Following our lecture on tissue engineering, I researched new techniques in tissue engineering and read an article on a woman who had a 3D-printed ear implanted using her cells after being born with a misshaped ear. It’s the first clinical application of 3D bioprinting.

The current goal of researchers is to develop more complex organs like hearts ready for transplant in the next 10 – 20 years. With a shortage of organs to transplant patients and nearly 7000 on a waiting list in the UK alone, the impact 3D bioprinting could have on organ transplantation is immense. It’s crucial progress towards personalized medicine that improves patient outcomes by reducing the risks associated with organ transplants.

As someone interested in working in the pharma industry, I was curious about the issues regarding the ethics of 3D bioprinted organs since all emerging biotechnologies must be ethically assessed before clinical use. Organ transplant currently creates a vast range of ethical dilemmas, so what would happen if we add artificial organs to the mix?

How it works

Although I won’t go into detail on the technique of bioprinting, it’s interesting to learn how 3D printers can print human tissue. Bioprinting relies on bio-ink, comprised of living cells surrounded by hydrogel molecules and acts as a digital file. Once loaded into the cartridge it’s deposited layer by layer of living cells to form 3D human tissue. It’s then crosslinked to become more stable by UV light or ionic solution, allowing it to grow and develop into a functional human organ.

Ethical Issues

The development of 3D bioprinting from laboratory to clinic brings with it established ethical concerns, such as the source of cells. Stems cells are widely used cell source obtained from living or aborted fetuses, raising a bioethical debate to determine their moral status, making their use heavily criticized. Xenogeneic cells are another option as a cell source, although their use has societal and religious concerns, and research has also shown there are psychological issues related to identity for xenotransplant patients. Personally, as a Muslim, I would object to an organ printed using pig cells and would be more inclined to an organ made from my cells. It eliminates the burden of knowing that another person died to save your life, as not all organs can be collected from living donors.

The clinical translation of this technology also brings emerging ethical issues related to personalized medicine to the forefront. Introducing 3D bioprinting into practice requires clinical trials. Generally, trials for 3D bioprinting involve testing patient safety and efficacy of the treatment using randomized placebo-controlled clinical trials e.g. (CAR T cells). Theoretically, it’s possible to test uncertainties related to the risk of harm to a limit, using small transplantable tissue. However, 3D-printed organs made from autologous cells are designed specifically for a patient, making it impossible to extrapolate the results from a randomized clinical trial. Ultimately the patient would have to be their own lab rat.

In addition, due to the invasive nature of the treatment the patient’s right to withdraw as a study participant is challenged. Since the reversibility of organ transplantation is limited, without causing harm to the patient and significantly impacting the chance of alternative treatment. It’s a critical issue for a patient to lose access to better treatment in the future because they participated in an experimental trial. Also, as an experimental therapy, it’s difficult for a healthcare provider to disclose all of the risks associated with treatment. So, even if the patient is conscious and has the capacity they might still not be able to provide informed consent.

A lecture on tissue engineering introduced me to the concept of Bioprinting. Although I am fully aware of the idea of 3D printing. I wanted to look more into how biological materials are incorporated into 3D printing to create tools that can be utilised within our bodies. Bioprinting is ‘the use of 3D technology with materials that incorporate living cells’. They are most commonly known for organ growth to battle the organ transplant crisis. But did you know that they are also being used to improve therapeutics, specifically drug delivery? I was particularly drawn to this as it shows potential in making medicine more personalised – a topic that I have always had an interest in.

Bioprinting and its biocompatibility

There are different types of 3D Bioprinting techniques such as stereolithography and fused deposition modelling. However, bioprinting with bioinks is able to produce structures that obtain many properties that can be used to  develop structures that can be efficient  for drug delivery.

Bioinks are hydrogels that can be made up from substances such as gelatin, alginate and hyaluronic acid – materials that are highly compatible within the body. The composition of the hydrogels can vary and as a result they can be modified so  the cross linkage  of the polymers can be made reversible or permanent depending on how the materials are treated physically or chemically. These are referred to as methacrylate hydrogels and the cross linkage can be used as a tool to be used to control the release of the drugs within the body. The bioinks can also incorporate synthetic polymers which can be used to further modify their properties such a degradation, increasing the biocompatibility.

Potential therapeutic uses

• Drugs

The main issue in drug therapeutics is the distribution of the drug itself within the body. In addition to this due to individual differences, a set dosage doesn’t work for everyone and a patient may not necessarily take their medication correctly. (Martinez et al., 2017) was able to print drug-loaded hydrogel with water which was able to release the drug at rates that were dependent on the water content. A delivery system, that would combat the improper use of medication, release the drug at the correct site of absorption, and could be further modified to be dose specific for each patient.  

