BIO-PRINTING
3-D printing bones and cartilage
Imagine this future scenario: A surgeon has removed a cancer that’s eaten into a patient’s bone. The procedure has left a ‘‘void’’ or hole in the bone.
The surgeon then implants bone tissue created from the patient’s own cells and some regenerative scaffolding materials.
They have been layered and shaped by three-dimensional bioprinting to match the anatomical shape of the void.
In the right circumstances, the scaffolding materials biodegrade as the bone cells grow to fill the hole.
‘‘Maybe in a year’s time, your knee or hip would be like it had never been damaged,’’ says Dr Tim Woodfield, principal investigator at the University of Otago’s Christchurch Regenerative Medicine and Tissue Engineering lab. ‘‘You would have beautiful new tissue that would have grown into the old tissue and the scaffolding would have biodegraded.’’
It might be 10-15 years away but that’s the promise of 3-D printing of human cells.
It’s one aspect of a field called regenerative medicine. ‘‘It’s the future of orthopaedic surgery,’’ says Woodfield.
He can imagine other scenarios where 3-D bio-printing might help with orthopaedics. Full knee and hip replacements are now common but the devices wear out after 10-15 years and need replacement. Doctors are also reluctant to undertake full transplants when the patients are in their 40s or 50s.
It might be possible to delay those full transplants with a less invasive and cheaper 3-D implant that could take a patient into their 60s or 70s, he says.
Orthopaedic 3-D printing is an immensely complex field and research is still embryonic.
Dozens of labs around the world are working on aspects and serious money beckons for those who secure intellectual property
"What we're getting good at now is printing small pieces of tissue." Dr Tim Woodfield
rights. Woodfield is careful not to oversell the accomplishments of his lab.
Rather his lab is contributing to the slow accumulation of knowledge that might some day result in filling bone voids and related procedures. It’s a bit like 3-D printing itself, a slow and deliberate accretion of layers that add up to something practical.
When 3-D bio-printing emerged earlier this decade, there was talk of constructing whole organs for transplant – a liver, for example.
‘‘I’ve always been reasonably sceptical that we’d ever get to the point ... because of the complexity,’’ Woodfield says.
‘‘What we’re getting good at now is printing small pieces of tissue,’’ Woodfield says. In orthopaedics, that means printing small, complex pieces of bone and cartilage.
Getting this far required important developments. First researchers needed 3-D printers that were friendly to living cells.
They had to operate at body temperatures instead of hot and not be toxic to cells.
Commercial bio-printing machines are now available, he says. ‘‘The major breakthroughs and developments aren’t coming up with fancier printers.’’
Designing suitable materials to use in 3-D bio-printing has needed work, however.
Tissues in our body are mostly water. They would sort of ‘‘puddle’’ without a supportive scaffolding around them.
The trick, then, is supplying a supportive ‘‘watery’’ environment in which the cells can happily exist and that can be 3-D printed.
Woodfield variously calls this a construct, a matrix or a bio-ink.
In creating bio-inks, many research groups around the world use gelatin, which provides the necessary 3-D scaffolding while still being malleable (like living tissue) and not too stiff.
In some cases, these substances are ‘‘set’’ using ultra-violet light in a way similar to how a dentist cures a modern filling with light.
This presents several challenges, not least that UV light can damage cells – UV is, after all, the main culprit in sunburn.
Dr Khoon Lim and Dr Gabriella Brown from Woodfield’s lab investigated replacing UV light with visible light to cure a bio-ink.
It turned out this required ‘‘some clever chemistry’’ but it worked. It’s one of the lab’s ‘‘points of difference’’, says Woodfield.
The science paper, authored by Lim, Brown and collaborators at Germany’s University of Wurzburg was recently published in Advanced Materials journal.
There is much still to be done before the technology can be used by surgeons.
One aspect is to potentially 3-D print constructs that combine bone and cartilage. In simple terms, cartilage is the connective tissue found between bones within joints. It sits on top of bone.
If both the cartilage and bone are damaged by disease or injury, then it would be good to implant new combined bone and cartilage constructs.
It should be possible to 3-D print bone cells and then 3-D print cartilage on top of the bone.
Another aspect is vascularity. Again, in simple terms, bones have blood vessels and need blood to thrive.
It would be best if 3-D printed bone materials had blood vessels in them.
Another avenue of research is using ‘‘allogeneic stem cells’’, cells donated by another person for culturing and eventual transplant.
Using a patient’s own cells is preferred at this time because it presents fewer complications around rejection.
But there might be circumstances where using a donor’s cells is preferred, Woodfield says.
For example, using a patient’s own cells will likely require two surgeries – one to harvest cells and a second for the implant.
If allogeneic cells are used, then a single surgery is possible, Woodfield says.
There’s also promise in drug testing. Future labs could 3-D print thousands of cancerous tumours, for example.
Experimental drugs could be applied and monitored. In theory, a 3-D printed tumour would be a more accurate reflection of reality than tumour cells lying flat in a petri dish.
Veterinary researchers also have interest in 3-D bio-printing.
Pet dogs suffer from a common knee condition that might be treated with the techniques, for example.
Meanwhile the horse racing industry is also curious, not surprising given the enormous investments top horses require.