Bioprinting: a myriad of (t)issues



By Abigail Pavey, Writer, Science Entrepreneur Club

Bioprinting uses 3D printing-like techniques to combine cells, growth factors, and biomaterials - collectively named ‘bioinks’ - to create living tissues that almost perfectly mimic their structure in the body. Bioinks are deposited layer by layer onto a supporting hydrogel, which functions like paper in conventional printing. However, unlike normal printing, the hydrogel dissolves once the product is mature, leaving it freestanding.

Bioprinting has huge potential, with its greatest value currently being realised in research and healthcare. Bioprinting allows scientists to move away from simplistic animal models of human disease. This will allow novel drug research to be conducted on a realistic human model and increase our understanding of disease pathology and drug efficacy. Recently, South Korean scientists have been using 3D printing to understand brain cancer treatments (1). In healthcare, tissue or bone that has been removed could be replaced using 3D bioprinting. This could be used in almost every surgical operation, erasing many of the problems associated with organ and tissue transplants, including immunological rejection and the long, sometimes fatal, waiting lists.



In the UK, 3Dynamic Systems Ltd aim to create high quality printers that are affordable to scientists and engineers in research. They have commercialised 3D bioprinting of vascular scaffolds and their latest printer, 3DS Omega, effectively produces experimental tissues and multiple tissue types on demand. Another company, OxSyBio is working on improving the resolution of the printed ‘bioproduct’ so that it can be used in healthcare. One of the major drawbacks of current printers is cells collapsing in on themselves; OxSybio’s technology allows cells to be printed within protective and supportive lipid-coated droplets making them more stable. What’s more, the lipid droplets extruded from the printer are significantly smaller than other extrusion bioprinters, allowing a higher resolution tissue or organ to be produced. Higher resolution is essential for tissues to be used clinically: it allows the synthetic tissue to more accurately mimic the cell-to-cell communications of native tissue.

Bioprinting is a revolutionary technology in its infancy, and as such throws up a myriad of ethical questions. One major concern surrounding its use in healthcare is access to the technology. Given its remarkable medical potential, how can bioprinting be distributed equally across an economically unequal society? Could the NHS even afford bioprinting? Globally, would bioprinting only be accessible to the Western world? It’s highly likely that the benefits of bioprinting would be limited at first to only the few who could meet the costs, as is the way with most personalised medicine. However, were it  to become affordable enough for everyone to access - like non-biological 3D printers - we would need to carefully consider carefully how such a revolutionary product is safely brought to the public market - who gains access to the technology.

As with many new technologies that have the ability to ‘enhance’ the human body, major legislation needs to be implemented for 3D bioprinting to enter the clinic as a regular tool. Never before has there been a product that begins with a data template and ends with a living entity. To create a template, the patient's data must be recorded and therefore carefully protected. Personalised medicine can lead just as quickly to personalised poison. Bioprinting may in the future lead to the printing of organisms, organs or tissues that could be used for all sorts of corrupt purposes. For example, bioprinted bacteria could be used as biological weapons; for example by printing millions of Ebola cells in any location across the globe. The “bioblueprints” available and the power to bioprint must be carefully protected and regulated. Is there are way to safely bring this technology into the market outside of healthcare?

A 3D bioprinter. Source: RegenHU

A 3D bioprinter. Source: RegenHU

Furthermore, there is disagreement among scientists over the best source of cells for use in bioinks(4). Stem cells are cells that have the ability to become any type of cell in a process called specialisation. Embryonic stem cells (ESCs) are removed from the embryo and grown into different cell types. Research on ESCs is ridden with ethical issues, including the concept of human dignity, informed consent, dealing with the early stages of human life and health and safety risks for women donating eggs.

An alternative to ESCs is the use of induced pluripotent stem cells (iPSCs), adult cells that are rolled back up the ‘specialisation hill’ to become stem cells again. With fewer ethical issues regarding their use, iPSCs come with direct and indirect benefits: they are more easily sourced and, in time, may provide feasible and affordable options for mass production and regular clinical use in 3D bioprinting. One unresolved issue, however, is that the placement of iPSCs into the human body could increase the risk of developing tumours and cancerous cells.
Addressing these questions isn’t easy. Whilst 3D bioprinting must be met with an open mind for its potential to be fulfilled, a robust consideration of its implementation is needed.

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2) Bioprinting of Stem Cells: Interplay of Bioprinting Process, Bioinks, and Stem Cell Properties Supeng Ding, Lu Feng, Jiayang Wu, Fei Zhu, Ze’en Tan, and Rui Yao ACS Biomaterials Science & Engineering 2018 4 (9), 3108-3124 DOI: 10.1021/acsbiomaterials.8b00399