With further reading, I discovered that tuberculosis required two drugs for it to be treated, rifampicin and isoniazid. Multiple studies have shown that these two drugs can negatively impact the effectiveness of the other and they are also required to be absorbed in different areas within the body for effective treatment. (Genina et al., 2017) designed an oral dual-compartmental dosage (dcDU) unit via 3D printing and hot melt extrusion

The dcDU  was tested in vitro and in vivo using rats, where drug release was analysed and it was noted that sealing and the compartments improved the drug release of each drug.  This study particularly opened my eyes to the amazing things that could be achieved with bioprinting, it was here when I begun to realise how much of a big impact on therapeutics that bioprinting would be. An infection that could require a 2-week course of 2 different antibiotics would be reduced to one oral dosage.

• Hormones

Like any other scientist, I began to work what else could we dispense and came across (Tappa et al., 2017). Intrauterine devices are the most common form of long term birth control. Although they are very efficient they are not necessarily personalised to the individual. Polycaprolactone pellets (PCL) were first coated with hormones and infused with silicone oil. Here is prime example of how synthetic polymers are used as the PCL allows for degradation and has a low melting temperature that will not interfere with the high degradation temperatures of the hormone. They then used this to print different 3D hormone-releasing IUDs which suggested promising uses in gynaecology applications.

• Growth factors

I am very familiar with the growth factor VEGF and its role in bone vasculature, so I really enjoyed (Poldervaart et al., 2014) paper on designing gelatin microparticles which had a controlled release of VEGF. Migration assays showed that the VEGF release from these microparticles lasted up to 3 weeks and was able to induce migration on endothelial progenitor cells. I began to wonder if 3D printing could be used for the potential treatment of bone cancer. What if we combined the biodegradable IUD concept but instead of hormones it contained angiogenesis inhibitors?

Organoids and chip in organs

To test my IUD hybrid idea, I could also utilise bioprinting to create organoids which are tiny 3D tissue culture that allows us to test the effects of infectious diseases and drug therapies. Organoids are rarely studied alone and are often in association with chip-in-organs, which replicate the organ environment so the results are more accurate to the behaviours that would be seen within the body.

Future Prospects

A lot of this research is very new and perhaps the two most obvious next steps for Bioprinting are refining the bioprinting mechanism itself and clinical trials, which some predict could occur within the decade. Most importantly, the ethical side of this needs to be discussed. Currently the FDA does not have an official definition for bioprinting, making it harder to set laws and guidelines for it. There is also a bit of worry about potential ‘black market’ uses of these resources – where do we draw the line? I could imagine that people could use this for recreational drugs such as nicotine for example or body builders could use it to increase their testosterone levels

However, the bioprinting world is such a new concept in the world of science with very promising results that could completely change the way we use therapeutics entirely and to be honest I am very excited to witness this.

Scoliosis is an abnormal lateral curvature of the spine, causing misalignment. In order to be considered true scoliosis, the curvature, measured by the Cobb angle, must be more than 10 degrees. Spine specialists recommend different treatment options depending on this angle, with more severe and progressive cases resulting in surgery.

Spinal Fusion

Spinal fusion, which has been the standard surgery for scoliosis for the past century, involves realigning and fusing the curved vertebrae with screws and rods. Although this procedure has good outcomes, with low complication and re-operation rates, it can diminish spinal mobility and flexibility. This means that those taking an interest in sports who undergo spinal fusion, for example, can lose their ability to perform. As someone with scoliosis myself (although mild), and having previously competed in tennis tournaments, this got me thinking about alternative spinal surgeries that do not have a negative impact on mobility.

Vertebral Body Tethering

As of recent, non-fusion spinal surgery has been used on those with scoliosis to correct curvature, while preserving flexibility and mobility. One method is through vertebral body tethering (VBT). This is where anchors (coated in hydroxyapatite, the substance that bones are composed of) are anteriorly attached to the vertebrae on the convex side of the scoliotic curve, with a flexible tether (made from polyethylene-terephthalate) connecting these anchors. The foundation of the procedure is that the tension from the tether slows the growth on the convex side of the spine, giving time for the concave side to catch up and driving the spine into the correct alignment. Due to the flexibility of the tether, and the absence of bone fusion, this allows for better spinal mobility post-surgery. Because VBT works via growth modulation, the most suitable candidates are those who have yet to reach skeletal maturity or are experiencing progressive scoliosis. This therefore means that VBT is less generalised than spinal fusion, and due to it being a new approach, there is some uncertainty with its long-term outcomes. Possible complications surround the fact that the tether may break through prolonged stress, though this does not pose much of an issue once spinal correction has completed. Early reports into the post-operative results of VBT do however demonstrate a high success rate and low revision rate.

