It’s pretty amazing what people can do with a 3D printer these days. From manufacturing and architecture to custom art and design, 3D printing plays a critical role. Crucially, however, one area where real strides are being made is in medicine – in particular, bone bioprinting. Who would have thought that when Hideo Kodama published the world’s first account of rapid prototyping, 3D printing system back in 1981, in 2019 we would be talking about the same technology as a means to recreate bone tissue.
One question you might ask, however, is why invest all that time, effort and money into trying to replicate nature?
The answer? Because the current standards for supplying and regenerating much-needed bone tissue are not without their problems. While the medical profession already utilizes natural bone tissue including:
- Autografts – Graft tissue is taken from one point of the body and re-introduced at another or,
- Allografts – a tissue graft taken from another individual or donor,
they can and do have multiple issues.
These include limited supplies, increased risk of complications, immune reactions, and the transmission of infections. Clearly, this isn’t an ideal scenario for any patient requiring new bone tissue.
Other alternatives such as synthetic bone material support, allow bone regeneration to occur naturally. While greater success has been reached in this area, the challenge from leading companies has been the ability to continually recreate a near-perfect tissue-mimicking structure. So, when 3D printing technology has already advanced far enough to be able to reconstruct incredibly complex shapes and designs, it probably isn’t too much of a leap of faith to imagine how 3D printing can be used to develop synthetic structures designed to replicate human bone tissue – Or is it?
Understanding the complexities of bone
The main challenge facing scientists is that bone is an incredibly complex tissue, diverse in content. It has distinctive mechanical and structural properties that undergo continual changes in response to varying demands. It’s also connected to a huge network of blood vessels making it a highly ordered and vascularised tissue. All of these factors together make bone one of the most complicated structures in the body to replicate.
Bone bioprinting – In the beginning…
Surprisingly, the key difficulty for effective 3D bone bioprinting was not about mastering the design of the intricate structure – that was easily achieved using advanced CT/MRI scanning and auto CAD software. Instead, the biggest hurdle to date has been in selecting the right bio-ink. Okay so, in this case, it’s not really an ink, but the substance or material used to build up the structure, layer by layer. Unlike regular 3D printing where any type of thermoplastic or resin is acceptable, for bone bioprinting at least, the printing material of choice has now become a living cell suspension. The problem then becomes a biological one and as a result, the right bio-ink needs to be many things. Naturally, it needs to be printable but in addition, it needs to:
- Achieve and maintain a stable structure
- Maintain any mechanical properties to allow bone tissue regeneration
- Be non-toxic in itself, to its carrying products or, any other products necessary to aid metabolism
In other words… it needs to wear many hats, and that is a tough ask! In the early days, many materials were tried and tested, yet only a few remained sufficiently stable for effective bone bio-printing. Fairly quickly however it was discovered that hydrated networks of polymers – more commonly known as hydrogels – were best suited. While singular hydrogels such as alginate, collagen, and hyaluronic acid (HA) were trialed, they either suffered from poor mechanical properties, low viscosity, or low bio-activity. As a result – and in true scientific style – the decision was taken to genetically modify the natural polymers so that when combined, they created a ‘super gel’. This was the first big breakthrough in effective 3D printing.
Although early results carried out ‘in vitro’ under laboratory conditions proved encouraging, the ultimate test for any key medical finding is whether the same results are mirrored when live tested. In one of the first studies carried out by Fedorovich et al, they recreated two different phases of bone marrow-derived mesenchymal stem cells (BMSC’s) along with specialised stem cells-known as EPC’s. Both were manufactured using the latest 3D bone bio-printing methods. When implanted into mice – and after several months – Fedorovich found that the man-made cells successfully integrated with the host tissue. Another experiment by Kang et al around that time involved placing constructs, which had been cultured for 15 days after printing, into the skull bone defects in rats. Again, the results proved promising, and new bone creation was found across all defects within 5 months.
So, where are we today?
While small scale in vitro studies remain promising, vascularisation issues – the organic process where body tissue becomes vascular – remains a problem. In addition, the size of supporting constructs can only be re-created at present to just a few centimeters. And then, of course, there’s the small matter of replicating any early success on a living breathing human patient. Once these barriers are overcome – and all the signs are there to suggest that they will – then the ability to bio-print composite tissues and indeed – entire organs at will – could become a real and distinct possibility.