Need to know: are we set for a bioprinting boom?

From refashioning foods to fabricating organs, bioprinting is the smart technology that could have a vast impact on human health and wellbeing in years to come, writes Matt Packer

Forward: features are independent pieces written for Mewburn Ellis discussing and celebrating the best of innovation and exploration from the scientific and entrepreneurial worlds.

When the US and Russia put their heads together for some serious problem-solving, the results tend to be rather impressive. With the International Space Station under their belts, for example, just imagine what they could do in the field of food innovation.

Well, imagine no more. Last summer, it emerged that all-American fast-food brand KFC had teamed up with a Russian technology firm in an effort to make chicken products entirely in the lab. In a move much in line with the objectives of cellular agriculture (aka cultured meat), the brand announced plans to ‘bioprint’ its new-style snacks from a blend of chicken and plant cells.

Although updates on this project don’t seem to be forthcoming, in an earlier press release KFC Russia’s CEO Raisa Polyakova said that as well as boosting the brand’s ‘restaurant of the future’ ambitions, the ‘experiment in testing 3D bioprinting technology to create chicken products can also help address several looming global problems’.

“The 3D bioprinting market is tipped to reach a total value of $1.7bn by the end of this year and $4.4bn by late 2028”

As recognition of these technologies has flourished, so too has their commercial potential. Recent figures from Grand View Research Inc. have tipped the 3D bioprinting market to reach a total value of $1.7bn by the end of this year and $4.4bn by late 2028: a projected compound annual growth rate of 15.8%.

So, what actually is bioprinting? Where is it used, and how does it work?

Organic content

For a major clue, we can refer to comments from Yusef D Khesuani, co-founder of KFC’s Russian business partner 3D Bioprinting Solutions. In the deal announcement, he pointed out that while 3D bioprinting technologies ‘are nowadays gaining popularity in producing foods such as meat’, they were initially ‘widely recognised in medicine’.

Indeed, many fundamental techniques of bioprinting were documented in the 2017 Elsevier book Nanotechnologies in Preventive and Regenerative Medicine: An emerging big picture. An entire chapter is devoted to advancements made over the few years up to the book’s publication in the use of 3D printers – or, in this context, ‘bioprinters’ – to build raw, cellular matter into slices of specific tissue types.

Essentially, the book explains, cells are fed into these machines as part of a ‘bioink’: a solution rich in organic content, typically including one or more biopolymer gels. Depending on which sort of tissue a lab wants to produce, it will choose between a number of available types of bioprinter, with the primary choices being inkjet, extrusion and laser-assisted (similar variations are found in 3D printers used in manufacturing). Each provides a different technique for directing cells into the required configuration. A fourth type – ultrasonic – uses sound waves to stimulate the assembly of cells into a desired pattern within a substrate. While some bioprinting efforts in the first three modes begin with the construction of a shape-defining ‘scaffold’ upon which tissue is gradually layered, others are scaffold-free and printed directly onto a sterile surface.

Case studies highlighted in the book include experiments to bioprint skin, cardiac tissue and even nerve endings, with one of those projects dating back to 2012. Indeed, work on bioprinting has been progressing, and patents have been issued in the field, since the early Noughties.

Bespoke blends

As bioprinting has evolved, so have perceptions of its capabilities, and a range of practical and theoretical use cases have been identified in a number of sectors. For example:

Consumer goods

In 2015, beauty brand L’Oreal struck up two separate partnerships with bioprinting firms to pursue R&D with potentially significant impacts for personal care products. With Organovo, the brand was reported to be exploring the scope for 3D printing human skin for in vitro testing of cosmetics – the objective being to eliminate tests on live subjects. And with Poietis, L’Oreal set out to print human follicles – the success of which would enable the brand to grow its own supply of hair for testing shampoo. While no news has emerged from Organovo, a 2019 update from Poietis published at folliclethought.com provided encouraging signs of progress, indicating that bioprinted follicles may also have future potential in the treatment of hair loss.

Horticulture

At least one scientific paper has examined the scope for bioprinting to be used for constructing plant life, with two main applications in mind. As well as enabling biologists to improve their understanding of plant shapes and the process through which they form (morphogenesis), the technology could be harnessed to create special plant-based biomaterials for use in a variety of industrial contexts.

Apparel

In a 2018 interview with AZO Materials, spokespeople for bioprinting company SunP Biotech highlighted the printing of leather as an area ‘ripe for research’. As well as potentially mitigating our reliance on animal-based clothing by providing an entirely humane alternative, printed leather could be used in domestic and automotive upholstery.

