Aerosol Jet® Printing of Poly(3,4-Ethylenedioxythiophene): Poly(Styrenesulfonate) onto Micropatterned Substrates for Neural Cells In Vitro Stimulation.

In neural tissue engineering (NTE), topographical, electrical, mechanical and/or biochemical stimulations are established methods to regulate neural cell activities in in vitro cultures. Aerosol Jet® Printing is here proposed as enabling technology to develop NTE integrated devices for electrically combined stimulations. The printability of a poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT: PSS) commercial ink onto a reference substrate was firstly investigated and the effect of the process parameters on the quality of printed lines was analyzed. The study was then extended for printing thick electrodes and interconnects; the print strategy was finally transferred to a silicon-based wafer with patterned microchannels of proven cellular adhesion and topographical guidance. The results showed values of electrical resistance equal to ~16 Ω for printed electrodes which are ~33 µm thick and ~2 mm wide. The electrical impedance of the final circuit in saline solution was detected in the range of 1 - 2 kΩ at 1 kHz, which is in line with the expectations for bioelectronic neural interfaces. However, cells viability assays on the commercial PEDOT: PSS ink demonstrated a dose dependent cytotoxic behavior. The potential cause is associated with the presence of a cytotoxic co-solvent in the ink's formulation, which is released in the medium culture, even after a post-sintering process on the printed electrodes. This work is a first step to develop innovative in vitro NTE devices via a printed electronic approach. It also sheds new insights the transfer of AJ® print strategies across different substrates, and biocompatibility of commercial PEDOT: PSS inks.

Cancer Cell Direct Bioprinting: A Focused Review.

Three-dimensional printing technologies allow for the fabrication of complex parts with accurate geometry and less production time. When applied to biomedical applications, two different approaches, known as direct or indirect bioprinting, may be performed. The classical way is to print a support structure, the scaffold, and then culture the cells. Due to the low efficiency of this method, direct bioprinting has been proposed, with or without the use of scaffolds. Scaffolds are the most common technology to culture cells, but bioassembly of cells may be an interesting methodology to mimic the native microenvironment, the extracellular matrix, where the cells interact between themselves. The purpose of this review is to give an updated report about the materials, the bioprinting technologies, and the cells used in cancer research for breast, brain, lung, liver, reproductive, gastric, skin, and bladder associated cancers, to help the development of possible treatments to lower the mortality rates, increasing the effectiveness of guided therapies. This work introduces direct bioprinting to be considered as a key factor above the main tissue engineering technologies.

Selective Laser Melting and Electron Beam Melting of Ti6Al4V for Orthopedic Applications: A Comparative Study on the Applied Building Direction.

The 3D printing process offers several advantages to the medical industry by producing complex and bespoke devices that accurately reproduce customized patient geometries. Despite the recent developments that strongly enhanced the dominance of additive manufacturing (AM) techniques over conventional methods, processes need to be continually optimized and controlled to obtain implants that can fulfill all the requirements of the surgical procedure and the anatomical district of interest. The best outcomes of an implant derive from optimal compromise and balance between a good interaction with the surrounding tissue through cell attachment and reduced inflammatory response mainly caused by a weak interface with the native tissue or bacteria colonization of the implant surface. For these reasons, the chemical, morphological, and mechanical properties of a device need to be designed in order to assure the best performances considering the in vivo environment components. In particular, complex 3D geometries can be produced with high dimensional accuracy but inadequate surface properties due to the layer manufacturing process that always entails the use of post-processing techniques to improve the surface quality, increasing the lead times of the whole process despite the reduction of the supply chain. The goal of this work was to provide a comparison between Ti6Al4V samples fabricated by selective laser melting (SLM) and electron beam melting (EBM) with different building directions in relation to the building plate. The results highlighted the influence of the process technique on osteoblast attachment and mineralization compared with the building orientation that showed a limited effect in promoting a proper osseointegration over a long-term period.

Numerical Optimization of the Blank Dimensions in Tube Hydroforming Using Line-Search and Bisection Methods.

The change from a consolidated manufacturing practice to a new solution is often a complex problem because of the operative limits of technologies and the strict constraints of industrial parts. Moreover, the new process must reflect or enhance the characteristics of the product and, overall, it must be more competitive in performances and costs. Accordingly, the development of a new process is a multilevel and multivariate problem that requires a systematic and hierarchical approach. The present paper focuses on the development of a Tube Hydroforming process capable to replace the current practice for production of T-Joint parts made of AISI 316L for the water pipes market. In particular, the problem must withstand many process and product constraints. Therefore, it was split in three steps focused on specific aspects of the process: identification of process parameters and configuration, numerical optimization of the blank tube dimensions (length and thickness), experimental tests and final improvements. In particular, two numerical methods were implemented in the optimization step: the line-search method to approach to the optimum point and Bisection method to refine the search. These approaches allowed us to identify the optimum process configuration and, in particular, the optimal dimensions of the blank tube that allows one to achieve the product requirements with the minimum cost of material.

Nebulized jet-based printing of bio-electrical scaffolds for neural tissue engineering: a feasibility study.

