3D printing: artificial limbs and biomaterials go main stream

Introduction:

Can the human race imagine being modified, rectified or substituted in a clinical environment using body parts better than those we were born with? Yes, that is likely to happen between now and 2020 according to (Canton 2014). For this innovative transformation to happen technological advancements need to evolve in 3 dimensional printing (3D).  Currently, 3D printing is in its trial and infancy stage. 3D printing offers huge potential and hope to medicine and the human race at large. In a nutshell, it’s to print out a part of the human body in 3D spatial orientation. It might be a bit hard to imagine now, that we have seen only 2D printers at work.

Printing, as we know now when founded in the 15^th century had revolutionary effect on all spheres of society (Atala & Murphy 2014) likewise 3 D printing is all poised to transform the way we live and think. At present 3D printing is confined to prototyping, manufacturing industry and customised production of goods such as jewellery and motor parts (Malone & Lipson 2007). Twenty to thirty motor parts for the present day cars are produced using 3 D printing. Its impact on science and education is immense. It allows for educationalists to create a prototype of rare artifacts which aid in knowledge transfer by helping to feel and visualize in real space (Allard et al. 2007, Gomez et al 2012)

3D printing was first coined by Charles W. Hull  using a principle called stereolithography. This included multiple layers being printed to a surface using materials that can be cured by ultra violet light (Hoffman 2011)) These were later used to create 3D scaffold on to which now, using 3D bio printing and tissue engineering, cell tissues are being printed. Another phrase used synonymously with 3D printing is Rapid prototyping (RP) (Narayan 2014)

It is noteworthy to understand the challenges faced by 3D printing. The researchers are still finding ways to adapt hardware which can only use molten plastic and metals to utilise sensitive living biological material. The main idea is to recreate the extra cellular matrix and reproduce its complex architecture so as to enable its biological function (Atala &Murphy 2014)

Technology utilised in 3D can be classified in to three major heading, approaches, design and strategies (Atala & Murphy  2014). The main three methods used are

·         Bio mimicry: this approach is highly advanced and requires identical replication of cellular and extra cellular environment. The cellular components should be able to perform its functions, hence, the intra cellular and extracellular forces’ knowledge is paramount (Ingber 2006). The hurdle in this approach is the lack of in-depth knowledge at the micro-finite level.

·         Autonomous self-assembly: here the technology uses embryonic development principles whereby basic stem cells are printed and from there on these cells regenerate in to tissues and organs (Marga et al. 2007). This is good in case of tissue mass generation unlike specific shaped organs e.g. Liver tissue can be prototyped using this approach, however it fails if skull bones or specifically structured parts of the body has to be created.

·         Mini tissues: This is a mid-micro level which encompasses of tissue building blocks such as muscle fibres (Kelm et al. 2010) and they self-assemble themselves with substrate they are printed. These need accurate tissue level biological data replicated to form a condusive environment.

Imaging is the first step in 3D printing. Images have to be captured to the exact dimensions of what is being produced. The surfaces, borders and angles of the product are captured using various methods, namely X-rays, CT scans or MRI scans.  The whole idea is to achieve layered 2 dimensional sliced images of the part to be reconstructed. This data is then converted to a 3D design using CAD. This design is transformed in to a manufacturing data using CAM which is the printer’s language. Both CAD and CAM are mathematical modelling techniques (Atala & Murphy 2014). Imaging, in fact, has two major purposes, it helps us to replicate structurally and also gives a detailed idea of the biological environment around  and within the part that is to be replicated. The 2D layered information is used by the printer to deposit tissue material in layers while printing.

Different techniques are used in 3D printing; however they all follow the basic principle of building layer by layer. Starting from the bottom layer, layers are laid on top of each other and bonded together in the end. Some of the techniques are inkjet printing, micro extrusion and laser assisted printing. Which one is used is decided by surface resolution of design, cell viability of the tissue being constructed and type of biological material used (Atala & Murphy 2014).