Posterior Dynamic Correction and The ApiFix

Another non-fusion surgery for scoliosis is posterior dynamic correction, which occurs with the use of the ApiFix. The ApiFix is a self-adjusting rod, implanted on the concave side of the spine using a posterior approach, serving as an internal brace, and helping straighten the spine. The device can expand and so accommodates skeletal growth and additional correction. It is fastened to the spine with a single-level fusion (meaning only two vertebrae are being fused), with a total of only three screws needed. The rod features two polyaxial joints in which the vertebrae are fused, providing a greater degree of motion than spinal fusion. The ApiFix is most suitable for those with single spine curves and a Cobb angle between 35 and 60 degrees. Because this device and the procedure is novel, questions have arisen about its success rates. For example, possible complications include rod breakage and osteolysis (destruction of bone tissue). Early reports into the post-operative results of posterior dynamic correction with the ApiFix do however display its success and provides preventative measures to decrease failure and re-operation rates.

Final Thoughts

As I researched into the topic of surgical treatments for scoliosis, I was pleased to find other options as well as spinal fusion that can help preserve the individuals spinal mobility and flexibility. I believe that it is important to offer various treatments, while considering patient suitability, in order to improve the patient’s condition while not having a negative impact on their lifestyle. With the nature of these procedures, it has given me insight into how individuals requiring scoliosis corrective surgery have to negotiate between greater spinal motion with some uncertainty in long-term outcomes, or a long-lasting solution with diminished spinal motion. Personally, I would decide to go with the former option, with spinal fusion becoming a last resort if long-term outcomes are not successful. Nevertheless, I am excited to observe the follow-up results of these newer procedures and the advances technology will have on scoliosis corrective surgery.

As a teenager, the movie “My Sister’s Keeper” initiated my interest in saviour siblings. It portrays a young girl who tries to gain medical emancipation from her parents when urged to donate a kidney to save her leukaemia-stricken sister. After further research, I discovered that the movie addresses the ethics of saviour siblings. Consequently, it prompted questions, like whether it is right to do whatever is necessary to save a child’s life at the expense of infringing upon the rights of another?; and ultimately, is creating a saviour sibling ethical in the first place?

For those unaware, a saviour sibling is a child conceived through IVF. An embryo undergoes pre-implantation genetic diagnosis such as HLA typing to create a genetically compatible individual who can provide stem cells, blood, or organs to a sibling requiring them to live. Although creating a saviour sibling appears to be a noble endeavour, when addressing the ethics; three arguments are considered.

1. Saviour siblings as commodities:

This perspective stems from the idea that saviour siblings are a continuous and potentially expendable resource, contradicting Immanuel Kant’s maxim, “Never simply use people as a means, but always at the same time as an end”, and subsequently opposes the view of ethics as “right”. However, some argue that Kant’s assertion, in this case, doesn’t distinguish between having a child as a saviour sibling and having a child for another objective, like completing a family or saving a marriage, as the child is still a tool for serving a purpose. Thus, from a Kantian perspective, what is wrong is to create saviour siblings for a specific reason and then just discard them afterwards.

2. Saviour Siblings could lead to designer babies.

No!! Designer babies are not Gucci babies! They refer to genetically engineering pre-implantation embryos to influence the traits children will have. The creation of saviour siblings could be seen as a step towards pre-determining a child’s purpose and characteristics, illustrating a desire for perfectionism in a child by a parent rather than wanting them for who they are, thereby limiting their development as individuals. Furthermore, like the genetically “perfect” society in the sci-fi movie Gattaca, this argument allowed me to consider the path to negative eugenics that creating saviour siblings could create, selecting favourable traits to the detriment of people who cannot compete, and with the development of gene-editing tools like CRISPR-Cas9, such societal perfection and extreme segregation could be a misguided future reality.

3. The welfare of the saviour sibling

This argument considers the physical and emotional well-being of the saviour sibling. Alnasir et al. 2020 argue that regarding saviour siblings, the principles of beneficence and nonmaleficence of medical ethics are violated; since their creation and donation process carries no medical benefits for them but does impose potential harm, as they risk not only a painful invasive transplantation procedure but also abandonment and long-term detriment to their self-worth; if their donation is unsuccessful since their identity and value originate from being a cure to their older sibling.

Final thoughts

The conception of saviour siblings is an ethically controversial practice to which there is no clear answer; fortunately, this delicate process is regulated by the Human Fertilisation and Embryology Authority, authorising the creation of saviour siblings as per approved set conditions. Overall, this topic expanded my learning and prompted the conclusion that though it appears impossible to grasp the full extent of saviour siblings, the answer is that there may be no good answer, but as humans and a society, we must make decisions and applicable regulations for a virtuous future for those born to save another.