Hospitality

And while, as noted earlier, KFC is working its way into the printed fast-foods space, there is also room for the technology to reshape fine dining. As Shannon Theobald, author of the 2018 book Printing Your Dinner: Personalization in the future of food, explains in a Medium column published alongside her book, bioprinting is ushering in tailored versions of traditional recipes, specially adapted to people’s nutritional needs – or even designed to work around food sensitivities. In enabling foodstuffs to be printed out of bespoke blends of bioinks, she adds, the technology increases a chef’s control ‘immensely’.

Spare parts

It is in medicine, though, that bioprinting continues to hold the greatest promise – and giant leaps from the experiments outlined in the Elsevier book are happening all the time.

As one recent report notes, several groups of researchers in the field of preventive medicine have already undertaken efforts to bioprint sections of tissue that deliberately include cancerous areas. Called ‘tumour modelling’, this approach enables scientists to examine the metastatic process under controlled conditions and then use the resulting data to shape the treatment of patients. In 2018, a special report on bioprinting from the European Parliament envisaged that one day, medical teams could even bioprint copies of entire sections of patients’ bodies to help inform surgical interventions.

Regenerative medicine, in particular, is a key focus area for bioprinting technologies. Some of the most prominent developments in that area from the past few years include:

• In 2018, Newcastle University’s Professor Che Connon and Dr Steve Swioklo created the world’s first bioprinted human cornea. In their proof-of-concept endeavour, they made the necessary bioink by mixing cells from a healthy donor cornea with a combination of alginate and collagen.
• The following year, biotech firm BIOLIFE4D made the first-ever bioprinted human heart. Another proof-of-concept project, the heart was built at miniature scale, but with the structure of a full-sized heart, including four internal chambers.
• Towards the end of last year, FC Barcelona announced that it will serve as a test bed for the EU-backed TRIANKLE project’s range of bioprinted, cell-restoring ankle implants, designed to promote healing from injury. The effort will be overseen by the club’s R&D wing, Barça Innovation Hub.

Collateral effect

The benefits to individuals are clear: once refined and optimised, these technologies will enable medical teams to fabricate organs and other body parts from cells provided by the patients for whom they are intended. This could dramatically cut instances of tissue rejection. Importantly, it also has the potential to offer a solution to the global shortage of organs and tissues for transplantation. According to WHO, data from its Global Observatory on Donation and Transplantation suggests that the number of transplants carried out annually represents less than 10% of need.

“Once refined and optimised, these technologies will enable medical teams to fabricate organs and other body parts from cells provided by patients”

So, with donor networks already badly stretched, bioprinting opens up the prospect of a fully fledged supply chain of manufactured organs – something that experts predict will be required as a result of another technology’s evolution. Last year, researchers at Louisiana Tech University pointed out that, as driverless cars become more and more widely accepted, they could significantly reduce road fatalities. ‘While no one will fault any technology that safely and effectively protects and saves lives,’ they wrote, ‘one collateral effect of [these cars] will be a reduction in the market supply of healthy organs for transplantation.’ That growing gap, they argue, could prove fertile terrain for the bioprinting sector.

In the ‘ones to watch’ file, manufacturing specialist 3D Systems has teamed up with medical enterprise United Therapeutics (UT) to 3D-print lungs. Working through UT’s wholly owned subsidiary Lung Biotechnology PBC, the partnership has already overcome the challenge of printing the intricate and complex structure of a workable lung at the ultra-thin wall width found in nature – an extraordinary achievement. This opens the way for trauma patients or people with long-term illnesses to receive 3D-printed lung tissue or even entire organs – a significant development at a time when respiratory disease is so high on the world’s agenda.

Meanwhile, at the University of Pennsylvania, researchers have leapt ahead on cardiac technology with a process that ‘enables the bioprinting of spatially complex, high-cell-density tissues’ – ensuring that 3D-printed hearts of the future will be a tougher, hardier breed.

It seems only fitting that durability will be a running theme in the ongoing development of bioprinting, as it seeks to make itself indispensable. Or should we say indelible?

Innovation isn’t done yet

Isobel Stone, Senior Associate and Patent Attorney at Mewburn Ellis comments:

"Bioprinting is an area of technology that has taken exponential leaps and bounds since the early demonstration of successful printing of viable cells using an inkjet printer in the early Noughties. As a technology that sits at the intersection of life sciences and engineering, it is hugely exciting to see how joint innovation across both of these fields – and in particular, in the biomaterials sector – offers potential solutions to issues that affect many of our lives. The impact may be direct, with innovations in the regenerative and preventative medicine space, or indirect, for instance by offering ethical or humane alternatives to existing consumer and food technology goods. However, it’s also clear that the innovation isn’t done yet. With the huge amount of growth forecast, it seems certain that there will be much valuable IP arising in the bioprinting space over the months and years to come."

Written by Matt Packer