The bioprinting evolution: Then, now, and where no organ has gone before

1984. A marking year for the sciences. Technology giants like Apple and Dell launching new personal computers. Biology making the evening news with Steen Malte Willadsen successfully cloning a sheep with nuclear transfer. And Tetris. Also the year Charles Hull developed the first stereolithography method for printing resin layer by layer. It was the year 3D bioprinting was born.

Early breakthroughs in bioprinting

In the 90s, 3D printing began to include the printing of hydrogel-based materials. In 1996, Dr. Gabor Forgacs began experimenting with growing cells on a spatial scaffold, a three-dimensional structure. And it was at the turn of the millennium, that the world’s first artificial bladder was successfully grown and transplanted into a child by Professor Anthony Atala and his team. The synthetic organ was created on a collagen structure and seeded with the patient’s own bladder tissue cells. The patient is still alive and healthy.

In 2003, Thomas Boland modified an office inkjet printer to make it print biomaterial. And a few years later in 2009, the same Dr. Forgacs ⁠— who was using spatial scaffolds to grow cells— broke ground by creating a 3D bioprinter capable of printing living cells without using a structure. Organovo’s bioprinter disrupted the industry in that new kinds of tissues, such as blood vessels, could directly be printed without first using a cell scaffold. This led to more bioprinting breakthroughs in the field of tissue engineering, and the recreation of more live materials such as skin, cartilage, liver and vascular tissues, as well as heart valves.

New bioprinters facilitating innovation

In 2015, it was CELLINK’s turn to shake up the industry with its breakthrough universal bioink, the very first on the market to be commercialized. Also, CELLINK matched its own disruption with its first affordable, high-quality design bioprinter, INKREDIBLE. An immediate hit, the commercial pneumatic-based extrusion bioprinter also forged a path for more kinds of bioprinters, using other 3D printing technologies such as light-based printing⁠— stereolithography (SLA)⁠— , laser-based printed and holographic printing.

More recent breakthroughs in bioprinting continue to broaden the spectrum of bioprinting applications. 3D bioprinted corneas were successfully grown based on human cells in the UK. A small-scale human heart consisting of coronary blood vessels and chambers such as the atria and ventricles, was grown from human cells in Israel. Poland was the birthplace of the world’s first bionic pancreas with blood vessels. While the bioprinted tissue is not a full-sized pancreas, it contains some of its functionality being entirely made up of pancreatic islets, which are small structures within the organ itself that produce insulin and glucagon. This is a big advancement for therapy for diabetics, who are not able to produce their own insulin and therefore currently rely on injections. The printed pancreatic islets are currently being tested on pigs.

Bioprinting on chips and in space

There’s also something called organ-on-a-chip (OOC). And it looks about as strange as it sounds. The technology consists of a small board with micro-holes which are connected by micro-grooves or channels. In a more scientific description, it’s a 3D microfluidic cell culture. Microfluidics is a field in which the behavior and manipulation of fluids is studied on a very small scale, typically, from microliters (10-6) to picoliters (10-12). Each small well on the platform contains tissue cells. Very, tiny organ pieces, such as part of a heart, liver, lung, kidney. The medium channels that connect them are filled with gel and carry cells. The ensemble is meant to mimic an organ system, or a basic living system on which pharmaceutical drugs can be tested.

Moving on to more uncharted territory, scientists are now also printing organs in space, in the mobile mini-lab on the International Space Station. Why so far? The weightlessness of space presents a unique culture condition for the growth of human cells in three dimensions. On Earth, structures are being printed layer by layer. In microgravity, both tested on Earth and in space, cells have shown the ability to grow spatially in an unrestricted way, to form complex structures. Human stem cells are being grown to differentiate into body and cartilage tissue, as well as into other organ tissues. In a month-long project on the ISS, scientists are also hoping to accomplish the printing of organoids, test tube versions of smaller, less complex organs.

The story of bioprinting isn’t linear. 1984 was the beginning of a field that has grown and will continue diverging in several branches at each question, each with its promising, innovative applications. Final frontier? Let’s print it and fly beyond.

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