As Additive Manufacturing (AM) develops into a true production technology – and is used in a host of mainstream industrial applications throughout numerous industry sectors – it is also being adapted to niche applications where it is disrupting traditional routes to product development.
Essentially, it is the growing demand for customised medical devices and pharmaceuticals that has seen the growth in interest in additive manufacturing (AM) in the medical and life sciences sectors. Throughout industry, but in the life sciences sector in particular, AM has been truly disruptive, and some would say revolutionary, and it has promoted the manufacture of personalised implants and prosthetics, personalised and adjustable dosage forms for drug delivery, tissue engineering, and disease modelling.
But the use of AM in life science applications is not necessarily straightforward. For example, the physiochemical and biopharmaceutical characteristics of active pharmaceutical ingredients (APIs) in drug formulations are extremely varied, and need to be considered alongside any proposed AM drug delivery solution. However, the over-riding demand for patient-centric drug and medical product development means that AM’s future is secured in the life sciences sector.
AM is now an established technology in the manufacture of models (phantoms) for surgical planning and training, implants and prostheses, patient specific anti-microbial wound dressings, and some novel forms of drug delivery, but a relatively less advanced area, and one in which FelixPrinters is working actively is in the field of bio-printing and so called “organs-on-chip”.
WHAT IS BIO-PRINTING?
The key stimulus behind AM driven bio-printing is to find a solution for organ/tissue rejection, and the requirement for lifelong immunosuppressant-based therapies. The area of regenerative medicine is constantly on the look-out for mechanisms that allow for the fabrication of multi-layer soft biological materials such as living cells, and in this extremely exacting area of research, AM is finding a foothold.
To date, AM has been mainly used for the preparation of tissue construct such as blood vessels, liver, kidneys, heart tissue, cartilage, and bone. But all developments in this area of the use of AM requires a focus on the long-term viability of the “printed” cells, the control of cell proliferation so as to provide sufficient amount of functional and supporting cells and tissue homeostasis, and the requirement for tissues used in 3D printing to be able to survive pressure and shear stress during the 3D printing process, as well as contact with potentially harmful compounds.
RESEARCHING BIO-PRINTING APPLICATIONS OF 3D PRINTING
FelixPrinters is working with the Technical University of Denmark (DTU) on bio-printing applications of 3D printing. Heading the research is Hakan Gürbüz, who explains the foundation of the work he is undertaking. “The aim of the 3D printing project is the printing of scalable and perfusable hybrid scaffold structures, incorporating in the same structure at least two different material properties. For this purpose, we are developing a hybrid 3D printing platform with Felix that will enable the printing of 3D scaffolds with dual material properties (e.g. mechanical [soft/medium/hard], conductive or biological) and perfusable micro-channel networks, enabling the continuous supply of oxygen, nutrients, and necessary factors to cells growing and differentiating throughout the scaffold.”
To facilitate this work, Gürbüz is working to adjust the Felix Pro 3 printer that he is using, combining different 3D printing principles, i.e. one printer head for traditional extrusion filament printing (thermal heating of polymers) and one for solution-based elastomer/hydrogel printing (using light- or (bio)chemical/ physical cross-linking).
“We are looking at indirect scaffold printing using the reconfigured 3D printing platform, basically the direct printing of a sacrificial dissolvable filament template (e.g. polyvinyl alcohol) that defines the microchannel networks, apply a hydrogel/elastomer casting (e.g. silicone, silk) around the template, and then we remove the template by dissolving it in water. This leaves behind a hydrogel/elastomer scaffold with a perfusable microchannel network,” explains Gürbüz.
“We are also working on direct or indirect 3D printing of conducting scaffolds, effectively using filament or polymer casting materials doped with conducting nanoparticles (CNTs, graphene, etc.) Alternatively, 3D printed polymer scaffolds can be pyrolysed, 3D printing with solution-based hydrogels and biomaterials (e.g. hydrogels containing hSCs, growth/differentiation factors). Finally, we are working on 3D printing of hybrid scaffolds, combining filament- and hydrogel/bioprinting, to obtain conducting- and soft/biological material properties in the same scaffold.”
3D printing has many advantages over conventional approaches to building scaffolds, not least its ability to position the cells precisely, but bio-printer technology needs to increase resolution and speed and needs to be compatible with a wider spectrum of biocompatible materials to progress as a technology in this area.
Gürbüz continues, “Biomaterials are undoubtedly the primary limitation of this technology. We are limited to a few biocompatible synthetic and natural polymers. Therefore, a blend of these polymers is needed with the biomaterial’s viscosity and crosslinking mechanism determining its printability. Technology choice is also key. Currently, there are three different classes of bioprinters that are used for deposition and patterning of biological materials including inkjet, microextrusion, and laser-assisted printing. Each of these bioprinters has unique methods of depositing 3D cell structures with good resolution and viability. With Felix, we have decided to build micro-extrusion bioprinters, essentially due to their ease-of-use.”
Microextrusion bioprinters usually consist of a temperature-controlled biomaterial dispensing system, a stage capable of moving in the x, y and z directions, light illuminated deposition area for photo-initiator activation, and a video camera for x-y-z command. Unlike other bioprinters, the microextrusion bioprinter generates a continuous string of bio-ink rather than many droplets of bio-ink by applying pressure – either pneumatically or mechanically – to force the bio-ink from a syringe. These strings are deposited in two-dimensional layers (as directed by the CAD-CAM software), and served as the base for the subsequent layers while the stage is moved up the z-axis, resulting in the formation of a 3D structure. Microextrusion bioprinters are compatible with a wider selection of bio-ink including high viscosity materials such as hydrogels, bio-compatible copolymers, and cell spheroids. Yet, the cell survival rate is lower in comparison with other types of bioprinters due to the substantial pressures being used.
Gürbüz explains. “User-friendly isn’t exactly the first term that comes to mind when one thinks of bioprinting, but the 3D printer that we are developing is designed to simplify the process by guiding the user through every step. It also gives users numerous options and a great deal of control, with the ability to print with a wide range of biomaterials that mimic the native environment of each specific type of cell. Users can optimise the process for heart tissue, skin, cartilage, bone, etc., thanks to special features such as exchangeable print heads that offer multiple options for heating and cooling according to the needs of the material. The dual extrusion bioprinter is capable of producing heterogeneous tissues.”
