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Before reaching humans, new medicines are first tested on mice, then rats, dogs and primates. “It can sometimes take 15 to 20 years for a drug discovery to happen,” said Dr Deepak Kalaskar, associate professor at University College London. “The reason is these animals do not replicate human genomics or physiology.”
In the future, said Kalaskar, pharmaceutical companies will bypass all those time-consuming pre-human stages. The enabling technology is bioprinting – 3D printing of living cells and other materials to create biological tissue and organs.
By using human cells in printers such as the NovoGen Bioprinter from Organovo, researchers can replicate ‘targeted’ tissues throughout the body, such as skin or liver tissue. They are exposed to viral particles, bacteria and drugs before microscopic and other observation.
Bioprinting made headlines last year after projects including the development of ‘organoids’ at the Wake Forest Institute for Regenerative Medicine in North Carolina. Led by Dr Anthony Atala, the team built miniature lungs and colons to assist Covid-19 research, the New York Times reported. Constructed by using a scaffold of biodegradable material followed by a ‘bioink’ of cells and hydrogels, the organoids were used for drug testing.
Off-the-shelf organs
In the future, researchers will go beyond organoids to create fully working printed human organs. For now, they are a “distant possibility”, said Kalaskar.
When fully optimised, the process will be “fantastic”, said Dr Piergiorgio Gentile, a biomedical engineer at Newcastle University. “We can absolutely reduce the time, we can understand much more – in the beginning – about the viability of a drug.”
Such a streamlined system would also be a huge boost to vaccine development in the fight against diseases, said Kalaskar. Organisations such as Oxford University, AstraZeneca and Pfizer worked at record speed to develop, test and prove the efficacy of their Covid-19 vaccines last year, but similar efforts could be completed even quicker by replacing not only animal testing but also volunteers with printed organs.
Risk-free testing
“If you have an off-the-shelf organ ready, we are not exposing these pathogens to healthy volunteers,” said Kalaskar. “We will be able to do this in a very safe manner, under laboratory conditions, and we will still get our relevant human information.”
The main challenge to creating fully functional human organs is keeping the tissues alive. In the body, networks of capillaries distribute oxygen and nutrition throughout tissues. Kalaskar and colleagues are developing blood vessel structures in the lab, aiming to perfuse blood through artificial tissue. The next stage is scaling up the process and ensuring it can be embedded within the printed tissue, before checking long-term survival.
Other teams have taken different approaches. In November 2020, bioengineers at Harvard Medical School in Massachusetts created liver-like tissue by combining human cells, a hydrogel matrix and photosynthetic algae.
(Credit: The Zhang Lab – Laboratory of Engineering)
“The study is the first true example of symbiotic tissue engineering combining plant cells and human cells in a physiologically meaningful way, using 3D bioprinting,” said senior study author Y Shrike Zhang. The algae provided a sustainable source of oxygen for the human cells, while they provided carbon dioxide.
The tissues could be used for drug testing – and eventually might be implanted for tissue regeneration within patients.
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