In this paper we investigate the application of a direct writing technique for printing conductive patterns onto a biocompatible electrospun-pyrolysed carbon-fibre-based substrate. The result is a first study towards the production of bio-electrical scaffolds that could be used to enhance the promotion of efficient connections among neurons for in vitro studies in the field of neural tissue engineering. An electrospinning process is employed for production of the materials derived from the precursor polyacrylonitrile, in which the embedding of carbon nanotubes (CNTs) is also investigated. Subsequently, the methodology of research into suitable parameters for the printed electronics, using a commercial silver nanoparticle (Øavg,particle size âˆ¼ 100 nm) ink, is described. The results show values of 2 Ω cm for the resistivity of the carbon-fibre materials and conductive printed lines of resistance ∼50 Ω on glass and less than ∼140 Ω on carbon-fibre samples. Biocompatibility results demonstrate the possibility of using electrospun-pyrolysed mats, also with embedded CNTs, as potential neural substrates for spatially localized electrical stimulation across a tissue. In addition, the data concerning the potential toxicity of silver suspensions are in accordance with the literature, showing a dose-dependent behaviour. This work is a pioneering feasibility study of the use of the flexible and versatile printed electronic approach, combined with engineered biocompatible substrates, to realize integrated bio-electrical scaffolds for in vitro neural tissue engineering applications.

Cell Bioprinting: The 3D-Bioplotter™ Case.

The classic cell culture involves the use of support in two dimensions, such as a well plate or a Petri dish, that allows the culture of different types of cells. However, this technique does not mimic the natural microenvironment where the cells are exposed to. To solve that, three-dimensional bioprinting techniques were implemented, which involves the use of biopolymers and/or synthetic materials and cells. Because of a lack of information between data sources, the objective of this review paper is, to sum up, all the available information on the topic of bioprinting and to help researchers with the problematics with 3D bioprinters, such as the 3D-Bioplotter™. The 3D-Bioplotter™ has been used in the pre-clinical field since 2000 and could allow the printing of more than one material at the same time, and therefore to increase the complexity of the 3D structure manufactured. It is also very precise with maximum flexibility and a user-friendly and stable software that allows the optimization of the bioprinting process on the technological point of view. Different applications have resulted from the research on this field, mainly focused on regenerative medicine, but the lack of information and/or the possible misunderstandings between papers makes the reproducibility of the tests difficult. Nowadays, the 3D Bioprinting is evolving into another technology called 4D Bioprinting, which promises to be the next step in the bioprinting field and might promote great applications in the future.

Manufacturing of polycaprolactone - Graphene fibers for nerve tissue engineering.

Nanofibrous structures have morphological similarities to extracellular matrix and have been considered as candidate scaffolds in tissue engineering. Scaffolds made from electrospun fibers have potential in cell adhesion, proliferation and cell function. In this study, different percentages of graphene have been dispersed in a polycaprolactone-cyclopentanone solution to produce electrospun fibers. The microstructure and morphology of the fibers and the mechanical behavior of the electrospun systems were evaluated to analyze the influence of graphene content on the performances of the fibers. A significant dimensional difference between the fibers diameters of was obtained due to the graphene percentage. Accordingly, the mechanical properties of the fibrous systems are found to be influenced by the presence of the graphene. Rat stem cells were cultured on the fibrous scaffolds to evaluate the effect of the arrangement of the fibers on the morphology of the cells and differentiation into neurons. In particular, a higher population of dopaminergic neurons has been identified on the fibers with a higher percentage of graphene.

An Experimental Study on Micro-Milling of a Medical Grade Co-Cr-Mo Alloy Produced by Selective Laser Melting.

Cobalt-chromium-molybdenum (Co-Cr-Mo) alloys are very promising materials, in particular, in the biomedical field where their unique properties of biocompatibility and wear resistance can be exploited for surgery applications, prostheses, and many other medical devices. While Additive Manufacturing is a key technology in this field, micro-milling can be used for the creation of micro-scale details on the printed parts, not obtainable with Additive Manufacturing techniques. In particular, there is a lack of scientific research in the field of the fundamental material removal mechanisms involving micro-milling of Co-Cr-Mo alloys. Therefore, this paper presents a micro-milling characterization of Co-Cr-Mo samples produced by Additive Manufacturing with the Selective Laser Melting (SLM) technique. In particular, microchannels with different depths were made in order to evaluate the material behavior, including the chip formation mechanism, in micro-milling. In addition, the resulting surface roughness (Ra and Sa) and hardness were analyzed. Finally, the cutting forces were acquired and analyzed in order to ascertain the minimum uncut chip thickness for the material. The results of the characterization studies can be used as a basis for the identification of a machining window for micro-milling of biomedical grade cobalt-chromium-molybdenum (Co-Cr-Mo) alloys.

Potential of modeling and simulations of bioengineered devices: Endoprostheses, prostheses and orthoses.

Modeling and simulation of prosthetic devices are the new tools investigated for the production of total customized prostheses. Computational simulations are used to evaluate the geometrical and material designs of a device while assessing its mechanical behavior. Data acquisition through magnetic resonance imaging, computed tomography or laser scanning is the first step that gives information about the human anatomical structures; a file format has to be elaborated through computer-aided design software. Computer-aided design tools can be used to develop a device that respects the design requirements as, for instance, the human anatomy. Moreover, through finite element analysis software and the knowledge of loads and conditions the prostheses are supposed to face in vivo, it is possible to simulate, analyze and predict the mechanical behavior of the prosthesis and its effects on the surrounding tissues. Moreover, the simulations are useful to eventually improve the design (as geometry, materials, features) before the actual production of the device. This article presents an extensive analysis on the use of finite element modeling for the design, testing and development of prosthesis and orthosis devices.