation FPGAs to prototype low latency network connections between low power CPUs. The third cluster, located in the Padova department, is based on traditional, non-low-power, CPUs, accelerators and network connections. This cluster is used as a reference for the performance of the scientific applications run on the other two cluster

The INFN COSA Project: Low-Power Computing and Storage

In the context of energy-efficient 'green' computing, we present the experience of the COSA project (Computing On SoC Architecture, www.cosa-project.it), started in 2014 and funded by the Italian Institute for Nuclear Physics (INFN). COSA explores the feasibility of executing scientific workloads, which are traditionally designed for power-hungry HPC clusters, on the CPUs and GPUs of low-power Systems on Chip derived from the embedded and mobile market, looking for a better trade-off between time-to-solution and energy-to-solution. In a laboratory based at CNAF (INFN, Bologna), COSA has assembled an unconventional cluster of SoCs from ARM and Intel vendors, interconnected through 1Gbit/s and 10Gbit/s Ethernet switches, where several scientific workloads were ported and successfully executed. Depending on the nature of the applications, and in particular for those which manage to exploit the GPU power, SoCs proved to be able to deliver satisfactory computing performances, in some cases comparable to those provided by a node of an HPC standard cluster, for the benefit of much lower power consumptions and, noticeably, reduced infrastructural costs and sizes. We report the results obtained for significant workloads from the Particle physics, X-Ray computed tomography, Statistical biology and Theoretical physics fields. Then, we investigate the possibility of using SoCs, and in particular Intel Xeon processors from the D family, as low-power, low-cost storage bricks of a BeeGFS file system, in the perspective of energy-efficient storage solutions which could be deployed in or out of data centers