High throughput bioprinting of cells into microwells. [Credit: Ozbolat Lab at Penn State]

3D printing adds depth to bioengineering research

3D printing holds out the hope of growing a working bladder, according to research roundup.

Advances in 3D ‘bioprinting’ could see the development of plug-in blood vessels and man-made skin, according to a special issue of Trends in Biotechnology published this month. This is partly thanks to ‘organ-on-a-chip’ technology – inexpensive microengineered structures that support the growth of human tissue.

Lung, gut and pancreatic tissue have already been grown from human stem cells on the specialist chips, which allow researchers to study physiological differences between patients as well as test the efficacy of new drugs. Producing these chips is a manufacturing challenge but 3D printing could reduce production time and cost.

"The intersection of 3D printing for microfluidic fabrication and bioprinting 3D tissues shows great promise for single-step organ-on-a-chip engineering and can allow greater flexibility and throughput in the research process," said Savas Tasoglu, assistant professor at the University of Connecticut, who works on developing new applications of 3D printing in microfluidics.

Advances in skin bioprinting are showing promise and researchers are at the beginning of the design process necessary to help patients, especially those with burns or chronic wounds.

"It is now a reality to utilise sophisticated machine control to create tissue-engineered constructs," according to Wei Long Ng and co-authors, of the Nanyang Technological University and the Agency for Science, Technology and Research in Singapore.

While bone, cartilage, skin, muscle, blood vessels and nerves have all been printed in the laboratory, constructing more complex designs that can be placed in patients is still in development. Craniofascial reconstruction, which would benefit people with cancer or who have experienced facial injuries, is a clear candidate to pursue because of the amount of work already done on these cell types. In the short term, 3D-printed cellular ‘scaffolds’ could be used to improve defects in the jaw or other areas of the face.

"With the need for long-term pre-clinical studies, intelligent polymers, and ultimately good production of bioprinted constructs, there is still a long road ahead," noted surgeon physician Dafydd Visscher and colleagues at the VU University Medical Center in Amsterdam.

3D bioprinting is also demonstrating that precise models can improve the way we evaluate new drugs, such as by generating ‘organoids’ made up of multiple cell types, as well as tumour models with engineered blood vessels. While such approaches could make it possible to quickly monitor drug interactions in real time in multiple organs, more iterations will be needed to realise this vision.

"Along with the development of novel advanced bioprinting techniques, fabrication of physiologically relevant tissue models will become a vital tool in pharmaceutical development in the next decade," said Ibrahim Ozbolat and Weijie Peng of Pennsylvania State University and Derya Unutmaz of The Jackson Laboratory of Genomics Medicine.

Even with all these advances, the researchers are keen to highlight that there are still many challenges ahead. Efforts to create 3D blood vessel networks within bioengineered tissues – which would be necessary to ensure tissue survival after implantation and an accurate replication of human anatomy – have focused on stacking 2D layers of cells or bioprinting 3D networks, which allows for high levels of spatial control. But one challenge is to create tissues with blood vessel networks that could directly connect to a patient's arteries or veins.

"Vascularisation is currently regarded as one of the main hurdles that need to be overcome to take tissue engineering to clinical applications at a large scale,” noted bioengineers Jeroen Rouwkema and Ali Khademhosseini, both of MIT and Harvard.

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