1.      Inkjet printing: in a 3D inkjet printer, the basic principles remain the same as that of a 2D printer. It uses a drop on demand feature. The printing material (ink) in the normal printers is replaced by biological material. The substrates on which materials are deposited are made up of electronically precise lift mechanism. This helps the material to be deposited in all the three axes (Xu et al. 2008). One of the major drawbacks of such printers lies in the potential danger caused to the material printed as these printers heat up to 200-300 degree Celsius (Okamoto et al. 2000). However, recent study results look encouraging as there is no evidence of negative effects on the stability of the biological molecule (Cui et al. 2010).  Owing to its nature of substance used in such printers, the scope is limited at present. The material needs to be in the liquid form while printing and should solidify later on but while do so, it should maintain the biological properties. Yet the major advantage of such printers is fast printing, low cost and easy availability of printers.

2.      Micro extrusion printing: they work by automated extrusion of tissue and depositing them on to a bio viable substrate. Micro extrusion printing varies in sizes from large industrial one’s to small laboratory ones. The deposits are made in 2D format as continuous beads of substance rather than liquid droplets as used in inkjet printers (Atala & murphy). The main advantage of these printers is the fact that printing substance need not to be in a liquid form and is a win- win scenario especially in tissue printing. They can be used to fill in tissue scaffoldings or can be placed in strategically calculated positions when then fills up the space by self-assembly. However, the drawback of micro extrusion is the cell viability when compared to inkjet printing (Chang et al. 2008). Therefore, usually, it is used for structural reproduction such as Heart valves or vascular tissues rather than tissue reproduction.

3.      Laser assisted bio printing: these are less commonly used than other forms. LAB uses pulsed laser beam to propel bubbled cellular components in a substrate space. The laser beams are received by laser absorbing layer of metal such as titanium or gold which acts as a guide to deposit tissues. Main advantage is the nozzle less mechanism compared to other printers. However due to the complexity of the process and lack of versatility. The printers are still in the early phase of development.

In general there are numerous software’s and interfaces, however commonly used ones are OpenGL and DirectX. OpenGL is used by everyone and Direct X is backed by Microsoft.  3D library based on Java is called java 3D which is a low level application programming interface using java and sits on top of OpenGL, thus allowing Java applications such as ImageJ to interoperate with graphics card of computer.  Since bioinformatics and bio 3D involves predominantly human body parts, its design phase definitely includes image capture and then designing.  Image processing software in the medical industry are numerous and either free or commercial such as Amira, Visage Imaging; MeVisLab, Mevis etc (Schmid et al. 2010). Design software can be an entry level such as Tinker Cad ( a free web based application) or an intermediate level  sketch up (owned by google until 2012)  or advanced blenders  used for animation and movies( Griffey 2014). Many open source software are available for designing and construction. Scotland has a fully functioning Rapid Design and Manufacturing centre that focuses on prosthetic body parts. They use tracerCad premier prosthetic system to do the initial scan of the limb of which they aim to produce the prosthesis. They scan the limb both horizontally and vertically. This digital data which holds surface data of the limb structure is transported back from the tracerCad software in DXF format and printed using Solid view pro a CAD package( Herbert et al. 2005).

One of the latest software launched in the area of 3D printing consists of two software combined together. Go!SCAN 3D white-light 3D scanners and VX model (a 3D scan to print software). The VX model software helps designers to avoid post scan adjustment steps and quickly produce a 3D printer ready file. Another advantage of this software is its seamless fit with CAD software and 3D printers (Knox 2014).

Most commonly used in the bioinformatics is CAD or computer assisted design. CAD’s generate digital data of sliced images in STL format. STL or sterolithography format are mathematical representation of sliced 3D image. They are not by far the best, but due to the ability to represent triangulation, they do perform well in bio 3D printing. Another form of 3D printable data is G Code format.

These data are then analysed by software such as Replicator G. They act as the interface between design phase and the 3D printer. Replicator G takes on both STL and G code data formats and is most commonly used open software in 3D printing.

Conclusion

3D printing has come a long way in the last two decades and rightly so the Economist quoted 3D printing as the “third industrial revolution.”(The economist, 2012) and the forecasted implications are overwhelming. Bio informatics takes its lessons from the generic 3D printing technology and customizes it to meet the medical demands.  3D printing has proven to be a life saver in re-constructional surgeries after accidents or anticancer treatments. Three areas are still to be explored and they are more robust imaging and designing techniques, printing hardware and material development which would approximate artificial and natural differences in materials. 

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